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Demonstration of luteotrophic responses of human recombinant gamma interferon in porcine corpora lutea using an in-vivo microdialysis system. Conceptuses from several mammalian species prior to implantation secrete proteins belonging to the family of interferons. The main species of interferons known to be secreted by the pig blastocyst is interferon gamma (IFNgamma), the precise role of which is unclear. We decided to explore its effects on corpus luteum (CL) function using the novel microdialysis technique in vivo. Six cycling miniature pigs were monitored for estrus by daily plasma progesterone analysis and visual symptoms. On day nine of the cycle (day zero being the day of ovulation) the animals underwent surgery, and microdialysis tubing (vitafiber, Amicon U.S.A, cut off mol. wt. 1 million) were implanted in 17 corpora lutea. The inlets and outlets of all tubings were exteriorized and the entry and exit points of tubings in the CLs sealed with tissue glue. The afferent extension tubings were connected to a fraction collector and the system was continuously flushed with Ringer at a flow rate of 2.4 ml/h. After an initial flushout phase of 8 h, fractions were collected every half hour over 3 days. On days 10, 11 and 12 post estrus 12 CLs were stimulated for 4 h with 10(-7) M, 2 x 10(7) M and 4 x 10(-7) M human recombinant IFNgamma (Pharma Biotechnologie) respectively. Simultaneously, fractions were also collected from the remaining five unstimulated corpora lutea which served as controls. Progesterone concentrations in the dialysates were estimated by a sensitive enzymeimmunoassay (EIA). A significant increase (P < 0.01) in progesterone release was observed in all 3 days following stimulation. The progesterone increase was more marked on the first day of stimulation (1 x 10[-7] M) with the hormone levels rising further even after the end of stimulation. The overall increase in progesterone concentration was 2-fold on day 10 in comparison to 15-30% on subsequent days even though IFN concentrations for stimulation were 2- and 4-fold higher. In the unstimulated CLs, a gradual decline (P < 0.01) in progesterone levels were observed over days. In conclusion, these data provide evidence that the early conceptus signals its presence by way of IFNgamma to maintain the CL in pigs.

The process of exiting vegetarianism: an exploratory study. The experience, reasons, and contexts associated with leaving vegetarianism were explored. Interviews were conducted with a convenience sample of 19 ex-vegetarians and 15 continuing vegetarians. Exiting vegetarianism is similar to the process of leaving other important individual identities, including exiting diets containing meat. It is a process, not an event, and partially a response to inconvenience, particularly when the person's table companions were not vegetarians. Major life changes and declines in self-perceived health provided occasions to reassess life choices, including the vegetarian commitment. Ex-vegetarians interpreted their vegetarianism as a transition to a new, healthier diet. Including a comparison group of continuing vegetarians revealed that the ex-vegetarians were more likely to have become vegetarians as a result of concern about the well-being of animals and the environment, not animal rights, a value more difficult to compromise. Exiting processes show the five central food values of taste, health, time, cost, and social relationships undermine people's commitment to a diet chosen largely for moral reasons.

Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis. Current therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are limited. A pilot study was conducted of autologous peripheral blood stem cell (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n = 2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 x 10(6) (range 0 to 410 x 10(6)) CD34(+) cells per kilogram were collected. Twenty-one patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC transplantation. The median times to neutrophil and platelet recovery after transplantation were 21 (range 10-96) and 21 (range, 13 to > or = 246) days, respectively. Five patients received back-up PBSC infusion because of delayed neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days after transplantation, and the 2-year actuarial survival is 61%. After transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC infusion) and 3 of disease progression. Erythroid response (hemoglobin > or = 100 g/L [10 gm/dL] without transfusion for > or = 8 weeks) occurred in 10 of 17 anemic patients. Four of 8 patients with a platelet count less than 100 x 10(9)/L (100 000/microL) responded with a durable platelet count more than 100 x 10(9)/L (100 000/microL). Symptomatic splenomegaly improved in 7 of 10 patients. It is concluded that (1) PBSC collection was feasible and stable engraftment occurred after transplantation in most patients with MMM, (2) myeloablation with busulfan was associated with acceptable toxicity, (3) a significant proportion of patients derived clinical benefit after treatment, and (4) further investigation of this novel approach is warranted. (Blood. 2001;98:586-593)

Laparoscopic fundoplication: a natural extension for the thoracic surgeon. Thoracic surgeons have historically played a significant role in surgical treatment of benign esophageal disorders. With the advent of video-assisted thoracic surgical techniques, chest surgeons have also become adept at minimally invasive procedures. Thus, it seems appropriate that thoracic surgeons participate in minimally invasive antireflux operations, such as laparoscopic Nissen fundoplication. From February 1993 to May 1995, 66 patients (32 male, 34 female) with a mean age of 45.5 years (range, 15 to 82 years) underwent a laparoscopic fundoplication. Gastroesophageal reflux disease was diagnosed on the basis of history and endoscopically documented esophagitis or abnormal esophageal pH testing or both. There were 45 type I, 3 type II, and 7 type III hiatal hernias. Eleven patients had gastroesophageal reflux disease with no hernia. Conversion to laparotomy occurred in 6 patients (9%) due to bleeding in 2 patients, inability to expose the gastroesophageal junction in 3, and gastric laceration in 1 patient. All but 1 patient underwent a Nissen fundoplication performed over a 50F to 60F dilator. The remaining patient (type II hernia without gastroesophageal reflux disease) underwent a reduction, closure, and anterior gastropexy. There was no operative mortality. Immediate postoperative morbidity included moderate dysphagia in 7 patients (11%), ileus in 2 patients (3%), and deep venous thrombosis and atrial arrhythmia in 1 each (1.5%). Excluding 1 patient hospitalized for 42 days due to severe psychosis, the mean postoperative stay was 4.0 +/- 2.5 days (median, 3 days). Three patients (5%) required dilation for dysphagia, and 1 (1.5%) has noted recurrent reflux during follow-up (mean, 14.4 months; range, 6 to 30 months). A single patient has undergone reoperation for persistent dysphagia (1.5%). A laparoscopic Nissen procedure is safe, effective treatment for refractory gastroesophageal reflux disease when performed by thoracic surgeons experienced in minimally invasive surgical procedures.

The "shrinking lung syndrome" in SLE, treatment with theophylline. We report on a patient with systemic lupus erythematosus who developed a shrinking lung syndrome. The dyspnoea of the patient and the results of pulmonary function tests significantly improved during treatment with theophylline 750 mg daily. This is the first report of a successful treatment of the shrinking lung syndrome with theophylline.

Chrysophanol attenuates nitrosative/oxidative stress injury in a mouse model of focal cerebral ischemia/reperfusion. Nitrosative/oxidative stress plays an important role in neuronal death following cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke, however, whether its mechanism is related to attenuating nitrosative/oxidative stress is not clear. In the present study, we investigated the effect of CHR on neuronal injury related to nitric oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO) model. Our results revealed that nitrite plus nitrate (NOx-) and 3-nitrotyrosine (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were subsequently attenuated by CHR treatment. Moreover, 3-NT is colocalized with NeuN and TUNEL, suggesting that neuronal apoptosis following I/R is associated with 3-NT and CHR suppresses NO-associated neuronal cell death. Accordingly, cleaved caspase-3 expression in ischemic brain was decreased by CHR treatment. I/R also decreased the activity of total superoxide dismutase (SOD) and manganese-dependent SOD (MnSOD), whilst increased reactive oxygen species (ROS) production significantly. Interestingly, CHR reversed this decrease in total SOD, and MnSOD activity, and inhibited ROS generation in the ischemic brain. Taken together, our results provide direct evidence suggesting that CHR attenuates nitrosative/oxidative stress injury induced by I/R, providing a novel therapeutic target in the treatment of acute ischemic stroke.

[Current status of diagnosis and nonoperative therapy of small bowel ileus]. In obstructed small bowel the number of stercoral bacteria increases due to stasis, inducing a liberation of mediators that are leading to ileus disease with facultative sepsis and breakdown of the circulatory system. The therapeutic procedures have to cure the stasis. In the case of mechanical obstruction cure is achieved by operation, while functional ileus may be healed by conservative treatment. Implantation of a gastric tube or Dennis' tube can evacuate the small intestine. Several peristalsis-inducing drugs are in use, although their clinical relevance remaines to be demonstrated. Clinical examination and anamnesis offer initial information; X-ray of the abdomen confirms the diagnosis of ileus and is the baseline examination. Addition of oral contrast medium, ultrasonography, CT and endoscopy may help to evaluate the underlying cause of small-bowel paralysis.

Inhibition of the mutagenicity of benzo[a]pyrene in the V79/HGPRT system by bioantioxidants. In the presence of metabolic activation (S9 microsomal fraction of mouse-liver homogenate) the mutagenicity of benzo[a]pyrene (BP) in Chinese hamster V79 cells was inhibited by the phenolic bioantioxidants (BA) Dibunol (2,6-di-tert-butyl-4-methylphenol-D) and 5-methylresorcine(5-MR). The mixture BP + D and BP + 5-MR at molar ratios of 1:1 and 1:85 respectively showed no mutagenic activity compared to the control. One can assume that D and 5-MR inhibited BP-induced mutagenesis by binding the free radicals of BP metabolites with the formation of less active phenolic derivatives and also by linkage with cytochrome P-450, which prevents further metabolic activation of BP.

Levels of metalloproteinase (MMP-3, MMP-9), NF-kappaB ligand (RANKL), and nitric oxide (NO) in peripheral blood of osteoarthritis (OA) patients. The aim of this study was to judge whether there is a correlation between some biochemical features of knee osteoarthritic blood and clinical characteristics and to evaluate the potential relationship between osteoarthitis (OA) severity and putative biomarkers for the disease. 105 patients suffering from knee OA were analyzed clinically (Lequesne's index) and radiographically (Kellgren and Lawrence, K&L). Plasma and peripheral blood mononuclear cells (PBMC) were harvested separately. Specimens were analyzed for concentrations of nitric oxide (NO), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9). Transcript levels of the receptor activator of NF-kB ligand (RANKL) mRNA, MMP-3mRNA, and MMP-9mRNA were measured using real-time quantitative RT-PCR. Data certified significantly increasing concentrations of plasma MMP-3, MMP-9, and NO as well as transcript levels of RANKL mRNA and MMP-9 mRNA in early OA (at grade I). There was a positive correlation of MMP-3 and MMP-9 content in plasma and MMP-9 mRNA expression levels in PBMC with the severity of clinical symptoms (total Lequesne's scores) in early OA. NO content in plasma correlated with total Lequesne's scores, pain scores in response to pressure, and swelling scores of early OA patients (atgGrade I). Analogously, there were positive correlations of RANKL mRNA expression with total Lequesne's scores, pain scores in response to pressure, and swelling scores in OA patients at Grade I. [corrected] Some biochemical factors, including content of NO, MMP-3, MMP-9, and transcript levels of some genes, including MMP-9 mRNA and RANKL mRNA, may be specific and sensitive enough to diagnose OA diseases at an early stage in the pathological process of OA when radiological features do not reflect degradation of articular cartilage. Therefore, proper regulation of these factors may be a promising and realistic new target for the treatment of degenerative osteoarticular diseases.

Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IκB-NF-κB signaling pathways. Naringenin, the aglycone of naringin, has been reported to attenuate MUC5AC secretion by inhibiting activity of nuclear factor kappa B (NF-κB) via EGFR-PI3K-Akt/ERK MAPKinase signaling pathways. However, previous studies demonstrated that the MUC5AC promoter was located in two different regions: an activator protein-1 (AP-1) binding site and a NF-κB binding site. The current study comprehensively determined the involvement of MAPKs/AP-1 and IKKs/IκB/NF-κB in epidermal growth factor (EGF)-induced A549 cells, and sought to ascertain the signaling pathways of naringin imparted in suppression of EGF-induced MUC5AC secretion. The results showed that naringin of 100 μM not only significantly decreased EGF-induced overexpressions of both MUC5AC mucin and mRNA in A549 cells, but also suppressed the phosphorylation of EGF receptor, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK), as well as nucleus NF-κB p65 and AP-1. Moreover, any of three MAPKs inhibitors (PD98059, SB203580, and SP600125) significantly inhibited EGF-induced MUC5AC secretion. And as compared to MG132, the inhibitor κB (IκB) phosphorylation inhibitor of SN50 was more effective in reducing EGF-induced MUC5AC secretion because of suppression of nucleus AP-1. Meanwhile, as compared to naringin, both SP600125 and azithromycin were less effective in suppressing EGF-induced secretion of MUC5AC because of the unchanged nucleus NF-κB p65. These results indicated that naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/IκB/NF-κB signaling pathways.

