Barrier contraceptive use and HIV infection among high-risk women in Cameroon.

OBJECTIVES: To measure the association between spermicide use and HIV infection, adjusting for condom use, and to measure the association between condom use and HIV infection, adjusting for spermicide use. DESIGN: Prospective study of women using nonoxynol-9 (N-9) spermicides and latex condoms, with up to 12 monthly clinic visits for interviews, examinations and tests, and re-supply. METHODS: A total of 273 HIV-negative women with multiple sexual partners were enrolled, given latex condoms and N-9 vaginal spermicidal suppositories, and advised to use both every time they had sexual intercourse. Participants recorded data on sexual activity on pictorial coital logs. New HIV infections were detected and confirmed by quarterly enzyme-linked immunosorbent assays and Western blots, respectively. RESULTS: Nineteen HIV infections occurred during mean follow-up of 8.1 months (an incidence rate of 10.4 infections per 100 women-years). The adjusted HIV rate ratio (RR) was 0.1 [95% confidence interval (CI), 0.1-0.6] for more consistent compared with less consistent spermicide users; and 1.1 (95% CI, 0.4-2.9) for more consistent compared with less consistent condom users. Among the subgroup of experienced condom users, the RR for more versus less consistent condom use was 0.3. CONCLUSIONS: This is the first epidemiological evidence that N-9 spermicides can reduce the incidence of HIV infection. A more definitive randomized clinical trial is urgently needed.

PIP: In a prospective study, the association between spermicide use and HIV infection was measured, adjusting for condom use, the association between condom use and HIV infection, and spermicide use. A total of 273 HIV-negative female prostitutes, the majority of them in their twenties, were enrolled in the study in Yaounde, Cameroon in 1989-1990. They made up to 12 monthly clinic visits for interviews, examinations, tests, and re-supply of condoms and spermicide. When they were admitted to the study, they were given plain lubricated latex condoms and N-9 vaginal spermicidal suppositories containing 100 mg N-9, and they were advised to use both every time they had sexual intercourse. Participants recorded data on sexual activity and barrier method use on pictorial coital logs (calendars on which coitus, condom use, and spermicide use could be marked). New HIV infections were detected and confirmed by quarterly enzyme-linked immunosorbent assays and Western blots, respectively. Both consistent spermicide use and consistent condom use were associated with lower incidences of gonorrhoea and genital ulcers. 19 HIV-seroconversions (7.0% of the 273 women) occurred during a mean follow-up of 8.1 months (an incidence rate of 10.4 infections per 100 woman-years). The HIV rate ratio (RR) for more consistent spermicide users ( or = 67% use) compared with less consistent users was 0.2 (95% CI, 0.1-0.7), indicating substantial protection against HIV. The HIV RR for more consistent condom users ( or = 63% use) compared with less consistent users was 0.8 (95% CI, 0.3- 2.0), suggesting slight protection. Adjusting for condom use, the RR for more versus less consistent spermicide use was 0.1 (95% CI, 0.1- 0.6). Adjusting for spermicide use, the RR for more versus less consistent condom use was 1.1 (95% CI, 0.4-2.9). Among the subgroup of experienced condom users, the RR for more versus less consistent condom use was 0.3. These findings prove that N-9 spermicides can reduce the incidence of HIV infection.

Production of antisera against electrophoretically separated relaxin and immunofluorescent localization of relaxin in the porcine corpus luteum.

Antisera to porcine relaxin were produced in rabbits injected with different fractions that had been separated by polyacrylamide gel electrophoresis (PAGE). Analyses by agar double immunodiffusion demonstrated that the different fractions of relaxin separated by PAGE have similar antigenic sites and the individual fractions are indistinguishable from one another by this procedure. Antiserum to porcine relaxin inhibited the interpubic ligament forming ability of the hormone in vivo. Indrict fluorescent antibody studies demonstrated that the hormone was localized only in the corpus luteum of the pregnant sow ovary. Large ovoid or polyhedral cells, assumed to be granulosa lutein cells, exhibited the heaviest fluorescence.

