Encouraging results despite complexity of multidisciplinary care of HIV-infected women using assisted reproduction techniques

BACKGROUND: Assisted reproduction technologies can treat infertility for human immunodeficiency virus (HIV) seropositive women. We assessed the efficacy of these techniques in the results and difficulties encountered while conducting our assisted reproduction programme for 49 couples in which at least the woman had HIV infection that was currently under control. METHODS: Treatments included intrauterine insemination (IUI), IVF and ICSI, with ovarian stimulation. Embryos were transferred on day 3 after oocyte retrieval. An elective single transfer was performed, except for patients aged > or = 40 years. RESULTS: The median age of the women was 36 years. Ten IUI, nine IVF, 53 ICSI and 10 frozen-thawed embryo transfers have been performed. No pregnancy occurred following the IUI trials but for the couples with IVF and ICSI attempts the clinical pregnancy rate per embryo transfer was 23.9%. Eight babies have been born leading to a 22.2% take home baby rate per treated couple. Contamination was not observed in any newborn. CONCLUSIONS: Assisted reproduction technologies and particularly ICSI can provide HIV seropositive women with a safe means of mothering children. Results are encouraging when considering the age of the patients and a preferential single embryo transfer.     

Two pericentric inversions, inv(2)(p11q13) and inv(5)(p13q13), in a patient referred for psychiatric problems

Two pericentric inversions were found in the karyotype of a male patient referred for psychiatric problems. Cytogenetic analysis, using conventional Giemsa staining and G and C banding techniques, revealed a pericentric inversion in chromosome 2, inv(2)(p11q13), and chromosome 5, inv(5)(p13q13) (fig 1). Subsequent family studies showed that the proband's father carried both inversions also (fig 2), while other members were found to be carriers of either the inverted 2 or the inverted 5. To our knowledge, this is the first report of two pericentric inversions to be found in the human genome.     

Critical effect of cubic phase on aging in 3mol% yttria-stabilized zirconia ceramics for hip replacement prosthesis

The isothermal tetragonal-to-monoclinic transformation of 3Y-TZP ceramics sintered at two different temperatures (1450 degrees C and 1550 degrees C) and duration (2 and 5h) is investigated at 134 degrees C in steam. Particular attention is paid to the presence of a cubic phase and its effect on isothermal aging. Sintering at 1550 degrees C can result in a significant amount of large cubic grains in the specimens, that have a detrimental impact on aging resistance, especially for the first stage of the aging process. Cubic grains appear to be enriched in yttrium, which in turn leads to a depletion of yttrium in the neighboring tetragonal grains. These grains will act as nucleation sites for tetragonal-to-monoclinic transformation. Even for specimens sintered at lower temperature, i.e. 1450 degrees C, the presence of a cubic phase is expected from the phase diagram, leading to a significant effect on aging sensitivity.     

Repetitive firing of rat cerebellar parallel fibres after a single stimulation

The excitatory postsynaptic currents (EPSCs) evoked in Purkinje cells (PCs) by stimulating parallel fibres (PFs) usually show a single peak, but EPSCs with multiple peaks (polyphasic EPSCs) can be observed in slices from animals older than 15 days. The EPSCs remain polyphasic when the postsynaptic current is reduced (either by reducing the intensity of the PF stimulation or by adding AMPA receptor antagonists) and when the PC membrane potential is made positive. Thus the late peaks are not due to postsynaptic active currents generated in the imperfectly clamped PC, and must arise from repetitive action potentials in the PF. Extracellular recordings from granule cell (GC) somata showed that a single PF stimulation can elicit a doublet or a train of action potentials. Both the late action potentials recorded in the GCs and the late peaks of the polyphasic EPSCs recorded in the PCs were reduced or abolished by paired-pulse stimulation of the PF or by bath application of the GABA_A agonist muscimol. The late action potentials in the GCs were also suppressed by local application of muscimol around the cell body. We propose that after a single stimulation of a PF, the antidromic invasion of the ascending axon and the granule cell can trigger a doublet or a burst of action potentials which back-propagate into the PF (except for the first, which finds the PF still in its refractory period). The repetitive activation of the PF by a single stimulation could play a role in the induction of long-term depression.     

Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide.

BACKGROUND: Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. OBJECTIVE: To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. METHODS: In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients). RESULTS: Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. CONCLUSIONS: Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.     

Interferon regulatory factor-6: a gene predisposing to isolated cleft lip with or without cleft palate in the Belgian population

Cleft lip with or without cleft palate is the most frequent craniofacial malformation in humans ( approximately 1/700). Its etiology is multifactorial; some are a result of a genetic mutation, while others may be due to environmental factors, with genetic predisposition playing an important role. The prevalence varies widely between populations and the mode of inheritance remains controversial. The interferon regulatory factor-6 (IRF6) gene has been shown to harbor mutations in patients with van der Woude syndrome, a dominant form of clefts associated with small pits of the lower lip. Moreover IRF6 has been associated with nonsyndromic cleft of the palate (CL/P) in two separate studies. We investigated the role of IRF6 in a set of 195 trios from Belgium. Cleft occurred as an isolated feature. We studied association of the IRF6 locus using two variants: one in the IRF6 gene and the other 100 kpb 3' of the gene. Our independent study group confirms that the IRF6 locus is associated with nonsyndromic cleft lip with or without palate. This result, with previous studies performed in the United States and Italy, shows for the first time the implication of IRF6 in isolated CL/P in northern Europe. It is likely that association to this locus can be identified in various populations and that the IRF6 locus thus represents an important genetic modifier for this multifactorial malformation.     

Heparan sulfate proteoglycan mediates the selective attachment and internalization of serotype 3 human adenovirus dodecahedron

During adenovirus type 3 (Ad3) infection cycle, the penton (Pt) of the viral capsid, a noncovalent complex of fiber and penton base proteins, is produced in large excess and self-assembles to form a highly organized dodecahedral structure, termed dodecahedron (Dd). The physiological role of these particles is poorly understood, but we have recently reported that they can penetrate cells with high efficiency and thus may constitute an attractive tool for gene or protein delivery approaches. Surprisingly, Dd displayed the ability to enter cells non-permissive to Ad3, suggesting the existence of additional internalization modes. In this study, we show that Ad3 Dd binds to cell surface heparan sulfate (HS) through high affinity interaction with the penton base. Furthermore, binding to HS was found to be the prerequisite for a novel and Dd specific entry pathway that could not be used by Ad3. Overall, these data provide new insights in the possible role of Dd during viral infection and potential therapeutic applications.     

End-Stage Respiratory Failure Secondary to Bronchiolitis Obliterans Syndrome Induced by Toxic Epidermal Necrosis,Also Known as Lyell Syndrome: A Case Report

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases. They can be associated with systemic manifestations such as bronchiolitis obliterans syndrome (BOS). SJS/TEN-induced BOS is associated with a poor prognosis, and no guidelines exist regarding its management. Several case reports have described the association between SJS/TEN and BOS, with few patients undergoing lung transplantation as a last resort therapy. Unfortunately, in the published reports, none of the transplanted patients were observed for a long period of time after the transplantation; therefore, the long-term mortality as well as the risk of recurrence of BOS could not be inferred from these reports.Case reportWe present the case of a young patient diagnosed with SJS complicated by BOS and end-stage respiratory failure refractory to corticosteroid therapy. She underwent bilateral lung transplantation with an outstanding outcome at 5-year follow-up.ConclusionSJS/TEN-induced BOS might have a favorable evolution and long-term outcomes following lung transplantation. However, prospective studies are needed to confirm this finding.