Increased mRNA expression of collagen V gene in pulmonary fibrosis of systemic sclerosis

Background Collagen V shows promise as an inducer of interstitial lung fibrosis in experimental systemic sclerosis (SSc). Materials and methods Remodelling of the pulmonary interstitium was evaluated based on the clinical data and open lung biopsies from 15 patients with SSc. Normal lung tissues obtained from eight individuals who died of traumatic injuries were used as control group. Immunofluorescence, immunohistochemistry, morphometry, tri-dimensional reconstruction and a real-time polymerase chain reaction were used to evaluate the quantity, structure and molecular chains of collagen V. The impact of these markers was tested on clinical data. Results The main difference in collagen V content between SSc patients and the control group was an increased, abnormal and distorted fibre deposition in the alveolar septa and the pre-acinar artery wall. The lungs from SSc patients presented [alpha 1(V)] and [alpha 2(V)] mRNA chain expression increased, but [alpha 2(V)] was proportionally increased compared with the control group. High levels of collagen V were inversely associated with vital capacity (r = -0.72; P = 0.002), forced vital capacity (r = -0.76; P < 0.001), forced expiratory volume in 1-s (r = -0.89; P < 0.001) and diffusing capacity for carbon monoxide (r = -0.62; P = 0.04). Conclusions Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [alpha 2(V)] gene of unknown origin.

In vitro fertilization, embryo development, and cell lineage segregation after pre- and/or postnatal exposure of female mice to ambient fine particulate matter

Objective: To evaluate effects of pre- and/or postnatal exposure to ambient fine particulate matter on fertilization, embryo development, and cell lineage segregation in preimplantation blastocysts using the IVF mouse model. Design: Animal model. Setting: Academic institution. Animal(S): Six-week-old, superovulated mice. Intervention(s): Pre- and postnatal exposure to filtered air (FA-FA), filtered-ambient air (FA-AA), or ambient air (AA-AA) in exposure chambers 24 hours a day for 9 weeks. Main Outcome Measure(S): Gestation length, litter size, sex ratio, ovarian response to superovulation, fertilization rate, embryo development, blastocyst and hatching rates, total cell count, and proportion of cell allocation to inner-cell mass (ICM) and trophectoderm (TE). Result(S): Gestation length, litter size and birth weight, live-birth index, and sex ratio were similar among exposure groups. Ovarian response was not affected by the exposure protocol. A multivariate effect for pre- and/or postnatal exposure to ambient fine particulate matter on IVF, embryo development, and blastocyst differential staining was found. Cell counts in ICM and ICM/TE ratios in blastocysts produced in the FA-FA protocol were significantly higher than in blastocysts produced in the FA-AA and AA-AA protocols. No difference in total cell count was observed among groups. Conclusion(S): Our study suggests that exposure to ambient fine particulate matter may negatively affect female reproductive health by disrupting the lineage specification at the blastocyst stage without interfering in early development of the mouse embryo. (Fertil Steril (R) 2009;92:1725-35. (C) 2009 by American Society for Reproductive Medicine.)

Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial

Background Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. Methods We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of >= 0.65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0.965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. Findings All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0.749, below the Bayesian success threshold of 0.965). The 6-month composite primary safety endpoint was 14.4% (30 of 208) for airway bypass versus 11.2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1.00 [Bayesian success threshold >0.95]). Interpretation Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema.

Pre- and postnatal exposure to ambient levels of urban particulate matter (PM(2.5)) affects mice spermatogenesis

This work characterizes the effects of ambient levels of urban particulate matter (PM(2.5)) from the city of Sao Paulo on spermatogenesis using mice exposed during the embryo-fetal and/or postnatal phases of development. Parental generations (BALB/c mice) were exposed to air pollution in chambers with or without filtering PM(2.5) for 4 months. Animals were mated, and half of the 1-day-old offspring were moved between chambers, which yielded prenatal and postnatal groups. Remaining offspring comprised the non-exposed and pre+postnatal exposed groups. After 90 days, the animals were sacrificed for testis collection and weighing. Optical microscopy was used for the morphometric analyses of the cell counts, spermatogenic cycle, proliferation, and apoptosis. Prenatally exposed animals presented reduced body and testicular weight with an increased gonadosomatic index (GSI). Testicular volume also decreased, as well as the tubular diameter in testes of the same animals. Proliferation, apoptosis, and spermatogenic cycle analyses showed no significant differences among groups. However, the tubules at stage VII of pre- and postnatal animals presented a reduced number of elongated spermatids. Pre+postnatal group presented higher spermatid head retention at stages VIII-XII. These results show that ambient levels of PM(2.5) from Sao Paulo city affect spermatogenesis by damaging sperm production.