Development and application of human virtual excitable tissues and organs: from premature birth to sudden cardiac death. The electrical activity of cardiac and uterine tissues has been reconstructed by detailed computer models in the form of virtual tissues. Virtual tissues are biophysically and anatomically detailed, and represent quantitatively predictive models of the physiological and pathophysiological behaviours of tissue within an isolated organ. The cell excitation properties are quantitatively reproduced by equations that describe the kinetics of a few dozen proteins. These equations are derived from experimental measurements of membrane potentials, ionic currents, fluxes, and concentrations. Some of the measurements were taken from human cells and human ion channel proteins expressed in non-human cells, but they were mostly taken from cells of other animal species. Data on tissue geometry and architecture are obtained from the diffusion tensor magnetic resonance imaging of ex vivo or post mortem tissue, and are used to compute the spread of current in the tissue. Cardiac virtual tissues are well established and reproduce normal and pathological patterns of cardiac excitation within the atria or ventricles of the human heart. They have been applied to increase the understanding of normal cardiac electrophysiology, to evaluate the candidate mechanisms for re-entrant arrhythmias that lead to sudden cardiac death, and to predict the tissue level effects of mutant or pharmacologically-modified ion channels. The human full-term virtual uterus is still in development. This virtual tissue reproduces the in vitro behaviour of uterine tissue biopsies, and provides possible mechanisms for premature labour.

[Amphiphilic drugs. 2. Relation between colloidal properties and pharmaceutic-technological, pharmacokinetic and pharmacodynamic behavior]. The physicochemical properties of amphiphilic drugs may affect the technological, pharmacokinetic and pharmacodynamic behaviours. Micelle formation of a drug is of considerable importance for its solubility, stability, adsorption pattern, mixed micelle formation and influences thus its pharmaceutical availability. The biological availability is in many cases decreased by interactions of a surface active drug with other substances before absorption, by altered diffusion behaviour and distribution properties. Colloidal association may also result in an alteration of pharmacodynamic effects. These relations depend on the fact, that discrete hydrophobic an hydrophilic parts in a molecule are also prerequisites for micelle formation and receptor interactions. Furthermore the high membrane affinity of these drugs is responsible for some therapeutic and toxic effects.

American nursing students experience shock during a short-term international program. When individuals plan to travel internationally, they frequently assume that they will have an enjoyable and memorable experience. But for some, the effects of culture shock may negatively impact their travels and memories. The purpose of this study was to describe culture shock as reported by student nurses who took part in an international short-term program. A phenomenological approach was utilized to elicit the essence of meaning attached to the experience. Eight student nurses in an upper Midwestern university, participated in this international experience. It was concluded that all of the student nurses experienced culture shock to a varying degree and they had varying perceptions of their experiences.

RNAi gene silencing using cerasome as a viral-size siRNA-carrier free from fusion and cross-linking. Surface-rigidified cerasomes (ceramic-coated liposomes) are neither fused nor cross-linked when bound to siRNA (short duplex RNA) but not to plasmid DNA (long duplex DNA) which induces cross-linking. Non-ceramic reference liposomes are easily fused by the siRNA. The cerasome can thus be used as a viral-size siRNA-carrier in a wide range of concentration for RNAi silencing of exogenous and endogenous genes.

Interindividual variation in the enzymatic 15-keto-reduction of 13,14-dihydro-15-keto-prostaglandin E1 in human liver and in human erythrocytes. The therapeutic response to PGE1 is highly variable, and a contribution by variable formation of its active tertiary metabolite PGE0 is in question. Hence, the objective of this study was to assess the person-to-person variation of the reduction of the inactive intermediate metabolite 15-KD PGE1 by human liver and human erythrocytes in forming the active metabolite PGE0. Source of enzyme was lysed erythrocytes from 29 donors, and a bank of 37 donor livers including specimens from 15 children. Tritium-labelled 13,14-dihydro-15-keto-prostaglandin E1 (15-KD PGE1) was used at low nanomolar concentrations and found to be converted almost exclusively to the more polar compound 13,14-dihydro-prostaglandin E1 (PGE0) by an NADPH-dependent carbonyl reductase. The identity of the product PGE0 was established by comparison of its chromatographic and mass spectral characteristics with authentic PGE0. Lysed erythrocytes had readily measurable enzymatic activity; differences between the preparations from 29 subjects were very small with only a twofold range of variation. In contrast to lysed erythrocytes, intact erythrocytes did not catalyse the reaction so that the erythrocyte activity should be medically immaterial. 15-KD PGE1 15-ketoreductase activity of liver cytosol averaged 61.1 fmol.min-1.mg-1 protein in preparations from 37 human livers. Individual activities varied over an almost tenfold range, with indications of a non-normal distribution. Kinetic studies of selected specimens showed substantially different Vmax values but indistinguishable kM values, suggesting that the individual variation in 15-KD PGE1 15-ketoreduction is the result of differences in enzyme concentration rather than of structural enzyme variations. The activity in 15 livers from children was significantly lower than in those from adults. Inhibition data suggest that both the liver and the erythrocyte enzymes belong to the class of carbonyl reductases. The variations in hepatic enzyme activity may be expected to affect the transformation of 15-KD PGE1 to the active metabolite PGE0 in vivo. The clinical significance remains to be explored.

On Obtaining Boltzmann-Distributed Configurational Ensembles from Expanded Ensemble Simulations with Fast State Mixing. In Expanded Ensemble (EXE) or Simulated Tempering simulations, the system's (effective) temperature is frequently updated to enhance configurational sampling. We investigated how short the EXE state update interval τ can become before too frequent updates impede Boltzmann sampling. Simulating alanine dipeptide in explicit water, we show that a hybrid MC/MD integrator reliably yields Boltzmann-distributed configurations regardless of τ. However, in MD-driven EXE simulations with short τ, configurational ensembles depend on the thermostat settings.

The actin-related protein hArp8 accumulates on the mitotic chromosomes and functions in chromosome alignment. The actin family consists of conventional actin and various actin-related proteins (Arps). Some of these Arps are localized in the nucleus, and a fraction of each of these nuclear Arps is functionally involved in chromatin remodeling and histone acetyltransferase complexes. On the other hand, in mitotic cells, the localization and function of the nuclear Arps are largely unknown. Human Arp8 (hArp8), an ortholog of yeast nuclear Arp8, was recently found to be associated with the hINO80-chromatin remodeling complex along with hArp5. Here we report that hArp8, but not hArp5, accumulates on mitotic chromosomes. This is the first example where a member of the actin family is found to be associated with mitotic chromosomes. Expression of truncated hArp8 proteins and depletion of endogenous hArp8 by RNA interference caused misalignment of mitotic chromosomes, suggesting that chromosome-associated hArp8 has a role in chromosome behavior. In contrast, depletion of hIno80 and hArp5 did not cause misalignment of chromosomes, suggesting that the role of hArp8 at mitotic chromosomes is independent of the activity of hINO80 complexes. These findings provide the first insight into a novel function of actin family members in mitosis.

Stillbirths and rate of neonatal deaths in 76,761 postterm pregnancies in Sweden, 1982-1991: a register study. To study stillbirths and neonatal mortality in the postterm period. Register study of information obtained from the Swedish Medical Birth Registry (MBR), National Board of Health and Welfare, Stockholm. Singleton pregnancies with deliveries occurring between 1982 and 1991 were selected involving 914,702 women (of whom 76,761 had a postterm pregnancy continuing beyond the 42nd week of amenorrhea). All 2,043 records of dead infants were scrutinized before analysis of neonatal deaths. Stratification was made for year of birth, maternal age, and parity. Generally, the rates of stillbirths and neonatal deaths were low. The stillbirth rate was highest for primiparas at 38 completed weeks (2.72%), lowest at 40 weeks (1.23%), then increasing to 2.26% in the postterm period. The difference vs. multiparas was significant from 41 weeks onwards. Neonatal mortality was increased at 41 completed weeks for primiparas, but for multiparas it changed significantly first in the postterm period. The OR for a primipara to have an intrauterine death increased from 1.50 at 41 weeks (1.0 at 40 weeks) to 1.79 at 42 weeks and beyond. The OR for multiparas showed no sign of increase as gestation progressed. The results of this study indicate an increased risk of stillbirth with gestational age for primiparas but not for multiparas. The neonatal death rate was increased for both primiparas and multiparas (after 42 completed weeks).

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function. The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015. Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

House dust mite-induced airway changes in hu-SCID mice. SCID (severe combined immunodeficiency) mice reconstituted with peripheral blood mononuclear cells (PBMC) from Dermatophagoides pteronissynus (Dpt)-sensitive patients and exposed to Dpt aerosol (allergic hu-SCID mice) develop human IgE and pulmonary inflammation. The present study investigated concomitant changes in airway hyperresponsiveness (AHR). No significant difference in baseline airway responsiveness was seen between nonreconstituted SCID mice exposed or not to Dpt aerosol at Day 35. Allergic hu-SCID mice developed AHR (provocative dose of carbachol causing a 50% increase in lung resistance [PD(50) RL] = 96.33 +/- 16.88 microg/kg) compared with nonallergic hu-SCID mice (PD(50) RL = 242.03 +/- 37.84 microg/kg) and nonreconstituted SCID mice (PD(50) RL = 297.60 +/- 45. 60 microg/kg) exposed to Dpt aerosol. An inverse correlation was observed between PD(50) RL (Day 35) and total human IgE at Day 7 (r = -0.58) and Day 15 (r = -0.64). However, no correlation existed between PD(50) RL and human cell number in the lungs of allergic hu-SCID mice. Moreover, despite the absence of eosinophils, the bronchoalveolar lavage fluid (BALF) of allergic hu-SCID mice had more human interleukin-5 (IL-5) (3.28 +/- 0.40 pg/ml, n = 13) than nonallergic hu-SCID mice (< 0.5 pg/ml) which inversely correlated with the PD(50) RL (r = -0.61). No tumor necrosis factor-alpha (TNF-alpha), IL-6, or IL-4 was detected. These observations indicate that humanized allergic hu-SCID mice may develop AHR after exposure to the relevant allergen, suggesting that this model may improve our understanding of AHR, one characteristic feature of allergic asthma.

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion. We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

The value of bronchoalveolar lavage for discrimination between healthy and diseased individuals. Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity. This study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals. More than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions. Bronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipulator of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS-proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%. In summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

Succinoglycan production by solid-state fermentation with Agrobacterium tumefaciens. Succinoglycan was produced by cultivating Agrobacterium tumefaciens on various solid substrates, including agar medium, spent malt grains, ivory nut shavings, and grated carrots, impregnated with a nutrient+ solution. Fermentations were performed on a laboratory scale, both under static conditions and with agitation, using bottles and a prototype horizontal bioreactor. Several fermentation parameters were examined and optimized, including carbon and nitrogen composition, water content and layer thickness of the substrate. The yields and rheological properties of the polymers obtained under different fermentation conditions were compared. The highest succinoglycan yield was achieved in static cultivation, reaching 42 g/l of impregnating solution, corresponding to 30 g/kg of wet substrate. The polymer production in the horizontal bioreactor was faster, but the final yield was lower (29 g/l of impregnating solution).

Non-two-state thermal denaturation of ferricytochrome c at neutral and slightly acidic pH values. Thermal denaturation of ferricytochrome c (cyt c) has been methodically studied by absorbance, fluorescence, circular dichroism spectroscopy, viscosimetry and differential scanning calorimetry in pH range from pH 3.5 to 7.5. Thermal transitions have been monitored by intrinsic local probes of heme region such as absorbance at Soret, 620nm and 695nm bands and circular dichroism signals at 417nm. Global conformational changes were analyzed by circular dichroism signal at 222nm, fluorescence of the single tryptophan, reduced viscosity and differential scanning calorimetry. We show that cyt c thermal denaturation above pH ~5 can be described by an apparent two-step transition in which the heme iron stays in a low-spin state. The thermal denaturations of cyt c below pH ~5 proceed in one step to an unfolded highly compact form with a high-spin state of the heme iron. Cyt c conformational plasticity is discussed in regard to its physiological functions.

Differences in synthesis of membrane proteins by leukemic cells from spleen and peripheral blood indicate distinct subsets of malignant cells in a patient with prolymphocytic leukemia. Morphological and biochemical differences were demonstrated between prolymphocytic leukemia cells obtained from the spleen and peripheral blood of one patient. Peripheral blood prolymphocytes had consistently smaller nuclear-cytoplasmic ratios than did splenic prolymphocytes. Percoll gradient-purified prolymphocytes from the spleen synthesized abundant amounts of some membrane proteins which were hardly expressed by peripheral blood prolymphocytes. Peripheral blood prolymphocytes did not change their expression of membrane proteins during three days in culture. These findings are consistent with the view that prolymphocytic leukemia cells from the spleen exist, on the average, at an earlier stage of differentiation than do circulating leukemic cells, and that peripheral blood leukemic cells are frozen at a specific phase of differentiation.

