Esophageal carcinoma multiplex with gastric metastasis.
We describe here the radiographic findings in a patient with multiple synchronous squamous carcinomas of the esophagus with a large metastasis to the gastric cardia. Radiographic documentation of this constellation of tumor involvement has not previously been reported. The mechanisms of esophageal metastasis are reviewed.


Iterative Design of a Biomimetic Catalyst for Amino Acid Thioester Condensation.
Herein, the design of a catalyst that combines lessons learned from peptide biosynthesis, enzymes, and organocatalysts is described. The catalyst features a urea scaffold for carbonyl recognition and elements of nucleophilic catalysis. In the presence of 10 mol % of the organocatalyst, the rate of peptide bond formation is accelerated by 10000-fold over the uncatalyzed reaction between Fmoc-amino acid thioesters and amino acid methyl esters.


Effect of Early Intervention With Positive Airway Pressure Therapy for Sleep Disordered Breathing on Six-Month Readmission Rates in Hospitalized Patients With Heart Failure.
Rehospitalization for congestive heart failure (CHF) is high within 6 months of discharge. Sleep disordered breathing (SDB) is common and underdiagnosed condition in patients with CHF. We hypothesized that early recognition and treatment of SDB in hospitalized patients with CHF will reduce hospital readmissions and emergency room visits. Patients admitted for CHF underwent overnight polysomnography within 4 weeks of discharge. Patients diagnosed with SDB were provided therapy with positive airway pressure therapy. Patients were identified as having good compliance if the device use was for a minimum of 4 hours 70% of the time for a minimum of 4 weeks during the first 3 months of therapy. Hospital admissions for 6 months before therapy were compared with readmission within 6 months after therapy in patients with good and poor compliance. A total of 70 patients were diagnosed with SDB after discharge. Of the 70 patients, 37 (53%) were compliant with positive airway pressure therapy. Compliant patients were more likely to be older (64 ± 12 vs 58 ± 11 years) and women (54% vs 33%) and less likely to be patient with diabetes (40% vs 67%) versus noncompliant patients. Although both groups experienced a decrease in total readmissions, compliant patients had a significant reduction (mean ± SE: -1.5 ± 0.2 clinical events vs -0.2 ± 0.3; p <0.0001). In this single-center analysis, identification and treatment of SDB in admitted patients with CHF with SDB is associated with reduced readmissions over 6 months after discharge. Adherence to the treatment was associated with a greater reduction in clinical events.


Aerobic fitness thresholds to define poor cardiometabolic health in children and youth.
Aerobic fitness is an apparent candidate for screening children and youth for poor cardiometabolic health and future risk of cardiovascular disease (CVD). Yet, age- and sex-specific cut points for children and youth determined using a maximal protocol and directly measured peak oxygen consumption (VO2peak ) does not exist. We used a nationally representative sample of 1462 Norwegian children and youth (788 boys and 674 girls aged 8.7-10.4 years and 14.7-16.7 years) who in 2005-2006 performed a maximal cycle ergometer test with direct measurement of VO2peak , along with measurement of several other risk factors for CVD (systolic blood pressure, waist circumference:height ratio, total:high-density lipoprotein cholesterol ratio, triglycerides, Homeostasis Model Assessment for Insulin Resistance). Based on the proportion of children having clustering (least favorable quartile) of 6 (1.6%), ≥5 (5.2%), and ≥4 (10.6%) CVD risk factors, we established the 2nd, 5th, and 10th percentile cut points for VO2peak (mL/kg/min) for children and youth aged 8-18 years. Classification accuracy was determined using the Kappa coefficient (k), sensitivity, and specificity. For boys, the 2nd, 5th, and 10th percentile VO2peak cut points were 33.6-36.4, 36.3-39.8, and 38.7-43.0 mL/kg/min, respectively. For girls, the corresponding cut points were 29.7-29.1, 32.4-31.4, and 34.8-33.5 mL/kg/min Together with BMI, but without more invasive measures of traditional risk factors for CVD, these cut points can be used to screen schoolchildren for poor cardiometabolic health with moderate discriminating ability (k ≤ 0.53).


An unusual case of IgA-mediated anti-glomerular basement membrane disease.
Anti-glomerular basement membrane (GBM) disease is mediated by circulating autoantibodies, principally IgG, targeted at the type IV collagen of GBM. The IgA variant of anti-GBM disease has rarely been described. We report a 65-year-old man with uremia, undergoing hemodialysis, who was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis. Circulating IgA anti-GBM antibody was found, as well as the presence of significant IgA deposition in a linear pattern along the GBM, suggesting an anti-GBM antibody-mediated disease. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.


Prolactin-induced prostate tumorigenesis.
The physiological role of prolactin (PRL) in the prostate gland is not clearly understood. Genetically-modified mouse models that have invalidated actors of the PRL signaling axis failed to identify an essential regulatory function on this tissue. However, a large body of evidence suggests an important role for PRL in prostate tumorigenesis. Mainly through the activation of its downstream target STAT5, PRL can induce growth and survival of prostate cancer cells and tissues in several experimental settings. In the clinic, PRL expression and STAT5 activation in human prostate tumors correlate with disease severity. Available data point to a role of local (autocrine/paracrine) rather than circulating (endocrine) PRL in the induction of disease progression. In mice, transgenic expression of PRL in the prostate leads to enhanced epithelial hyperplasia and dysplasia, with amplification of basal/stem cells which have been recently identified as prostate cancer-initiating cells. Thus, targeting PRL receptor (PRLR)/STAT5 signaling may provide an alternative therapy for the treatment of prostate cancer. Corresponding targeted therapies currently in preclinical development include antagonists or blocking antibodies for the PRLR and small molecule inhibitors directed against the tyrosine kinase JAK2 upstream of STAT5. Present efforts are aimed at validating these therapies for the treatment of prostate cancer, while understanding the mechanisms of disease progression induced by PRL/STAT5.


Cerebral blood flow and rheologic alterations by hyperosmolar therapy in patients with brain oedema.
Cerebral blood flow was assessed as initial slope index by 133-Xenon inhalation in 36 patients with brain tumours subjected to osmotic dehydration. The following solutions were employed: I. 20% mannitol, II. 40% sorbitol, III. 10% glycerol. Parameters affecting blood rheologic properties as Hct, plasma viscosity, red blood cell aggregation and fluidity were simultaneously studied. CBF which was reduced in the oedematous hemisphere with brain tumour increased during infusion and thereafter by mannitol or sorbitol, respectively. The blood flow response to glycerol was more delayed, less intense, but maintained longer. Hct and plasma viscosity were significantly reduced by all osmotic agents, while red blood cell fluidity fell and aggregation rose under mannitol. It is concluded that sorbitol (40%) is superior for emergency treatment with high ICP, whereas glycerol seems to be preferable to improve cerebral blood flow in oedematous brain.


Use of biologic mesh for a complicated paracolostomy hernia.
Parastomal hernias are among the most frustrating and incapacitating complications of permanent colostomies. Because the traditional surgical options of primary repair with or without ostomy repositioning have led to disappointing results, the use of mesh is indicated, especially in the setting of multiple recurrences. After laparoscopic lyses of adhesions, the colostomy is pushed against the lateral abdominal wall, and a bovine pericardium graft is gently stretched and draped over the colostomy (the Sugarbaker technique). Transfascial sutures and tacks are placed along the perimeter of the mesh and around the colon to prevent small bowel herniation. The patient developed a small seroma postoperatively, which resolved spontaneously. At his 17-month follow-up, the patient had no evidence of recurrence, he was pain free, and he was satisfied with his cosmetic results. Although several studies indicate the feasibility and efficacy of synthetic permanent mesh repair, the concerns of mesh infection, erosion, and ostomy obstruction still persist. The authors suggest parietalizing the bowel and using a biologic mesh.


[Inhibitory serum factors in MLR and in PHA-stimulation in sera from normal, allogenic hyperimmunized and transplantation tolerant mice].
Sera from normal, allogeneically hyperimmunized and transplantation tolerant mice show an inhibitory effect on MLR and PHA stimulation. After gel chromatography these inhibitory factors are preferably found in fraction III for MLR (MW 250-750 KD) and III and IV for PHA stimulation. These factors are not identical with the IL-2 inhibitor. A specific inhibitory component with a MW of about 1000 KD is found in sera from transplantation tolerant mice. This suppressor factor could have a synergistic function in induction of specificity and activity of suppressor cell.


Feasibility of molecular diagnosis of alpha-thalassemia in the evaluation of microcytosis.
Microcytosis is a common hematological finding, usually related to iron deficiency or beta-thalassemia. When both of these conditions are excluded, alpha-thalassemia must be considered in the differential diagnosis. No simple biochemical test is able to diagnose the alpha-thalassemia trait. Using PCR amplification of the breakpoint in deletional forms, and amplification of the alpha 2 gene and restriction enzyme digestion in non-deletional forms, we identified the alpha-thalassemia carrier status in 42 out of 51 (82%) patients with microcytosis or slight microcytic anemia, unrelated to iron deficiency or beta-thalassemia. Our results underline the usefulness of molecular tests in clinical practice.