Separation of relaxin activities in extracts of ovaries of pregnant sows by polyacrylamide gel electrophoresis.

Polyacrylamide gel electrophoresis has been employed to separate three fractions that have relaxin activity from crude extracts of ovaries of pregnant sows. Bioassays indicated that all fractions had the ability to inhibit spontaneous uterine contractions in vitro and to induce formation of interpubic ligaments in oestrogen-primed mice. The presence of the various fractions in crude extracts of sow ovaries was monitored with the polyacrylamide gel system on days 40, 70 and 100 of pregnancy. Both the total amount and the relative proportions of the fractions were found to change as pregnancy progressed.

Right ventricular function at rest and during exercise in chronic obstructive pulmonary disease. Comparison of two radionuclide techniques.

Right ventricular function was assessed in 24 patients with COPD, at rest and during submaximal exercise, using both technetium-99m (99mTc) blood-pool and krypton-81m (81mKr) equilibrium ventriculography. Technetium-99m right ventricular ejection fraction (RVEF) at rest was lower than 81mKr RVEF (0.39 +/- 0.12 and 0.54 +/- 0.08, respectively; p < 0.001). During submaximal exercise, there was no increase in RVEF using either imaging technique. This observation contrasted with an increase in RVEF in a group of age-comparable normal subjects during modest submaximal exercise. An inability to obtain spatial separation of right heart structures using 99mTc imaging leads to a value for RVEF that is consistently lower than that measured using 81mKr ventriculography. Resting RVEF is well preserved at rest in most patients with COPD. In contrast to normal subjects, many show an inability to augment right ventricular function during exercise that may contribute to the reduced exercise capacity observed in these patients.

Doxazosin in renal impairment.

The pharmacokinetics of doxazosin given once daily are similar in patients both with normal and with impaired renal function and consequently doxazosin can be used effectively in both at similar doses. Renal blood flow is well preserved during long-term treatment but effects on glomerular filtration rates are less consistent and small reductions may occur. It is uncertain whether these reflect a reduction in perfusion pressure, progression of the underlying renal disease or a combination of the two. Postural hypotension may occur in some patients after an initial dose of 1 mg.

The effect of acute hypoxia on right ventricular function in healthy adults.

Right ventricular ejection fraction and right ventricular volumes were derived in 12 healthy male subjects using krypton-81m equilibrium radionuclide ventriculography whilst subjects breathed 30% (high inspired oxygen) and then 8-12% oxygen in nitrogen mixture (hypoxia). 'Physiological' tricuspid valve regurgitation was identified in 7 of the subjects by Doppler echocardiography, and right ventricular peak systolic pressure was estimated during high inspired oxygen and during hypoxia. Mean right ventricular peak systolic pressure was 24.1 +/- 3.3 mmHg during high inspired oxygen and increased to 41.3 +/- 8.4 mmHg during hypoxia (P less than 0.01). Mean right ventricular ejection fraction was 0.612 +/- 0.075 during high inspired oxygen and was unchanged at 0.590 +/- 0.073 during hypoxia. There was no significant change in right ventricular end-diastolic volume or stroke volume in response to hypoxia. The systolic performance of the normal right ventricle is well-maintained during an acute rise in afterload induced by hypoxia.

Dosimetry assessment of 81Krm peripheral venous infusion studies.

Calculation of S factors for 81Krm for a full range of target organs from each source organ relevant in 81Krm peripheral venous infusion imaging has been performed. Typical equilibrium activities in the source organs have been measured using quantitative planar gamma camera imaging for a generator with a mean activity at imaging time of 468 MBq eluted at 10 ml min-1. Based on the above measurements and assuming a 10 min infusion period, the mean effective dose equivalent for 81Krm infusion imaging in the assessment of right heart function in adults was found to be 0.365 mSv.

Right ventricular function at rest and during submaximal exercise assessed by 81Krm equilibrium ventriculography in normal subjects.

