The relationship between nickel chloride-induced peroxidation and DNA strand breakage in rat liver.

Inorganic nickel chloride induces hepatic DNA strand breaks, chromosome aberrations, and lipid peroxidation under in vitro and in vivo conditions. The objective of this research was to determine if a relationship exists between NiCl2 genotoxicity and lipid peroxidation in vivo. Male Sprague-Dawley rats (210-250 g) were dosed with 0.56 or 0.75 mmol/kg NiCl2 subcutaneously and euthanized after specific time periods, ranging from 30 min to 24 hr. Livers were perfused and excised for the measurement of nickel content using atomic absorption spectrometry, lipid peroxidation using a thiobarbituric acid assay, and DNA strand breakage using single-stranded DNA extraction and the diaminobenzoic acid assay. The lower dose (0.56 mmol/kg) did not induce lipid peroxidation or strand breakage. The higher dose (0.75 mmol/kg) induced DNA strand breakage at 4 hr and lipid peroxidation at 12 hr in rat liver. Nickel was seen to accumulate in liver nuclei of rats receiving 0.75 mmol/kg. Deferoxamine (1 g/kg, ip, 15 min before the NiCl2 injection) completely inhibited DNA strand breakage at 4 hr but had no effect on lipid peroxidation. This suggests that lipid peroxidation is not causally related to genetic damage. NiCl2-induced DNA strand breakage may be caused by the induction of the Fenton reaction, generating hydroxyl radicals.     

Feasibility of cellular microencapsulation technology for evaluation of anti-human immunodeficiency virus drugs in vivo

We investigated the feasibility of micro-encapsulation technology for the evaluation of anti-human immunodeficiency virus (HIV) drugs in vivo. The ability to place human cells in microcapsules with semipermeable membranes for implantation into test animals led to the development of this assay. The anti-HIV activity assay involves microencapsulating human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV; the encapsulated cells are then implanted into athymic nude mice and recovered after drug treatment in vivo. A positive antiviral effect of the test substance is indicated by growth or survival of the virus-infected cells in the microcapsules. Several HIV-sensitive cell lines of T-lymphocyte, monocyte, and nonlymphocyte origin were examined for growth in microcapsules in vitro and in vivo. Light and electron microscopic analysis of the capsules and the human cells contained therein revealed the invasion of mouse immune cells and other adverse effects that could not be overcome by any of numerous technical modifications attempted. We conclude that cellular microencapsulation technology is not feasible for in vivo drug-testing protocols because of immunogenic reactions.     

Clinical experience with phototherapy

Thirty subjects with seasonal affective disorder (SAD) and three subjects with a non-seasonal depression had a trial of phototherapy in an open assessment of the feasibility of phototherapy in clinical practice. 43% of the SAD subjects met the criteria for 'successful treatment', but none of the subjects with non-seasonal depression showed any response. Due to personal constraints, not all were able to receive light exposure up to the amount recommended. Results indicated that the more severe the atypical symptoms of depression the more likely they were to respond to phototherapy, while greater severity of 'endogenous' symptoms predicted a poor response. Several subjects used the trial to decide whether to purchase equipment to continue treatment. Follow-up information on these subjects is presented.     

Metabolism of lipid molecular species in rat rod outer segments

We have studied the metabolism of selected diacyl molecular species of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and diacylglycerol (DG) from rat rod outer segments (ROS). Rats were injected intravitreally with [2-3H]glycerol. At 1, 2, 3, 4 and 6 days post-injection, ROS phospholipids and DG were isolated by two-dimensional thin-layer chromatography (TLC), derivatized, and fractionated into molecular species by high-performance liquid chromatography (HPLC). Selected molecular species were quantitated and counted for radioactivity. We found the following. In PC and PE, the specific activities of 22:6-22:6, 18:1-22:6 and 16:0-22:6 were highest at day 1 and then decreased in a nearly exponential manner. In contrast, the specific activities of 18:0-22:6 and 18:0-20:4 were substantially lower than these three molecular species and changed little over the 6-day period. In PS, the specific activities of 22:6-22:6, 18:0-22:6 and 18:1-22:6 were similar and did not reach their maximum until the 3rd or 4th days. In PC, the specific activities of the five molecular species examined were two to three times higher at day 1 than the same species in PE and PS. In PI and DG, the major molecular species were 16:0-20:4 and 18:0-20:4. The specific activities of these two molecular species at day 1 were about ten times higher than those of 20:4-containing species in PE and PC, and showed the most rapid turnover of any of the molecular species examined in this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical treatment of degenerative mitral regurgitation