Comparison and utility of King-Devick and ImPACT® composite scores in adolescent concussion patients.
The King-Devick (KD) oculomotor test has recently been advocated for sideline diagnosis of concussion. Although visual processing and performance are often impaired in concussion patients, the utility of KD as a concussion diagnostic tool is not validated. To examine the diagnostic value of KD, by comparing KD with post-concussion symptom scale (PCSS) and ImPACT® composite scores. We hypothesized that KD would be correlated with visual motor speed/memory (VMS, VIS) and reaction time (RT), because all require cognitive visual processing. We also expected parallel changes in KD and PCSS across recovery. Thirty-five concussed individuals (12-19 y; 18 females, 17 males) were evaluated with PCSS, ImPACT® composite and KD scores over four clinical visits (V). KD times improved with each visit (ΔV1-V2: 7.86±11.82; ΔV2-V3: 9.17 ± 11.07; ΔV3-V4: 5.30 ± 7.87 s) and paralleled improvements in PCSS (ΔV1-V2: 8.97 ± 20.27; ΔV2-V3: 8.69 ± 14.70; ΔV3-V4: 6.31 ± 7.71), RT (ΔV1-V2: 0.05 ± 0.21; ΔV2-V3: 0.09 ± 0.19; ΔV3-V4 0.03 ± 0.07) and VMS (ΔV1-V2: -5.27 ± 6.98; ΔV2-V3: -2.61 ± 6.48; ΔV3-V4: -2.35 ± 5.22). Longer KD times were associated with slower RT (r = 0.67; P<0.0001) and lower VMS (r = -0.70; P<0.0001), respectively. Cognitive visual performance testing using KD has utility in concussion evaluation. Validation would further establish KD as an effective ancillary tool in longitudinal concussion management and research.


An easy and safe procedure for temporal artery biopsy.
Temporal arteritis is a very serious form of vasculitis. Early treatment is essential to avoid blindness. Surgical biopsy of the temporal artery is the gold standard for the diagnosis, but facial nerve injuries may occur. To describe a simple and safe procedure for temporal artery biopsy. Case report. A 62-year-old-woman with presumed temporal arteritis was referred. Precise localization of temporal arteries and its branches was obtained with color duplex ultrasonography. Arterial wall thickening (halo sign) was observed in the affected arterial segments. A frontal branch was precisely localized and infiltrated with 1% lidocaine. About 1 cm was removed for histopathologic examination. Thirty minutes was required to perform this outpatient procedure. The diagnosis of temporal arteritis was confirmed, and the patient was rapidly and successfully treated with prednisone. Color duplex ultrasonography allows precise localization of temporal arteries and its branches. This echocardiography-guided surgical procedure is easy and safe. Most dermatologic surgeons can perform it.


Cryptogenic cirrhosis: Old and new perspectives in the era of molecular and genomic medicine.
Cryptogenic cirrhosis (CC) is defined as cirrhosis of unknown etiology despite extensive clinical, laboratory and pathologic work-up, and constitutes approximately 5-10% of all cirrhosis cases. Histologic examination can provide important clues and help identify the potential etiology of CC. Most CC cases can still be classified into four histologic patterns: hepatitic, steatotic, biliary, and patternless (bland). The use of genetic testing has significantly improved diagnostic ability and treatment, especially in pediatric patients with acute and chronic liver diseases. More recently, whole exome sequencing has been used for identifying genetic alterations that lead to a diagnosis in adults with liver disease of unknown etiology. Recent advances in genomic analysis has allowed the unraveling of the underlying etiology in a subset of CC cases, and also helped identify new disorders. Providing a diagnosis for these patients has several important implications for treatment, possible genetic counseling, and transplant eligibility. However, detailed clinical and histologic characterization of the patients still remains an important part of the CC work-up, since clinicopathologic and genomic correlation is crucial in making a diagnosis, or in some cases, discovery of a new entity. This article summarizes the main histologic findings that can be observed in CC cases, potential causes of CC, and recent advances in the field.


Isolation and partial characterization of the photoreceptive organelle for phototaxis of a flagellate green alga.
We report on the isolation and purification of structurally intact eyespot apparatuses from the naked, biflagellate green alga Spermatozopsis similis. Two eyespot-enriched fractions, separated by sucrose gradient centrifugation, retained the typical reflective properties of eyespots in situ as demonstrated by reflection confocal laser scanning microscopy. Ultrastructurally, both fractions contained eyespot plates consisting of a single layer of lipid globules. Structurally intact eyespot apparatuses, including patches of plasma membrane and chloroplast envelope overlying the eyespot plate and a single thylakoid subtending the eyespot plate, were particularly enriched in one of the two fractions (fraction 2a). Measurement of several marker enzymes and chlorophyll content (less than 0.001% of total) established the absence of most other cell organelles from the eyespot fractions. The absorption spectra of the two fractions were dominated by carotenoids with an additional shoulder at 540 nm. Following extraction with organic solvents and sodium dodecyl sulfate polyacrylamide gel electrophoresis, several proteins were found to be considerably enriched in the two fractions. In addition to several proteins in the high Mr range, at least 4 polypeptides of 35, 29, 23, and 20 kDa are selectively enriched in fraction 2a with the 29 and 20 kDa proteins being the most prominent. The presence of glycoproteins in fraction 2a was demonstrated by binding of the mannose-specific lectin Galanthus nivalis agglutinin to several high molecular weight polypeptides. In addition, a hydrophobic component with abnormal electrophoretic mobility that reacts strongly with periodic acid-Schiff and thymol/sulfuric acid was prominent in both fractions. Mass isolation and purification of the intact phototactic apparatus of a flagellate green alga now greatly facilitates the biochemical and molecular characterization of the signal transduction chain involved in green algal phototaxis.


The occurrence of autoimmune diseases in patients with multiple sclerosis and their families.
The aims of this study were to determine whether the occurrence of autoimmune diseases is increased in patients with multiple sclerosis (MS) and their families and whether this is influenced by the type of MS. We conducted a case-control study using a questionnaire design to determine whether the prevalence of 11 autoimmune diseases is increased in patients with MS and their first-degree relatives compared to a random population control group and their first-degree relatives. We found that the total combined prevalence of the 11 autoimmune diseases was higher in the MS patients than in the controls, with an odds ratio of 1.7 (95% confidence interval 0.9-3.2; P = 0.10) increasing to 1.9 (1.0-3.5; P = 0.05) after adjusting for age. For persons aged under 60 years, the odds ratio was 2.3 (1.1-4.6). We also found that there was a significant increase in the total combined prevalence of the autoimmune diseases in the first-degree relatives of MS patients compared to the first-degree relatives of the control group (P = 0.003, odds ratio 2.2, confidence interval 1.3-3.7). Patients with primary progressive MS did not differ from patients with relapsing-remitting or secondary progressive MS in the personal or familial occurrence of autoimmune disease. In conclusion, although there were sources of possible bias, this study suggests that individuals with MS have a genetic predisposition to autoimmunity in general.


Preparation, characterization and in vivo pharmacodynamic evaluation of thymopentin loaded poly(lactide acid)/poly(lactide-co-glycolide acid) implants.
To avoid the clinical inconvenience of repeated injection of the immune modulator thymopentin (TP5), biodegradable implants comprising a mixed polymer matrix of poly(lactide acid) (PLA) and poly(lactide-co-glycolide acid) (PLGA) were produced using a simple extrusion method. Drug release from these TP5-loaded implants was characterized both in vitro and in vivo. Pharmacodynamic studies were carried out in immunosuppressed rats using the ratio of CD4(+)/CD8(+) cells, determined by flow cytometry, as an index of immunity. The results indicated that the entrapment efficiency of the implants was greater than 98%, but the release rate of TP5 depended on the drug loading. Implants containing less than 10% TP5 showed consistent release over 30 days, with low burst-release both in vitro and in vivo. Improved immunity and survival rates were observed in rats treated by TP5 injection and in rats given middle-to-high dose implants. When the release of TP5 exceeded 0.1 mg/kg body weight/day the CD4(+)/CD8(+) ratios increased in the 3 weeks after implantation, reaching a maximum (91.6% of the normal level) by the end of the third week. The TP5-loaded implants presented here provide a promising alternative to injections and the results support the further development of controlled-release TP5 formulations.


Sliding hernia of the bladder presenting as suprapubic pain in a female.
We report a case of bilateral sliding hernia of the bladder in a 64-year-old woman who presented with suprapubic pain and nocturia and was diagnosed by voiding diary and cystogram.


Operator Experience and Outcomes After Left Main Percutaneous Coronary Intervention.
This review was performed with the goal of summarizing the role of operator experience in the treatment of severe left main stenosis by percutaneous intervention techniques. The Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial demonstrated that percutaneous coronary intervention and coronary artery bypass grafting had similar clinical outcomes for severe left main disease. However, PCI of the left main coronary stenosis is considered to be a high-risk intervention because of the large area of myocardium at jeopardy that can quickly cause hemodynamic compromise. Operator experience and familiarity with the use of hemodynamic support devices, plaque modification techniques, and intravascular imaging tools is associated with better clinical outcomes. In patients with severe left main stenosis undergoing percutaneous coronary intervention by high-volume operators, the clinical outcomes are superior.


Volumetric and spectrophotometric determination of oxcarbazepine in tablets.
Two cerimetric procedures are described for the assay of oxcarbazepine (OXC) in bulk drug and in tablets. Titrimetry (method A) is based on the reaction of OXC by a measured excess cerium(IV) sulphate in sulphuric acid medium and the determination of the unreacted oxidant by titration with iron(II) solution using ferroin as indicator. Spectrophotometry (method B) is based on oxidation of OXC by cerium(IV) in perchloric acid (HClO4) medium and the determination of the unreacted oxidant using a colour reaction with p-dimethylaminobenzaldehyde (p-DMAB) having an absorption maximum of 460 nm. The titrimetric method is applicable in the range of 2.0-20.0 mg OXC with a 1:2 reaction stoichiometry [OXC:Ce(IV)]. In the spectrophotometric method a rectilinear relationship is obtained over the concentration range of 0.3-6.0 µg mL-1 OXC. The linear regression equation of the calibration graph is A = 0.9820-0.1477 C with a regression coefficient (r) of -0.9967 (n = 6). The molar absorptivity is calculated to be 3.76 × 104 L mol-1 cm-1 and the Sandell sensitivity is 0.0067 µg cm-2. The limits of detection (LOD) and quantification (LOQ) values are calculated according to ICH guidelines. The methods are successfully applied to the determination of OXC in tablets.


