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[Myasthenia onset in elderly patients]. Possibility of myasthenia debut at old age is shown. 5 cases of 73-87 year-olds with the diagnosis-generalized form of myasthenia are reported. Peculiarities of clinical manifestations in this age group are described. Polymorbidity in the individuals of old age is noted. It is recommended to include vasoactive preparations in the scheme of therapy.

Effects of respiratory muscle training (RMT) in patients with mild to moderate obstructive sleep apnea (OSA). Different forms of training focusing on the muscles of the upper airways showed limited effects on obstructive sleep apnea (OSA) and/or snoring. We investigated the effect of generalized respiratory muscle training (RMT) in lean patients with mild to moderate OSA. Nine male subjects (52.0 ± 10.8 years, BMI 29.1 ± 2.1 kg/m2) with obstructive sleep apnea (apnea-hypopnea index (AHI) 9-29) participated in an open, single-arm pilot study. After a 1-week build-up phase, patients underwent 4 weeks of normocapnic hyperpnea RMT five times a week for 30 min each. The initial and final measurements comprised polysomnography, pulmonary function tests, Epworth sleepiness scale (ESS), and SF-36 questionnaire (quality of life (QoL) self-assessment). The investigational site was a university-affiliated hospital for pulmonary diseases and sleep medicine, Solingen/Germany. Patients trained effectively, seen by a significant (p < 0.01) increase of breathing frequency (23.3 ± 1.5 /min vs. 30.6 ± 2.9 /min) and minute volume (81.2 ± 13.7 L vs. 109.1 ± 21.9 L). AHI, snoring and ESS remained unchanged after training. QoL as measured by SF-36 significantly (p < 0.05) improved after the training in the subscales "bodily pain" (79 ± 21 vs. 90 ± 12) and "change of health" (3.1 ± 0.3 vs. 2.4 ± 0.5). There is no evidence that AHI, pulmonary function or daytime sleepiness are affected by 5 weeks of RMT. Nevertheless, there is an improvement of parameters of quality of life. ClinicalTrials.gov , register no. NCT 00936286.

Bisexual erotomania with polycystic ovary disease. The case of a women with polycystic ovary disease and delusional disorder is reported. During the course of her paranoid illness she developed firstly "homosexual' erotomania and later "heterosexual' erotomania. We suggest that this is a rare presentation of delusional disorder.

Heparan sulphate interacts with tropoelastin, with some tropoelastin peptides and is present in human dermis elastic fibers. A number of reports point to the presence of proteoglycans and/or glycosaminoglycans within elastic fibers in normal and in pathological conditions. We present data that heparan sulphate (HS)-containing proteoglycans are associated with normal elastic fibers in human dermis and that isolated HS chains interact in vitro with recombinant tropoelastin and with peptides encoded by distinct exons of the human tropoelastin gene (EDPs). By immunocytochemistry, HS chains were identified as associated with the amorphous elastin component in the human dermis and remained associated with the residual elastin in the partially degenerated fibers of old subjects. HS appeared particularly concentrated in the mineralization front of elastic fibers in the dermis of patients affected by pseudoxanthoma elasticum (PXE). In in vitro experiments, HS induced substantial changes in the coacervation temperature and in the aggregation properties of recombinant tropoelastin and of synthetic peptides (EDPs) corresponding to sequences encoded by exons 18, 20, 24 and 30 of the human tropoelastin gene. In particular, HS modified the coacervation temperature and favoured the aggregation into ordered structures of tropoelastin molecules and of EDPs 18, 20 and 24, but not of EDP30. These data strongly indicate that HS-elastin interactions may play a role in tissue elastin fibrogenesis as well as modulating elastin stability with time and in diseases.

Bronchial sleeve resection distal to the main bronchi with complete pulmonary preservation. Report on three successful cases. Three successful cases of low grade malignant bronchial tumors resected by means of a bronchial sleeve resection distal to the main bronchi with complete pulmonary preservation are presented. Reconstruction of the bronchial tree was accomplished by suturing together the distal lobar bronchi and then anastomosing the double-barrel suture to the proximal residual bronchus. All patients presented excellent results, although in one patient postoperative course was complicated by persistent mucopurulent secretions. Bronchial sleeve resection distal to the main bronchi can be successfully performed for benign or low-grade malignant bronchial tumors. Technically, the operation is more complex than standard sleeve resection of the main bronchus and requires an experienced team. Postoperatively, an increased morbidity rate, mostly represented by secretions retention, may usually be anticipated, necessitating an aggressive medical and bronchoscopic management.

Measuring nanoscale diffusion dynamics in cellular membranes with super-resolution STED-FCS. Super-resolution microscopy techniques enable optical imaging in live cells with unprecedented spatial resolution. They unfortunately lack the temporal resolution required to directly investigate cellular dynamics at scales sufficient to measure molecular diffusion. These fast time scales are, on the other hand, routinely accessible by spectroscopic techniques such as fluorescence correlation spectroscopy (FCS). To enable the direct investigation of fast dynamics at the relevant spatial scales, FCS has been combined with super-resolution stimulated emission depletion (STED) microscopy. STED-FCS has been applied in point or scanning mode to reveal nanoscale diffusion behavior of molecules in live cells. In this protocol, we describe the technical details of performing point STED-FCS (pSTED-FCS) and scanning STED-FCS (sSTED-FCS) measurements, from calibration and sample preparation to data acquisition and analysis. We give particular emphasis to 2D diffusion dynamics in cellular membranes, using molecules tagged with organic fluorophores. These measurements can be accomplished within 4-6 h by those proficient in fluorescence imaging.

Effect of sensory substitution on suture-manipulation forces for robotic surgical systems. Direct haptic (force or tactile) feedback is not yet available in commercial robotic surgical systems. Previous work by our group and others suggests that haptic feedback might significantly enhance the execution of surgical tasks requiring fine suture manipulation, specifically those encountered in cardiothoracic surgery. We studied the effects of substituting direct haptic feedback with visual and auditory cues to provide the operating surgeon with a representation of the forces he or she is applying with robotic telemanipulators. Using the robotic da Vinci surgical system (Intuitive Surgical, Inc, Sunnyvale, Calif), we compared applied forces during a standardized surgical knot-tying task under 4 different sensory-substitution scenarios: no feedback, auditory feedback, visual feedback, and combined auditory-visual feedback. The forces applied with these sensory-substitution modes more closely approximate suture tensions achieved under ideal haptic conditions (ie, hand ties) than forces applied without such sensory feedback. The consistency of applied forces during robot-assisted suture tying aided by visual feedback or combined auditory-visual feedback sensory substitution is superior to that achieved with hand ties. Robot-assisted ties aided with auditory feedback revealed levels of consistency that were generally equivalent or superior to those attained with hand ties. Visual feedback and auditory feedback improve the consistency of robotically applied forces. Sensory substitution, in the form of visual feedback, auditory feedback, or both, confers quantifiable advantages in applied force accuracy and consistency during the performance of a simple surgical task.

Metabolic development in erythropoietin-dependent maturation of erythroid cells. 1. Metabolic development was investigated in splenic erythroblasts isolated from Friend virus infected mice and maintained in culture with erythropoietin. 2. We found that immature erythroid cells not only possess a highly oxidative metabolism, but also glycolytic activity, both of which decrease drastically in the course of maturation. 3. Most purine and pyrimidine compounds which are found in immature erythroid cells are still present in mature erythrocytes. 4. While total adenine nucleotide levels fall, the 2,3-DPG pool increases during erythroid development.

Shifting the focus toward rare variants in schizophrenia to close the gap from genotype to phenotype. Schizophrenia (SZ) is a disorder with a high heritability and a complex architecture. Several dozen genetic variants have been identified as risk factors through genome-wide association studies including large population-based samples. However, the bulk of the risk cannot be accounted for by the genes associated to date. Rare mutations have been historically seen as relevant only for some infrequent, Mendelian forms of psychosis. Recent findings, however, show that the subset of patients that present a mutation with major effect is larger than expected. We discuss some of the molecular findings of these studies. SZ is clinically and genetically heterogeneous. To identify the genetic variation underlying the disorder, research should be focused on features that are more likely a product of genetic heterogeneity. Based on the phenotypical correlations with rare variants, cognition emerges as a relevant domain to study. Cognitive disturbances could be useful in selecting cases that have a higher probability of carrying deleterious mutations, as well as on the correct ascertainment of sporadic cases for the identification of de novo variants.

Reduction of lesion-induced deficits in visual reversal learning following cross-modal training. Two experiments examined the effects of postoperative auditory intensity training on serial brightness reversal learning of visual decorticate rats. In Experiment 1 rats learned an avoidance response cued by a high intensity light prior to visual decortication. Six days later the rats were given either avoidance training with an auditory intensity cue, additional training with the preoperative visual cue, or no training. The next day all rats began a series of 8 brightness discrimination reversals. The no-training lesion group failed the early reversals but reached criterion in later reversals. Lesion rats retrained with visual cues failed early reversals with the low intensity light cue but not reversals with the high intensity cue. In contrast, lesion rats given auditory training easily reached criterion in all reversals. Experiment 2 followed a similar training sequence except auditory training was given after the second reversal. All rats showed rapid acquisition of all visual reversals subsequent to auditory training. These data suggest that generalization of a learning set by cross-modal transfer training with an intact modality can reduce reversal learning deficits following brain damage more efficiently than comparable training with the damaged system.

Effects of PAF and BN 52021 on cardiac function and regional blood flow in conscious rats. The effect of intravenous injections (0.1-3 nmol/kg) of platelet-activating factor (PAF) on blood pressure, heart rate, cardiac output, and blood flow (hindquarter, renal, mesenteric) were studied in conscious rats. PAF decreased blood pressure and total peripheral resistance (TPR) but increased heart rate; cardiac output was reduced by the highest dose. Low doses of PAF increased blood flow and decreased vascular resistance in all vascular beds, whereas high doses reduced mesenteric blood flow in part by increasing mesenteric vascular resistance. The hypotensive and cardiac effects of PAF were blocked by intravenous infusions of the selective PAF-receptor antagonists, 15 mg/kg BN 52021 and 1 mg/kg SDZ 63-441. BN 52021 also attenuated the hindquarter and renal responses to PAF, but the mesenteric responses remained relatively unchanged. The results indicate that PAF is a potent vasodilator of mesenteric greater than hindquarter = renal vessels at low doses and a cardiac depressant at high doses. A therapeutic role for the PAF antagonists BN 52021 and SDZ 63-441 is suggested in endotoxemia, anaphylaxis, and other disease states in which increased release of PAF contributes to key hemodynamic derangements.

Circulating KL-6/MUC1 as an independent predictor for disseminated intravascular coagulation in acute respiratory distress syndrome. Acute respiratory distress syndrome (ARDS) patients show high levels of circulating mucin including KL-6/MUC1 (soluble MUC1 mucin). Because cancer mucin can bind vascular endothelial cells and platelets via selectins, mucin-selectin interactions are reported to trigger platelet aggregation and intravascular coagulation. Therefore, we hypothesized that KL-6/MUC1 is involved in the pathogenesis of disseminated intravascular coagulation (DIC) in ARDS. The aim of the current study is to evaluate the association between circulating KL-6/MUC1 and DIC in ARDS patients. Observational study with structured follow-up. Intensive care unit in Hiroshima University Hospital. Fifty-six newly diagnosed patients with ARDS. Circulating levels of KL-6/MUC1 were measured during diagnosis and serially measured during the clinical course along with indices of respiratory failure, inflammation, coagulation and fibrinolysis and multiple organ dysfunction. Acute respiratory distress syndrome patients complicated with DIC showed significantly higher levels of serum KL-6/MUC1 than patients without DIC during the clinical course. Amongst the parameters analysed at diagnosis of ARDS, KL-6/MUC1 was an independent predictor for DIC complication. The baseline level of circulating KL-6/MUC1 at diagnosis of ARDS was significantly correlated with an increased DIC score following ARDS diagnosis. Using an optimum cutoff level of KL-6/MUC1 obtained by a receiver operating characteristic curve, the sensitivity and specificity for predicting future DIC development in ARDS patients were 88.9% and 55.3%, respectively. These results suggest that KL-6/MUC1 is associated with DIC development in ARDS patients. Elevated levels of KL-6/MUC1 at diagnosis could be a predictor of DIC complication in ARDS.

Assessing the quality of care for paediatric depression and anxiety in Australia: A population-based sample survey. We examine the prevalence of quality care (as measured by adherence to recommendations in clinical practice guidelines) for Australian paediatric patients (⩽15 years) with depression and/or anxiety, using data from the CareTrack Kids study; a population-based study of the quality of healthcare practice in inpatient and ambulatory healthcare settings. A multistage stratified sample identified records of 6689 children. Of these, 156 records were identified for depression and 356 for anxiety. These were assessed for adherence to 15 depression and 13 anxiety indicators, respectively, using a review of medical records. Adherence to assessment and management guidelines was low for both conditions: assessment bundle (depression = 33%, 95% confidence interval = [20, 48]; anxiety = 54%, 95% confidence interval = [43, 64] and depression management bundle = 35%, 95% confidence interval = [15, 60]). Across both conditions, the highest adherence was recorded for indicators that addressed prescription of medications (e.g. venlafaxine, 100%; benzodiazepines, 100%; selective serotonin reuptake inhibitor, 94% and antidepressants, 91%), while compliance was the lowest for ensuring children with depression had an emergency safety plan (44%), informing parents of the risks and benefits of prescribed anxiety medication (51%) and assessment for other causes (59% for depression; 68% for anxiety). These findings suggest that strategies are needed to improve guideline adherence for mental health disorders in children and adolescents, particularly among general practitioners. Learning from these indicators could inform clinical prompts in electronic medical records, as well as links to additional information, to assist in decision-making and streamline work practices.

Effects of dietary crude oil exposure on molecular and physiological parameters related to lipid homeostasis in polar cod (Boreogadus saida). Polar cod is an abundant Arctic key species, inhabiting an ecosystem that is subjected to rapid climate change and increased petroleum related activities. Few studies have investigated biological effects of crude oil on lipid metabolism in this species, despite lipids being a crucial compound for Arctic species to adapt to the high seasonality in food abundance in their habitat. This study examines the effects of dietary crude oil exposure on transcription levels of genes related to lipid metabolism (peroxisome proliferator-activated receptors [ppar-α, ppar-γ], retinoic X receptor [rxr-β], palmitoyl-CoA oxidase [aox1], cytochrome P4507A1 [cyp7α1]), reproduction (vitellogenin [vtg-β], gonad aromatase [cyp19a1]) and biotransformation (cytochrome P4501A1 [cyp1a1], aryl hydrocarbon receptor [ahr2]). Exposure effects were also examined through plasma chemistry parameters. Additional fish were exposed to a PPAR-α agonist (WY-14,643) to investigate the role of PPAR-α in their lipid metabolism. The dose-dependent up-regulation of cyp1a1 reflected the activation of genes related to PAH biotransformation upon crude oil exposure. The crude oil exposure did not significantly alter the mRNA expression of genes involved in lipid homeostasis except for cyp7α1 transcription levels. Plasma levels of cholesterol and alanine transaminase showed significant alterations in fish exposed to crude oil at the end of the experiment. WY exposure induced a down-regulation of ppar-α, an effect contrary to studies performed on other fish species. In conclusion, this study showed clear effects of dietary crude oil exposure at environmentally relevant concentrations on xenobiotic biotransformation but revealed only weak alterations in the lipid metabolism of polar cod.

Conservation of blood in cardiac surgery. The rising costs of surgical care and decreasing third-party reimbursement mandate conservation of surgical resources and supplies whenever possible. One such resource is autologous blood. Its conservation has the added benefit of protecting the patient from the potential dangers of homologous blood and its products. This article presents conservation techniques found to be feasible in open-heart surgery.

Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Dissolving microneedles, three-dimensional polymer structures with microscale cross-sectional dimensions, have been introduced as a means of safe transdermal drug delivery. Most dissolving microneedles have been fabricated using a traditional micro-casting method that cures biopolymers within three-dimensional mold, nevertheless, repeated molding process may cause damage to encapsulated drugs, a critical hurdle for clinical application. Here, we describe the stepwise controlled drawing technique that can directly fabricate dissolving microneedle from maltose by precise controlling the drawing time and the viscosity of the maltose. Controlled drawing shaped the particular sharp-conical microneedles of 1200 μm length with tip diameter of 60 μm, and dissolved within 20 min in-vivo after inserting to the skin. This technique surpasses the limitations of micro-casting for dissolving microneedle. Furthermore, transdermal delivery of impermeable hydrophilic molecules such as ascorbic acid-2-glucoside and niacinamide was confirmed as inhibition of cutaneous hypermelanosis. We anticipate that controlled drawing technique will be suitable to design dissolving microneedles for use in minimally invasive transcutaneous drug delivery to patients.

Kinetic properties of human dopamine sulfotransferase (SULT1A3) expressed in prokaryotic and eukaryotic systems: comparison with the recombinant enzyme purified from Escherichia coli. Sulfation, catalyzed by members of the sulfotransferase enzyme family, is a major metabolic pathway which modulates the biological activity of numerous endogenous and xenobiotic chemicals. A number of these enzymes have been expressed in prokaryotic and eukaryotic systems to produce protein for biochemical and physical characterization. However, the effective use of heterologous expression systems to produce recombinant enzymes for such purposes depends upon the expressed protein faithfully representing the "native" protein. For human sulfotransferases, little attention has been paid to this despite the widespread use of recombinant enzymes. Here we have validated a number of heterologous expression systems for producing the human dopamine-metabolizing sulfotransferase SULT1A3, including Escherichia coli, Saccharomyces cerevisiae, COS-7, and V79 cells, by comparison of Km values of the recombinant enzyme in cell extracts with enzyme present in human platelets and with recombinant enzyme purified to homogeneity following E. coli expression. This is the first report of heterologous expression of a cytosolic sulfotransferase in yeast. Expression of SULT1A3 was achieved in all cell types, and the Km for dopamine under the conditions applied was approximately 1 microM in all heterologous systems studied, which compared favorably with the value determined with human platelets. We also determined the subunit and native molecular weights of the purified recombinant enzyme by SDS-PAGE, electrospray ionization mass spectrometry, dynamic light scattering, and sedimentation analysis. The enzyme purified following expression in E. coli existed as a homodimer with Mr approximately 68,000 as determined by light scattering and sedimentation analysis. Mass spectrometry revealed two species with experimentally determined masses of 34,272 and 34,348 which correspond to the native protein with either one or two 2-mercaptoethanol adducts. We conclude that the enzyme expressed in prokaryotic and eukaryotic heterologous systems, and also purified from E. coli, equates to that which is found in human tissue preparations.

Myoid hamartoma of breast with chondroid metaplasia: a case report. Breast hamartoma is an uncommon poorly recognised benign breast neoplasm. Hamartoma displaying marked smooth muscle components known as myoid hamartoma of the breast is a much rarer entity. We present a case of myoid hamartoma of breast with chondroid differentiation in a 46-year-old woman. The painless breast lump was circumscribed and mammography showed a well-encapsulated large, dense mass with no calcification. Core needle biopsy was reported as fibroadenoma. The lesion was excised. Microscopically, it composed of many groups of mammary glandular components with dense fibrous stroma, adipose tissue and marked groups of smooth muscle fibres. Foci of chondroid differentiation were noted in the lesion. The smooth muscle cells showed strong and diffuse immunoreactivity for vimentin, myogloblin, alpha-smooth muscle actin, desmin and CD34 and failed to express pan-cytokeratin or S100 protein. The ducts lined by epithelial cells were reactive to pan-cytokeratin while the myoepithelial cells were reactive to S100 protein. The various immuno-histochemical staining as well as the cyto-histological changes encountered in myoid hamartomas are discussed with clinical, radiological and pathological correlation to differentiate it from other benign and malignant breast lesions.

Royal Darwinian Demons: Enforced Changes in Reproductive Efforts Do Not Affect the Life Expectancy of Ant Queens. One of the central tenets of life-history theory is that organisms cannot simultaneously maximize all fitness components. This results in the fundamental trade-off between reproduction and life span known from numerous animals, including humans. Social insects are a well-known exception to this rule: reproductive queens outlive nonreproductive workers. Here, we take a step forward and show that under identical social and environmental conditions the fecundity-longevity trade-off is absent also within the queen caste. A change in reproduction did not alter life expectancy, and even a strong enforced increase in reproductive efforts did not reduce residual life span. Generally, egg-laying rate and life span were positively correlated. Queens of perennial social insects thus seem to maximize at the same time two fitness parameters that are normally negatively correlated. Even though they are not immortal, they best approach a hypothetical "Darwinian demon" in the animal kingdom.

Changes in low right atrial conduction times during pulmonary vein isolation for atrial fibrillation: correlation with inducibility of typical right atrial flutter. Isthmus-dependent right atrial flutter (RAFL) is a common sequela of pulmonary vein isolation (PVI). It is unclear as to whether RAFL is a result of PVI or a concealed phenomenon unmasked by the elimination of atrial fibrillation (AF). We measured low right atrial conduction times (LRACTs) before and after PVI and examined their relationship to the inducibility of RAFL. Twenty consecutive patients with paroxysmal AF but no history of RAFL were studied during the initial PVI procedure by radiofrequency ablation. Antiarrhythmic agents were discontinued for at least five half-lives. The clockwise and counterclockwise LRACTs were measured before and after PVI by pacing the proximal coronary sinus or low-lateral RA. Programmed atrial stimulation was performed post-PVI. Right atrial flutter, if inducible, was confirmed by entrainment mapping. Right atrial flutter was induced in six patients (Group A). No arrhythmias or only AF was induced in the remaining 14 patients (Group B). The average change in the clockwise LRACT was 19.8±17.5 ms in Group A vs. 0.3±10.7 ms in Group B (P<0.05). The average change in the counterclockwise LRACT was 25.7±30.4 ms in Group A vs. 0.0±6.7 ms in Group B (P<0.05). There were no significant differences between the groups in absolute LRACT or number of ablation lesions around the right pulmonary veins. Right atrial flutter post-PVI is associated with prolongation of LRACTs. Ablation over the septal left atrium near the posterior right atrium during isolation of the right pulmonary veins may cause conduction delays that can lead to RAFL.

Acute interstitial nephritis in Singapore: a report of five cases. Interstitial nephritis is an uncommon cause of acute renal failure. Reported incidence varies widely in the literature and may depend on several factors i.e. geographical location, diagnostic criteria, dietary, environmental factors and therapeutic practices. This is a retrospective study of biopsy proven interstitial nephritis in National University Hospital Singapore. We report five cases out of a total of 349 biopsies carried out during a five-year period between September 1997 and August 2002. Four patients presented acutely with fever and or cough. In four patients, there was exposure to traditional Chinese medications and/or drugs. Renal failure in four out of the five patients progressed rapidly, three of whom required dialysis. One patient was treated with steroids. Renal function recovered in all patients with one patient who had significant residual renal impairment after one month.

Malignant lymphoma of the thyroid gland: a clinicopathologic study. This study reviews 21 cases of thyroid lymphoma diagnosed between 1969 and 1980. The thyroid gland was the primary site in all but two cases. The 20 patients with non-Hodgkin lymphoma had a mean age of 66 years, 75% were women, and all were Caucasian. A rapidly growing thyroid mass with hoarseness, dysphagia, and difficulty in breathing was the initial finding. Most patients had diffuse histiocytic lymphomas. Associated Hashimoto thyroiditis was found histologically in 57% of the cases. Using the immunoperoxidase stain method on tissue sections, intracytoplasmic monoclonal immunoglobulin was demonstrated in 5 of 15 cases. All but two patients received radiation therapy, and 13 received chemotherapy. The median survival was 8 months; 20% died of unrelated causes and 32% are alive (average duration: 27 months). Dissemination, after local control by radiation therapy, was the leading cause of death. The prognosis was better in men, in patients under the age of 65 years, and in those patients who, on biopsy, did not have involvement of the extrathyroid soft tissue or regional lymph nodes.

Late postacute neurologic rehabilitation: neuroscience, engineering, and clinical programs. This lecture highlights my career in rehabilitation research. My principal efforts in rehabilitation have been to study (1) mechanisms of brain plasticity related to reorganization of the brain and recovery of function; (2) late postacute rehabilitation; (3) sensory substitution; and (4) rehabilitation engineering. A principal goal has been to aid in the development of a strong scientific base in rehabilitation.

The impact of for-profit hospital status on the care and outcomes of patients with non-ST-segment elevation myocardial infarction: results from the CRUSADE Initiative. We sought to determine whether for-profit status influenced hospitals' care or outcomes among non-ST-segment elevation myocardial infarction (NSTEMI) patients. While for-profit hospitals potentially have financial incentives to selectively care for younger, healthier patients, perform highly reimbursed procedures, reduce costs by limiting access to expensive medications, and encourage shorter in-patient length of stay, there are limited data available to investigate these issues objectively. Using data from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) Initiative, we investigated whether for-profit status influenced hospitals' patient case mix, care, or outcomes among 145,357 patients with NSTEMI treated between January 1, 2001, and December 31, 2005, at 532 U.S. hospitals. Impact of for-profit status on care and outcomes was analyzed overall and after adjustment for clinical and facility factors using regression modeling. Patients (n = 11,658) treated at 58 for-profit hospitals were of similar age and gender, but were more likely to be nonwhite (black, Asian, Hispanic, and other) and have health maintenance organization/private insurance, diabetes mellitus, congestive heart failure, hypertension, and renal insufficiency compared with 133,699 patients treated at 474 nonprofit hospitals. For-profit hospitals were less likely to use discharge beta-blockers, but all other treatments were similar including the use of interventional procedures (cardiac catheterization and revascularization procedures) compared with nonprofit centers. In-hospital length of stay and mortality were also similar by hospital type. We found no evidence that for-profit hospitals selectively treat less sick patients, provide less evidence-based care, limit in-hospital stays, or have patients with worse acute outcomes than nonprofit centers.

