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Although Dapsone can be effective, it is not a benign drug without side effects, and the risks/benefits must be discussed with the patient.Deplin (L-methyl folate) can also be included in the protocol.Average decreases in hemoglobin of about 2 to 3 grams can be expected with Dapsone using the above doses of folic acid, which stabilizes over time.She had failed multiple combinations of intracellular drug therapy (two- and three-drug combinations), and was effectively treated with a four-drug intracellular antibiotic regimen for relapsing Bartonella and tularemia, including a tetracycline (doxycycline), rifampin, Dapsone, and a quinolone (Avelox). Intracellular persister bacteria in chronically ill, debilitated patients with Lyme, associated co-infections and/or autoimmune disease may require multiple intracellular drugs, including the addition of persister drugs (Dapsone and Pyrazinamide), used in novel ways to obtain positive clinical results. For my most resistant patients I now use several different combinations of intracellular drugs, including combinations of tetracyclines (minocycline and/or doxycycline), rifampin, macrolides (Zithromax or Biaxin), and Dapsone (two to three intracellular drugs, occasionally four), combined with Plaquenil and grapefruit seed extract (two cyst-busters), pulsed cell-wall drugs (Ceftin, Omnicef, penicillins or IV Rocephin), nystatin (for preventing yeast), biofilm busters (like Serrapeptase, Stevia, and monolaurin, which is a coconut oil extract), with extra folic acid to help prevent side effects of Dapsone. I use Leucovorin, a pharmaceutical folic acid, and a nutraceutical high-strength activated folic acid from Xymogen called 5-MTHF-ES (5-methyltetrahydrofolate extra-strength) or Folify-ER. A total of at least 30 mg of folic acid a day must be used (sometimes higher, i.e., 45 to 60 mg/day) to minimize the anemia associated with Dapsone. Average decreases in hemoglobin of about 2 to 3 grams can be expected with Dapsone using the above doses of folic acid, which stabilizes over time. Deplin (L-methyl folate) can also be included in the protocol. Although Dapsone can be effective, it is not a benign drug without side effects, and the risks/benefits must be discussed with the patient.Herxheimer (JH) reactions are seen in the majority of patients using Dapsone, and they can be severe, in which case the dose will need to be temporarily decreased or held for several days, especially if the JH reactions persist despite using LDN, high-dose glutathione with NAC, alpha-lipoic acid, alkalizing the body and drainage remedies.

Pack into sprinkler and use.Shake daily for 7 days.Add a few drops of essential oil (say Patchouli, Bergamot, Rose).Sieve to rub out lumps.Take cornflour.**TALCUM POWDER**.Thus, an unknown herbalist rose to be the first to introduce Peruvian bark (Quinine) into Europe for the cure of malaria.Valerian 2; Strophanthus 1. Mix. Dose: Liquid extracts: 8-15 drops. Tinctures: 15-30 drops. Thrice daily. _Dr Finlay Ellingwood_. "Give Poke root, Blue Flag root, Bugleweed and Cactus." _Spartiol Drops_ (Broom). 20 drops thrice daily for periods of 4 weeks. ( _Klein_ ) **Diet**. See: DIET – HEART AND CIRCULATION. _Note_. Tachycardia may often be relieved by pressure of the eyeballs. **TAENIFUGE**. An agent, such as Male Fern, to induce expulsion of tapeworms from the body of the host. See: ANTHELMINTICS. **TALBOR, SIR ROBERT**. English herbalist who settled near the Essex Marshes to study the ague which was endemic. A scholarly man, he proceeded by observation and experiment to employ herbs in the treatment of fevers. Though unqualified, he attracted rich and poor and was so successful that visits from high European society compelled him to open in London where he developed the most famous and fashionable practice of his day. After curing King Charles II of a malignant fever he was granted a knighthood and made Physician to the King much to the chagrin of the College of Physicians. Stung by this affront and by his refusal to purge or bleed his patients his life was a running battle with the Medical Establishment. However, neither the College nor the illustrious Thomas Sydenham could any longer hold back the flood-tide demand for the remedy responsible for Talbor's success, known in those days as Jesuit's powder. Thus, an unknown herbalist rose to be the first to introduce Peruvian bark (Quinine) into Europe for the cure of malaria. **TALCUM POWDER**. Take cornflour. Sieve to rub out lumps. Add a few drops of essential oil (say Patchouli, Bergamot, Rose). Shake daily for 7 days. Pack into sprinkler and use.When changing nappies, Aloe Vera or Evening Primrose lotion or cream – or even warm towels – should be used in its place.**TAMARINDS**.Tamarind fruit._Tamarindus indica, L. German_ : Tamarinde._French_ : Tamarin._Spanish_ : Tamarindo._Italian_ : Tamarindizio._Iranian_ : Ambala._Indian_ : Tentula._Chinese_ : An-me-lo._Part used_ : fruit pulp.

There is a low sibling and offspring recurrence risk.The underlying mechanism is thought to be of somatic mosaicism, and no known causal genes have been identified to date.The patient has no syndromic features and is of normal intelligence.intestinal lymphangiectasia, recurrent chylous pleural effusions).The development of _in utero_ oedema may cause dysmorphic facial features such as epicanthic folds, a broad nasal bridge and neck webbing with low-set ears [15]. Systemic lymphatic abnormalities may present with pericardial and pleural effusions, chylous ascites and pulmonary and intestinal lymphangiectasia in the postnatal period. An individual with intestinal lymphangiectasia will complain of abdominal pain and diarrhoea following the ingestion of foods with a high fat content (as the intestinal lymphatics are responsible for fat absorption). Management of systemic lymphatic impairment is not straightforward and a multidisciplinary approach is key. Management includes the drainage of effusions and implementation of a medium-chain triglyceride diet to manage intestinal lymphangiectasia and chylous disorders [16]. Patients with systemic lymphatic abnormalities can be classified into one of two categories depending upon the clinical presentation: a multisegmental lymphatic dysplasia with systemic involvement (MLDSI) or a generalized lymphatic dysplasia (GLD). **Multisegmental lymphatic dysplasia with systemic involvement. ** Patients with MLDSI have a segmental pattern of lymphoedema. The swelling affects different body parts in association with a systemic lymphatic abnormality. For example, they may have lymphoedema of one or more limbs or body sites (including the face), in association with previous or current systemic lymphatic abnormalities (e.g. intestinal lymphangiectasia, recurrent chylous pleural effusions). The patient has no syndromic features and is of normal intelligence. The underlying mechanism is thought to be of somatic mosaicism, and no known causal genes have been identified to date. There is a low sibling and offspring recurrence risk.** Patients with GLD have a more global pattern of lymphoedema.Swelling typically affects all body parts and often presents _in utero_ with hydrops fetalis.A number of patients with GLD will have a family history of lymphoedema suggestive of autosomal recessive inheritance, inferring a higher recurrence risk than MLDSI.

Taking Care of a Cast When bathing, enclose the cast in a plastic bag and carefully seal the top with rubber bands or tape.In contrast, surgical stabilization usually enables people to walk with crutches or a walker within days.These conditions may be due to a developing pressure sore or compartment syndrome. The combination of rest, ice, compression (for example, with a splint, cast, or sometimes an elastic bandage), and elevation is often called RICE therapy. Surgical Treatment: Fractures sometimes require surgical treatment, as for the following: Open fractures: A doctor must explore and carefully clean these fractures to remove all traces of foreign material that may have contaminated the bone ends. Displaced fractures that cannot be aligned or kept aligned by closed reduction: When a bone fragment or a tendon is trapped in the bone ends, a doctor may not be able to reduce a displaced fracture. Sometimes the fracture can be reduced, but the natural pull of muscles on the fracture fragments keeps them from staying reduced. Comminuted fractures: Multiple pieces are often too unstable for a cast to keep them aligned against the forces of muscle contraction. Joint fractures: A near-perfect alignment of the joint surfaces is required to prevent people from developing arthritis later. Pathologic fractures: If possible, these fractures are stabilized surgically before they break further and become displaced. This approach avoids the pain, disability, and the more complex surgery involved with a displaced fracture. Fractures of the thighbone (femur) and hip: If these fractures are not treated surgically, they require months of immobilization in bed before people are strong enough to bear weight. In contrast, surgical stabilization usually enables people to walk with crutches or a walker within days. Taking Care of a Cast When bathing, enclose the cast in a plastic bag and carefully seal the top with rubber bands or tape.If a cast becomes wet, the underlying padding may retain moisture.A hair dryer can remove some dampness.Otherwise, the cast must be changed to prevent the breakdown of skin.Never push a sharp or pointed object down inside the cast (for example, to scratch an itch).Check the skin around the cast every day, and apply lotion to any red or sore area.

## Prepotency The ability of one parent, in greater degree than the other, to transmit a characteristic (e.g.Where this is practised, the calf when born must be provided with colostrum from another cow.## Prepartum Milking Milking a heifer or cow a few days before the birth of her calf.## Pre-Ovulatory Ovarian Stress (POOS) (See EGG-BOUND; VITELLOGENESIS.)## Prehension The act of taking hold of food prior to ingestion. The diet dictates the method that is used by each species to prehend food. Herbivores usually use the mouth as the organ of prehension – cattle use the tongue and lower incisors. Carnivores use their incisor and canine teeth. Grazers, like rabbits and sheep use their lips and incisors. Primates use their forelimbs, handling their food on its way to the mouth. Birds generally use their beaks, but some, e.g. woodpeckers, use their tongues. ## Premature Occurring before the expected time, usually referring to birth. ## Premature Birth PARTURITION that occurs before the usual time from conception. (See ABORTION and PARTURITION, and the table under PREGNANCY AND GESTATION.) ## Premedication Use of a drug or drugs before administration of a general anaesthetic. An analgesic will relieve pain in an animal awaiting surgery, and a tranquilliser will relieve anxiety and facilitate handling. Both effects may be obtained by the same drug. (See ANALGESICS; TRANQUILLISERS.) ## Premilking (See under PREPARTUM MILKING.) ## Premolar Teeth A type of tooth situated between the front teeth (incisors and canines) and the molars. The premolar are found in the temporary and permanent dentition. They are used to mainly grind up the food. ## Premunition Resistance to a disease following an injection. Animals which are premunised are infected with a micro-organism but are not affected by it. The term has often been used in veterinary medicine in relation to trypanosomiasis (see TRYPANOSOMES, TSETSE FLY). ## Preocular Film (See PRECORNEAL FILM.) ## Pre-Ovulatory Ovarian Stress (POOS) (See EGG-BOUND; VITELLOGENESIS.) ## Prepartum Milking Milking a heifer or cow a few days before the birth of her calf. Where this is practised, the calf when born must be provided with colostrum from another cow. ## Prepotency The ability of one parent, in greater degree than the other, to transmit a characteristic (e.g.## Prepubic Tendon, Rupture of A possible complication of pregnancy, especially in heavy mares.Diagnosis is difficult but the condition should be suspected whenever ventral oedema occurs suddenly in late gestation, and is associated with considerable pain (due to the trauma).The condition is usually fatal, and may be a cause of sudden death.

2.6 Late result of skin grafting of the plantar aspect of the skin.Fig.2.6) (Wassermann).This powerful antimicrobial agent should be used only over limited surfaces (no more than 30% TBSA), the risk of inducing methemoglobinaemia being a real and life-threatening complication (Fig.Scar improvement was observed when using double layer dermal substitutes (Integra, Purdue, Heimbach, Renoskin, Hyalomatrix Pelnac), and more recently with single layer dermal substitutes (Matriderm™) being immediately covered using thin skin grafts (Van Zuijlen). Cadaver skin can safely be used, especially to cover temporarily deep burns wound (Sheridan). The use of these materials is dependent on the availability, which is an issue linked to tissue banks which are necessary to store them under adapted freezing conditions. Allografts can be used as a sandwich technique when autograft donor sites are limited (extensive TBSA) or when the patient is in poor general health, thereby limiting the possibility of general anaesthesia. Autografts can be extensively meshed (×6) and covered using ×2 meshed allografts (Fig. 2.5). Keratinocyte Autologous Cell cultures provide hope for the future, if a functional dermis has been obtained (Rheinwald, Compton, Boyce). Fig. 2.5 Mesh grafting (×2) over the lower limb burns The use of xenograft has also been proposed, either to replace dermal components or to secure skin grafts. Early skin grafting may be contraindicated, due to various situations such as contraindications for surgery, exposure of joints, tendons or vascular bundles. Flammacerium (silver sulfadiazine plus 2% cerium nitrate) was proposed in the 90s, and was mainly used over extensive surfaces of third degree burns where surgery cannot be performed on a single occasion. Flammacerium presents the unique possibility of combining with necrotic tissue, transforming it into a calcified tissue strongly adhering to the wound edges for a very long period of time. This powerful antimicrobial agent should be used only over limited surfaces (no more than 30% TBSA), the risk of inducing methemoglobinaemia being a real and life-threatening complication (Fig. 2.6) (Wassermann). Fig. 2.6 Late result of skin grafting of the plantar aspect of the skin.This technique has indications when doubts persist on the vitality of the exposed tissues before skin grafts.## Conclusion Burns management is mainly based on excision and grafting techniques, in deep burns with the recent introduction of the use of dermal substitutes and on the use of antimicrobials in superficial burns, with the recent use of modern dressings.References 1.

IVC obstruction induces marked lower extremity edema, distention of the superficial collateral veins of the lower abdomen, and—with renal vein involvement—massive proteinuria. ### Lymphangitis and Lymphedema Although primary disorders of lymphatic vessels are extremely uncommon, secondary processes frequently develop in association with inflammation or malignancies. Lymphangitis represents acute inflammation elicited by the spread of bacterial infections into lymphatics; group A β-hemolytic streptococci are the most common agent, although any microbe can be causal. Affected lymphatics are dilated and filled with an exudate of neutrophils and monocytes; the infiltrates can extend through the vessel wall, and in severe cases, can produce cellulitis or focal abscesses. Lymphangitis is manifested by red, painful subcutaneous streaks (the inflamed lymphatics), and painful enlargement of the draining lymph nodes (lymphadenitis). If bacteria are not successfully contained within the lymph nodes, subsequent escape into the venous circulation can result in bacteremia or sepsis. Primary lymphedema can occur as an isolated congenital defect (simple congenital lymphedema) or as the familial Milroy disease (heredofamilial congenital lymphedema), which results in lymphatic agenesis or hypoplasia. Secondary or obstructive lymphedema stems from blockage of a previously normal lymphatic; examples include: • Malignant tumors obstructing lymphatic channels or the regional lymph nodes • Surgical procedures that remove regional groups of lymph nodes (e.g., axillary lymph nodes in radical mastectomy) • Postirradiation fibrosis • Filariasis • Postinflammatory thrombosis and scarring Regardless of the cause, lymphedema increases the hydrostatic pressure in the lymphatics distal to the obstruction and causes increased interstitial fluid accumulation.Rupture of dilated lymphatics (e.g., secondary to obstruction from a tumor) leads to milky accumulations of lymph designated as chylous ascites (abdomen), chylothorax, and chylopericardium.

The standard trephine has an internal diameter of at least 7.5 mm in order to obtain an adequate amount of tissue sample.The usual biopsy site is 2 cm posterior to the anterior superior iliac spine, immediately inferior to the iliac crest.Confirming a normal coagulation profile is imperative before the procedure.Iliac bone biopsy can be performed in an out-patient setting.The biopsy from a normal subject (a) shows thicker cancellous bone and better network connection than the one from an osteoporotic subject (b). 10× magnification enhanced Fig. 2 Photomicrograph shows features with toluidine blue stain in osteomalacia. The mineralized bone stains dark blue, and the thickened osteoid is in light blue. 40× magnification enhanced Fig. 3 Photomicrograph shows features commonly observed in bone disease from hyperparathyroidism. Mineralized bone matrix is in magenta and osteoid is in blue. Both bone resorption by osteoclasts (top left corner and bottom right corner) and bone formation by osteoblast covering osteoid are active. Marrow fibrosis is evident and replaces the normal adipose tissue and hematopoietic cells. 100× magnification enhanced ## Bone Biopsy Bone biopsies can be performed using manual or powered trephines. The latter is less prone to artifacts of crushing and fragmentation, but more prone to the generation of bone powder and thermal injury. The most favored site is the anterior iliac crest, for which the most histomorphometric data is available. This site has the advantage of easy accessibility; large histomorphometric database contains both cortical and cancellous bone. The trans-iliac biopsy (as opposed to the vertical iliac crest) produces two cortices besides cancellous bone and is better. Iliac bone biopsy can be performed in an out-patient setting. Confirming a normal coagulation profile is imperative before the procedure. The usual biopsy site is 2 cm posterior to the anterior superior iliac spine, immediately inferior to the iliac crest. The standard trephine has an internal diameter of at least 7.5 mm in order to obtain an adequate amount of tissue sample.A second biopsy site for a follow-up is preferred to be one of the opposite of the pelvis or at least 2 cm from the first biopsy on the same side if a third biopsy is elected.Complications are rare, and include pain at the biopsy site (non-narcotic analgesia is recommended), hematoma, wound infections, osteomyelitis, and fracture through the iliac crest.

Depending on their phenotype and activation status, T cells can cross-talk with neurons and microglia, and either protect or damage neurons from stressful stimuli.However, infiltrating T cells of the adaptive immune response are also present in areas of CNS motoneuron degeneration.When WT mice donor bone marrow was used to transplant doubly transgenic mice (mSOD1–PU.1−/−), the CNS microglia had a WT phenotype and motoneuron loss was decreased, and disease duration and survival were prolonged when compared with mice receiving mSOD1 mice donor–derived bone marrow. Furthermore, when another independent laboratory generated and employed transgenic mice with a different SOD1 mutation, and a different technique to reduce the expression of mSOD1 (i.e. the Cre–Lox system), a similar conclusion was reached, namely, that the reduction of mSOD1 in microglia prolonged disease duration and survival. A further suggestion from this latter study was that the onset of disease may be more related to the expression of mSOD1 in motoneurons, while, in accord with the previous study, the duration of disease may be related to expression of mSOD1 in microglia. Thus, the _in vivo_ data demonstrate that the neurotoxicity and neuroprotection noted _in vitro_ may be induced by a decrease in specific neurotoxic substances and an increase in a neurotrophic molecule from WT microglia relative to mSOD1 microglia, suggesting potential mechanisms for how WT microglia, by either the reduction or the elimination of mSOD1 expression, are less toxic _in vivo_. ## Immunologic aspects of ALS: part 2 – T cells Research linking immunity and neurodegeneration has focused primarily on microglia and innate immunity. However, infiltrating T cells of the adaptive immune response are also present in areas of CNS motoneuron degeneration. Depending on their phenotype and activation status, T cells can cross-talk with neurons and microglia, and either protect or damage neurons from stressful stimuli.Others have found perivascular and intraparenchymal T cell infiltrates in the corticospinal tracts and ventral horns of 18 of 27 consecutive ALS autopsy cases compared to 1 of 11 control brains; no B cells were detected.CD4+ T cells were present in the proximity of degenerating corticospinal tracts, whilst both CD4+ and CD8+ T cells were demonstrated in ventral horns.

**Probenecid** | Increased toxicity of dapsone.**Methotrexate** | May increase blood toxicity.**Hemolytics*** | May increase adverse effects on blood cells.**Dideoxyinosine (ddI)** | Decreased dapsone effect.Reduced absorption of both drugs.**Antivirals, HIV/AIDS*** | Increased risk of peripheral neuropathy.Avoid.Discuss risks and benefits with your doctor. **Infants & children up to age 18:** Follow instructions provided by your child's doctor. **Prolonged use:** • Request liver function studies. • Talk to your doctor about the need for follow-up medical examinations or laboratory studies to check complete blood counts (white blood cell count, platelet count, red blood cell count, hemoglobin, hematocrit). **Skin & sunlight:** May cause rash or intensify sunburn in areas exposed to sun or ultraviolet light (photosensitivity reaction). Avoid overexposure. Notify doctor if reaction occurs. **Driving, piloting or hazardous work:** Don't drive or pilot aircraft until you learn how medicine affects you. Don't work around dangerous machinery. Don't climb ladders or work in high places. Danger increases if you drink alcohol or take medicine affecting alertness and reflexes, such as antihistamines, tranquilizers, sedatives, pain medicine, narcotics and mind-altering drugs. **Discontinuing:** Don't discontinue without consulting doctor. Dose may require gradual reduction if you have taken drug for a long time. Doses of other drugs may also require adjustment. **Others:** • This drug has been associated with serious, and sometimes fatal blood or liver problems. • Contact your doctor right away if you develop a rash while using the gel. In rare cases it has been associated with serious, and sometimes fatal, skin reactions. • For full effect you may need to take dapsone for many months or years. ** POSSIBLE INTERACTION WITH OTHER DRUGS** **GENERIC NAME OR DRUG CLASS** | **COMBINED EFFECT** ---|--- **Aminobenzoic acid (PABA)** | Decreased dapsone effect. Avoid. **Antivirals, HIV/AIDS*** | Increased risk of peripheral neuropathy. Reduced absorption of both drugs. **Dideoxyinosine (ddI)** | Decreased dapsone effect. **Hemolytics*** | May increase adverse effects on blood cells. **Methotrexate** | May increase blood toxicity. **Probenecid** | Increased toxicity of dapsone.**Rifampin** | Decreased effect of dapsone.**Trimethoprim** | May increase blood toxicity.** POSSIBLE INTERACTION WITH OTHER SUBSTANCES** **INTERACTS WITH** | **COMBINED EFFECT** ---|--- **Alcohol:** | Increased chance of toxicity to liver.**Beverages:** | None expected.**Cocaine:** | Increased risk of side effects.Avoid.**Foods:** | None expected.

However, there is still much resistance among the medical community to the idea that low T is a legitimate and common condition that merits treatment.Eventually, people do catch on.How times have changed.Today, those same meetings devote entire days to testosterone research.At scientific meetings I would often make the only presentation involving testosterone.During medical school and urology residency, I was taught almost nothing about testosterone. However, when I began my own urological practice in the late 1980s, I was curious about testosterone because of my prior research. I was surprised at how many of my patients had low testosterone levels. I was further surprised at how many reported feeling improved so quickly after I started them on testosterone therapy. Most had come to see me for sexual problems, yet when I saw them in follow-up, I was impressed by how often they would say something like, "My erections are better and so is my sex drive, but the thing I like best is how good I feel overall." I soon began treating large numbers of men with testosterone, with excellent results. Many of my patients who did well had been told by their regular physicians that there was nothing wrong with them. "You're just getting older," their doctors would tell them. It wasn't true. These men had _low T_ , as I called it. (I coined this term in the early 1990s to make it easier for discussions with patients and even some of my colleagues, who would feel uncomfortable when saying testosterone deficiency.) Their symptoms were real and caused by a hormone deficiency. When I started doing this work, I didn't know a single physician treating men routinely with testosterone for sexual symptoms such as erectile dysfunction or diminished libido, and my colleagues regarded my work as bizarre. Soon I discovered a small cadre of like-minded physicians around the United States with similar interests in researching the benefits of testosterone, but our work was almost unknown. At scientific meetings I would often make the only presentation involving testosterone. Today, those same meetings devote entire days to testosterone research. How times have changed. Eventually, people do catch on. However, there is still much resistance among the medical community to the idea that low T is a legitimate and common condition that merits treatment.As Dr. Comite discusses in detail, low T is also associated with symptoms of fatigue, depressed mood, reduced muscle mass and strength, and osteoporosis.Men with low T are at increased risk for developing diabetes, the metabolic syndrome (a set of conditions that predispose to cardiovascular risks, including obesity and high blood pressure), and atherosclerosis.

**Discharge diagnosis:** Observation for possible intracranial injury.A small abrasion on his upper right arm, where the box scraped the skin, was cleansed and Neosporin applied.No injury was found.A CT scan of the head was negative for any abnormalities, but hourly neurological checks were made to rule out an intracranial injury.S72.301A Unspecified fracture of shaft of right femur, initial encounter for closed fracture J98.11 Atelectasis J95.89 Other postprocedural complications and disorders of respiratory system, not elsewhere classified W01.0xxA Fall on same level from slipping, tripping and stumbling without subsequent striking against object, initial encounter Y92.039 Unspecified place in apartment as the place of occurrence of the external cause Y93.E2 Activity, laundry Y99.8 Other external cause status 0QS804Z Reposition right femoral shaft with internal fixation device, open approach **Comments:** The information in the narrative is used to assign a more specific code for the fracture. Assign codes J98.11 and J95.89 because the fever and atelectasis were specified as postoperative. The fever is a symptom of the atelectasis. Postoperative atelectasis is often an incidental radiographic or physical finding that is frequently a self-limiting condition, in which case it would not be coded or reported. In this case, it was associated with fever and required further diagnostic (e.g., chest X-ray) and therapeutic (e.g., incentive spirometry) workup. Get a HintShow Answer Previous QuestionNext Question 1. **11. Inpatient admission:** The patient was admitted after a box fell on his head at the service garage where he works. A CT scan of the head was negative for any abnormalities, but hourly neurological checks were made to rule out an intracranial injury. No injury was found. A small abrasion on his upper right arm, where the box scraped the skin, was cleansed and Neosporin applied. **Discharge diagnosis:** Observation for possible intracranial injury.The abrasion was a minor injury that did not require hospital admission.Therefore, the observation code is assigned as the principal diagnosis.This situation is consistent with the inclusion note with category Z04, "when a person without a diagnosis is suspected of having an abnormal condition, without signs or symptoms, which requires study, but after examination and observation, is ruled out."