Ultrasonic broadband characterization of a viscous liquid: methods and perturbation factors.
The perturbation factors involved in ultrasonic broadband characterization of viscous fluids are analyzed. Precisely, the normal incidence error and the thermal sensitivity of the properties have been identified as dominant parameters. Thus, the sensitivity of the ultrasonic parameters of attenuation and phase velocity were measured at room temperature in the MHz frequency range for two reference silicone oils, namely 47V50 and 47V350 (Rhodorsil). Several methods of characterization were carried out: time of flight, cross-correlation and spectral method. These ultrasonic parameters are measured at room temperature. For this family of silicone oil, the dispersion of the attenuation spectrum is modeled by a power law. The velocity dispersion is modeled by two dispersion models: the quasi-local and the temporal causal. The impact of the experimental reproducibility of the phase velocity and acoustic attenuation was measured in the MHz frequency range, using a set of ultrasonic transducers with different center frequencies. These measurements are used to identify the dispersion of the ultrasonic parameters as a function of the frequency. A first experimental and descriptive approach is developed to assess the reproducibility of the normal incidence between the acoustic beam and the viscoelastic material. Thus, the relative error on the measurements of velocity and attenuation are directly related to the angular deviation of the ultrasonic wave, as well as the sampling and signal-to-noise ratio. A second experimental and phenomenological approach deals with the effect of a temperature change, typical of a polymerization reaction. As a result, the sensitivity of the phase velocity of silicone oil 47V50 was evaluated around -2 ms(-1) K(-1).


Sitting Time: An Increasing Heath Risk Among Nurse Educators.
Prolonged sitting time (ST) is a distinct risk factor for early mortality and cardiovascular disease. The purpose of this descriptive correlational study was to examine ST and health of Kentucky nurse educators. The written survey included demographic items, general health items, and ST. Total average ST was 10.8 hours (workdays) and 8 hours (non-workdays). There was no relationship between body mass index and ST; however, the medication used to treat hypertension and hypercholesterolemia was associated with increased ST. Nurse educators are at risk for negative health effects of prolonged ST, and effective interventions are imperative.


Psychometric evaluation of the Spiritual Coping Strategies scale in English, Maltese, back-translation and bilingual versions.
The little research that has been done on the topic considers spiritual coping as consisting mainly of religious coping strategies. This limits spiritual coping solely to believers. However, it is argued that spiritual coping should address both believers and non-believers. The development of the new Spiritual Coping Strategies (SCS) scale, which consists of both religious and non-religious coping strategies attempts to fill this research gap. Aim. The aim of this article is to discuss the psychometric assessment of the SCS scale designed in four versions, namely English, Maltese, back-translation and bilingual. The Likert-type SCS scale comprises 20 items, each represented by the frequency and helpfulness of both religious and non-religious coping strategies. Test-retest of the four versions was conducted between October 1999 and January 2000, with 55 final year nursing students, mean age of 24.5 years, recruited from the same class to facilitate supervision and prevent contamination of results. Test-retest reliability of the scale was investigated by cross-tabulations, Kappa (kappa) measures and Spearman's correlation coefficient. Internal consistency was tested by Cronbach's alpha. The correlation structure was examined by the multivariate techniques of R-type cluster analysis and direct oblimin factor analysis. Cross-tabulations between tests and retests gave highly significant values of chi-squared (P < or = 0.0001) for most items in all versions of the scale. These cross-tabulations also yielded reasonably good values for kappa. Additionally, satisfactory values for Spearman's coefficient of correlation resulted between tests and retests. Twelve frequency variables and 13 helpfulness variables had test-retest correlations in the range 0.5 < or = rs < or = 0.79 in at least three of the versions. Optimum values of Cronbach's alpha were observed for the helpfulness variable in retests namely, 0.81 for the English version, 0.73 for the Maltese version, 0.79 for the back-translation, and 0.82 for the bilingual version. These values were all above the acceptable minimum value of 0.7. The correlation structure identified two factors, namely religious and non-religious coping strategies. Although the two factors together explained only between 33% and 40% of the variance in the different versions, the religious factor had good reliability, with 0.77 < or = alpha < or = 0.82 for the four versions, whilst the non-religious factor also had alpha > or = 0.71 for all versions except the Maltese one, for which alpha = 0.59. Therefore, psychometric assessment suggests that the SCS scale, in any of the four versions, is a reliable tool which can be used in future studies on SCS in Maltese patients.


Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy.
To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4mm and 6mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively. Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.


Gastroparesis: A Review of Current Diagnosis and Treatment Options.
Gastroparesis (GP) is a chronic neuromuscular disorder of the upper gastrointestinal tract. The incidence of GP is not well described; however, the number of individuals affected by symptoms of GP in the United States is estimated to be over 4 million. The etiology of GP is diverse. Approximately 25% of cases are associated with diabetes, whereas nearly 50% are classified as idiopathic; many of these latter cases likely represent a postinfectious process. Connective tissue disorders, autoimmune disorders, prior gastric surgery, ischemia, and medications make up the vast majority of the remaining cases. The pathophysiology of GP is also diverse. Abnormalities in fundic tone, antroduodenal dyscoordination, a weak antral pump, gastric dysrhythmias, and abnormal duodenal feedback all contribute to delays in gastric emptying and symptom expression. Characteristic symptoms of GP include nausea, vomiting, epigastric pain, early satiety, and weight loss. The diagnosis of GP is made using a combination of characteristic symptoms in conjunction with objective evidence of delayed gastric emptying in the absence of mechanical obstruction. Once the diagnosis is made, treatment options include dietary modification, medications to accelerate gastric emptying, antiemetic agents, gastric electrical stimulation, and surgery. In the following sections we will provide an overview of the health care impact of GP, describe the underlying pathophysiology, and review treatment options using an evidence-based approach.


Response of Cervical Intra-epithelial Lesions to Vitamin E Supplementation - A Preliminary Report.
Carcinoma of the uterine cervix is preceded by well characterized pre-cancerous lesions which if left untreated may progress to invasive carcinoma. In the present study women in the age group of 35-55 years with cervical intraepithelial lesions (CIN I & II) were treated with vitamin E and advised to come for follow up after every three months for one year. This preliminary report shows vitamin E can restrict and regress CIN I & II lesions with elevation in circulating vitamin E levels. Improvement in immune status as reflected in mitogenic responses of peripheral blood lymphocytes was also noted.


Risk factors for extremely long length-of-stay among pediatric emergency patients.
Over time, we observed more visits in our pediatric emergency department with length-of-stay (LOS) of more than 10 hours, whereas our mean LOS was approximately 3 hours. We sought to characterize factors associated with this extremely long LOS. Eighty-one visits with LOS more than 10 hours were identified from January 1, 2001, to June 30, 2003. In this retrospective study, we compared these cases with 405 randomly selected age-matched controls with LOS less than 10 hours (5 controls per case). The groups were similar for sex, visit month, arrival mode, and level of training of the supervising physician. Cases more frequently arrived during night shifts (30% vs 13%) and had laboratory tests (93% vs 32%), radiological studies (83% vs 34%), procedures (28% vs 15%), sedations (24% vs 4%), subspecialty consultations (84% vs 20%), chief complaints of abdominal pain (42% vs 6%) and diagnoses of appendicitis (10% vs 1%), and had a greater hospitalization rate (67 vs 19%). Although more cases involved white patients (57% vs 31%), race was not associated with LOS more than 10 hours in adjusted analysis. In multivariable analysis, longer waiting time (odds ratio [OR], 1.013; 95% confidence interval [CI], 1.007-1.019), night shift arrival (OR, 5.0; 95% CI, 1.9-12.8), higher triage acuity (lowest acuity: OR, 0.003; 95% CI, 0.0-0.286), radiology study other than radiographs (OR, 18.0; 95% CI, 7.5-43.1), and subspecialty consultation (OR, 7.6; 95% CI, 3.2-18.3) were associated with LOS more than 10 hours. In our pediatric emergency department, risk factors for LOS more than 10 hours included longer waiting time, night shift arrivals, high triage acuity, radiology studies, and subspecialty consultations. These factors may also be important considerations for quality improvement initiatives at other institutions.


Feature Selection for Automatic Tuberculosis Screening in Frontal Chest Radiographs.
To detect pulmonary abnormalities such as Tuberculosis (TB), an automatic analysis and classification of chest radiographs can be used as a reliable alternative to more sophisticated and technologically demanding methods (e.g. culture or sputum smear analysis). In target areas like Kenya TB is highly prevalent and often co-occurring with HIV combined with low resources and limited medical assistance. In these regions an automatic screening system can provide a cost-effective solution for a large rural population. Our completely automatic TB screening system is processing the incoming CXRs (chest X-ray) by applying image preprocessing techniques to enhance the image quality followed by an adaptive segmentation based on model selection. The delineated lung regions are described by a multitude of image features. These characteristics are than optimized by a feature selection strategy to provide the best description for the classifier, which will later decide if the analyzed image is normal or abnormal. Our goal is to find the optimal feature set from a larger pool of generic image features, -used originally for problems such as object detection, image retrieval, etc. For performance evaluation measures such as under the curve (AUC) and accuracy (ACC) were considered. Using a neural network classifier on two publicly available data collections, -namely the Montgomery and the Shenzhen dataset, we achieved the maximum area under the curve and accuracy of 0.99 and 97.03%, respectively. Further, we compared our results with existing state-of-the-art systems and to radiologists' decision.