Myoglobin in polyacrylamide hydrogel films: direct electrochemistry and electrochemical catalysis. Electrochemical behavior of myoglobin (Mb) incorporated in polyacrylamide (PAM) hydrogel films cast on pyrolytic graphite (PG) electrodes were investigated. Mb-PAM film electrodes showed a pair of well-defined and nearly reversible cyclic voltammetric peaks for Mb Fe(III)/Fe(II) redox couple at about -0.27 (vs. SCE) in pH 5.5 buffers. The electron exchange of Mb with PG electrodes was greatly enhanced in PAM films. The apparent heterogeneous electron transfer rate constant (k(s)) and formal potential (E degrees ') were estimated by fitting the data of square wave voltammetry (SWV) with non-linear regression analysis. The formal potential of Mb-PAM films shifted linearly with pH with a slope of -0.52 V, showing the electron transfer was accompanied by a single-proton transportation. Positions of Soret absorbance band of Mb-PAM films suggest that Mb maintains its secondary structure similar to its native state in the films in the medium pH range. Oxygen, trichloroacetic acid (TCA) and nitrite were catalytically reduced by Mb-PAM film electrodes with significant lowering of overpotential. Potential application of Mb-PAM films as biosensors to monitor some substrates was proposed.

Female size constrains egg size via the influence of reproductive organ size and resource storage in the seed beetle Callosobruchus chinensis. The standard egg size model predicts that a mother lays an optimal size of eggs in a given environment. However, there is evidence that larger females lay larger eggs across diverse animal taxa. This positive correlation suggests there are morphological constraints on egg size imposed by the size of the maternal organ through which eggs pass during oviposition. There is also evidence that large mothers that have greater capital resources produce large eggs. We tested whether morphological (ovipositor width) or physiological (maternal body weight as a measure of capital resources) mechanisms constrain egg size, using an inbred line of seed beetles, Callosobruchus chinensis. In addition, we tested whether having a wide ovipositor relative to body size is costly in terms of egg production. Egg width but not length increased with ovipositor width. Egg length and width increased with body weight. The cost of wider ovipositor was not detected. We conclude that females adjust egg size depending on capital resource level under the morphological constraint.

Expression of CD105 (endoglin) in arteriolar endothelial cells of human endometrium throughout the menstrual cycle. The cellular mechanisms underlying normal and pathological endometrial bleeding are not well understood, although abnormalities in the structure of endometrial blood vessels may lead to menstrual disorders. Endothelial cells in different organs are heterogeneous and differ in structure, function, antigen composition, metabolic properties and responses to growth factors. Immunostaining was performed with anti-CD105, CD31, CD34 and von Willebrand factor (vWF), and lectin binding with Ulex europaeus agglutinin 1 (UEA 1), Bandeieraea simplicifolia agglutinin 1 (BS 1), Dolichos biflorus agglutinin (DBA) and Peanut agglutinin (PNA) to characterize endothelial cells in human endometrium throughout the menstrual cycle. Serial sections fixed with formalin were stained with primary antibodies and lectins after antigen retrieval. Positive staining for CD31, CD105 and vWF was confined to the vascular endothelium. Endothelial expression of CD31 was observed in all types of vessel, including single cells, and strong staining was found during the early proliferative and mid-secretory phases. Anti-vWF stained arterioles and veins, but there was little positive staining of capillaries. In contrast, staining for CD105 was confined to the arterioles. Although anti-CD34 strongly stained endothelial cells of small vessels and capillaries, staining was also observed on some non-endothelial stromal cells. Strong positive staining for UEA 1 was observed in endothelial cells of all types of vessel throughout the menstrual cycle. Binding of PNA, DBA and BS 1 was confined to the apical region of glandular epithelial cells. This study demonstrates that the differential binding of anti-CD31, CD34, CD105, vWF and UEA 1 distinguishes between endometrial populations of endothelial cells.

Recruitment of single motor units in the human blink reflex. The recruitment of single motor units (MU) in the early (R1) and late (R2) components of the electrically evoked human blink reflex (BR) was studied using bipolar needle electrodes with a limited take-off area. It could be shown that the same MUs can discharge in R1 and R2 of a BR as well as during voluntary eyelid contraction. At repetitive stimulation (1 Hz), facilitation of MU discharges in R1 and habituation in R2 became apparent. The visible reflex eyelid contraction may mainly be due to repetitive MU discharges in R2. The discharges of the same MUs in R1, however, contribute to it and shorten the latency between stimulus and reflex response.

Effect of cholecystectomy on plasma lipid and lipoprotein levels. This study was designed to elucidate the effect of cholecystectomy, a common surgical procedure, on the concentrations of plasma lipids and lipoproteins. 19 consecutive patient with symptomatic gallstone disease and emptying gallbladder, and 16 control patients (Nissen-Rosetti fundoplication) were studied. Cholesterol, triglyceride, and protein concentrations of various lipoproteins were analysed. Plasma total and LDL cholesterol levels were significantly reduced in cholecystectomy patients (p = 0.0048 and p=0.0239) at day 3 after the operation, the values returning to the preoperative level thereafter. In the control patients similar trends were observed for total and LDL cholesterol levels but these changes did not reach statistical significance. In cholecystectomy patients a significant increase was noticed in the very-low-density lipoprotein and intermediate density lipoprotein apoprotein B concentration three years after surgery (p= 0.0019 and p=0.0001). These minor changes in plasma lipoproteins following cholecystectomy are unlikely to have any importance in the development coronary heart disease. They indicate, however, altered enterohepatic metabolism of cholesterol after the removal of the gallbladder.

A multiscale mechanism of drug release from polymeric matrices: confirmation through a nonlinear theoretical model. In this paper, we propose a new approach for the dynamics of drug delivery systems, assimilated to complex systems, an approach based on concepts like fractality, non-differentiability, and multiscale evolution. The main advantage of using these concepts is the possibility of eliminating the approximations used in the standard approach by replacing complexity with fractality, that imposes, in mathematical terms, the mandatory use of the non-differential character of defined physical quantities. The theoretical model presented, validated for other physical systems, demonstrates its functionality also for drug delivery systems, highlighting, in addition, new insights into the complexity of this system. The spatio-temporal scales of system evolution are characterized through the fractality degree, as a measure of the complexity of the phenomena occurring at each scale. Numerical analysis of the experiment showed that the overall drug release kinetics can be obtained by composing "smaller release kinetics" occurring at scales appropriate for each phase of the drug release mechanism, phases whose expansion depends on the system density. Moreover, the uncertainties in establishing the exact limits of the phases were removed by applying the principle of scale superposition, resulting in a global fractality degree corresponding to the entire release kinetics. Even if the theoretical model is perfectible by identifying constants specific to each delivery system, this paper is intended to be the beginning of an alternative approach to drug delivery mechanisms.

Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies. An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.

Structural equation modeling of paired-comparison and ranking data. L. L. Thurstone's (1927) model provides a powerful framework for modeling individual differences in choice behavior. An overview of Thurstonian models for comparative data is provided, including the classical Case V and Case III models as well as more general choice models with unrestricted and factor-analytic covariance structures. A flow chart summarizes the model selection process. The authors show how to embed these models within a more familiar structural equation modeling (SEM) framework. The different special cases of Thurstone's model can be estimated with a popular SEM statistical package, including factor analysis models for paired comparisons and rankings. Only minor modifications are needed to accommodate both types of data. As a result, complex models for comparative judgments can be both estimated and tested efficiently.

An assessment of the effectiveness of the revised FDA checklist. In 1978, the Food and Drug Administration (FDA), developed a generic anesthesia equipment preuse checklist. The checklist was first released by the FDA in August 1986 and endorsed by the American Association of Nurse Anesthetists on October 18, 1986. The FDA checklist was revised in 1992 to improve the abilities of anesthesia providers to detect machine faults. In the present study, the investigators attempted to determine the effectiveness of the revised FDA checklist in detection of anesthesia machine faults as compared to providers' usual methods. Whereas no published study of preanesthesia safety inspection had been performed since the revision of the FDA checklist, the authors compared the detection abilities of anesthesia providers before and after inclusion of the revised FDA checklist. Twenty-two anesthesia providers were tested to compare the number of prearranged anesthesia machine faults that could be detected with (1) their usual checkout methods, and (2) with the revised FDA checklist. Data describing the subjects' fault detection abilities were analyzed using the t test for paired observation (P value < 0.05 considered significant). Statistical analysis revealed no significant difference (P = 0.479) when subjects used the FDA checklist and when they used their usual method. Use of the FDA machine checklist was no more effective than the provider's usual method in discovering machine faults. When using their normal method, 54.5% of providers did not discover more than 50% of programmed faults. Approximately 40.9% of providers who used the revised FDA checklist did not discover over 50% of programmed faults.

A unified relation for the solid-liquid interface free energy of pure FCC, BCC, and HCP metals. We study correlations between the solid-liquid interface (SLI) free energy and bulk material properties (melting temperature, latent heat, and liquid structure) through the determination of SLI free energies for bcc and hcp metals from molecular dynamics (MD) simulation. Values obtained for the bcc metals in this study were compared to values predicted by the Turnbull, Laird, and Ewing relations on the basis of previously published MD simulation data. We found that of these three empirical relations, the Ewing relation better describes the MD simulation data. Moreover, whereas the original Ewing relation contains two constants for a particular crystal structure, we found that the first coefficient in the Ewing relation does not depend on crystal structure, taking a common value for all three phases, at least for the class of the systems described by embedded-atom method potentials (which are considered to provide a reasonable approximation for metals).

Weak Van der Waals Stacking, Wide-Range Band Gap, and Raman Study on Ultrathin Layers of Metal Phosphorus Trichalcogenides. 2D semiconducting metal phosphorus trichalcogenides, particularly the bulk crystals of MPS3 (M = Fe, Mn, Ni, Cd and Zn) sulfides and MPSe3 (M = Fe and Mn) selenides, have been synthesized, crystallized and exfoliated into monolayers. The Raman spectra of monolayer FePS3 and 3-layer FePSe3 show the strong intralayer vibrations and structural stability of the atomically thin layers under ambient condition. The band gaps can be adjusted by element choices in the range of 1.3-3.5 eV. The wide-range band gaps suggest their optoelectronic applications in a broad wavelength range. The calculated cleavage energies of MPS3 are smaller than that of graphite. Therefore, the monolayers used for building of heterostructures by van der Waals stacking could be considered as the candidates for artificial 2D materials with unusual ferroelectric and magnetic properties.

Colors and contact dermatitis. The diagnosis of skin diseases relies on several clinical signs, among which color is of paramount importance. In this review, we consider certain clinical presentations of both eczematous and noneczematous contact dermatitis in which color plays a peculiar role orientating toward the right diagnosis. The conditions that will be discussed include specific clinical-morphologic subtypes of eczematous contact dermatitis, primary melanocytic, and nonmelanocytic contact hyperchromia, black dermographism, contact chemical leukoderma, and others. Based on the physical, chemical, and biologic factors underlying a healthy skin color, the various skin shades drawing a disease picture are thoroughly debated, stressing their etiopathogenic origins and histopathologic aspects.

The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis. We have previously reported a heteroplasmic mtDNA mutation (T1095C) in the 12SrRNA gene of an Italian family with features of maternally-inherited parkinsonism, antibiotic-mediated deafness and peripheral neuropathy. In the present study, we demonstrate that a transmitochondrial cybrid line derived from the proband of this family shows selective depletion of mitochondrial glutathione and decreases in the activity of complex II/III. Moreover, when exposed to an aminoglycoside antibiotic these cells responded with a ten-fold increase in the number of apoptotic cells compared to controls. These results support a pathogenic role for the T1095C mutation and indicate that the mutation increases the risk for aminoglycoside-induced toxicity.

Selective endo and exo iodocyclizations in the synthesis of quinolines and indoles. [reaction: see text] A simple, efficient method for a divergent synthesis of indoles, quinolines, and quinolinones using a highly selective endo/exo iodocyclization procedure is described.

Graduated guidance delivered by parents to teach yoga to children with developmental delays. We evaluated the effects of a parent-implemented intervention to teach yoga poses to 3 children with developmental delays. Graduated guidance, provided by the participants' mothers, was introduced in a multiple baseline design across the participants. With the introduction of intervention, imitation of the response chains increased over baseline for all participants. Generalization to novel and live models occurred for 2 participants. Results are discussed in terms of using behavior-analytic procedures to teach physical fitness activities to individuals with developmental disabilities.