81Krm equilibrium ventriculography was used to study right ventricular function in 37 healthy male volunteers. 'Anatomical' lung subtraction using 99Tcm lung perfusion scintigraphy was compared with conventional background correction in the calculation of resting right ventricular ejection fraction (RVEF). Resting RVEF was significantly greater following 'anatomical' lung subtraction than that using background correction (0.59 +/- 0.06 versus 0.55 +/- 0.05). The exercise response of the normal right ventricle was defined in 23 subjects during exercise. Right ventricular ejection fraction showed a progressive increase during graded submaximal exercise (0.55 +/- 0.05 at rest, 0.60 +/- 0.05 at 50 W and 0.66 +/- 0.05 at 100 W). Right heart 81Krm equilibrium ventriculography is well suited to the evaluation of right ventricular function at rest and during exercise. The absolute value of RVEF will however be dependent upon the method of image analysis.

Chest pain in the emergency department.

The assessment of patients with chest pain is challenging for any emergency physician because of the spectrum of illness covered by this symptom. Patients may have a serious life-threatening condition or a trivial self-limiting illness. This article presents an approach to the assessment and early management of patients presenting with acute non-traumatic chest pain in the emergency department.

Toxic effects of 2,3,7,8 tetrachlorodibenzo 1,4 dioxin in laboratory workers.

The toxic effects on three young scientists who had transient minimal exposure to 2,3,7,8 tetrachlorodibenzo 1,4 dioxin (dioxin) are described. Two of them suffered from typical chloracne. Delayed symptoms about two years after initial exposure occurred in two of the scientists. These symptoms included personality changes, other neurological disturbances, and hirsutism. All three scientists were found to have raised serum cholesterol but no other biochemical disturbances, and no porphyrinuria nor liver damage was demonstrated. The question whether the unusually delayed physiological effects were in fact due to the initial dioxin exposure is discussed. Although conclusive evidence is lacking, it seems likely that these delayed effects were in fact due to dioxin intoxication.

Progressive apical pleural fibrosis: a 'constrictive' ventilatory defect.

We report two patients with bilateral apical pleural fibrosis which may be a form of benign asbestos-related pleurisy, one of these being steroid responsive. The pulmonary function defect of reduced lung volumes with raised gas transfer coefficient is characteristic and is best described as 'constrictive'.

Cardiac tamponade due to pneumopericardium.

Pneumopericardium is rare in acute asthma and cardiac tamponade has not been reported. The case is reported of a 20 year old asthmatic patient in whom assisted ventilation and high airway pressures resulted in tension pneumopericardium with clinical signs of cardiac tamponade that were relieved by pericardial aspiration.

The time dependence of single file diffusion.

The single file diffusion of particles through a narrow pore membrane separating two media is treated as a stochastic birth and death process. A set of differential-difference equations is derived to describe the probability of finding n particles in the pore at any time whose source is the left-hand medium. Explicit time-dependent solutions for an arbitary number of sites are obtained. These can be used to calculate both one-way and net flux as a function of time. Parameters are estimated from steady state permeability data, and the results of some numerical calculations are presented to illustrate the time required to approach a steady state. In many cases, significant time delays can occur.

Crystallization and preliminary structural analysis of dihydrolipoyl transsuccinylase, the core of the 2-oxoglutarate dehydrogenase complex.

Dihydrolipoyl transsuccinylase, one of the three enzymes comprising the Escherichia coli 2-oxoglutarate dehydrogenase (EC 1.2.4.2) complex, has been crystallized. Studies by x-ray diffraction and electron microscopy establish that the transsuccinylase has octahedral (432) symmetry, i.e., it consists of 24 subunits that are structurally identical.