Clinical and ultrasonographic findings, diagnosis and treatment of pyelonephritis in 17 cows.
The goal of the present study was to describe the clinical, haematological and ultrasonographic findings and treatment of 17 cattle with pyelonephritis. Fifteen cattle had an abnormal general condition, which varied in severity; five animals had signs of colic. The urine was brownish-red in 11 animals and cloudy in 13. Clumps of purulent material were seen in the urine of nine animals and clots of blood in two. The specific gravity was lower than normal in 13 animals and ranged from 1.005 to 1.020. A urine test strip revealed protein in 16 animals, blood in 16 and leukocytes in 12. Bacteriological examination of urine yielded Corynebacterium renale in 11 animals, Arcanobacter pyogenes in two and Escherichia coli in one. Rectal examination revealed abnormalities of the urinary tract in 11 animals; there was dilatation of the left ureter and/or enlargement of the left kidney in eight cases, and dilatation of the right ureter and/or enlargement of the right kidney in three others. The most frequent abnormal haematological finding was an increase in the serum concentrations of total protein, fibrinogen, urea and creatinine, a decreased haematocrit and a positive glutaraldehyde test. In 13 animals, ultrasonography via the rectum and right flank using a 5.0MHz transducer revealed dilatation of the right or left ureter, cystic lesions in one or both kidneys and dilatation of the renal sinus. Eight animals were euthanased or slaughtered at the owners' request or because of a poor prognosis. Nine (53%) animals were successfully treated; five received antibiotics and four underwent unilateral nephrectomy and antibiotic therapy. The treated animals were clinically healthy when discharged from the clinic 10-21 days after admission. A follow-up via telephone 8-24 months later revealed that none had experienced complications and all were in full production. In cattle with severe unilateral pyelonephritis, unilateral nephrectomy is the treatment of choice.


[Cricoid pressure--safety necessity or unnecessary risk?].
Cricoid pressure is a simple and effective measure to prevent regurgitation of gastric juice and content. This procedure, which prevents a possible reflux by compression of the oesophagus between the cricoid cartilage and the cervical vertebral bodies, is generally acknowledged in clinical practice, although there is lack of scientific evidence regarding its effect on the outcome of patients at risk of aspiration. However, there is only a rare incidence of complications as long as cricoid pressure is used with exact indication, considering the contraindications and correct performance. Especially important are the optimal force applied on the cricoid and the duration of application. However, there is a lot of evidence in the literature that the knowledge of anaesthetists about the method and technique of cricoid pressure is rather unsatisfactory. Thus, the starting point for improving the efficiency and safety of cricoid pressure seems to be better teaching and training.


Small-conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+ release in a feedback regulation of pyramidal cell excitability.
Cooperative regulation of inosiol-1,4,5-trisphosphate receptors (IP(3)Rs) by Ca(2+) and IP(3) has been increasingly recognized, although its functional significance is not clear. The present experiments first confirmed that depolarization-induced Ca(2+) influx triggers an outward current in visual cortex pyramidal cells in normal medium, which was mediated by apamin-sensitive, small-conductance Ca(2+)-dependent K(+) channels (SK channels). With IP(3)-mobilizing neurotransmitters bath-applied, a delayed outward current was evoked in addition to the initial outward current and was mediated again by SK channels. Calcium turnover underlying this biphasic SK channel activation was investigated. By voltage-clamp recording, Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs) was shown to be responsible for activating the initial SK current, whereas the IP(3)R blocker heparin abolished the delayed component. High-speed Ca(2+) imaging revealed that a biphasic Ca(2+) elevation indeed underlays this dual activation of SK channels. The first Ca(2+) elevation originated from VDCCs, whereas the delayed phase was attributed to calcium release from IP(3)Rs. Such enhanced SK currents, activated dually by incoming and released calcium, were shown to intensify spike-frequency adaptation. We propose that spike-induced calcium release from IP(3)Rs leads to SK channel activation, thereby fine tuning membrane excitability in central neurons.


Structural characteristics of heparin-line domain required for interaction of midkine with embryonic neurons.
Midkine is a heparin binding growth/differentiation factor with neurite promoting activity. We examined inhibitory activities of various heparin derivatives toward interaction of midkine with neurons and elucidated the structural requirements of the heparin-like domain necessary for the interaction. All of the three sulfate groups in the heparin disaccharide unit (6-O-sulfate, 2-O-sulfate and N-sulfate) were necessary for full inhibitory activity. Among these, the N-sulfate group was critically important. The minimum size with inhibitory activity was approximately 7,000 Da. Thus, the highly sulfated region in cell surface heparan sulfate proteoglycan is required for neurons to interact with midkine.


Sexual dysfunction and sex therapy: an historical perspective.
Summary Sexual dysfunction has been reported across cultures and across time. The Hindu literature and the Ayurvedic system offer insights into assessment and management of various kinds of sexual dysfunction. Behavioural regimes were fairly well known in the traditional Ayurvedic texts. Religious writings have often proved to be the richest source of information about sexual behaviour. The relationship between the nature of creation, the need for reproduction and the importance of sex in life has often been discussed in religions. Artificial sexual aids were well known in both ancient China and India. This paper attempts to draw an historical analysis of varieties of sexual dysfunction across various societies. It also comments on the historical development of sex therapy.


[Surgical treatment of bronchial carcinoid].
84 patients with bronchial carcinoid tumors were analysed on during of 28 years. 26 of them were detected by radiography and 58 by symptoms. The bronchoscopy with biopsy is the most important diagnostic procedure. The preoperative histological or cytological diagnosis was correct in 25 cases. The suspicion was given only in 39 patients. The surgical therapy was carried out in all cases with conventional resection of lung as well as parenchyma preserving methods. We used atypical or typical segmental lung resections, bronchotomy with direct suture, sleeve or wedge resection of the bronchus and fenestration of bronchus with closure of the window with free skin graft. The prognosis after surgical treatment is very good. The 5-year-survival was 89%.


Multimodal Management and Triple Nerve Transfer for Optimal Recovery of Shoulder Function Following Neonatal Brachial Plexus Palsy: A Case Report.
Neonatal brachial plexus palsy is a complex disorder that requires evaluation of the primary nerve injury and associated sequelae. There is no standardized approach to management, and many treatment options are available. We present a case of Erb palsy with a unique multidisciplinary approach to nonsurgical and surgical management. Inherent in the case is the complexity of decision-making, and we review the literature on treatment options and the rationale for the approach, which resulted in near normal functional recovery.


[Tuberculosis and acute respiratory insufficiency. Apropos of 2 cases].
We report two cases of death from acute respiratory insufficiency of tuberculous origin. There were rare clinical presentations in which the clinical and radiological aspects were particularly atypical, suggesting a diagnosis of an acute respiratory distress syndrome. Bacteriological confirmation is necessary but it is worth considering this aetiology with each case of unexplained respiratory distress because the mortality is high and the prognosis is related to how early drug therapy is given.


Ecological, energetic and economic comparison of anaerobic digestion with different competing technologies to treat biogenic wastes.
In order to get more detailed information for better decision making in future biogenic waste treatment, different processes to treat biogenic wastes in plants with a treating capacity of 10,000 tons of organic household wastes per year were compared. The comparison included life cycle assessments as well as economic considerations for different treating methods. Measurements on compost plants showed that methane emissions are higher than estimated so far. With the tools ECOINDICATOR and UBP anaerobic digestion shows to be advantageous as compared to composting, incineration or combination of digestion and composting, mainly because of a better energy balance. In fully enclosed, professional treatment plants, the specific biotechnological treatment costs are in the range of about 150.-sFr/ton for aerobic, anaerobic and combined technologies. It can be concluded, that anaerobic processes will become considerably more important in the future mainly for ecological reasons.


Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension.
The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy. Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients. A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic "paper-less" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet. Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs. The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.


A randomized controlled trial to determine the efficacy of a high carbohydrate and high protein ready-to-eat food product for weight loss.
Incorporating meal replacements has been shown to produce a significantly greater weight loss than a conventional reduced calorie diet. Ready-to-eat conventional foods may also be effective in this role and provide additional benefit because of their palatability, acceptance and enjoyment and thus increase dietary compliance. This trial investigated the efficacy of a ready-to-eat food product (Vita-Weat biscuit) that is both high in carbohydrate and high in protein as part of a diet prescription for weight loss in an overweight and obese population group. A total of 76 participants were randomized to a 6-week weight loss intervention including the ready-to-eat food product (intervention group) or advice on the 'Australian Guide to Healthy Eating' (control group). Both groups lost approximately 2 kg weight which equated to a reduction in body mass index of 0.70 kg m(-2) . There was no significant difference in percentage weight loss from screening to 6 weeks between the two groups; mean difference for the intervention vs. -0.20% (95% confidence interval: -0.96, 1.36); P = 0.73. Both diets were nutritionally matched and well-accepted over the 6-week period. This study shows that the inclusion of a ready-to-eat food product can be included as part of a dietary programme to achieve a clinically significant weight loss over a short period. This may have benefit when incorporated into an individual's meal plan intermittently to assist weight control. It also provides support for current public health nutritional guidelines as the participants in this study following such advice were also successful in achieving a clinically meaningful weight loss.


Monochromatic phototherapy in elderly patients: a new way of treating chronic pressure ulcers?
Monochromatic pulsating light may have effects of importance for wound healing, and promising results were obtained in an open study on the healing of pressure ulcers, which motivated the present study. One hundred and sixty-four in- and outpatients with grade II and III ulcers were treated with monochromatic pulsating light or placebo over the ulcerated area, according to a specific therapeutic program. No significant effects were observed in the total material. In a subanalysis of grade II ulcers, there was a tendency toward better healing in the monochromatic light group (p = 0.06). A significantly larger reduction in pressure ulcer size was noted among patients in the treatment group with low body weight (BMI < 20). Monochromatic pulsating light may have effects on pressure ulcer healing, and a new study focusing only on grade II ulcers is under way.