Cholinergic control of catechol metabolism in the rat locus coeruleus as studied by in vivo voltammetry. Differential pulse voltammetry with treated carbon fibre electrodes was used to study the effect of cholinergic drugs on the metabolism of locus coeruleus (LC) noradrenergic cells in vivo. A catechol peak corresponding to DOPAC synthesized by noradrenergic cells and reflecting their metabolic activity, was recorded every two minutes in the LC of freely moving rats. Cholinergic agonists like eserine (0.5 mg/kg s.c.) and oxotremorine (0.1 and 0.4 mg/kg s.c.) increased the DOPAC peak. This effect seemed to be mediated by muscarinic receptors since it was antagonized by scopolamine (5 mg/kg i.p.). Oxotremorine in high doses (1.5 mg/kg s.c. for 3 days) induced 'delayed activation' of tyrosine hydroxylase (+273%). In these conditions LC cells were no longer responsive to a challenge dose of oxotremorine though they maintained normal responsiveness to noradrenergic drugs. The results show that cholinergic drugs can greatly influence the metabolism of LC noradrenergic neurons.

Myocarditis related to drug hypersensitivity. Hypersensitivity myocarditis is an inflammatory disease of the myocardium usually related to a drug allergy. The clinical manifestations may be nonspecific, and the diagnosis is seldom suspected or established during life. We report a case that demonstrates both typical and atypical features of this disease and review the clinicopathologic correlations. This case illustrates the potential occurrence of both electrical conduction block and ventricular tachyarrhythmias, either of which may account for the mechanism of sudden death in these patients. When cardiac symptoms or electrocardiographic abnormalities (or both) occur in a setting consistent with drug allergy, hypersensitivity myocarditis should be considered. Treatment consists of discontinuation of use of the drug responsible for the reaction and, possibly, administration of corticosteroids and immunosuppressive therapy.

Uncontrollable epistaxis. Angiographic localization and embolization. The method of choice for uncontrollable epistaxis that is refractory to anterior and posterior nasal packing is controversial. In a retrospective study, the therapeutic results in 42 patients with uncontrollable epistaxis were reviewed, with special consideration of 11 cases in which the patients received angiography and embolization of branches of the internal maxillary artery. Out of this collective, only one patient received surgery, ie, transantral internal maxillary artery ligation. The results of primary embolization demonstrated the effectiveness and illustrated the potential role of embolizing procedures in uncontrollable epistaxis.

A randomised controlled trial of patient information leaflets as a medication counselling aid. Medication counselling improves patient safety, adherence and satisfaction but is poorly done in clinical practice. Written aids further improve outcomes when used with verbal counselling. No studies have previously compared two types of written counselling aid. To compare the utility of a patient information leaflet (PIL) with a drug monograph as a medication counselling tool for patients starting a new medicine. A single-blinded randomised controlled trial of medical students counselling simulated patients during a clinical examination. The PIL was compared with the drug monographs as counselling aids by assessing information transfer and aid usage. A total of 96 students was recruited. The PIL was superior to the drug monograph for counselling relating to missed doses (P = 0.02), and non-inferior for other domains of information transfer. The aid was used more frequently in the PIL arm (91% vs 77%, P = 0.09) and for longer (4.6 min vs 2.9 min, P < 0.01). The PIL was non-inferior to the drug monograph for overall information transfer, but superior for contingency planning. Aid usage was greater in the PIL arm, which may reflect greater student satisfaction with the tool.

PCR-Based Assays for the Detection of Puccinia horiana on Chrysanthemums. Puccinia horiana, the causal agent of chrysanthemum white rust, is a pathogen of quarantine status in many countries where Chrysanthemum × morifolium cultivars are grown. Historically, identification protocols for white rust relied upon macroscopic symptom development and microscopic examination of infected leaves for teliospores. Symptoms become visible 7 to 10 days after initial infection under favorable conditions followed by the production of telia. Infected plants can therefore evade detection before symptoms and fruiting bodies are evident. Conventional and real-time polymerase chain reaction (PCR) assays were developed to detect P. horiana using primers designed to amplify portions of the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA (rDNA). The species-specific primers could detect the pathogen from 1 ng of DNA isolated from infected leaf tissue in conventional PCR assays and from 1 pg in real-time PCR assays. While both assays were capable of detecting P. horiana in symptomatic tissue, the greater sensitivity offered by the real-time PCR assay makes it more reliable for detecting the pathogen during the latent stage of infection. The P. horiana primers did not amplify the rDNA target using DNA isolated from leaf tissue infected with P. chrysanthemi.

Chaotic Brillouin optical correlation-domain analysis. We propose and experimentally demonstrate a chaotic Brillouin optical correlation-domain analysis system for distributed fiber sensing. The utilization of a chaotic laser with a low coherence state ensures high spatial resolution. The experimental results demonstrate a 4 cm spatial resolution over a 906 m measurement range. The uncertainty in the measurement of the local Brillouin frequency shift is ±1.2 MHz. The analysis of the expected spatial resolution and signal-to-noise ratio is also given.

In vitro and in vivo expression of endothelial von Willebrand factor and leukocyte accumulation after fractionated irradiation. Previous investigations have demonstrated an increased release of von Willebrand factor (VWF; also known as vWF) in endothelial cells after high single-dose irradiation in vitro. We have also found increased levels of Vwf protein in mouse glomeruli after a high single dose of renal irradiation in vivo. In addition, increased numbers of leukocytes were observed in the renal cortex after irradiation in vivo. The aim of the present study was to investigate and quantify these biological processes after clinically relevant fractionated irradiation and to relate them to changes in renal function. A significantly greater increase in release of VWF was observed in cultured human umbilical vein endothelial cells (HUVECs) after fractionated irradiation (20 x 1.0 Gy) than after a single dose of 20 Gy (147% compared to 115% of control, respectively, P < 0.0005). In contrast with the in vitro observations, glomerular Vwf staining was lower after fractionated irradiation in vivo (20 x 2.0 Gy or 10 x 1.6 Gy +/- re-irradiation) than after a single dose of 16 Gy. The number of leukocytes accumulating in the renal cortex was also lower after fractionated in vivo irradiation than after a single radiation dose. The onset of these events preceded renal functional and histopathological changes by approximately 10 weeks. These data indicate that radiation-induced changes in endothelial VWF expression after in vivo irradiation may be distinct from the in vitro observations. Increased VWF expression may reflect pivotal processes in the pathogenesis of late radiation nephropathy and provide a clue to appropriate timing of pharmacological intervention.

Transgenic mouse model integrating siRNA targeting the foot and mouth disease virus. We have constructed 2 small interfering RNAs (siRNAs) specifically targeting homogenous 3D and 2B1 regions of 7 serotypes of the foot and mouth disease virus (FMDV) and tested the ability of siRNAs to inhibit virus replication in baby hamster kidney (BHK-21) cells and suckling mice. In this study, we generated transgenic mouse models integrating short hairpin RNA (shRNA) targeting microinfected FMDV. When examined at the 7th passage in transgenic mice, the target gene was still found by PCR to be integrated in the genome. Compared to the control mice, the transgenic mice showed only slightly abnormal pathology when they were infected with the FMDV serotype Asia 1. The number of viruses in the tissues of the transgenic mouse was very low and in some tissues no virus could be detected by immunohistochemistry.

Verbena officinalis essential oil and its component citral as apoptotic-inducing agent in chronic lymphocytic leukemia. We evaluated the pro-apoptotic activity of Verbena officinalis essential oil and of its main component citral, on lymphocytes collected from normal blood donors and patients with chronic lymphocytic leukemia (CLL). The number of apoptotic cells was greater in CLL patients than in healthy subjects at all different times of incubation (4, 8 and 24 hours) for samples treated with Verbena officinalis essential oil (A) and citral (B) as well vs controls at different concentrations (0.1% and 0.01%). The greater pro-apoptotic ability was shown by both essential oil of Verbena officinalis and citral at lower concentrations (after 4 h A 0.1%: 17.8% vs 37.1%; A 0.01%: 15.8% vs 52%; B 0.1%: 18.4% vs 46.4%; B 0.01%: 15.8% vs 54.2%; after 8 h A 0.1%: 23% vs 38%; A 0.01%: 22.2% vs 55%; B 0.1%: 32% vs 42.2%; B 0.01%: 22% vs 54.3%; after 24 h A 0.1%: 5% vs 20.7%; A 0.01%: 25.8% vs 47.2%; B 0.1%: 18.4% vs 46.4%; B 0.01%: 15.8% vs 54.2%). Patients carrying deletion 17p13 (p53 mutation) showed a reduced ability to undergo apoptosis with respect to patients with other genomic aberrations or normal karyotype. The proapoptotic activity of Verbena officinalis essential oil and citral is thought to be due to a direct procaspase 3 activation. These data further support evidence that indicate natural compounds as a possible lead structure to develop new therapeutic agents.

Postnatal management and outcome for neural tube defects including spina bifida and encephalocoeles. The incidence of neural tube defects (NTDs) has declined in recent decades, however myelomeningocele and encephalocele still represent one of the commoner prenatally diagnosed congenital malformations. Improved perinatal and post natal care mean that the mortality associated with these conditions has also fallen. Advances in the multidisciplinary management of children with myelomeningocele have led to significant improvements in functional outcome for many with this condition. However, there remains a substantial population of patients born with NTDs whose life expectancy is substantially reduced and who suffer significant cognitive and physical disability remaining wholly or partially dependant on the care of others into adult life. This article aims to outline the contemporary early management of these conditions and examine the prospects for functional outcome where possible, attempting to show how early anatomical features of these conditions can help predict where, along the wide spectrum of outcome, a given individual may lie.

A novel cell-to-cell interaction between mast cells and other cell types. Time-lapse cinephotomicrography and transmission electron microscopy (TEM) have been used to study the interactions between rat mast cells and different cell monolayers in culture (fibroblasts, vascular endothelial cells and cardiac muscle cells). This report documents a novel form of behavior between mast cells and certain other cell types. We have tentatively termed this cellular behavior 'transgranulation', which involves sequential changes not seen in control cells, including: (1) formation of a granule-containing mast cell pseudopod that becomes closely applied to an adjacent cell; (2) development of specialized plasma membrane interrelationships between apposing cells; (3) alteration of granules and perigranular membranes within the mast cell pseudopod; (4) occasional transfer of exocytosed mast cell granules to the cytoplasm of the adjacent cell; (5) presence of a specialized inclusion body in the mast cell; and finally, (6) either withdrawal of the pseudopod by the mast cell, or casting-off of the pseudopod from the mast cell, leaving it on the surface of the adjacent cell (pseudopod translocation). These mast cell interactions occur specifically with fibroblasts and endothelial cells in vitro and are never observed with cardiac muscle cells or non-cellular substrates. Our investigations of rat mesenteries in situ confirm that these cell-cell interactions also occur in vivo. We suggest it represents a form of cell-to-cell communication involving secretion from a mast cell pseudopod to another cell type. The significance of specialized contacts between mast cells and other cell types in vivo is discussed.

[Pyrazinamide monoresistant Mycobacterium tuberculosis in Manisa region, Turkey]. Pyrazinamide (PZA) is a primary antituberculous drug. BACTEC 460TB is the recommended reference method for the detection of PZA resistance in Mycobacterium tuberculosis. This method is more expensive than the conventional susceptibility methods and therefore, it is recommended that each laboratory should establish their own protocol for the inclusion of PZA in the panel of primary drugs tested. One of the most important factors that help this decision is the prevalence of PZA resistance, particularly PZA monoresistance in the related community. The aim of the present study was to determine the extent of PZA monoresistance in M. tuberculosis complex (MTBC) isolates in our region. In this study, PZA susceptibility testing of 109 MTBC strains (susceptible to isoniazid, rifampicin, ethambutol and streptomycin) isolated from Manisa province in the Aegean region of Turkey was performed by using the BACTEC 460TB radiometric system (Becton Dickinson, MD). Two (1.8%) of the 109 isolates which were susceptible to all primary drugs revealed monoresistance against PZA. One of the PZA-monoresistant isolates has been identified as M. bovis and the other as M. tuberculosis by molecular method (Genotype MTBC, Hain Lifescience, Germany). The results of our study indicated that since the rate of PZA monoresistance was low, susceptibility testing of a panel of primary drugs without PZA may be an economical alternative in our region.

Suprarenal abscess in a newborn. A case report of a new born with unilateral suprarenal abscess extending in to the right kidney is represented. Both the adrenal gland and the kidney had to be surgically removed. Early diagnosis is important, so the surgical intervention, the only successful therapy, can be kept as conservative as possible.

Prevalence of anti-endothelial cell antibodies in patients with autoimmune diseases. The prevalence of anti-endothelial cell antibodies (AECA) of IgA, IgG and IgM classes was studied by means of enzyme-linked immunosorbent assays (ELISA) in 466 patients with autoimmune/inflammatory disorders. The reference limits in the ELISAs for the AECA were determined from a random population sample of 249 subjects. The frequency of AECA was highest in patients with SLE (n = 42), 14.6% mainly of IgG class, and the presence of AECA correlated with disease activity in these patients. In the RA patient group (n = 200), 9.5% had AECA, mostly of IgA type. We found no association between the presence of AECA and extra-articular manifestations of RA or survival rate. In patients with undefined connective tissue disease (n = 57), ankylosing spondylitis (n = 109), and psoriatic arthritis (n = 58), the frequency of AECA corresponded to that of the random population sample. In a cohort of samples sent to the laboratory for determination of anti-nuclear antibodies (ANA) there was a correlation between the presence of ANA and AECA. Our findings indicate that RA patients are characterized by IgA class AECA, whereas SLE patients have IgG class AECA also correlating to disease activity.