In vivo evaluation of a MR-guided 980nm laser interstitial thermal therapy system for ablations in porcine liver. To evaluate the use of a 980-nm diode laser for magnetic resonance-guided laser interstitial thermal therapy (MR-guided LITT) ablations in liver tissue in an in vivo porcine model. MR-guided guided LITT was performed on nine juvenile pigs placed under general anesthesia. Target ablation sites were selected in the left and right lobes of the liver. Laser applicators were placed in the liver using intermittent MR guidance. Up to four separate ablations were performed in each animal using a 15 or 30 W laser generator using one or two applicators. During the ablations, continuous MR-based temperature mapping (MR-thermal mapping), using a proton resonance frequency technique, was performed to monitor the size of the ablation in real-time. Extent of thermal tissue damage was continuously estimated based on Arrhenius model. Two-minute ablations were performed at each site. MR-thermal mapping of ablations within the posteroinferior liver were accomplished with continuous breathing at low tidal volume. In the mid right lobe of the liver, due to motion artefacts, MR-thermometry was performed intermittently during breath hold periods. In the left lobe of the liver, ablations were performed with ventilation using positive end expiratory pressure (PEEP) of 10 cm of water. Upon completion, MR imaging with gadolinium contrast was performed to assess the extent of treatment. Thermal lesions were subsequently measured using both, MR-thermal dose and MR gadolinium images, for comparison. Following the animal euthanasia, the liver was harvested and subjected to formalin fixation and paraffin embedding for histological examination. Between one and four focal liver ablations (total 24 ablations) were successfully performed in nine animals with either a 15 or 30 W laser generator. For the 15-W laser generator, the average single applicator ablation size was (2.0 ± 0.5) × (2.6 ± 0.4) cm(2) , as measured by magnetic resonance (MR) thermometry, or (1.7 ± 0.4) × (2.2 ± 0.6) cm(2) , as measured with gadolinium contrast, with the difference being not statistically significant. For the 30-W laser generator, the average single applicator ablation size was (2.4 ± 0.3) × (3.3 ± 0.5) cm(2) by MR thermometry and (2.1 ± 0.4) × (2.9 ± 0.3) cm(2) by gadolinium enhancement, with no statistically significant difference. Simultaneously activating two applicators with the 15 W generator demonstrated ablation sizes of (3.7 ± 0.9) × (3.2 ± 0.1) cm(2) using MR thermometry and (2.3 ± 0.6) × (2.4 ± 0.3) cm(2) with gadolinium contrast, while using two applicators in the 30-W laser generator, yielded (4.5 ± 0.6) × (3.9 ± 0.2) cm(2) using MR thermometry and (4.4 ± 1.1) × (3.6 ± 0.5) cm(2) with gadolinium contrast enhancement. In our experience, we found that liver ablations performed with a MR-guided 980-nm diode LITT system through the saline cooled catheter applicator could be performed throughout the liver. Additionally, liver ablations were safe and produced a clinically applicable ablation zone. These results suggest the 980-nm diode laser MR-guided LITT system could be effective in treatments of hepatic tumors.

Povidone-Iodine, 0.05% Chlorhexidine Gluconate, or Water for Periurethral Cleaning Before Indwelling Urinary Catheterization in a Pediatric Intensive Care: A Randomized Controlled Trial. The aim of this study was to evaluate the efficacy of periurethral cleaning with 10% povidone-iodine, 0.05% chlorhexidine gluconate, or sterile water in preventing catheter-associated urinary tract infections (CAUTIs) prior to indwelling urinary catheter insertion in a pediatric intensive care unit. A secondary aim was to identify pathogens resulting in CAUTIs in this group. Randomized controlled trial. One hundred twenty-two patients cared for in a pediatric intensive care unit of a university hospital between September 2012 and December 2013 participated in the study. Subjects were randomly allocated to 1 of 3 groups: periurethral cleansing with 0.05% chlorhexidine; 10% povidone-iodine; or sterile water. The patients in each group were cleansed 3 times using different sterile pads and assigned cleansing solutions for as long as the patients were observed or until the urinary catheter was removed. Daily monitoring forms, which included physiologic and physical parameters and catheter-related infections, were completed for all patients. We used Centers for Disease Control and Prevention/National Health and Safety Network criteria to determine the presence of a CAUTI. CAUTIs occurred in 6 patients (15%) allocated to periurethral cleansing with povidone-iodine, 2 (4.8%) in the chlorhexidine gluconate group, and 3 (7.5%) in the sterile water group. Although more patients in the povidone-iodine group had CAUTI than in the other 2 groups, differences were not statistically significant (P > .05). We found no statistically significant differences in CAUTI rates in the 3 groups. Further investigation with a larger study group is needed to more definitively identify any difference in CAUTI occurrences based on periurethral cleansing solution.

Infection levels of plerocercoids of the tapeworm Triaenophorus crassus and feeding strategy in two fish species from the ultra-oligotrophic Lake Achensee, Austria. Thus far, high burdens of Triaenophorus crassus plerocercoids have been reported only in old age groups of coregonid and salmonid fishes. Here we show heavy infection with T. crassus in young whitefish Coregonus lavaretus in the ultra-oligotrophic and regulated Achensee in Tyrol, Austria. Prevalence of T. crassus on C. lavaretus was 100% in all age groups and abundance significantly increased with fish age. The mean annual accumulation of T. crassus was 5.2 parasites in 0- to 7-year-old C. lavaretus, and 2-year-old specimens already harboured a mean of 19.4 plerocercoids. In Arctic charr Salvelinus umbla, however, the prevalence of T. crassus was less than 16% and the majority of infected fish contained only one or two plerocercoids. Triaenophorus nodulosus was present neither in C. lavaretus nor in S. umbla. We assume that the heavy T. crassus infection in C. lavaretus is largely related to their zooplankton-dominated diet and to the characteristics of Achensee, while habitat choice and feeding strategy of the S. umbla population are seen to be the main reasons for their low burdens of T. crassus.

First experimental evidence of potassium ordering in layered k4co7o14. The layered P2-K4Co7O14 oxide has been prepared and characterized by means of X-ray diffraction, electrical conductivity, thermopower, and magnetic measurements. The crystal structure of K4Co7O14 (P6(3)/m space group, Z=2, a=7.5171(1) A, and c=12.371(1) A) consists of a stacking of slabs of edge-shared CoO6 octahedra with K+ ions occupying ordered positions in the interslab space, leading to a a0 radical7xa0 radical7 supercell. Potential energy calculations at 0 K are in good agreement with the ordered distribution of potassium ions in the (ab) plane. This oxide is metallic, and the magnetic susceptibility is of Pauli-type, which contrasts with the Curie-Weiss behavior of the homologous NaxCoO2 (x approximately 0.6) oxide with close alkali content. The thermopower at room temperature is about one-third that of polycrystalline Na0.6CoO2.

Activation of the complement system and leukocyte recruitment by Tityus serrulatus scorpion venom. The scorpion Tityus serrulatus is considered one of the most dangerous species in Brazil. Its venom evokes an inflammatory response, although the exact mechanism of this effect is still unknown. The aim of the present study was to investigate the effect of Tityus serrulatus venom (TsV) on the complement system (CS) and on leukocyte recruitment. Complement consumption by TsV was evaluated using in vitro hemolytic assays, immunoelectrophoresis and two-dimensional immunoelectrophoresis of complement components (factor B and C3). In order to evaluate neutrophil migration induced in normal human serum (NHS) in the presence of TsV, in vitro chemotaxis assays were performed using the Boyden chamber model. In vitro TsV induced a concentration- and time-dependent reduction in hemolytic activity of the classical/lectin and alternative complement pathways, with samples of 43.0 microg and 43.4 microg, respectively, inhibiting 50% of the lytic activity. Alterations in C3 and factor B electrophoretic mobility after incubation of NHS with TsV, were identical to those obtained with zymosan (positive control). Incubation of NHS with TsV induced neutrophil chemotaxis similar to that observed with zymosan-activated serum. Our results show that TsV activates the CS, leading to factor B and C3 cleavage, to reduction of serum lytic activity and generation of complement chemotactic factors. Therefore, CS may play an important role in the inflammatory response observed upon scorpion envenomation.

[Lithium induced dysfunction of the parathyroid hormone]. The prevalence of hyperparathyroidism (HPT) in patients treated with lithium is higher than that in controls. Lithium seems to affect calcium metabolism, by acting directly parathyroid hormone cells, and distal tubuli in the kidneys. Because hypercalcaemic HPT can cause psychiatric symptoms mistakenly attributed to the lithium treatment, ionised calcium should be a standard control.

Distal urethral plate adhesions: New anatomical perspective in hypospadias. We found midline epithelial adhesions in the glandar urethral plate in patients with hypospadias. After dissolution, a blind epithelized channel becomes visualized inside of the plate pointing to immature embryonic luminization. In addition it reveals that the epithelized surface of the distal urethral plate is larger than previously considered. To determine the incidence and extent of these new anatomical details of urethral plate in hypospadias patients. We prospectively assessed the detailed anatomy of the urethral plate in 72 consecutive patients with hypospadias. We recorded the presence of adhesions in the middle of the glandar urethral groove that can be easily dissoluted (dissolution line - D-line). We recorded the plate width before and after D-line dissolution, the presence of the hidden blind channel at continuation of D-line (channel type-A) and of the visible blind channel between D-line and urethral hypospadiac meatus (type-B) (Figure). In 62 patients, where the urethral plate tubularization was considered (Duplay, TIP), septs between channels were opened in the midline and a final width of the plate was measured by rolling the plate around a tube. Midline adhesions (D-line) were found in all 72 patients. Mean length of D-line was 5.13 ± O.17 mm. Mean plate width before dissolution was 5.9 ± 0.15 mm, and after dissolution 7.8 ± 0.16 mm. A blind channel of type A was detected in 22 patients (31%), type B in 24 (33%), type A and B in 16 (22%), and none in 10 patients (14%). Mean final plate width after D-line dissolution and opening of septs between channels in 62 patients with urethral plate tubularization was 8.7 ± 0.15 mm. The main contribution of our study is a new perspective of distal urethral plate anatomy that enables enlargement of the epithelized surface of the distal urethral plate by dissolution of the preexisting epithelized groove and opening of epithelized channels within the plate. To the best of our knowledge, this anatomical anomaly has not been described previously. The distal urethral plate of all hypospadias patients is partially "folded" in the midline by epithelial adhesions of different depth and extent that may be easily dissoluted. In half of the patients (53%) the "folded" part of the plate continues proximally as a blind channel inside the urethral plate (type A channel). Opening of these structures together with the well-known urethral plate pits (type B channel) helps augment the width and the overall epithelized surface of the distal urethral plate.

Technique for insertion of the superior loop of the Shearing-style posterior chamber lens. An angulated lens guide and iris hook are described for inserting the superior loop of a Shearing-style lens implant.

[Time trend study of firearm mortality in Argentina, 1980-2012]. This work analyzes the impact of firearm mortality between 1980 and 2012 in Argentina. For this purpose a descriptive epidemiological time trend study was carried out including the following variables: sex, age group, intentionality and jurisdiction. Data was obtained from the Office of Health Statistics and Information of the Argentine Ministry of Health. A total of 87,671 deaths due to firearms were discovered, of which 85.7% occurred in men. The highest mortality rate due to firearms corresponded to the year 2002, reaching 21.2 deaths per 100,000 inhabitants. The age group concentrating the largest number of deaths due to firearms was that of 20-29 years, accounting for 25.6% of all deaths. The highest adjusted rates corresponded to the years 2000-2002, with values of 10.0 to 11.6 deaths per 100,000 inhabitants. This time period coincides with the institutional-economic crisis the country experienced. The province of Buenos Aires was the place of residence of 49.1% of the deceased. In the discussion, political-economic and ideological-cultural dimensions of the relations among firearms, violence, science and society are considered.

[Effect of a plant immunostimulant on phagocytosis of erythrocytes by the reticulohistiocytary system of isolated perfused rat liver]. By the help of the isolated, perfused rat liver, the influence of an immune stimulant of plant origin (Esberitox N; composition: herb. thujae occid. rec., rad. baptisiae tinct., rad. echinaceae ang. et purp.) on the activity of Kupffer cells was tested. It was shown that the phagocytosis of erythrocytes was improved significantly by the single extracts and the combination of this. The extract of thuja occidentalis had the most prominent effect on the first phase of phagocytosis, whereas the extract of echinacea purpurea dominantly influenced the phagocytosis dependent metabolism.

Haemodynamic evaluation during small volume resuscitation in patients with acute respiratory failure. In addition to the invasive haemodynamic monitoring procedures, an on-line assessment of cardiac performance by means of transoesophageal echocardiography might have a certain role in small volume resuscitation of patients with acute respiratory failure or Adult Respiratory Distress Syndrome (ARDS). The goal of this investigation was therefore to determine the effects of a hypertonic hyperoncotic solution, hypertonic hydoxyethl-starch (HHES), (HHES = HES [200.000/0.6-0.66; 60 g l-1; Leopold, Graz; Austria] combined with NaCl [75 g l-1) on haemodynamics and cardiac performance using the transoesophageal echocardiography. After institutional approval we investigated 23 patients suffering from septic ARDS after trauma or major surgery during four periods of resuscitation. Phase I = control values after infusion of 20 ml kg-1 crystalloid solution, phase II = 50% hypertonic hydroxyethyl-starch solution (2 ml kg-1), phase III = at the end of HHES (4 ml kg-1), IV = 30 min after the end of HHES. Before HHES-infusion, all patients showed arterial hypotension with mean arterial pressures of 64 +/- 2 mmHg. The infusion of 2 ml kg-1 HHES resulted in a significant increase of systemic and pulmonary arterial pressures over the study period. A significant improvement in cardiac output was associated with increasing stroke volumes, oxygen delivery and oxygen consumption (see Tables 1 and 2). Small volume resuscitation also resulted in significant increases of endsystolic and endiastolic left ventricular areas and the corresponding calculated wall stress (Figs 1-3). We conclude from our preliminary data that when using HHES, only modest fluid resuscitation was sufficient to restore adequate preload and oxygen delivery in patients with sepsis-related acute respiratory failure.

