Primary care intervention and management for adults with early HIV infection.

Recent clinical drug trials have demonstrated that early intervention with zidovudine will delay disease progression in asymptomatic or minimally symptomatic HIV-infected individuals. These trials will encourage larger numbers of seropositive persons to seek access to primary care, overloading specialized clinics for AIDS and HIV care. The care of early HIV-infected individuals will need to be delivered by mainstream primary care providers. This article discusses the initiation and management of zidovudine, and chemoprophylaxis against Pneumocystis carinii pneumonia in early HIV infection.     

Mathematical modelling in risk/exposure assessment of tobacco related lung cancer

The existence of a dose-related increase of lung cancer riskin cigarette smokers has been indisputably established. Thisfinding, however, is not confirmed at low doses (< 5 cigarettes/day),there still being a lack of epidemiological data. The use ofmathematical models of carcinogenesis to extrapolate from higherdoses allows estimation of the risk for very light smokers.The present study has been designed to compare a set of mathematicalmodels, i.e. one-hit, two-stage, multi-stage, logit, probit,and Weibull, in extrapolating relative risks at low doses fromthe data of nine large cohort studies on cigarette smokers reportedin the IARC Scientific Monograph on tobacco smoking. All modelsevaluated, apart from the one-hit, achieved a good fit, withthe proportion of explained variance ranging between 61% and67%. The relative risk estimates for passive smokers from themost updated epidemiological studies were taken into accountto evaluate, on the basis of these models, the correspondingexposure in terms of ‘cigarette equivalent’ smoked.These values ranged from 0.21 to 0.43 cigarettes/day for thetwo-stage and multistage model, while probit, logit and Weibullmodels, yielded estimates one or even two orders of magnitudelower. The authors emphasize the substantial agreement betweenthe estimates of ‘cigarette equivalent9 based on the applicationof two-stage and multi-stage models to the epidemiological evidenceon the effect of passive smoking and to the data based on thecomparison of tobacco metabolites in active and passive smokers.     

The simultaneous occurrence of renal artery stenosis and an aldosteronoma in a patient with hypertension

The simultaneous occurrence of renovascular hypertension and an adrenocortical adenoma is a rare entity. The case of a 64-year-old woman who underwent an aortorenal bypass graft for renovascular hypertension requiring a multidrug antihypertensive regimen is presented. Persistently elevated blood pressures in the postoperative period prompted further workup for other causes of hypertension. Laboratory evaluation showed hyperaldosteronism and hyporeninemia despite enalapril administration. Abdominal computerized tomography (CT) revealed a left adrenal mass which, on surgical removal, was found to be a cortical adenoma. Subsequently, her antihypertensive therapy has been reduced to a single agent. Previous authors have described only four patients with malignant hypertension who had the rare clinical combination of renal artery stenosis and an aldosteronoma. This case reemphasizes the critical need for a thorough search for other surgically correctable lesions in those patients who remain severely hypertensive after the "definitive" operation.     

Detection and typing of herpes simplex viruses by using recombinant immunoglobulin fragments produced in bacteria.

Thirty-seven bacterial clones producing human recombinant monoclonal antibody Fab fragments (rFabs) reactive to herpes simplex virus (HSV) antigens were selected from a human combinatorial antibody library constructed in a phage-display vector by a panning procedure against an HSV lysate. Thirty-four of the HSV-specific rFabs were able to specifically recognize HSV-infected cells in indirect immunofluorescence (IF) assays; of these, 25 recognized cells infected by either HSV type 1 (HSV-1) or HSV-2, while 9 recognized only HSV-1-infected cells. One HSV type-common rFab (rFab H37) and one HSV-1-specific rFab (rFab H85) were further evaluated as reagents for viral detection and typing by IF staining in 134 HSV-positive (72 HSV-1 and 62 HSV-2) viral cultures from clinical specimens. The results obtained with these two rFabs were fully consistent with those obtained with a commercial preparation of fluorescein-labeled anti-HSV type-specific murine monoclonal antibodies. The detection sensitivity with the type-common rFab in indirect IF assays was higher overall than that provided by the type-specific murine monoclonal antibodies. Preparations of rFabs suitable for IF staining can be easily and inexpensively obtained in a clinical microbiology laboratory from Escherichia coli cultures. Similar HSV-specific rFabs, therefore, could be advantageous for in vitro diagnostic purposes.     

Psychoactive drug use among practicing physicians and medical students

We surveyed random samples of 500 practicing physicians and 504 medical students in a New England state during 1984-1985; 70 percent of the physicians and 79 percent of the students responded. Fifty-nine percent of the physicians and 78 percent of the students reported that they had used psychoactive drugs at some time in their lives. In both groups, recreational use most often involved marijuana and cocaine, and self-treatment most often involved tranquilizers and opiates. In the previous year, 25 percent of the physicians had treated themselves with a psychoactive drug, and 10 percent had used one recreationally. Although most of the use was experimental or infrequent, 10 percent of the physicians reported current regular drug use (once a month or more often) and 3 percent had histories of drug dependence. More physicians and medical students had used psychoactive drugs at some time than had comparable samples of pharmacists and pharmacy students. The results suggest a need for renewed professional education about the risks of drug misuse.     

