Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy

OBJECTIVES: To assess the prevalence of abnormal testosterone and gonadotropin values in HIV-infected men before and after 2 years of combination antiretroviral therapy (cART). DESIGN: Multicentre cohort of HIV-infected adults. METHODS: We identified 139 Caucasian antiretroviral-naive male patients who started zidovudine/ lamivudine-based cART that was virologically successful over a 2 year period. Ninety-seven were randomly chosen and plasma hormone determinations of free testosterone (fT) and luteinizing hormone (LH) at baseline and after 2 years of cART were evaluated. RESULTS: At baseline 68 patients (70%) had subnormal fT levels. In these, LH levels were low in 44%, normal in 47% and high in 9%. There was a trend for an association between lower CD4+ T-cell counts and hypogonadism. Most participants had normal FSH levels. No significant changes of fT, LH and FSH levels were observed after 2 years of cART. CONCLUSIONS: Low fT levels, mainly with normal or low LH levels and thus indicating secondary hypogonadism, are found in the majority of HIV-infected men and do not resolve during 2 years of successful cART.     

Maternal complications and procedures in pregnancy and at birth and wheezing phenotypes in children

RATIONALE: There is increasing interest in the potential influence of fetal and early life conditions on childhood wheezing. OBJECTIVES: To investigate the associations between maternal complications and procedures in pregnancy and at birth and the risk of various wheezing phenotypes in young children. METHODS: We studied 15,609 children, aged 6-7 yr, enrolled in a population-based study. Standardized questionnaires were completed by the children's mothers. RESULTS: Of the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal hypertension or preeclampsia was associated with an increased risk of all three wheezing phenotypes (for transient early wheezing: odds ratio [OR], 1.40; 95% confidence interval [95% CI], 1.08-1.82; for persistent wheezing: OR, 1.59; 95% CI, 1.15-2.19; and for late-onset wheezing: OR, 1.47; 95% CI, 1.06-2.01). Use of antibiotics for urinary tract infections was associated with transient early wheezing (OR, 1.52; 95% CI, 1.16-2.00), whereas antibiotic administration at delivery was associated with both transient early wheezing (OR, 1.21; 95% CI, 1.01-1.46) and persistent wheezing (OR, 1.39; 95% CI, 1.10-1.75). Children who had a mother with diabetes were also more likely to have persistent wheezing (OR, 1.72; 95% CI, 0.99-3.00). Neither amniocentesis/chorionic villus sampling, nor weight gain in pregnancy, nor cesarean section was associated with the subsequent development of wheezing. Maternal asthma or atopy was not an effect modifier of the associations found. CONCLUSIONS: Some maternal complications during pregnancy and at delivery may increase the risk of developing different phenotypes of wheezing in childhood.     

A case of Bernard-Soulier Syndrome due to a homozygous four bases deletion (TGAG) of GPIbalpha gene: lack of GPIbalpha but absence of bleeding

More than 20 DNA mutations with different inheritance pattern have been described in patients with Bernard-Soulier Syndrome (BSS), leading to abnormal or absent synthesis and/or expression of GPIbalpha. Clinical phenotype shows considerable variation between individuals, such as bleeding, platelet count and the percentage of large platelets. We describe in a BSS patient the first case of homozygous four bases deletion (TGAG) in the gpIbalpha gene coding sequence, leading to a premature stop codon. In the propositus, blood smears revealed giant platelets (30 x 10(9) platelets/L), and platelet agglutination to ristocetin was absent. Propositus' parents are consanguineous. His father and paternal grandmother showed a mild thrombocytopenia (108 x 10(9)/L and 120 x 10(9)/L platelets respectively) while mothers and sister's referred normal platelet counts. The surface expression of GPIbalpha was practically undetectable by flow-cytometry and western blot in the patient and was reduced in the father. Proband's DNA analysis revealed a homozygous four-base-pair deletion (TGAG), starting from the last base of the codon for Ser39, leading to a coding frame shift with a new termination codon after 11 novel amino acids. The same mutation was seen in heterozygosis in both parents. This is the first report of GPIbalpha TGAG deletion in homozygous state even if the defect has already been described in a case of compound heterozygosis. Surprisingly, the propositus does not report any spontaneous bleeding tendency.     