[Case of post-anoxic reticular reflex myoclonus].
Reticular reflex myoclonus is a rare condition with only a few cases clearly documented on video. The purpose of this paper is to report a patient manifesting typical clinical picture documented on video and characteristic electrophysiological features of reticular reflex myoclonus. A 60-year-old woman presented with spontaneous and stimulus-sensitive myoclonic jerks involving the face, neck and upper extremities following anoxic episode. The patient was investigated electrophysiologically. Surface electromyogram showed brief myoclonic activity starting from the sternocleidomastoid and spreading up to the orbicularis oculi as well as down to the upper limb muscles. Cortical somatosensory evoked potentials and long-latency reflex were not enhanced. Clinical features and electrophysiological findings of this case are consistent with those of reticular reflex myoclonus originally reported by Hallett et al. in 1977.


Creating your own leadership brand.
Building equity in a brand happens through many encounters. The initial attraction must be followed by the meeting of expectations. This creates a loyalty that is part of an emotional connection to that brand. This is the same process people go through when they first meet a leader and decide if this is a person they want to buy into. People will examine your style, your competence, and your standards. If you fail on any of these fronts, your ability to lead will be severely compromised. People expect more of leaders now, because they know and recognize good leaders. And, predictably, people are now more cynical of leaders because of the well-publicized excess of a few leaders who advanced their own causes at the expense of their people and their financial future. This will turn out to be a good thing, because it will create a higher standard of leadership that all must aspire to achieve. When the bar is raised for us, our standards of performance are also raised.


Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels.
The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments.


Purification human PON1Q192 and PON1R192 isoenzymes by hydrophobic interaction chromatography and investigation of the inhibition by metals.
In this study, a new purification strategy for human PON1 enzyme was developed using two-step procedures, namely ammonium sulfate precipitation and sepharose-4B-L-tyrosine-9-aminophenantrene hydrophobic interaction chromatography. SDS polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43kDa. Overall purification rate of our method was found 901-fold for R isoenzyme and 453-fold for Q isoenzyme. The V(max) and K(M) of the purified enzyme were determined for Q isoenzyme 55 EU and 0.599 mM and for R isoenzyme 50 EU and 0.492 mM, respectively. The in vitro effects of some heavy metals (Hg, Cd, Cu, Mn and Ni) were investigated on the purified human serum PON1Q and R isoenzyme, using paraoxon as substrate. Metals were more effective inhibitors on purified human serum PON1(R192) activity than PON1(Q192) activity. The kinetics of interaction of metals with the purified human serum PON1(R192) and PON1(Q192) indicated a different inhibition pattern. Kinetic constants K(M), V(max), and inhibition type were determined.


Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study.
To evaluate potential changes in cognitive functions over a 5-yr period in patients with systemic lupus erythematosus (SLE). Twenty-eight patients with SLE were examined at baseline and after a mean follow-up of 60.7+/-5.0 months using standardized neuropsychological tests. Group changes in performance over time were measured and the effects of baseline values for subsequent changes in individual variables after 5 yr were evaluated. When all SLE patients were considered as a group, seven out of nine (78%) neuropsychological variables remained unchanged and two (22%) improved significantly during the observation period, possibly due to methodological bias. Analysis of the importance of the level of initial cognitive performance for subsequent changes during the observation period, demonstrated that cognitive changes were not significantly influenced by baseline levels, except for a trend in three of nine variables. Neither demographic nor disease-associated quantitative factors were associated with cognitive changes over time. Cognitive dysfunction seems to be a relatively stable feature of central nervous system involvement in SLE. A decrease in performance over time was not demonstrated consistently in the majority of domains.


Prosopis juliflora--a green solution to decontaminate heavy metal (Cu and Cd) contaminated soils.
Soil and plant samples (root and shoot) of Prosopis juliflora were collected in the vicinity of metal based foundry units in Coimbatore and assessed for their heavy metal content (Cu and Cd) to ascertain the use of P. juliflora as a green solution to decontaminate soils contaminated with Cu and Cd. The results showed that Cu and Cd content was much higher in plant components compared to their extractable level in the soil. Furthermore, there exist a strong correlation between the distance of the sources of industrial units and accumulation of heavy metals in plants. Accumulation of Cd in roots is comparatively higher than that of shoots. However, in case of Cu no such clear trend is seen. Considering the accumulation efficiency and tolerance of P. juliflora to Cd and Cu, this plant can be explored further for the decontamination of metal polluted soils. On the other hand, in view of heavy metal accumulate the practice of providing foliage and pods as fodder for live stock should be avoided.


Mechanisms of general anesthesia.
Anesthetics influence a wide variety of transmitter- and voltage-gated ion channels in the mammalian central nervous system. At the molecular level, the gamma-aminobutyric acid (GABA) subtype A receptor has emerged as a primary therapeutic target. This review highlights recent advances in our understanding of how anesthetics modify GABA(A) receptor function. Anesthetics bind to discrete selective binding sites on GABA(A) receptors--a discovery that challenges lipid-based theories of anesthesia. Not all GABA(A) receptors are equally sensitive to anesthetics because positive allosteric modulation is critically dependent on receptor subunit composition. Moreover, GABA(A) receptors located in extrasynaptic regions of hippocampal neurons display a greater sensitivity to propofol and benzodiazepines than do receptors located in subsynaptic regions. Enhancement in GABAergic inhibition may not account for all of the behavioral end-points associated with the anesthetic state. In particular, the immobilizing properties of anesthetics may not be solely mediated by GABA(A) receptors. Finally, synthetic neurosteroids are being developed as improved general anesthetics. Detailed insights into anesthetic-GABA(A) receptor interactions have resulted in intense efforts to develop safer drugs that selectively target subtypes of GABA(A) receptors.


ESCMID* guideline for the diagnosis and management of Candida diseases 2012: developing European guidelines in clinical microbiology and infectious diseases.
The process to develop a guideline in a European setting remains a challenge. The ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour. After two face-to-face meetings, numerous telephone conferences, and email correspondence, an ESCMID task force (basically composed of members of the Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/therapeutic guideline for Candida diseases. By appreciating various patient populations at risk for Candida diseases, four subgroups were predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with malignancies including haematopoietic stem cell transplantation. Besides treatment recommendations, the ESCMID guidelines provide guidance for diagnostic procedures. For the guidelines, questions were formulated to phrase the intention of a given recommendation, for example, outcome. The recommendation was the clinical intervention, which was graded by a score of A-D for the 'Strength of a recommendation'. The 'level of evidence' received a score of I-III. The author panel was approved by ESCMID, European Organisation for Research and Treatment of Cancer, European Group for Blood and Marrow Transplantation, European Society of Intensive Care Medicine and the European Confederation of Medical Mycology. The guidelines followed the framework of GRADE and Appraisal of Guidelines, Research, and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of discussion occurring during that meeting were incorporated into the manuscripts. These ESCMID guidelines for the diagnosis and management of Candida diseases provide guidance for clinicians in their daily decision-making process.


[Long-term therapy of chronic schizophrenic patients with haloperidol decanoate].
Haloperidol decanoate injected every 4 weeks is a very important basic therapy for the treatment of chronic psychiatric patients. The results of this investigation compared to a long-term treatment with neuroleptic polytherapy showed a superior action of HDD monotherapy in chronic schizophrenia. The dosage schema can be adapted individually whenever necessary. Antiparkinson medication could be reduced and sometimes omitted.


Preparing for the return home. Discharge information following prostatectomy.
Effective patient education is required for sustained recovery following hospital discharge. This article describes how an information booklet was devised for men who have undergone transurethral prostatectomy, helping to prepare them to look after themselves at home.


Malabsorption and pouch ulcerations following the Martin repair for total colonic aganglionosis.
A late complication of the Martin repair for total colonic aganglionosis is described. Pouch malfunction resulted in stasis and ulceration, excessive blood and protein loss, and bacterial overgrowth of the small intestine. The severity and nature of the lesion was identified by colonoscopy.


Treponema denticola PurE Is a bacterial AIR carboxylase.
De novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N(5)-carboxy-AIR (N(5)-CAIR) synthetase (PurK) and N(5)-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE). The CAIR carboxylate derives from bicarbonate or CO(2), respectively. Class I PurE is a promising antimicrobial target. Class I and class II PurEs are mechanistically related but bind different substrates. The spirochete dental pathogen Treponema denticola lacks a purK gene and contains a class II purE gene, the hallmarks of CO(2)-dependent CAIR synthesis. We demonstrate that T. denticola PurE (TdPurE) is AIR carboxylase, the first example of a prokaryotic class II PurE. Steady-state and pre-steady-state experiments show that TdPurE binds AIR and CO(2) but not N(5)-CAIR. Crystal structures of TdPurE alone and in complex with AIR show a conformational change in the key active site His40 residue that is not observed for class I PurEs. A contact between the AIR phosphate and a differentially conserved residue (TdPurE Lys41) enforces different AIR conformations in each PurE class. As a consequence, the TdPurE·AIR complex contains a portal that appears to allow the CO(2) substrate to enter the active site. In the human pathogen T. denticola, purine biosynthesis should depend on available CO(2) levels. Because spirochetes lack carbonic anhydrase, the corresponding reduction in bicarbonate demand may confer a selective advantage.


Induction of autophagy in human neuroblastoma SH-SY5Y cells by tri-ortho-cresyl phosphate.
Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester and has been widely used in industry. It is found that TOCP induced delayed neurotoxicity in humans and sensitive animal species. However, the mechanism of TOCP-induced neural cytotoxicity remains unclear. In this study, we studied whether autophagy is involved in TOCP-induced neural cytotoxicity in human neuroblastoma SH-SY5Y cells. We found that 0.5 and 1.0 mM TOCP treatment significantly increased the ectopic accumulation of microtubule-associated protein 1 light chain 3 (LC3)-immunopositive puncta, Beclin 1, and LC3-II/LC3-I levels in SH-SY5Y cells in a dose-dependent manner. Notably, by monodansylcadaverine staining method, we found abundant punctate fluorescent acidic vesicular organelles in TOCP-treated cells. Furthermore, ultrastructural observation under the transmission electron microscope indicated that the cytoplasm was occupied by autophagosomes in TOCP-treated SH-SY5Y cells. Thus, these results suggest that TOCP may induce autophagy, and autophagy may be involved in the development of TOCP-induced neural cytotoxicity.