Effectiveness of aromatherapy massage on the stress of the surgical center nursing team: a pilot study. To verify the effectiveness of aromatherapy with essential oils of lavender (Lavandula angustifolia) and geranium (Pelargonium graveolens) associated with massage for stress relief of a nursing staff of the surgical center through evaluation of biophysiological and psychological parameters. Pilot study, controlled and randomized clinical trial performed with the nursing team of a surgical center of a teaching hospital in the interior of the state of São Paulo. The intervention comprised six aromatherapy massages with essential oils diluted in neutral cream at concentration 1% each. Heart rate and blood pressure levels were measured before and after each massage session. The Work Stress Scale (WSS) and the List of Stress Symptoms (LSS) were applied before and at the end of the intervention. Statistical analysis was performed with the paired t-test and chi-square test, 95% confidence interval and p <0.05. There was a statistically significant reduction in heart rate and blood pressure levels after massage sessions. The use of aromatherapy has demonstrated effectiveness for lowering biophysiological parameters of the surgical center nursing staff. Brazilian Registry of Clinical Trials: RBR-6mgqn3.

An investigation of the effects of late-onset dietary restriction on prostate cancer development in the TRAMP mouse. In our previous work we showed that dietary restriction initiated at puberty reduced prostate cancer development in the TRAMP mouse model. The current study was conducted to ascertain whether a dietary restriction regime would similarly reduce lesion development if imposed once tumor development was well established. Male TRAMP mice were maintained on an ad libitum diet until 20 weeks of age when proliferative prostate lesions are clearly evident. Mice were then subjected to a 20% restriction in dietary calories compared to matched controls, which were continued on ad libitum feeding. Mice were sacrificed at 20, 24, 32, and 39 weeks of age and proliferative epithelial lesions of the prostate were assessed using an established grading scheme. In this study, although dietary restriction reduced mean sex pluck weight (prostate and seminal vesicles), and mean grade of epithelial proliferative lesions in the dorsal and lateral lobes of the prostate, the effect was not as pronounced as was the case with dietary restriction from puberty. There was no relationship between serum insulin like growth factor (IGF-1) and prostate lesion grade. Additionally, we also report the relationship between lobe specific lesion development and SV40 immunostaining and, the occurance of neuroendocrine tumors (NETs) in the ventral prostate and urethra of the TRAMP mouse. NETs stained with high specificity and sensitivity for the neuroendocrine markers, synaptophysin and neuron-specific enolase (NSE), less for serotonin, but not for chromogranin A. NETs did not stain for cyclo-oxygenase-2 (COX-2) nor androgen receptor (AR). SV40 positive tubulo-acinar tumors seen occasionally in the kidney, did not stain for synaptophysin nor NSE.

[Methods for intravenous injection and blood collection in the guinea pig via veins of the forelimb without anesthesia (author's transl)]. Methods for intravenous injection and blood collection by way of the forelimb in guinea pigs without anesthesia were investigated, with the results as follows: 1) Both the accessory cephalic and cephalic veins were found available for injection as well as for drawing blood samples. Venipuncture was accomplished with greater ease by using the accessory cephalic vein. 2) The following procedure has proven practical. (i) Clip the hair over the site. (ii) Restrain the animal to immobilize the foreleg in slight extension by grasping it at the elbow joint with the thumb and forefinger over its dorsal and ventral aspects, respectively. (iii) After disinfecting the skin surface with alcohol, perform injection using an appropriate syringe with a 27 (1/4) or 25 (1/3) gauge intravenous needle, or puncture the vein with a 23 (1/2) gauge i. v. needle to collect the blood that drips out.

Paraneoplastic syndromes associated with small cell lung cancer. Small cell lung cancer (SCLC) is the most frequent cancer histology associated with paraneoplastic syndromes. These syndromes are typically caused by ectopic hormone production or immune-mediated tissue destruction caused by neural antigen expression from cancer cells. This antigen expression induces the production of antibodies that cross-react with neural tissue. This article discusses the most common ectopic hormone and neurologic paraneoplastic syndromes and emphasizes the relationships among antigens, clinical syndromes, and outcomes. Although ectopic hormone production has been associated with extensive-stage disease and a poorer outcome, the antibody-mediated paraneoplastic syndromes are prognostic factors associated with more favorable outcomes. Both have the potential for improvement with cancer treatment.

Flexural eczema versus atopic dermatitis. Flexural eczema and atopic dermatitis are frequently synonymized. As respiratory atopy is rarely tested for and found in these patients, systematically equating a flexural distribution of dermatitis with atopic dermatitis may too frequently result in misclassified diagnoses and potentially missed opportunity for intervention toward improving patients' symptoms and quality of life. We present a critical review of the available evidence for the atopic dermatitis diagnosis and discuss the similarities between atopic dermatitis and allergic contact dermatitis. Because neither flexural predilection nor atopy is specific for atopic dermatitis, we conclude that the term atopic dermatitis is a misnomer and propose an etymologic reclassification of atopic dermatitis to "atopy-related" dermatitis. Allergic contact dermatitis can induce an atopic dermatitis-like phenotype, and thus, flexural dermatitis cannot be assumed as atopic without further testing. Patch testing should at least be considered in cases of chronic or recurrent eczema regardless of the working diagnosis.

The Controlled Direct Effect of Early-Life Socioeconomic Position on Periodontitis in a Birth Cohort. This study used data from the 1982 Pelotas Birth Cohort Study, Brazil, to estimate the controlled direct effect of early-life socioeconomic position (SEP) on periodontitis at age 31 years, controlling for adulthood income and education, smoking, and dental hygiene. Sex was included as a covariate. Early-life SEP was measured at participant birth based on income, health services payment mode, maternal education, height, and skin color (lower versus middle/higher SEP). Periodontitis was assessed through clinical examination at age 31 years (healthy, mild periodontitis, or moderate-to-severe disease). Adulthood behaviors (smoking, dental hygiene) were the mediators, and adulthood SEP (education and income) represented the exposure-induced mediator-outcome confounders. A regression-based approach was used to assess the controlled direct effect of early-life SEP on periodontitis. Multinomial regression models were used to estimate risk ratios and their 95% confidence intervals. The prevalences of mild and moderate-to-severe periodontitis were 23.0% and 14.3%, respectively (n = 539). Individuals from the lowest early-life SEP had a higher risk of moderate-to-severe periodontitis controlled for mediators and exposure-induced mediator-outcome confounders: risk ratio = 1.85 (95% confidence interval: 1.06, 3.24), E value 3.1. We found that early-life SEP was associated with the development of periodontitis in adulthood that was not mediated by adulthood SEP and behaviors.

Stability analysis and optimal control of an epidemic model with awareness programs by media. The impact of awareness campaigns and behavioral responses on epidemic outbreaks has been reported at times. However, to what extent does the provision of awareness and behavioral changes affect the epidemic trajectory is unknown, but important from the public health standpoint. To address this question, we formulate a mathematical model to study the effect of awareness campaigns by media on the outbreak of an epidemic. The awareness campaigns are treated as an intervention for the emergent disease. These awareness campaigns divide the whole populations into two subpopulation; aware and unaware, by inducing behavioral changes amongst them. The awareness campaigns are included explicitly as a separate dynamic variable in the modeling process. The model is analyzed qualitatively using stability theory of differential equations. We have also identified an optimal implementation rate of awareness campaigns so that disease can be controlled with minimal possible expenditure on awareness campaigns, using optimal control theory. The control setting is investigated analytically using optimal control theory, and the numerical solutions illustrating the optimal regimens under various assumptions are also shown.

Extrapancreatic effects of sulfonylureas--a comparison between glimepiride and conventional sulfonylureas. The contribution of extrapancreatic effects of sulfonylureas to the blood glucose-decreasing activity was reevaluated in vivo and in vitro with several conventional sulfonylureas and with the new one glimepiride. In vivo, in dogs, after single approximately equipotent blood glucose-decreasing doses, the sulfonylureas were tested for a ranking in the ratios of mean plasma insulin-increasing and blood glucose-decreasing activity. Studies were also performed in hyperglycemic hyperinsulinemic KK-Ay mice under once daily treatment for 8 weeks. In vitro, glimepiride and glibenclamide were tested for the ranking of their extrapancreatic activity with respect to the stimulation of glucose transport and glucose metabolizing processes in normal and insulin-resistant fat cells as well as in the isolated diaphragm. Furthermore, in vitro studies were performed, especially with glimepiride, in order to characterize the molecular mechanism for the extrapancreatic activity. The dog studies revealed a marked ranking in the ratios of plasma insulin-increasing and blood glucose-decreasing activity between the different sulfonylureas (glimepiride < glipizide < gliclazide < glibenclamide). In the hyperglycemic hyperinsulinemic KK-Ay mice, glimepiride reduced blood glucose by 40%, plasma insulin by 50% and HBA1c by 33%, whereas glibenclamide and gliclazide had no effect on these parameters. In vitro, glimepiride and glibenclamide had extrapancreatic effects within the lower microM range, with glimepiride exhibiting 2-3-fold lower ED50 values than glibenclamide. In the absence of insulin, both stimulated glucose transport--up to 60% of the maximum insulin response in the rat diaphragm and up to 35% in 3T3 adipocytes. Glycogenesis was stimulated in the rat diaphragm--up to 55% of the maximum insulin effect; lipogenesis in 3T3 adipocytes--up to 40%. The studies on the molecular mechanism of extrapancreatic activity with rat adipocytes and diaphragm suggest that these direct insulin-mimetic effects rely on the induction of GLUT4 translocation from internal stores to the plasma membrane and on the activation of the key metabolic enzymes, glycogen synthase and glycerol-3-phosphate acyltransferase. These processes occur within the same drug concentration range and with the same ranking between glimepiride and glibenclamide as observed for glucose utilization and transport. The direct effects of sulfonylureas may ultimately be regulated by a glycosyl-phosphatidylinositol-specific phospholipase C, shown to be activated by glimepiride in rat adipocytes. Lipolytic cleavage products thereby generated from glycolipidic structures may in turn stimulate specific protein phosphatases which activate key regulatory proteins/enzymes of glucose and lipid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of the allosteric interactions between antagonists and amiloride analogues at the human alpha2A-adrenergic receptor. The purpose of this study was to determine whether there is a well-defined allosteric site on the human alpha2A-adrenergic receptor. To explore this question, we examined the effects of amiloride analogues on the dissociation of [3H]yohimbine, [3H]rauwolscine, and [3H]RX821002. The dissociation data fitted well to an equation derived from the ternary complex allosteric model with amiloride analogue concentration and time as two independent variables. The estimated maximal increase in the [3H]yohimbine dissociation rate caused by the 5-N-alkyl amilorides varied from 2-fold for the parent amiloride to 140- and 160-fold for 5-(N, N-hexamethylene)-amiloride and 5-(N-ethyl-N-isopropyl)-amiloride, respectively. The calculated log affinities at the yohimbine-occupied receptor ranged from 1.75 for 5-(N-ethyl-N-isopropyl)-amiloride to 2.5 for 5-(N, N-hexamethylene)-amiloride. The increase in affinity found at the yohimbine-occupied receptor was not correlated with increase in size of the 5-N-alkyl side chain, in contrast to the situation found at the unoccupied receptor. The effect of competition between two amilorides on yohimbine dissociation also was explored. The data obtained were well fitted by the equation derived from the relevant model, with the off-rate increases caused by 5-(N, N-hexamethylene)-amiloride being either decreased or increased by the competing amiloride analogue in line with predictions, and the parameters derived from the fits were in good agreement with those obtained in the above dissociation assays. Thus, the data are compatible with the amilorides competing at the one allosteric site on the alpha2A-adrenergic receptor and rules out the possibility that the amilorides are acting in a nonspecific fashion.

Evaluation of the polarographic technique for assay of the viability of freeze-dried BCG vaccine: I. The polarographic technique. In this paper, a new assay based on oxygen uptake assessed by polarography was evaluated with the aim of establishing the viability of freeze-dried BCG vaccine. An oxygen electrode possessing a temperature sensor was designed for this purpose. The polarographic method used had several advantages, particularly its rapidity and use of small amounts of biological material. These advantages are ideal for quality control of BCG vaccine.