Chromoblastomycosis: study of 27 cases and review of medical literature

BACKGROUND: Chromoblastomycosis is a subcutaneous mycosis that occurs mainly in rural workers although is being more commonly found among people working in other sectors. The fungus penetrates the skin after its inoculation and the most frequently isolated agent is the Fonsecaea pedrosoi. OBJECTIVES: This study aims at evaluating patients suffering from chromoblastomycosis admitted into the Department of Dermatology of the University Hospital of the Faculty of Medicine of Sao Paulo State during the ten-year period from 1997 to 2007. METHODS: It is a retrospective study and the medical report cards of 27 Brazilian patients diagnosed as suffering from Chromoblastomycosis from 1997 to 2007 at the Dermatology Department of the Medical School, University of Sao Paulo were reviewed. The following items were analyzed: previous therapeutic approaches; treatment implemented by the group; length of time between the appearing of the lesion and diagnosis; age; gender; profession; origin; site of lesions; isolated agents found in culture and histopathology. RESULTS: Twenty two patients were from the state of Sao Paulo whereas the others came from the states of Bahia and Rondonia. 37% of them were rural workers. Men were more frequently infected (85%). Lesions were more commonly found on the lower limbs (59.2%). In 52% of the cases the isolated agent was the dematiaceous fungus Fonsecaea. pedrosoi. Biopsies showed sclerotic bodies in 92.5% of the cases. CONCLUSION: Data found are in accordance with medical literature on the subject. The disease had been previously studied in our institution in 1983 by Cuce et al. This present study is the second retrospective one about the characteristics of patients suffering from chromoblastmycosis which has been published in indexed medical literature in the state of Sao Paulo.

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

Background: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. Study Design: Retrospective case series. Setting & Participants: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the Sao Paulo University Medical School (Sao Paulo, Brazil). Outcomes & Measurements: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. Results: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P = 0.001), lower gestational age (P = 0.001), and birth weight (P = 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P = 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. Limitations: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. Conclusions: Outcomes of pregnancy in women undergoing hemodialysis often are good. Preeclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight. Am J Kidney Dis 56:77-85. (C) 2010 by the National Kidney Foundation, Inc.Inc

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log-rank = 0.0002) and deaths (log-rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007-5.11; p = 0.04). The incidence of cardiac events (log-rank = 0.349) and deaths (log-rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre-emptive myocardial revascularization for renal transplant candidates.

International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials

Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors Few studies have described the international epidemiology of pre-existing immunity to adenoviruses We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36 Clinical trial samples were used to assess NA titers from the US and Europe The proportions of participants that were negative were 14 8%(Ad5), 31 5%(Ad6),41 2%(Ad26) and 53.6% (Ad36) Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers, participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR = 3 53,95% CI 224,557) Regardless of location. titers of Ad5NA were the highest and Ad36 NA were the lowest Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations (C) 2009 Published by Elsevier Ltd

MLPA analysis in 30 Sotos syndrome patients revealed one total NSD1 deletion and two partial deletions not previously reported

Sotos syndrome (MIM #117550) is an autosomal dominant condition characterized by pre and postnatal overgrowth, macrocephaly and typical facial gestalt with frontal bossing, hypertelorism, antimongoloid slant of the palpebral fissures, prominent jaw and high and narrow palate. This syndrome is also frequently associated with brain, cardiovascular, and urinary anomalies and is occasionally accompanied by malignant lesions such as Wilms turnout and hepatocarcinoma. The syndrome is known to be caused by mutations or deletions of the NSD1 gene. To detect both 5q35 microdeletions and partial NSD1 gene deletions we screened 30 Brazilian patients with clinical diagnosis of Sotos syndrome by multiplex ligation dependent probe amplification. We identified one patient with a total deletion of NSD1 and neighbouring FGFR4, other with missing NSD1 exons 13-14 and another with a deletion involving FGFR4 and spanning up to NSD1 exon 17. All deletions were de novo. The two NSD1 partial deletions have not been previously reported. The clinical features of the three patients included a typical facial gestalt with frontal bossing, prominent jaw and high anterior hairline; macrocephaly, dolichocephaly, large hands; neonatal hypotonia and jaundice. All presented normal growth at birth but postnatal overgrowth. Two patients with NSD1 and FGFR4 gene deletions presented congenital heart anomalies. (C) 2009 Elsevier Masson SAS. All rights reserved.

Absence of bifurcation of the portal vein

Absence of the horizontal segment of the left portal vein (PV) or absence of bifurcation of the portal vein (ABPV) is extremely rare anomaly. The aim of this study was to study the extra-hepatic PV demonstrating the importance of its careful assessment for the purpose of split-liver transplantation. Human cadaver livers (n = 60) were obtained from routine autopsies. The cutting plane of the liver consisted of a longitudinal section made immediately on the left of the supra-hepatic inferior vena cava through the gallbladder bed preserving the arterial, portal and biliary branches in order to obtain two viable grafts (right lobe-segments V, VI, VII, and VIII and left lobe-segments II, III, and IV) as defined by the main portal scissure. The PV was dissected out and recorded for application of the liver splitting. The PV trunk has been divided into right and left branch in 50 (83.3%) cases. A trifurcation of the PV was found in 9 (15.2%) cases, 3 (5%) was a right anterior segmental PV arising from the left PV and 6 (10%) a right posterior segmental PV arising from the main PV. ABPV occurred in 1 (1.6%) case. Absence of bifurcation of the portal vein is a rare anatomic variation, the surgeon must be cautious and aware of the existence of this exceptional PV anomaly either pre or intra-operatively for the purpose of hepatectomies or even split-liver transplantation.