Reproductive problems can be encountered including infertility and low hatchability due to weakness in the pipping muscle of the chick • Hypovitaminosis K can occur with coccidiostats and long-term antibiosis that destroys the normal gut flora.Splayed legs and oedema of the neck, wings and breast may be seen.If the gizzard is affected, then undigested seed may be passed.Sneezing may occur, and there is a predisposition towards respiratory infections. In severe cases, metaplasia of the renale tubules can result in visceral gout • Hypervitaminosis D3: can result in calcification of viscera, especially the kidneys, triggering a visceral gout • Metabolic bone disease. This is often a hypovitaminosis D3 combined with a hypocalcaemia and hyperphosphataemia. In particular, African grey Parrots appear to have difficulty in mobilizing skeletal calcium reserves. Such birds often present with a hypocalcaemic tetany - wings fluttering violently in apparent 'fits'. Such birds often have high parathormone levels, low 25-hydroxycholecalciferol levels as well as low serum ionized and non-ionized calcium levels Clinical signs of metabolic bone disease is birds • General weakness (Fig. 5.19) • Pathological fractures and/or bending of bones • Rickets • Paralysis • Tetany • Dystocia • Low clutch size, thin or soft shelled eggs and low hatchability. (Egg laying hens may have an episode of acute hypocalcemia that can result in partial paresis and perhaps egg binding.) • Polydipsia/polyuria occasionally seen due too increased phosphorus turnover triggering a diuresis • Birds, especially the young, with bone and joint deformities might be deficient in both calcium and vitamin D3. Fig. 5.19 Hypocalcaemia in an African grey parrot - _note_ the three-point stance using the beak to aid support. • Hypovitaminosis E: affected birds may become lethargic and show coordination and equilibrium problems. Complete paralysis can occur. Other signs include white muscle disease. If the gizzard is affected, then undigested seed may be passed. Splayed legs and oedema of the neck, wings and breast may be seen. Reproductive problems can be encountered including infertility and low hatchability due to weakness in the pipping muscle of the chick • Hypovitaminosis K can occur with coccidiostats and long-term antibiosis that destroys the normal gut flora.However, adult hens deficient in B2 develop fatty livers, elongated flight feathers, have low egg production and low hatchability.

Bradycardia with hypoperfusion (without pulselessness) is a very common hemodynamic state for critically ill children during the prearrest phase.Conversely, illnesses or injuries resulting in negative chronotropy (e.g., heart block, toxicity from beta-blockers or calcium channel blockers) tend to result in more profound shock and hypoperfusion in children than in adults with similar processes.This emphasis is balanced against the increasing evidence that VF in children is not rare, that outcomes after arrhythmogenic VF arrests are superior to those after other types of cardiac arrests, and that early rhythm recognition is necessary for optimal care. Because of the increasing awareness that "shockable" rhythms are not uncommon in children, greater attention has been focused on the dose for pediatric defibrillation. The recommended shock dose is 2 to 4 joules (J)/kg, which is based on animal studies of short-duration VF and a single retrospective study of in-hospital (short-duration) VF with 91% (52 of 57) defibrillation success.89 More recent animal and pediatric data indicate that 2 J/kg is often ineffective at terminating fibrillation, and higher doses up to 10 J/kg may be needed to terminate VF.89,91 Thus recent recommendations suggest an initial dose of 2 to 4 J/kg followed by 4 J/kg if VF is not terminated; if VF continues, consider increasing the defibrillation dose up to 10 J/kg, not to exceed adult maximum doses. ### Cardiopulmonary Resuscitation in Pediatric Bradycardia Neonates, infants, and children are primarily dependent on heart rate for maintenance of CO. Their ability to augment stroke volume to increase CO is limited, and physiologic or pathophysiologic states leading to an increase in CO are hallmarked by tachycardia. Conversely, illnesses or injuries resulting in negative chronotropy (e.g., heart block, toxicity from beta-blockers or calcium channel blockers) tend to result in more profound shock and hypoperfusion in children than in adults with similar processes. Bradycardia with hypoperfusion (without pulselessness) is a very common hemodynamic state for critically ill children during the prearrest phase.Neonatal resuscitation algorithms have recommended escalation of respiratory and cardiac support for the neonate whose heart rate is less than 60 beats/min, including the provision of chest compressions if bradycardia does not resolve with effective ventilation and oxygenation.

An analysis of the Star*D trial pointed out that approximately 25% of patients nonresponsive to citalopram may benefit from switching not only to bupropion or venlafaxine but also to sertraline.Whereas most guidelines recommend a switch to an antidepressant with another mode of action, this is not necessarily true.As described below, several pharmacological treatment strategies are suitable to deal with treatment refractoriness, including increase of dosage, switch to an antidepressant of the same class, switch to an antidepressant of another class, combination therapies with more than one antidepressant, and pharmacological and nonpharmacological augmentation strategies. However, it is impossible to predict the most effective treatment strategy for an individual patient. Strategies to enhance therapeutic effectiveness such as lithium augmentation or augmentation using thyroid hormones or other medications, for example antipsychotics or mood stabilizers, are described below. Nevertheless, in case of further nonresponse the use of ECT may be clinically more effective than all of these strategies and is still the method of choice for treatment-resistant depression, although not all of these patients will respond to ECT. _Psychopharmacological strategies in case of nonresponsiveness to antidepressant treatments_ Dose escalation strategies Before switching antidepressants, sufficient length of treatment and the adequacy of dosage should be considered. If in doubt, therapeutic drug monitoring may help ensure adequate blood levels of medication. A systematic review of whether dose escalation may lead to additional benefit after a medium-dose treatment fails revealed some evidence that this may be true for TCA, but there is no evidence for SSRIs. When the previous monotherapy was not efficacious at all, even at maximum dosage, the question arose as to which medication to test next. Whereas most guidelines recommend a switch to an antidepressant with another mode of action, this is not necessarily true. An analysis of the Star*D trial pointed out that approximately 25% of patients nonresponsive to citalopram may benefit from switching not only to bupropion or venlafaxine but also to sertraline.**Figure 26-1** _A step-wise approach to management of patients with inadequate response to antidepressant therapy._ General introduction to combination and augmentation With a partial response it may often be unwise to discontinue the medication and risk a worsening of symptoms.

Most surgeons prefer the standing position.Dental extraction can be performed with the surgeon sitting or standing.### Surgeon's Position The optimal position is when both patient and surgeon are comfortable (Figs 8.10, 8.11 and 8.12).The surgeon is in a sitting position for an extraction from the mandible.There are various local anesthetics in use. They can be used with or without vasoconstrictor. They differ in their concentration, and duration of anesthesia. Each local anesthetic has a recommended maximum dose to ensure safety of the patient and this must always be considered, especially when administering in very old or young patients. ## Preparation for Extraction To prevent injury or transmission of disease to their patients, themselves, and their assisting staff the surgeons should wear surgical gloves, surgical masks, gowns, surgical caps, and glasses or eye screens with side shields even for simple extractions (Figs 8.10, 8.11 and 8.12). For the patient, a sterile draping over the neck and chest is recommended. Preoperative mouthrinse with antiseptic, such as chlorhexidine, can be used to reduce the number of microorganisms at the surgical site. Fig. 8.10 Surgeon with proper clinical attire: gloves, mask, cap, and protective eye shield. Patient with sterile drape across the chest and a cap. The surgeon is in a standing position for extracting maxillary anterior teeth. Fig. 8.11 Surgeon with proper clinical attire: gloves, mask, cap, and protective eye glasses. Patient with sterile drape across the chest and a cap. The surgeon is in a standing position for an extraction from the maxilla. Fig. 8.12 Surgeon with proper clinical attire: gloves, mask, cap, and protective eye shield. Patient with sterile drape across the chest and a cap. The surgeon is in a sitting position with the patient lowered as low as possible so the mouth is level with the surgeon's elbow. The surgeon is in a sitting position for an extraction from the mandible. ### Surgeon's Position The optimal position is when both patient and surgeon are comfortable (Figs 8.10, 8.11 and 8.12). Dental extraction can be performed with the surgeon sitting or standing. Most surgeons prefer the standing position.The patient's chair should be tilted backwards.The correct position allows the surgeon to provide stability and support and to enable a controlled force on the extraction forceps delivered from the arm and shoulder without engaging the wrist.When extracting teeth in the maxilla, the surgeon should stand in front or by the side of the patient.

Initially, most people with such a blockage vomit and feel an urgent need to have a bowel movement.Superior Mesenteric Artery: Sudden, complete blockage of the superior mesenteric artery is a medical emergency.Less than 5% of people with high blood pressure have renovascular hypertension.In some people who have had predictable, stable claudication, claudication can suddenly worsen. For example, calf pain that occurs after walking 10 blocks may suddenly occur after walking one block. This change may indicate that a new clot has formed in a leg artery. Such people should be evaluated by a specialist as soon as possible. Lower Aorta and Common Iliac Arteries: Sudden blockage of the lower aorta where it divides into the common iliac arteries causes both legs to suddenly become painful, pale, and cold. No pulse can be felt in the legs, which may become numb. Gradual narrowing of the lower aorta or of both common iliac arteries can cause intermittent claudication that affects the buttocks and thighs of both legs. The legs may also feel cold or appear pale, although they usually appear normal. This combination of symptoms is sometimes called Leriche syndrome. Leriche syndrome usually occurs in men and commonly also causes erectile dysfunction. Renal Arteries: Sudden, complete blockage of one of the renal arteries, which supply the kidneys, may cause a sudden pain in the side, and the urine may become bloody. These symptoms indicate a medical emergency. Gradual, moderate narrowing of one or both renal arteries may not cause symptoms or affect kidney function. Rarely, more complete narrowing of one or both renal arteries contributes to the development of kidney failure or high blood pressure (a disorder called renovascular hypertension). Less than 5% of people with high blood pressure have renovascular hypertension. Superior Mesenteric Artery: Sudden, complete blockage of the superior mesenteric artery is a medical emergency. Initially, most people with such a blockage vomit and feel an urgent need to have a bowel movement.The abdomen may feel tender when a doctor presses on it, but the severe abdominal pain is usually more prominent than the tenderness, which is widespread and vague.The abdomen may be slightly swollen (distended).Through a stethoscope, a doctor initially hears fewer bowel sounds in the abdomen than normal.Later, no bowel sounds can be heard.

Most of the interventions recommended for this purpose are known to reduce cancer morbidity and mortality.**Recommendations for High-Risk Individuals** The ultimate goal of risk assessment and predictive testing is to reduce the morbidity and mortality of cancer in high-risk families.• Will the information gained allow me to consider medical options that are not available or relevant now? Mrs. H wanted to proceed with the testing for the benefit of her children and her unaffected sister, nieces, and nephews. **After the Results** For someone with a history of cancer, receiving a positive result may have different implications than for a family member without such a history. When informed that her test result identified a gene mutation, Mrs. H said she was relieved there would be a better chance for early identification of cancers in the next generation and also talked of her fears for her children who may have received the mutation from her. She then made plans for informing her family. Genetic counseling includes working toward the best possible adjustment to each situation. For the genetic counselor, this aspect of the counseling process may include providing a supportive presence when times are difficult, helping to negotiate and resolve diverse opinions within a family, and providing referrals to social workers, psychologists, or support groups. For the patient, it may mean an explanation for the personal and family history, and assistance with understanding and coming to grips with the implications of the test result. For others, there may not be an answer, but by working together, there may be additional testing or new information that will provide answers for these other high-risk families in the future. **Recommendations for High-Risk Individuals** The ultimate goal of risk assessment and predictive testing is to reduce the morbidity and mortality of cancer in high-risk families. Most of the interventions recommended for this purpose are known to reduce cancer morbidity and mortality.**HBOC** The current breast cancer screening recommendations for females at risk or known to have a BRCA1 or BRCA2 mutation include breast self-examination every month starting in the late teens and clinical breast examination by a health care provider twice a year.

Relapse has been reported in approximately 1 % of patients after 5 years [279, 290, 296].For other tumors of the head and neck, the 5-year survival is about 75 %.For patients with orbit tumors and clinical group I (completely excised) head and neck tumors, the 5-year survival is >85 % [279, 290, 296].In clinical group III, IRS-IV recommends patient with gross residual disease receive 50.4 Gy except in orbital RMS in which 45 Gy is recommended. Patients with parameningeal tumors do benefit from higher radiation doses so the current recommendation is 50.4+ Gy to the site of the tumor with 2 cm margins of normal tissue [302, 304, 305]. Intracranial extension, cranial bone erosion, and/or cranial nerve palsy do not require whole-brain irradiation or intrathecal therapy, though tumor cells in CSF are indications for additional therapy [305]. Intraparenchymal brain metastases may be treated with CNS RT in addition to chemoradiation directed at the primary tumor. Though tumor cells in CSF may signify metastasis, it does not necessarily mean the patient is not treatable. Raney et al. noted that patient without other signs of metastasis were alive 6–16 years after diagnosis [306]. Intracranial extension should receive prompt radiation for delay is associated with worse outcomes [302]. After receiving therapy, patients are reimaged and if residual tumor is noted, resection needs to be entertained. Resection may be a first attempt at an oncologic resection or a second-look operation to confirm/evaluate response and to completely resection disease without loss of function. For patients with metastatic disease chemoradiation is recommended for the primary and metastatic tumors with organ preservation [307] IMRT or fractionated stereotactic radiation therapy and chemotherapy has been used in patients with rhabdomyosarcoma of the head and neck with good results [308–310]. For patients with orbit tumors and clinical group I (completely excised) head and neck tumors, the 5-year survival is >85 % [279, 290, 296]. For other tumors of the head and neck, the 5-year survival is about 75 %. Relapse has been reported in approximately 1 % of patients after 5 years [279, 290, 296].The treatment for recurrent RMS is again chemotherapy, radiation, and surgical resection is possible.There are no clear guidelines on chemotherapeutic regimens and radiation dosing in patients with recurrent rhabdomyosarcoma, but suggestions include vincristine, dactinomycin, and cyclophophamide and also possibly doxorubicin, ifosfamide and etoposide, mesna and actinomycin D [311–316].

36.3).Conversely, for a posterior mediastinal lesion, the patient should be positioned approximately 30° prone, which allows the lung to fall anterior and improve exposure to the posterior mediastinum (Fig.Following lung collapse, the lung should fall more posteriorly and improve visualization of the anterior mediastinum.Therefore, if a thoracoscopic operation is planned for a younger patient and collapse of the ipsilateral lung is important, other modalities should be considered to effect collapse of the ipsilateral lung. If the patient is undergoing a left thoracoscopic operation, a relatively easy technique is to place an uncuffed endotracheal tube into the right main stem bronchus, which usually allows minimal ventilation into the left lung. If a right thoracoscopy is needed, it is sometimes possible to position an uncuffed endotracheal tube down the left main stem bronchus, although this is not as easy as on the right side. A bronchial blocker can also be introduced down the right main stem bronchus with the endotracheal tube positioned in the trachea to collapse the right lung. Positive pressure insufflation is a useful technique to create working space in the thoracic cavity. Most surgeons who perform thoracoscopic procedures frequently now use valve cannulas and positive pressure insufflation to effect lung collapse. An insufflation pressure of 6–8 torr usually will result in good parenchymal collapse in most patients. Also, positive pressure helps augment the initial lung collapse if endobronchial blockade is being employed. An important consideration for a thoracoscopic operation is patient positioning. By positioning the patient on the operating room table in different positions, the surgeon can take advantage of gravity to improve visualization. For an anterior mediastinal lesion, the patient should be placed about 30° supine with a roll under the ipsilateral side. Following lung collapse, the lung should fall more posteriorly and improve visualization of the anterior mediastinum. Conversely, for a posterior mediastinal lesion, the patient should be positioned approximately 30° prone, which allows the lung to fall anterior and improve exposure to the posterior mediastinum (Fig. 36.3).For a lesion on the diaphragm which requires evaluation for possible biopsy or excision, the patient should be positioned more in a reverse Trendelenburg position to allow the lung to fall away from the diaphragm.Conversely, for a lesion in the apex of the thoracic cavity, the table can be placed more in a head-up position to promote the lung falling more caudal and away from the target area.

Can you compartmentalize the stressors?Do you obsess over situations?Do you overreact to situations because that's the way you grew up?Dr. Z's Tips to Control Stress How do you deal with stressors?Although her diet was pretty good, we redesigned it to fit her lifestyle better. To control the cortisol and get her body to release glucagon, we increased her protein intake to three or four servings a day. She replaced less desirable carbs with high-fiber carbs that didn't spike her blood sugar. Next, she ate before exercising and right after to replenish her energy—keeping her cortisol under control. Finally, she decreased the time she spent exercising and increased the intensity for shorter periods. As a result, Susan was able to control her cortisol and increase her glucagon levels. In eight weeks she dropped 17 pounds of body fat, had more energy, and started to get a good night's sleep. Her shoulder pain and lower back pain were caused by unresolved muscle imbalances that required joint manipulation and therapeutic exercises. In less than four weeks, she was 90 percent symptom-free, and she canceled the unneeded surgery. * * * Stress and Autoimmune Disease Psychological stressors are also implicated in the development of autoimmune disease. In fact, a study in _Autoimmunity Reviews_ states that up to 80 percent of those who developed an autoimmune disease reported having uncommon emotional stress beforehand. It is presumed the surge of cortisol, adrenaline, and norepinephrine lead to immune dysregulation and increased cytokine production, resulting in autoimmune disease. The stress response has also been known to cause an imbalance of inflammatory and anti-inflammatory cytokines. Cortisol, adrenaline, and norepinephrine have been shown to alter the balance between Th1 and Th2 white blood cells and their specific cytokines, tipping the immune response from defense to attacking one's own body— autoimmune disease. Dr. Z's Tips to Control Stress How do you deal with stressors? Do you overreact to situations because that's the way you grew up? Do you obsess over situations? Can you compartmentalize the stressors?The best way of dealing with stress is to manage it as it occurs.Try these methods to prevent the health issues associated with long-term stress.**CHANGE YOUR PERCEPTION.** Life is filled with frustration, pain, disappointments, and unpredictable actions of others.You can't change this endless loop, but you can change your perception of the stressor.

The intensity of infant crying may thus be regulated by contextual cues representing the relative risk or benefit of the behavior present at that time.Two other more complex forms of infant crying (maternal potentiation and inhibition by unfamiliar male scent) are described as adaptations within a set of opposing evolutionary selection pressures.Summary and perspective I have approached infant crying as an evolving trait. From classic studies of the larynx, the organ of crying, we find that while the larynx developed initially to regulate airflow, its structure became more complex as a mechanism in mammals to stabilize the thorax for upper arm movement, rather than to facilitate vocalization. In our experiments, we have found an unexpected adaptation still present today, hypothermic vocalization, in which the laryngeal–thoracic act of calling itself functions to maintain intra-thoracic pressure and avoid pulmonary edema as rat pups warm after severe hypothermia. Crying in a communicative role appears to have been the most recent evolutionary step. Yet, even in a relatively simple mammal such as the laboratory rat, it is a highly-regulated response that is controlled by many different environmental and social signals, cues that connect crying with the risks and benefits of this behavior in the environments within which mammals evolved. Recent research is beginning to elucidate the neurochemical pathways by which ultrasonic infant calling responses are transduced in the brain of the infant, and to shed new light on the nature of the emotional state underlying the infant's vocal response to isolation, one that appears to be highly similar to human anxiety. Two other more complex forms of infant crying (maternal potentiation and inhibition by unfamiliar male scent) are described as adaptations within a set of opposing evolutionary selection pressures. The intensity of infant crying may thus be regulated by contextual cues representing the relative risk or benefit of the behavior present at that time.#### Acknowledgments The work described in this chapter was supported by project grants and a Research Scientist Award from NIMH, and by the Sackler Institute for Developmental Psychobiology at Columbia University.My colleagues Harry Shair and Susan Brunelli played crucial roles in carrying out and interpreting the results of the research.

• Should my family members be examined?• Will I need radioactive iodine?• Why do I need to take thyroid hormone after surgery?• What is the chance of complications of surgery, especially damage to the parathyroid glands and the risk of nerve malfunction?**The Most Important Questions You Can Ask** • How extensive should my surgery be?After the thyroid gland is removed and thyroid hormone is stopped for an appropriate time, a tracer dose of radioactive iodine is given. If hot spots appear at sites outside the thyroid area, suggesting metastases, a therapeutic dose of radioactive iodine is given. Radioactive iodine effectively irradiates microscopic metastases. Larger metastases should be removed surgically before radioactive iodine is given. If the thyroglobulin level is detectable or elevated after a total thyroidectomy, residual tumor is present. • External-beam radiation is used in patients whose tumors do not take up radioactive iodine or are undifferentiated. • Some patients respond to chemotherapy, with regimens containing doxorubicin (Adriamycin) having the highest response rate. The combination of cisplatin (Platinol) and doxorubicin may produce some complete and partial remissions in metastatic thyroid cancer. In a few cases, the complete responders survived more than two years. Another combination (doxorubicin + bleomycin [Blenoxane] + vincristine [Oncovin] + melphalan [Alkeran]) was reported to show responses in about one-third of patients. Paclitaxel (Taxol) has been used in some protocols. • In patients with anaplastic thyroid cancer, chemotherapy is occasionally effective and is usually combined with external-beam radiation. • Patients with metastatic thyroid carcinoma, especially those unsuitable for or unresponsive to radioactive iodine, should be considered for entry into clinical trials in the hope of finding a more effective chemotherapy program. New trials became available in 2006 for patients with various types of thyroid cancer. **The Most Important Questions You Can Ask** • How extensive should my surgery be? • What is the chance of complications of surgery, especially damage to the parathyroid glands and the risk of nerve malfunction? • Why do I need to take thyroid hormone after surgery? • Will I need radioactive iodine? • Should my family members be examined?• What is my chance of cure, and when can you be sure?Trophoblastic Disease _Jeffrey L. Stern, M.D._ Gestational trophoblastic diseases (GTD) are disorders of abnormal growth of the placenta.They are always associated with a pregnancy.A key to understanding and managing patients with GTD is human chorionic gonadotropin (HCG), a protein hormone produced by the placenta.

**primary prevention** Strategies used to avoid or delay the actual occurrence of a specific disease.Because the fluid cannot leave the eye at the same rate it is produced, intraocular pressure gradually increases.**primary open-angle glaucoma (POAG)** The most common form of primary glaucoma; characterized by reduced outflow of aqueous humor through the chamber angle.**pretibial myxedema** Dry, waxy swelling of the front surfaces of the lower legs. **preventive therapy drugs** For asthma, drugs that are used every day regardless of symptoms to change airway responsiveness and prevent asthma attacks from occurring. **priapism** An abnormal, long-maintained erection without sexual desire, which causes the penis to become large, hard, and painful. It can occur from neural, vascular, or pharmacologic causes. **primary angle-closure glaucoma** A form of glaucoma characterized by a narrowed angle and forward displacement of the iris so that movement of the iris against the cornea narrows or closes the chamber angle, obstructing the outflow of aqueous humor. It can have a sudden onset and is an emergency; also called "closed-angle glaucoma," "narrow-angle glaucoma," or "acute glaucoma." **primary arthroplasty** A total joint arthroplasty procedure that has been performed for the first time. **primary epilepsy** Epilepsy that is not associated with any identifiable brain lesion or other specific cause; however, genetic factors most likely play a role in its development. **primary gout** The most common type of gout; results from one of several inborn errors of purine metabolism. **primary lesions** In describing skin disease, the initial reaction to a problem that alters one of the structural components of the skin. **primary open-angle glaucoma (POAG)** The most common form of primary glaucoma; characterized by reduced outflow of aqueous humor through the chamber angle. Because the fluid cannot leave the eye at the same rate it is produced, intraocular pressure gradually increases. **primary prevention** Strategies used to avoid or delay the actual occurrence of a specific disease.Patients with this type of MS are usually between 40 and 60 years of age at onset of the disease and experience progressive disability with no acute attacks.**primary survey** Priorities of care addressed in order of immediate threats to life as part of the initial assessment in the emergency department.

Moreover, their sensitivity is low in the initial stages of fibrosis.It should be noted that these markers are not exclusively found in liver tissue; therefore, they reflect fibrogenic processes in various other organs and their diagnostic value become questionable in aging patients with comorbidities such as atherosclerosis and chronic lung disorders.The NILTs can be broadly divided into three categories: simple or indirect serum markers, direct serum markers, and imaging modalities [4]. Indirect serum markers or class II biomarkers consist of the combination of routine biochemical tests, such as transaminases, platelet count and albumin, and patient demographics that are associated with fibrosis, such as age or the presence of diabetes [4]. These tests usually have dual cutoffs: a high cutoff with high specificity and a low cutoff with high sensitivity. Depending on the clinical scenario and the disease prevalence, the low or high cutoff is used at the expense of increased false positives and false negatives, respectively. If these cutoffs are combined, then the numbers of false positives and false negatives are minimized. However, a number of patients will fall in the indeterminate range of fibrosis (i.e., their score will be between the low and the high cutoff) and will need either further noninvasive testing or liver biopsy. Direct serum noninvasive tests (class I biomarkers) are supposed to detect extracellular matrix turnover and/or fibrogenic cell changes [4]. The most common markers used in current assays involve measuring products of extracellular matrix synthesis or degradation and the enzymes that regulate their production or modification, such as hyaluronic acid, serum collagenases and their inhibitors, and profibrogenic cytokines. It should be noted that these markers are not exclusively found in liver tissue; therefore, they reflect fibrogenic processes in various other organs and their diagnostic value become questionable in aging patients with comorbidities such as atherosclerosis and chronic lung disorders. Moreover, their sensitivity is low in the initial stages of fibrosis.In the case of NAFLD, these are FibroTest, ELF, and FibroMeters.Among them, FibroTest (FibroSure in the United States) is the most widely validated panel: it consists of five parameters and has been studied in viral hepatitis, NAFLD, and alcohol-related liver disease (ALD) [6].

