Comparative effects of pimecrolimus cream vehicle and three commercially available moisturizers on skin hydration and transepidermal water loss

Background: Hydration and integrity of the horny layer is essential to normal skin function. Objective: Comparison of the hydrating properties of three moisturizers with pimecrolimus cream vehicle. Methods: Four test preparations (high-quality skin cream, cold cream emulsion, emollient oil, pimecrolimus cream vehicle) were applied to four different regions of the forearms and legs. Transepidermal water loss (TEWL) was assessed by evaporimetry at baseline, and 3 and 6 hours after arm application, and electrical capacitance was assessed by corneometry at baseline, and 1, 2, 3 and 6 hours after leg application. Results: Corneometry assessment - in terms of efficacy in moisturizing the skin, test preparations were ranked (best to worst): high-quality skin cream (45.9 arbitrary units versus 75.3; p < 0.001) > pimecrolimus vehicle cream (46.6 versus 61.5; p < 0.001) > emollient oil (43.5 versus 54.8; p = 0.006) > cold cream emulsion (44.8 versus 49.9; p = 0.738). Untreated skin (control) had a mean capacitance of 44.8 units at baseline and 48.5 units at endpoint. Evaporimetry (assessment of TEWL) revealed no significant differences between control and any test preparation at any timepoint. Conclusions: Pimecrolimus cream vehicle has skin hydration properties comparable with highly effective commercially available products. No test preparation had a significant effect on TEWL.

PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas

Background Basal cell carcinomas (BCCs) are the most frequent human cancer that results from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2. Objectives To search for mutations and genomic instability in sporadic and inherited BCCs. Methods DNA obtained from leukocytes and tumor cells was amplified by polymerase chain reaction regarding five exons of PTCH1 and PTCH2 and neighboring microsatellites. Exons were sequenced and compared with the GenBank database. Results Only D9S180, of six microsatellites, showed loss of heterozygosity in three BCCs (two sporadic and one inherited). One sporadic BCC presented the mutation g. 2885G>C in exon 17 of PTCH1, which predicts the substitution p.R962T in an external domain of the protein. In addition, the leukocytes and tumor cells of one patient with Gorlin syndrome showed the mutation g. 2839T>G in the same exon and gene, which predicts a p.E947stop and truncated protein. All control and tumor samples presented IVS9 + 217T in intron 9 of PTCH1. Conclusion Mutations found in the PTCH1 gene and neighboring repetitive sequences may have contributed to the development of the studied BCCs.

Bioimpedance Analysis: Should it be Used in Morbid Obesity?

Objectives: Questions about reliability of bioimpedance analysis (BIA) in morbidly obese subjects have curtailed its use in this setting, but metabolic implications might reignite the debate. In a prospective study, it was aimed to analyze anthropometric and clinical associations. Methods: Bariatric candidates (n = 94) with or without metabolic syndrome were consecutively investigated. Age was 34.9 +/- 10.4 years (68.1% females), and BMI was 40.8 +/- 4.6 kg m(-2). Methods included single-frequency BIA, anthropometrics, inflammatory indices, and general biochemical profile. Results: Body composition results (water, fat) in females, but not in males, were entirely consistent with the literature. In both genders good association was observed with anthropometrics (BMI, waist circumference), inflammatory indices (ferritin, C-reactive protein) and general biochemical variables. Anthropometric measurements also displayed comparable associations. Multivariate tests including the two sets of measurements indicated no predominance of one method over the other, one complementing the other as metabolic marker. Conclusions: BIA limitations were mostly relevant for males, not females. Despite such discrepancies, good associations with anthropometry were demonstrated for both genders. Correlations with liver enzymes, and indices of protein, carbohydrate, and lipid metabolism could be demonstrated. BIA deserves more investigations concerning liver steatosis and ongoing inflammation, and it could contribute as well, synergistically with anthropometry, to monitor weight loss, body fat shifts, and metabolic risk. Am. J. Hum. Biol. 23: 420-422, 2011. (c) 2011 Wiley-Liss, Inc.