An Overview of Novel Unconventional Mechanisms of Hematopoietic Development and Regulators of Hematopoiesis - a Roadmap for Future Investigations. Hematopoietic stem cells (HSCs) are the best-characterized stem cells in adult tissues. Nevertheless, as of today, many open questions remain. First, what is the phenotype of the most primitive "pre-HSC" able to undergo asymmetric divisions during ex vivo expansion that gives rise to HSC for all hemato-lymphopoietic lineages. Next, most routine in vitro assays designed to study HSC specification into hematopoietic progenitor cells (HPCs) for major hematopoietic lineages are based on a limited number of peptide-based growth factors and cytokines, neglecting the involvement of several other regulators that are endowed with hematopoietic activity. Examples include many hormones, such as pituitary gonadotropins, gonadal sex hormones, IGF-1, and thyroid hormones, as well as bioactive phosphosphingolipids and extracellular nucleotides (EXNs). Moreover, in addition to regulation by stromal-derived factor 1 (SDF-1), trafficking of these cells during mobilization or homing after transplantation is also regulated by bioactive phosphosphingolipids, EXNs, and three ancient proteolytic cascades, the complement cascade (ComC), the coagulation cascade (CoA), and the fibrinolytic cascade (FibC). Finally, it has emerged that bone marrow responds by "sterile inflammation" to signals sent from damaged organs and tissues, systemic stress, strenuous exercise, gut microbiota, and the administration of certain drugs. This review will address the involvement of these unconventional regulators and present a broader picture of hematopoiesis.

Ultrastructural localization of milk fat globule membrane antigens in human breast carcinomas. The localization of milk fat globule membrane components has been assessed using post-fixation immunoelectron microscopy with three different antibodies for a group of breast carcinomas of different type and histological differentiation. For well differentiated carcinomas localization was in relation to the cell membrane, with polarization being evident in a proportion of cases. Moderately differentiated carcinomas showed a combined picture of cell membrane, vesicular, and intracytoplasmic luminal localization. The latter is a feature of infiltrating lobular carcinomas. Poorly differentiated carcinomas exhibited vesicular labelling throughout the cytoplasm, with no cell membrane localization. No labelling was seen over endoplasmic reticulum. It is proposed that carcinomas exhibit defects in intracellular transport of milk fat globule membrane components resulting in failure of expression at the cell surface and accumulation of vesicles within the cytoplasm, the extent of change relating to tumour differentiation.

Reversible Gas-Solid Ammonia N-H Bond Activation Mediated by an Organopalladium Complex. N-H bond activation of gaseous ammonia is achieved at room temperature in a reversible solvent-free reaction using a solid dicyclopalladated azobenzene complex. Monitoring of the gas-solid reaction in real-time by in situ solid-state Raman spectroscopy enabled a detailed insight into the stepwise activation pathway proceeding to the final amido complex via a stable diammine intermediate. Gas-solid synthesis allowed for isolation and subsequent structural characterization of the intermediate and the final amido product, which presents the first dipalladated complex with the PdII-(μ-NH2)-PdII bridge. Gas-solid reaction is readily followed via color changes associated with conformational switching of the palladated azobenzene backbone. The reaction proceeds analogously in solution and was characterized by UV-vis and NMR spectroscopies showing the same stepwise route to the amido complex. Combining the experimental data with density functional theory calculations we propose a stepwise mechanism of this heterolytic N-H bond activation assisted by exogenous ammonia.

Predictors of sexual well-being after endometrial cancer: results of a national self-report survey. We examined whether sociodemographic, physical, reproductive, psychological and clinical factors at the time of diagnosis were related to women's sexual well-being 3-5 years following treatment for endometrial cancer. Of the 1,399 women in the Australian National Endometrial Cancer Study, 644 completed a follow-up questionnaire 3-5 years after diagnosis. Of these, 395 women completed the Sexual-Function Vaginal Changes Questionnaire, which was used to assess sexual well-being. Based on two questions assessing worry and satisfaction with their sexuality, women were classified into lower and higher sexual well-being. Multivariable-adjusted logistic regression models were used to examine sexual well-being 3-5 years following cancer treatment and the factors associated with this at diagnosis and at follow-up. Of the 395 women, 46 % (n = 181) were categorized into the "higher" sexual well-being group. Women who were older (odds ratio [OR] = 1.97; 95 % confidence limit [CI], 1.23-3.17), high school educated (OR = 1.75; 95 % CI, 1.12-2.73), who reported good mental health at the time of diagnosis (OR = 2.29; 95 % CI, 1.32-3.95) and whose cancer was treated with surgery alone (OR = 1.93; 95 % CI, 1.22-3.07) were most likely to report positive sexual well-being. At 3-5 years post-diagnosis, women with few symptoms of anxiety (OR = 2.28; 95 % CI, 1.21-4.29) were also most likely to report positive sexual well-being. Psychological, sociodemographic and treatment factors are important to positive sexual well-being post-cancer. Care that focuses on maintaining physical and psychosocial aspects of women's lives will be more effective in promoting positive sexual well-being than care that focuses solely on physical function.

Genetics for the practicing dermatologist. In the era of robust genome sequencing, a working understanding of genetics has become important for the clinician. For the dermatologist, understanding the flow of genetic information from genotype to phenotype can aid in the delivery of effective patient care. In this article, we will review concepts in genetics and the human genome and how they contribute to clinical dermatology.

Molecular phylogenetic analyses of reverse-transcribed bacterial rRNA obtained from deep-sea cold seep sediments. A depth profile of naturally occurring bacterial community structures associated with the deep-sea cold seep push-core sediment in the Japan Trench at a depth of 5343 m were evaluated using molecular phylogenetic analyses of RNA reverse transcription-PCR (RT-PCR) amplified 16S crDNA fragments. A total of 137 clones of bacterial crDNA (complimentary rDNA) phylotypes (phylogenetic types) obtained at three different depths (2-4, 8-10 and 14-16 cm) were identified in partial crDNA sequencings. crDNA phylotypes from the cold seep sediment were dominantly composed of delta- and epsilon-Proteobacteria (36% and 42% respectively). Phylotype analysis of crDNA clone libraries and terminal restriction fragment length polymorphism (T-RFLP) analysis revealed that the majority of bacterial components shifted from delta- Proteobacteria to epsilon-Proteobacteria with increasing depth. Among the delta-proteobacterial crDNA clones, the sequences related to the genus Desulfosarcina were dominant. Almost all sequences of crDNA belonging to epsilon-Proteobacteria were affiliated with the same cluster (epsilon-CSG: epsilon-proteobacterial cold seep group), and were closely related with rDNA sequences from deep-sea hydrothermal vent environments.

Improved ECG pre-processing for beat-to-beat QT interval variability measurement. The aim of this study was to enhance the ECG pre-processing modalities for beat-to-beat QT interval variability measurement based on template matching. The R-peak detection algorithm has been substituted and an efficient baseline removal algorithm has been implemented in existing computer software. To test performance we used simulated ECG data with fixed QT intervals featuring Gaussian noise, baseline wander and amplitude modulation and two alternative algorithms. We computed the standard deviation of beat-to-beat QT intervals as a marker of QT interval variability (QTV). Significantly a lower beat-to-beat QTV was found in the updated approach compared the original algorithm. In addition, the updated template matching computer software outperformed the previous version in discarding fewer beats. In conclusion, the updated ECG preprocessing algorithm is recommended for more accurate quantification of beat-to-beat QT interval variability.

Insights Into Glucan Polysaccharide Recognition Using Glucooligosaccharide Microarrays With Oxime-Linked Neoglycolipid Probes. Glucans are polysaccharides of increasing biomedical interest because of their involvement in mechanisms of pathogen recognition, modulation of the immune system and anticancer, and health-promoting activities. Most of these biological activities occur through specific interactions with glucan-recognizing proteins. However, detailed molecular studies of glucan recognition remain a challenge mainly due to the inherent sequence heterogeneity and polydispersity of glucan polysaccharides, and associated difficulties in their purification and sequence characterization. It is thus ideal to have a series of sequence-defined glucooligosaccharides to represent the sequence diversity of glucan polysaccharides and to apply these to gain insight into glucan recognition processes. In this chapter, we describe the the methods for developing of oligosaccharide microarrays derived from a collection of glucans with different linkages based on the neoglycolipid (NGL) microarray system. The microscale oxime-ligation method has provided access in microarrays to over 150 sequence-defined glucooligosaccharides with different chain lengths, linkages, and branching patterns. We focus on the essential steps in the preparation of NGL-based glucooligosaccharide microarrays, which include (1) the depolymerization and purification methods to obtain oligosaccharide fractions of defined chain lengths; (2) a mass spectrometry-based method for linkage and sequence analysis of glucooligosaccharides; (3) improved procedures for preparation of oxime-linked NGLs from glucooligosaccharides for construction of microarrays; and (4) analyses of the recognition of these oligosaccharide sequences by various glucan-recognizing proteins: monoclonal antibodies, other proteins of the immune system such as Dectin-1 and DC-SIGN, and carbohydrate-binding modules of bacterial glycoside hydrolases.

Snail represses the expression of human phospholipid scramblase 4 gene. Human phospholipid scramblases (hPLSCRs) are a group of transmembrane ATP independent lipid transporters mediating bi-directional transport of phospholipids. There are four homologues hPLSCR1-hPLSCR4 and hPLSCR1 is the extensively studied homologue among them. hPLSCR4 shares 48% homology with hPLSCR1 and mediates scrambling of PLs similar to hPLSCR1 in Ca(2+) dependent manner. Transcriptional regulation helps in better understanding of the function and the expression of a protein. Till date there are no reports suggesting the transcriptional regulation of hPLSCR4. In this study, we identified Snail to be a potent regulator of hPLSCR4. ConSite tool predicted the presence of a putative Snail binding site with a consensus sequence of (-1521)CAGGTG(-1516) on hPLSCR4 promoter. Luciferase assays depicted a dose dependent decrease in hPLSCR4 promoter activity with an increase in amount of Snail. Deletion analysis revealed that the region from -1380 to -2100 to be the regulatory region of hPLSCR4. Knock down studies further confirmed Snail mediated downregulation of hPLSCR4, as the mRNA and the protein levels of hPLSCR4 considerably increased under knock down conditions. The in vivo interaction of Snail with hPLSCR4 promoter was further confirmed by ChIP assay. This is the first report on the transcriptional regulation of hPLSCR4, where Snail was shown to downregulate the expression of hPLSCR4.

A systematic review of medical mistrust measures. Medical mistrust is seen as a barrier to health promotion and addressing health disparities among marginalized populations. This study seeks to examine how medical mistrust has been measured as a step towards informing related health promotion efforts. A systematic review of medical mistrust scales was conducted using four major databases: PubMed, PsycINFO, ERIC, and Communication & Mass Media Complete. Databases were searched using the terms "medical mistrust scale" "medical mistrust" and "medical distrust." The search returned 1595 non-duplicate citations; after inclusion and exclusion criteria were applied, 185 articles were retained and coded. Almost a quarter of studies used a single-item or a few items. Among validated scales, the Group-Based Medical Mistrust Scale, Medical Mistrust Index, and Health Care System Distrust Scale were most frequently used. There were important differences among these scales such as the object of mistrust (e.g., system, individual physician) and referent specificity (e.g., group). The measurement of medical mistrust varied by health topic and sample population. These differences in scales and measurement should be considered in the context of intervention goals. Researchers should be aware of differences in measures and choose appropriate measures for a given research question or intervention.

Cost-effectiveness of case-based training for primary care physicians in evidence-based medicine of patients with coronary heart disease. We have shown that a case-based training programme for general practitioners, aimed to implement evidence-based care of patients at very high risk of coronary death, was associated with decreased mortality. In the present study we assessed long-term cost-effectiveness of this programme. Registry-based long-term cost-effectiveness analysis on a clinical trial. Costs of the programme, health care, drugs and added years of life were included. Costs were adjusted to 2012 level and discounted by 3%. Life-years gained were estimated as the difference between the survival curves of the trial. The effectiveness measure, quality adjusted life-years (QALYs), was constructed by multiplying each life-year with a quality of life weight corresponding to the health status of that year. QALYs were also discounted by 3%. Incremental cost-effectiveness ratio (ICER) was estimated as the incremental cost per QALY gained. The number of undiscounted life-years gained was 365 days in the intervention group as compared to control (p = 0.02). The number of discounted QALYs gained was 0.66. The net increase in total costs was estimated as 17,862 € when costs of added years of life were included and 4621 € exclusive of these costs. This implied an ICER of 27,063 € per gained QALY. This ICER is well below commonly used threshold values of the societal willingness to pay for a QALY. The results show that a case-based training programme of general practitioners is a cost-effective way to save years of life in patients with very high risk of coronary death.

