High prevalence of cytomegalovirus (CMV) infection in infants born to HIV infected mothers–ANRS French Perinatal Cohort (EPF)

Whenever there is a sensational criminal case involving HIV transmission, the media cover it with far more gusto than they usually devote to scientific advances in the field. For example, a murder trial is now taking place in Canada involving a man who has been accused of sexually transmitting HIV to 11 different women, two of whom have died of their infections. Moreover, it is alleged that the accused perpetrator deliberately withheld from these women the fact that he was HIV-positive and that he refused to use a condom during intercourse. Notwithstanding that the suspect is possibly psychopathic and uncaring, or possibly of low intelligence and unable to assess the consequence of his actions, most people probably hope that he is convicted, sentenced, and imprisoned for his acts. Furthermore, most people probably wish for the criminal justice system to pursue these cases with vigour. In fact, however, people should understand that such legal action, and the willingness of the courts to hear these cases, will only weaken the global battle against HIV transmission.     

Beta 3-adrenoceptor knockout in C57BL/6J mice depresses the occurrence of brown adipocytes in white fat.

White and brown adipocytes are usually located in distinct depots; however, in response to cold, brown adipocytes appear in white fat. This response is mediated by beta-adrenoceptors but there is a controversy about the subtype(s) involved. In the present study, we exposed to cold beta 3-adrenoceptor knockout mice (beta 3KO) on a C57BL/6J genetic background and measured in white adipose tissue the density of multilocular cells and the expression of the brown adipocyte marker uncoupling protein-1 (UCP1). In brown fat of beta 3KO mice, UCP1 expression levels were normal at 24 degrees C as well as after a 10-day cold exposure. Strikingly, under both conditions, in the white fat of beta 3KO mice the levels of UCP1 mRNA and protein as well as the density of multilocular cells were decreased. These results indicate that beta 3-adrenoceptors play a major role in the appearance of brown adipocytes in white fat and suggest that the brown adipocytes present in white fat differ from those in brown fat.     

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents

Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 microg/mL. The synergistic effect shown by our novel compounds is due to their inherent amphiphilicity. The fractional inhibitory concentrations reported are comparable to those reported for Polymyxin B derivatives.     

Trichosporon insectorum sp. nov., a new anamorphic basidiomycetous killer yeast

Three killer yeasts, isolated from the gut of insects in Panama and artisanal cheese in Brazil, were shown to be related to the Ovoides clade of the genus Trichosporon. Sequencing of the D1/D2 region of the LSU rDNA and physiological characterization revealed a distinct taxonomic position in relation to known species of the genus. Conspecificity of the three killer isolates was reinforced by similar M13 fingerprinting and killer profiles. We propose a new species in this genus: Trichosporon insectorum. The type strain is CBS 10422^T (syn. NRRL Y-48120). This anamorphic species produces arthroconidia but not appressoria, and its killer character seems to be associated with dsRNA.     

Epidemiological Profile of Cryptococcal Meningitis Patients in Rio Grande do Sul,Brazil

Cryptococcosis is a major opportunistic mycosis which has meningitis as its most frequent clinical presentation and can be fatal in the absence of antifungal therapy. The aetiological agents are Cryptococcus neoformans, which affects mainly immunocompromised subjects, and C. gattii, the aetiologic agent for cryptococcosis in healthy individuals. A recent outbreak of cryptococcosis on Vancouver Island, Canada, raised the level of concern about the epidemiology of this disease. In Brazil, between 1980 and 2002, six per cent of AIDS patients had cryptococcosis in course at the time of diagnosis. To identify the profile of cryptococcal meningitis patients in Rio Grande do Sul (RS), Brazil, a retroactive study was realized using data from patients registered at Laboratório Central de Saúde Pública IPB-LACEN/RS from 2000 to 2005. Most of the patients were men (77.12%), Caucasian (83.5%), median age between thirty and thirty-nine years old (46.24%) and HIV positive (95%).     

Is hematoxylin-eosin staining in rectal mucosal and submucosal biopsies still useful for the diagnosis of Hirschsprung disease?