### How to use It's best to get your vitamin C from food.Supplements are available in health food stores, pharmacies and supermarkets.Where to find Buy vitamin C-packed fruit and vegetables in supermarkets.These symptoms normally disappear once a normal intake of the vitamin is resumed.Vitamin B12 is generally available as a tablet or capsule. Follow label instructions or take as professionally prescribed. ## VITAMIN C use for ✓ Allergies ✓ Colds and flu ✓ Cuts and scrapes ✓ Shingles ✓ Skin rashes ✓ Stroke prevention VITAMIN C, ALSO KNOWN AS ASCORBIC acid, is vital for growth and development. The body is not able to make vitamin C—and cannot store it—but a well-balanced diet should contain plenty of the nutrient. Fruit and vegetables are good sources of the vitamin. In addition, some cereals and drinks are fortified with vitamin C. Raw or uncooked foods are the best source of the vitamin, the levels of which decline if foods are cooked or stored for long periods. Groups of people most at risk of a vitamin C deficiency include smokers—smoking affects the absorption of the nutrient—older people with a less varied diet, people with medical conditions that affect digestion and absorption and those on a poor diet. * * * ### How it works Vitamin C is the body's primary water-soluble antioxidant, helping to protect cells from the effects of free radicals, the unstable molecules that damage cells, triggering dangerous mutations. The vitamin is needed to make collagen, the main structural protein in the body's various connective tissues. This gives it an important part to play in wound healing, repairing cuts and scrapes and preventing bruising. Safety first Taking large amounts of vitamin C—more than 2000 mg/day—could cause stomach pain, diarrhea and flatulence. These symptoms normally disappear once a normal intake of the vitamin is resumed. Where to find Buy vitamin C-packed fruit and vegetables in supermarkets. Supplements are available in health food stores, pharmacies and supermarkets. ### How to use It's best to get your vitamin C from food.Good sources include all types of fresh fruits and vegetables.Long considered a remedy for the common cold and flu, research suggests that while vitamin C won't prevent you from catching a bug, it can alleviate symptoms and shorten the duration of the illness.Its antiviral properties augment the body's immune system so it can help to treat viral syndromes such as shingles.

_Lewy bodies_ (eosinophilic cytoplasmic inclusions) → composed of alpha-synuclein (normally found in unfolded form, but in Lewy bodies, high concentrations aggregate as filaments) and ubiquitin.Loss of pigmented neurons in substantia nigra & other pigment nuclei (more widespread pathology identified)._Tx_ : Stop offending agent (may take a long time in pts receiving chronic antipsychotics), largely supportive tx (cardiac monitoring, ICU admission, mech ventilation, electrolyte monitoring, IV fluids, cooling blanket, Tylenol), cons dantrolene (start 1 mg/kg IV, up to 10 mg/kg/d in divided doses; watch for hepatotoxicity & CHF), bromocriptine (2.5–10 mg IV or PO q4–6 h), amantadine (100–300 mg PO bid), Sinemet (25/250 PO tid/qid). _Other side effects_ (see Mvmt d/o chapter). **Anxiolytics** (benzodiazepines [w/ the exception of BuSpar]): _Important side effects_ : short-acting benzos can lead to rebound anxiety, respiratory depress, hypotension, teratogenicity in first trimester. _Mechanism_ : stimulate GABA-A receptors. See _Toxin_ chapter for discussion of overdose & w/d. # MOVEMENT DISORDERS # HYPOKINETIC MOVEMENT DISORDERS # Parkinson Disease (PD) **Introduction:** Most common neurodegenerative mvt d/o affecting ~1% of people >60. Men:Women 3:2 predominance (unclear why), mean onset 60 yo (range: 40–70). Course variable. Primarily sporadic dz, but several familial forms identified. To date, 18 genes identified that can cause early-onset (<40) familial dz or late-onset familial dz or predispose to sporadic dz. Routine genetic screening not recommended. **Pathophysiology:** _Pathologic hallmark_ : Degeneration of dopaminergic nigrostriatal projection neurons. Loss of pigmented neurons in substantia nigra & other pigment nuclei (more widespread pathology identified). _Lewy bodies_ (eosinophilic cytoplasmic inclusions) → composed of alpha-synuclein (normally found in unfolded form, but in Lewy bodies, high concentrations aggregate as filaments) and ubiquitin.Features pointing to an alternate dx are early (<3 yr) prominent instability/falls, early (<3 yr) freezing, early (<3 yr) hallucinations, dementia preceding motor symptoms or in 1st yr; supranuclear gaze palsy; symptomatic dysautonomia; documented condition known to cause parkinsonism, e.g., drugs.Definite dx only w/ autopsy.

If there is a metabolic acidosis calculate an anion gap and delta ratio.If both disturbances occur in the same direction, correct each for each other to demonstrate independence.If the primary disturbance is respiratory, correct the HCO3- for the CO2.If the primary disturbance is metabolic, correct the CO2 for the HCO3-.Correct the dependent variable for the major disturbance.Candidates should note the observations given in this case: * HR: 135 /min * BP: 82/45 mmHg * RR: 39 /min * Sats: 88% (15L NRB) * T: 36.8 oC This patient is clearly peri-arrest, and could reasonably be expected to have systemic underperfusion manifesting as a lactic acidosis. Systemic working will reveal the two independent processes occurring, namely respiratory acidosis with a massive A-a gradient and a RAGMA, but the key here is to show perspective. The patient is critically ill, and there are multiple indications given for consideration of thrombolytic therapy[44]. The role of echocardiography in urgent assessment has long been established[45] and strong candidates will mention this as an important risk stratification tool. The importance of excluding other causes of obstructive shock prior to any intervention should also be made clear. * * * [44] Goldhaber SZ. Modern treatment of pulmonary embolism. Eur Respir J 2003; Suppl 35:22s [45] Come PC. Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions. Chest 1992; 101:151s ## Acid base balance Comment on the pH: acidaemia, alkalaemia Comment on the CO2: hyper/hypocarbia, respiratory acidosis/alkalosis. Comment on the bicarbonate: high/low, metabolic acidosis/alkalosis. Decide on the major disturbance. This always is in the same direction as the pH. Correct the dependent variable for the major disturbance. If the primary disturbance is metabolic, correct the CO2 for the HCO3-. If the primary disturbance is respiratory, correct the HCO3- for the CO2. If both disturbances occur in the same direction, correct each for each other to demonstrate independence. If there is a metabolic acidosis calculate an anion gap and delta ratio.In clinical practice having a simple summary of the major acid-base disturbance established before the interpretation of the rest of the results is key to understanding the implications of your test.## PROBLEM 17 A 3 year old boy presents with his parents after ingesting an unknown amount of iron tablets earlier in the day.He is vomiting profusely.His venous blood gas is shown below.

Infection with cytomegalovirus (CMV), a herpes-virus, is very common.Often, no treatment is required, but if the infection is severe, antiviral drugs may be used.Doctors may diagnose the infection by culturing a sample of infected body fluid, such as urine.Finding many characteristic mononuclear white blood cells (atypical lymphocytes) may be the first clue that the diagnosis is infectious mononucleosis. Treatment There is no specific treatment. People with infectious mononucleosis may be as active as they want. However, because of the risk of rupturing the spleen, heavy lifting and contact sports should be avoided for 1 month, even if the spleen is not noticeably enlarged. Before such activities are resumed, doctors may wish to confirm that the spleen has returned to normal size. Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin or ibuprofen) can relieve fever and pain. However, aspirin should not be given to children because of the risk of Reye's syndrome, which can be fatal. Some complications, such as severe swelling of the airways, may be treated with corticosteroids. Currently available antiviral drugs have little effect on the symptoms of infectious mononucleosis and should not be used. Cytomegalovirus Infection Cytomegalovirus infection is a common herpesvirus infection with a wide range of symptoms: from no symptoms to fever and fatigue (resembling infectious mononucleosis) to severe symptoms involving the eyes, brain, or other internal organs. This virus is easily spread through sexual and nonsexual contact with body secretions. Most people have no symptoms, but some feel ill and have a fever, and people with a weakened immune system or an infected fetus can have serious symptoms, including blindness. Doctors may diagnose the infection by culturing a sample of infected body fluid, such as urine. Often, no treatment is required, but if the infection is severe, antiviral drugs may be used. Infection with cytomegalovirus (CMV), a herpes-virus, is very common.Usually, this infection causes no symptoms.Serious infections typically develop only in infants infected before birth (see Some Infections of Newborns) and in people with a weakened immune system—for example, people with AIDS or those who have received an organ transplant.

_Source_ : Brodaty, H et al.**Table 37.1** Comparison of different tests of cognitive function.For instance, someone who has never been able to read very well or do mental arithmetic may never have been able to score full marks, whereas for someone who used to be a barrister, a loss of any point on the MMSE may be significant.The patient's ability to draw a clockface and indicate the time on it is a particularly informative part of these two tests. Figure 37.1 shows an attempt by a patient with dementia to draw a clockface showing the time at half past four. **Figure 37.1** Attempt by a patient to draw a clockface showing the time at half past four. The longer and best known test of cognitive function is the Mini-Mental State Examination (MMSE), also known as the Folstein test. This has been used for long time both in general practice and in hospitals, but it is now under patent, and as a result many clinicians in the UK have started using other tests, such as the Montreal Cognitive Assessment (MoCA) or the Addenbrooke's Cognitive Examination (ACE)-III. The value of all three of these tests is that they have subsections which test different aspects of cognitive function, such as orientation, attention, language, visuospatial memory, execution, registration and recall. The total scores of the MMSE, MOCA and ACE-III provide a rough gauge for describing the severity of someone's dementia, and they are useful for monitoring the progression of dementia. However, a lot of information comes from the way in which patients answer each question, so it is important to record each answer in full, not just note it as being correct or incorrect. The disadvantage of these tests is that they take much more time to complete than the GPCOG, so they are not so useful as screening tests in primary care. Table 37.1 compares the different tests. All of them need to be interpreted in the light of the individual's baseline IQ and level of functioning. For instance, someone who has never been able to read very well or do mental arithmetic may never have been able to score full marks, whereas for someone who used to be a barrister, a loss of any point on the MMSE may be significant. **Table 37.1** Comparison of different tests of cognitive function. _Source_ : Brodaty, H et al.Reproduced with permission of John Wiley & Sons.

* Papillomavirus infection may progress to bowenoid in situ carcinoma.* Dependent upon the causal virus, animals may self-cure.* Systemic signs may eventually develop as a result of viral infection.POSSIBLE COMPLICATIONS Bacteremia and septicemia EXPECTED COURSE AND PROGNOSIS * Skin lesions may not respond to therapy.* Dogs—zinc deficiency syndromes, hepatocutaneous syndrome, nasal hyperkeratosis. * Neoplasia—with extensive crusting and ulceration, consider mast cell tumors and epitheliotropic lymphoma. CBC/BIOCHEMISTRY/URINALYSIS Normal OTHER LABORATORY TESTS * Skin biopsy—necessary to prove the skin lesions are viral in origin. * Virus isolation. * Serology—confirms FeLV, FIV, or other viral infection. IMAGING N/A DIAGNOSTIC PROCEDURES * Skin scrapings and trichograms—parasitic infestations. * Dermatophyte culture—fungal infections. * Epidermal cytology—bacterial folliculitis. * Skin biopsy is the definitive diagnostic test. * Immunohistochemical staining for viral particles. * Viral serology. PATHOLOGIC FINDINGS * Hyperplasia. * Ballooning degeneration. * Hydropic interface dermatitis. * Syncytial-type giant cell formation within the epidermis and/or outer root sheath of the hair follicle. * Keratinocyte inclusion bodies. TREATMENT * Usually outpatient, except for systemically ill patients. * Prevent exposure to other animals that could become infected. MEDICATIONS DRUG(S) OF CHOICE * Supportive care and treatment of secondary infections. * Cats—herpesvirus: L-lysine 200–500 mg/cat q12h; interferon-α 30 units/cat/day orally. * Cats—bowenoid in situ carcinoma: topical imiquimod. * Dogs—papilloma virus; interferon-α 1.5 MU subcutaneously three times weekly reported. CONTRAINDICATIONS Corticosteroids or other therapies causing immunosuppression. FOLLOW-UP PREVENTION/AVOIDANCE Prevent hunting behavior and exposure to potentially infectious materials and infected animals. POSSIBLE COMPLICATIONS Bacteremia and septicemia EXPECTED COURSE AND PROGNOSIS * Skin lesions may not respond to therapy. * Systemic signs may eventually develop as a result of viral infection. * Dependent upon the causal virus, animals may self-cure. * Papillomavirus infection may progress to bowenoid in situ carcinoma.SEE ALSO * Papillomatosis * Upper respiratory diseases—cats * Viral infections—cats * Viral infections—dogs ABBREVIATIONS * FeLV = feline leukemia virus * FIV = feline immunodeficiency virus Suggested Reading Scott DW, Miller WH, Griffin CE.Muller & Kirk's Small Animal Dermatology, 6th ed.Philadelphia Saunders, 2001.

When Will I Have Energy Again?16 Why Am I So Exhausted?If friends and family members do want to donate blood as a sign of support, they can do so at a blood bank, knowing that they may be saving someone else's life.But there are other proteins of lesser importance that are present on the surface of red blood cells. An allergic reaction happens when your body is incompatible with one or more of these lesser proteins and your immune system attacks the red blood cells. In rare instances, this reaction can cause lung injury or other complications. That's why your doctors and nurses will be monitoring your reaction to the transfusion as it happens and for several days afterward, looking for any signs of an adverse reaction. At the first sign of a problem, they will stop the transfusion and treat you for the reaction. Even if this happens, most patients fully recover. Some people ask whether they can have a friend or family member donate blood to limit the risks of an adverse reaction or infection. You can do this, but there is no evidence that these donations are safer than pooled volunteer donations. In fact, some hospitals discourage these direct donations, however heartfelt, because of the time and effort required to test the blood after it has been collected. All donations, regardless of source, must be screened for infections, including HIV and hepatitis, before they can be used. And donors have to go through the same screening process and questionnaire that they would at a blood bank, and they may have to submit to this process more than once. While friends and family may say that they are eager to help, most doctors have found that this process introduces delays and stress into a situation that is already emotionally fraught. If friends and family members do want to donate blood as a sign of support, they can do so at a blood bank, knowing that they may be saving someone else's life. 16 Why Am I So Exhausted? When Will I Have Energy Again?Cancer fatigue is not like any kind of exhaustion that you've experienced before.It might not improve much with rest or a good night's sleep.In fact, some patients refer to fatigue as an unwanted partner in treatment and complain that this more than anything makes them feel isolated from family and from the life they used to lead.

Within macrophages or giant cells, C. immitis is present as thick-walled, nonbudding spherules 20 to 60 µm in diameter, often filled with small endospores.Morphology The primary and secondary lung lesions of C. immitis are similar to the granulomatous lesions of Histoplasma.It has a thick, double-contoured cell wall, and visible nuclei (Fig. 15-38). Involvement of the skin and larynx is associated with marked epithelial hyperplasia, which may be mistaken for squamous cell carcinoma. Figure 15-38 Blastomycosis. A, Rounded budding yeasts, larger than neutrophils, are present. Note the characteristic thick wall and nuclei (not seen in other fungi). B, Silver stain. #### Coccidioidomycosis Almost everyone who inhales the spores of Coccidioides immitis becomes infected and develops a delayed-type hypersensitivity reaction to the fungus. Indeed, more than 80% of people in endemic areas of the southwestern and western United States and in Mexico have a positive skin test reaction. One reason for the infectivity of C. immitis is that infective arthroconidia, when ingested by alveolar macrophages, block fusion of the phagosome and lysosome and so resist intracellular killing. As is the case with Histoplasma, most primary infections with C. immitis are asymptomatic, but 10% of infected people develop lung lesions, fever, cough, and pleuritic pains, accompanied by erythema nodosum or erythema multiforme (the San Joaquin Valley fever complex). Less than 1% of people develop disseminated C. immitis infection, which frequently involves the skin and meninges. Certain ethnic groups (e.g., Filipinos and African Americans) and the immunosuppressed are at particularly high risk for disseminated disease. Morphology The primary and secondary lung lesions of C. immitis are similar to the granulomatous lesions of Histoplasma. Within macrophages or giant cells, C. immitis is present as thick-walled, nonbudding spherules 20 to 60 µm in diameter, often filled with small endospores.15-39).Rare progressive C. immitis disease involves the lungs, meninges, skin, bones, adrenals, lymph nodes, spleen, or liver.At all these sites, the inflammatory response may be purely granulomatous, pyogenic, or mixed.Purulent lesions dominate in patients with diminished resistance and with widespread dissemination.Figure 15-39 Coccidioidomycosis.Intact and ruptured spherules are seen.

The habitual use of lablab-bean, black gram, _til_ preparations, irritant spicy food, and _kapha_ -producing diet may also be involved in development of the disease.2–5 In modern medicine the risk factors for asthma are classified under two categories: host factors and environmental factors.Cough and coryza have also been implicated as etiologic agents.The differences among various populations may be consequences of responses to environment, industrialization, or different allergen loads.1 Asthma may develop less frequently in children who are exposed to infections and parasitic infestations early in life.6,7 ### **13.3.2 Adults** The prevalence of asthma symptoms in adults varies from 1 to 25%.8–11 Similar symptoms from cardiac failure and chronic obstructive pulmonary disease make accurate estimates of asthma in older individuals difficult.8–11 Mortality data from developed countries show that the rates vary from 0.1 to 0.8 per 100,000 persons aged 5 to 34.12–14 ## **13.4 Etiology** According to Ayurveda, the general etiology of _svasa roga_ is that all things, materials, and conditions that could help increase _vata dosa_ and _kapha dosa_ are causally responsible for _tamaka svasa_. This develops from an increase in cough ( _kasa_ ), undigested materials ( _ama_ ), diarrhea, vomiting ( _vamathu_ ), poison ( _visa_ ), anemia ( _pandu_ ), and fever ( _jvara_ ); coming into contact with air containing dust, irritant gases, pollens, or smoke; injuring vital spots; using very cold water; and residing in cold and damp places.2–5 Excessive use of dry food and astringent food and irregular dietary habits may also trigger an attack. In addition, constipation, excessive fasting, excessive use of cold water, excessive sexual indulgence in adults, exposure to extremes of temperature, anxieties, grief, disturbance of peace of mind, and debility may all precipitate an attack. Cough and coryza have also been implicated as etiologic agents. The habitual use of lablab-bean, black gram, _til_ preparations, irritant spicy food, and _kapha_ -producing diet may also be involved in development of the disease.2–5 In modern medicine the risk factors for asthma are classified under two categories: host factors and environmental factors.Asthma can be considered to be a heritable disorder.15,16 More boys than girls develop asthma during childhood; this difference disappears by age 10.17,18 Subsequently, females are at greater risk for developing asthma.Environmental factors influence the susceptibility to developing asthma in predisposed individuals, precipitate asthma exacerbations, and cause persistence of asthma.

These were the foundation for herbal formulas, the ingredients of some of which in recent times have been found to have antibacterial and antiviral properties.Theories such as the Four Levels (Wen Bing) and Six Divisions (Shang Hun Lun) explained these diseases.Whilst infectious agents were not recognized, epidemic diseases were understood in terms of Invasion of Wind Heat or Heat Toxins.Measles, when caught in pregnancy, can lead to loss of the pregnancy, but not to fetal abnormalities. •Treatment: there is no direct treatment of the infection available. Measles in a healthy person generally requires only supportive treatment. However, if the patient is vulnerable because of immunodeficiency or malnutrition, or if neurological or respiratory signs develop, hospital admission and intravenous nutrition may be necessary. Information about infectious diseases structured under these five headings encapsulates the essential facts required for medical practitioners to understand how a disease will impact on the life of a patient. Awareness of these headings can help structure information for the purposes of the study of infectious diseases. Information box 2.4b-I Infectious disease: comments from a Chinese medicine perspective The concept of epidemic disease was well established in China from at least the 3rd century CE. It has been understood for centuries that certain diseases with contagious properties and manifesting with Heat symptoms could progress through deepening levels of the body with more serious consequences. These diseases no doubt included viral upper respiratory illnesses, and also more serious life-threatening diseases such as epidemic influenza, smallpox, plague, typhoid and typhus. These diseases were seen to be more likely to seriously afflict those who had Deficiency. For this reason, prevention by Nourishing Deficiency was fundamental to the management of epidemics. Whilst infectious agents were not recognized, epidemic diseases were understood in terms of Invasion of Wind Heat or Heat Toxins. Theories such as the Four Levels (Wen Bing) and Six Divisions (Shang Hun Lun) explained these diseases. These were the foundation for herbal formulas, the ingredients of some of which in recent times have been found to have antibacterial and antiviral properties.However, not all diseases that are described as infectious in conventional medicine will equate to these classically recognized epidemic warm diseases.To help us to describe conventionally described infectious diseases in Chinese medical terms, two important concepts need to be grasped.These are: •The origin of the Pathogenic Factor.

D) Rest and breathe in this position.C) Exhale, raising the trunk and crown of the head off the floor.The palms are on the ground, fingers facing the shoulders (hands are shoulder-width distance apart).B) Arms are raised over the head with elbows facing the sky.Soles of the feet are on the floor, and knees are together.Eventually you can rest your back on the floor. Benefits: These poses tone the spinal region, circulate blood around the spine, and stretch the pelvic region and lower back. The heart is massaged and healed; the diaphragm is lifted, and the chest is expanded. Kapha—diabetes, bronchitis; V yu—insomnia, rheumatoid arthritis, varicose veins, sciatica, reproductive organs, constipation, asthma, backache. Organs Helped: Reproductive, diaphragm, heart. _Do has: _All; especially VK- **Standing** **Bow** STANDING BOW Method: A) Stand erect, arms at sides; breathe easily. B) Bend elbows, bringing the palms together at the chest in prayer position C) Slowly raise the hands up over the head (the arms cover the ears). Notice the rhythm of your breathing. D) Inhale, slowly bending from the lower back; leaning backwards as far as is comfortable. Keep hands and arms in the same position at the head. E) Exhale, slowly bringing the upper torso upright. F) Slowly lower the "prayer hands" to the chest; then return the hands to the sides. Precaution: Extreme care is required; especially if persons have a bad back or neck. Benefits: This pose stretches the lower back and kidney area _Do has: _All ** rdhva Dhanur sana (Upward Bow)** RDHVA DHANUR SANA (UPWARD BOW) Method: _Advanced Beginner_ A) Lie on the back, bend knees. Soles of the feet are on the floor, and knees are together. B) Arms are raised over the head with elbows facing the sky. The palms are on the ground, fingers facing the shoulders (hands are shoulder-width distance apart). C) Exhale, raising the trunk and crown of the head off the floor. D) Rest and breathe in this position.Breathe naturally.F) Stretch the arms from the shoulders and the legs from the thighs.G) Eventually the elbows are straight and the thighs are stretched.H) Exhale and stretch some more, pulling the thigh muscles by lifting the heels off the floor.I) Extend the chest, stretching up the sacral region of the spine until the abdomen is taut; then lower the heels to the floor again.

Valerian is a safe muscle relaxant and can be used in muscle cramping, uterine cramps, and intestinal colic.For elders who do not need as much sleep as they once did, it also ensures that simply lying in bed becomes a restful and relaxing experience, one that can often be as revivifying as sleep itself.Never believe advertisements about herbs; question them instead. The claims may be true, but get the evidence and make up your own mind. The conditions that _Melaleuca_ is claimed to heal include sinusitis, the common cold, sinus blockage, laryngitis, coughs, canker sores, boils, cuts, bites, sunburn, miliaria, parasites, head lice, herpes simplex, herpes progenitalis, impetigo, psoriasis, infected seborrheic dermatitis, ringworm of the scalp, ringworm, athlete's foot, fungal infections of the nails, thrush, and trichomoniasis. _Preparation and Dosage:_ The oil is for external use, and for those with sensitive skin, it should be diluted with a bland fixed oil such as almond oil. Many products currently on the market contain the oil, including toothpastes, soaps, shampoos, and deodorants. **Valerian** _Valeriana officinalis_ _Part Used:_ Rhizome, stolons, and roots. _Actions:_ Nervine, hypnotic, antispasmodic, carminative, hypotensive, emmenagogue. _Indications:_ Valerian's main indications are anxiety, nervous sleeplessness, and the bodily symptoms of tension such as muscle cramping or indigestion. It may be used safely where tension and anxiety are present, whether the symptoms are purely psychological and behavioral or physical in nature. For some people valerian can be an effective mild pain reliever. As one of the best gentle herbal sleeping remedies, it promotes the natural process of slipping into sleep. For elders who do not need as much sleep as they once did, it also ensures that simply lying in bed becomes a restful and relaxing experience, one that can often be as revivifying as sleep itself. Valerian is a safe muscle relaxant and can be used in muscle cramping, uterine cramps, and intestinal colic.Its effect goes beyond simple nerve relaxation, as its constituents include mild hypotensives._Preparation and Dosage:_ To be effective valerian has to be used in sufficiently high dosage.The tincture dosage is from 2.5–5 milliliters (½–1 tsp) to as much as 10 milliliters in some cases (2 tsp).

