Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland

OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. CONCLUSIONS: Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.     

Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and report of two cases

Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma, called chondroid chordoma that was found to have a significantly better prognosis than classic chordoma. However, recent evidence suggests that many of the tumors diagnosed as chondroid chordoma may, in fact, be low-grade myxoid chondrosarcomas. This report presents the diagnosis and treatment of two cases of skull base tumor that were diagnosed preoperatively as schwannoma because they were thought initially to be centred on the jugular foramen. Initial histologic evaluation suggested chondroid chordoma, but immunohistologic techniques and a review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.     

Gene recognition via spliced sequence alignment

Gene recognition is one of the most important problems in computational molecular biology. Previous attempts to solve this problem were based on statistics, and applications of combinatorial methods for gene recognition were almost unexplored. Recent advances in large-scale cDNA sequencing open a way toward a new approach to gene recognition that uses previously sequenced genes as a clue for recognition of newly sequenced genes. This paper describes a spliced alignment algorithm and software tool that explores all possible exon assemblies in polynomial time and finds the multiexon structure with the best fit to a related protein. Unlike other existing methods, the algorithm successfully recognizes genes even in the case of short exons or exons with unusual codon usage; we also report correct assemblies for genes with more than 10 exons. On a test sample of human genes with known mammalian relatives, the average correlation between the predicted and actual proteins was 99%. The algorithm correctly reconstructed 87% of genes and the rare discrepancies between the predicted and real exon-intron structures were caused either by short (less than 5 amino acids) initial/terminal exons or by alternative splicing. Moreover, the algorithm predicts human genes reasonably well when the homologous protein is nonvertebrate or even prokaryotic. The surprisingly good performance of the method was confirmed by extensive simulations: in particular, with target proteins at 160 accepted point mutations (PAM) (25% similarity), the correlation between the predicted and actual genes was still as high as 95%.     

Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal]

BACKGROUND: Short-chain fatty acids (SCFA), produced in the normal colon by bacterial fermentation, are decreased in acute diarrhoea. This may have deleterious effects on epithelial function in the colon. METHODS: The ability of several diarrhoeal pathogens to produce SCFA when incubated with starch in vitro was studied. Isolated pathogens were incubated for 24 h with either no added substrate, glucose, or starch under anaerobic conditions, and SCFA were quantitated by gas-liquid chromatography. RESULTS: Unlike the normal colonic flora, the pathogens produced acetate but not propionate or butyrate. D-Lactate was also produced by all the pathogens studied. When the pathogens were incubated in anaerobic medium containing starch, significantly greater amounts of acetate and significantly lesser amounts of lactate were produced. CONCLUSIONS: The inability of enteric pathogens to produce butyrate may impair epithelial cell function, whereas production of D-lactate may enhance mucosal damage in diarrhoeal disease. The presence of luminal starch may be helpful in shifting the fermentation profile to a more favourable pattern.     

Sinonasal undifferentiated carcinoma: CT and MR imaging of an uncommon neoplasm of the nasal cavity

C1 domains are compact alpha/beta structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain 2 C1 domains (C1A and C1B) in their N-terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain-containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site-directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty-six C1 domains fit the profile for phorbol-ester binding and are termed "typical." Twenty-eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed "atypical." Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not.     

Clinical informatics and the dental curriculum. A review of the impact of informatics in dental care, its implications for dental education

Important advances have been made in the field of supraventricular and ventricular tachycardias. Catheter ablation procedures are potentially curative in many patients suffering of supraventricular tachycardias. The technique uses radiofrequency current. This form of energy is already very familiar to surgeons. Expected benefits as well as potential complications have to be discussed with the patient prior to the ablation procedure. The automatic internal defibrillator has been commercially available since the end of the eighties. It delivers electrical therapy in case of ventricular malignant arrhythmias, for instance ventricular fibrillation. The sudden death rate is markedly reduced in implanted patients. The long term prognosis however remains critically dependent of the left ventricular function and possible progressive heart failure. Reimbursement depends on pre-implant agreement by the Social Security. At the present time, no reimbursement is provided for prophylactic indications. These two techniques facilitates the treatment of patients previously described as "resistant cases".     