Metasynthesis findings: potential versus reality. Early on, qualitative researchers predicted that metasynthesis research had the potential to significantly push knowledge development forward. More recently, scholars have questioned whether this is actually occurring. To examine this concern, a randomly selected sample of metasynthesis articles was systematically reviewed to identify the types of findings that have been produced. Based on this systematic examination, it appears that findings from metasynthesis investigations might not be reaching their full potential. Metasynthesis investigations frequently result in isolated findings rather than findings in relationship, and opportunities to generate research hypotheses and theoretical models are not always fully realized. With this in mind, methods for moving metasynthesis findings into relationship are discussed.

New approaches to antiplatelet therapy. The importance of platelets in the pathophysiology of cardiovascular and cerebrovascular disorders has been demonstrated by numerous clinical and pathological studies. Conventional antiplatelet agents are effective in both the primary and secondary prevention of vascular disorders, but suffer for the combined shortcomings of lack of selectivity and relative potency. Many new antiplatelet agents have been developed to overcome these differences, including serotonin receptor antagonists, prostanoid derivatives and antagonists, fibrinogen receptor antagonists, and selective thrombin inhibitors. In this review we consider the mechanisms by which these novel antiplatelet agents impair platelet function and their potential clinical utility.

An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Myogenic tone is an important determinant of vascular tone and blood flow in small resistance arteries of certain vascular beds. The role of the endothelium in myogenic responses is unclear. We hypothesized that endothelium-derived NO release modulates myogenic constriction in small resistance arteries and that mesenteric small arteries from mice with targeted disruption of the gene for endothelial NO synthase (eNOS) (knockout mice) demonstrate greater myogenic tone than do wild-type mice. Third-order mesenteric arteries (approximately 200 micrometer) were isolated and mounted in a pressure myograph. Internal diameter was recorded over a pressure range of 10 to 80 mm Hg. Removal of the endothelium significantly (P<0.05) enhanced the magnitude of myogenic constriction in wild-type mice. Similarly, pretreatment of arteries with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/L) produced a comparable significant (P<0.05) increase in myogenic tone, whereas indomethacin (5 micromol/L) had no effect. eNOS knockout arteries also exhibited myogenic constriction. Neither L-NAME nor indomethacin had any effect on myogenic tone in the arteries of eNOS knockout mice. However, blockade of potential endothelium-derived hyperpolarizing factor-like mechanisms via inhibition of K(+) flux using either apamin (100 nmol/L) with charybdotoxin (100 nmol/L), Ba(2+) (30 micromol/L) with ouabain (1 mmol/L), or 18alpha-glycyrrhetinic acid (100 micromol/L) significantly (P<0.01) enhanced myogenic constriction. This study demonstrates that basal endothelium-derived NO modulates myogenic tone in mesenteric small arteries of wild-type mice. However, eNOS knockout arteries display normal myogenic responsiveness despite the absence of basal NO activity. The data suggest that this compensatory effect is due to the activity of an endothelium-derived hyperpolarizing factor to normalize vascular tone.

Failure of anticytokeratin 18 antibody to improve flow cytometric detection of bladder cancer. Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods. The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis. Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis. However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity.

A phase I safety and pharmacokinetic study of OGT 719 in patients with liver cancer. OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000 mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity), area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.

Regio- and Enantioselective Rhodium-Catalyzed Addition of 1,3-Diketones to Allenes: Construction of Asymmetric Tertiary and Quaternary All Carbon Centers. An unprecedented highly regio- and enantioselective rhodium-catalyzed addition of 1,3-diketones to terminal and 1,1-disubstituted allenes furnishing asymmetric tertiary and quaternary all-carbon centers is reported. By applying a RhI /phosphoramidite/TFA catalytic system under mild conditions, the desired chiral branched α-allylated 1,3-diketones could be obtained in good to excellent yields, with perfect regioselectivity and in high enantioselectivity. The reaction shows a broad functional-group tolerance on both reaction partners highlighting its synthetic potential.

Development of an Automatic Diagnostic Algorithm for Pediatric Otitis Media. The artificial intelligence and image processing technology can develop automatic diagnostic algorithm for pediatric otitis media (OM) with accuracy comparable to that from well-trained otologists. OM is a public health issue that occurs commonly in pediatric population. Caring for OM may incur significant indirect cost that stems mainly from loss of school or working days seeking for medical consultation. It makes great sense for the homecare of OM. In this study, we aim to develop an automatic diagnostic algorithm for pediatric OM. A total of 1,230 otoscopic images were collected. Among them, 214 images diagnosed of acute otitis media (AOM) and otitis media with effusion (OME) are used as the database for image classification in this study. For the OM image classification system, the image database is randomly partitioned into the test and train subsets. Of each image in the train and test sets, the desired eardrum image region is first segmented, then multiple image features such as color, and shape are extracted. The multitask joint sparse representation-based classification to combine different features of the OM image is used for classification. The multitask joint sparse representation algorithm was applied for the classification of the AOM and OME images. The approach is able to differentiate the OME from AOM images and achieves the classification accuracy as high as 91.41%. Our results demonstrated that this automatic diagnosis algorithm has acceptable accuracy to diagnose pediatric OM. The cost-effective algorithm can assist parents for early detection and continuous monitoring at home to decrease consequence of the disease.

Prognostic significance of arrhythmia inducibility or noninducibility at initial electrophysiologic study in survivors of cardiac arrest. The value of arrhythmia inducibility or noninducibility at initial electrophysiologic study to predict the likelihood of arrhythmia recurrence was assessed in 150 consecutive survivors of cardiac arrest. Ventricular tachycardia (greater than or equal to 6 beats) or ventricular fibrilation was induced in 113 patients (75%); ventricular arrhythmia could not be induced in 37 patients (25%). During follow-up of a mean of 16 months (range 1 to 72), there were 65 arrhythmia recurrences, 34 of them fatal, in 58 patients. Multivariate regression analysis showed that inducibility at initial study of ventricular tachycardia or ventricular fibrilation was an independent predictor of total arrhythmia recurrence (p less than 0.0001) and fatal arrhythmia recurrence (p = 0.02). At 1 year, 25 +/- 5% of patients with an inducible arrhythmia had a fatal arrhythmia recurrence compared with only 4 +/- 4% of patients without (p = 0.003). The nature of the inducible arrhythmia had no additional predictive value. Inducibility or noninducibility of ventricular arrhythmias at initial electrophysiologic study is a powerful, independent predictor of subsequent arrhythmia recurrence in survivors of cardiac arrest. Patients without inducible arrhythmias have a low frequency of fatal arrhythmia recurrence.

Simultaneous SERS detection of copper and cobalt at ultratrace levels. We report a SERS-based method for the simultaneous and independent determination of two environmental metallic pollutants, Cu(ii) and Co(ii). This was achieved by exploiting the coordination-sensitive Raman bands of a terpyridine (TPY) derivative for detecting transition metal ions. Changes in the vibrational SERS spectra of dithiocarbamate anchored terpyridine (TPY-DTC) were correlated as a function of each metal ion concentration, with limits of detection comparable to those of several conventional analytical methods. Simultaneous detection of ultratrace levels of Co(ii) in the presence of high Cu(ii) concentration was also demonstrated, supporting the potential of this sensing strategy for monitoring potable water supplies.

The discrimination potential of amalgam restorations for identification: part 2. The standard dental bitewing radiograph is used to detect interproximal caries but it also provides a specific view of the dental restorations that can be duplicated for identification purposes. The antemortem and postmortem bitewing radiographs are often not at the same angle and result in distorted images of the restorations. The aim of this study was to investigate the progressive increase in angulations of a bitewing radiograph of the same restoration and to determine at what angle the image is distorted sufficiently as not to be recognized. Bitewing radiographs were taken of the same two restorations at 5 ̊, 10 ̊, 15 ̊ and 20 ̊ superior, inferior, mesial and distal to the original 0 ̊bitewing radiograph. Twenty examiners were required to determine at what angle the distortion prevented matching of the image with the original bitewing radiograph. The results showed that the image distortion at 15 ̊became suspect but at 20 ̊none of the images could be matched to the original bitewing radiograph.

Domain structure of the large subunit of Escherichia coli carbamoyl phosphate synthetase. Location of the binding site for the allosteric inhibitor UMP in the COOH-terminal domain. The large subunit of Escherichia coli carbamoyl phosphate synthetase (a polypeptide of 117.7 kDa that consists of two homologous halves) is responsible for carbamoyl phosphate synthesis from NH3 and for the binding of the allosteric activators ornithine and IMP and of the inhibitor UMP. Elastase, trypsin, and chymotrypsin inactivate the enzyme and cleave the large subunit at a site approximately 15 kDa from the COOH terminus (demonstrated by NH2-terminal sequencing). UMP, IMP, and ornithine prevent this cleavage and the inactivation. Upon irradiation with ultraviolet light in the presence of [14C]UMP, the large subunit is labeled selectively and specifically. The labeling is inhibited by ornithine and IMP. Cleavage of the 15-kDa COOH-terminal region by prior treatment of the enzyme with trypsin prevents the labeling on subsequent irradiation with [14C]UMP. The [14C]UMP-labeled large subunit is resistant to proteolytic cleavage, but if it is treated with SDS the resistance is lost, indicating that UMP is cross-linked to its binding site and that the protection is due to conformational factors. In the presence of SDS, the labeled large subunit is cleaved by trypsin or by V8 staphylococcal protease at a site located 15 or 25 kDa, respectively, from the COOH terminus (shown by NH2-terminal sequencing), and only the 15- or 25-kDa fragments are labeled. Similarly, upon cleavage of the aspartyl-prolyl bonds of the [14C]UMP-labeled enzyme with 70% formic acid, labeling was found only in the 18.5-kDa fragment that contains the COOH terminus of the subunit. Thus, UMP binds to the COOH-terminal domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunomodulation of lambs following treatment with a proteasome preparation from infective larvae of Trichostrongylus colubriformis. Proteinases are known to be capable of prolonging the survival of endoparasites in a host. We were therefore interested in knowing whether immunization of lambs against a proteasome (multisubunit proteinases) preparation obtained from Trichostrongylus colubriformis infective third-stage larvae (L3) would have any effect on the immune response to a single challenge infection with the same organism. A total of 21 penned lambs aged 8 months were divided into 3 equal groups. Group 1 was immunized on three occasions with increasing amounts of a proteasome-enriched fraction obtained from infective L3. Group 2 was given a similar amount of protein from the initial supernatant of homogenized larvae. Group 3 (controls) received adjuvant plus saline solution only. All groups were challenged with 60,000 infective T. colubriformis larvae at 28 days after the last immunization. Significant protection was obtained only when the initial supernatant extract was used to immunize lambs. The proteasome preparation seemed to have immunosuppressive effects through the stimulation of nonspecific IgE production. Significantly lower levels of specific IgE were observed in lambs immunized with the proteasome-enriched fraction, and levels of specific IgG antibodies were increased. We suggest that proteasome fractions of T. colubriformis may serve as useful preparations for the study of mechanisms of IgE production in parasitized sheep.

Abnormal secretory response to parasympathomimetic and sympathomimetic stimulations from the submaxillary gland of rats treated with reserpine. Rats treated with 0.5 mg/kg of reserpine per day for 7 days were anesthetized and submaxillary saliva was collected and analyzed for Na+, K+, Ca++ and protein concentrations. Salivary secretion was elicited by i.p. injections of carbamylcholine (50-100 mug/kg), phenylephrine (5 mg/kg) and isoproterenol (10 mg/rat). Saliva was also collected from untreated controls. Submaxillary glands were excised from both groups of animals at the termination of the secretory response, homogenized and analyzed. Glands from other animals were removed in the resting state and similarly processed. Pretreatment with reserpine resulted in decreased volumes of salvia and in elevated salivary concentrations of Ca++ and protein. Saliva from the reserpine-treated animals secreted in response to carbamylcholine had higher concentrations of Na+ and K+ than control saliva, particularly at the low rates of flow. Saliva secreted after stimulation with the two sympathomimetic secretagogues had lower concentrations of these two ions. Resting glands from the treated animals showed significant elevations in protein and Ca++ content and a significant decrease in K+ content. At the end of the secretory response to the three secretagogues, glands from treated animals showed a significantly higher Na+ content and a significantly lower K+ content than control glands. It is concluded that pretreatment with reserpine alters the secretory response of the rat submaxillary gland to both parasympathomimetic and sympathomimetic stimulation. This alteration results from a toxic lesion caused by reserpine in the salivary cells, which involves changes in their permeability to ions and in their energy resources. These in turn, result in an abnormal stimulus-secretion coupling mechanism. The possibility that the toxic lesion is related to alterations in Ca++ homeostasis is discussed.