A computer model analysis of the active-site coupling mechanism in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

A computer modeling system developed to analyze experimental data for inactivation of the Escherichia coli alpha-ketoglutarate dehydrogenase complex (KGDC) accompanying release of lipoyl moieties by lipoamidase and by trypsin [Hackert, M.L., Oliver, R.M. & Reed, L.J. (1983) Proc. Natl. Acad. Sci. USA 80, 2226-2230] was used to analyze analogous data for the E. coli pyruvate dehydrogenase complex (PDC). The model studies indicate that the activity of PDC, as found for KGDC, is influenced by redundancies and random processes, which we describe as a multiple random coupling mechanism. In both complexes more than one lipoyl moiety services each pyruvate dehydrogenase (EC 1.2.4.1) or alpha-ketoglutarate dehydrogenase (EC 1.2.4.2) (E1) subunit, and an extensive lipoyl-lipoyl interaction network for exchange of electrons and possibly acyl groups must also be present. The best fit between computed and experimental data for PDC was obtained with a model that has four lipoyl domains with four or, more probably, eight lipoyl moieties servicing each E1 subunit. The lipoyl-lipoyl interaction network for PDC has lipoyl domain interactions similar to those found for KGDC plus the additional possibility of interaction of a lipoyl moiety and its paired mate on each dihydrolipoamide acetyltransferase (EC 2.3.1.12) (E2) subunit. The two lipoyl moieties on an E2 subunit in PDC appear to be functionally indistinguishable, each servicing the acetyltransferase site of that E2 subunit and a dihydrolipoamide dehydrogenase (EC 1.6.4.3) (E3) subunit if the latter is bound to that particular E2 subunit. The observed difference between inactivation of PDC by lipoamidase and by trypsin appears to be due to dead-end competitive inhibition by lipoyl domains that have been modified by excision of lipoyl moieties by lipoamidase.

Hyperammonaemic coma in ureterosigmoid urinary diversion.

We report on a patient with ureterosigmoid anastomosis, who presented with recurrent episodes of confusion, agitation and aggressive behaviour, culminating in coma. Investigations revealed profound hyperammonaemia, which responded to treatment with sodium benzoate and sodium phenylacetate. No definite cause was found for the abnormality, apart from possible urinary tract infection. The patient remains well on a protein restricted diet with mildly elevated levels of plasma ammonia.

Bleeding intracranial aneurysm? Pituitary apoplexy!

Pituitary apoplexy describes the clinical syndrome characterised by headache, visual impairment and ophthalmoplegia caused by sudden enlargement of a pituitary adenoma. This is usually due to extensive tumour infarction or haemorrhage. Pituitary apoplexy is rare, mimics spontaneous intracranial bleeding, and thus may be easily mistaken for acute subarachnoid haemorrhage. Urgent surgical intervention and hormone replacement therapy are required.

Evidence for a multiple random coupling mechanism in the alpha-ketoglutarate dehydrogenase multienzyme complex of Escherichia coli: a computer model analysis.

A computer modeling system was used to analyze experimental data for inactivation of the Escherichia coli alpha-ketoglutarate dehydrogenase complex accompanying release of lipoic acid residues by lipoamidase and by trypsin [Stepp, L. R., Bleile, D. M., McRorie, D. K., Pettit, F. H. & Reed, L. J. (1981) Biochemistry 20, 4555-4560]. The results provide insight into the active-site coupling mechanism in the alpha-ketoglutarate dehydrogenase complex. The model studies indicate that the overall activity of the alpha-ketoglutarate dehydrogenase complex is influenced by redundancies and random processes that we describe as a multiple random coupling mechanism. More than one lipoyl moiety services each E1 subunit (alpha-ketoglutarate dehydrogenase, EC 1.2.4.2), and an extensive lipoyl-lipoyl interaction network for exchange of electrons and possibly acyl groups must also be present. The best fit between computed and experimental data was obtained with a model that has two lipoyl moieties servicing each E1 subunit and a lipoyl-lipoyl interaction network that links all lipoyl moieties on the E2 cube (dihydrolipoamide succinyltransferase, EC 2.3.1.61). The single lipoyl moiety on an E2 subunit is assumed to service the coenzyme A-dependent succinyltransferase site of that E2 subunit as well as an E3 subunit (dihydrolipoamide dehydrogenase, EC 1.6.4.3) if the latter is bound to that particular E2 subunit.