Motor responses evoked by microstimulation of restiform body in the cat

Motor effects produced by microstimulation of restiform body (RB) were studied in acute unanesthetized cats, using tungsten electrodes for stimulating the peduncle and bipolar steel electrodes for recording muscular activity (EMG). The main results were the following. 1. Threshold microstimulation (18.24 microA +/- 8.77 S.D.) of effective foci within RB elicited single muscle contractions of ipsilateral limbs, primarily of forelimb; overthreshold activation (32.83 microA +/- 9.25S.D.) of the same points produced complex movements in 61.54% of cases that involved muscles of shoulder, neck, and trunk. 2. Single muscle contractions exhibited a mean latency (20.09 msec +/- 2.04 S.D.) which was significantly longer than that shown by complex movements (10.00 msec +/- 3.10 S.D.). Furthermore, a decrease in frequency of stimulating train below 300 Hz and a reduction in duration below 30 msec caused a steep rise of threshold for single muscle responses that was not observed when studying complex movements. 3. Acute RB interruption between stimulating electrode and cerebellum abolished single muscle contractions; conversely, complex movements remained unmodified even when the RB was lesioned in cats chronically submitted to interruption of brachium conjunctivum (BC). 4. The pathway involved in promoting RB induced single muscle activation includes interpositus nucleus, BC and rubrospinal tract. Possible modalities of RB afferent participation to the motor control are briefly discussed.     

Effects of 5-hydroxytryptamine on the firing rates of neurons of the lateral vestibular nucleus in the rat

Summary 5-hydroxytryptamine (5-HT) was delivered microiontophoretically (20–80 nA) to cells of the lateral vestibular nucleus of anaesthetized rats to test its influence on the spontaneous activity of single neurons. 5-HT increased the rate of firing of 94% of the units tested. The enhancement persisted for up to 700 s after the end of the 5-HT ejection and the maximum magnitude of the excitation (10–3400%) showed a hyperbolic correlation (=0.86) with background firing. In 43% of units the enhancement was preceded by a short-lasting (less than 105 s) depression of the neuronal firing rate, the magnitude of which was unrelated to the background mean firing rate. Both components of the 5-HT response were dose-dependent. Only the excitatory responses were antagonized by metergoline, methysergide and ketanserin. The putative 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine, applied microiontophoretically, depressed the background firing rate and was not antagonized by methysergide. These results demonstrate that 5-HT modifies the responsiveness of vestibular neurons and suggest that at least two mechanisms and maybe two types of receptors are activated by 5-HT in this nucleus.     

Human herpesvirus 8 seroprevalence and evaluation of nonsexual transmission routes by detection of DNA in clinical specimens from human immunodeficiency virus-seronegative patients from central and southern Italy, with and without Kaposi's sarcoma

In order to investigate the seroprevalence of human herpesvirus 8 (HHV-8) infection in central and southern Italy, sera from human immunodeficiency virus (HIV)-seronegative subjects, with and without Kaposi's sarcoma (KS), were analyzed by immunofluorescence assay, using BC-3, a cell line latently infected with HHV-8. High titers of antibody against HHV-8 lytic and latent antigens were detected in all 50 KS patients studied, while in 50 HIV-seronegative subjects without KS, 32 (64%) were found positive for HHV-8 antibodies. Titers in the sera of these patients were lower than those for KS patients. This data suggests that HHV-8 infection is not restricted to KS patients and that the prevalence of HHV-8 infection in the general population may be correlated with differing rates of prevalence of KS in different parts of the world. In view of these findings, possible nonsexual transmission routes were evaluated. Nested PCR was used to test for the presence of HHV-8 DNA in saliva, urine, and tonsillar swabs from KS and non-KS patients. In KS patients, 14 out of 32 tonsillar swabs (43.7%), 11 out of 24 saliva samples (45.8%), and just 2 out of 24 urine samples (8.3%) tested positive for HHV-8 DNA. In the control group, on the contrary, none of the 20 saliva and 20 urine specimens was positive for HHV-8 DNA; only 1 out of 22 tonsillar swabs gave a positive result. This data supports the hypothesis that HHV-8 infects the general population in a latent form. The reactivation of viral infection may result in salivary shedding of HHV-8, contributing to viral spread by nonsexual transmission routes.     

The physical state of a meal affects hormone release and postprandial thermogenesis

There is evidence that food consistency may influence postprandial physiological responses. Recently we found that homogenization of a vegetable-rich meal significantly delayed the gastric emptying rate and was more satiating than the same meal in solid-liquid form. In this present study we investigated whether homogenization also influences endocrine and metabolic responses to the meal. Eight healthy men, aged 21-28 (mean 24.5) years, were given the meal (cooked vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, with water 300 ml; total energy 2.6 MJ) in both solid-liquid (SM) and homogenized (HM) form, in random order, at 1-week intervals. Variables assayed were plasma glucose, insulin and glucose-dependent insulinotropic peptide (GIP) levels for 2 h and diet-induced thermogenesis (DIT) for 5 h. Plasma glucose pattern was similar after both meals. However, HM induced significantly greater insulin, GIP and DIT responses than SM. Mean integrated areas under the curves (AUC) were 1.7 (SEM 0.38) v. 1.2 (SEM 0.33) U/l per 120 min (P = 0.005) for insulin, 19.9 (SEM 2.44) v. 16 (SEM 1.92) nmol/l per 120 min (P = 0.042) for GIP, and 237.7 (SEM 16.32) v. 126.4 (SEM 23.48) kJ/300 min (P = 0.0029) for DIT respectively. Differences between GIP-AUC after HM and SM correlated significantly with differences between insulin-AUC after HM and SM (r2 0.62, P = 0.021). These findings demonstrate that homogenization of a meal results in a coordinated series of changes of physiological gastroentero-pancreatic functions and confirm that the physical state of the meal plays an important role in modulating endocrine and metabolic responses to food.