Some children are also hyperactive.Attention-Deficit/Hyperactivity Disorder Attention-deficit/hyperactivity disorder (ADHD) is poor or short attention span and impulsiveness inappropriate for the child's age.These disorders may be mild and easily manageable with educational interventions, or they may be more severe and affected children may require more support.The outcome is usually better in children who are Younger Have smaller tumors Have a tumor that has not spread Even older children and children with widespread tumors have a very good prognosis. However, one type of Wilms' tumor (which accounts for less than 5% of cases) is more resistant to treatment. Children with this type of tumor, which is recognized by examining a sample of the tumor under a microscope, have a poorer prognosis. Treatment Doctors treat Wilms' tumor by removing the kidney that contains the tumor. During the operation, the other kidney is examined to determine whether it also has a tumor. After surgery, doctors give the child chemotherapy drugs—most commonly actinomycin D and vincristine. Other drugs such as doxorubicin, cyclophosphamide, and etoposide are sometimes used. Children with larger or widespread tumors are also treated with radiation therapy. Sometimes the tumor cannot be removed initially. In such cases, children are first treated with chemotherapy and radiation therapy to shrink the tumor. Then the tumor is removed. CHAPTER 284 Learning and Developmental Disorders Developmental disorders, including attention-deficit/ hyperactivity disorder, autism spectrum disorders, learning disabilities, and mental retardation/intellectual disability (see page 1858), are neurologically based conditions that can interfere with the acquisition, retention, or application of specific skills or sets of information. They may involve dysfunction in attention, memory, perception, language, problem-solving, or social interaction. These disorders may be mild and easily manageable with educational interventions, or they may be more severe and affected children may require more support. Attention-Deficit/Hyperactivity Disorder Attention-deficit/hyperactivity disorder (ADHD) is poor or short attention span and impulsiveness inappropriate for the child's age. Some children are also hyperactive.Affected children have difficulty with sustained attention, concentration, and ability to complete tasks, and some children are also overactive and impulsive.Doctors use questionnaires completed by parents and teachers as well as observations of the child to make the diagnosis.

In two recent studies, Pavlova et al.Different studies have attempted to explain the origin of native fluorescence in oral tissue.Without this filter, the image would be formed only by the scattered excitation photons, since this light–tissue interaction is much more intense than the induced native tissue fluorescence. Red–green–blue (RGB) images are obtained by placing a Bayer filter mask on the detector. **Figure 39.5** A fluorescence imaging system. (a) A handheld device coupled to a CCD is used for illumination and detection of native tissue fluorescence. (b) This device is composed of a dichroic beam splitter that reflects the excitation light and directs it to the tissue. Re-emitted tissue fluorescence is transmitted by the dichroic mirror and reaches the camera. A longpass filter is placed in front of the CCD for additional blocking of the excitation light (image created by P.M. Lacerra (2012). Provided by Kurachi). The spectral information in the widefield image is reduced to three scalar values. This imaging modality provides two-dimensional (2D) biomorphological information: homogeneity, relative fluorescence intensity, distribution pattern for each of the RGB colors. Typical fields of view are of the order of several square centimeters,9,10 making this modality more suitable for cancer screening than endomicroscopy or fluorescence spectroscopy, which usually provides information for just a few square millimeters. From a clinical point of view, the widefield fluorescence pattern of the cancer and potentially malignant lesions appears as a dark-brownish area, while healthy tissue shows a pale green retained fluorescence.10,13–17 Usually, a contralateral normal tissue, chosen by an expert clinician, is imaged to provide a reference standard. Different studies have attempted to explain the origin of native fluorescence in oral tissue. In two recent studies, Pavlova et al.For this reason, an extended margin of clinically healthy tissue needs to be defined by the surgeon.Compared to normal WL inspection, better visual contrast between healthy and potentially malignant tissue was achieved by means of fluorescence imaging.9,14,16,17 Poh et al.

Some cases of primary anal tumors may also be misclassified as squamous carcinoma of the skin.It should also be borne in mind that a tumor in the anal canal is more likely to be due to caudal spread of a rectal cancer than a primary anal carcinoma, simply because rectal cancer is vastly more common.Axial T2-weighted image showing a right anterior quadrant external anal sphincter tear (arrow) and perineal scarring (compare to normal left side) following vaginal delivery A study of 30 patients who both underwent external phased array and endoanal MRI found that they did not differ significantly in their ability to depict external sphincter atrophy (Williams et al. 2001). However, as ever, accuracy was contingent on observer experience and authors have concluded that both techniques could only be recommended if sufficient expertise for interpretation was available (Terra et al. 2006). A study of 200 incontinent patients found that MR features of external sphincter atrophy on phased-array imaging correlated with impaired anal squeeze pressures as assessed by anal manometry, implying that MR could be used to identify patients whose muscle quality was poor (Terra et al. 2006). ## 19.3 MR Imaging of Anal Malignancy Anal tumors are very rare and account for <1% of large bowel tumors. In contrast to colorectal tumors, which are nearly always adenocarcinomas, anal tumors tend to be epidermal in origin, for example squamous cell carcinoma. The anus is however one of the most pluripotential sites for tumors (because it is a junctional zone anatomically) and many cell types can be encountered, including melanomas, Paget's and anal gland carcinoma. Like cervical carcinoma, there is a strong association with human papillomavirus infection. HIV infection and smoking are also associated with increased relative risk. Anal tumors typically spread upwards, into the rectum, with the result that they may be difficult to distinguish from rectal cancers on clinical grounds. It should also be borne in mind that a tumor in the anal canal is more likely to be due to caudal spread of a rectal cancer than a primary anal carcinoma, simply because rectal cancer is vastly more common. Some cases of primary anal tumors may also be misclassified as squamous carcinoma of the skin.Local nodal spread is to the mesorectal nodes and, importantly, the inguinal nodes, which should be encompassed in the imaging field.Metastatic spread tends to be to the liver, lungs, and bone.Treatment of anal tumors is radically different from that of rectal carcinoma.Specifically, combined modality therapy using chemoradiation is the mainstay of treatment.

Mock implantation was done by following the complete surgical procedure but without inserting any implant.The wound was closed by interrupted suturing using polyglactin filaments (Ethicon, Germany).An incision of 1 cm was made in the dorsal skin and a small pouch was made under the skin to insert the implant.The back was shaved using an electronic razor (Aesculap, Germany).### 2.3 Implant Preparation For biocompatible and inflammatory implant preparation, respectively, plain material samples or samples coated with bacterial products were used. Porous implants were used to increase the carrier capacity and the stability of the coatings to prolong the release after implantation. Porous glass beads obtained from VitraPOR, Germany (Size 4 mm, Pore size-60 m) were used as biocompatible implants. Inflammatory porous glass implants were prepared by soaking the beads for 2 min in heat inactivated Staphylococcus aureus suspensions and left to dry under ambient conditions. Porous titanium discs of 7 mm diameter and 2 mm thickness were prepared from micro-beads by an injection molding and sintering procedure. Magnesium discs with a diameter of 5 mm and height of 2 mm were prepared by extrusion of a rod followed by cutting off individual discs. Poly-L-lactic acid beads with a diameter of 5 mm were purchased from Good Fellow, England. ### 2.4 Subcutaneous Implantations in Mice Wild-type BALB/c mice were obtained from Harlan–Winkelmann laboratories, Germany. Animals were housed under pathogen free conditions in a group of maximum five animals per cage. Mice were anesthetized by intraperitoneal injection of ketamine (10 mg/kg) and xylazine (4 mg/kg). The back was shaved using an electronic razor (Aesculap, Germany). An incision of 1 cm was made in the dorsal skin and a small pouch was made under the skin to insert the implant. The wound was closed by interrupted suturing using polyglactin filaments (Ethicon, Germany). Mock implantation was done by following the complete surgical procedure but without inserting any implant.### 2.5 In Vivo Imaging of the Oxidation Potential After anesthesia 30 g of hydrocyanine solution was injected subcutaneously at the site of implantation.After 30 mins, fluorescent imaging was done in the near infrared spectrum using in vivo imaging system (IVIS200, Xenogen, USA).The excitation wavelength of hydrocyanines was 750 nm and the emission wavelength was 840 nm.

B, High-power view reveals smooth muscle ingrowth between the crypts and misplaced non-neoplastic crypts and acellular mucin.The epithelium often has a serrated architectural appearance that can cause diagnostic confusion with a serrated neoplasm.The pathogenesis of ICP is thought to be similar to that of other mucosal prolapse disorders.34 It is likely related to chronic mucosal prolapse that occurs in long-term disorders with constipation and defecation and with associated ischemic, inflammatory, and reactive changes of the overlying mucosa.35-37 #### Pathology ICPs are located in the anterior anal canal, may be single or multiple, and are typically sessile (see Chapter 22). The gross size varies, but most are between 1 and 2 cm in the greatest dimension. The histologic features include fibrosis of the lamina propria, thickening of the muscularis mucosae, hyperplasia of mucosal glands (often with a villous-like configuration) leading to a serrated contour of the epithelium, and telangiectasia of surface vasculature with or without fibrin thrombi (Fig. 32.5). The muscularis mucosae is typically thickened and irregular, with frequent extension of fibromuscular strands into the lamina propria that results in the formation of diamond-shaped crypts and deposition of mucosal elastin. The finding of elastin is distinctive because it is otherwise not seen in the normal rectum. The surface epithelium is characteristically composed of a mixture of colorectal, transitional, and squamous mucosa. Ischemic-type erosion of the surface epithelium is a common finding, and it may contribute to regenerative or hyperplastic (serrated) epithelial changes. FIGURE 32.5 A, Low-power view of an inflammatory cloacogenic polyp. These lesions have a villiform appearance, incorporate anal squamous epithelium, display prominent crypt distortion, and show reactive epithelial changes. The epithelium often has a serrated architectural appearance that can cause diagnostic confusion with a serrated neoplasm. B, High-power view reveals smooth muscle ingrowth between the crypts and misplaced non-neoplastic crypts and acellular mucin.Recognition of the regenerative (non-neoplastic) epithelial cytology and eroded surface in ICPs and of the absence of cytologic dysplasia helps to distinguish an ICP from an adenoma.ICPs typically contain transitional and squamous epithelium.The fact that adenomas are somewhat uncommon in the age group in which ICPs are often diagnosed is also useful.

He held out a folder of reading material."I'm sorry," Bob said, "I wish I could spare you all, this but I can't."They both rose.Julius nodded.Okay?"My nurse will call you later today with all the details about time and place and prep instruction.Okay?Trust my judgment on this; I've been involved with hundreds of these cases.As you asked, I'll take care of you."Look, Bob," replied Julius, "I know our previous relationship makes this hard for you, but please don't ask me to do your work. Don't assume I know anything about this. Keep in mind that right now my state of mind is terror veering toward panic. I want you to take charge, to be entirely honest with me, and take care of me. Just as I did for you. And, Bob, look at me! When you avoid my gaze like that, it scares the shit out of me." "Right. Sorry." He looked him straight in the eyes. "You took damn good care of me. I'll do the same for you." He cleared his throat, "Okay, my strong clinical impression is that it's a melanoma." Noting Julius's wince, he added, "Even so, the diagnosis itself tells you little. Most—remember that—most melanomas are easily treated, though some are bitches. We need to know some things from the pathologist: Is it melanoma for certain? If so, how deep is it? Has it spread? So, first step is biopsy and getting a specimen to the pathologist. "Soon as we finish I'll call a general surgeon to excise the lesion. I'll be by his side throughout. Next, an examination of a frozen section by the pathologist, and if it's negative, then great: we're finished. If it's positive, if it is a melanoma, we'll remove the most suspicious node or, if necessary, do a multiple node resection. No hospitalization required—the whole procedure will be done in the surgery center. I'm pretty sure no skin graft will be needed, and, at most, you miss only a day of work. But you'll feel some discomfort at the surgical site for a few days. Nothing else to say now until we learn more from the biopsy. As you asked, I'll take care of you. Trust my judgment on this; I've been involved with hundreds of these cases. Okay? My nurse will call you later today with all the details about time and place and prep instruction. Okay?" Julius nodded. They both rose. "I'm sorry," Bob said, "I wish I could spare you all, this but I can't." He held out a folder of reading material.Depends on the person: some are comforted by information, others would rather not know and just toss it on the way out of the office.Hope after the surgery to tell you something brighter."But there was never to be anything brighter—the later news was darker yet.Three days after the biopsy procedure, they met again."Do you want to read this?said Bob, holding out the final pathologist's report.

Some vegetable (V) material is seen adjacent Fig.Small fragments of meat (M) are present within irregular mucoid and degenerate matrix.4.127 Aspirated material is often best appreciated in the small airways by histology.The airway was closed, causing the death of this patient in a case of penicillin allergy Fig.4.121 Fluid collections can be assessed by ladling out the content into measuring jugs or by direct mechanical aspiration into fluid drainage devices Fig. 4.122 Undisplaced fractures of the ribs are often apparent with local bruising, even if there is no penetration of the pleural cavity by the fracture itself Fig. 4.123 Multiple fractures are seen in this chest, with clear evidence of local haemorrhage into the soft tissues and pleural compartment. If the ribs are broken on both sides, then the chest wall integrity is lost and it becomes a 'flail' chest Fig. 4.124 This large thoracostomy was required for chronic sepsis following pneumonectomy. The persistent production and accumulation of septic material in the right hemithorax required a large drainage route. The object of such surgery is to permit complete drainage and treatment of any septic focus, with subsequent chest closure (if possible) Fig. 4.125 Significant allergic reactions (anaphylactic shock) are classically associated with extensive tenacious mucoid secretions within the airways. These are best appreciated early in the thoracic dissection, as the trachea is opened with the cut extended towards the lobar bronchi. This is not to be confused with bronchopneumonia Fig. 4.126 Acute anaphylaxis is seen with laryngeal oedema in a case of drug-related allergy. The airway was closed, causing the death of this patient in a case of penicillin allergy Fig. 4.127 Aspirated material is often best appreciated in the small airways by histology. Small fragments of meat (M) are present within irregular mucoid and degenerate matrix. Some vegetable (V) material is seen adjacent Fig.4.129 Histological examination in a case of allergic lung reactions shows epithelial denudation with inflammatory cells and degenerate cellular material being seen within the bronchial lumen (L).The basement membrane (bm) is slightly corrugated but is clearly thickened and eosinophilic.

When this fails, the result is "webbed hands."Instead, after the hand develops, apoptosis takes hold to eliminate the cells in between the digits.An example from Lane's book describes how we don't form distinct extensions from our hands to form fingers.For example, activated immune cells send chemical signals to initiate apoptosis in cancer cells, DNA mutations from UV radiation, environmental toxins and pollutants, viruses and bacteria, various physical stresses and trauma, and inflammation (to name a few). However, all these diverse triggers activate the caspase cascade. In other words, all these signals somehow converge at the stage of the caspase enzymes; these enzymes, in turn, are activated by the burst in free radicals that follow the depolarization of the inner mitochondrial membrane and the release of cytochrome c. Numerous studies show the value of apoptosis outside of controlling cancer growth and balancing cell division. It's also a key occurrence that happens all throughout nature. For example, during embryonic development in humans, vast amounts of neurons die in waves. In some areas of the brain, more than 80 percent of the nerve cells formed during the early phases of development disappear before birth (a rate similar to the loss of oocytes from embryonic development to birth). The death of all these neurons allows the brain to be "wired" with great precision. Functional connections are made between specific neurons, enabling the formation of neuronal networks, while others are eliminated. When some of these connections are not eliminated, there may be some unusual connections between different areas of the brain that normally do not communicate directly with one another. The result may explain some cases of autism, where some "higher functioning" individuals on the spectrum see colors and textures when reading numbers, or where specific numbers are connected to specific emotions. An example from Lane's book describes how we don't form distinct extensions from our hands to form fingers. Instead, after the hand develops, apoptosis takes hold to eliminate the cells in between the digits. When this fails, the result is "webbed hands."By contrast, necrotic cell death, or necrosis, is where the cell swells and ruptures, organelles disintegrate, and inflammation tends to occur.This process can also begin with the opening of a channel in the inner mitochondrial membrane of the mitochondria called the megachannel (also called the mitochondrial permeability transition pore, or mPTP).

Although the disease is progressive in the adult, it is compatible with long life.Pathologic fractures and bone pain occur if there has been extensive expansion of the marrow space.Most commonly there is pancytopenia or thrombocytopenia secondary to hypersplenism.In type I, symptoms and signs first appear in adult life and are related to splenomegaly or bone involvement.With the electron microscope the fibrillary cytoplasm can be resolved as elongated, distended lysosomes, containing the stored lipid in stacks of bilayers. Figure 5-13 Gaucher disease involving the bone marrow. Gaucher cells (A, Wright stain; B, Hematoxylin and eosin) are plump macrophages that characteristically have the appearance in the cytoplasm of crumpled tissue paper due to accumulation of glucocerebroside. (Courtesy of Dr. John Anastasi, Department of Pathology, University of Chicago, Chicago, IL.) In type I disease, the spleen is enlarged, sometimes up to 10 kg. The lymphadenopathy is mild to moderate and is body-wide. The accumulation of Gaucher cells in the bone marrow occurs in 70% to 100% of cases of type I Gaucher disease. It produces areas of bone erosion that are some­times small but in other cases sufficiently large to give rise to pathologic fractures. Bone destruction occurs due to the secretion of cytokines by activated macrophages. In patients with cerebral involvement, Gaucher cells are seen in the Virchow-Robin spaces, and arterioles are surrounded by swollen adventitial cells. There is no storage of lipids in the neurons, yet neurons appear shriveled and are progressively destroyed. It is suspected that the lipids that accumulate in the phagocytic cells around blood vessels secrete cytokines that damage nearby neurons. ###### Clinical Features. The clinical course of Gaucher disease depends on the clinical subtype. In type I, symptoms and signs first appear in adult life and are related to splenomegaly or bone involvement. Most commonly there is pancytopenia or thrombocytopenia secondary to hypersplenism. Pathologic fractures and bone pain occur if there has been extensive expansion of the marrow space. Although the disease is progressive in the adult, it is compatible with long life.The diagnosis of homozygotes can be made by measurement of glucocerebrosidase activity in peripheral blood leukocytes or in extracts of cultured skin fibroblasts.In principle, heterozygotes can be identified by detection of mutations.However, because more than 150 mutations in the glucocerebroside gene can cause Gaucher disease, currently it is not possible to use a single genetic test.

Arterial Embolization is another unique treatment method for cancer.Targeted therapy is a broad-based term used to describe a new class of drugs that seek to stop or inhibit the growth of new cancer cells by interfering with specific molecules that "signal" for new cancer cells to grow and develop. Since targeted therapy drugs are directed only at the molecules that "allow" the process of creating cancer cells, they generally do not harm healthy cells in the way that chemotherapy and radiation does, and is generally considered less harmful with side-effects than chemotherapy and radiation. The two targeted therapy drugs approved for renal cell carcinoma include: Sorafenib and Sunitinib Immunotherapy is a new treatment method which uses natural substances to encourage the body's own immune system to fight off disease, or laboratory made immune system components to fight off unwanted disease. Immunotherapy agents are not called drugs or medication, but rather, Biological Immune Response Modulators (BIRMS). There are many types of BIRMS, including cancer vaccines which are just one form of immunotherapy. Targeted therapy and immunotherapy also have some drugs and BIRMs that overlap since these two fields are closely related. However, the two most commonly used BIRMs for the treatment of renal cell carcinoma are Interferon, a natural protein produced by the immune system cells to fight against foreign agents including cancerous cells, and Interleukin, which is used in patients with advanced stages of this disease by boosting their immune system and slowing down the cancer growth. Arterial Embolization is another unique treatment method for cancer.As stated above, surgery, as a treatment option, is approached carefully where tumor-only removal or partial removal is preferred over complete removal of the kidneys.Nevertheless, in advanced cases, a total nephrectomy as well as radical nephrectomy is done.## Wrap Up Thank you for downloading this book!

This is especially important during pregnancy.If your partner has an active HSV lesion on his penis, he should wear a condom during intercourse so you don't become infected.With both, you will suffer from small painful ulcers on the skin, which can occur at any time but typically are preceded by a tingling feeling.Chlamydia in pregnancy should be treated with erythromycin, not tetracycline, as the latter can affect your baby's bone growth. Hepatitis B This viral liver infection is carried in blood and body secretions and is most commonly transmitted by having sex with an infected person, infection during childbirth, or using dirty needles. If you've been infected you're likely to carry the virus forever and remain infectious to others. In the long-term, hepatitis B can cause liver damage. In some parts of the world, such as West Africa and Southeast Asia, hepatitis B is widespread as the virus can be passed from mothers to their unborn baby. _**Management**_ If you are a hepatitis B carrier, you should be referred to a liver specialist for monitoring during pregnancy. Your partner should be tested as well, as he can be immunized against this virus if he hasn't already caught it. Hepatitis B can be transmitted to your baby at the time of birth, but this can be prevented from developing by giving your baby a course of vaccinations, starting immediately after the birth. This will protect your baby when breastfeeding. Herpes simplex virus (HSV) There are two types of herpes simplex virus: type 1 typically affects the lips and causes cold sores, and type 2 affects the genitalia. Both types can be transmitted by close contact such as kissing or sexual intercourse. With both, you will suffer from small painful ulcers on the skin, which can occur at any time but typically are preceded by a tingling feeling. If your partner has an active HSV lesion on his penis, he should wear a condom during intercourse so you don't become infected. This is especially important during pregnancy.This is usually only a problem if you have your first ever attack during childbirth.If you already have HSV, your body will have developed antibodies, which will be transmitted to your baby before she's born and therefore give her protection until she's three months old.If your baby is affected by HSV during childbirth she could develop a brain infection known as encephalitis.

But susceptibility also depends on lifestyle and exposure to other stressors such as poor nutrition and environmental factors.""A person with very strong stock will last a long time before the immune system breaks down."How you react depends on your genetics," says Dr. Huggins.Aluminum: Research indicates that, because of the high levels of aluminum found in the brain cells of Alzheimer's victims, this metal may be a causal factor in the development of the disease. While the source of aluminum toxicity in the body has not yet been proven, aluminum can enter the body through inhalation (by factory workers in certain industries) and by oral ingestion. It has been suggested that aluminum ions may leach into the body from aluminum cooking utensils, cans, and foil, as well as underarm deodorants, antacid pills, and other common products, many of which contain traces of aluminum. Mercury: Postmortem examination of brain tissue from Alzheimer's victims has also indicated the presence of high levels of mercury. Another study makes a clear connection between the presence of mercury in brain tissue and the presence of "silver" amalgam dental fillings, which contain approximately 50% mercury as well as silver, tin, copper, and zinc. "In a recent test of 7,000 patients, we found 90% to be sensitive to mercury," says Hal A. Huggins, D.D.S., of Colorado Springs, Colorado. "What this means is that while different people will react in different ways to mercury, in 90% of the people with amalgam fillings, the mercury will significantly suppress the immune system." Reactions to high levels of mercury in the body can range from nervousness and depression to suicidal tendencies and severe neurological diseases such as multiple sclerosis, Lou Gehrig's disease (a syndrome marked by muscular weakness and atrophy due to degeneration of motor neurons), and Alzheimer's. "How you react depends on your genetics," says Dr. Huggins. "A person with very strong stock will last a long time before the immune system breaks down. But susceptibility also depends on lifestyle and exposure to other stressors such as poor nutrition and environmental factors."While the electrical mechanism created by metals in the mouth does not itself directly suppress the immune system, Dr. Huggins cautions that it enables metals to leave the fillings faster and to be absorbed into the blood.

* The patient states that the pain in his lower legs is "hard to explain" and feels as though someone is "pumping them up with fluid" * In the past 4 to 5 months he has now developed low back pain * Orthopedic evaluations suggest that he has degenerative disc disease and may at some point require back surgery * In an attempt to avoid this, the patient has escalated his opiate use to 80 to 120 mg of hydrocodone per day and has also had epidural blocks * The epidural blocks were helpful for his low back pain for a short period of time but actually, if anything, made the pain in his legs worse * The hydrocodone is now sedating and interferes with his ability to concentrate and makes him too sedated to do creative or consulting work during the day; however, if he lowers the dose of hydrocodone below 80 mg/day, he is in too much pain to work anyway * His pain is distressing to him and interferes with his ability to function as a self employed entrepreneur, inventor and consultant, but does not really make him feel sad, hopeless, apathetic, loss of interest, or in the midst of a major depressive episode now or in the past * Over the past few years has had an extensive history of psychotropic drug utilization and has had numerous agents which caused unusual or difficult side effects * – Numerous TCAs not tolerated (urinary retention, constipation, sedation) and did not work on his pain * – Gabapentin, far too sedating but also seemed to cause a withdrawal reaction with increased tinnitus, paresthesias and gastrointestinal pain when he stopped it * – Numerous SSRIs not effective, caused burning sensation in upper and lower distal extremities * – Quetiapine very sedating even at low doses * A few years back when he was living in another city, a US physician prescribed low dose sulpiride for him for an unknown reason which he had shipped to him from France and which helped his pain * When the patient ran out of medication and moved, he stopped the sulpiride Social and Personal History * Married 9 years * One daughter 8 years old * Non smoker * No illicit drug or alcohol abuse * Graduate of an elite engineering school * Successful patent holder and entrepreneur until 2 years ago when he could no longer work full time, but only consult and not invent Medical History * Hypercholesterolemia * BMI 29 * Obstructive sleep apnea * Dercum's disease * Sinus surgery several years ago Family History * Father: chronic pain and anxiety Current Medications * Synthroid 75 mcg * Duloxetine (Cymbalta) 60 mg * Atomoxetine (Strattera) 40 mg * Hydrocodone up to 120 mg/day * Zolpidem 10 mg for sleep * Zetia for hypercholesterolemia * Uses CPAP (continuous positive airway pressure) machine most nights for obstructive sleep apnea Based on just what you have been told so far about this patient's history and various pain conditions, what do you think is his diagnosis?