Gastrojejunal anastomotic strictures following laparoscopic Roux-en-Y gastric bypass surgery: analysis of 1291 patients. The development of an anastomotic stricture at the site of the gastrojejunostomy following Roux-en-Y gastric bypass (RYGBP) is associated with substantial morbidity. Various techniques are available for creating the gastrojejunal anastomosis, including hand-sewing and using a circular or linear stapler, to reduce complication rates. The aim of this study was to assess the incidence of gastrojejunal anastomotic strictures in patients who underwent antecolic antegastric Roux-en-Y gastric bypass (AA-RYGBP) with the use of a linear stapler and to evaluate the outcomes of endoscopic pneumatic dilatation as a treatment option for patients with anastomotic stricture. All patients who met the National Institutes of Health (NIH) criteria for bariatric surgery and underwent AA-RYGBP using a linear stapler technique between July 2000 and November 2004 were included in the study. Following Institutional Review Board approval, the medical records of these patients were retrospectively reviewed. Two surgeons performed all of the surgical procedures in this series using a standardized surgical protocol. Between July 2000 and November 2004, 1291 patients (1016 females [79%] and 275 male [11%]) underwent AA-RYGBP. The patients' mean age was 43 years (range, 19-75 years), and mean preoperative body mass index (BMI) was 49.6 kg/m2 (range, 34-97.5 kg/m2). Out of 1291 procedures, 1265 were performed laparoscopically (98.3%), with the reminder performed by laparotomy. A linear stapler was used to create the gastrojejunal anastomosis in all of the procedures. A total of 405 (31%) complications occurred, with gastrojejunal anastomotic strictures the most common complication, found in 94 (7.3%) patients more than 30 days after the procedure. All of these cases of stricture were treated by endoscopic pneumatic dilatation with a through the scope (TTS) balloon, requiring between one and four dilatory sessions. Of the 94 patients (2.1%) who underwent balloon dilatation, 2 developed perforation, only 1 of whom required surgical intervention. The mean postoperative hospital stay for the 94 patients was 4.2 days (range, 2-24 days); there was no perioperative patient mortality. Our results demonstrate that AA-RYGBP can attain a relatively low complication rate and no mortality. Gastrojejunal anastomotic strictures were the most common complication and were diagnosed 30 days after the procedure. Endoscopic balloon dilatation can be offered as a first-line treatment for gastrojejunal anastomotic strictures. Perforation is a potential complication of this treatment and may necessitate surgical intervention.

[Complex diagnosis of breast diseases in a polyclinic]. In 159 patients with malignant and in 170 patients with benign tumors the diagnosis was established on the basis of clinical data, cytographic findings, obtained in puncturing the node and the results of roentgenological studies of mammary glands. In patients with malignant tumors all these methods yielded the similar results in 71.7% of cases, none of the methods concerned helped to diagnose the lesion in 2.5% of cases. The ultimate diagnosis in patients to be directed to the clinic coincided with histological findings in 97.5%. The coincidence of diagnoses, while using the mentioned three methods in patients with benign breast tumors was noted in 72.9% of cases. The methods under consideration failed to establish the diagnosis in 3% of cases. The ultimate diagnosis coincided with histological findings in 97.0%. The presence of negative results while using each of these methods is shown to be the characteristic of their resolving power.

The rise and fall of medicaid managed care in Mississippi: lessons for public health policy makers. This article describes the development, implementation, and termination of a primary care case management program in the State of Mississippi. The study provides policy makers with critical information as to factors associated with successful implementation of current health care initiatives.

[The role of bone marrow macrophages in regulating erythropoiesis in different states of the erythron]. Stimulation and inhibition of erythropoiesis were modelled in rats to study the functional condition of central macrophages of the erythroblastic islets (EI) in the bone marrow by determining the total content of lysosomes, pH of lysosomes, activity of acid phosphatase, and 3H-thymidine inclusion in DNA. The properties of the surface charges of the EI cells were judged according to the electrophoretic mobility, the number of acid glycoproteins--according to the staining of the preparations with alcian blue. It is shown that the intensity of erythropoiesis in the EI determines the studied values. Sensitivity of EI macrophages to erythropoietin was demonstrated in EI cultivation.

The management of anorectal malformation with congenital vestibular fistula: a single-stage modified anterior sagittal anorectoplasty. This study aimed to evaluate the mid-term outcomes of single-stage modified anterior sagittal anorectoplasty (ASARP) for anorectal malformation with vestibular fistula. Twenty-six patients with congenital imperforate anus and vestibular fistula underwent single-stage modified sphincter-saving ASARP between January 2008 and December 2012. The ages of the patients at the time of operation ranged from 1 month to 5.1 years. Standard ASARP procedure was modified to avoid the incision of the external sphincter complex. Instead a potential tunnel was created through the center of external sphincter complex under the endoscopic guidance. The patients were evaluated for fecal continence and complications. Modified ASARP was successfully performed in all patients. The mean operation time was 52.2 ± 3.5 min (range 47-61 min). The operative blood loss was minimal. There was no operative complication. Wound infection occurred in 3 patients (3/26, 11.5%). All patients were followed up for 4.2 ± 1.5 years (range 2-6 years). No patient developed fecal incontinence. Three patients (3/26, 11.5%) had soiling once or twice per week. Four patients (4/26, 15.4%) had constipation amenable to diet management. Mucosal prolapse occurred in 1 patient (1/26, 3.8%). There was no recurrence of fistula, anal stenosis or anterior displacement of the neorectum. Mid-term results show that single-stage modified ASARP is an effective and safe option for patients with anorectal malformation and congenital vestibular fistula.

Shape-controlled synthesis of porous carbons for flexible asymmetric supercapacitors. N-Doped carbon nanomaterials have gained tremendous research interest in energy storage because of their high capacitance and chemical stability. Here, N-doped porous carbons (NPCs) with multiple shape-controlled and tunable morphologies are developed through a direct one-step pyrolysis/activation method. Typically, NPC-700-1, which is 5 nm thick and 6 μm wide, shows a high surface area (1591.5 m2 g-1) and hierarchical micro-, meso-, and macroporous architecture. The maximum specific capacitance of the as-prepared carbon nanosheets is 406 F g-1 at 1 A g-1 in KOH electrolyte. Moreover, flexible all-solid-state asymmetric supercapacitor devices assembled from NPCs and NiCo2O4 deliver a superior energy density of 42.7 W h kg-1 at 794.6 W kg-1, and good cycling ability (94% after 10 000 cycles). All the results suggest that NPCs have great potential for high performance wearable electronics and energy storage devices.

Psychology and climate change. Research and theory from psychology are increasingly being utilized to understand potential impacts of climate change and to promote positive responses. In this Primer, Clayton describes three main areas in which psychological research provides relevant insights, and provides suggestions for encouraging mitigation and adaptation behavior.

My changed body: breast cancer, body image, distress and self-compassion. Bodily changes after breast cancer treatment can lead to long-term distress. Self-compassion, the ability to be kind to oneself, is an internal resource that may enhance a woman's ability to adjust to cancer-related bodily changes. The aim of the present study was to test the hypothesis that self-compassion mediates the relationship between body image and distress, controlling for alternate plausible mediators. Members of a nationwide breast cancer consumer network were invited to participate. A total of 279 women who had finished active cancer treatment completed the online survey. Assessments included the Body Image Scale; Self-compassion Scale; Depression, Anxiety and Stress Scale and items measuring perceived normative pressure and comfort with one's weight. Possible mediating effects of proposed variables on the body image-distress relationship were assessed. Tests using a bootstrapping approach with multiple mediators were significant for self-compassion on distress. Body image disturbance was indirectly associated with distress through low self-compassion. Body image disturbance and lower self-compassion were associated with increased psychological distress among these breast cancer survivors. This study provides preliminary evidence for a mediating role of self-compassion between body image disturbance and psychological distress, suggesting a potentially protective effect of higher levels of self-compassion for women at risk of experiencing body image disturbance.

A developmental study of the relationship between geometry and kinematics in drawing movements. Trajectory and kinematics of drawing movements are mutually constrained by functional relationships that reduce the degrees of freedom of the hand-arm system. Previous investigations of these relationships are extended here by considering their development in children between 5 and 12 years of age. Performances in a simple motor task--the continuous tracing of elliptic trajectories--demonstrate that both the phenomenon of isochrony (increase of the average movement velocity with the linear extent of the trajectory) and the so-called two-thirds power law (relation between tangential velocity and curvature) are qualitatively present already at the age of 5. The quantitative aspects of these regularities evolve with age, however, and steady-state adult performance is not attained even by the oldest children. The power-law formalism developed in previous reports is generalized to encompass these developmental aspects of the control of movement.

Imaging of the Vasa Nervorum Using Contrast-Enhanced Ultrasound. We describe the use of intravenous contrast-enhanced ultrasonography to study vasa nervorum using contrast-enhanced ultrasound. We imaged the median, femoral, or sciatic nerves in 4 patients in longitudinal plane using high-resolution ultrasound after intravenous bolus of activated Perflutren lipid microspheres. The images were acquired as photopic images (in brown color) in real time using 2-dimensional B-Flow mode scan within a selected region of interest. The vasa nervorum was seen as focal ovoid enhancement along either the superior and inferior aspects of the nerve most pronounced during arterial phase (peak enhancement) in all 4 patients. The fluctuating intensity of enchancement during cardiac cycle confirmed the arterial origin of enhacement. Punctate, linear, or diffuse enhancement was also seen along the trunk of the nerve. We were able to identify the vasa nervorum along the outer aspect of the studied nerves using contrast-enhanced ultrasound.

Comparison of primary lung tumor incidences in the rat evaluated by the standard microscopy method and by multiple step sections. The data presented in this paper have been derived from a carcinogenicity experiment with rats as part of a comprehensive research project focused on experimental studies on the toxicity and carcinogenicity of intratracheally instilled granular dusts [Ernst H, Rittinghausen S, Bartsch W, Creutzenberg O, Dasenbrock C, Görlitz B-D et al. Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphous SiO(2), carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO). Exp Toxicol Pathol 2002; 54: 109-26; Ernst H, Kolling A, Bellmann B, Rittinghausen S, Heinrich U, Pott F. Pathogenetische und immunbiologische Untersuchungen zur Frage: Ist die Extrapolation der Staubkanzerogenität von der Ratte auf den Menschen gerechtfertigt? Teil II: Histologie. Abschlussbericht. Umweltforschungsplan des Bundesministeriums für Umwelt, Naturschutz und Reaktorsicherheit. November 2005. http://www.umweltdaten.de/publikationen/fpdf-l/3033.pdf]. The results of the standard approach to histological sampling in rodent carcinogenicity inhalation studies were compared to those obtained after supplemental evaluation of step sections at intervals of 250microm through the entire lung. Seven lung tissue specimens (six sections) each of 251 rats (55 rats of the control group, 53 rats of the group treated with quartz DQ 12, 56 rats of the group treated with quartz DQ 12 and PVNO (poly-2-vinylpyridine-N-oxide), 53 rats of the group treated with amorphous SiO(2), and 17 rats each of the groups treated with coal dust and carbon black) were evaluated by light microscopy. At least 60 hematoxylin and eosin (H&E)-stained sections per lung were evaluated of 99 female rats (30 rats of the control group, 7 rats each of the groups treated with quartz, quartz and PVNO, and carbon black, 31 rats of the group treated with amorphous SiO(2), and 17 rats treated with coal dust). For the neoplastic and pre-neoplastic lesions detected in the serial slides an approximate value of the whole tumor volume was calculated. The detection of tumors with a diameter of 0.25mm was possible. Based on the size distribution of 75 tumor volumes, the probability of detecting a tumor was 86% when using 12 sections. The addition of step sections enhanced the tumor detection rate from 17 to a total number of 44 lung tumors in the quartz-treated rats, from 6 to 10 in the quartz- and PVNO-treated rats, from 4 to 11 in the amorphous SiO(2)-treated rats, and from 4 to 10 in the carbon black-treated rats. Both the tumor multiplicity and the number of rats with pre-neoplastic lesions increased. These additional data corroborated the initial findings in all experimental groups and provided statistically significant results confirming the equivocal evidence of carcinogenic activity of amorphous SiO(2) in female Wistar rats. This technique offered accurate information on the incidence, histological type, size, and location of proliferative lesions in the entire lung, but the benefit must be balanced against the extra financial effort.

On the replication of Kristofferson's (1980) quantal timing for duration discrimination: some learning but no quanta and not much of a Weber constant. This study revisited Kristofferson's (Perception & Psychophysics 27:300-306, 1980) report showing that, with sufficient practice at interval discrimination, the relationship between timing variability and physical time is a step function-in other words, that psychological time is quantized. Two participants completed 260 sessions of a temporal discrimination task, 20 consecutive sessions for each of 13 base durations ranging from 100 to 1,480 ms. The data do not replicate Kristofferson's (Perception & Psychophysics 27:300-306, 1980) quantal finding, and it is argued that the effect Kristofferson reported may have been due to specific methodological decisions. Importantly, the data show (1) some limitation of Weber's law for time, even for the narrow range of the present investigation, and (2) that extensive training provides some modest benefit to temporal discrimination, mainly for longer intervals, and that this benefit primarily occurs in the first few sessions.