New insights into the origin, structure and role of CD52: a major component of the mammalian sperm glycocalyx. The sperm glycocalyx represents the primary interface between the male gamete and its environment, and gamete interaction inevitably involves interaction with this structure. Thus, it has potential significance as a target for antibodies that inhibit sperm function. Still, little is known about the components and biological role of the sperm glycocalyx. Despite the apparent complexity of the sperm membrane, surface carbohydrate labelling experiments show a high selectivity suggesting that carbohydrate side chains of CD52, an unusually short, bipolar glycopeptide of epididymal origin, form major components of the sperm glycocalyx in all mammalian species investigated. Acquisition of the highly sialylated, lipid-anchored CD52 antigen is one of the few well-defined modifications that occur to the sperm membrane during epididymal passage. It would explain changes in lectin-binding patterns and also the remarkable surface charge differences occurring during epididymal transit, most probably attributable to its terminal sialic acid residues. CD52 seems to be immunodominant on human spermatozoa, and antibodies directed against it can agglutinate and completely immobilize human sperm in the presence of complement. Expression of the same peptide backbone in lymphocytes had largely discounted its consideration as a candidate for contraceptive development. However, the recent proof of male-specific modifications indicates the feasibility of this approach.

HLA-B*40:356, identified by next-generation sequence based typing in a Chinese tuberculosis patient. HLA-B*40:356 differs from B*40:02:01 by only one nucleotide transition, C>A 1040 in exon 6.

Elastic stable intramedullary nailing versus Kirschner wire pinning: outcome of severely displaced proximal humeral fractures in juvenile patients. Significantly displaced juvenile proximal humeral fractures (Neer-Horowitz type 3 and 4) usually require reduction and fixation. The most commonly used fixation methods are Kirschner wire (K-wire) pinning or retrograde elastic stable intramedullary nailing (ESIN). However, results comparing the long-term outcome of both methods are absent in the literature. The aim of this study was to provide an outcome comparison of both techniques. Included were 40 patients treated between 1998 and 2008 and who had complete records concerning operation time, duration of hospital stay, and time until implant removal. The assessment of clinical (Disabilities of Arm, Shoulder and Hand [DASH] and Constant-Murley scores) and radiologic long-term outcome was possible in 31 patients (78%). Preoperative, postoperative and follow-up radiographs of these patients were evaluated for angular deformity, reduction, and remodeling. The mean follow-up of the 31 patients (16 ESIN; 15 K-wire) was 5.8 ± 3.6 (standard deviation) years. The operative time of the primary fixation procedure was shorter in the ESIN group (P < .001), but the hospital stay and the time until implant removal were significantly longer. No significant difference was seen between the groups at follow-up for the mean DASH (ESIN, 1.44; K-wire, 1.66) or Constant-Murley (ESIN, 89.5; K-wire, 92) scores. The neck-shaft angle was significantly improved by reduction in both groups (P < .001) and remained unchanged at follow-up. ESIN and K-wire pinning have a favorable and comparable functional outcome and therefore seem to be adequate methods for treating Neer-Horowitz type 3 and 4 proximal humeral fractures in juvenile patients. The initially achieved improvement of the neck-shaft angle can be maintained at long-term follow-up.

Atypical Kawasaki Disease in a 4 Years Old Child with Mumps. Kawasaki disease is an acute febrile condition seen in children. However, it is also well recognized that some patients do not fulfill the classic diagnostic criteria for the diagnosis of Kawasaki disease. The incomplete form of Kawasaki disease is termed as 'Incomplete KD' or 'Atypical KD'. This is a case of 4 years old child with fever and mumps. He had bilateral cervical adenitis. Patient failed to respond to IV antibiotics fulfilled the criteria of incomplete Kawasaki disease. The child was managed with high dose aspirin until the child was afebrile for 48 hours. Kawasaki disease is a common vasculitis in children. Atypical cases might be missed if there is concomitant viral illness. Hence the identification and management of Kawasaki disease is paramount to decrease the mortality related to the cardiac disease. Keywords: bilateral cervical adenitis; fever and mumps; failed to respond IV antibiotics; incomplete kawasaki disease.

Preventing infectious disease with passive immunization. Antibodies can prevent infectious diseases by providing passive immune protection. Here we review successful clinical trials of passive immunization and consider some of the unique qualities monoclonal antibodies are now beginning to offer for developing methods for passive immunization against a wide range of infectious diseases.

Transductional efficacy and safety of an intraperitoneally delivered adenovirus encoding an anti-erbB-2 intracellular single-chain antibody for ovarian cancer gene therapy. We have previously shown that adenoviral-mediated delivery of an anti-erbB-2 intracellular single-chain antibody (sFv) causes specific cytotoxicy in erbB-2-overexpressing ovarian carcinoma cells. Furthermore, intraperitoneal delivery of the anti-erbB-2 sFv enhances survival and reduces tumor burden in a xenograft model of human ovarian carcinoma in SCID mice. These findings have led to an RAC-approved Phase I clinical trial for patients with ovarian cancer. In this report, we show that expression of the anti-erbB-2 sFv could be readily detected in target tumor cells by in situ hybridization methodology. PCR analysis of DNA extracted from various murine tissues demonstrated that the anti-erbB-2 sFv remained localized to the peritoneum. Delivery of the sFv to the non-erbB-2-overexpressing REN mesothelial and Hep G2 hepatocellular carcinoma cell lines was not deleterious to either one, affirming the tumor specificity of this gene therapy strategy. In addition, histopathological analysis of various tissues showed that adenoviral-mediated delivery of the anti-erbB-2 sFv to immunocompetent mice with either primary exposure or previous vector challenge at different doses produced no abnormal changes when compared to untreated animals. These findings suggest that adenoviral-mediated delivery of the anti-erbB-2 sFv in a human context can be effectively assayed, is potentially free of vector-associated toxicity, and retains biologic utility based on tumor specificity.

Inhibition of osteoblast function in vitro by aminobisphosphonates. Bisphosphonates are analogues of pyrophosphate, a key physicochemical inhibitor of mineralisation. We examined the direct actions of bisphosphonates on the function of cultured osteoblasts derived from rat calvariae. Treatment with zoledronate, the most potent bisphosphonate studied, reduced osteoblast number at concentrations > or = 100 nM and was strongly toxic at 10 microM, causing a threefold decrease in osteoblast viability after 2 days and a 90% decrease in cell numbers after 14 days. In control osteoblast cultures on plastic, abundant formation of 'trabecular' mineralised bone matrix nodules began after 10 days. Continuous exposure to zoledronate inhibited bone mineralisation at concentrations as low as 10 nM. Pamidronate and clodronate exerted similar effects but at higher doses > or = 1 and > or = 10 microM, respectively). Short-term or intermittent exposure of osteoblasts to zoledronate and pamidronate (1-10 microM) was sufficient to inhibit bone mineralisation by > or = 85%. Zoledronate but not pamidronate or clodronate also strongly inhibited osteoblast alkaline phosphatase activity at concentrations > or = 100 nM and soluble collagen production at concentrations > or = 1 microM. We additionally studied the effects of zoledronate on osteoblasts cultured on dentine, a bone-like mineralised substrate, observing similar inhibitory effects, although at concentrations 10-100-fold higher; this shift presumably reflected adsorption of zoledronate to dentine mineral. Thus, zoledronate blocked bone formation in two ways: first, a relatively non-toxic, selective inhibition of mineralisation at concentrations in the low nanomolar range and second, a cytotoxic inhibition of osteoblast growth and function at concentrations > or = 1 microM. Although no data are available on the bisphosphonate concentrations that osteoblasts could be exposed to in vivo, our results are consistent with earlier observations that bisphosphonates may inhibit bone formation.

How diagnosis-related group 559 will change the US Medicare cost reimbursement ratio for stroke centers. Thrombolysis for acute ischemic stroke saves societal costs, but hospitals that practice acute stroke care appear to shoulder the burden of the cost, which exceeds reimbursement. With creation of the diagnosis-related group (DRG) 559, the US Centers for Medicare and Medicaid Services pays hospitals approximately US $6000 more per case when thrombolysis is administered. We sought to determine the total cost of, and reimbursement for, acute stroke treatment with thrombolysis at a single stroke center and the economic impact of DRG 559. Between September 2001 and December 2004, we collected data on all patients with acute stroke who received thrombolysis. We identified all hospital costs and reimbursement per patient. Financial results were expressed as a cost-reimbursement ratio: average total cost to average total reimbursement per patient. We then reanalyzed data using the projected Medicare hospital reimbursement with DRG 559. Sixty-seven patients with stroke (mean age, 72 years) were treated (mean length of stay, 4.4 days; mean stroke severity, National Institutes of Health Stroke Scale score of 15; and symptomatic intracranial hemorrhage rate, 7%). The cost-reimbursement ratio was 1.41 (95% CI=0.98 to 2.28) before DRG 559 and estimated to be 0.82 (95% CI=0.66 to 0.97) after DRG 559. Our hospital costs have traditionally exceeded Medicare reimbursement for the acute care of thrombolyzed patients with ischemic stroke, but with DRG 559, a new economically favorable cost-reimbursement ratio for hospitals will be established.

Seasonal influence on gene expression of monoterpene synthases in Salvia officinalis (Lamiaceae). Garden sage (Salvia officinalis L., Lamiaceae) is one of the most important medicinal and aromatic plants and possesses antioxidant, antimicrobial, spasmolytic, astringent, antihidrotic and specific sensorial properties. The essential oil of the plant, formed mainly in very young leaves, is in part responsible for these activities. It is mainly composed of the monoterpenes 1,8-cineole, α- and β-thujone and camphor synthesized by the 1,8-cineole synthase, the (+)-sabinene synthase and the (+)-bornyl diphosphate synthase, respectively, and is produced and stored in epidermal glands. In this study, the seasonal influence on the formation of the main monoterpenes in young, still expanding leaves of field-grown sage plants was studied in two cultivars at the level of mRNA expression, analyzed by qRT-PCR, and at the level of end-products, analyzed by gas chromatography. All monoterpene synthases and monoterpenes were significantly influenced by cultivar and season. 1,8-Cineole synthase and its end product 1,8-cineole remained constant until August and then decreased slightly. The thujones increased steadily during the vegetative period. The transcript level of their corresponding terpene synthase, however, showed its maximum in the middle of the vegetative period and declined afterwards. Camphor remained constant until August and then declined, exactly correlated with the mRNA level of the corresponding terpene synthase. In summary, terpene synthase mRNA expression and respective end product levels were concordant in the case of 1,8-cineole (r=0.51 and 0.67 for the two cultivars, respectively; p<0.05) and camphor (r=0.75 and 0.82; p<0.05) indicating basically transcriptional control, but discordant for α-/β-thujone (r=-0.05 and 0.42; p=0.87 and 0.13, respectively).

Three-base deletion and one-base insertion of the alpha(1,4)galactosyltransferase gene responsible for the P phenotype. Recently, an alpha(1,4)galactosyltransferase gene that is responsible for synthesis of P(k) (Gb3) was isolated. The P individuals who did not express the P(k), P, and P(1) antigens on RBC membranes were shown to lack the P(k) (Gb3) synthase activity because of multiple distinct mutations in the alpha(1,4)galactosyltransferase gene. DNA sequences of the P(k) (Gb3) synthase gene in three Japanese individuals with the p phenotype were analyzed. One individual was found to be homozygous for an allele containing a three-base deletion of CTTCTTC to CTTC from bases 237 through 243 in the coding region. The other two individuals were found to be homozygous for an allele containing a single cytosine insertion in a cytosine repeat at positions 1026 through 1029, resulting in a reading frame shift. The P blood group phenotype is due to several distinct nonfunctional alleles without any predominant allele.

Exploring anti-MRSA activity of chitosan-coated liposomal dicloxacillin. One of the greatest disturbing global health problems is antibiotic-resistant bacterial infections, which have rendered numerous currently used antibiotics ineffective. Thus, the feasibility of chitosan-coated deformable liposomes (C-Lips) containing dicloxacillin (DLX) were evaluated for their efficacy against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are resistant to beta lactam antibiotics. DLX-loaded liposomes (DLX-Lip) were prepared by a lipid film hydration method and then chitosan (CS) coated (C-DLX-Lip) by the electrostatic deposition method. Both DLX-Lips and C-DLX-Lips showed a particle size distribution with a nano-range and a narrow polydispersity index (PDI). After CS coating, the zeta potential was shifted from negative to positive value. The DLX entrapment efficiency (EE) and drug loading (DL) were 62% and 5.6% for C-DLX-Lips compared to 38% and 3.1% for DLX-Lip, respectively. The in vitro release profile of C-DLX-Lips possessed a slow release behavior. Moreover, the DLX-Lips and C-DLX-Lips demonstrated an enhanced anti-MRSA activity. These results revealed that DLX-Lips and C-DLX-Lips may serve as promising carriers for DLX to increase the efficacy against MRSA, which offers considerably clinical value for long-term use of DLX.

A novel megakaryocyte differentiation factor from mouse placenta. Megakaryocyte differentiation and subsequent platelet production are regulated by a network of growth factors and cytokines. We hypothesized that pregnancy-specific regulatory factors also may participate in the modulation of megakaryocytopoiesis and thrombopoiesis. We identified a mouse placental prolactin-like protein hormone with an activity similar to interleukin 6 in targeting megakaryocytes and inducing cell differentiation. The receptor for this placental hormone is present on megakaryocytes from pregnant and nonpregnant female mice and from male mice, and from humans, suggesting that this signaling pathway (if not necessarily this particular ligand) is broadly functional both in terms of physiologic state and evolution. Thus, studying the biologic activities of the large family of placental prolactin-like proteins represents a potentially valuable approach to the discovery of novel hematopoietic signaling pathways.

