Prevention of mother-to-child transmission of HIV--what next?

Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) is a global problem. HIV can be transmitted from mother-to-child at various stages of pregnancy including in utero, intrapartum and during breastfeeding. A number of interventions have, therefore, been aimed at effectively providing alternatives to breastfeeding and limiting the risk of newborn infection during delivery, by using caesarian section as the mode of delivery and administering antiretroviral (ARV) drugs prepartum and peripartum. However, these approaches are not always possible in developing countries and the use of ARV drugs, in particular nevirapine, zidovudine and zidovudine/lamivudine, have been investigated in both developing countries and developed countries. The studies have involved the administration of various ARV prophylaxis regimens to HIV-infected pregnant women perinatally, either as monotherapy or in various combinations. In some studies, infants have also received ARV prophylaxis. Although studies have enrolled different populations and utilized various ARV drugs and regimens, encouraging reductions in the MTCT rates have been reported. These interventions have raised concerns regarding the development of ARV-resistant HIV strains. Mutations that confer resistance to nevirapine have been detected in pregnant women who received this drug, but the emergence of these mutations was not associated with an increased risk of transmission of HIV-1 to their infants. Studies are ongoing to determine if the presence of these mutations has implications for the subsequent administration of nevirapine, either to prevent MTCT of HIV-1 or for the mother's own health. Effective interventions that can reduce MTCT of HIV are now available worldwide. However, a number of issues remain to be resolved, particularly methods to reduce the transmission of the virus during breastfeeding and to deliver effective treatment for the mothers' own HIV infection.     

Corticosterone influences on Mammalian neonatal sensitive-period learning

Infant rats exhibit sensitive-period odor learning characterized by olfactory bulb neural changes and odor preference acquisitions critical for survival. This sensitive period is coincident with low endogenous corticosterone (CORT) levels and stress hyporesponsivity. The authors hypothesized that low corticosterone levels modulate sensitive-period learning. They assessed the effects of manipulating CORT levels by increasing and removing CORT during (Postnatal Day 8) and after (Postnatal Day 12) the sensitive period. Results show that (a) exogenous CORT prematurely ends sensitive-period odor-shock-induced preferences; (b) adrenalectomy developmentally extends the sensitive period as indicated by odor-shock-induced odor-preference learning in older pups, whereas CORT replacement can reinstate fear learning; and (c) CORT manipulation modulates olfactory bulb correlates of sensitive-period odor learning in a manner consistent with behavior.     

Problems in the long-term assessment of risks from drugs used in pregnancy maintenance

Progestogens and oestrogens used to maintain pregnancy in casesof threatened abortion could have side-effects on the motheror fetus. The difficulties in interpreting epidemiological studieson the effects of sex hormones on pregnancy are discussed inrelation to the combination of hormones employed, their purpose,time of usage and dosage. ^*Based on a paper presented at the Conference on Post-MarketingSurveillance of Drugs Used in Fertility Regulation, organizedby the International Committee for Research in Reproduction,Leuven 17–19 October 1985.     

Investigation of an outbreak of antibiotic-associated colitis by various typing methods.

During an outbreak of diarrheal disease due to Clostridium difficile in a surgical ward, 16 C. difficile isolates were cultured from fecal samples of 15 patients. Agarose gel electrophoresis for the detection of plasmid DNA, crossed immunoelectrophoresis for the detection of extracellular antigens and toxins, polyacrylamide gel electrophoresis for analyses of soluble proteins, assays for cytotoxicity, and a comparison of susceptibility to antimicrobial agents were employed. At least 12 of the 16 isolates were shown to be phenotypically the same strain. These findings suggest that in a hospital setting, diarrhea and pseudomembranous colitis caused by C. difficile can be of nosocomial origin and that they can spread from patient to patient.     

Pinacidil,a new vasodilator,in the treatment of mild to moderate essential hypertension

Summary Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or -receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell by 44/25 mmHg and 37/24 mmHg respectively over the study period of 12 weeks. Side-effects such as dizziness, headache, facial flushing and mild oedema were experienced by 10 patients during the study, all of which were mild and transient and did not require withdrawal from pinacidil therapy. Pinacidil is an effective and well tolerated agent in the treatment of essential hypertension.     

Food costs and nutrition of aborigines in remote areas of northern Australia

A locally-relevant "market basket" has been devised to help to assess the cost of usual food purchases for Aborigines who live in the Kimberley region. The range of foods in the market basket is relatively restricted, especially for fresh vegetables. In some communities, basic food items cost over 40% more than they would in the Perth metropolitan area. Price differentials and other difficulties encourage unsatisfactory dietary patterns for Aborigines in the region. A food-voucher system is proposed as one possible way to help to overcome serious nutritional imbalances for pregnant women and their infants and young children who are especially vulnerable to nutritional deficiencies. This proposal is likely to be politically unpopular, so other ways should be sought to help to improve the health of Aboriginal mothers and their children.     

Comparison of risk estimates using life-table methods

Risk estimates promulgated by various radiation protection authorities in recent years have become increasingly more complex. Early "integral" estimates in the form of health effects per 0.01 person-Gy (per person-rad) or per 10(4) person-Gy (per 10(6) person-rad) have tended to be replaced by "differential" estimates which are age- and sex-dependent and specify both minimum induction (latency) and duration of risk expression (plateau) periods. These latter types of risk estimate must be used in conjunction with a life table in order to reduce them to integral form. In this paper, the life table has been used to effect a comparison of the organ and tissue risk estimates derived in several recent reports. In addition, a brief review of life-table methodology is presented and some features of the models used in deriving differential coefficients are discussed. While the great number of permutations possible with dose-response models, detailed risk estimates and proposed projection models precludes any unique result, the reduced integral coefficients are required to conform to the linear, absolute-risk model recommended for use with the integral risk estimates reviewed.     

A morphologic study of childhood lymphoma of the diffuse "histiocytic" type. The Pediatric Oncology Group experience

Of 227 cases of pediatric non-Hodgkin's lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse "histiocytic" lymphoma (DHL). These cases were further divided into different morphologic subtypes according to the Lukes-Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T-immunoblastic lymphomas; an additional two had polymorphous features also consistent with T-cell type: 17 had plasmacytoid features, and were morphologically classified as B-immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease-free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease-free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type were younger (P = 0.01); had less nodal involvement (P = 0.03); and had more organ involvement (P less than 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance.     

Neural map of interaural phase difference in the owl''s brainstem.

Neurons of the barn owl's (Tyto alba) nucleus laminaris, the first site of binaural convergence, respond in a phase-locked fashion to a tone delivered to either ear. It may take longer to elicit phase-locked spikes from one ear than from the other. This disparity in delay differs from neuron to neuron and is independent of tonal frequency. In binaural stimulation, neurons respond best when sound in one ear leads that in the other by an amount equal to their delay disparities but opposite in sign. This condition causes simultaneous arrival of phase-locked spikes from the two sides. Laminaris neurons can thus be described as coincidence detectors. The phase of a tone-induced evoked potential, termed "neurophonic," varies systematically with position in nucleus laminaris. From dorsal to ventral within the nucleus, the phase delay of a contralaterally elicited potential decreases and that of its ipsilateral counterpart increases. Therefore, if the neurophonic delay is due to the delay of phase-locked spikes, an orderly representation of delay disparities is shown. Because they act as coincidence detectors, laminaris neurons should show selectivity for interaural phase difference based on their place in the nucleus. Thus, nucleus laminaris presumably measures and maps interaural phase differences by using the principles of delay lines and coincidence detection.