A study of actinic cheilitis treatment by two low-morbidity CO(2) laser vaporization one-pass protocols

Therapeutic approaches to chronic actinic cheilitis focus on the removal or destruction of diseased epithelium. The CO(2) laser has become an important therapeutic alternative, achieving clinical resolution in around 90% of patients. Although many laser physical parameters have been reported, some are known for their low potential for scar induction without compromising the success of the results. The aim of this clinicohistological study was to compare the therapeutic responses to two low-morbidity protocols involving a single laser pass. A total of 40 patients with chronic multicentric and microscopically proven disease were randomly submitted to two conservative CO(2) laser protocols using a bilateral comparative model. The degree of histological atypia of the epithelium was determined in 26 patients both pre- and postoperatively for both protocols. Other histological phenomena were assessed in addition to this central analysis parameter. Clinical recurrence occurred in 12.5% of patients for each protocol, together with a significant reduction in the degree of epithelial atypia (p < 0.001), which was occasionally complete. However, no difference was found between the protocols (p > 0.05). Using these morphological parameters it was not possible to determine whether postoperative epithelial atypias in part of the sample were reactive or residual in nature. A few patients may show minor postoperative lesions. Due to their potential to achieve clinical and importantly microscopic resolution, the studied protocols may be used for mild through moderate dysplastic epithelium and clinically diffuse disease.

Epstein-Barr virus detection in invasive and pre-invasive lesions of the uterine cervix

In the present study, our aim was to investigate whether EBV DNA could be found in association with invasive and pre-invasive cervical cancer lesions. We hypothesize that EBV is not merely a commensal agent when present in malignant cervical lesions. DNA was extracted from cervical scrapings followed by nested PCR-based amplification. The patients were 66 women with high grade cervical intraepithelial neoplasia and 14 women with invasive cervical cancer. The control group consisted of 89 women with a normal Pap smear and colposcopy as well as a negative HPV DNA test. Analysis of our results, in conjunction with the work of other authors, leads us to propose that EBV is not merely a commensal agent when present in malignant cervical lesions. The presence of DNA from EBV is significantly associated with cervical cancer.

Optimizing Medical Therapy of Acromegaly: Beneficial Effects of Cabergoline in Patients Uncontrolled with Long-Acting Release Octreotide

Background: Previous data indicate a beneficial effect of cabergoline (CAB) association to somatostatin analogs (SA) in acromegalics resistant to SA monotherapy. Objective: To assess the efficacy of CAB association on acromegalics with high IGF-I on stable long-acting release octreotide (OCT-LAR) (30 mg/28 days). Design, Subjects and Methods: 34 patients (17 male, 25-85 years, 33 macroadenomas) were enrolled in this prospective study. OCT-LAR was administered as primary (n = 4) and as secondary (n = 30) treatment: after surgery (n = 16), after surgery + radiotherapy (RT) (n = 11), and after RT only (n = 3). Duration of OCT-LAR therapy prior to CAB was 24 8 12 months. The immunohistochemical features of the tumors disclosed GH/PRL co-secretion in 11/21 patients. 13 patients had high PRL levels prior to CAB. The initial CAB dose was 1.5 mg/week. No IGF-I normalization led to a dose increase to 3.5 mg/week. The OCT-LAR dose was kept stable during treatment. IGF-I, GH and PRL levels were compared before and after CAB association. OCT-LAR was withdrawn in patients who achieved IGF-I normalization, in order to assess the influence of CAB. Results: Comparing OCT-LAR to OCT-LAR/CAB treatment, there was a significant decrease in mean GH, IGF-I, %ULNR- IGF-I and PRL levels. During OCT-LAR/CAB treatment, IGF-I normalized in 19 patients (56%). IGF-I normalization was correlated to lowest IGF-I levels on OCT-LAR monotherapy, but not to baseline PRL levels or GH/PRL co-expression. OCT-LAR withdrawn in all who had achieved IGF-I normalization on combined therapy resulted in IGF-I elevation to abnormal levels in all patients. Gastro intestinal symptoms were reported by 12 patients. Conclusion: OCT-LAR and CAB association has been shown to be an effective alternative therapy for those acromegalics who still have active acromegaly despite monotherapy with SA, mainly for those with lower pretreatment IGF-I concentrations. According to previous studies, the beneficial effects of CAB occur even when pretreatment PRL is normal and/or there is no tumor GH/PRL co-expression. Copyright (C) 2009 S. Karger AG, Basel