All six modules of the gelatin-binding domain of fibronectin are required for full affinity.
The gelatin-binding sites of fibronectin are confined to a 42-kDa region having four type I and two type II modules in the following order: I(6)-II(1)-II(2)-I(7)-I(8)-I(9). To determine the relative importance of each module for recognition of gelatin, recombinant green fluorescent fusion proteins were prepared in which individual modules or groups of modules were deleted, and the resulting proteins were tested for binding to gelatin by analytical affinity chromatography. Deletion of both type II modules did not eliminate binding, confirming that at least some of the type I modules in this region are able to bind gelatin. It was found that deletion of type I module 6 tends to increase the affinity, whereas deletion of any other module decreases it. Deletion of module I(9) had a large effect but only if module II(2) was also present, suggesting an interaction between these two noncontiguous modules. Analysis of more than 20 recombinant fusion products led to the conclusion that all modules contribute to the interaction either directly by contacting the ligand or indirectly through module-module interactions.


Agreement Between Autorefraction and Subjective Refraction in Keraring-Implanted Keratoconic Eyes.
To assess the agreement between subjective refraction and autorefraction and to explore the relationship between the magnitude of higher order aberration, and visual acuity and refraction, before and after keraring implantation. This prospective, randomized, interventional study enrolled 27 subjects (mean age 28.1±6.5 years) with keratoconus. Noncycloplegic refraction was performed subjectively by one clinician and with an autorefractor by another clinician, before and 6 months after surgery. The limit of agreement (LoA) between methods was assessed, and the relationships between the corrected distance visual acuity, logMAR on the one hand and refraction measurements and higher-order aberrations on the other, were examined. The agreement in mean spherical equivalent refraction (MSER) between methods was good postoperatively but poor preoperatively. The autorefractor gave a more myopic refraction than subjective refraction preoperatively (-3.28±3.06 D; LoA -9.27 to +2.71 D, P<0.0001) and postoperatively (-0.63±1.64 D; LoA -3.85 to +2.58 D, P=0.055), and returned higher negative cylinders preoperatively (-1.10±1.17 D; LoA -3.40 to +1.19 D, P<0.0001) and postoperatively (-1.08±1.27 D; LoA -3.60 to +1.41 D, P<0.0001) in keratoconic eyes. The difference in MSER between methods was significantly related to the refractive error at both visits (P<0.05) and to the magnitude of higher-order aberrations in keratoconic eyes preoperatively (P<0.05). The logMAR visual acuity achieved subjectively worsened as the magnitude of higher-order aberrations increased preoperatively (P<0.001). The autorefractor returns values that are significantly more myopic in MSER and higher negative cylinders than subjective refraction, preoperatively, but the MSER was similar between devices postoperatively. The autorefactor seems a valid starting point for subjective refraction in keratoconic eyes treated with keraring, but the cylinder should be corrected by about +1 D. The instruments agree more in less myopic than high myopic eyes.


Electrocardiographic features of inherited diseases that predispose to the development of cardiac arrhythmias, long QT syndrome, arrhythmogenic right ventricular cardiomyopathy/dysplasia, and Brugada syndrome.
Analysis of the 12-lead electrocardiogram (ECG) provides important diagnostic and prognostic information in the long QT syndrome. The clinical diagnosis of long QT syndrome is determined by the presence of a QTc > or = 0.44 sec. A normal QTc does not exclude a family member from being a genetic carrier. The ECG patterns of depolarization, the ST segment and shape of the T-wave can provide important clues as to the affected gene, particularly in conjunction with clinical information as to the precipitating causes of syncope or cardiac events. In arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), the typical ECG pattern consists of T-wave inversion beyond lead V1. Evidence of right ventricular parietal block is manifest by a QRS duration in V1 > or = 110 msec and a longer QRS duration in the right then left precordial leads. Evidence of slow fractionated conduction is present as epsilon waves. The signal averaged ECG may show exceedingly long and low late potentials. Information regarding the risk of sudden death may also be obtained from the ECG. The ECG changes alone or in combination can provide strong evidence for the diagnosis of ARVC/D and helps to differentiate ARVC/D from right ventricular outflow tract (RVOT) tachycardia. The typical pattern of the ECG in the Brugada syndrome is ST segment elevation in the right precordial leads. This abnormality can be dormant and elicited by administration of drugs that cause Na channel blockade, such as ajmaline or type 1a or 1C antiarrhythmic drugs. Individuals who do not have the Brugada ECG findings at baseline but have this pattern induced by antiarrhythmic drugs are also at risk for sudden death. Further risk stratification may be obtained in the asymptomatic patients if ventricular fibrillation is induced at electrophysiological study.


Differential expression and cell envelope incorporation of small proline-rich protein 1 in different cornified epithelia.
In the final stages of terminal differentiation in the epidermis and other squamous epithelia, a approximately 15 nm thick protein layer called the cornified cell envelope (CE) assembles on the keratinocytes' inner surface. Its constituent proteins are covalently crosslinked by the action of transglutaminases. Recent studies have indicated that the expression of CE precursor proteins may vary in different tissues. To investigate such variations further, we have studied the CEs of two different keratinizing epithelia of mouse: epidermis and forestomach, with particular focus on their contents of loricrin and the small proline-rich proteins (SPRs). To this end, we have applied electron microscopic immunocytochemistry and estimated the CE protein compositions by mathematical modeling of their amino acid compositions. Ultrastructurally, forestomach resembles the epidermis in having well defined cornified and granular layers. Minor but significant differences are: in forestomach, striated material resembling lamellar granules is intercalated between the cornified squames; and in forestomach granular layer cells, loricrin-containing L-granules are more abundant, and filaggrin-containing F-granules less abundant than in epidermis. In forestomach, dense labeling with anti-SPR1 antibody was observed at the margin of cornified layer cells; and in the granular layer, diffuse but positive labeling of both cytoplasm and nucleus. In contrast, epidermis was uniformly negative. Isolated forestomach CEs (but not epidermal CEs), labeled positively on the cytoplasmic side, consistent with the presence of covalently crosslinked SPR1. Our compositional analysis predicts the content of loricrin in forestomach CEs to be very high (approximately 65%), as in the epidermis, and accompanied by approximately 18% content of total SPRs. Of these, a substantial proportion should be SPR1, according to our immunolabeling data. In contrast, epidermal CEs are calculated to have a much lower amount of SPRs or SPR-like proteins (approximately 8%), with a negligible content of SPR1. Thus both kinds of CEs have loricrin as their major constituent but differ in their respective complements of SPRs, which are thought to inter-connect loricrin molecules in the final phase of CE assembly. Applying a basic concept of materials science, it may be that the observed differences in their SPR contents reflect differences in the mechanical and chemical properties required for the function of the respective CEs.


Survey and evaluation methods: smoking prevention among children and adolescents.
Past behavioral research on the special characteristics of tobacco smoking among children and adolescents is fraught with definitional ambiguities. More precise benchmarks of these age groups will facilitate mutually advantageous investigations. Researchers ought to agree on their target age cohorts. Too, investigators should account for the peculiar tobacco smoking patterns of children and adolescents who are research subjects. Finally, researchers should reach a consensus on how they categorize various kinds of young nonsmokers, smokers, and exsmokers. Recommendations put forth here are an attempt toward common parameters for researching tobacco use among American children and adolescents.


Do Calcium Supplements Predispose to Urolithiasis?
The purpose of this study was to investigate the role of calcium supplements, with or without vitamin D, in urinary stone formation in healthy population and in osteoporotic patients as well. Moreover, this review aims to clarify whether or not, and above which dose, they are associated with the risk of lithiasis. A research in Medline, Embase, and Scopus databases up to September 2015 was conducted using the following keywords: calcium, supplements, vitamin D, complications, lithiasis, and urinary stone. All types of studies were taken into account (cohort studies, reviews, meta-analyses), and in case they fulfilled the inclusion criteria, they were included in our review. The analysis of the data showed that calcium supplements, probably in association with anti osteoporotic treatment, do not create a predisposition towards lithiasis formation among women suffering from osteoporosis, neither among non-osteoporotic older men. In healthy postmenopausal as well as younger women, the supplements might increase susceptibility to urinary stone formation in long-term basis. The consumption of calcium supplements with the meals could play a protective role in women and younger males. There is certain evidence that supplements containing citrate may be more beneficial over the rest of calcium supplements, particularly when consumed during the meal. Osteoporotic women and healthy men are not at risk of stone formation. On the contrary, healthy women should be aware of the potential risk of developing urinary lithiasis in long-term basis.


Lipopolysaccharide enhances oxidative modification of low density lipoprotein by copper ions, endothelial and smooth muscle cells.
The effect of lipopolysaccharide (LPS, endotoxin) on low density lipoprotein (LDL) oxidative modification by copper ions, endothelial and smooth muscle cells was studied by determination of the level of lipid peroxidation products (thiobarbituric acid reactive substances or TBARS), the diene level and the electrophoretic mobility of the LDL particle. LPS 25-75 microg/ml induced a dose-dependent increase in LDL oxidation by copper ions, endothelial and smooth muscle cells. At 75 microg LPS/ml, the TBARS content was 1.9, 1.6, and 1.8-fold increased, respectively. The LDL degradation by J774 macrophage-like cells was concomitantly stimulated. Preincubation of the LDL particle with LPS induced a marked increase in the subsequent LDL oxidative modification either by copper ions or by endothelial and smooth muscle cells. In addition, pretreatment of endothelial and smooth muscle cells with LPS also induced an enhancement of LDL oxidative modification performed in the absence of LPS. This effect was accompanied by a parallel increase in superoxide anion release by the cells. These results point at one of the mechanisms involved in the described association between bacterial infection and acute myocardial infarction as well as coronary heart disease.