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400?copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.     

Colorectal cancer:Current imaging methods and future perspectives for the diagnosis,staging and therapeutic response evaluation

In the last 10 years the mortality rate of colorectal cancer(CRC)has decreased by more than 20%due to the rising developments in diagnostic techniques and optimization of surgical,neoadjuvant and palliative therapies.Diagnostic methods currently used in the evaluation of CRC are heterogeneous and can vary within the countries and the institutions.This article aims to discuss in depth currently applied imaging modalities such as virtual computed tomography colonoscopy,endorectal ultrasound,computed tomography(CT)and magnetic resonance imaging(MRI)in the diagnosis of CRC.Special focus is put on the potential of recent diagnostic developments as diffusion weighted imaging MRI,MRI biomarkers(dynamic enhanced MRI),positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose(FDG-PET)combined with computed tomography(PET/CT)and new hepatobiliary MRI contrast agents.The precise role,advantage and disadvantages of these modalities are evaluated controversially in local staging,metastatic spread and treatment monitoring of CRC.Finally,the authors will touch upon the future perspectives in functional imaging evaluating the role of integrated FDG-PET/CT with perfusion CT,MRI spectroscopy of primary CRC and hepatic transit time analysis using contrast enhanced ultrasound and MRI in the detection of liver metastases.Validation of these newer imaging techniques may lead to significant improvements in the management of patients with colorectal cancer.     

Evaluation of an automated spectrophotometric assay for reactive oxygen metabolites in serum.

The in vivo assessment of free radicals concentration is hampered by their instability and extremely short half-life. The Diacron Reactive Oxygen Metabolites (D-ROM) test is a recently introduced method to evaluate the peroxidation of organic compounds. Since the manual performance of the test provides excessive analytical imprecision, the aim of this study was to evaluate the automation of this test. Within- and between-run imprecision and interference were assessed according to the guidelines proposed by the NCCLS. The reactive oxygen metabolites' (ROM) stability was evaluated in different physical conditions. For within-run and between-run imprecision the coefficients of variation were consistently lower than 5%. The maximum allowable concentration was 28.2 mmol/l, 0.068 mmol/l and 171 mmol/l for triglycerides, haemoglobin and bilirubin, respectively. Serum storage at -20 degrees C provided adequate ROM stability for up to 3 months, whereas storage at 4 degrees C yielded non-reproducible results. In conclusion, our data provide evidence that the D-ROM assay has both an acceptable stability and an adequate imprecision. The automated assay may be regarded as a fast and reproducible method for the quantitative evaluation of oxidative stress. Since it is easily performed, the method is suitable for routine in clinical laboratories and may provide an accurate estimation of oxidative stress in vivo.     

Late recurrence of Wilms’ tumour with exclusive skeletal muscle phenotype 23 years after primary diagnosis

A late recurrence of Wilms’ tumour (WT) 23 years after the primary diagnosis is described. The primary tumour occurred in a 10-month-old girl and showed various degrees of differentiation, including skeletal muscle phenotype. A postoperative chemotherapy was performed. Twenty-three years after the surgery, the tumour relapsed: the lesion was exclusively composed of mature skeletal muscle elements (diffuse and intense desmin reactivity) derived from the primary tumour as confirmed by WT1 immunoreactivity. Chemotherapy and radiotherapy have been reported previously to ablate the immature components of WT; especially, chemotherapy can modify the histological type, reducing the immature elements while leaving mature cells unaffected. We can hypothesise that both morphological and molecular features of the tumour as well as the effect of therapy can influence a tumour relapse in WT. The latter results in a high degree of differentiation and a long disease-free interval after the first diagnosis.