The first and worst strain perished on Bhola Island in 1975, but wiping out its siblings took another two years.A 12 percent killer surfaced in 1963.A milder strain that appeared in the late nineteenth century killed a mere 1 percent.The strain of _Variola major_ that emerged three thousand years ago killed about 30 percent of its victims.To pick just one example among the many (less inflammatory) examples discussed throughout the rest of this book, it is easy to cobble together statistics to suggest that contraception and abortion are—or are not—linked to higher rates of breast and cervical cancer (see Chapter 4). But, good or bad, statisticians must now compete with modern medicine's most powerful antidote to the health care policies of the Great Stink past: the sniffing technologies that allow medicine to read and track—and then develop antidotes to treat—molecules and cells, rather than crowds. MEDICINE'S RECENTLY ACQUIRED ability to read every letter of the code of life has added a short, rightward-leaning codicil to the smallpox story, a familiar account of the discovery that led to socialized medicine's finest hour and which surely still warms every left-leaning political heart. On May 14, 1796, Jenner injected eight-year-old James Phipps with cowpox pus taken from lesions on the hand of milkmaid Sarah Nelmes, and found that this mild infection protected Phipps from deliberate attempts to infect him with an aged and thus weakened form of the human pox. Jenner published his findings two years later, content to gift the most valuable pharmaceutical discovery of all time to suffering humanity. "Yours is the comfortable reflection that mankind can never forget that you have lived," wrote Thomas Jefferson in a letter sent to Jenner in 1806. But as vaccinators ramped up their attack, the smallpox virus fought back. The strain of _Variola major_ that emerged three thousand years ago killed about 30 percent of its victims. A milder strain that appeared in the late nineteenth century killed a mere 1 percent. A 12 percent killer surfaced in 1963. The first and worst strain perished on Bhola Island in 1975, but wiping out its siblings took another two years.We do know, however, that the vaccine that ended up beating them all wasn't Jenner's.The details are lost in history and Koplow himself doesn't speculate about them, but it's easy to surmise how this vaccine came into being.Picture how the market for what began as Jenner's vaccine operated through all but the last few decades of its two-century run.

[16] reported an average quadriceps tendon width of 27 mm and an average thickness of 8 mm.In an anatomical study, Harris et al.In the distal 6 cm of the tendon, the vastus medialis and the vastus lateralis unite to form the middle layer.Some surgeons consider the bone-patellar tendon-bone (BPTB) as the gold standard for reconstruction in spite of well-documented morbidities [3, 4]. Defenders of hamstring autograft refer to low donor-site morbidity, better strength in extension [5], and a lower incidence of mid- and long-term degenerative joint disease [6, 7]. However, decrease strength in hip extension and terminal knee flexion [8], residual laxity, higher infection rate [9, 10], and variable sizes and lengths of grafts remain a problem [11]. Actually, the quadriceps tendon (QT) is the least used autograft for ACL reconstruction [4]. In 2010, a review on graft choice showed that 2.5 % of all anatomic ACL reconstructions were performed with a QT autograft [12]. Recently, during an international meeting on anatomic ACL reconstruction, Middleton et al. [13] surveyed the practice of 35 surgeons from more than 20 countries. These experts polled averaged over 2,100 ACL reconstructions over their careers, and the use of QT autograft represented 11 % of all ACL reconstructions. However, several studies have shown excellent clinical results and low morbidity with the use of the QT autograft [14, 15], and a recent systematic review has confirmed that the use of QT for ACL reconstruction was safe, reproducible, and versatile [4]. The anatomy of the QT is highly variable with sometimes an unequal contribution of its tendinous components. The usual description of the quadriceps tendon consists of a trilaminar pattern, with the rectus femoris as the major contributor to the superficial layers and the vastus intermedius as a contributor of the deepest layer. In the distal 6 cm of the tendon, the vastus medialis and the vastus lateralis unite to form the middle layer. In an anatomical study, Harris et al. [16] reported an average quadriceps tendon width of 27 mm and an average thickness of 8 mm.These anatomical features allow for harvesting of a custom-shaped graft, either rectangular, ribbonlike, triangular, or ovoid.The size and the length can also be determined according to the patient needs.It also allows for the choice of a graft with or without a bone plug.

* Local extension may occur either from tumors of the middle ear cavity (e.g., squamous cell carcinoma), the nasal cavity (e.g., nasal adenocarcinoma), or the skull (e.g., osteosarcoma).* Secondary tumors that have been reported to occur in the brains of cats include pituitary macroadenomas and macrocarcinomas, and metastatic carcinoma.* Classification of the glial subset of neuroepithelial tumors is based on the predominant cell type (e.g., astrocyte or oligodendrocyte). Dogs * Embryonal tumors have been consolidated under the single term "primitive neuroectodermal tumors" (or PNETs) to accommodate their anaplastic nature. * Brain tumors arising from lymphoreticular cells traditionally have been grouped under a heading of reticulosis or histiocytic lymphoma. * Skull tumors that affect the brain by local extension include osteosarcoma, chondrosarcoma, and multilobular osteochondrosarcoma. * The most frequently seen secondary tumors of dogs include local extension of nasal adenocarcinoma; metastases from mammary, prostatic, or pulmonary adenocarcinoma; metastases from hemangiosarcoma; and extension of pituitary adenoma or carcinoma. * Nerve sheath tumors arising from cranial nerves (particularly oculomotor nerve and trigeminal nerve) may occur in dogs. Cats * Meningiomas involving multiple intracranial sites (including the third ventricle) are relatively common in cats. * Primary brain tumors other than meningiomas occur infrequently in cats. * Tumors that have been reported include astrocytoma, ependymoma, oligodendroglioma, choroid plexus papilloma, medulloblastoma, lymphoma, olfactory neuroblastoma, and gangliocytoma. * Lymphoma of the brain may be primary or secondary, or may be an aspect of multicentric lymphoma of cats. * Secondary tumors that have been reported to occur in the brains of cats include pituitary macroadenomas and macrocarcinomas, and metastatic carcinoma. * Local extension may occur either from tumors of the middle ear cavity (e.g., squamous cell carcinoma), the nasal cavity (e.g., nasal adenocarcinoma), or the skull (e.g., osteosarcoma).* Three methods of therapy for a brain tumor are currently available for use in dogs and cats: surgery, irradiation, and chemotherapy.Surgery * Neurosurgical intervention is an essential consideration in the management of brain tumors in cats or dogs, whether for complete excision, partial removal, or biopsy.

Based on this report, Badjatia and colleagues152 decided to treat with low-dose IA nicardipine only.Badjatia and colleagues noted that although Kaku and colleagues117 treated vasospastic patients with IA papaverine, all vessels were also treated with IA nicardipine (0.5 to 1.0 mg).More selective IA nicardipine infusion was then investigated.Hui and Lau146 published a retrospective study of 9 patients with a reported 66% increased vessel diameter after IA nimodipine; 8 of 9 patients improved clinically (89%) and this was sustained in 7 of 9 patients (78%). Cho and colleagues147 published their retrospective study of 42 patients and 101 sessions of IA nimodipine and found angiographic improvement in 82.2%, immediate clinical improvement in 68.3%, and a favorable clinical outcome in 76.2% at discharge and 84.6% at 6 months. Transient hypotension (<90 systolic blood pressure) occurred in 14% of patients. Successful treatment of vasospasm using IA nimodipine has also been reported by Kim and colleagues148 and combination therapy using both nimodipine and milrinone by Anand and colleagues.143 Although widely considered safe, IA nimodipine has been associated with blood-brain barrier disruption149 and, in one report, basal ganglia vasogenic edema with deleterious consequences from blood-brain barrier disruption.150 ##### Nicardipine Nicardipine is a dihydropyridine calcium channel blocker similar to nimodipine and can significantly improve TCD velocities and neurologic condition in medically refractory patients. Initial dose-escalation studies of IV nicardipine demonstrated notable improvement in angiographic and symptomatic vasospasm151; however, these and subsequent IV studies were hampered by significant systemic hypotension. More selective IA nicardipine infusion was then investigated. Badjatia and colleagues noted that although Kaku and colleagues117 treated vasospastic patients with IA papaverine, all vessels were also treated with IA nicardipine (0.5 to 1.0 mg). Based on this report, Badjatia and colleagues152 decided to treat with low-dose IA nicardipine only.Significant improvement in TCD velocities were noted in all patients for 4 days after infusion and 42% also improved neurologically.Increased ICP was observed in 6 patients but only persistently elevated in 1 patient; no clinical deterioration occurred in any patient.

The tonic inhibitory control usually exerted by the PFC is compromised, resulting in a state of disinhibition.An ANS imbalance highlighted by decreased parasympathetic tone emerges.A prolonged state of alarm, action-readiness, uncertainty, threat (real or imagined), or negative emotions, places excessive demands on the system.Prolonged activation of this system can induce depression through modifications of tryptophan metabolism. The role of IL-1, TNF, and nerve growth factor (NGF) in pain and being sick has been detailed by Watkins and Maier (2000). A study by Wallace and his colleagues (2001) compared fibromyalgia (FM) patients with non-pain controls and found increased levels of IL-6 and IL-8 in the FM group. IL-6 is associated with hyperalgesia, fatigue, and depression; IL-8 is associated with sympathetic related pain. Dantzer also notes that the brain cytokine system can undergo sensitization as a result of stimulation during the early stages of development, repeated activation by exposure to environmental stressors, and prior activations by exposure to environmental stressors. Thayer and Brosschot (2005) have proposed a neurovisceral-integration model which involves the autonomic nervous system (ANS), central nervous system (CNS), and central autonomic network (CAN). The CAN is made up of PFC and limbic structures and comprises the internal regulation system via which the brain controls visceromotor, neuroendocrine, and behavioral responses related to goal-directed activity, adaptability, and health. Thayer and Brosschot also apply some of the concepts from complexity theory, such as "organized variability," which characterizes dynamic adaptive systems, in contrast to "rigid regularity," which is associated with morbidity, ill health, and mortality. In general, stress and alarm conditions precipitate the fight-or-flight response, including activation of the ANS. A prolonged state of alarm, action-readiness, uncertainty, threat (real or imagined), or negative emotions, places excessive demands on the system. An ANS imbalance highlighted by decreased parasympathetic tone emerges. The tonic inhibitory control usually exerted by the PFC is compromised, resulting in a state of disinhibition.This common reciprocal inhibitory corticosubcortical neural circuit links psychological processes with health-related physiological processes.Sympathetic dominance alters CNS network activity that typically regulates autonomic balance via the CAN and thus influences social, attentional, affective executive, and motivated behavior.

For patients with moderate or severe COPD, SpO2 should be measured on air using a pulse oximeter before flights are booked.In patients with COPD, oxygenation may fall causing breathlessness and this desaturation will be exacerbated by minimal exercise.At this pressure, inspired O2 is the equivalent of breathing 15% oxygen; even in healthy subjects, SpO2 will fall.# Short Burst Oxygen Despite maximal inhaled and oral pharmacological treatment, many patients with advanced COPD remain breathless on exertion. Oxygen delivered via cylinders is frequently prescribed for breathlessness at rest or during recovery after exercise. However, studies in patients who do not fulfil the arterial blood gas criteria for prescription of LTOT generally demonstrate that oxygen after exercise does not consistently influence breathlessness scores or rate of symptomatic recovery. Oxygen used in this way has been shown to reduce the degree of dynamic hyperinflation during recovery from exercise, but fails to significantly alter the degree of breathlessness. Whether there is actually a role for 'short burst' oxygen therapy in COPD is therefore controversial. Patients with episodes of severe breathlessness not relieved by other treatments should be thoroughly assessed including measurement of arterial blood gas tensions. Short burst oxygen should only be prescribed if clear improvement in breathlessness or exercise tolerance can be confirmed. # Air Travel and Oxygen Increasing numbers of individuals at extremes of age and with a variety of medical problems such as COPD are travelling by air. Commercial aircraft fly at 27,000–37,000 feet (9,000–11,000 metres) and are required to maintain cabin pressure at the equivalent of 8,000 feet (2,438 m). At this pressure, inspired O2 is the equivalent of breathing 15% oxygen; even in healthy subjects, SpO2 will fall. In patients with COPD, oxygenation may fall causing breathlessness and this desaturation will be exacerbated by minimal exercise. For patients with moderate or severe COPD, SpO2 should be measured on air using a pulse oximeter before flights are booked.All patients with COPD who require in-flight oxygen should inform the relevant airline when booking and be aware that some airlines charge for this service.The need for oxygen while changing flights must also be considered and many airports can provide wheelchairs for transport to and from aircraft.

Areas of bone or contiguous surrounding tissue that have abnormal viability, blood supply, sensation, or edema are at increased risk for bacterial infection.#### **OSTEOMYELITIS** • **Pathogenesis** Osteomyelitis is typically caused either by direct spread from a contiguous focus of infection or by hematogenous spread.Vancomycin (1 g IV q12h) should be used to cover the possibility of MRSA when there are gram-positive cocci on the smear. – In IV drug users and other susceptible pts, treatment for gram-negative organisms such as _P. aeruginosa_ should be considered. – If a pathogen is identified by culture, treatment should be adjusted according to the specific bacterial organism and its antibiotic susceptibility. • Treatment for _S. aureus_ should be given for 4 weeks, that for enteric gram-negative bacilli for 3–4 weeks, and that for pneumococci or streptococci for 2 weeks. Treatment of gonococcal arthritis should commence with ceftriaxone (1 g/d) until improvement; the 7-day course can be completed with an oral fluoroquinolone (e.g., ciprofloxacin, 500 mg bid). If fluoroquinolone resistance is not prevalent, a fluoroquinolone can be given for the entire course. • Prosthetic joint infections should be treated with surgery and high-dose IV antibiotics for 4–6 weeks. The prosthesis often has to be removed; to avoid joint removal, antibiotic suppression of infection may be tried. A 3- to 6-month course of ciprofloxacin and rifampin has been successful in _S. aureus_ prosthetic joint infections of relatively short duration, although prospective trials confirming the efficacy of this regimen are still needed. #### **OSTEOMYELITIS** • **Pathogenesis** Osteomyelitis is typically caused either by direct spread from a contiguous focus of infection or by hematogenous spread. Areas of bone or contiguous surrounding tissue that have abnormal viability, blood supply, sensation, or edema are at increased risk for bacterial infection.aureus_ —elaboration of bacterial adhesins and toxins.• **Epidemiology** In the U.S., 0.1–1.8% of otherwise healthy adults are affected by acute osteomyelitis; 30–40% of adults with diabetes develop osteomyelitis after a foot puncture.

The study was not designed to determine any differences in the _safety_ between the two medicines.At the end of 2 years of treatment, bevacizumab was shown to be noninferior to ranibizumab.The CATT was a large, prospective, multicenter, randomized, noninferiority clinical trial comparing intravitreal bevacizumab and ranibizumab for the treatment of neovascular ARMD.C) Focal grid laser Approximately 1% of patients undergoing routine phacoemulsification may develop the Irvine–Gass syndrome, or postcataract CME. The natural history of untreated CME is quite good, but may take up to 6 to 9 months. Generally accepted methods of treatment include observation, topical steroids, and/or topical NSAIDs. Focal grid laser would not be indicated in this setting, unless there was concominant diabetic macular edema with leaking microaneursyms on IVFA. A) Intravitreal bevacizumab ( _Avastin™_ ) The treatment of neovascular (wet) ARMD has revolutionized with the advent of intravitreal anti-VEGF agents. As of 2013, both intravitreal ranibizumab (­ _Lucentis™_ , Genentech, South San Francisco) and aflibercept ( _Eylea™_ , Regeneron, NY) are FDA-approved for the treatment of neovascular ARMD. _Visudyne™_ (photodynamic therapy, PDT) is an older treatment modality that is FDA-approved for the treatment of wet ARMD, but was shown to have inferior visual outcomes compared to intravitreal ranibizumab in the ANCHOR study. According the PAT survey in 2012, approximately 67% of retina specialists in the United States use intraviteral bevacizumab off-label as first-line treatment of wet ARMD. D) Intravitreal bevacizumab is noninferior to ranibizumab. The CATT was a large, prospective, multicenter, randomized, noninferiority clinical trial comparing intravitreal bevacizumab and ranibizumab for the treatment of neovascular ARMD. At the end of 2 years of treatment, bevacizumab was shown to be noninferior to ranibizumab. The study was not designed to determine any differences in the _safety_ between the two medicines.D) 30% The anti-vascular endothelial growth factor antibody for the treatment of predominately classic choroidal neovacularization in Age-related Macular Degeneration (ANCHOR) Trial was a prospective, randomized clinical trial that compared intravitreal ranibizumab with verteporfin PDT for neovacular ARMD.

• Lung contusions usually occur with blunt trauma.Look for associated rib fractures and evidence of tension (a mediastinal shift to the opposite side).• Pneumothoraces appear as gas within the pleural spaces.• In addition, CT can identify any pulmonary masses which are not visible on X-ray and is used as part of the staging of many cancers. • These scans are often performed with IV contrast. • The size and appearance of any mass, along with other findings such as lymph node enlargement, are used to help determine whether the lesion is benign or malignant. • Large, spiculated masses are suspicious for malignancy; however, a biopsy (CT guided or via bronchoscopy) may be required for a definitive diagnosis. ### Assessment of the lung parenchyma • To further assess abnormalities of the lung parenchyma identified on X-ray. • A non-contrast high resolution CT (HRCT) is often performed. • Pathologies such as pulmonary fibrosis, bronchiectasis, sarcoidosis, or occupational lung disease (such as silicosis, asbestos exposure, etc.) can be demonstrated. • Differentiating these pathologies on CT can be difficult and their specific CT features are beyond the scope of this book. One example (bronchiestasis) is shown in figure 16. _**Figure 16. ** Axial slice from a HRCT of the chest. There are dilated bronchioles in the left lower lobe (the diameter of the bronchus/bronchiole should not be greater than the adjacent pulmonary artery) indicating bronchiectasis. This has various causes and the clinical assessment will be important for narrowing the differential diagnosis._ ### Trauma • Contrast enhanced CTs are used as part of the trauma CT to identify thoracic injuries (see figure 17). • Pneumothoraces appear as gas within the pleural spaces. Look for associated rib fractures and evidence of tension (a mediastinal shift to the opposite side). • Lung contusions usually occur with blunt trauma.They are often multifocal.• Mediastinal haemorrhage appears as abnormal areas of soft tissue density within the mediastinum.There may be evidence of active bleeding (high attenuation extending from a blood vessel).The haemorrhage may compress structures within the mediastinum, such as the airway, oesophagus, vena cava or aorta.• Fractures of the ribs, clavicles, spine and sternum are common.

What are you worried about?On examination, you don't notice any swelling, but see that her left lower limb is externally rotated and noticeably shorter than the right.She reports it is very painful.** Quadriceps **An osteoporotic woman slips, hears a snap, and is unable to bear weight.** No **When is MRI indicated for the evaluation of scoliosis in kids? ** Onset prior to 8 years old, rapid curve progression greater than 1° per month, left thoracic curve, neurologic deficit, or pain **What is the location of the fracture seen in spondylolysis? ** Pars interarticularis **What is the classic exam finding in spondylolysis? ** Pain with extension of the back with single leg loading in the presence of normal neurologic exam **What are the risk factors for malignancy associated with lower back pain? ** Personal history of cancer, age >50 years, pain not relieved by rest, pain that worsens at night or wakes patient from sleep, symptoms longer than 4 weeks, constitutional symptoms **In the absence of risk factors for malignancy or neurologic findings, when is imaging indicated for lower back pain? ** Failure of conservative treatment for 2-4 weeks #### **HIP AND GROIN INJURIES** **Name the soft tissue injury most commonly associated with the following clinical scenario? ** **Pain in hip after a direct blow that increases with rotation or with lateral bending** Iliac crest bone contusion (hip pointer) **Runner started running stairs to prepare for upcoming climbing trip. Point tenderness posterior to greater trochanter, pain with resisted abduction, and lateral thigh rotation** Trochanteric bursitis **What is the most common site for a thigh hematoma? ** Quadriceps **An osteoporotic woman slips, hears a snap, and is unable to bear weight. She reports it is very painful. On examination, you don't notice any swelling, but see that her left lower limb is externally rotated and noticeably shorter than the right. What are you worried about?** Anticoagulate to decrease risk of DVT while in the hospital, bone health evaluation, appropriate medication prior to discharge (calcium, vitamin D, bisphosphonate) **What is the most common cause of a limp in toddlers?** Infected joint (septic joint, osteomyelitis, toxic synovitis) **What is the initial workup for a child that presents with a limp?

For this reason, the detection of a recurrence of the malignant neoplasm (usually squamous cell carcinoma) in the presence of osteoradionecrosis may be very difficult.### Differential Diagnosis Bone resorption, stimulated by high levels of irradiation, may simulate bone destruction from a malignant neoplasm, especially in the maxilla.### Radiologic Examination The prescription of diagnostic imaging would be the same as used for chronic phase osteomyelitis, with CT imaging being the imaging modality of choice. ### Imaging Features Changes to the appearance of bone are the same as seen with osteomyelitis and radiation-induced changes (see preceding descriptions) and often with prominent bone sclerosis. However, the radiologic identification of osteoradionecrosis relies on the identification of dead bone in the form of sequestra. Bone sequestra are seen more commonly in the mandible, and often the sequestra seen are segments of detached cortical bone (Fig. 20-24). In contrast to osteomyelitis, there is no periosteal bone reaction in most cases. The presence of a pathologic fracture (Fig. 20-25) is suggestive of osteoradionecrosis. The presence of osteoradionecrosis cannot always be diagnosed from the diagnostic image, and often clinically obvious signs of exposed necrotic bone may not have significant changes in the panoramic image. In these cases, CT imaging is required. FIGURE 20-24 Examples of osteoradionecrosis. **A,** Axial CT image showing extensive bone resorption and the presence of a sequestrum _(arrow)_. **B,** Axial CT image showing more prominent sclerotic bone reaction and sequestrum _(arrow)_. In both examples, the sequestra represent detached segments of the former outer cortical bone. FIGURE 20-25 **A,** Cropped panoramic image of a patient with bone resorption secondary to therapeutic radiation exposure. **B,** Development of a pathologic fracture in the same patient after 3 months. ### Differential Diagnosis Bone resorption, stimulated by high levels of irradiation, may simulate bone destruction from a malignant neoplasm, especially in the maxilla. For this reason, the detection of a recurrence of the malignant neoplasm (usually squamous cell carcinoma) in the presence of osteoradionecrosis may be very difficult.Differentiation from other sclerotic lesions, as in chronic osteomyelitis, is less difficult because of the history of radiation therapy.### Management Treatment of osteoradionecrosis at the present time is unsatisfactory.Decortication with sequestrectomy and hyperbaric oxygen with antibiotics have been used with limited success because of poor healing after surgery.

### Nerve tumours Tumours of the peripheral nerves arise from the neurilemmal sheath of Schwann;13 hence the terms neurilemmoma, neurofibroma or schwannoma.Surgical treatment consists of excision, but this is a difficult procedure as the cysts ramify throughout the structures of the neck.They may respond to injection of sclerosant agents such as alcohol or doxycycline.They are dilations of normal capillaries and are seen in a number of circumstances, such as on the weather-beaten faces of country people and on the legs of young women, who may complain of their cosmetic appearance. _Hereditary haemorrhagic telangiectasia_ (HHT; Osler–Weber–Rendu syndrome12) is an inherited autosomal dominant disease characterized by tiny capillary angiomas of the skin, lips and mucous membranes; they may give rise to repeated nose bleeds and gastrointestinal haemorrhage. The genetic abnormality is a mutation of either endoglin (HHT type 1) or activin receptor-like kinase (HHT type 2) genes. Typically, the telangiectases are visible around the mouth and in the fauces, and present with nose bleeds. Occult arteriovenous malformations are common. ### Lymph vessel tumours Lymphangiomas are congenital in origin and similar to haemangiomas; they are lined by endothelium but contain lymph. They are relatively uncommon, but occur mainly on the lips, tongue and cheek, resulting in macrocheilia or macroglossia. ### Cystic hygroma A form of lymphangioma, the aetiology of cystic hygromas is thought to be a combination of a failure of lymphatics to connect to the venous system, abnormal growth of embryonal lymphatics and sequestered lymphatic rests. Most occur in the neck, usually the left side, and were thought to be related to the embryonic precursor of the jugular part of the thoracic duct. They consist of a multilocular cystic mass, which is often present at birth or noticed in early infancy. Characteristically, they are supremely transilluminable. They may respond to injection of sclerosant agents such as alcohol or doxycycline. Surgical treatment consists of excision, but this is a difficult procedure as the cysts ramify throughout the structures of the neck. ### Nerve tumours Tumours of the peripheral nerves arise from the neurilemmal sheath of Schwann;13 hence the terms neurilemmoma, neurofibroma or schwannoma.The tumours may be solitary or multiple and may involve any peripheral nerve in the body.Of the cranial nerves, the eighth is most commonly involved, often as a solitary tumour (the acoustic neuroma; see Chapter 14).Tumours may arise within the spinal canal, particularly from the dorsal nerve roots, resulting in an extramedullary, intrathecal, slow-growing spinal tumour (see Chapter 16).