Spirometric Function Improves in the Morbidly Obese After 1-Year Post-surgery

Obesity can negatively affect pulmonary function tests, with or without clinical symptoms, but the impact of bariatric weight loss is still debated. Aiming to document such profile in a consecutive homogeneous population, a prospective cohort study was undertaken. Sixty-one patients (100% females, age 40 +/- 8 years, BMI 49 +/- 5 kg/m(2) and without respiratory disease) were enrolled. Spirometric analysis was carried out to compare preoperative respiratory pattern with outcome after 6 and 12 months. Variables included vital capacity (VC), expiratory reserve volume (ERV), forced expiratory volume (1 s) (FEV1), FEV1/FVC ratio and maximum voluntary ventilation (MVV). Correlation of results with weight loss was examined. The following initial variables exhibited significant difference when compared to the 12-month postoperative control: FVC (P = 0.0308), FEV1/FVC (P = 0.1998), MVV (P = 0.0004) and ERV (P = 0.2124). Recovery of FVC and FEV1/FVC occurred earlier by 6 months. The most seriously depressed preoperative finding was ERV, which even after 1 year still remained inadequate. (1) Pulmonary limitations were diagnosed in approximately one third of the population. (2) Changes were demonstrated for FVC, FEV1/FVC, ERV and MVV. (3) FEV1 and FEV1/FVC were acceptable due to the absence of an obstructive pattern. (4) Two variables increased by 6 months (FEV1/FVC and ERV), whereas recovery for others was confirmed after 1 year. (5) The only exception was ERV which continued below the acceptable range.

Long-Term Nutritional Outcome After Gastric Bypass

Weight loss and nutritional status 5 or more years after Roux-en-Y gastric bypass was prospectively documented. The hypothesis was that even after clinical adaptation, imbalances might still occur. Seventy-five consecutive patients (age 49.3 +/- 10.6 years, 89.3% females) were recruited 83.4 +/- 14.3 months after the intervention. Weight loss and nutritional abnormalities were registered. Body mass index (BMI) was 56.5 +/- 10.0 preoperatively, 29.4 +/- 6. 2 by 24 months and 34.4 +/- 14.6 when last seen. Major current deficit occurred for magnesium (32.1% of the patients), hemoglobin (50.8%), iron (29.8%), ferritin (36.0%), zinc (40.5%), vitamin B(12) (61.8%), vitamin D(3) (60.5%), and beta-carotene (56.8%). Low preoperative measurements had already been unveiled for iron, transferrin, zinc, and vitamin B(12). Total drug consumption tended to decrease after operation, and present findings correlated with excess weight loss (EWL). Also presence of diabetes and BMI value were predictors of long-term EWL, along with biochemical profile by 2 years. Multivitamin supplementation and gastrointestinal complaints partially correlated with nutritional results. (1) Good initial weight loss with moderate late regain, anemia, and multiple nutrient deficits was the common pattern. (2) Massive weight loss, frequent vomiting, dumping syndrome, and women in reproductive age were risk factors for hemoglobin or vitamin deficits, whereas superobesity, diabetes, and use of multiple drugs were associated with EWL result. (3) Most laboratory tests became stable by 2 years and along with BMI correlated with late EWL. (4) Two-year nutritional investigation is especially recommended because of its long-term predictive value.

Long-term nutritional assessment of patients with severe short bowel syndrome managed with home enteral nutrition and oral intake

Background: Parenteral nutrition (PN) is used to control the nutritional state after severe intestinal resections. Whenever possible, enteral nutrition (EN) is used to promote intestinal rehabilitation and reduce PN dependency. Our aim is to verify whether EN + oral intake (01) in severe short bowel syndrome (SBS) surgical adult patients can maintain adequate nutritional status in the long term. Methods: This longitudinal retrospective study included 10 patients followed for 7 post-operative years. Body mass index (BMI), percentage of involuntary loss of usual body weight (UWL), free fat mass (FFM), and fat mass (FM) composition assessed by bioelectric impedance, and laboratory tests were evaluated at 6, 12, 24, 36, 48, 60, 72, and 84 months after surgery. Energy and protein offered in HPN and at long term by HEN+ oral intake (01), was evaluated at the same periods. The statistical model of generalized estimating equations with p <0,05 was used. Results: With long term EN + 01 there was a progressive increase in the UWL, a decrease in BMI, FFM, and FM (p < 0,05). PN weaning was possible in eight patients. Infection due to central venous catheter (CVC) contamination was the most common complication (1.2 episodes CVC/patient/year). There was an increase in energy and protein intake supply provided by HEN+OI (p <0.05). All patients survived for at least 2 years, seven for 5 years and six for 7 years of follow-up. Conclusions: In the long term SBS surgical adult patients fed with HEN+OI couldn`t maintain adequate nutritional status with loss of FM and FFM. (Nutr Hosp. 2011;26:834-842) DOI:10.3305/nh.2011.26.4.5153