Between October 1965 and April 1975, mitral valve replacement was performed In 66 patients with myxomatous degeneration of the mitral valve (“floppy valve syndrome”). Operative mortality was 6 percent (four patients). Current evaluation was obtained for all patients; the average postoperative follow-up interval for surviving patients was 3.5 years (range 1 month to 9.9 years); the total duration of postoperative follow-up for all patients was 180 patient-years. Overall survival rates, calculated by the actuarial method, were 81, 68 and 50 percent, respectively, 1, 2 and 5 years after mitral valve replacement.Preoperative variables with a significantly adverse effect on patient survival included patient age greater than 50 years, New York Heart Association functional class IV, left ventricular end-diastolic pressure greater than 12 mm Hg and mean pulmonary arterial wedge pressure greater than 16 mm Hg. Support is advanced for the concept that mitral valve dysfunction associated with myxomatous degeneration constitutes a broad spectrum of clinicopathologic involvement. Acute clinical and hemodynamic deterioration may often occur in the setting of chronic mitral valve dysfunction. Postoperative mortality is directly related to preoperative functional disability and hemodynamic evidence of impaired left ventricular function. Consideration should be given to earlier operative intervention in patients with myxomatous mitral degeneration and mitral insufficiency before severe and probably irreversible impairment of ventricular function occurs.     

Pregnant women's experiences of male partner involvement in the context of prevention of mother-to-child transmission in Khayelitsha,South Africa

Male partner involvement (MPI) has been identified as a priority intervention in programmes for the prevention of mother-to-child transmission (PMTCT) of HIV, but rates of MPI remain low worldwide. This study used a quantitative survey (n = 170) and two focus group discussions (FGDs) with 16 HIV-positive pregnant women attending a public sector antenatal care service in Khayelitsha, South Africa, to examine the determinants of high levels of involvement and generate a broader understanding of women's experiences of MPI during pregnancy. Among survey participants, 74% had disclosed their status to their partner, and most reported high levels of communication around HIV testing and preventing partner transmission, as well as high levels of MPI. High MPI was significantly more likely among women who were cohabiting with their partner; who had reportedly disclosed their HIV status to their partner; and who reported higher levels of HIV-related communication with their partner. FGD participants discussed a range of ways in which partners can be supportive during pregnancy, not limited to male attendance of antenatal care. MPI appears to be a feasible intervention in this context, and MPI interventions should aim to encourage male partner attendance of antenatal care as well as greater involvement in pregnancy more generally. Interventions that target communication are needed to facilitate HIV-related communication and disclosure within couples. MPI should remain a priority intervention in PMTCT programmes, and increased efforts should be made to promote MPI in PMTCT.     

Increasing pericardial effusion in cardiac transplant recipients

Although pericardial effusion after cardiac surgery is frequent and usually benign, its etiology and prognosis after cardiac transplantation are unknown. During 1 year (1985-1986), 12 of our current transplant population (total, 189) developed moderate or large pericardial effusions confirmed by two-dimensional echocardiography. These effusions occurred within 1 month of transplantation in 10 patients and at 3 months and 4.5 years in the other two. Pericardiocentesis was performed because of clinical evidence of increasing effusions in eight patients, with demonstrable hemodynamic compromise secondary to tamponade in five. Pericardial fluid was sterile in all but one. Endomyocardial biopsy at the time of increasing effusion revealed moderate acute rejection in five patients, mild rejection in three, and no rejection in four. All three patients with mild rejection had moderate acute rejection on subsequent biopsy performed within 7 days. In two of the four with no rejection, repeat biopsy within 5 days showed moderate acute rejection; in a third, moderate rejection was present on biopsy performed 14 days later. Legionella dumoffii was isolated from the pericardial fluid of the fourth patient, whose subsequent biopsies never showed rejection. Three of the 12 patients developed progressive ventricular dysfunction sufficiently severe to require retransplantation. One patient died suddenly 12 months after transplantation, and autopsy examination revealed severe coronary artery disease. Two died of sepsis within 3 months of transplantation. Intense inflammatory infiltrates and thickening of the pericardium and epicardium were characteristically present in explanted and autopsy hearts.(ABSTRACT TRUNCATED AT 250 WORDS)