Screening for known mutations in <Emphasis Type="Italic">EIF2B</Emphasis>genes in a large panel of patients with premature ovarian failure

Background  

Premature Ovarian Failure (POF), defined as the development of hypergonadotropic amenorrhea before the age of 40 years, occurs in about 1% of all women. Other than karyotype abnormalities, very few genes are known to be associated with this ovarian dysfunction. Recently, in seven patients who presented with POF and white matter abnormalities on MRI (ovarioleukodystrophy) eight mutationswere found in EIF2B2, 4 and 5.     

Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.     

Lenticulostriate echogenic vessels: clinical and sonographic study of 70 neonatal cases

Background Neonatal branching echogenic streaks in the basal ganglia or 'lenticulostriate vasculopathy' (LSV) has no clear comprehensive aetiology.Objective To provide some clinical evidence, possibly relevant to aetiology, by analysis of a large series.Materials and methods Seventy cases (9 deaths, 3 post mortem) identified between 1981 and 2000 out of 9,138 neonates with routine brain sonograms (578 in a protocol for neonates from HIV+ mothers). Review of maternal/neonatal charts for clinical data and serologic status. Retrospective analysis of sonograms for grading and time course of LSV and coexistent abnormalities.Results LSV was unilateral in 31 cases (22 right), bilateral in 39. Grading separated 8 major, 27 moderate and 35 minor patterns. In 42 cases, LSV was isolated, and in 28 it was mixed with peri-intraventricular haemorrhage grades I or II and/or leucomalacia. LSV was detected in the first postnatal week in 56 instances and appeared later in 13. Disappearance occurred mostly within 2 months. Perinatal circumstances: 13 recipient monochorionic twins (polycythaemia from twin-twin transfusion syndromes), 20 HIV+ mothers (possible immunological disturbances; only 2 infected neonates), 10 congenital anomalies, 1 toxoplasmosis, 1 postnatal cytomegalovirus infection, 25 miscellaneous conditions. Numerous maternal and neonatal factors were non-contributory.Conclusions These results do not support congenital toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections as the main causative factor. Polycythaemia and various immunological disturbances may be involved, as well as infectious agents not appropriately screened by routine serodiagnoses.     

In vitro control of human bone marrow stromal cells for bone tissue engineering

For the clinical application of cultured human mesenchymal stem cells (MSCs), cells must have minimal contact with fetal calf serum (FCS) because it might be a potential vector for contamination by adventitious agents. The use of human plasma and serum for clinical applications also continues to give rise to considerable concerns with respect to the transmission of known and unknown human infectious agents. With the objective of clinical applications of cultured human MSCs, we tested the ability of autologous plasma, AB human serum, FCS, and artificial serum substitutes containing animal-derived proteins (Ultroser G) or vegetable-derived proteins (Prolifix S6) to permit their growth and differentiation in vitro. To conserve as much autologous plasma as possible, we attempted to mix it at decreasing concentrations with the serum substitute containing vegetable-derived mitogenic factors. Under control conditions, by day 10 all the fibroblast colony-forming units (CFU-Fs) were alkaline phosphatase (ALP) positive. However, their number and size were highly variable among donors. Better CFU-F formation was obtained with Ultroser G, and with human AB serum and autologous plasma mixed at, respectively, 5 and 1% with Prolifix S6. The effects of these mixtures on CFU-F formation demonstrate synergy, with the human serum or plasma supplying the factors that favor differentiation of MSCs while Prolifix S6 supplies the mitogenic factors. Finally, we demonstrated the possibility of controlling human MSC growth and differentiation in vitro. Notably, by means of a minimal quantity of human serum or human plasma mixed with a new serum substitute containing vegetable-derived proteins, we displayed growth and differentiation of human MSCs comparable to that obtained with FCS or serum substitutes containing animal-derived proteins. These results will have crucial significance for future applications of cultured human MSCs in bone tissue engineering.     