The impact of gender, age and hearing loss on tinnitus severity

Tinnitus is a symptom present in approximately 15% of the world population. Most patients are between 40 and 80 years of age; the prevalence above 60 reaches 33%. About 20% have moderate to severe impact in the quality of life but the factors associated with the tinnitus annoyance are not completely known. Aim: The objective of this study is to evaluate the relationship between age, gender and hearing loss on tinnitus annoyance. Materials and methods: 68 patients were evaluated at the tinnitus center at our hospital, from March 2007 to march 2008, with a detailed interview, complete otolaryngological examination, the Portuguese version of the Tinnitus Handicap Inventory and pure tone audiometry. Results: Age varied from 24 to 83 (mean=59); the mean THI value was 39 (females: 36; males: 44). THI grades were: slight: 32.3%; mild: 19.1%; moderate: 20.6%; severe: 13.2% and catastrophic: 14.7%. No significant correlation was found between gender (p=0.30), age (p=0.77) hearing loss (p>0.05 for all averages analyzed) and tinnitus severity. Conclusion: Gender, age and hearing loss do not influence tinnitus annoyance, using the THI.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < 18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI > 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >= 30 kg/m(2) (0.43, 0.33-0.57), compared with BMI > 18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < 18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Because of the advent of a new influenza A H1N1. strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barre syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barre syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Body Mass Index Increase, Serum Leptin, Adiponectin, Neuropeptide Y and Lipid Levels during Treatment with Olanzapine and Haloperidol

Introduction: Body mass index (BMI) increase is an undesired effect associated with antipsychotics, and crucial for patients` global health and treatment compliance. We aimed to investigate the relation between BMI during olanzapine or halopericlol treatments and leptin, neuropeptide Y (NPY), adiponectin and lipid serum levels. Methods: In this 9-month, randomized and naturalist study, 34 male patients, 18 on olanzapine and 16 on haloperidol group were enrolled, all were under monotherapy. Patient outcome was evaluated with positive and negative syndrome scale (PANSS) at every 3-month period. In each visit, BMI, leptin, NPY, lipid, olanzapine or haloperidol levels were also monitored. Results and Discussion: Leptin levels positively correlated with BMI in olanzapine (r = 0.64, p < 0.001) and haloperidol (r = 0.73, p < 0.001) groups; only in olanzapine patients, the former also correlated with PANSS score (r = 0.54, p < 0.05). NPY levels negatively correlated with olanzapine levels (r = -0.65, p < 0.01). Adiponectin levels had not significantly varied. Conclusion: Antipsychotics probably interfere on leptin and NPY signalling ways and disturb these hormones in eating behaviour control.

Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine

The persistent nature of addiction has been associated with activity-induced plasticity of neurons within the striatum and nucleus accumbens (NAc). To identify the molecular processes leading to these adaptations, we performed Cre/loxP-mediated genetic ablations of two key regulators of gene expression in response to activity, the Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) and its postulated main target, the cAMP-responsive element binding protein (CREB). We found that acute cocaine-induced gene expression in the striatum was largely unaffected by the loss of CaMKIV. On the behavioral level, mice lacking CaMKIV in dopaminoceptive neurons displayed increased sensitivity to cocaine as evidenced by augmented expression of locomotor sensitization and enhanced conditioned place preference and reinstatement after extinction. However, the loss of CREB in the forebrain had no effect on either of these behaviors, even though it robustly blunted acute cocaine-induced transcription. To test the relevance of these observations for addiction in humans, we performed an association study of CAMK4 and CREB promoter polymorphisms with cocaine addiction in a large sample of addicts. We found that a single nucleotide polymorphism in the CAMK4 promoter was significantly associated with cocaine addiction, whereas variations in the CREB promoter regions did not correlate with drug abuse. These findings reveal a critical role for CaMKIV in the development and persistence of cocaine-induced behaviors, through mechanisms dissociated from acute effects on gene expression and CREB-dependent transcription.

Biological Effects and Dose-Response Assessment of Diesel Exhaust Particles on In Vitro Early Embryo Development in Mice

An increased risk of early pregnancy loss in women briefly exposed to high levels of ambient particulate matter during the preconceptional period was recently observed. The effects of this exposure on early embryo development are unknown. This study was designed to assess the dose-response and biological effects of diesel exhaust particles (DEP) on in vitro embryo development using the in vitro fertilization (IVF) mouse model. Zygotes obtained from superovulated mice after IVF were randomly cultured in different DEP concentrations (0, 0.2, 2, and 20 mu g/cm(2)) for 5 days and observed for their capacity to attach and develop on a fibronectin matrix until day 8. Main outcome measures included blastocyst rates 96 and 120 h after insemination, hatching discriminatory score, total cell count, proportion of cell allocation to inner cell mass (ICM) and trophectoderm (TE), ICM morphology, attachment rate and outgrowth area, apoptosis and necrosis rates, and Oct-4 and Cdx-2 expression. Multivariate analysis showed a negative dose-dependent effect on early embryo development and hatching process, blastocyst cell allocation, and ICM morphology. Although blastocyst attachment and outgrowth were not affected by DEP, a significant impairment of ICM integrity was observed in day 8 blastocysts. Cell death through apoptosis was significantly higher after DEP exposure. Oct-4 expression and the Oct-4/Cdx-2 ratio were significantly decreased in day 5 blastocysts irrespective of DEP concentration. Results suggest that DEP appear to play an important role in disrupting cell lineage segregation and ICM morphological integrity even at lower concentrations, compromising future growth and viability of the blastocyst.

