Assay of cytomegalovirus susceptibility to ganciclovir in renal and heart transplant recipients

Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management.     

Stability of risk factors for cardiovascular diseases in Portuguese children and adolescents from the Porto area.

An important aspect of preventive medicine is to identify subjects at risk as soon as possible, so preventive strategies can be introduced at early ages. The justification for this strategy is twofold: firstly, the assumption that children maintain a particular high value of a risk factor for disease throughout life; and secondly, the assumption that lowering the level of the risk factor in early life will have a greater impact on the disease than will risk factor changes in later life. In epidemiology the analysis of such factors over time is referred to as tracking. Tracking analysis has been applied to risk factors for cardiovascular diseases (CVD) in pediatric years. The aims of this study were: I) to analyze the stability of biological risk factors [high blood pressure (BP), high percentage of fat mass (%FM) and high total cholesterol (TC)] and lifestyle risk factors [low physical activity index (PAI)] in isolation; and II) to analyze the stability of zero, one, two or three biological risk factors. There were two evaluations in 692 children and adolescents (325 boys and 367 girls), aged between 8 and 15 years. The quartiles, adjusted for age and gender, were the criterion used to identify subjects with biological risk factors (fourth quartile) and with lifestyle risk factors (first quartile) for CVD. The stability was calculated through the relative frequency of subjects who maintained or changed quartile between the two evaluations. There is stability for biological risk factors as well as for behavioral and/or lifestyle risk factors. However, the highest stability is seen in biological risk factors.     

Acute Effects Evaluation of HgCl2 on Epidermis of Trichomycterus brasiliensis (Siluroidei; Trichomycteridae)

The effects of HgCl₂ on the epidermis of Trichomycterus brasiliensis were studied by histological, histochemical, and ultrastructural methods. First, the normal organization of the tissue was described in order to study the HgCl₂ effects on the skin structure. The epithelial cells presented a typical structural organization found in many fishes. Basically five types of cells could be detailed: goblet cells, club cells, germinative stratum cells, intermediate layer cells, and epithelial cells in the superficial layer. The goblet cells in the superficial layer present evidence of secretory activity by positive histochemical reactions. In cells exposed to HgCl₂, different morphological alterations were observed in the epithelium structure, such as an increase in the lymphocyte number, hypertrophied epithelial cells at the surface, modified taste buds, obstruction of the goblet cells pore, and high cellular proliferation. Moreover, the chemical nature of the goblet cells was not modified by the presence of the HgCl₂ dissolved in water. All animals died within 24 hr after the contamination with inorganic mercury at concentrations of 0.2 and 0.1 mg HgCl₂/liter.     

Adjuvant tamoxifen for male breast cancer (MBC).

A study was started in 1976 whereby patients with Stage II and operable Stage III MBC were given adjuvant Tamoxifen for 1 year, increasing to 2 years from 1988. All patients had axillary nodal involvement. Primary treatment consisted of a radical mastectomy or simple mastectomy with radiotherapy. The rarity of the disease precluded a randomised trial. Thirty-nine patients are available for analysis at a median follow-up of 49 months. The actuarial survival of the Tamoxifen treated patients is 61% (range 42-80%) at 5 years compared to 44% (range 35-53%) for historical controls (P = 0.006). Disease-free survival was 56% (37-75%) vs 28% (17-33%) at 5 years (P = 0.005). There were no serious side-effects recorded. The conclusion from this, the first reported series on adjuvant Tamoxifen therapy for MBC, is that significant improvement in disease-free survival can be achieved with minimal upset to the patients. Recruitment to the study continues.     

The effect of oral appliance therapy on blood pressure in patients with obstructive sleep apnea

The objective of the study was to investigate the effects of oral appliance (OA) therapy on ambulatory blood pressure in patients with obstructive sleep apnea (OSA). Eleven OSA patients who received OA therapy were prospectively investigated. Ambulatory blood pressure was measured for 20 h from 4:00 p.m. to 12:00 noon the next day using an ambulatory blood pressure monitor. The Respiratory Disturbance Index (RDI) was measured in the pretreatment and posttitration periods. The OA was titrated to reach a therapeutic jaw position over 2 to 8 months, and posttitration measurements were repeated. At posttitration, the RDI was significantly decreased from a mean (SD) of 24.7 (20.1) to 6.1 (4.5). Significant reductions in diastolic blood pressure (DBP) and mean arterial pressure (MAP) were found for the 20-h periods, and systolic blood pressure (SBP), DBP, and MAP while asleep. The mean values were 79.5 (5.5) to 74.6 (6.0) for DBP and 95.9 (5.4) to 91.2 (5.9) for MAP, for over a 20-h period, and 118.4 (10.0) to 113.7 (9.1) for SBP, 71.6 (8.0) to 67.2 (7.9) for DBP, and 88.4 (8.0) to 83.9 (7.5) for MAP, while asleep. This study suggests that successful OSA treatment with an OA may also be beneficial to lower blood pressure in OSA patients, as previously suggested for nasal continuous positive airway pressure therapy. This study was conducted in the Division of Orthodontics, The University of British Columbia, Canada     

1,3-Dipropyl-8-cyclopentylxanthine attenuates the NMDA response to hypoxia in the rat hippocampus

Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the (NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A₁ receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A₁ receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA₁ area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects.