Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy.

The BUN and FASTER studies, two prospective multicenter trials in the United States, validated the accuracy and detection rates of first and second trimester screening previously reported abroad. These studies, coupled with the 2007 release of the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin that endorsed first trimester screening as an alternative to traditional second trimester multiple marker screening, led to an explosion of screening options available to pregnant women. ACOG also recommended that invasive diagnostic testing for chromosome aneuploidy be made available to all women regardless of maternal age. More recently, another option known as Non-invasive Prenatal Testing (NIPT) became available to screen for chromosome aneuploidy. While screening and testing options may be limited due to a variety of factors, healthcare providers need to be aware of the options in their area in order to provide their patients with accurate and reliable information. If not presented clearly, patients may feel overwhelmed at the number of choices available. The following guideline includes recommendations for healthcare providers regarding which screening or diagnostic test should be offered based on availability, insurance coverage, and timing of a patient's entry into prenatal care, as well as a triage assessment so that a general process can be adapted to unique situations.

A line scanning confocal fluorescent microscope using a CMOS rolling shutter as an adjustable aperture.

Traditional confocal microscopy uses a physical aperture barrier to prevent out-of-focus light from reaching the detector. The physical nature of a conventional aperture limits control over the system confocality. We describe a new line scanning confocal microscope that eliminates a need for a physical aperture by employing a software-controllable rolling shutter on a CMOS camera. A confocal image is obtained by synchronizing motion of the rolling shutter and the laser line scanning over a sample. Confocal resolution of this microscope is adjustable in real time and independently established for each fluorescence channel by changing the rolling shutter width. This technology has been implemented in the IN Cell Analyzer 6000 system by GE Healthcare.

Accidental discharge of brodifacoum baits into a freshwater lake: a case study.

Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of brodifacoum bait for an aerial baiting operation. In the month after the spill no residual brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.

A comparison of the National Center for Health Statistics and new World Health Organization growth references for school-age children and adolescents with the use of data from 11 low-income countries.

BACKGROUND: In 2007 new World Health Organization (WHO) growth references for children aged 5-19 y were introduced to replace the National Center for Health Statistics (NCHS) references. OBJECTIVE: This study aimed to compare the prevalence of stunting, wasting, and thinness estimated by the NCHS and WHO growth references. DESIGN: NCHS and WHO height-for-age z scores were calculated with the use of cross-sectional data from 20,605 schoolchildren aged 5-17 y in 11 low-income countries. The differences in the percentage of stunted children were estimated for each year of age and sex. The z scores of body mass index-for-age and weight-for-height were calculated with the use of the WHO and NCHS references, respectively, to compare differences in the prevalence of thinness and wasting. RESULTS: No systematic differences in mean z scores of height-for-age were observed between the WHO and NCHS growth references. However, z scores of height-for-age varied by sex and age, particularly during early adolescence. In children for whom weight-for-height could be calculated, the estimated prevalence of thinness (WHO reference) was consistently higher than the prevalence of wasting (NCHS reference) by as much as 9% in girls and 18% in boys. CONCLUSIONS: In undernourished populations, the application of the WHO (2007) references may result in differences in the prevalence of stunting for each sex compared with results shown when the NCHS references are used as well as a higher estimated prevalence of thinness than of wasting. An awareness of these differences is important for comparative studies or the evaluation of programs. For school-age children and adolescents across all ranges of anthropometric status, the same growth references should be applied when such studies are undertaken.

Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer.

OBJECTIVES: To evaluate the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate. METHODS: Patients (n = 269) were randomized to receive open-label abarelix 100 mg or leuprolide acetate 7.5 mg by intramuscular injection. The results of the first 84 days of the study are reported. The primary efficacy endpoints included avoidance of testosterone surge, castration on day 8, and achievement and maintenance of castration from days 29 through 85. The secondary endpoints included castration on days 2, 4, and 15; a reduction in prostate-specific antigen level; and measurements of other hormones. Patients were monitored for clinical adverse events and laboratory abnormalities. RESULTS: No men in the abarelix group and 82% of men in the leuprolide acetate group experienced a testosterone surge (P <0.001). Abarelix caused rapid medical castration: 24% of men 1 day after treatment and 78% after 7 days compared with 0% of men treated with leuprolide acetate on either day. A comparable percentage of men achieved and maintained castration between days 29 and 85 in each group. Prostate-specific antigen had a statistically significant decrease for the first month in patients treated with abarelix. Dihydrotestosterone, luteinizing hormone, prostate-specific antigen, and follicle-stimulating hormone showed similar rapid reductions without an initial increase. The overall occurrence of adverse events was similar across the treatment groups, and most were sequelae of comorbid disorders. CONCLUSIONS: Treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, luteinizing hormone, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.

Use of situational judgment tests to predict job performance: a clarification of the literature.

Although situational judgment tests have a long history in the psychological assessment literature and continue to be frequently used in employment contexts, there has been virtually no summarization of this literature. The purpose of this article is to review the history of such tests and present the results of a meta-analysis on criterion-related and construct validity. On the basis of 102 coefficients and 10,640 people, situational judgment tests showed useful levels of validity (rho = .34) that were generalizable. A review of 79 correlations between situational judgment tests and general cognitive ability involving 16,984 people indicated that situational judgment tests typically evidence relationships with cognitive ability (rho = .46). On the basis of the literature review and meta-analytic findings, implications for the continued use of situational judgment tests are discussed, particularly in terms of recent investigations into tacit knowledge.

The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: initial results of endocrinological and biochemical efficacies in patients with prostate cancer.