In regard to hypertension, blood pressure significantly decreased in group I, but did not in group II, thus showing that G. lucidum has an ameliorating effect on hypertension.Biochemical and hematologic examination were performed for 21 test items, and the following results were obtained.The patients were instructed to take six tablets containing 240 mg of the extract per day.There are no known contraindications or restrictions to the use of this herb during pregnancy or lactation.- ### Reishi Although not classically used for the treatment of hypertension in pregnancy, it is worth mentioning that the medicinal mushroom Ganoderma lucidum has demonstrated positive results in research looking at its antihypertensive effects, as well as effects against diabetes and hyperlipidemia.- One interesting study looked at the effects of reishi on glomerular function, and found that it was able to improve hemodynamic flow in glomerular disease and reduce proteinuria. The beneficial effect of G. lucidum appears to be multifactorial, including the modulation of immunocirculatory balance; antilipid, vasodilator, and antiplatelet effects; and improved hemodynamics. Together with vitamins C and E, this herb helped to neutralize oxidative stress and suppress the toxic effect to the glomerular endothelial function. Extracts of reishi polysaccharides have demonstrated significantly improved basal nitrous oxide (NO) release and endothelium-dependent relaxation but without affecting endogenous nitrous oxide synthase (NOS) activity. These results suggest that this herb has the potential to improve endothelium-dependent relaxation in mineralocorticoid hypertension. In a study evaluating the clinical effects of lyophilized G. lucidum extract, 53 patients were divided into two groups: group I consisted of essential hypertensive patients, and group II consisted of mild hypertensive or normotensive patients. The patients were instructed to take six tablets containing 240 mg of the extract per day. Biochemical and hematologic examination were performed for 21 test items, and the following results were obtained. In regard to hypertension, blood pressure significantly decreased in group I, but did not in group II, thus showing that G. lucidum has an ameliorating effect on hypertension.It was therefore concluded that G. lucidum has blood pressure lowering effects on patients with essential hypertension and will not have any side effects on patients with essential or border line hypertension during 6 months of oral intake.

Improvement was described in 79% of cases but was more variable in those treated with methotrexate alone.Four retrospective reviews documented the response to methotrexate alone in 52 cases, and in combination with corticosteroids in 67 cases [365, 366, 379, 380].Systemic corticosteroids should be considered in patients with severe, active inflammatory disease and in patients with eosinophilic fasciitis who appear particularly steroid responsive [253]. Methotrexate is a cornerstone of morphoea management [363–370). Methotrexate is thought to exert its effects at multiple levels. It has been shown to enhance monocyte differentiation [371], reduce peripheral blood mononuclear cell production of IL-8 [372] and stimulate IL-1 receptor antagonist and soluble TNF receptor p75 _in vitro_ in rheumatoid arthritis [373]. Reductions in circulating sIL-2R and IL-6 following successful therapy with methotrexate in children and adults with rheumatoid arthritis [374, 375] suggest a possible mechanism for its effects in morphoea, since reductions in serum IL-2, -4 and -6 have been found to parallel improvement in cutaneous sclerosis [123]. Furthermore, mast cell numbers and levels of tenascin – an extracellular matrix protein previously shown to be increased in the skin and circulation of morphoea patients [376, 377] – are both reduced in lesional skin after methotrexate therapy [378]. Two early uncontrolled case series (17 patients, 9 adults) suggested some improvement in skin lesions with methotrexate alone [262, 363]. Four retrospective reviews documented the response to methotrexate alone in 52 cases, and in combination with corticosteroids in 67 cases [365, 366, 379, 380]. Improvement was described in 79% of cases but was more variable in those treated with methotrexate alone.In these studies, significant improvements were noted based on mLoSSI (mLoSSI score of 0 in 32/36 cases at 36 months) and PGA-A [368] or physician assessment [364] in children.A 50% reduction in skin scores, corroborated by biopsy and ultrasound measurements, was documented in 13/15 adults after a mean treatment duration of 9.8 months [370].

There are many different types of dermal filler on the market including products that contain hyaluronic acid (e.g.just the jowls); it is important to maintain balance and harmony in the whole face and so a complete facial aesthetic assessment should be carried out prior to any treatment.It is bad practice to treat individual areas in isolation (e.g.Many people come to me worried they will look overdone and frozen, or concerned their partner will notice if they have treatment. It is important to find a healthcare practitioner you trust and have a rapport with so you can explain exactly what you want of them. Choose a reputable clinic with good reviews and avoid places offering cut-price deals. Personally, I think it is all about subtle results, and all my patients have the option to come back and see me two weeks after their injections to make any small adjustments. In my experience, it is far easier to add more in two weeks; you can't take it out once it's in! The injections themselves are done with fine needles and are not usually painful. They can cause some minor discomfort at worst, but nearly everyone tolerates Botox well without any problems. It is, however, still a medical procedure and a proper consultation should take place first including a thorough medical history. ### Dermal fillers As we age, collagen and elastin in the skin break down. At the same time, fat compartments lose volume and become thinner, particularly in the upper half of the face. The facial skeleton changes due to bone loss at strategic sites such as the mid-face and orbital bone around the eye. These factors combined together result in skin sagging, prominent skin creases such as nose-to-mouth lines (nasolabial fold) and jowl formation. This volume loss cannot be addressed by Botox and requires dermal fillers to fill or plump out the areas that have effectively become deflated. It is bad practice to treat individual areas in isolation (e.g. just the jowls); it is important to maintain balance and harmony in the whole face and so a complete facial aesthetic assessment should be carried out prior to any treatment. There are many different types of dermal filler on the market including products that contain hyaluronic acid (e.g.The vast majority of fillers now used are the hyaluronic acid varieties.These have increased in popularity over the years because they are non-permanent but long-lasting, cause few allergies and can be reversible and dissolved if necessary.Before filler is injected, a medical consultation is necessary.Full facial assessment is vital to determine which areas require filling or volumizing.

A patient with an open wound over the anticipated distal anastomosis site or without adequate single segment vein would best be served with PTA.The surgeon should be both flexible and creative.Bypass is the first choice with significant tissue loss (ulcer larger than 1 cm or gangrene involving the foot; Figure 1).These objectives must be tempered by the patient's general medical condition, current ambulatory status, and previous operations. In general, the success of surgical bypass is the availability of a single segment of autogenous vein of suitable diameter, whereas success of endovascular treatment is determined by extent of atherosclerotic disease, as quantified by the Trans-Atlantic Inter-Society Consensus (TASC) I Working Group in 2000. Infrapopliteal lesions are categorized in severity from classes A to D (Table 1). The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial is the only randomized trial (452 patients) in which outcomes of surgical bypass and percutaneous transluminal angioplasty (PTA) were compared and provides level 1 evidence in the field. At 1 year, the amputation-free survival (AFS) rates were equivalent; however, at 2 years, AFS rates were better among the patients undergoing bypass. The BASIL authors concluded that bypass with autogenous vein is the best treatment for patients with severe limb ischemia expected to survive more than 2 years and that bypass with prosthetic grafts in patients without sufficient autogenous vein are associated with poor results. Thus endovascular interventions are the preferred option for TASC classes A, B, and single-level C lesions, whereas surgical bypass is recommended for multilevel TASC classes C and D lesions in a surgical patient with average risk. Bypass is the first choice with significant tissue loss (ulcer larger than 1 cm or gangrene involving the foot; Figure 1). The surgeon should be both flexible and creative. A patient with an open wound over the anticipated distal anastomosis site or without adequate single segment vein would best be served with PTA._GSV,_ Greater saphenous vein; _TASC,_ Trans-Atlantic Inter-Society Consensus (class).(From Conte MS: Critical appraisal of surgical revascularization for critical limb ischemia, _J Vasc Surg_ 57:2, 2013.)## Surgical Bypass All patients are maintained on an aspirin regimen before the surgical procedure.

Fig.87.In general, they run at right angles to the underlying muscles.6.1 The relaxed skin tension lines of the face which are the sites of choice for surgical incisions.Fig.86.5.45 Steam autoclave.Fig.85.5.44 Piezoelectric bone-removal system.Fig.84.5.43 Piezoelectric bone-removal system.Fig.83.5.42 Gelfoam®.Fig.82.5.41 Surgicel®.Fig.81.5.40 Bone wax.Fig.80.5.8 Mosquito and Kelly-type forceps. 49. Fig. 5.9 Needle holders. 50. Fig. 5.10 Dean scissors. 51. Fig. 5.11 Iris scissors. 52. Fig. 5.12 Metzenbaum scissors. 53. Fig. 5.13 Woodson periosteal elevator. 54. Fig. 5.14 Molt #9 periosteal elevator. 55. Fig. 5.15 Langenbeck retractor. 56. Fig. 5.16 Curettes. 57. Fig. 5.17 Rongeurs. 58. Fig. 5.18 Bone files. 59. Fig. 5.19 Surgical drill. 60. Fig. 5.20 Straight elevator. 61. Fig. 5.21 Straight elevator. 62. Fig. 5.22 Coupland's chisel. 63. Fig. 5.23 Cryer's elevators. 64. Fig. 5.24 Potts elevators. 65. Fig. 5.25 Crane's elevators. 66. Fig. 5.26 Root pick elevators. 67. Fig. 5.27 Warwick-James elevator. 68. Fig. 5.28 Upper right/left molar forceps: 53 R/L. 69. Fig. 5.29 Upper premolar forceps: 150. 70. Fig. 5.30 Upper incisor and canine forceps. 71. Fig. 5.31 Lower premolar in-line forceps: 151. 72. Fig. 5.32 Cowhorn forceps. 73. Fig. 5.33 Ash pattern lower molar forceps. 74. Fig. 5.34 Ash pattern lower premolar incisor and canine forceps. 75. Fig. 5.35 Yankauer suction tip. 76. Fig. 5.36 Surgical suction tip. 77. Fig. 5.37 The active electrode (tip) and indifferent electrode (plate) in a monopolar diathermy system. 78. Fig. 5.38 The insulated tips of a bipolar diathermy system. Each tip is a separate electrode. 79. Fig. 5.39 A disposable low-power cautery unit. 80. Fig. 5.40 Bone wax. 81. Fig. 5.41 Surgicel®. 82. Fig. 5.42 Gelfoam®. 83. Fig. 5.43 Piezoelectric bone-removal system. 84. Fig. 5.44 Piezoelectric bone-removal system. 85. Fig. 5.45 Steam autoclave. 86. Fig. 6.1 The relaxed skin tension lines of the face which are the sites of choice for surgical incisions. In general, they run at right angles to the underlying muscles. 87. Fig.88.Fig.6.3 A horizontal sulcular incision suitable for access to periapical pathology and sinus procedures.89.Fig.6.4 An intrapapillary or sulcular incision used to give access to the palatal surface of the alveolus.90.Fig.6.5 A gingival margin incision incorporating a releasing incision which is wider at its base than its apex to protect the vascularity of the flap (arrows).

Consequently, the left main coronary artery originates more posterior than usual, at approximately the 7 o'clock location on the aortic clock face in the axial view. The right coronary artery origin is likewise rotated clockwise, with the ostium at the 2 o'clock location. Percutaneous intervention for repair of the homograft stenosis was inadvisable due to the close proximity of the right coronary artery to the pulmonary conduit. Given the close proximity of cardiovascular structures to the sternum, the patient was placed on cardiopulmonary bypass via right groin vessels prior to redo sternotomy in order to decompress the right ventricle. Revision of the right ventricular outflow tract, and pulmonary valve replacement were performed. During conduit/homograft resection, the posterior layer of the conduit was left intact in order to avoid injury to the anomalous right coronary artery. Ao aorta, CX circumflex coronary artery, LAD left anterior descending coronary artery, LM left main coronary artery, PA pulmonary artery, RCA right coronary artery, RV right ventricle (Reprinted from Shinbane et al. [35] with permission from SAGE Publications) ### CCTA for Surgical Versus Percutaneous Approach to Mitral Valve Disease Research and clinical approaches to mitral valve disease include a spectrum of options including percutaneous clipping of valve leaflets, percutaneous mitral annuloplasty, transcatheter mitral valve replacement, minimally invasive robotic mitral valve repair or replacement, and open sternotomy mitral valve repair or replacement.Mitral annular size and geometry factors including valve tenting, height and tethering of the mitral leaflets variability in number of heads and insertions of the posterior papillary muscle, interpapillary muscle distance, mitral valve sphericity index, intercommissural and septolateral distance , and anterior and posterior circumference of the mitral annulus can be assessed [36–38].

However, complete excision at the time of surgery is usually difficult due to the large size and deep location.###### Treatment and Prognosis Surgical resection with wide clear margins is the treatment of choice.The most commonly seen nonlipogenic element is fibrosarcomatous with variable myxoid and pleomorphic features (Fig. 51). However, chondroblastic, osteogenic, myogenic, angiomatous, and neural elements can be seen as well. The dedifferentiated elements can be histologically high or low grade. Not infrequently, the dedifferentiated component occupies the majority of the tumor mass and only very small portion of well-differentiated liposarcoma can be found in the periphery of the specimen. This well-differentiated area can be misinterpreted as normal fat. Careful search for atypical cells in the remnant of "normal appearing fat" adjacent to dedifferentiated area is the key for a proper diagnosis. Immunohistochemical study might be useful to confirm the presence of nonlipogenic elements in tumors. Fig. 51 Another dedifferentiated liposarcoma shows hemangiopericytoma-like vasculature and large globoid rhabdoid cell differentiation ###### Differential Diagnosis When the separate areas of well-differentiated liposarcoma and high-grade sarcoma are seen juxtaposed, the diagnosis of dedifferentiated liposarcoma is straightforward. Otherwise, the tumors need to be differentiated from pleomorphic lipoma, spindle cell lipoma, sclerosing liposarcoma, well-differentiated liposarcoma, pleomorphic fibrosarcoma, myxofibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and extraskeletal osteosarcoma. Thorough sampling and examination of a large well-differentiated liposarcoma or a seemingly nonlipogenic sarcoma in areas where liposarcoma is common are crucial to establish the diagnosis. ###### Treatment and Prognosis Surgical resection with wide clear margins is the treatment of choice. However, complete excision at the time of surgery is usually difficult due to the large size and deep location.Recurrence is very high after surgery and occurs in 40% of all cases and in almost all retroperitoneal cases in long-term follow-up.The distant metastasis occurs in 15–20% of the cases and the overall mortality is around around 30% in 5 years.The retroperitoneal lesions have the worse prognosis.The extent and grading of the dedifferentiation do not seem to have significant prognostic impact (63).

reported that it took 2.5–10 years for five of nine children with growth delay who were in Tanner stage I to attain their pre-illness height percentile following surgery [73].Alperstein et al.studied the relationship between adolescent psychosocial adjustment and chronological age, pubertal status, and serum hormone levels [70]. In boys, adjustment problems were associated with low sex hormones or lower pubertal stage in conjunction with higher chronological age. These included sadness/anxiety and problems with body and self-image. In girls, adjustment problems in social relationships were also associated with lower pubertal stage and higher age. Both groups had elevated levels of androstenedione, an adrenal hormone responsive to stress, which the authors suggested may be due to self-comparison with same-age peers. They speculated that boys may be more sensitive to hormonal influences and girls to environmental influences. Delayed sexual maturation may have significant adverse effects on self-esteem and socialization, as the child with delayed puberty looks younger than their chronological age, and often are treated as such [71]. Thus, an adolescent with IBD must cope not only with the impact of having a chronic disease, but also with the psychological issues of delayed puberty. In addition to the psychological response to pubertal delay, stress itself may interfere with the functioning of the brain–pituitary–gonadal axis. Evidence suggests that this may be mediated by elevated cortisol levels over a protracted period of time. Consten et al. noted that cortisol administration to male carp caused delayed testicular development, reduced testosterone levels, and impaired maturation of pituitary gonadotrophs [72]. ## Therapeutic Approach to Addressing Pubertal Issues in IBD The observations and studies described above suggest that prolonged control of active inflammation and providing adequate nutrient intake are both essential in promoting normal puberty. Alperstein et al. reported that it took 2.5–10 years for five of nine children with growth delay who were in Tanner stage I to attain their pre-illness height percentile following surgery [73].Although experience with GH treatment in pediatric patients with IBD is limited, improvement of growth velocity may be observed when there is reasonable disease control with reduced corticosteroid exposure.Furthermore, steroid-related growth effects may be in part ameliorated with GH treatment [74–76].

## **Experimental Treatments** Parathyroid fragments and growth factors are under study and appear promising.## **Fluoride** Slow-release fluoride (25 mg twice a day for twelve months followed by two months off) has been shown to increase bone mass and decrease vertebral fractures but is not yet available in the United States.Calcitonin can actually help build back strong bones, not just slow down the process of bone loss. The major drawback to the treatment has been its expense and the need for patients to learn how to self-administer injections. The medication may cause transient flushing and nausea in about 20% of patients. Calcitonin administration by nasal spray is now possible and is considerably easier. ## **Biphosphonates** Etidronate (Didronel) was the first of a class of drugs called biphosphonates, followed by Clordronate. These "first-generation" biphosphonates were usually given for a two-week period each three months (cyclic therapy), since they don't work if given continuously. These drugs have been shown to produce a small increase in bone density and to decrease the frequency of spine fractures. Because biphosphonates are poorly absorbed, they must be taken on an empty stomach and only with water. "Second-generation" biphosphonates are now available, led by alendronate (Fosamax) and including pamidronate, tiludronate, and ibandronate. These can be taken continuously and decrease the risk of spinal fractures by 50 to 90%, even in people who have already had a fracture. These drugs can irritate the esophagus, so they are best taken in the morning with a glass of warm water. The standard approach has changed from 10 mg fosomax daily to 10 mg once a week; this is equally effective and better tolerated. The "third-generation" drug residronate appears to cause less stomach irritation. ## **Vitamin D** Vitamin D comes with sunlight and diet. If you are usually indoors or malnourished, supplementation (as with a multivitamin) may be a good idea. ## **Fluoride** Slow-release fluoride (25 mg twice a day for twelve months followed by two months off) has been shown to increase bone mass and decrease vertebral fractures but is not yet available in the United States. ## **Experimental Treatments** Parathyroid fragments and growth factors are under study and appear promising.The body reacts to such exercise by increasing the calcium content and thus the strength of the bones.Walking is the best example.If at all possible, walk half a mile to a mile (1 to 1.5 km) a day.If this is unrealistic for you, remember that even a little weight-bearing exercise is important.Do as much as you can.For suggestions on developing a walking program, see chapters 9 and 12.

Syphilis can be cured with a course of antibiotics; however, if the condition has been allowed to go unchecked for a long period of time, the outlook may not be as positive.If a blood test detects the presence of syphilis antibodies in the blood, the diagnosis can be confirmed with an analysis of spinal fluid.### Hypercalcemia Hypercalcemia is an electrolyte imbalance caused by too much calcium in the blood. Elevated levels of serum calcium are generally associated with a tumor or _primary hyperparathyroidism,_ a condition that occurs when the parathyroid glands secrete too much hormone. When the level of calcium in the bloodstream gets too high, it may produce an altered mental status and memory problems that are similar to Alzheimer's Disease. A blood test that measures the levels of both calcium and parathyroid hormone can identify the condition. Surgery to remove the parathyroid glands cures hypercalcemia associated with hyperparathyroidism; when the hypercalcemia is associated with a tumor, particularly a malignant tumor, the outlook is less optimistic. After the parathyroid glands are removed and calcium levels fall back to normal, the accompanying Alzheimer's-like symptoms diminish. In some cases, the patient may have to take calcium-lowering drugs to help manage the condition. ### Neurosyphilis Syphilis can cause dementia if it spreads to the brain. Although syphilis can readily be cured with antibiotics if it's diagnosed and treated early on, in patients who don't seek treatment, the infection can spread to the brain — although it generally takes at least a decade to do so. This infection can produce mental confusion, difficulty in walking, and dementia that mimics Alzheimer's Disease. If a blood test detects the presence of syphilis antibodies in the blood, the diagnosis can be confirmed with an analysis of spinal fluid. Syphilis can be cured with a course of antibiotics; however, if the condition has been allowed to go unchecked for a long period of time, the outlook may not be as positive.Well, believe it or not, we've got a few more to discuss.Because of the number of possible causes for dementia, your doctor will want to take a thorough medical history, including what drugs your loved one is taking and the start/stop dates for those drugs.

Studies have shown that zinc lozenges can soothe sore throat and reduce a cold's duration.**Zinc** is an important immune-stimulating mineral._Best juice sources of vitamin E:_ spinach, watercress, asparagus, carrots, and tomatoes.It plays a role in a broad range of defense mechanisms on the cellular level.**Vitamin E** is another strong ally in supporting the immune system.Because pineapple juice has a lot of fruit sugar, it is best to take a bromelain supplement when fighting a respiratory infection. **Vitamin A** and **beta-carotene** are recommended for combating respiratory illnesses. Vitamin A contributes to the health of the epithelial cells that coat the respiratory tract. It is also capable of stimulating various immune processes, including natural killer cell activity and antibody response. Beta-carotene and other carotenes are the only form of pro-vitamin A found in fruits and vegetables; they are converted to vitamin A within the body as needed. _Best juice sources of carotenes in general:_ carrots, kale, parsley, spinach, Swiss chard, beetroot greens, watercress, broccoli, and romaine lettuce. **Vitamin C** and **bioflavonoids** are important immune-system stimulators. Vitamin C is found in great quantities in white blood cells, and the supply needs to be constantly replenished when the body is fighting infection or inflammation. One study showed that if vitamin C levels were low, the individual was more likely to develop bronchitis. Bioflavonoids make vitamin C more effective. _Best juice sources of vitamin C:_ kale, parsley, broccoli, Brussels sprouts, watercress, cauliflower, cabbage, spinach, lemons, limes, turnips, and asparagus. _Best juice sources of bioflavonoids:_ bell peppers, broccoli, cabbage, parsley, and tomatoes. **Vitamin E** is another strong ally in supporting the immune system. It plays a role in a broad range of defense mechanisms on the cellular level. _Best juice sources of vitamin E:_ spinach, watercress, asparagus, carrots, and tomatoes. **Zinc** is an important immune-stimulating mineral. Studies have shown that zinc lozenges can soothe sore throat and reduce a cold's duration.# **Herb Recommendations** **Echinacea** contains several compounds that make it a good immune-system support herb.For example, two components of the herb are key.Inulin directly affects important cellular processes involved in fighting infection and inflammation.Caffeic acid is antibacterial and contains compounds that help to keep mucous membranes strong.

And we would also create a nation of healthy, slender, vibrant people who rely less on a bloated, profit-seeking healthcare system that costs more than any other system in the world.The first year of not having acid reflux, for example, can save $2,000 in healthcare costs that year alone because you did not undergo the obligatory (and often unnecessary) endoscopy and were not prescribed the stomach acid–blocking medications that would have led to distortions of bowel flora and the associated bloating, constipation, intermittent bowel urgency, and inflammation, as well as loss of bone density and nutrient deficiencies, downstream health problems resulting from what is often regarded as a "benign" drug treatment. Instead, you institute simple measures that not only address the cause of the problem but also bring about other health benefits without causing unwanted side effects. And your approach costs, at most, a few dollars, or even results in saving money. You are, in effect, failing to contribute to the physicians, nurses, dietitians, technicians, hospital executives, pharmacies, prescription management services, armies of salespeople, pharmaceutical executives, and medical device manufacturers that would have otherwise pocketed the money you would have been forced to spend. Multiply this cost savings by thousands, then millions, of people for just this one condition and you get a sense of what we could achieve if we persuaded the population to follow us and cut a path of health across hundreds of health conditions. And we would also create a nation of healthy, slender, vibrant people who rely less on a bloated, profit-seeking healthcare system that costs more than any other system in the world.I will explain how and why I chose to cultivate this daring path.In truth, I did not set out to develop a program that seized control over health or saved money.As with many things, it all happened through a series of fortuitous accidents, coupled with a desire for better answers, all unfolding on the cusp of an exciting and empowered Information Age.

However, in chronic inflammatory disease the initial activation continues unabated.In the normal response to perturbation, the immune system goes from a state of activation to one of deactivation as the body becomes repaired from the effects of the invasion.Further knowledge in this area will pave the way to personalised clinical nutrition. * * * # 17.1 Introduction Humans live in the presence of many types of microorganism, which exert pathological effects if they succeed in penetrating the surface defences of the body. Once entry is gained, rapid multiplication occurs, which, if unchecked, can end in death. However, we possess an immune system that has a great capacity for immobilising invading microbes, creating a hostile environment for them, and bringing about their destruction. Humans and warm-blooded animals have survived because their immune systems have the ability to focus a range of lethal activities upon the invader. This biological property is important because many microbes can multiply at least 50 times faster than the cells of the system. The immune system must therefore become rapidly effective once invasion has occurred. The immune system can also become activated, in a similar way to the response to microbial invasion, by a wide range of stimuli and conditions; these include burns, penetrating and blunt injury, the presence of tumour cells, environmental pollutants, radiation, exposure to allergens, and the presence of chronic inflammatory diseases. This latter group of stimulatory conditions includes such diseases as rheumatoid arthritis, Crohn's disease, asthma, and psoriasis, as well as more common conditions such as atherosclerotic heart disease, obesity, diabetes, and Alzheimer's disease. The strength of the response to this disparate range of stimuli may vary, of course, but it will contain many of the hallmarks of the response to invading pathogens. In the normal response to perturbation, the immune system goes from a state of activation to one of deactivation as the body becomes repaired from the effects of the invasion. However, in chronic inflammatory disease the initial activation continues unabated.Inappropriate prolongation of the response will have a deleterious effect upon the nutritional status of the patient.# 17.2 The response of the immune system to activation The immune system is located throughout the body.It consists of clearly recognised structures, such as the spleen, thymus, and lymph nodes, and diffuse populations of cells.