Background

Hematoxylin-eosin (HE) staining of a full-thickness rectal wall fragment is classically used for the diagnosis of Hirschsprung disease (HD). However, this technique requires large fragments for a better diagnosis. Additionally, the histochemical and immunohistochemical methods of staining small fragments of rectal mucosal and submucosal biopsies are not available in all centers. Therefore, the possibility of diagnosing HD through HE staining in these biopsies could be a valuable alternative for centers that do not have more specific techniques. The objectives of the current investigation were to evaluate the concordance of the results obtained by HE staining and the calretinin method with acetylcholinesterase (AChE) activity in fragments of mucosa and submucosa in the diagnosis of HD.

Methods

For this study, 50 cases from our laboratory were selected. The tissue material was embedded in paraffin. Sixty levels of each fragment were utilized for HE, and the other 3 levels were used for calretinin. These slides were analyzed under the microscope, photographed and classified as either positive for HD when no ganglion cells were found with nerve trunks present or as negative when ganglion cells were found. The results from reading the slides were compared with those of AChE.

Results

Of the 50 cases evaluated by the HE technique, only 5 contradicted the diagnosis based on AChE, with a Kappa value of 0.800 and an accuracy of 90%. In the comparison between calretinin and AChE, 8 cases were discordant, with a Kappa value of 0.676 and an accuracy of 84%.

Conclusions

The concordance of results from AChE and HE methods was satisfactory, allowing for the potential use of the HE method for fragments of mucosa and submucosa as a valid alternative in the diagnosis of HD. The immunohistochemical technique of calretinin did not show good agreement with the AChE activity in our study.

     

Spatial variation in the management and outcomes of acute coronary syndrome

Background

Aprotinin has been shown to be effective in reducing peri-operative blood loss and the need for re-operation due to continued bleeding in cardiac surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are cheaper, but it is not known if they are as effective as aprotinin.

Methods

Studies were identified by searching electronic databases and bibliographies of published articles. Data from head-to-head trials were pooled using a conventional (Cochrane) meta-analytic approach and a Bayesian approach which estimated the posterior probability of TXA and EACA being equivalent to aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of transfusion or re-operation because of bleeding.

Results

Peri-operative blood loss was significantly greater with TXA and EACA than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority boundary, the posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion of one small trial.

Conclusion

The available data are conflicting regarding the equivalence of lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion and the need for re-operation. Decisions are sensitive to the choice of clinical outcome and non-inferiority boundary. The data are an uncertain basis for replacing aprotinin with the cheaper lysine analogues in clinical practice. Progress has been hampered by small trials and failure to study clinically relevant outcomes.     

Clinical benefit of metaphase I oocytes

Background  

We studied the benefit of using in vitro matured metaphase I (MI) oocytes for ICSI in patients with a maximum of 6 mature metaphase II (MII) oocytes at retrieval.     

Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo

In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis. Six4 and Six5 single knockout (KO) mice have no developmental defects, while Six1 KO mice die at birth and show multiple organ developmental defects. We have generated Six1Six4 double KO mice and show an aggravation of the phenotype previously reported for the single Six1 KO. Six1Six4 double KO mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia. At the limb bud level, Six1 and Six4 homeogenes control early steps of myogenic cell delamination and migration from the somite through the control of Pax3 gene expression. Impaired in their migratory pathway, cells of the somitic ventrolateral dermomyotome are rerouted, lose their identity and die by apoptosis. At the interlimb level, epaxial Met expression is abolished, while it is preserved in Pax3-deficient embryos. Within the myotome, absence of Six1 and Six4 impairs the expression of the myogenic regulatory factors myogenin and Myod1, and Mrf4 expression becomes undetectable. Myf5 expression is correctly initiated but becomes restricted to the caudal region of each somite. Early syndetomal expression of scleraxis is reduced in the Six1Six4 embryo, while the myotomal expression of Fgfr4 and Fgf8 but not Fgf4 and Fgf6 is maintained. These results highlight the different roles played by Six proteins during skeletal myogenesis.