PURPOSE: We contrasted the endocrinological and biochemical efficacies of abarelix depot, a pure gonadotropin-releasing hormone antagonist, with a prospective concurrent control cohort receiving luteinizing hormone releasing hormone (LH-RH) agonists with or without antiandrogen for treatment of patients with prostate cancer receiving initial hormonal therapy. MATERIALS AND METHODS: In this phase 2 open label study 242 patients with prostate cancer requiring initial hormonal treatment received abarelix depot (209) or LH-RH agonists (33) with or without antiandrogen. A total of 100 mg. abarelix depot was delivered intramuscularly every 28 days with an additional injection on day 15. LH-RH agonists with or without antiandrogen were administered according to the depot formulation used. Endocrine efficacy was measured by the absence of testosterone surge and rapidity of castration onset. The rate of prostate specific antigen decrease was assessed. RESULTS: No patient treated with abarelix depot had testosterone surge during week 1 compared with 82% of those treated with LH-RH agonists. The concomitant administration of antiandrogen had no effect. During the first week of drug administration, in 75% of patients treated with abarelix depot and in 0% of those treated with LH-RH agonist medical castration was achieved. Prostate specific antigen decrease was faster, with no flare or surge in patients treated with abarelix depot. Abarelix depot was well tolerated. CONCLUSIONS: Abarelix depot represents a new class of hormonal therapy, gonadotropin releasing hormone antagonists, that has rapid medical castration and avoids the testosterone surge characteristic of LH-RH agonists.

[Access of developing countries to essential drugs: a process of equity]. / L'accès des pays en développement aux médicaments essentiels: une démarche d'équité.

In the context of the fight against poverty, the access of developing countries to essential drugs mobilizes the international community. It leads to envisage new and intricates politics. If donations or tiered prices are studied, the manufacturing of generics and even of patented drugs through voluntary or compulsory licensing is evoked. At a longer terms, it's the setting of health national politics and industrialisation which are concerned. These new orientations are not without consequence on the global drug market.

Abarelix Depot, a GnRH antagonist, v LHRH superagonists in prostate cancer: differential effects on follicle-stimulating hormone. Abarelix Depot study group.

PURPOSE: A Phase II clinical study contrasted the endocrinologic and biochemical efficacy of Abarelix Depot, a gonadotropin-releasing hormone (GnRH) antagonist, with luteinizing hormone releasing-hormone (LHRH) superagonists, with or without additional antiandrogens, in men with prostate cancer. METHODS: This study was open-label and treated 242 men. Abarelix Depot 100 mg was administered by intramuscular injection to 209 men, and LHRH, with or without an antiandrogen, was administered to 33 men according to the formulation used. Serum concentrations of follicle-stimulating hormone (FSH) and other hormones were measured at baseline and at specified time points for the first 85 days of the study. Median serum concentrations of FSH at baseline were similar for the two treatment groups. RESULTS: Men treated with LHRH superagonists, with or without an antiandrogen, had a surge in the serum concentration of FSH on day 2 before FSH concentrations started to decline. Men in the Abarelix Depot group had an immediate and sustained decrease in the serum concentration of FSH. CONCLUSION: Recent data suggest that FSH may be an independent growth factor for prostate cancer. The Abarelix Depot-induced decreased in FSH may have a role in the treatment of men with endocrine- responsive disease or for those men whose disease has escaped from hormone sensitivity.

A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of interferon beta-1a. Multiple Sclerosis Collaborative Research Group.

BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFNbeta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. RESULTS: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r2 = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these lesions in the brain.

Delayed posterior dislocation of silicone plate-haptic lenses after neodymium:yag capsulotomy.

We report 4 cases of posterior dislocation of silicone plate-haptic intraocular lenses (iols) into the vitreous cavity occurring a mean of 16 months after neodymium:YAG laser posterior capsulotomy. In each case, no peripheral capsule defect was observed at the time of laser capsulotomy or at subsequent follow-ups. One case was treated with sulcus implantation of a 3-piece IOL, with the plate-haptic IOL left in the vitreous cavity. The other cases were managed with vitrectomy (2 pars plana, 1 anterior) to remove the plate-haptic lens with subsequent sulcus placement of a 3-piece IOL. Patients should be informed that posterior dislocation is an infrequent but possible complication of these lenses and may occur months and even years after implantation or laser capsulotomy.

Contemporary experience with the management of vulvar intraepithelial neoplasia.

Experience with 40 cases of vulvar intraepithelial neoplasia seen during the 7-year period 1992-98 is detailed. The average age was 46.2 years and 27 of the patients (67.5%) were aged 50 years or younger. There was a significant association with cigarette smoking when compared with age-matched control patients attending the Vulvar Clinic with non-neoplastic conditions (67.5 vs. 12.5%; P = 0.001). Twenty-five percent of the patients had a past history of cervical intraepithelial neoplasia (CIN). The disease was multifocal in 77.5% of patients-92.6% of women aged less than 50 years and 53.8% of older women (P = 0.014). Treatment was by surgical excision supplemented in some cases by laser ablation. Occult stromal invasion was detected histologically in 15% of cases and in half of these, the invasion was to a depth considered to have significant metastatic potential. Recurrence occurred in 50% of patients and was more common in patients with multifocal disease. One patient (2.5%), aged 30, developed invasive vulvar carcinoma 4 years after treatment.

A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG).

OBJECTIVE: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon beta-1a (Avonex). METHODS: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. RESULTS: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. CONCLUSION: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.