[Ultrasound-guided Truncal Block for Abdominal Surgery: Present and Future Perspectives].
Patients undergoing abdominal surgery can experi- ence severe pain due to the abdominal wall incision. Epidural anesthesia has been considered as the gold standard for perioperative analgesia in abdominal sur- gery. However, currently, many patients receive pro- phylactic anticoagulation therapy preoperatively with potential complications. For such cases, while epidural anesthesia is contraindicated, the use of ultrasound- guided peripheral nerve block is increasing. In abdomi- nal surgery, ultrasound-guided rectus sheath block and transversus abdominis plane block are commonly used for perioperative analgesia. The use of ultrasound ren- ders these block techniques safe and reliable. Cur- rently, a new abdominal peripheral nerve block, qua- dratus lumborum block, is gaining attention because it is thought to have a wider range of analgesia and a longer duration of effect As the analgesic properties of these blocks are limited in extent and duration, it is important to select the appropriate approach. Ultrasound-guided abdominal trunk block can con- tribute to perioperative multimodal analgesia.


Iodine-deficiency disorders.
2 billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficiency disorders. Iodine deficiency is the most common cause of preventable mental impairment worldwide. Assessment methods include urinary iodine concentration, goitre, newborn thyroid-stimulating hormone, and blood thyroglobulin. In nearly all countries, the best strategy to control iodine deficiency is iodisation of salt, which is one of the most cost-effective ways to contribute to economic and social development. When iodisation of salt is not possible, iodine supplements can be given to susceptible groups. Introduction of iodised salt to regions of chronic iodine-deficiency disorders might transiently increase the proportion of thyroid disorders, but overall the small risks of iodine excess are far outweighed by the substantial risks of iodine deficiency. International efforts to control iodine-deficiency disorders are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges.


Impaired apoptosis in lymphoblasts from Alzheimer's disease patients: cross-talk of Ca2+/calmodulin and ERK1/2 signaling pathways.
We have analyzed the intracellular signals that allow lymphoblasts from Alzheimer's disease (AD) patients to escape from serum deprivation-induced apoptosis. The following observations suggested that modulation of ERK1/2 activity by Ca(2+)/calmodulin (CaM) is involved in preventing apoptosis: (i) ERK1/2 activity seems to support lethality in control cells, as PD98059, the inhibitor of the activating MEK prevented cell death; (ii) control cells show a persistent and higher stimulation of ERK1/2 than that of AD cells in the absence of serum; (iii) CaM antagonists have no effects on control cells, but sensitize AD cells to death induced by serum withdrawal and increased ERK1/2 phosphorylation, and (iv) no apoptotic effects of CaM antagonists were observed in AD cells treated with PD98059. These results suggest the existence of an activation threshold of the ERK1/2 pathway setting by Ca(2+)/CaM-dependent mechanisms, which appears to be the critical factor controlling cell survival or death decision under trophic factor withdrawal.


Aneurysmal dilatation of a patent umbilical vein masquerading as a pancreatic pseudocyst: CT characteristics.
A large cystic mass in a jaundiced patient had the appearance by sonography of a pancreatic pseudocyst. Computed tomography showed that the mass represented an aneurysmally dilated patent umbilical vein.


Technical modifications for laparoscopic cholecystectomy by the left-handed surgeon.
There is a complete paucity of literature for left-handed surgeons. Some studies revealed that left-handed surgical residents have lesser operating skills and some surgeons have considered leaving surgery at some point in their career owing to laterality-related frustrations. Most important, whereas minimally invasive surgical techniques have had a profound impact on the treatment of diseased gallbladder, these procedures do not eliminate laterality related to the discomfort of left-handed surgeons. Usually, left-handed surgeons must teach themselves a procedure. They must make modifications and learn some technical tips to make a more comfortable, convenient, and safe intervention. The aim of this study was to describe some modifications made by a left-handed surgeon to perform 52 safe laparoscopic cholecystectomies with standard right-handed instruments in our hospital. These surgical steps could be used in a reproducible way to minimize the recurring difficulties of left-handed learners in a surgical residency program.


Real-Time Cardiopulmonary Resuscitation Feedback and Targeted Training Improve Chest Compression Performance in a Cohort of International Healthcare Providers.
Optimal cardiopulmonary resuscitation (CPR) performance is the foundation of successful cardiac arrest resuscitation. However, health care providers perform inadequate compressions. Better training techniques and real-time CPR feedback may improve compression performance. We sought to evaluate the impact of a targeted training program combined with real-time defibrillator CPR feedback on chest compression performance in an international cohort of health care providers. Physicians, nurses, respiratory therapists, and technicians from 6 hospitals in 5 countries (Taiwan, Singapore, China, Bahrain, and Kuwait) participated in a standardized resuscitation workshop. Chest compression was measured before and after didactics and activation of CPR feedback. Compressions were performed for 1 min on standard CPR manikins placed on a hospital bed and backboard and measured using ZOLL R Series defibrillators. The percentage of compressions meeting target values for depth and rate were compared before and after the workshop and activation of real-time CPR feedback. No depth maximum was defined to allow for mattress compression. Chest compressions were more likely to meet targets for depth (71-95%, odds ratio [OR] 8.61 [95% confidence interval {CI} 4.42-16.77], p < 0.001), rate (41-81%, OR 6.4 [95% CI 4.2-9.8], p < 0.001), and both depth and rate (5-42%, OR 2.4 [95% CI 6.7-22.9], p < 0.001) after the workshop and activation of real-time CPR feedback. A targeted training intervention combined with real-time CPR feedback improved chest compression performance among health care providers from various countries.


In Vitro and In Vivo Evaluation of a nHA/PA66 Composite Membrane for Guided Bone Regeneration.
A nano-hydroxyapatite/polyamide 66 (nHA/PA66) composite with good bioactivity and osteoconductivity is employed to develop a novel porous membrane with an asymmetric structure. In order to investigate the biocompatibility and the effect on guided bone regeneration (GBR) of nHA/PA66 porous membrane, the proliferation, viability, morphology and alkaline phosphatase activity (ALP) of the osteoblast-like cell line (MG63) cultured on the membrane were studied in vitro. In vivo biocompatibility and osteogenesis of the fabricated membrane were assessed by comparing guiding rats calvarial bone defects regeneration with "gold standard" GBR material, expanded polytetrafluoroethylene (e-PTFE) membrane. In vitro experiments showed that the nHA/PA66 composite membrane had good cell affinity and cytocompatibility, in favor of cell proliferation. The in vivo study showed that the nHA/PA66 asymmetric porous membrane had a good GBR effect. All the results indicate that the asymmetric porous nHA/PA66 composite GBR membrane with good biocompatibility, high bioactivity and osteoconductivity exhibits good GBR effect and has a potential to be applied in GBR fields, especially in dental tissue regeneration.


Large conductance calcium-activated potassium channels: their expression and modulation of glutamate release from nerve terminals isolated from rat trigeminal caudal nucleus and cerebral cortex.
Large conductance, calcium-activated potassium channels [big potassium (BK) channel] consist of a tetramer of pore-forming α-subunit and distinct accessory β-subunits (β1-4) that modify the channel's properties. In this study, we analyzed the effects of BK channel activators and blockers on glutamate and γ-aminobutyric acid (GABA) release from synaptosomes isolated from the cerebral cortices or trigeminal caudal nuclei (TCN) of rats. Real-time polymerase chain reaction was used to characterize BK channel α and β(1-4) subunit expression in the cortex and in the trigeminal ganglia (TG), whose neurons project primary terminal afferents into the TCN. Immunocytochemistry was used to localize these subunits on cortical and TCN synaptosomes. The BK channels regulating [(3)H]D-aspartate release from primary afferent nerve terminals projecting into the TCN displayed limited sensitivity to iberiotoxin, whereas those expressed on cortical synaptosomes were highly sensitive to this toxin. BK channels did not appear to be present on GABAergic nerve terminals from the TCN since [(3)H]-γ-aminobutyric acid release in this model was unaffected by BK channel activators or blockers. Gene expression studies revealed expression levels of the α subunit in the TG that were only 31.2 ± 2.1% of those found in cortical tissues. The β4 subunit was the accessory subunit expressed most abundantly in both the cortex and TG. Levels of β1 and β2 were low in both these areas although β2 expression in the TG was higher than that found in the cortex. Immunocytochemistry experiments showed that co-localization of α and β4 subunits (the accessory subunit most abundantly expressed in both brain areas) was more common in TCN synaptosomes than in cortical synaptosomes. On the basis of these findings, it is reasonable to hypothesize that BK channels expressed on glutamatergic terminals in the TCN and cortex have distinct pharmacological profiles, which probably reflect different α and β subunit combinations. Channels in the cortex seem to be composed mainly of α subunits and to a lesser degree by α and β4 subunits, whereas in the TG the α + β4 combination seems to prevail (although α and/or α + β2 channels cannot be excluded). In light of the BK channels' selective control of excitatory transmission and their pharmacological diversity, their effects on primary glutamatergic afferents projecting to TCN represent a potential target for drug therapy of migraines and other types of orofacial pain.


Emotional intelligence: growing your self-regard.
This column focuses on one of the most important competencies in emotional intelligence--self-regard.