Statistically, the most common psychosomatic disorder today is TMS, which I have described in its many forms in my previous books.This will be documented as we proceed.More expense.More time lost.More distress.All of a sudden, the "cured" patient has a brand-new disorder that demands medical attention.On occasion, however, the choice of symptom location may even contribute to the diversion process, something that is common with psychosomatic disorders. For example, a man who experiences the acute onset of pain in his arm while swinging a tennis racket will naturally assume that it was something about the swing that hurt his arm. The reality is that his brain has decided that the time is ripe for a physical diversion and chooses that moment to initiate the pain, because the person will assume that it stems from an injury, not a brain-generated physical condition that caused the pain. How does the brain manage this trick? It simply renders a tendon in the arm slightly oxygen deprived, which results in pain. This is how "tennis elbow" got its name. If that sounds bizarre, diabolical, or self-destructive, you will see later that it is in reality a protective maneuver. My colleagues and I have observed it in thousands of patients. But in time, such a symptom may lose its power to distract. Then the psyche has another trick up its sleeve. It will find another symptom to take its place, one that is viewed by both patient and doctor as "physical," that is, not psychological in origin. For instance, if a treatment—let's say surgery—neutralizes a particular psychogenic symptom, so that the symptom loses its power to distract, the brain will simply find another target and create another set of symptoms. I have called this the symptom imperative and it has enormous public health implications, because psychogenic symptoms are commonly misinterpreted and treated as physical disorders. All of a sudden, the "cured" patient has a brand-new disorder that demands medical attention. More distress. More time lost. More expense. This will be documented as we proceed. Statistically, the most common psychosomatic disorder today is TMS, which I have described in its many forms in my previous books.Since then, I have come to learn that nerve and tendon tissue may also be targeted by the brain; in fact, it now appears that nerve involvement is more common than muscle.Accordingly, a more inclusive name, like musculoskeletal mindbody syndrome, might be more appropriate.However, because the term TMS is now so well known, I have been urged by my colleagues not to change it, so TMS it remains.

Unlike ablation procedures, DBS can be adjusted to control symptoms better and is reversible—that is, the device can be removed.The device is programmed to deliver a specific current to the targeted brain location.DBS involves placing an electrode in one of the thalamus, globus pallidus or subthalamic nucleus and connecting it to a generator placed in the upper chest (like a pacemaker).The use of only one drug is preferred because there are fewer side effects and the drug dosage is easier to adjust than when several drugs are used. However, as the disease progresses, combination therapy is often required. Excessive amounts of dopaminergic drugs can lead to paradoxic intoxication (aggravation rather than relief of symptoms). TABLE 58-10 Parkinson's disease DRUG THERAPY AST, aspartate aminotransferase; Hct, haematocrit; MAO, monoamine oxidase; WBCs, white blood cells. ### Surgical therapy Surgical procedures are aimed at relieving the symptoms of Parkinson's disease and are usually used in patients who are unresponsive to drug therapy or who have developed severe motor complications. Surgical procedures fall into three categories: ablation (destruction), deep brain stimulation (DBS) and transplantation. Ablation surgery involves stereotactic ablation of areas in the thalamus (thalamotomy), globus pallidus (pallidotomy) and subthalamic nucleus (subthalamic nucleotomy). Ablative procedures have been used in patients with Parkinson's disease for more than 50 years but recently they have been replaced by DBS. DBS involves placing an electrode in one of the thalamus, globus pallidus or subthalamic nucleus and connecting it to a generator placed in the upper chest (like a pacemaker). The device is programmed to deliver a specific current to the targeted brain location. Unlike ablation procedures, DBS can be adjusted to control symptoms better and is reversible—that is, the device can be removed.This form of therapy is still in the experimental stages.### Nutritional therapy Diet is of major importance to the patient with Parkinson's disease because malnutrition and constipation can be serious consequences of inadequate nutrition.Patients who have dysphagia and bradykinesia need appetising foods that are easily chewed and swallowed.

A report on autopsy studies of brain tissue concluded, "Magnesium values are found to be significantly decreased in brain regions of Alzheimer's patients compared to controls."Similar findings were reported in the PATH Through Life Project, which published "Dietary Mineral Intake and Risk of Mild Cognitive Impairment."He found that people with Alzheimer's have elevated amounts of aluminum, iron, and zinc and have reduced amounts of alkaline metals such as magnesium, calcium, and potassium, which neutralize the acidity in the diet. A typical Western diet—high in protein, fat, and sugar—is acid-forming and may be an additional factor in creating aluminum overload in Alzheimer's. Neurosurgeon Dr. Russell Blaylock reports that when scientists study the soil of regions that have a high incidence of neurological diseases, they find high levels of aluminum and low levels of magnesium and calcium. The neurons from victims of the disease also show high levels of aluminum and low levels of magnesium. On the island of Guam the areas with the lowest levels of magnesium and calcium in the soil are also the areas of highest incidence for all neurological diseases. Fortunately, magnesium plays a vital role in protecting neurons from the lethal effects of aluminum. A study published in _Magnesium Research_ that used ionized magnesium testing found alterations in magnesium levels in patients with mild to moderate Alzheimer's. Similar findings were reported in the PATH Through Life Project, which published "Dietary Mineral Intake and Risk of Mild Cognitive Impairment." A report on autopsy studies of brain tissue concluded, "Magnesium values are found to be significantly decreased in brain regions of Alzheimer's patients compared to controls."It is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine.Statistically, it is estimated that 7 to 10 million people worldwide are living with Parkinson's disease.Only about 4 percent of people with Parkinson's are diagnosed before the age of fifty.Men are 1.5 times more likely to have Parkinson's than women.

It has also been used for years by alternative therapists as a way of detoxifying individuals who, simply through normal everyday exposures, have accumulated levels of toxins that impair optimal health.In HBOT, a patient sits or lies on a stretcher for 30-120 minutes in a sealed chamber, which is pressurized at up to two-and-a-half atmospheres (the pressure of air at sea level) with pure oxygen. The increased pressure makes it possible to breathe oxygen at a concentration higher than allowed by any other means. After treatment, the chamber is depressurized slowly with the patient resting inside. Most of the hyperbaric facilities in the U.S. are affiliated with hospitals or the military. ### Vitamin C Therapy Each year, more and more studies on vitamin C confirm its importance in healing and maintaining health. The relationship between vitamin C and body toxicity is complex. For example, people deficient in vitamin C are far more susceptible to environmental pollutants. Conversely, exposure to various toxins, like lead or benzene, will deplete a person's vitamin C stores. Evidence also suggests that vitamin C deficiency hampers the body's own detoxification process. As a detoxification agent, vitamin C combines with certain toxins in the body and destroys them. According to Robert Cathcart III, M.D., of Los Altos, California, vitamin C functions as a free-radical scavenger, neutralizing the immunosuppressive toxins produced by infectious diseases. Dr. Cathcart has successfully treated over 11,000 patients with vitamin C therapy, and his results have been widely published in professional journals. ### Chelation Therapy Since the late 1940s, chelation therapy has been routinely used to draw lead, mercury, and other heavy metals out of the body, if a person has been exposed to life-threatening levels. It has also been used for years by alternative therapists as a way of detoxifying individuals who, simply through normal everyday exposures, have accumulated levels of toxins that impair optimal health.In chelation therapy, a synthetic amino acid known as EDTA (ethylenediaminetetraacetic acid) is administered intravenously and binds to various toxic metals in the blood, such as lead, mercury, cadmium, and aluminum.The toxins are then flushed from the body through the kidneys.EDTA is three times less toxic than common aspirin.

**Figure 8.58** Improved possibility to perform proper oral hygiene.Alignment and de-crowding facilitated proper oral hygiene by the patient (Figure 8.58).The patient was placed in supportive periodontal therapy with recall appointments every 2 months during orthodontic treatment and every 3 months at de-bracketing.**Figure 8.57** Final photographs at 1 year.(c) Detail of the left upper quadrant.Piezocision was performed in the anterior upper sextant at first, to facilitate the use of elastic archwires (0.012" to 0.016") in solving the crowding (Figure 8.53). 2. Once alignment of the anterior teeth was completed and it was possible to pass to a rectangular wire (0.019″ × 0.025″ nickel–titanium, followed by 0.019″ × 0.025″ stainless steel), Piezocision was performed in the posterior sextants to facilitate correction of the posterior crossbites. A flap approach with bone graft may have been indicated in this case, since CBCT analysis showed a maintenance of attachment level, but a decrease in thickness of buccal plate, confirming the importance of combination of corticotomy and graft use in the expansion cases. A flap approach may allow a more precise and controlled positioning at the graft, especially close to the cervical margin, as indicated in Chapter 6 (Figures 8.54–8.56). The case was completed in a year (Figure 8.57). **Figure 8.53** Flapless corticotomy in the upper anterior sextant. **Figure 8.54** Flapless corticotomy in the upper posteriors sextants. **Figure 8.55** (a) Occlusal view at the resolution of anterior crowding. (b) Detail of upper right quadrant with insertion of rectangular wire. (c) Detail of the upper left quadrant. **Figure 8.56** (a) Arch expansion completed. (b) Detail of the right upper quadrant. (c) Detail of the left upper quadrant. **Figure 8.57** Final photographs at 1 year. The patient was placed in supportive periodontal therapy with recall appointments every 2 months during orthodontic treatment and every 3 months at de-bracketing. Alignment and de-crowding facilitated proper oral hygiene by the patient (Figure 8.58). **Figure 8.58** Improved possibility to perform proper oral hygiene.**Figure 8.59** Full mouth final radiograph.**Figure 8.60** (a) Pre-operative lower jaw 3D reconstruction, showing a generalized advanced bone loss at the incisors.(b) Post-operative lower jaw 3D CBCT reconstruction, showing a generalized improvement of bone support at the incisors level.

Analysis shows that through elaboration and displacement this pain has become the gratification substitute for a whole series of libidinous phantasies or reminiscences.Let us take as an illustration the hysteric headache or backache.The types of neuroses we have mentioned occur occasionally in pure form; more often they are blended with one another or with a psychoneurotic condition. This need not discourage us to the extent of abandoning the task of distinction. Think of the difference between the study of minerals and that of ores in mineralogy. Minerals are described as individuals; frequently of course they occur as crystals, separated sharply from their surroundings. Ores consist of an aggregate of minerals which have coalesced not accidentally, but as a result of the conditions of their origin. We understand too little of the process of development of neuroses, to create anything similar to the study of ores. But we are surely working in the right direction when we isolate the known clinical factors, comparable to the separate minerals, from the great mass. A noteworthy connection between the symptoms of the true neuroses and the psychoneuroses adds a valuable contribution to our knowledge of symptom formation in the latter. The symptom in the true neuroses is frequently the nucleus and incipient stage of development of the psychoneurotic symptom. Such a connection is most easily observed between neurasthenia and the transference neuroses, which are termed conversion hysteria, between anxiety neurosis and anxiety hysteria, but also between hypochondria and paraphrenia (dementia praecox and paranoia), forms of neuroses of which we shall speak subsequently. Let us take as an illustration the hysteric headache or backache. Analysis shows that through elaboration and displacement this pain has become the gratification substitute for a whole series of libidinous phantasies or reminiscences.We do not wish to assert, by any means, that all hysteric symptoms can be traced to such a nucleus, but it is true that this is frequently the case, and that all influences upon the body through libidinous excitation, whether normal or pathological, are especially significant for the symptom development in hysteria.

In some sense, it was a happy coincidence that Whipple's liver therapy to replace iron in iron-deficient anemia also led to a cure for PA, which involved B12 deficiency.PA is an autoimmune disease in which IF and parietal cells are destroyed.Anemias come in many forms but generally involve a decrease in the number of red blood cells (RBCs) and the hemoglobin that they contain. Hemoglobin is an ironcontaining molecule that can carry oxygen for use by tissues in the body. In 1925, American physician George Whipple showed that iron played an essential role in canine anemia, which he caused by draining blood from dogs. When he fed liver to the anemic dogs, their symptoms eased, and it was soon determined that the iron in liver played a key role in their recovery. In 1926, American physicians George Minot and William Murphy showed that when PA patients ate huge quantities of raw liver, symptoms decreased, and "liver therapy" was subsequently often prescribed. Some patients were so weak from PA that they had to be fed liquefied raw liver through stomach tubes inserted in nostrils. American physician William Castle wondered exactly why so much liver was necessary to elicit an effect in PA patients. It turned out that the PA patients also lacked hydrochloric acid in the stomach. Castle found that if he gave raw hamburger to PA patients after he regurgitated the meat by self-induced vomiting, the PA symptoms diminished. He suggested that something in the liver and some "intrinsic factor" related to the gastric juices were likely both needed to avoid PA. Today, we know that the needed factor in liver is vitamin B12, which is required for the production of hemoglobin. Additionally, normal parietal cells of the stomach secrete both acid and intrinsic factor (IF, a protein), the latter of which is necessary for the absorption of vitamin B12 in the small intestine. PA is an autoimmune disease in which IF and parietal cells are destroyed. In some sense, it was a happy coincidence that Whipple's liver therapy to replace iron in iron-deficient anemia also led to a cure for PA, which involved B12 deficiency.

Osteochondromas appearing on a chest radiograph show a deformity or expansion of the bone with calcification of the cartilaginous cap.Osteochondromas may cause a mass effect on adjacent structures, may induce frictional bursitis, and may undergo malignant transformation.It develops sporadically during the period of skeletal growth and may involve any bone of the skeleton. This nonhereditary disorder can be either monostotic (80% of cases) or polyostotic. This latter condition may be a part of a McCune-Albright syndrome (fibrous dysplasia, patchy cutaneous pigmentation, and precocious puberty) or Mazabraud syndrome (fibrous dysplastic lesion in close proximity to soft-tissue myxomas) (Kransdorf et al. 1990). The radiographic appearance of fibrous dysplasia includes an osteolytic expansile lesion involving the medullary cavity of the bone with endosteal scalloping. Periosteal reaction should be absent if there is no fracture. The lesion may be surrounded by a rim of sclerotic reactive bone (rim sign). Usually the matrix of the lesion can be well recognized on CT images and shows relatively homogeneous aspect (ground glass appearance) with a moderate increase in Hounsfield units to around 200–250. Irregular areas of sclerosis can be present within the lesions. Fig. 13.9 Posteroanterior chest radiograph of a 32-year-old man demonstrates multiple expansile rib lesions. The presence of several normal rib segments (paravertebral and lateral segments) is a keyfinding for the differentiation from disorders related to marrow expansion (compare with Fig. 13.3) Osteochondroma is a frequent benign tumor of the skeleton that consists of a bony outgrowth in continuity with the medullary cavity of the parent bone and that is covered by a thin cartilage layer (Murphey et al. 2000) (Fig. 13.10). Because they are derived from the physeal cartilage, most osteochondromas involve the metaphyseal region of the rib or of the scapula. Osteochondromas may cause a mass effect on adjacent structures, may induce frictional bursitis, and may undergo malignant transformation. Osteochondromas appearing on a chest radiograph show a deformity or expansion of the bone with calcification of the cartilaginous cap.Actually, in an adult, a cartilage cap thickness greater than 20 mm should indicate malignant transformation, whereas malignancy is unlikely if the cartilage thickness is lower than 10 mm.CT is accurate in the assessment of the cartilage thickness when the lesions develop on the inner side of the chest wall and are in contiguity with the lungs.

DNA repair efficiency declines with age, whereas microsatellite instability (MSI), a consequence of suboptimal repair, increases [136].In these instances, sirtuin activity is linked to increased cancer transformation.Tumor suppression was the consequence of lowered gene expression of the tumor growth promoter survivin, resulting from binding of Sirt1 to the survivin promoter and the deacetylation there of histone H3 by Sirt1. Levels of Sirt2 are downregulated in gliomas [72], an indication that it may possess cancer-inhibitory activity. Indicative of the complexity of sirtuin involvement in cancer etiology, not only can sirtuin activators act against cancer, but also the sirtuin inhibitors sirtinol, salermide [32] and cambinol-related molecules [132] also show anticancer activity. Counterbalancing these findings of tumor suppression and the generally beneficial contributions of sirtuins to homeostasis are other indications that high expression levels and activity of sirtuins are associated with cancer incidence and aggressiveness. Poor prognosis in one type of B-cell lymphoma is associated with increased biopsy levels of Sirt1 [133]. A possible contributing mechanism for this relationship involves Sirt1 regulation of Bcl6 activity. Bcl6 is a transcriptional repressor that is normally acetylated and inactive but that can induce B-cell transformation when activated; Bcl6 is a Sirt1 deacetylation target, and Sirt1 inhibition results in accumulation of inactive Bcl6 and cell cycle arrest of B-cell lymphoma cells [134]. Levels of Sirt7 expression are significantly increased in human breast cancer biopsy tissue, and increased levels of both Sirt3 and Sirt7 transcription are associated with node-positive breast cancer [135]. In these instances, sirtuin activity is linked to increased cancer transformation. DNA repair efficiency declines with age, whereas microsatellite instability (MSI), a consequence of suboptimal repair, increases [136].In human colon cancer, in particular, increased Sirt1 levels correlate with the excessive quantities of MSI present.Metastasizing cancer cells require facile migratory activity, a capability promoted by the F1-actin-binding protein cortactin.

Siddhartha Mukherjee's TED Talk, available online: www.TED.com Meet the authors, watch videos and more at: SimonandSchuster.com authors.simonandschuster.com/Siddhartha-Mukherjee ## WATCH SIDDHARTHA MUKHERJEE'S TED TALK Siddhartha Mukherjee's TED Talk, available for free at TED.com, is the companion to The Laws of Medicine.Read the book and watch the talk.I owe a special debt to Sarah Sze, Nell Breyer, Sujoy Bhattacharyya, Suman Shirokar, Gerald Fischbach, Brittany Rush, and Ashok Rai for their comments and criticisms and to Bill Helman for helping me understand some of the most important ideas about uncertainty and the future of technology. ## ABOUT THE AUTHOR PHOTO: BRET HARTMAN/TED Siddhartha Mukherjee is a cancer physician and researcher. He is the author of The Laws of Medicine and The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction. Mukherjee is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. A Rhodes scholar, he graduated from Stanford University, University of Oxford, and Harvard Medical School. He has published articles in Nature, Cell, The New England Journal of Medicine, and The New York Times. In 2015, Mukherjee collaborated with Ken Burns on a six-hour, three-part PBS documentary on the history and future of cancer. Mukherjee's scientific work concerns cancer and stem cells, and his laboratory is known for the discovery of novel aspects of stem cell biology, including the isolation of stem cells that form bone and cartilage. He lives in New York with his wife and two daughters. Read the book and watch the talk. Siddhartha Mukherjee's TED Talk, available online: www.TED.com Meet the authors, watch videos and more at: SimonandSchuster.com authors.simonandschuster.com/Siddhartha-Mukherjee ## WATCH SIDDHARTHA MUKHERJEE'S TED TALK Siddhartha Mukherjee's TED Talk, available for free at TED.com, is the companion to The Laws of Medicine.Only patients don't know that data, making choosing a surgeon a high-stakes guessing game.Stefan Larsson looks at what happens when doctors measure and share their outcomes on hip replacement surgery, for example, to see which techniques are proving the most effective.Could health care get better—and cheaper—if doctors learn from each other in a continuous feedback loop?

Fluorosis is a defect of the enamel (hypomineralization or hypoplasia) due to excessive intake of fluoride during enamel formation.Although these two have a similar appearance on the enamel of the teeth, namely, a white spot, they have distinct physical characteristics.In this case, for the upper peg lateral incisors, a composite bonding procedure was performed by a skilled GD (Dr. Mindy Nguyen) to yield the proper size and shape (Figure 9.15c). The patient was also considering tooth whitening at a later time. #### Underbite Underbite is the term that a layperson would typically use, but dentists would use the correct term: anterior crossbite or negative OJ. This condition is often associated—but not always—with class III malocclusion. ##### Complications and how to avoid and treat them There are many different techniques that can be used to treat this kind of problems. A thorough discussion of these techniques is beyond the scope of this chapter. For some patients with mild anterior crossbite and class III malocclusion, class III mechanics with rubber bands could be used successfully if the patient is highly motivated. When the patient has moderate negative OJ, one of the proposed treatments would be extracting the lower first premolars and upper second premolars—provided that the rest of the teeth are healthy and worth keeping. For class III malocclusion, extracting only the lower first premolars often leads to poor occlusion at the end of orthodontic treatment. Again, it should be emphasized that these extraction recommendations are oversimplified because the decision of which teeth to be extracted is based on multiple factors, including the possibility of orthognathic surgery especially for young adults with severe skeletal Class III. #### White spot lesion White spot lesion (WSL) on teeth is typically a manifestation of either mild fluorosis (slightly excessive intake of fluoride) or demineralization/decalcification (loss of minerals or mineral salts). Although these two have a similar appearance on the enamel of the teeth, namely, a white spot, they have distinct physical characteristics. Fluorosis is a defect of the enamel (hypomineralization or hypoplasia) due to excessive intake of fluoride during enamel formation.Mild fluorosis results in white flecks or white lines or opaque patches in the enamel, whereas moderate and severe fluorosis would display chalky and opaque or mottling enamel (Cameron, 2003).Enamel with mild fluorosis would be smooth, shiny, and noncarious.Lesion is derived from the Latin word _laesio_ , meaning _injury_ , so mild fluorosis should not be considered as a lesion.

NUTRITIONAL THERAPY: • L-lysine cream applied directly on blisters • Lysine (4 g daily for the first four days, then 500 mg three times daily for two weeks).DIET: Whole foods diet with more raw vegetables and cultured products such as yogurt and sauerkraut.Some conditions, including yours, may require a physician's care.Stay off alcohol, chemicals, and fats. TRADITIONAL CHINESE MEDICINE: The Chinese herb Bupleurum (chai-hu) may be helpful. ## COLD SORES (HERPES SIMPLEX) Small fever blisters, often recurrent, found anywhere around the mouth, caused by the herpes simplex virus 1 (HSV1). Groupings of these blisters are called a cluster. SYMPTOMS: The first bout may be accompanied by flu-like symptoms, with fever, neck pain, lymph node enlargement, and fatigue, or it may go unnoticed. After the first attack, the virus remains dormant in nerve cells, but can be reactivated by stress, colds, hot weather, anxiety, nutrient deficiencies, or other illnesses, especially ones with accompanying fever. Prolonged bouts may occur in people with immune suppression or in healthy people under high stress. Recurrent attacks start with a burning sensation that soon is followed by blisters that can be very sore and itch. Within a few days to several weeks, they burst, dry, encrust, and disappear. OCCURRENCE: 90% of people have this infection at least one time during their lives. CONSIDER: Herpes zoster, Coxsackie virus, low thyroid, health problems depressing immune function. SPECIAL NOTES: These sores are very contagious. Oral sex can spread HSV1 from the mouth to the genitalia. The drug acyclovir is prescribed orally and topically. However, it may cause an increase in symptoms on cessation of the drug. Also, antiviral drugs are very strong to be able to penetrate the well-protected viruses, so they are hard on the body and especially the liver. ## Alternative Treatments Refer to alternative therapy chapters for more information before evaluating or applying any treatment. Some conditions, including yours, may require a physician's care. DIET: Whole foods diet with more raw vegetables and cultured products such as yogurt and sauerkraut. NUTRITIONAL THERAPY: • L-lysine cream applied directly on blisters • Lysine (4 g daily for the first four days, then 500 mg three times daily for two weeks).If continual daily lysine is the only way for you to prevent recurrent attacks, then decrease wheat and add other grains to diet and take lysine in small dosages with amino acid blends and consider amino-acid testing.• Vitamin B complex • Zinc gluconate • Vitamin C with bioflavonoids • Thymus extract • Acidophilus • Vitamin E • The flavonoid quercetin has been shown to inhibit the herpes virus.

Copyright 2013.)(With permission from Waschke J, Paulsen F (eds), Sobotta Atlas of Human Anatomy, 15th ed, Elsevier, Urban & Fischer.55.7 The distribution of the right and left phrenic nerves.Fig.There is some evidence that the crural fibres contract slightly before the costal part, and this may be functionally significant for non-respiratory tasks.### Lymphatic Drainage The diaphragm is drained by anterior, middle and posterior groups of lymph nodes that lie on its superior surface; they also drain the superior portion of the liver, the gastro-oesophageal junction and the abdominal surface of the diaphragm. In addition, lymph drains anterosuperiorly to parasternal and anterior mediastinal nodes, and posterosuperiorly to posterior mediastinal and brachiocephalic nodes. Hepatocellular carcinoma Successful control of hepatocellular carcinoma often requires chemo­embolization of the hepatic artery, as well as any extrahepatic collaterals; the right inferior phrenic artery is often found to be associated with hepatocellular carcinoma as a major collateral pathway. Transcatheter oily chemoembolization regresses the tumour with increased survival rates. The inferior phrenic vein is one of the major sources of collateral venous drainage in hepatocellular carcinoma (and in retroperitoneal malignant disease). As well as conventional angiography, the use of 64+ slice computed tomography (CT) scanners enables clear visualization of the right and left inferior phrenic arteries, making CT a reliable method of diagnosing thrombosis and aneurysm of these vessels (Loukas et al 2008). ## Innervation The diaphragm receives its motor supply via the phrenic nerves (Fig. 55.7). Sensory fibres are distributed to the peripheral part of the muscle by the lower six or seven intercostal nerves. The fibres of the right crus of the diaphragm divide to the right and left of the oesophagus and are innervated by both right and left phrenic nerves. There is some evidence that the crural fibres contract slightly before the costal part, and this may be functionally significant for non-respiratory tasks. Fig. 55.7 The distribution of the right and left phrenic nerves. (With permission from Waschke J, Paulsen F (eds), Sobotta Atlas of Human Anatomy, 15th ed, Elsevier, Urban & Fischer. Copyright 2013.)Derived mostly from the fourth cervical ramus, it also receives contributions from the third and fifth cervical ventral rami (see Figs 29.17, 29.18).The course of the cervical part of the phrenic nerve is described on page 464.