Self-care in the community: moving away from a culture of dependency. As ever greater pressure is brought to bear by the current economic climate, one simple step may yield a very significant release of time and money. Leaders from primary care and the non-prescription medicines industry are in agreement that the time has come to break the national culture of dependency on the NHS, estimated to cost every general practice in England an average of pound250,000 annually, equivalent to an astonishing pound2 billion across primary care. It also actively denies people the confidence to take control of their own, and their families' health and therefore 'the opportunity to set up good behaviours for the longer term' according to Dr Laurence Buckman. This paper examines the role community nurses can play in helping to change this culture.

Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin. Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (+/+) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved.

Concurrent functional endoscopic sinus surgery and rhinoplasty: pros. Despite historical concerns about the spread of infection from the sinuses to the nasal tissues,concurrent septorhinoplasty and endoscopic sinus surgery may be performed safely in most patients who meet the criteria for sinus surgery. However, otolaryngologists should use good medical judgment in selecting patients appropriate for the combined procedures.Patients with extensive sinus pathology or systemic illness are not the ideal candidates for concurrent surgery. It is recommended to perform the septal and sinus surgery first, so that the surgeon may postpone the elective rhinoplasty procedure if unfavorable intraoperative circumstances develop. Overall, when performed in carefully selected patients, contemporaneous rhinoplasty and endoscopic sinus surgery is safe and effective and offers many advantages for the patient.

The (non-)sense of detecting anti-cardiolipin and anti-β2glycoprotein I IgM antibodies in the antiphospholipid syndrome. The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of lupus anticoagulant (LAC), anti-cardiolipin (aCL) and/or anti-β2glycoprotein I (aβ2GPI) antibodies of the immunoglobulin G/immunoglobulin M (IgG/IgM) isotype. However, the role of aCL and aβ2GPI IgM as a serologic marker in APS is debated. We aimed to assess the diagnostic and clinical value of IgM antiphospholipid antibodies (aPL) in APS within the classification criteria. Our multicenter study comprised 1008 patients, including APS patients and controls. Anti-CL and aβ2GPI IgG and IgM antibodies were detected with four commercially available solid phase assays. Positivity for aCL and/or aβ2GPI antibodies was significantly correlated with thrombosis and pregnancy morbidity, independent of the isotype and solid phase assay. Higher odds ratios were obtained for IgG compared to IgM positivity. Isolated IgM was rare in thrombotic APS, but more frequent in obstetric APS, ranging from 3.5% to 5.4% and 5.7% to 12.3%, respectively, dependent on the solid phase assay. In a multivariate logistic regression analysis of aPL, IgM positivity was found to be associated with pregnancy morbidity. However, detection of IgM was not independently associated with thrombosis. Combined positivity for LAC, IgG, and IgM was highly associated with thrombosis and pregnancy morbidity. Our data support testing for aCL and aβ2GPI IgM in women suspected of obstetric APS. However, no added value was found for testing IgM in patients suspected of thrombotic APS. Still, IgM aPL might be useful as a second-line test to improve thrombotic risk stratification.

Antizyme delays the restoration by spermine of growth of polyamine-deficient cells through its negative regulation of polyamine transport. Effects of antizyme on polyamine transport and spermine restoration of the growth of polyamine-deficient cells were examined by using mouse FM3A cells transfected with pMAMneoZ1 possessing rat antizyme cDNA under the control of glucocorticoid-inducible promoter. Treatments of the transfected cells with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and dexamethasone, an inducer of antizyme, both caused a decrease in ODC activity and polyamine contents and inhibition of cell growth. However, spermine uptake of the transfected cells was repressed by dexamethasone but stimulated by DFMO. The decrease in the rate of spermine uptake in dexamethasone-treated cells was attributed to an increase in Km value and a slight decrease in Vmax value. Accordingly, restoration of cell growth by spermine was less effective in dexamethasone-treated cells than DFMO-treated cells. These results clearly indicate that antizyme has dual functions: one for ODC degradation and the other for negative regulation of polyamine transport.

[Appearance of the resection area of brain tumors in intraoperative MRI imaging]. During MRI-controlled resection of brain tumors using an open MRI system, operation-induced alterations may occur, especially enhancement of the resection cavity wall. This may simulate tumor areas, resulting in false assessment of the resection or resection of non-tumorous areas. Based on 42 MRI- and biopsy-controlled brain tumor resections in an 0.5 T open MRI (Signa SP, GE), the appearance and origin of operation-induced reactions are analyzed. In our opinion, there is a superposition of preformed peritumoral reactions by operation-induced microcontusions. The beginning of the cavity wall enhancement needs at least 10-15 min. MRI-controlled analysis of the intraoperative steps by the neurosurgeon and neuroradiologist allows discrimination of operation-induced reactions from tumor areas and leads to safe operation.

Quantitative study on the correlation between p53 gene mutation and its expression in endometrial carcinoma cell lines. Mutant p53 protein is not degradated but accumulates in the nuclei. However, the relation between p53 gene mutation and quantity of p53 protein has not been clarified yet in endometrial carcinoma. We investigated the correlation between p53 gene mutation and its protein expression quantitatively using 11 cell lines of endometrial adenocarcinoma, endometrioid type and two serous-type cell lines. To examine p53 mutation, PCR-SSCP analysis in exon 5 to 8 and direct sequence were carried out. p53 expression was determined by immunocytochemistry and immunoblotting. The percentage of positive staining in the nuclei by immunocytochemistry was calculated as a labeling index (LI). The amount of p53 detected by immunoblotting was expressed as a comparative value of Ishikawa cells. Point mutation of p53 gene was detected in four of 11 (36.4%) cell lines of endometrioid adenocarcinoma, and all two of serous adenocarcinoma. There was a significant positive correlation between p53 LI and p53 values. The LI and the values of p53 were significantly higher in the mutant group than the wild one, thus showing a quantitative correlation between p53 protein expression and p53 gene mutation in endometrial carcinoma cell lines. It is plausible that immunohistochemical analysis of p53 could be qualified to be a convenient indicator of p53 gene mutation on clinical materials, if p53 LI is more than 40 (M-SD in mutant p53).

Metabolism of diphenylhydantoin (phenytoin) during pregnancy. Plasma levels of diphenylhydantoin (DPH) and the 24 hour urinary excretion of both DPH and its major metabolite 5-(p-hydroxyphenyl)-phenylhydantoin (HPPH) were measured serially during pregnancy in a group of five unselected epileptic patients. Plasma DPH levels fell and on average were some 40 per cent lower at term than they had been in early pregnancy. With one exception, the patients were well controlled during pregnancy but two patients who regularly had plasma DPH levels below 10 microgram/ml both suffered seizures in the puerperium. There was no convincing change in the excretion of either DPH or HPPH which together accounted for less than half the administered dose. Gestational length exceeded 41 weeks in 4 of the 5 patients studied but all were delivered of normal healthy infants, of average birthweight, with no congenital defects or clotting disorders.

Pedestrian Behavior at Five Dangerous and Busy Manhattan Intersections. Technology-related distracted behavior is an emergent national concern. Listening to, looking at or talking into an electronic device while walking divides attention, increasing the risk of injury. The purpose of this study was to quantify technology-related distracted pedestrian behavior at five dangerous and busy Manhattan intersections. Data were collected over ten cycles of signal changes at each of the four corners of five intersections at four times of day. Data for 'Walk' and 'Don't Walk' signals were tallied separately. A total of 21,760 pedestrians were observed. Nearly one-third crossing on a 'Walk' signal (n = 5414, 27.8%), and nearly half crossing on a 'Don't Walk' signal (n = 974; 42.0%) were wearing headphones, talking on a mobile phone, and/or looking down at an electronic device. Headphone use was the most common distraction.

Independence of valence modulation and prepulse inhibition of startle. This study sought to determine whether prepulse inhibition and valence modulation of startle are independent, both within and across individuals. Acoustic probes (105 dB) were delivered as 68 undergraduates viewed pleasant, neutral, and unpleasant pictures. Weak acoustic stimuli (8 dB above background) preceded half of the probes by 120 ms. As expected, startles were larger during unpleasant than during pleasant pictures, and smaller on prepulse than no-prepulse trials. In general, valence modulation and prepulse inhibition of startle were unrelated. That is, prepulse inhibition was consistent across affective states, valence modulation did not differ between no-prepulse and prepulse trials, and valence modulation and prepulse inhibition effects were uncorrelated across individuals. Analysis of raw and percent modification scores generally led to similar conclusions. It is concluded that valence modulation and prepulse inhibition are independent startle modulatory phenomena, although this conclusion is tempered by a finding of poor internal consistency reliability for valence modulation.

The perception of frequency peaks and troughs in wide frequency modulations. This work was concerned with the perception of "instantaneous pitch" in continuously frequency modulated sounds. In experiment 1, a 70-dB sinusoidal carrier, close to 1 kHz, was modulated by the exponential of periodic functions corresponding to the sum of a few sinusoids [e.g., sin(at)+sin(3at)]. Each modulation had a fundamental frequency (a/2 pi) of 1.5 Hz and was symmetric on the dimensions of time and log frequency. Thirty listeners identified discrete melodic motifs within these stimuli. The pitches of the identified notes mainly corresponded to the local frequency maxima; generally, the local minima were not heard as auditory "events" (pitch singularities). A similar perceptual asymmetry was not observed for comparable sequences of discrete tones. In experiments 2-4, frequency difference limens were measured for the maxima and minima of continuous frequency modulations, using an adaptive forced-choice method. Sinusoidal carriers were modulated by the exponential of one cycle of a 5-Hz cosine function, starting at phase pi or phase 0 and giving an overall frequency swing of about 0.5 oct. For maxima and minima around 1 kHz, frequency shifts of maxima were better detected than frequency shifts of minima, by an average factor of 2. Generally, this asymmetry did not decrease as a function of subjects' training in the discrimination task, and was still present when frequency minima were given a 6-dB intensity advantage over frequency maxima. No explanation was found for the advantage of frequency maxima with respect to perceptual salience (experiment 1) or discriminability (experiments 2-4).

Evidence for an NGF-induced autocrine neurotrophic potential of glial cells in nervous system development. NGF receptor bearing peripheral glial cells, purified from chicken embryo dorsal root ganglia, were found to secrete neurite growth promoting activity (NGPA) but no NGF (detection limit 1 pM). If, however, minute concentrations of NGF (2 pM) were added to the glial cultures, an autocrine response was observed. Levels of NGF-like activity in the medium rose up to 50-fold. Induction of this autocrine response occured within a narrow range of NGF concentrations. NGPA production was not affected by addition of NGF. Coculture with neurons influenced the neurotrophic factor production. The data suggest that glial cells can "sense" traces of NGF and regulate its availability during neural development.

Transcript profiling of human platelets using microarray and serial analysis of gene expression. Human platelets are anucleate blood cells that retain cytoplasmic mRNA and maintain functionally intact protein translational capabilities. We have adapted complementary techniques of microarray and serial analysis of gene expression (SAGE) for genetic profiling of highly purified human blood platelets. Microarray analysis using the Affymetrix HG-U95Av2 approximately 12 600-probe set maximally identified the expression of 2147 (range, 13%-17%) platelet-expressed transcripts, with approximately 22% collectively involved in metabolism and receptor/signaling, and an overrepresentation of genes with unassigned function (32%). In contrast, a modified SAGE protocol using the Type IIS restriction enzyme MmeI (generating 21-base pair [bp] or 22-bp tags) demonstrated that 89% of tags represented mitochondrial (mt) transcripts (enriched in 16S and 12S ribosomal RNAs), presumably related to persistent mt-transcription in the absence of nuclear-derived transcripts. The frequency of non-mt SAGE tags paralleled average difference values (relative expression) for the most "abundant" transcripts as determined by microarray analysis, establishing the concordance of both techniques for platelet profiling. Quantitative reverse transcription-polymerase chain reaction (PCR) confirmed the highest frequency of mt-derived transcripts, along with the mRNAs for neurogranin (NGN, a protein kinase C substrate) and the complement lysis inhibitor clusterin among the top 5 most abundant transcripts. For confirmatory characterization, immunoblots and flow cytometric analyses were performed, establishing abundant cell-surface expression of clusterin and intracellular expression of NGN. These observations demonstrate a strong correlation between high transcript abundance and protein expression, and they establish the validity of transcript analysis as a tool for identifying novel platelet proteins that may regulate normal and pathologic platelet (and/or megakaryocyte) functions.

Characterization and cloning of celR, a transcriptional regulator of cellulase genes from Thermomonospora fusca. CelR, a protein that regulates transcription of cellulase genes in Thermomonospora fusca (Actinomycetaceae) was purified to homogeneity. A 6-kilobase NotI-SacI fragment of T. fusca DNA containing the celR gene was cloned into Esherichia coli and sequenced. The celR gene encodes a 340-residue polypeptide that is highly homologous to members of the GalR-LacI family of bacterial transcriptional regulators. CelR specifically binds to a 14-base pair inverted repeat, which has sequence similarity to the binding sites of other family members. This site is present in regions upstream of all six cellulase genes in T. fusca. The binding of CelR to the celE promoter is inhibited specifically by low concentrations of cellobiose (0.2-0.5 mM), the major end product of cellulases. The other sugars tested did not affect binding at equivalent or 50-fold higher concentrations. The results suggest that CelR may act as a repressor, and that the mechanism of induction involves a direct interaction of CelR with cellobiose.