[Fetal plasma erythropoietin concentration during intrauterine transfusion therapy in isoimmunohemolytic anemia due to rhesus incompatibility].
Prenatal plasma concentrations of erythropoietin in fetuses with Rh disease should contribute information to the clinical course and therapeutic control of this disease. Fetal plasma erythropoietin (Epo) and haemoglobin (Hb) concentrations were measured in 145 umbilical venous blood samples of 30 fetuses with Rh disease at 20 to 38 weeks' gestation. Both Epo and Hb concentrations were independent of the gestational age in red blood cell-isoimmunised pregnancies. The Hb concentration correlated significantly with Epo concentration without intrauterine transfusion (IUT) (r = -0.519, p = 0.005) and after IUT (i = -0.212, p = 0.01). A haemoglobin deficit of 3 g/dl at 20 weeks' gestation increased to 6 g/dl at 38 weeks' gestation in spite of IUT (p = -0.354, p < 0.001). Even with IUT, Epo concentrations increase with gestational age during these pregnancies. This is due to increasing Hb deficits indicating fetal hypoxia which might be prevented by increasing volumes of transfusion.


Characterization of the clathrin heavy chain from Dictyostelium discoideum.
We report the cloning and analysis of a clathrin heavy-chain cDNA from the eukaryotic microorganism, Dictyostelium discoideum. A single gene, designated chcA, for the clathrin heavy chain encoded a protein of 1,694 amino acids with a molecular mass of 193,618 daltons. Comparison of the amino acid sequence with the rat and with the yeast sequence showed that the highly conserved protein was more similar to the mammalian clathrin heavy chain (57% identity) than to the yeast heavy chain (45% identity). The mRNA for the clathrin heavy chain was regulated during development. mRNA levels were highest during vegetative growth and declined as the cells progressed through the 24-hr developmental cycle. The concentration of clathrin heavy-chain protein was the same in cells grown in liquid media (high rates of pinocytosis) as in cells grown with bacteria (low rates of pinocytosis), which suggests that regulation of pinocytosis in these cells is not achieved by altering the concentration of clathrin.


Experimental pathogenicity of a clinical isolate of Trichosporon dermatis in a murine model.
The pathogenicity of Trichosporon dermatis isolated from skin lesions of a patient has been examined in mice. Balb/c mice were treated with two intraperitoneal injections of 100 mg/kg cyclophosphamide on days 4 and 1 and one subcutaneous injection of 10 mg/kg dexamethasone on day 1 pre-inoculation, and then challenged with 0.2 ml T. dermatis inoculum (1 × 10(8) CFU/ml) by topical application on an abrasive wound in the dermabrasive group and by hypodermic injection in the subcutaneous group. In the intravenous group, 0.2 ml of high (1 × 10(8) CFU/ml) or low (1 × 10(7 )CFU/ml) inoculum was injected into the tail vein. Histopathology and inverse fungal culture were performed on the skin lesion and viscera, and renal fungal burden was also determined. Inoculated sites developed localized infections after dermabrasive and subcutaneous challenge in all mice, but the maximum area of skin lesions, and number of positive cultures from the lesions, were higher for immunocompromised mice. In the intravenous group, all immunocompetent animals survived during the four-week period, whereas 100 and 70% of immunocompromised animals died by 3 and 5 days in the high and low-inoculum groups, respectively. The incidence of disseminated infection and the renal fungal burden of immunocompromised mice were higher than those of immunocompetent mice. Our results demonstrate that subcutaneous and intravenous injection of T. dermatis can successfully establish cutaneous and systemic infection models in immunocompromised mice, with the kidney and lung being most susceptible.


A logistic dose-ranging method for phase I clinical investigations trials.
This paper describes an alternative to the continual reassessment method (CRM) for phase I trials. The logistic dose ranging strategy (LDRS) uses logistic regression and a dose allocation scheme similar to the CRM. It can easily be implemented from any logistic regression program. The LDRS can be a stand alone dose allocation scheme or it can be incorporated into standard three on a dose strategies to indicate when escalation can proceed more rapidly. Finally, the effect of covariates such as age or comorbid conditions on the toxicity expected for the dose selected for a phase II trial can be examined.


A statistical approach for optimization of polyhydroxybutyrate production by marine Bacillus subtilis MSBN17.
The important biological macromolecule polyhydroxybutyrate (PHB) producing Bacillus subtilis was isolated from the marine sponge Callyspongia diffusa and identified by means of 16S rRNA analysis. The central composite design (CCD) was used to optimize the PHB production using cheap raw materials such as pulp industry waste (PIW), tamarind kernel powder (TKP), palm jaggery (PJ) and green gram flour (GGF). The extracted polymer was characterized by (1)H NMR analysis. The PIW was fed at three different intervals and the maximum production of PHB (19.08g/L) was attained after a period of 40h of incubation of B. subtilis. Dissolved oxygen, sodium chloride and nitrogen source were found to be the critical control factors that affected the PHB polymer production. The present investigation demonstrates an inexpensive model of producing PHB green thermoplastics in vitro for biomedical applications.


Preserved pelvic circulation after stent-graft treatment of complex aortoiliac artery aneurysms: a new approach.
To describe an endovascular technique that allows stent-graft treatment of aortoiliac aneurysmal disease affecting both common iliac arteries (CIA), with maintenance of pelvic circulation on one side. For patients with aortoiliac aneurysms, both common femoral arteries (CFA) were surgically exposed. One internal iliac artery (IIA) was initially embolized with coils. A bifurcated stent-graft main body was deployed with the proximal end just below the renal arteries. On the ipsilateral side, the stent-graft limb was extended 3 cm beyond the orifice of the embolized IIA into the external iliac artery (EIA) using stent-graft limb extenders. On the contralateral side, the stent-graft limb was deployed so that the distal end was 10 to 15 mm proximal to the patent IIA orifice. Via a left brachial artery access, the IIA was catheterized, and stent-grafts were deployed from the distal end of the contralateral AAA stent-graft limb into the IIA. A femorofemoral crossover graft provided circulation to the leg ipsilateral to the IIA stent-graft, and the EIA on the same side was ligated. The technique can also be modified to treat isolated bilateral CIA aneurysms. By extending the distal aspect of the stent-graft into an IIA, bilateral CIA aneurysms can be excluded while preserving pelvic circulation on one side.


Multiresolution decomposition of non-stationary EEG signals: a preliminary study.
Wavelet representation is a recent development in the analysis of non-stationary signals. Its possibilities for use in the description of time-frequency characteristics of both transients in spontaneous EEG and time-varying rhythms in event related brain activity are explored here. By way of illustration, multiresolution decompositions of a wide variety of EEG transients are carried out in this work, including spike-and-waves, single spikes, sharp waves, blink artifacts, frontal intermittent rhythmic delta activity (FIRDA) and paroxysmal delta activity. Also, the application of the wavelet representation to study related spectra perturbations is illustrated with data from psychophysical experiments on the perception of image motion. The results demonstrate the capabilities of the wavelet transform, as an alternative to the Fourier transform, for the representation and analysis of non-stationary EEG signals.


Carbon banks: an efficient means to exchange sequestered carbon.
Carbon sequestration is one of the options that can be used to reduce atmospheric carbon, but its use in an offset market is complicated by the temporary nature of sequestered carbon and the risks associated with carbon release and price. In this paper a carbon bank is proposed to handle these problems. The bank is both an aggregator and a risk bearer. Sink generators deposit their credits with the bank and are paid for maintaining their "savings" with the bank. The carbon bank is also the source where large-scale emitters can come and buy either a temporary or permanent credit and pay the bank in return for the credit and services provided. The advantages of the bank over alternative institutional designs include lower transaction costs, flexible carbon credits and price, and lower risk to risk-averse parties. The carbon bank could be an effective means to deal with many of the unresolved issues within the forthcoming Canadian offset system.


Clinical efficacy and tolerability of Xeomin in the treatment of blepharospasm.
Blepharospasm is classified as a focal dystonia, and botulinum toxin type A (BoNT/A) has been shown to be a highly effective and well-tolerated symptomatic treatment. Xeomin, the latest addition to BoNT/A preparations, is a purified, freeze-dried BoNT/A that is free from complexing proteins. In a double-blind, parallel-group, multicentre study, 300 patients with blepharospasm received either Xeomin or Botox 15-80 U (J Neural Transm 2006; 113: 303). Both treatments produced statistically significant improvements from baseline in the Jankovic Rating Scale at week 3 (primary efficacy variable; Xeomin: -2.90; Botox: -2.67; P < 0.0001 from baseline for both), with the difference between treatments (-0.23) indicating that Xeomin was clinically non-inferior to Botox. No significant differences were found between Xeomin and Botox for all secondary variables. There were no clinically relevant differences between Xeomin and Botox in safety parameters, with 40 of 148 patients (27.0%) treated with Xeomin reporting adverse events versus 45 of 155 patients (29.0%) treated with Botox. The most common adverse event was ptosis (6.1% Xeomin and 4.5% Botox). Clinical evidence to date suggests that Xeomin is an effective treatment for blepharospasm that does not differ from Botox in terms of its potency, duration of effect or adverse reaction profile.


Light and electron microscopic studies on Myxobolus cotti el-Matbouli and Hoffmann, 1987 infecting the central nervous system of the bullhead (Cottus gobio).
Myxobolus cotti (Myxozoa: Myxosporea) is described as found in the central nervous system of the bullhead (Cottus gobio) caught in the Alpine lake Königssee and in a brook in the Bavarian Forest, Federal Republic of Germany (El-Matbouli and Hoffmann 1987). Aggregations of spores and polysporoblastic trophozoites compressed and replaced large areas of the white and grey matter of the brain and spinal cord. These aggregations may be surrounded by a thin, connective tissue capsule; in a few cases they were associated with loose infiltrates of glial cells. Neither conspicuous tissue reactions nor inflammatory responses were evident. No other organs were seen to be infected with M. cotti. Mature spores are oval, with a tapering anterior end, and the pyriform polar capsules are nearly equal in size. Fresh spores measured 8.9-15.1 microns in length (mean, 12.4 microns) and 8-12.4 microns in width (mean, 9.6 microns); polar capsules were 4.3-9 microns long (mean, 6.4 microns) and 2-3.8 microns wide (mean, 2.9 microns). Light microscopy, the ultrastructure of pansporoblasts, sporogenesis and mature spores are described.