Applying HFMEA to prevent chemotherapy errors. To evaluate risk and vulnerability in the chemotherapy process using a proactive risk analysis method. Healthcare failure mode and effect analysis (HFMEA) was adopted to identify potential chemotherapy process failures. A multidisciplinary team is formed to identify, evaluate, and prioritize potential failure modes based on a chemotherapy process flowchart. Subsequently, a decision tree is used to locate potential failure modes requiring urgent improvement. Finally, some recommended actions are generated and executed to eliminate possible risks. A total of 11 failure modes were identified with high hazard scores in both inpatient and outpatient processes. Computerized physician order entry was adopted to eliminate potential risks in chemotherapy processes. Chemotherapy prescription errors significantly decreased from 3.34% to 0.40%. Chemotherapy is regarded as a high-risk process. Multiple errors can occur during ordering, preparing, compounding, dispensing, and administering medications. Subsequently, these can lead to serious consequences. HFMEA is a useful tool to evaluate potential risk in healthcare processes.

Cholinergic influences on the spinal cardiovascular neurones. 1 In bilaterally vagotomized and spinal cord (C1) transected dogs, intrathecal (i.t.) injection of pilocarpine decreased while DMPP increased the blood pressure. These responses were antagonized by i.t. pretreatment with ethylbenztropine and chlorisondamine respectively. 2 No change in the resting heart rate occurred after intrathecal injection of cholinergic drugs in these animals. 3 The post-coronary artery ligation cardiac arrhythmia, in bilaterally vagotomized and spinal (C1) transected dogs, was inhibited by i.t. pilocarpine and chlorisondamine and facilitated by ethylbenztropine and DMPP. 4 The effects of muscarinic and nicotinic receptor agonists on the arrhythmia were blocked by their respective blockers. 5 It appears that the muscarinic receptors are inhibitory while nicotinic receptors are facilitatory for spinal control of vasomotor tone and the post-coronary artery ligation cardiac arrhythmia. However, the spinal muscarinic and nicotinic receptors do not appear to have a significant role in the regulation of normal heart rate.

The use of contrast echocardiography in the diagnosis of an unusual cause of congestive heart failure: achalasia. Extrinsic compression of the left atrium is a potentially life-threatening but unusual cause of congestive heart failure. Achalasia is a motility disorder characterized by impaired relaxation of the lower esophageal sphincter and dilation of the distal two-thirds of the esophagus. We report only the third known case in the world literature of massive left atrial compression by a dilated esophagus in a patient with achalasia. The use of contrast echocardiography with perflutren protein-type A microspheres allowed for differentiation between a compressive vascular structure and the esophagus. This resulted in prompt treatment leading to hemodynamic stability after nasogastric decompression and Botulinum toxin injection at the gastroesophageal junction.

Effective medium theory for drag-reducing micro-patterned surfaces in turbulent flows. Many studies in the last decade have revealed that patterns at the microscale can reduce skin drag. Yet, the mechanisms and parameters that control drag reduction, e.g. Reynolds number and pattern geometry, are still unclear. We propose an effective medium representation of the micro-features, that treats the latter as a porous medium, and provides a framework to model turbulent flow over patterned surfaces. Our key result is a closed-form expression for the skin friction coefficient in terms of frictional Reynolds (or Kármán) number in turbulent regime, the viscosity ratio between the fluid in and above the features, and their geometrical properties. We apply the proposed model to turbulent flows over superhydrophobic ridged surfaces. The model predictions agree with laboratory experiments for Reynolds numbers ranging from 3000 to 10000.

[The isomorphism of univalent thallium and potassium in membrane transport processes]. Thallium ions (T1+) are able to isomorphous replacement of K+ in various minerals. The similarity between. T1+ and K+ is based upon the closeness of their crystal radii, hydration energy and mobility in aqueous solutions. Under certain conditions, the behaviour of T1+ can be substantially different from that of K+. As distinguished from K+, thallium ions tend to associate with different anions forming ion pairs and complexes. As a rule, the stability of these compounds is rather low, but in many cases the T(1+)-anion interactions appear to play an important role in discriminating between T1+ and K+ involved in transport processes. T1+/K(+)-selectivity characterizes K(+)-transport mechanisms operating in different kinds of cells membranes. In excitable membranes (muscles, nerves) the rates of passive transport of T1+ and K+ are similar. In non-excitable membranes (epithelial cells, red blood cells, mitochondrial membranes, bacteria) the T1+ passive permeability is about one or two orders of magnitude higher than that of K+. A moderate T1+/K(+)-selectivity was reported for various types of K+ active transport mechanisms.

Profound reduction in allergen sensitivity following treatment with a novel allergy vaccine. A novel approach is described for the treatment of IgE-mediated allergic reactions which is based on the induction of a strong anti-IgE response in the host. Vaccination of ovalbumin-sensitized rats with constant domains two and three of rat IgE coupled to a heterologous carrier protein resulted in a profound decrease in serum levels of IgE, and later in a nearly complete block of histamine release from mast cells and basophils upon challenge with either a cross-linking polyclonal anti-IgE antiserum or a specific allergen.

Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer. Polyamines are essential for tumor growth; consequently, agents that interfere with their metabolisms have been developed as antineoplastic agents. Diethylnorspermine (DENSPM) is one such agent. A focused Phase I clinical trial in patients with advanced non-small cell lung cancer was undertaken. Twenty-nine patients were treated with DENSPM using a dosing schedule of once daily for 5 days. Doses ranged from 25 mg/m(2)/day to 231 mg/m(2)/day. The dose-limiting toxicity was determined to be gastrointestinal including asthenia, abdominal cramps, diarrhea, and nausea. The maximal tolerated dose was 185 mg/m(2)/day for 5 days. At drug dosages for which it was possible to estimate, serum half-life ranged from 0.5 to 3.7 h without apparent dose dependence. Maximal serum concentrations increased with dosage. However, the increase was greater than the proportional increase of the administered dose. There were no objective disease responses observed during the Phase I trial. The results of the Phase I clinical trial suggest that DENSPM can safely be administered to patients with minimal toxicity. Furthermore, the observed dose-limiting toxicity is unique to DENSPM, thus underscoring the potential for DENSPM to be a suitable agent for chemotherapy in combination with agents possessing different spectrums of toxicities.

On high-order denoising models and fast algorithms for vector-valued images. Variational techniques for gray-scale image denoising have been deeply investigated for many years; however, little research has been done for the vector-valued denoising case and the very few existent works are all based on total-variation regularization. It is known that total-variation models for denoising gray-scaled images suffer from staircasing effect and there is no reason to suggest this effect is not transported into the vector-valued models. High-order models, on the contrary, do not present staircasing. In this paper, we introduce three high-order and curvature-based denoising models for vector-valued images. Their properties are analyzed and a fast multigrid algorithm for the numerical solution is provided. AMS subject classifications: 68U10, 65F10, 65K10.

Effect of a visual-based sensory motor task on muscle tuning during a dynamic balance task. In this research, we explored visually-based sensory motor learning when a transformation was applied to the trajectory used to move and track a visual target in a virtual environment. The virtual task was controlled by the subject's center of foot pressure (COP), where the COP position was mapped to an on-screen cursor. Target balloons appeared randomly on the screen; the subject was instructed to move the COP-controlled cursor to intersect and burst the balloons. A transformation was applied to the movement trajectory, which rotated the on-screen cursor counter-clockwise by 60 degrees . The transformation required the subjects to update their spatial reference coordinates between the physical COP position and the on-screen cursor. To investigate learning during the transformation, electromyogram (EMG) data was recorded from the tibialis anterior and peroneus longus muscles. The muscle activity, calculated as the root mean square (RMS) of the EMG data, was calculated for each muscle as a function of the movement direction during movement initiation. The preferred direction (PD) for each muscle was then determined as the directional sum of the RMS values. The results showed a shift in the preferred direction (PD) of the muscles with learning.

Role of serine esterase in hydrogen peroxide-mediated activation of phospholipase A2 in rabbit pulmonary arterial smooth muscle cells. Exposure of rabbit pulmonary arterial smooth muscle cells to hydrogen peroxide cause dose-dependent stimulation of [14C] arachidonic acid (AA) release and enhancement of the cell membrane-associated phospholipase A2 activity as well as of the cell membrane-bound serine esterase activity tested against synthetic substrate p-tosyl-L-arginine methyl ester. While pretreatment of cells with serine protease inhibitors, viz. phenyl methyl sulphonyl fluoride, diisopropyl fluorophosphate and alpha-1-proteinase inhibitor, and antioxidant vitamin E prevents H2O2 stimulation of AA release and the cell membrane-bound serine esterase and PLA2 activities, that with actinomycin D and cycloheximide is devoid of any effect on H2O2 caused stimulation of AA release and the smooth muscle cell membrane associated serine esterase and PLA2 activities. Treatment of the smooth muscle cell membrane suspension with the serine protease trypsin markedly stimulates PLA2 activity. These results suggest that on exposure to H2O2 the smooth muscle cell membrane-bound serine esterase plays an important role in stimulating the cell membrane associated PLA2 activity thereby resulting in an increase in AA release.

Effects of amygdala kindling and electroconvulsive seizures on the expression of corticotropin-releasing hormone in the rat brain. Wjile low doses of corticotropin-releasing hormone (CRH) induce behavioral activation as part of the stress response, higher doses cause pathological excitability and seizures. Single CRH-induced convulsions resemble those following amygdala "kindling" in which intermittent exposure to a subconvulsive electrical stimulus eventually produces a motor seizure. To examine the possibility that alterations in CRH activity occur in kindling we used in situ hybridization to determine if electrical kindling of the amygdala or electroconvulsive seizures (ECS) could alter the expression of CRH mRNA in the rat brain. Amygdala kindling resulting in either after-discharges alone or full-blown motor seizures produced a dramatic increase in CRH but not glutamic acid decarboxylase (GAD) mRNA in the dorsal hippocampus, specifically in the large interneurons of the polygonal layer of the dentate hilus. CRH mRNA per cell and the number of cells expressing CRH increased at 30 min, 2 h, and 24 h but not at 3 weeks following the last kindled seizure. Repeated ECS also induced an up-regulation of CRH mRNA in the dentate hilus. Immunohistochemistry confirmed that seizures increased the number of hilar cells expressing CRH peptide. This induction of CRH could not be explained by nonspecific stress effects as neither restraint stress nor adrenalectomy had any influence on CRH mRNA in the dentate hilus. Both repeated ECS and kindled seizures also caused an increase in CRH mRNA in the hypothalamic paraventricular nucleus similar to that induced by chronic stress. Our results indicate that epileptiform activity induces CRH mRNA in the dentate hilus where normally very little CRH is expressed, suggesting that CRH may be important in mediating electrical excitability in the dentate gyrus and hippocampus.

Relationship between human papillomavirus type 16 in the cervix and intraepithelial neoplasia. To evaluate a temporal relationship between the presence of cervical human papilloma virus (HPV) type 16 and the risk of developing cervical intraepithelial neoplasia (CIN). Fifty-four women with HPV 16 polymerase chain reaction (PCR)-positive tests were selected from the gynecologic outpatient clinic of the Reinier de Graaf Hospital, Delft, The Netherlands. At least three successive PCR tests were performed in each woman at intervals of 6 months. The PCR HPV 16 assay was performed in conjunction with cervical smear, and colposcopy and biopsy, if indicated. Women with at least three consecutive positive PCR tests were defined as having persistent HPV 16 infections. Women with one positive test followed by two negative tests were defined as having transient infections. Subdivided into two groups, 25 women had persistent infections and 29 had transient infections. In significantly more women in the persistent group compared with the transient group, CIN developed (11 of 25 versus six of 29, P = .036). Lesions in women with persistent HPV 16 infection were more severe (six of 11 were CIN III versus one of six P = .041). Persistent infection with HPV 16 is associated with a higher risk of developing CIN, which is often high-grade.

Lumbar synovial cysts: experience with nine cases. Nine patients treated surgically for lumbar spinal synovial cyst were reviewed. Four patients had synovial, two had ganglion, one had posterior longitudinal ligament, and two had ligamentum flavum cyst. Synovial cysts had a single layer of epithelial cells in the inner layer of the cyst with continuity with the facet joint. Ganglion cyst had no continuity with the facet joint and epithelial lining was present in one and absent in one case. Posterior longitudinal ligament and ligamentum flavum cysts had no continuity with the facet joint and no epithelial lining. Magnetic resonance imaging showed the cysts better than computed tomography. All patients treated for nerve root compression or lumbar spinal canal narrowing. One patient suffered recurrence 1 year later and was reoperated. Operative results were excellent in six and good in three patients. Lumbar spinal synovial cysts should be considered in differential diagnosis of lumbar radiculopathy/neurogenic claudication and is surgically treatable.