Impact of the Delaney Clause in the EPA

The U.S. Environmental Protection Agency serves as the lead agency of the Federal government for the regulation of pesticide use in the United States. Regulatory responsibilities are mandated in the Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and several sections of the Federal Food Drug and Cosmetic Act (FFDCA). In order for a pesticide to be used in the U.S., it must either be granted a full registration under Section 3, or offered special consideration under Section 18 or 24 of FIFRA. Tolerances (maximum allowable residue limits) for pesticides to be used on agricultural commodities meant for human consumption or animal feed are established under Sections 408 and/or 409 of FFDCA. This presentation will describe the underlying conflict between Section 409 of FFDCA and both Section 408 and FIFRA, the recommendations made by the National Academy of Sciences in its 1987 publication Regulating Pesticides in Food--The Delaney Paradox, EPA's attempts to implement these recommendations, the true impact of "Delaney" on the ability of EPA to grant tolerances on raw or processed foods for chemicals determined to meet the "induce cancer" criterion and the status of legislation designed to "fix" Delaney.     

Nasal lavage as tool for health effect assessment of photochemical air pollution

In order to achieve esthetically more satisfying results, it has been proposed to place ITI implants with their border between the rough and smooth surfaces below the level of the alveolar crest, thereby obtaining a submucosally located implant shoulder following healing. The aim of the present experimental study was to clinically and radiographically evaluate the tissue response to the placement of one-stage transmucosal implants with the border between the rough and the smooth surfaces sunk by 1 mm into a subcrestal location. 11 patients underwent comprehensive dental care including the placement of 2 implants of the ITI Dental Implant System in the same quadrant (test and control). Randomly assigned control implants were placed according to the manufacturer's instructions, i.e. the border between the rough titanium plasma-sprayed and the smooth polished surfaces precisely at the alveolar crest. At the test implant the apical border of the polished surface was placed approximately 1 mm below the alveolar crest. Probing bone levels were assessed at implant placement (baseline), 4 and 12 months later. Modified plaque and modified gingival indices were recorded at 1, 2, 3, 4 and 12 months. Clinical probing depth and "attachment" levels were measured at 4 and 12 months. All parameters were assessed at 6 sites around each implant. The mean for each implant was calculated and used for analysis. The Wilcoxon matched pairs signed rank test and the Student t-test were applied to detect differences over time and between the test and control implants. At baseline, a mean difference in probing bone level of -0.86 mm (SD 0.43 mm, p < 0.05) was found between test and control implants with the test implants being placed more deeply. Both test and control implants lost a significant amount of clinical bone height during the first 4 months (test 1.16 mm, p < 0.05; control 0.58 mm, p < 0.05). However, only the test implants significantly lost clinical bone height from 4-12 months (test 1.04 mm, p < 0.05; control 0.45 mm, p = 0.08). Overall, the test implants lost 2.26 mm and the control implants 1.02 mm of bone height during the first year of service. On the average, the test implants demonstrated a bone level of 0.38 mm lower than the controls at 12 months. Except for the modified gingival index at 4 months (mean difference 0.21, SD 0.19, p < 0.05), no clinical parameters yielded significant differences between test and control implants at any time. It is concluded that in addition to the crestal bone resorption occurring at implants placed under standard conditions, the bone adjacent to the polished surface of more deeply placed ITI implants is also lost over time. From a biological point of view, the placement of the border between the rough and the smooth surfaces into a subcrestal location should not be recommended.     

Molecular lipophilicity potential (MLP) in drug design. Complementing theoretical tools with experimental results

The Molecular Lipophilicity Potential (MLP) is a versatile tool in drug design whose present state and potential developments are reviewed here. The MLP offers a three-dimensional representation of lipophilicity as calculated from partition coefficients. The intermolecular recognition forces and intramolecular effects encoded in lipophilicity are presented, followed by the theoretical foundations and validation of the MLP. It is then demonstrated that the MLP allows for the first time to investigate the dependence of lipophilicity on conformation. As a matter of fact, the MLP combined with an exploration of the conformational space of a solute reveals its "chameleonic" behaviour, i.e. its capacity to adapt to the molecular environment. Other applications of the MLP are presented and illustrated, namely its integration into 3D-QSAR (Comparative Molecular Field Analysis, CoMFA) and its interest as a docking tool.