Microwave spectroscopy of the Mars atmosphere. A study of the use of millimeter-wavelength spectral transitions to investigate the atmosphere of Mars is presented. In the model experiments investigated it is assumed that a spectrometer in the frequency range from 100 to 260 GHz looks into a modest-sized telescope of from 30 to 50 cm aperture from a near-Mars orbit. The molecules H(2)O, CO, O(2), O(3), and H(2)O(2) all have intense spectral lines in the Mars atmosphere in this frequency range and in addition are all very important in understanding the water cycle, the photochemistry, and the circularization in that atmosphere. It is shown that the altitude and the zonal distribution of H(2)O can be mapped even in atmospheric columns as dry as 0.25 precipital µm. Ozone can be mapped over the entire planet, independent of solar-lighting conditions, dust loading, or clouds in the atmosphere, because millimeter waves are insensitive to any particles that can be suspended in the Mars atmosphere. Because the signal-receiving techniques use superheterodyne devices and narrow spectral lines, zonal and meridional winds can be measured at altitudes above 10 km with a precision approaching approximately 3 m/s by the use of Doppler shifts. Temperature-pressure profiles can be measured to altitudes of 100 km by the use of CO lines in the limb-sounding mode.

Evaluations of the Carcinogenicity of Carbon Nanotubes, Fluoro-Edinite, and Silicon Carbide by the International Agency for Research on Cancer (IARC). We reported the evaluations of the carcinogenicity of fluoro-edinite, silicon carbide, and carbon nanotubes performed by IARC working group in October 2014. For carbon nanotubes (CNTs), multi-walled carbon nanotube (MWCNT)-7 was classified as Group 2B, and MWCNTs without MWCNT-7 and single-walled carbon nanotubes (SWCNTs) were classified as not classifiable in terms of their carcinogenicity to humans. There is sufficient evidence of carcinogenicity for MWCNT-7 in experimental animals, limited evidence for other MWCNTs, and inadequate evidence for SWCNTs. The mechanic evidence for CNTs was not strong. Fluoro-edinite was classified as carcinogenic to humans (Group 1) on the basis of sufficient evidence of carcinogenicity to humans and experimental animals. Silicon carbide was classified into silicon carbide fibers and whiskers. Silicon carbide fibers were evaluated as possibly carcinogenic to humans (Group 2B) on the basis of limited evidence of carcinogenicity to humans. Silicon carbide whiskers were evaluated as probably carcinogenic to humans (Group 2A) on the basis of sufficient evidence of carcinogenicity to experimental animals and the similarity of their physicochemical properties to those of asbestos in terms of the mechanism of carcinogenicity. We report the process of progression in meeting and discuss how to determine the evidence and the evaluation of the carcinogenicity of the three materials.

Bacterial antibiotic resistance studies using in vitro dynamic models: Population analysis vs. susceptibility testing as endpoints of mutant enrichment. Emergence of bacterial antibiotic resistance is usually characterised either by population analysis or susceptibility testing. To compare these endpoints in their ability to demonstrate clear relationships with the ratio of 24-h area under the concentration-time curve (AUC24) to the minimum inhibitory concentration (MIC), enrichment of ciprofloxacin-resistant mutants of four clinical isolates of Pseudomonas aeruginosa was studied in an in vitro dynamic model that simulates mono-exponential pharmacokinetics of ciprofloxacin over a wide range of the AUC24/MIC ratios. Each organism was exposed to twice-daily ciprofloxacin for 3 days. Amplification of resistant mutants was monitored by plating on media with 2×, 4×, 8× and 16× MIC of ciprofloxacin. Population analysis data were expressed by the area under the bacterial mutant concentration-time curve (AUBCM). Changes in P. aeruginosa susceptibility were examined by daily MIC determinations. To account for the different susceptibilities of P. aeruginosa strains, post-exposure MICs (MICfinal) were related to the MICs determined with the starting inoculum (MICinitial). For each organism, AUC24/MIC relationships both with AUBCM and MICfinal/MICinitial were bell-shaped, but the latter were more strain-specific than the former. Using combined data on all four isolates, AUBCM showed a better correlation than MICfinal/MICinitial (r(2)=0.75 vs. r(2)=0.53). The shift of MICfinal/MICinitial relative to AUBCM vs. AUC24/MIC curves resulted in a weak correlation between AUBCM and MICfinal/MICinitial (r(2)=0.41). These data suggest that population analysis is preferable to susceptibility testing in bacterial resistance studies and that these endpoints should not be considered interchangeable.

Predictive validity of the pain and impairment relationship scale in a chronic nonmalignant pain population. To examine the predictive and incremental validity of the Pain and Impairment Relationship Scale (PAIRS) and to determine its ability to measure changes in pain beliefs following interdisciplinary treatment. A before-after treatment design. A comprehensive interdisciplinary pain center at a large midwest university medical center. A cognitive-behavioral approach to pain management. The day-long program lasted 5 days a week for 4 weeks. Interventions were designed to improve physical functioning, reduce use of health care, and improve pain coping. Six-month follow-up outcome measures included interference with daily activity, pain severity, and life control as measured by the Multidimensional Pain Inventory, medication use measured by the Medication Quantification Scale, depression measured by the Beck Depression Inventory, and the number of health care visits and pain-related hospitalizations. Pretreatment PAIRS scores correlated significantly with interference with daily activities, pain severity, life control, health care visits, and depression. Stronger correlations were obtained between posttreatment PAIRS scores and all follow-up outcome measures. Posttreatment PAIRS scores accounted for a significant portion of the variance beyond that in demographic variables and pretreatment PAIRS scores in all but one of the follow-up measures. PAIRS scores changed significantly (p < .0001 ) in a positive direction after treatment. The PAIRS has excellent predictive validity, and can be used effectively to monitor individual and programmatic changes.

The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial. The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism. The immunosuppressive drug mizoribine has been demonstrated to inhibit T lymphocyte proliferation by depleting these cells of guanine ribonucleotides as a consequence of inhibiting the enzyme inosine monophosphate (IMP) dehydrogenase. Because the immunosuppressive agents azathioprine and 6-mercaptopurine (6MP) are both converted to the IMP analog 6-thio-IMP, we postulated that these drugs might inhibit T cell activation and/or proliferation by a similar mechanism. Incubation of isolated peripheral blood T cells with either mizoribine or the selective IMP dehydrogenase inhibitor mycophenolic acid caused a dose-dependent inhibition of T cell proliferation, which was reversible with the addition of 50 microM guanosine to replete guanine ribonucleotide pools. In contrast, guanosine exacerbated the inhibition of proliferation induced by azathioprine and restored proliferation at IC50 concentrations of 6MP by only 10%. Complete restoration of proliferation in the presence of 6MP, but not azathioprine, was achieved with the addition of adenine. The inhibitory effects of azathioprine, as well as those of mizoribine, 6MP, and mycophenolic acid, were identical in cells stimulated with antibody to the T cell receptor and in cells stimulated with phorbol ester and ionomycin. We conclude from these studies that mizoribine selectively inhibits guanine ribonucleotide formation in purified T cells, whereas the effect of 6MP appears to be more dependent on adenine ribonucleotide depletion. Azathioprine, on the other hand, inhibits proliferation by a mechanism independent of purine ribonucleotide depletion. None of these agents inhibits T cell proliferation by interfering with signal transduction mediated by the T cell receptor. Inhibition of guanine ribonucleotide biosynthesis appears to be a novel and perhaps more selective mechanism of inhibiting T cell proliferative responses after T cell activation.

Incidence trends in oesophageal cancer by histological type: An updated analysis in Sweden. We aimed to update incidence trends of oesophageal cancer by histological type in Sweden. Using data from the Swedish Cancer Registry, we examined incidence trends of oesophageal cancer by histological types in individuals aged ≥50 years in 1970-2014 using log-linear joinpoint regressions. The age-standardised incidence rate of oesophageal adenocarcinoma in men increased on average by 3.0% per year in 1970-1994, followed by a more rapid increase of 13.7% per year in 1994-2000, and a slower increase of 2.6% per year in 2010-2014. The rate of oesophageal adenocarcinoma in women increased on average by 4.2% per year during the entire period. The rate of squamous cell carcinoma generally decreased over the past 2-3 decades in both sexes. The incidence of oesophageal adenocarcinoma continues to rise in Sweden, although the increase seems to have slowed down in men since 2000. The incidence of oesophageal squamous cell carcinoma is decreasing.

Maximization of signal derived from cDNA microarrays. Microarray technology is a powerful tool for generating expression data on a large number of genes simultaneously. However, as for any assay, it must be reproducible to give confidence in the results. Using a classical statistical method--the factorial design of experiments--we have assessed the effects of different experimental factors in our system. Significant effects on signal were seen when the standard components were substituted with a different enzyme, fluorescent label, or RNA purification method. This has led to the implementation of an improved procedure that maximizes signal without affecting the variability of the system, thus increasing the signal-to-noise ratio. In addition, we were able to quantify the variability between microarrays and replicates within microarrays.

[Study on the molecular mechanism of lingual epithelial cell apotosis and its related genes in different tongue furs]. To investigate the molecular mechanism ot lingual epithelial cell (LEC) apoptosis and its related genes expression in different tongue furs. The LEC apoptosis and its related genes expression including bax, fas, TGF-beta 3 mRNA and protein product in tongue fur was determined using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL), in situ hybridization, immunohistochemical technique and image analysis. LEC apoptosis could always be seen in 4 types commonly encountered tongue fur. The tendency of changing in thickness of tongue fur was opposite to that of apoptotic index. Compared with normal thin fur, bax and fas genes were over-expressed in exfoliative fur with increased apoptosis, while in thick fur, bax and TGF-beta 3 genes were low-expressed and accompanied with decreased apoptosis. The level of apoptosis promoting genes, bax, fas, TGF-beta 3 gene expression in LEC showed a tendency parallel to that of LEC apoptosis. Change of apoptosis related genes expression, bax, fas and TGF-beta 3 may effect the LEC apoptosis and be the important factor for changing of the thickness of tongue fur.

[Spatial variability of soil C/N ratio and its influence factors at a county scale in hilly area of Mid-Sichuan Basin, Southwest China]. Spatial distribution characteristics of soil C/N ratio and its affecting factors at a county scale in hilly area of Middle Sichuan Basin were analyzed based on field sampling. Result indicated that soil C/N ranged from 4.84 to 21.79, with a mean value of 11.93. The coefficient of variation was 26.3%; which suggested soil C/N had moderate variability in this study area. The ratio of nugget to sill was 73.0%, which suggested the spatial variability of soil C/N was determined by both structural and random factors, and the random factors played a more important role. The soil C/N was higher in northeast and southwest while the central part of the study area was characterized by relatively lower values of soil C/N. The soil C/N ranged from 10.0 to 13.5 in most parts of the study area. Parent material, soil type, topographic factors and land use type had significant impacts on soil C/N (P<0.05). Soil C/N showed a significant positive correlation with elevation and slope (P<0.05). The soil parent materials were able to explain 8.7% of soil C/N spatial variability. The explanatory power of soil group, subgroup and soil genus were 3.8%, 5.0%, 8.7%, respectively. Topographic factors showed the lowest explanatory power of only 0. 8%. However, land use type could explain 23.9% of the spatial variability, which suggested that land use type was the dominant factor in controlling the spatial variability of soil C/N.

Ethanol fraction of Aralia elata Seemann enhances antioxidant activity and lowers serum lipids in rats when administered with benzo(a)pyrene. Aralia elata Seemann is an edible mountain vegetable in Korea containing saponin, alkaloid, palmitic acid, linoleic acid, methyl eicosanoate and hexacosol, and is known to manifest an effect on cardiac infarction, gastric ulcer, colitis, and enervation. This study has examined the effects of Aralia elata Seemann ethanol extract on antioxidant enzyme systems and lipid metabolism in rats along with benzo(a)pyrene (B(a)P) administration. Rats were divided into four groups: control (C), an extract fed group (CE), a B(a)P fed group (CB), and a B(a)P and extract fed group (CBE). The ethanol extracts of Aralia elata Seemann (50 mg/kg body weight) were fed to the rats for 4 weeks by stomach tubing. Extract administration increased the antioxidant activities of glutathione sulfur transferase (GST). Total superoxide dismutase (SOD) and Cu,Zn-SOD activities were stimulated. Catalase activities were increased by 50% with extract feeding. Cu,Zn-SOD was greatly enhanced from 0.10 unit to 0.18 unit and catalase activity also was increased. Serum alpha-tocopherol was markedly increased by the extracts. The ethanol fraction of Aralia elata Seemann decreased total serum cholesterol. However, serum HDL-cholesterol was increased by 35% (p<0.05). The results indicate that Aralia elata Seemann exerts antioxidant and strong hypocholesterolemic and hypolipidemic effects in vivo with the administration of B(a)P.