Selective Inner Hair Cell Loss in Prematurity: A Temporal Bone Study of Infants from a Neonatal Intensive Care Unit

Premature birth is a well-known risk factor for sensorineural hearing loss in general and auditory neuropathy in particular. However, relatively little is known about the underlying causes, in part because there are so few relevant histopathological studies. Here, we report on the analysis of hair cell loss patterns in 54 temporal bones from premature infants and a control group of 46 bones from full-term infants, all of whom spent time in the neonatal intensive care unit at the Hospital de Nios in San Jose, Costa Rica, between 1977 and 1993. The prevalence of significant hair cell loss was higher in the preterm group than the full-term group (41% vs. 28%, respectively). The most striking finding was the frequency of selective inner hair cell loss, an extremely rare histopathological pattern, in the preterm vs. the full-term babies (27% vs. 3%, respectively). The findings suggest that a common cause of non-genetic auditory neuropathy is selective loss of inner hair cells rather than primary damage to the cochlear nerve.

Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss

We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss. The Hajdu-Cheney syndrome mutations are predicted to lead to the premature truncation of NOTCH2 with either disruption or loss of the C-terminal proline-glutamate-serine-threonine-rich proteolytic recognition sequence, the absence of which has previously been shown to increase Notch signaling.

Influence of Modified Posterior Reconstruction of the Rhabdosphincter on Early Recovery of Continence and Anastomotic Leakage Rates after Robot-Assisted Radical Prostatectomy

Background: Posterior reconstruction (PR) of the rhabdosphincter has been previously described during retropubic radical prostatectomy, and shorter times to return of urinary continence were reported using this technical modification. This technique has also been applied during robot-assisted radical prostatectomy (RARP); however, contradictory results have been reported. Objective: We describe here a modified technique for PR of the rhabdosphincter during RARP and report its impact on early recovery of urinary continence and on cystographic leakage rates. Design, setting, and participants: We analyzed 803 consecutive patients who underwent RARP by a single surgeon over a 12-mo period: 330 without performing PR and 473 with PR. Surgical procedure: The reconstruction was performed using two 6-in 3-0 Poliglecaprone sutures tied together. The free edge of the remaining Denonvillier`s fascia was identified after prostatectomy and approximated to the posterior aspect of the rhabdosphincter and the posterior median raphe using one arm of the continuous suture. The second layer of the reconstruction was then performed with the other arm of the suture, approximating the posterior lip of the bladder neck and vesicoprostatic muscle to the posterior urethral edge. Measurements: Continence rates were assessed with a self-administrated, validated questionnaire (Expanded Prostate Cancer Index Composite) at 1, 4, 12, and 24 wk after catheter removal. Continence was defined as the use of ""no absorbent pads."" Cystogram was performed in all patients on postoperative day 4 or 5 before catheter removal. Results and limitations: There was no significant difference between the groups with respect to patient age, body mass index, prostate-specific antigen levels, prostate weight, American Urological Association symptom score, estimated blood loss, operative time, number of nerve-sparing procedures, and days with catheter. In the PR group, the continence rates at 1, 4, 12, and 24 wk postoperatively were 22.7%, 42.7%, 91.8%, and 96.3%, respectively; in the non-PR group, the continence rates were 28.7%, 51.6%, 91.1%, and 97%, respectively. The modified PR technique resulted in significantly higher continence rates at 1 and 4 wk after catheter removal (p = 0.048 and 0.016, respectively), although the continence rates at 12 and 24 wk were not significantly affected (p = 0.908 and p = 0.741, respectively). The median interval to recovery of continence was also statistically significantly shorter in the PR group (median: 4 wk; 95% confidence interval [CI]: 3.39-4.61) when compared to the non-PR group (median: 6 wk; 95% CI: 5.18-6.82; log-rank test, p = 0.037). Finally, the incidence of cystographic leaks was lower in the PR group (0.4% vs 2.1%; p = 0.036). Although the patients` baseline characteristics were similar between the groups, the patients were not preoperatively randomized and unknown confounding factors may have influenced the results. Conclusions: Our modified PR combines the benefits of early recovery of continence reported with the original PR technique with a reinforced watertight closure of the posterior anastomotic wall. Shorter interval to recovery of continence and lower incidence of cystographic leaks were demonstrated with our PR technique when compared to RARP with no reconstruction. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.