Cerebrospinal fluid lactate and pyruvate concentrations and their ratio in children: age-related reference intervals

BACKGROUND: Lactate (L) and pyruvate (P) concentrations in cerebrospinal fluid (CSF) and the L/P ratio have diagnostic value in numerous primary and acquired disorders affecting the central nervous system, but age-related reference values are not available for children. METHODS: We analyzed CSF and blood lactate and pyruvate concentrations and their ratio in a 4-year retrospective survey of a children's hospital laboratory database. Reference intervals (10th-90th percentiles) were established from data on 197 hospitalized children. A recent regression modeling method was used to normalize and smooth values against age. The model equation of best fit was calculated for each variable. RESULTS: Slight age-related variations were shown by the model, with an increase in lactate, a decrease in pyruvate, and a resulting increase in the L/P ratio with increasing age. However, the SD did not vary with age. We defined the upper limit of the reference intervals as the 90th percentiles, which from birth to 186 months of age varied continuously from 1.78 to 1.88 mmol/L (6%), 148 to 139 micro mol/L (6%), and 16.9 to 19.2 (14%) for lactate, pyruvate, and the L/P ratio, respectively. At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively. CONCLUSIONS: In children, CSF lactate and pyruvate concentrations and their ratio appear to vary slightly with age. Average 90th percentile values of 1.8 mmol/L, 147 micro mol/L, and 17, respectively, could be used in infants up to 24 months of age. In older children, age-adjusted reference intervals should be used, especially when values are close to the 90th percentile.     

Herpes as viewed by the French: result of a survey conducted on 10,000 persons

Herpes is a viral infection which increases, specifically genital herpes. The aim of this survey was to assess the perception of herpes in the general population and in patients with herpes in France using a self-administered questionnaire. A total of 10,000 persons answered the questionnaire among which 128 patients presented herpes. This study showed that only 5% of the French population knew that herpes was a viral infection, and 7% a sexually transmitted disease. Among patients with genital herpes only 34% indicated a sexual relationship and a mode of contamination. The interference with sexual and social life is important. Development of information and communication on herpes appears crucial.     

Anti-CD20 monoclonal antibody (Rituximab) treatment for Epstein-Barr virus-associated, B-cell lymphoproliferative disease in pediatric liver transplant recipients

OBJECTIVES: Anti-B-cell immunotherapy has been used with success in adults with posttransplant B-cell lymphoproliferative disease (PTLD), but such treatment has rarely been reported in children. We report the outcome of anti-CD20 antibody (rituximab) therapy for Epstein-Barr virus (EBV)-associated PTLD in six pediatric liver transplant recipients. METHODS: In these six patients, PTLD was diagnosed within 2 to 4 months after transplantation. The tumors were classified as monomorphic or polymorphic B-cell infiltrate expressing CD20 antigen and EBV genome. Anti-CD20 therapy was associated with withdrawal of tacrolimus or ciclosporine therapy in all patients. Intravenous rituximab was administered at 375 mg/m2 once a week for 3 to 4 consecutive weeks. RESULTS: Rituximab treatment was associated with decreased EBV load, disappearance of abnormal serum immunoglobulin concentration, and disappearance of tumoral masses, which occurred 1 to 2.5 months after treatment onset. Despite rituximab therapy, one patient was diagnosed subsequently with a cerebral tumor. Five patients experienced acute liver graft rejection episodes within 10 days to 2.5 months after beginning treatment. In these patients, immunosuppression was reintroduced, but three children experienced fatal chronic rejection, whereas two experienced complete tumor remission. Three children are alive and in complete remission, with normal liver tests, 15 months to 3 years after PTLD onset. CONCLUSIONS: Rituximab therapy is an interesting approach for children with early EBV-associated PTLD after liver transplantation. It does not prevent cerebral localization, and rapid resumption of immunosuppression may be advisable to prevent lethal chronic liver graft rejection.