Prostaglandin E2 suppositories as a second-trimester abortifacient. Despite the large number of second-trimester abortions performed each year in the United States through labor induction, the optimal method of inducing labor has not been developed. This study was performed to evaluate the efficacy and safety of vaginal prostaglandin E2 suppositories as an abortifacient. We analyzed the abortions at 14-24 menstrual weeks' gestation performed at Women's Hospital, Los Angeles, in 1985 and 1986. The abortion rate at 24 hours was 90.4%, with a mean induction-to-abortion time of 13.8 hours. Although gastrointestinal side effects were frequent, hemorrhage, infection and live births were infrequent. Prostaglandin E2 suppositories are a simple, effective and safe means of effecting second-trimester abortion that requires little surgical skill.

Genetic predisposition to obesity in bulimia nervosa: a mutation screen of the melanocortin-4 receptor gene. Obesity has been identified as a risk factor for the development of bulimia nervosa (BN). Accordingly, we hypothesize that genotypes predisposing to obesity can be detected in patients with this eating disorder. In order to investigate this hypothesis we screened the melanocortin-4 receptor gene (MC4R) for mutations using single strand conformation analysis in 81 female inpatients treated for BN. A single patient with both extreme obesity and BN had a haplo-insufficiency mutation in the MC4R. Comparison of current and maximal body mass index (BMI) of all patients with cross-sectionally obtained BMI in the general population revealed an age appropriate distribution for current BMI and a substantially increased frequency for overweight at time of maximal BMI. Our findings suggest that overweight is a risk factor for BN in clinically ascertained patients. For the first time a genotype predisposing to obesity has been detected in an extremely obese patient with BN.

Ecteinascidin 770, a tetrahydroisoquinoline alkaloid, sensitizes human lung cancer cells to anoikis. The strategies for achieving anti-metastasis have received increased research interest and clinical attention. The anoikis-sensitizing effect of ecteinascidin 770 (ET-770) was investigated in the present study in non-small cell lung cancer cells. ET-770 isolated from Ecteinascidia thurstoni was tested for its anoikis-sensitizing effect on H23 and H460 human lung cancer cells by 2,3-b-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. The levels of proteins being involved in anoikis of cells were determined by western blot analysis. ET-770 was shown to enhance anoikis response of human lung cancer H23 cells in a dose-dependent manner. The underlying mechanism was investigated and it was found that ET-770 sensitized the cells by activating the p53 protein, which in turn down-regulated anti-apoptotic myeloid cell leukemia sequence-1 (MCL1) and up-regulated BCL2-associated X protein (BAX) proteins. However, B-cell lymphoma-2 (BCL2) proteins were not significantly affected by ET-770. Further, the anoikis sensitization of ET-770 was observed in H460 lung cancer cells. The present results reveal for the first time that ET-770 can sensitize anoikis through the p53 pathway and further development of this compound for therapeutic use is warranted.

FT-IR Hyperspectral Imaging and Artificial Neural Network Analysis for Identification of Pathogenic Bacteria. Identification of microorganisms by Fourier transform infrared (FT-IR) spectroscopy is known as a promising alternative to conventional identification techniques in clinical, food, and environmental microbiology. In this study we demonstrate the application of FT-IR hyperspectral imaging for rapid, objective, and cost-effective diagnosis of pathogenic bacteria. The proposed method involves a relatively short cultivation step under standardized conditions, transfer of the microbial material onto suitable IR windows by a replica method, FT-IR hyperspectral imaging measurements, and image segmentation by machine learning classifiers, a hierarchy of specifically optimized artificial neural networks (ANN). For cultivation, aliquots of the initial microbial cell suspension were diluted to guarantee single-colony growth on solid agar plates. After a short incubation period when microbial microcolonies achieved diameters between 50 and 300 μm, microcolony imprints were produced by using a specifically developed stamping device which allowed spatially accurate transfer of the microcolonies' upper cell layers onto IR-transparent CaF2 windows. Dry microcolony imprints were subsequently characterized using a mid-IR microspectroscopic imaging system equipped with a focal plane array (FPA) detector. Spectral data analysis involved preprocessing, quality tests, and the application of supervised modular ANN classifiers for hyperspectral image segmentation. The resulting easily interpretable segmentation maps suggest a taxonomic resolution below the species level.

Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo. Human blood neutrophils exposed to appropriate stimuli aggregate, degranulate and generate superoxide anion (O2-). These responses are anteceded by mobilization of membrane-associated calcium, monitored as a decrease in fluorescence of cells preloaded with chlortetracycline (CTC). We studied the effects, both in vitro and in vivo, of non-steroidal anti-inflammatory agents (aspirin, indomethacin, ibuprofen and piroxicam) on these neutrophil responses to three stimuli: a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP); a tumor promotor, phorbol myristate acetate (PMA); and a lectin, concanavalin A (Con A). The effects of these drugs were compared with those of two polyenoic inhibitors of arachidonate metabolism: eicosatrienoic acid (ETI) and eicosatetraynoic acid (ETYA). The pattern of inhibition of neutrophil functions varied both with inhibitor and the nature of the stimulus. Thus, aspirin, piroxicam, ETYA and ETI inhibited neutrophil aggregation, degranulation, and O2- generation in response to FMLP, whereas ibuprofen inhibited only aggregation and degranulation and indomethacin only inhibited aggregation. None of the agents inhibited aggregation or degranulation induced by PMA or Con A: only piroxicam inhibited O2- generation in response to PMA or Con A. ETI and ibuprofen inhibited decrements of CTC fluorescence induced by FMLP, but whereas ETI inhibited the CTC response to PMA or Con A, ibuprofen was without effect. The agents had varying effects on binding of the stimulus [( 3H]FMLP, [3H]Con A), but these did not correlate with neutrophil responses to the ligands. Neutrophils from subjects taking therapeutic doses of ibuprofen, indomethacin, or piroxicam showed profiles of inhibited responses to FMLP similar to those observed with these agents in vitro. These data suggest that, although non-steroidal anti-inflammatory agents may inhibit discrete neutrophil functions both in vitro and in vivo, their effects do not duplicate those of polyenoic inhibitors of arachidonate metabolism. Moreover, since the susceptibility of neutrophils differed not only with respect to each inhibitor, but also to the stimulus, it is unlikely that all neutrophil responses are necessarily linked by a common pathway that is blocked by inhibitors of arachidonic acid metabolism.

Considering the employee point of view: perceptions of job satisfaction and stress among nursing staff in nursing homes. To document job satisfaction and sources of stress among nursing staff working in nursing homes and to evaluate the extent to which the reasons of stress differ by type of nursing staff. Cross-sectional study. Twenty-five nursing homes in North Carolina participating in a demonstration project of a new model of long-term care pharmacy. Nurses and nursing assistants employed at the time of the survey in the spring and summer of 2002 (n = 1283). Health Professional Stress Inventory modified for use in the nursing home setting and ratings of job satisfaction. The situations most stressful for nurses were not having enough staff, having too much work to do, interruptions, having non-health professionals determine how to do their job, poor pay, and ultimately being responsible for patient outcomes. The top most stressful situations for nursing assistants included poor pay, not enough staff, and too much work to do. Nursing assistants were more likely than nurses to report stress because they do not have adequate information regarding a patient's condition. Nurses were more likely than nursing assistants to report stress because non-health professionals (eg, surveyors) determine how they must do their job. The findings of this study support the need to improve recognition for nursing, improve staffing, and provide competitive compensation in nursing homes.

Acne cosmetica revisited: a case-control study shows a dose-dependent inverse association between overall cosmetic use and post-adolescent acne. Case-control studies to support the concept of acne cosmetica are lacking. To examine the association of post-adolescent acne with the use of cosmetics and cosmetic procedures. 910 post-adolescent patients with acne and an equal number of matched controls were studied for exposure to cosmetics and cosmetic procedures. A cumulative cosmetic exposure index was stratified into four quarters of increasing exposure. Comparison of different cumulative exposure categories with the lowest exposure category (multivariate analysis, logistic regression) showed that the odds ratios, which were always <1, progressively declined as cosmetic exposure increased [odds ratios (95% confidence intervals): 0.679 (0.501-0.922), 0.355 (0.258-0.487), 0.307 (0.217-0.433)]. However, some individual cosmetics had odds ratios >1. Overall cosmetic use was negatively associated with post-adolescent acne. The term 'acne cosmetica' is appropriate in the sense that some cosmetics may cause acne.

Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns. In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH. Eighty-three infants ≤30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3. Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life. Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH.

The effect of electron correlation on the adsorption of hydrogen fluoride and water on magnesium fluoride surfaces. We have performed periodic density functional and periodic local MP2 calculations for the adsorption of hydrogen fluoride and water on the four low index surfaces (001), (100), (101) and (110) of magnesium fluoride. While the adsorption of HF is described well using B3LYP, MP2 is required for a good description of the adsorption of H2O. Post-optimization dispersion corrections of B3LYP are found to consistently overestimate the adsorption energy. The coordination of surface cations, the presence of hydroxyls on the surface, as well as the coverage appear to play an equally important role in the adsorption.

Arbitrary-order all-fiber temporal differentiator based on a fiber Bragg grating: design and experimental demonstration. A new technique to design an all-fiber temporal differentiator that has a large bandwidth and an arbitrary differentiation order is proposed and investigated. The proposed temporal differentiator is a special fiber Bragg grating (FBG) that is designed by controlling its magnitude and phase responses with the discrete layer peeling (DLP) method. There are three important features of this technique: 1) the temporal differentiator has an arbitrary magnitude response and a controllable bandwidth; 2) the temporal differentiator can be designed and fabricated with an arbitrary differentiation order that is realized in a single FBG; 3) the required maximum index modulation of the FBG-based differentiator is largely decreased by using a Gaussian windowing function. The use of the proposed technique to design temporal differentiators with a differentiation order up to the fourth and with a bandwidth up to 500 GHz is studied. A proof-of-concept experiment is then carried out. A first- and a second-order temporal differentiator with a bandwidth of 25 GHz are experimentally demonstrated.

Mental disorders in patients with metabolic syndrome. The key role of central obesity. The Authors sought to evaluate current prevalence of mental disorders in patients affected by metabolic syndrome compared with patients affected by central obesity alone. 186 (63.5%) patients affected by central obesity and 107 (36.5%) affected by metabolic syndrome according to ICF criteria were interviewed by means of SCID I. Axis I current prevalence was respectively 45.7% and 44.9% among patients with central obesity and patients with metabolic syndrome, differences which were not significant. No statistically significant differences were found between groups as far as each single axis I diagnostic category was concerned. Moreover, current prevalence of any axis I, anxiety and mood disorders were independent of the number of components of metabolic syndrome. metabolic syndrome is associated to an higher risk for current mental disorders, which seems to be mainly due to the strong association of central obesity to psychopathology.

A successful re-trial after clozapine myopericarditis. Clozapine-induced myopericarditis is a well-described adverse drug reaction. Clozapine is also the most efficacious agent in refractory schizophrenia. We report a case of a patient who was successfully re-trialled on clozapine two years after developing myopericarditis, after which multiple lines of alternative treatment failed. We propose a protocol for safely attempting a re-trial of clozapine in such cases.

PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a Parkinson's disease-related protein. The effect of PAMAM dendrimers (generations G3, G4 and G5) on the fibrillation of alpha-synuclein was examined by fluorescence and CD spectroscopy, TEM and SANS. PAMAM dendrimers inhibited fibrillation of alpha-synuclein and this effect increased both with generation number and PAMAM concentration. SANS showed structural changes in the formed aggregates of alpha-synuclein--from cylindrical to dense three-dimensional ones--as the PAMAM concentration increased, on account of the inhibitory effect. PAMAM also effectively promoted the breaking down of pre-existing fibrils of alpha-synuclein. In both processes--that is, inhibition and disassociation of fibrils--PAMAM redirected alpha-synuclein to an amorphous aggregation pathway.

Influence of volatile compounds produced by yeasts predominant during processing of Coffea arabica in East Africa on growth and ochratoxin A (OTA) production by Aspergillus ochraceus. The effects of volatile compounds produced during coffee processing by Pichia anomala, P. kluyveri and Hanseniaspora uvarum on growth of Aspergillus ochraceus and production of ochratoxin A (OTA) were studied. On malt extract agar (MEA) and on coffee agar (CA), exposure of A. ochraceus to the gaseous phase of malt yeast glucose peptone (MYGP) plates inoculated with P. anomala, P. kluyveri and H. uvarum inhibited fungal growth, with the two Pichia spp. showing the strongest effect. The main esters and alcohols produced by the three yeasts were ethyl acetate, isobutyl acetate, 2-phenyl ethyl acetate, ethyl propionate and isoamyl alcohol. The individual esters and alcohols were found to affect fungal growth. The most effective compound in inhibiting fungal growth was 2-phenyl ethyl acetate; which at 48 microg/l headspace completely inhibited growth of A. ochraceus. Exposure of A. ochraceus to the gaseous phase of MYGP plates inoculated with P. anomala, P. kluyveri and H. uvarum prevented production of OTA. On CA medium, only the headspace of P. anomala and P. kluyveri prevented OTA production. Furthermore, when A. ochraceus was exposed to the headspace of the individual volatile compounds, 2-phenyl ethyl acetate was the most effective in preventing OTA production. Prevention of OTA seems to be due to reduction of fungal biomass.