However, the cardiovascular mortality and morbidity of this patient group is only partially explained by traditional risk factors [50], and disorders of mineral metabolism may contribute substantially to the high incidence of events [51–56].For a long time microscopic organisms called nanobacteria were thought to be implicated in the process of atherosclerosis where they operated as nucleating factors for CAC. More recently what was once believed to be an infectious agent has been described as a core of phosphate and calcium crystals with adherent molecules of fetuin-A; these complexes have been shown to act as nucleating factors for fast growth of calcification [47]. Nonetheless, before such knowledge was acquired tetracyclines – as treatment for nanobacteria – were combined with ethylenediaminetetraacetic acid disodium salt (EDTA) – as a chelating agent, as well as vitamins and CoQ10 and administered to 77 volunteers with stable coronary artery disease [48]. EBT scans were performed at baseline and after a short follow-up of 4 months. Of the 77 patients, 44 (57 %) showed CAC score regression (average −14 %), while the remaining 33 showed either no change or an increase in score. Of interest, serum lipid levels were reduced in a large proportion of patients despite the fact that most patients were already receiving statins prior to enrollment. No liver, renal or hematological side effects were recorded. Obviously, these studies were very small and mainly exploratory in nature and the utility of such interventions will need to be confirmed in larger prospective studies. ## Cardiovascular Calcification in End Stage Renal Disease and the Effect of Therapies on Its Progression The cardiovascular disease rates of patients suffering from end-stage chronic kidney disease receiving dialysis (CKD stage 5D) are 30–50 fold higher than in the general population [49]. However, the cardiovascular mortality and morbidity of this patient group is only partially explained by traditional risk factors [50], and disorders of mineral metabolism may contribute substantially to the high incidence of events [51–56].Vascular and valvular calcifications are very extensive in CKD-5D (Fig.6.3) and progress rapidly.In an attempt to curb the rapid progression of calcification, the Treat-to-Goal Study—a randomized, multicenter clinical trial—compared the calcium-free, non-absorbable polymer sevelamer with traditional calcium-based phosphate binders [58].

Nowadays, CT is routinely used as the first-step diagnostic modality in neuroimaging, in many cases even before MRI, in order to detect or exclude intracranial haemorrhage, either traumatic or non-traumatic, or to detect other causes of neurological disease, such as stroke, cerebral tumours, haematoma, or neurodegenerative disorders._J Peripher Nerv Syst_ 2012; **17** Suppl 3:9–13. 242. Shy ME, et al. Phenotypic clustering in MPZ mutations. _Brain_ 2004; **127** (Pt 2):371–84. 243. Vinci P, et al. Psychological distress in patients with Charcot-Marie-Tooth disease. _Eur J Phys Rehabil Med_ 2009; **45** :385–9. 244. Bateman RJ, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. _N Engl J Med_ 2012; **367** :795–804. ## SECTION 2 ## Imaging technique ## CHAPTER 6 ## Computed tomography Michele Anzidei, Fabrizio Boni, Giuseppe Pelle, and Carlo Catalano ### Introduction Computed tomography (CT) has been a revolution in the field of brain diagnostic imaging, both for its technical characteristics and for its range of applications, which are progressively expanding even today. Since its introduction, CT has continually undergone technological improvement and optimization in order to increase its use in everyday medical practice. In the early 1990s, the transition from spiral single-detector scanners to multi-detector technology has enabled a significant reduction of acquisition time, allowing an excellent balance between spatial and temporal resolution, both of which are fundamental requirements in imaging, especially for vascular studies. Nowadays, CT is routinely used as the first-step diagnostic modality in neuroimaging, in many cases even before MRI, in order to detect or exclude intracranial haemorrhage, either traumatic or non-traumatic, or to detect other causes of neurological disease, such as stroke, cerebral tumours, haematoma, or neurodegenerative disorders.The advent of innovative techniques such as perfusion CT and multi-spectral CT is also constantly expanding the indications for CT in neuroimaging.### Physical principles and standard CT technique In order to adapt CT examinations to various clinical scenarios, it is essential to know how to handle the main technical parameters during image acquisition and reconstruction.

There are many more studies than these; this just gives a very good overview of the range of actions of the plant and its constituents.baicalensis_ extract stimulates the formation of red blood cells and their precursors under conditions of cyclostatic myelosuppression and sleep deprivation._S.The herb is both anti-inflammatory and antinociceptive.It reverses the reduction of extracellular ERK phosphorylation and the level of BDNF (brain-derived neurotrophic factor) expression in the hippocampus of CMS (chronic mild stress) model rats. Oral administration of baicalein in mice infected with Sendai virus results in a significant reduction of viral titers in the lungs and a reduction in the death rate. Oral administration of baicalein in mice infected with influenza A virus shows significant effects in preventing death, increasing life span, inhibiting lung consolidation, and reducing lung virus titer in a dose-dependent manner. Amounts as low as 1.2 mcg/ml of baicalin (the metabolite of baicalein) result in significant inhibition of the virus. (Note: Plasma levels of baicalin from the ingestion of skullcap root are significantly higher than this after dosing with 3–9 grams per day.) Baicalein is highly synergistic with ribavarin against H1N1 influenza. The combination produces much better outcomes in mice infected with influenza A infected than ribavirin alone. Baicalein and wogonin inhibit irradiation-induced skin damage by suppressing increases in MMP-9 and VEGF through the suppression of COX-2 and NF-κB. In mice infected with hepatitis C virus and treated with _S. baicalensis_ , the serum virus content of the mice decreases after treatment with the herb. _S. baicalensis_ treatment inhibits passive cutaneous anaphylaxis and reduces histamine release in rats receiving intradermal injections of anti-DNP (dinitrophenol) IgE. It is also effective in reducing IL-6 and TNF-α in mouse models of pelvic inflammatory disease. The herb is both anti-inflammatory and antinociceptive. _S. baicalensis_ extract stimulates the formation of red blood cells and their precursors under conditions of cyclostatic myelosuppression and sleep deprivation. There are many more studies than these; this just gives a very good overview of the range of actions of the plant and its constituents.(Details are unfortunately sketchy.)The herb is almost always used in combination, so individual studies are few.But there are some here and there: Sixty-three people with bacterial meningitis were split into two groups; 32 were treated with both an antibiotic and baicalin, 31 were treated with an antibiotic alone.

Reviews by da Costa showed that substantia nigra was modulated by omega-3 fatty acids, while Dyall found that they modulated hippocampal neurogenesis.## Omega-3 Fatty Acids in Structural and Functional Neurological Changes Actual brain and neuron structural changes are important in brain dysfunction.In the past several decades there has been approximately a 10-fold increase in the ratio of omega-6 compared to omega-3 consumption. As expected, Tokuyama found that omega-3 fatty acids modulated other aspects of neurological dysfunction, especially pain. In addition, Judge and coworkers found significant confirmatory research on the role of fatty acids in maternal and child mental health. At the other end of the age spectrum, Alfos defines the role of fish oil containing omega-3 fatty acids in preventing age-related memory loss via hormone receptors, while Tan reviews blood levels of fatty acids in aging brain function to understand their mechanisms of action. Paul also found limited evidence that omega-3 fatty acids acted on Alzheimer's disease. Clearly the companion omega-6 fatty acids have adverse effects in high or disproportionate levels. Unfortunately, omega-6 fatty acids are the primary fatty acids consumed in most Western diets. Freeman described the association between the accumulation of other fats and fatty acids and obesity and changed cerebrovascular functions. The actions of such fatty acids in clinical depression are outlined by Chandola and coworkers, and their effects on major depression are outlined by Lawson. In children, their potential functions incorporated in fish oil in the growing epidemic of attention deficit hyperactivity disorder (ADHD) are summarized and reviewed by Ali. ## Omega-3 Fatty Acids in Structural and Functional Neurological Changes Actual brain and neuron structural changes are important in brain dysfunction. Reviews by da Costa showed that substantia nigra was modulated by omega-3 fatty acids, while Dyall found that they modulated hippocampal neurogenesis.As might be expected, Parisi's review found that obese children with high levels of fat and non-omega-3 fatty acids were at more risk of migraine headaches.Lower back pain was similarly susceptible to a kinematic approach in the obese, as summarized by Cimonlin and coauthors.

Finally, patients with Refsum disease are maintained on a diet with no phytanic acid (found in beef, lamb, tuna, cod, and haddock); attempts to find alternative/natural therapies are also ongoing.Further research is attempting to provide further support for this treatment and to elucidate the mechanism of Lorenzo's oil.Refsum disease is caused by a specific mutation on either chromosome 6 or 10, which decreases the breakdown of phytanic acid, a 16-carbon fatty acid found normally in the human diet. Patients with Refsum disease usually present with symptoms in childhood or early adolescence. The three diseases of the Zellweger spectrum share many similar symptoms. Absent β-oxidation of VLCFA leads to damaging increases in levels of 24- to 30-carbon fatty acids, which result in an enlarged liver, jaundice, and intestinal bleeding. Without production of plasmalogen, the insulating myelin membrane is compromised, leading to progressive brain and nerve damage with seizures, loss of vision and hearing, decreasing muscle tone and strength culminating in the inability to move (again due to decreased production of the myelin sheath), and, in infants, poor or absent suckling or swallowing ability. ALD patients often develop adrenal gland failure secondary to buildup of the VLCFAs in these organs. A variant of ALD predominately strikes the spinal cord with symptoms including weakness and numbness of the limbs and problems with urination and defecation. Death usually occurs in childhood or early adolescence due to problems occurring in the affected organs. Treatment for Zellweger syndrome is mainly supportive, including prevention of infections; however, death usually occurs before the first birthday. Some success in the treatment of ALD has been reported with bone marrow transplantation and a diet with low intake of VLCFA and inclusion of **Lorenzo's oil** , a mixture of 18- and 22-carbon triglycerides. Further research is attempting to provide further support for this treatment and to elucidate the mechanism of Lorenzo's oil. Finally, patients with Refsum disease are maintained on a diet with no phytanic acid (found in beef, lamb, tuna, cod, and haddock); attempts to find alternative/natural therapies are also ongoing.In the case of **very-long-chain fatty acids** ( **VLCFA** ), breakdown occurs in peroxisomes, organelles found in all eukaryotes that provide specialized lipid metabolism as well as processing of toxic substances.Peroxisomes metabolize VLCFA down to an eight-carbon octanyl-CoA, which is then further processed by mitochondria as described above.

intestinal atresia [L, _intestinum_ \+ Gk, _a_ \+ _tresis,_ boring], a pathological obstruction of the continuous lumen of the intestinal tract caused by a defect of development in utero.See also **atherosclerosis**.The occlusion is removed, and often the affected portion of the bowel is resected.Treatment is usually surgical.A **problem-solving interview** focuses on problems that have been identified by the patient or health care professional. intervillous space /in′t rvil′ s/ [L, _inter_ \+ _villus,_ hair, _spatium_ ], one of many spaces between the chorionic villi of the endometrium of the gravid uterus, beneath the placenta. The intervillous spaces act as small reservoirs for oxygenated maternal blood from which the fetal circulation may take up the nutrients and gases by osmosis, hydrostatic pressure, and diffusion. intestinal. See intestine. intestinal absorption [L, _intestinum,_ intestine, _absorbare,_ to swallow], the passage of the products of digestion from the lumen of the small intestine into the blood and lymphatic vessels in the wall of the gut. The surface area of the intestine is greatly increased by the presence of fingerlike projections called villi, each of which contains capillaries and a lymphatic vessel, or lacteal. Most dissolved nutrients pass quickly into the capillary bed for transport through the portal circulation to the liver. Lipids enter the lymphatic channels, which eventually rejoin the venous circulation at the thoracic duct in the neck. intestinal amebiasis. See **amebic dysentery**. intestinal angina, chronic vascular insufficiency of the mesentery caused by atherosclerosis and resulting ischemia of the smooth muscle of the small bowel. Also called **chronic intestinal ischemia**. intestinal apoplexy, the sudden occlusion of one of the three principal arteries to the intestine by an embolism or a thrombus. This condition leads rapidly to necrosis of intestinal tissue and is often fatal. Treatment is usually surgical. The occlusion is removed, and often the affected portion of the bowel is resected. See also **atherosclerosis**. intestinal atresia [L, _intestinum_ \+ Gk, _a_ \+ _tresis,_ boring], a pathological obstruction of the continuous lumen of the intestinal tract caused by a defect of development in utero.It is performed so that less intestinal surface will be available to absorb nutrients from the digested food passing through, as in morbid obesity, or to bypass a blocked or diseased portion of the intestine.The technique usually involves anastomosing the jejunum to the ileum.See also [**ileal bypass**.

Patients experiencing nausea and vomiting, bowel disturbances, mucositis and taste alterations typically have little desire for, and actual mechanical difficulty with, eating and drinking.Other treatment-induced GI side effects can also interfere with appetite.Large tumours produce more of these factors, thus resulting in the cachexia seen in advanced cancer.This is thought to lead to faster replacement of these cells when killed by cancer treatment and is believed to speed up the healing process of mouth ulcers.31 Paliferm is currently recommended for mucositis prevention in patients with haematological malignancies undergoing high-dose chemotherapy and total body irradiation with autologous stem cell transplant.31 The safety and efficacy of palifermin for patients with non-haematological malignancies have not been established. Soft, non-irritating, high-protein and high-kilojoule foods should be offered frequently throughout the day. Extremely hot or cold food and drinks should be avoided; so should tobacco and alcohol. The patient should be encouraged to take nutritional supplements as an adjunct to meals and fluid intake and should be weighed at least twice per week to monitor for weight loss. Families are an integral part of the healthcare team. As symptom severity increases, the family's role in assisting the patient to eat becomes increasingly critical. If family members are not available, alternative support, such as volunteers and home aides, may be helpful. ##### Anorexia Anorexia may develop as a general reaction to treatment. The mechanisms for anorexia are unclear but several theories exist. Macrophages release TNF and IL-1 in an attempt to fight the cancer. Both TNF and IL-1 have an appetite-suppressing (anorectic) effect. As tumours are destroyed by therapy, it is thought that increased levels of these factors may be released into the system and cross the blood–brain barrier, exerting an influence on the satiety centre. Large tumours produce more of these factors, thus resulting in the cachexia seen in advanced cancer. Other treatment-induced GI side effects can also interfere with appetite. Patients experiencing nausea and vomiting, bowel disturbances, mucositis and taste alterations typically have little desire for, and actual mechanical difficulty with, eating and drinking.The nurse should monitor the patient with anorexia carefully during treatment to ensure that weight loss does not become excessive and offer dietary counselling.Small, frequent meals of high-protein, high-kilojoule foods are better tolerated than large meals.Nutritional supplements can be helpful as well.

Dermatologists advise rubbing salad oils or fats on the skin, particularly on babies and older persons.NIL **SALAD OIL •** Any edible vegetable oil.That does not mean, however, that it cannot be used for other purposes.The FDA issued a notice in 1992 that Saint John's wort has not been shown to be safe and effective as claimed in OTC ( _see_ ) digestive-aid products.Greek sage oil, obtained by steam distillation, is used in berry, grape, liquor, meat, crème de menthe, nutmeg, and sage flavorings for beverages, ice cream, ices, candy, baked goods, chewing gum, condiments, meats, and pickles. Greek sage oleoresin ( _see_ ) is used in sausage and spice flavorings for condiments and meats. Spanish sage oil is used in fruit and spice flavorings for beverages, ice cream, ices, candy, baked goods, condiments, and meats. It is also used as a meat preservative. Greek sage is used in medicine. Used by herbalists to treat sore gums, mouth ulcers, and to remove warts. Arabs believed it prevents dying. GRAS. ASP **SAIGON CINNAMON and SAIGON CINNAMON LEAF OIL •** _See_ Cinnamon. **SAINT JOHN'S BREAD •** _See_ Locust Bean Gum. GRAS **SAINT JOHN'S WORT FLOWERS, LEAVES, and CAULIS •** _Hypericum perforatum_. Amber. Blessed. Devil's Scourge. God's Wonder Herb. Grace of God. Goatweed. Hypericum. Klamath Weed. The plant contains volatile oil, tannin, resin, pectin, and glycosides ( _see all_ ). It was believed to have infinite healing powers derived from the saint, the red juice representing his blood. It was used as an antivenereal. It is used to treat pains and diseases of the nervous system, arthritic pains, and injuries. An infusion made from its leaves is used for stomach disorders, diarrhea, depression, and bladder problems, and to remove threadworms in children. It is now being studied by researchers from the National Cancer Institute and various universities as a potential treatment for cancer and AIDS. The FDA listed Saint John's wort as an "unsafe herb" in 1977. The FDA issued a notice in 1992 that Saint John's wort has not been shown to be safe and effective as claimed in OTC ( _see_ ) digestive-aid products. That does not mean, however, that it cannot be used for other purposes. NIL **SALAD OIL •** Any edible vegetable oil. Dermatologists advise rubbing salad oils or fats on the skin, particularly on babies and older persons.This is a family of reduced-calorie fats that are only partially absorbed in the body.It contains 5 calories per gram.It is used in such products as Hershey's reduced-fat, semisweet chocolate-flavor baking chips.GRAS **SALICARIA EXTRACT •** Spiked Loosestrife.Extract of the flowering herb _Lythrum salicaria_ , which has purple or pink flowers.

## II Arteriosclerosis A **Definition** • Thickening and loss of elasticity of arterial walls Arteriosclerosis: thickening of arterial wall; loss of elasticity B **Medial calcification** Medial calcification: dystrophic calcification of muscular arteries (uterine, radial) 1.**Pharmacologic therapy** consists of nicotinic acid or fibric acid derivatives.Note the slightly yellow nodular lesions at the distal end of the Achilles tendon. **B,** Xanthelasma. Yellow, raised lesions are noted on the lower left eyelid. **C,** Palmar xanthomas. Note the yellow macules on the palm that are accentuated in the creases. **D,** Eruptive xanthomas. Note the numerous small yellow papular lesions distributed over the buttocks. ( **A** courtesy A.F. Lant, MD, and J. Dequeker, MD, London; **B** from Yanoff M, Duker J: Ophthalmology, 3rd ed. St. Louis, Mosby, 2009, Fig. 12-9-18; **C** and **D** courtesy R.A. Marsden, MD, St George's Hospital, London.) **Nonpharmacologic treatment of type II hyperlipoproteinemia** includes dietary modification, increasing activity with aerobic exercises, and cessation of smoking. Dietary modification consists of a low CH, low-fat diet (fat intake <30% of total caloric intake); polyunsaturated fat up to 10% of total calories; monounsaturated fat up to 20% of total calories; saturated fat <7% of total calories; no more than 200 mg/day of CH; and dietary fiber 20 to 30 g/day. Pharmacologic treatment includes HMG (Hydroxy Methyl Glutaryl)-CoA reductase inhibitors ("statins"; most effective); nicotinic acid (least expensive lipid-lowering agent; also decreases TG, and increases HDL greater than other drugs); bile salt sequestrants; and cholesterol absorption inhibitors. **Nonpharmacologic treatment of type IV hyperlipoproteinemia** is to reduce alcohol intake and carbohydrate intake and increase intake of ω-3 fatty acids from fish, flaxseed oil, or other sources (up to 3 g/day). **Pharmacologic therapy** consists of nicotinic acid or fibric acid derivatives. ## II Arteriosclerosis A **Definition** • Thickening and loss of elasticity of arterial walls Arteriosclerosis: thickening of arterial wall; loss of elasticity B **Medial calcification** Medial calcification: dystrophic calcification of muscular arteries (uterine, radial) 1.Can be seen in plain radiographs b. Examples—calcification in uterine arteries and radial arteries 2._No_ clinical consequence unless it is associated with atherosclerosis C **Atherosclerosis** 1.Epidemiology a.More common in men than women b.

The flap can be a valuable adjunct in the initial perineal and thigh coverage of defects following necrotizing fasciitis.It is particularly suited for the repair of radiation pros-tato-membranous strictures, recurrent failed post anastomotic urethral distraction defects and the rare rectourethral fistula associated with a proximal stricture.The distal tendon medial to the semitendinosis is divided and the flap is elevated after the skin flap is prepared Fig. 16.15. The flap is rotated on its pedicle with tension in the defect after dividing the groin skin bridge If compression potential exists, then the skin bridge is divided. If further skin paddle rotation or advancement is required at the recipient site, the legs are then brought down with some adduction and muscle shortening which provides an additional 3 to 6 cm in length. The thigh and perineal incisions are closed with a suction drain (Blake) that is left in for 72 h. The leg is firmly wrapped and the patient is immobilized for 72 h, and subcutaneous heparin is administered for 7 d. If any of the surface demonstrates necrosis then early debri-dement with a stented skin graft is instituted. Fig. 16.16. The postoperative urethrogram reveals fistula closure under an effective perineal skin cover The anatomical approach to the harvest of the myofasciocutaneous flap with aggressive inclusion of the perigracilis fascia creates the most reliable vascular inflow to the middle third of the skin island (Fig. 16.17). All the cases have been retrieved by preseptic debridement and a stented split thickness skin graft cover. Fig. 16.17. The perigracilis septocutaneous perforators that come around the muscle result in a well perfused viable myocutaneous axial flap ## 4 4. Perineal Artery Fasciocutaneous Flap (Singapore) The perineal artery medial thigh fasciocutaneous flap is another concept in tissue transfer that has the potential of salvaging the complex proximal prostato-membranous and bulb stricture. It is particularly suited for the repair of radiation pros-tato-membranous strictures, recurrent failed post anastomotic urethral distraction defects and the rare rectourethral fistula associated with a proximal stricture. The flap can be a valuable adjunct in the initial perineal and thigh coverage of defects following necrotizing fasciitis.Its robust blood supply, predictable measurements, minimal donor site morbidity, and prior reported success in vaginoplasty make this flap an ideal alternative option for complex proximal ure-thral reconstruction.

These methods are discussed in more detail below.The selected antigen can be carried and introduced to its target using various mechanisms, including a virus vector or DNA plasmid or using one of the host own antigen presenting cell as a vehicle.The third antigen is the prostate-specific membrane antigen (PSMA).A high level of CD4+ andCD8+ T-cell immune responses was observed. The GM-CSF attracts antigen-presenting cells to the injection site. Other cytokines did not show similar anti-tumour activity. The treatment works by recruiting antigen-presenting cells (APC) such as dendritic cells to injection sites. The vaccine cells are lysed and the debris are taken up by APC, resulting in TH1 and TH2 cell activation which activates cytotoxic cell tumour lysis. The whole cell allogeneic immunotherapy treatment has been developed further and has used prostate cancer cell lines including the hormone sensitive cell line LNCaP and hormone resistant cell line PC3. In a Phase II trial studying the effect of this type of treatment, dendritic cells and macrophages in addition to eosinophils were present at the site of the intradermal injection, confirming the ability of the transduced cells to secrete GM-CSF in vivo. Several patients mounted LNCaP and PC3 reactive antibodies. There is a possible correlation between the antibody titre and time from vaccination. This treatment strategy exposes multiple tumour antigens to potentiate the anti-tumour immune response. Antigen-specific approach This strategy focuses on one antigen to evoke an anti-tumour immune response. Various tumour-associated antigens (TAA) antigens have been studied for this type of treatment. Three of them have been targeted. Prostatic-specific antigen (PSA) is a glycoprotein and a serine protease enzyme secreted by the epithelial cells of the prostate gland. Another antigen is prostate acid phosphatase (PAP), which is expressed in the vast majority of prostate cancer cells. The third antigen is the prostate-specific membrane antigen (PSMA). The selected antigen can be carried and introduced to its target using various mechanisms, including a virus vector or DNA plasmid or using one of the host own antigen presenting cell as a vehicle. These methods are discussed in more detail below.The most commonly used vector is Vaccinia virus as prime vaccine and fowlpox virus as the booster vaccine (ProstVac VF).This vaccine has a DNA plasmid encoding PSA, in addition to co-stimulatory molecules (lymphocyte function-associated antigen 3 LFA3, CD80 and intracellular adhesion molecule 1 (ICAM1)).

Each, of course, carries its own potential side effects, and multiple drugs complicate the task of assessing one's progress.In fact, clinical guidelines often mention this kind of augmentation to deal with the common side effects of psychotropics—Ritalin to counteract decreased libido and weight gain, Viagra for problems with sexual arousal, Wellbutrin for both sexual problems and drowsiness.For a long time I maintained that I was just one of those people who needed lots of sleep, and lectured friends who slept less, saying they didn't know how impaired they were. But my lingering daytime tiredness has me wondering if I was wrong about myself—if turning into someone who on some fundamental level needed lots of sleep was a side effect of my medication. Drowsiness is a potential side effect of practically every psychotropic drug, except the stimulants. Wellbutrin, the antidepressant I've taken for five years, is supposedly "activating," but most of the time I have also been taking an SSRI antidepressant to help temper my anxiety, and those might well make me sleepy. Or maybe, as Claire had surmised about her own situation before trying Cymbalta, my underlying depression is mostly treated by the meds, but the disrupted sleep remains. Doctors have not been very sympathetic. My primary care physicians keep testing for thyroid problems, vitamin deficiencies, and the like. My psychiatrists say, "Well, maybe you're just someone who needs a lot of sleep." We've broached the topic of my taking some sort of stimulant, like Provigil, to counteract the effects of the other meds; I know other people who do this. But the idea of adding a drug to treat the side effects of another drug vaguely disturbs me, as it does many people. In fact, clinical guidelines often mention this kind of augmentation to deal with the common side effects of psychotropics—Ritalin to counteract decreased libido and weight gain, Viagra for problems with sexual arousal, Wellbutrin for both sexual problems and drowsiness. Each, of course, carries its own potential side effects, and multiple drugs complicate the task of assessing one's progress.