Detection and quasispecies analysis of hepatitis C virus in the cerebrospinal fluid of infected patients.

Hepatitis C virus (HCV) is a leading cause of liver damage and has also been implicated in extrahepatic pathologies. We examined for HCV RNA paired CSF and plasma samples from 12 viremia positive patients using PCR. The CSF from 5/5 HIV-infected patients and 5/7 HIV-negative patients were HCV RNA positive. Branched DNA analysis showed that HCV loads in CSF were much lower than in plasma. Several HCV-positive CSF showed no evidence of blood contamination, impaired blood-brain barrier, or intrathecal IgG production. Comparison of HCV quasispecies in three sets of samples suggested that the virus in CSF was of plasma origin.

Psychopathology in 90 consecutive human immunodeficiency virus-seropositive and acquired immune deficiency syndrome patients with mostly intravenous drug use history.

This report presents systematic clinical data regarding psychiatric diagnoses, personal and family psychiatric histories, and symptomatologic aspects of 90 consecutive human immunodeficiency virus (HIV)-seropositive and acquired immune deficiency syndrome (AIDS) patients, of whom slightly less than two thirds were at risk due to intravenous drug abuse. In addition, a comparison was made between the distribution patterns of these variables at various stages of HIV illness and related at-risk behaviors. Eighty-four percent of the patients met criteria for a spectrum of DSM-III-R diagnoses (mostly affective) that were associated with high rates of affective and alcohol abuse disorders among first-degree relatives. Mood disorders did not differ significantly between the two main groups at risk (intravenous drug users [IVDUs] v others) by gender, age, or stage of illness. The overall data from the rating scales show high levels of psychic and somatic anxiety in the early stages of illness, whereas cognitive symptoms, retardation, and disorientation are dominant in later stages. A noteworthy finding in this study is that many depressed patients demonstrated current and/or past hypomanic, hyperthymic, or cyclothymic features with no evidence of brain damage detectable by computed axial tomography (CAT). These temperamental attributes, which preceded HIV infection, may have served as risk factors for both drug abuse and impulsive sexual behavior in all types of at-risk groups.

Feasibility of pharmacotherapy in HIV-related affective spectrum disorders: an open trial with fluvoxamine.

Among HIV patients treated for AIDS-related adjustment, major depressive disorders and other affective disorders, we assessed in an open study the feasibility of using a serotonergic antidepressant (fluvoxamine). Thirty-five seropositive patients with the above conditions (22 men and 13 women) were followed over a minimum period of four weeks. At the end of the treatment, a large number of patients (77%) showed marked improvement. "Nuclear" depressive and anxiety symptoms remitted, while the "somatic" ones seemed less sensitive to treatment. Treatment had to be terminated prematurely due to side effects in only two patients (6%).

Diagnosis and clinical use of bromperidol in HIV-related psychoses in a sample of seropositive patients with brain damage.

We evaluated in an open trial the safety and effectiveness of a high-potency neuroleptic (bromperidol) for the treatment of AIDS-related organic mental syndromes. Eleven (nine men and two women) seropositive patients with psychotic features were included; six were intravenous drug users (IVDU) and five were not IVDU (NON-IVDU). On the basis of the achievement of a CGI score of 1 or 2 (much improved or very much improved) at the fourth week, nine patients were considered responders, one was a partial responder and one was a non-responder. From a clinical point of view, "positive" psychotic symptoms had a significant remission, while the "negative" ones seemed to be less sensitive or insensitive to bromperidol treatment.

Acute dose-response curve of enalapril in renovascular hypertensives.

We evaluated the acute blood pressure lowering effect of enalapril in terms of dose-response curve and compared this effect with that on humoral parameters. Eleven renovascular patients with acute angiotensin-converting enzyme (ACE) inhibition received (according to a randomized double-blind cross-over design) placebo, 10, 20, and 40 mg of enalapril with a 72-hour interval between each dose. Seated blood pressure and heart rate were measured every hour for 6 hours and then again at the twelfth and twenty-fourth hour, while venous blood samples for plasma renin activity, plasma aldosterone and serum ACE measurements were obtained at the fourth and twenty-fourth hour after receiving the placebo or drug. Blood pressure was significantly reduced by all three doses of enalapril at hour 4, while at hour 24 it was reduced only by the 20- and 40-mg doses. A significant correlation (r = 0.68; P less than 0.001) was found between percentage decrements of mean blood pressure and the log of the doses at hour 4 with a similar (although not significant) trend at hour 24. Plasma renin activity was significantly and to a similar extent increased by the three doses of enalapril at hour 4, while at hour 24 it was significantly increased only by the 40-mg dose. Serum ACE and plasma aldosterone were significantly reduced both at hours 4 and 24 without any difference between doses. No correlation was found between mean blood pressure changes and those of humoral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute response to captopril as a predictive test for surgery in renovascular hypertension.

To test the hypothesis that acute angiotensin-converting enzyme (ACE) inhibition might predict the postoperative blood pressure outcome, a single oral dose of captopril ranging from 12.5 to 100 mg, was given to 26 patients with renovascular disease and its hypotensive effect was compared with that of surgery (21 patients) or of percutaneous transluminal angioplasty (PTA) (5 patients). Both systolic and diastolic blood pressure fell significantly (p less than 0.001) from 179.9 +/- 5.4/114.1 +/- 2.1 to 148.4 +/- 3.8/94.1 +/- 1.9 after captopril and to 141.1 +/- 3.7/88.9 +/- 2.0 at least 3 months after operation. Postoperative pressure values were directly related to those after captopril (SBP: r = 0.65, p less than 0.001; DBP: r = 0.45, p less than 0.05) as were their absolute decrements (SBP: r = 0.70, p less than 0.001; DBP: r = 0.64, p less than 0.001). However, after captopril, individual pressure tended to be higher (and their decrements to be lower) than after operation. 12 out of 19 patients cured by surgery were considered cured by captopril, while 5 out of the remaining 7 were improved and 2 not cured. The 6 patients improved by surgery or PTA were also improved by captopril and the only patient not cured by surgery was not cured by captopril. Therefore, if we consider both cure and improvement as a positive result, the captopril test gave 23 true-positive, 1 true-negative and 2 false-negative responses. Taken together, these data suggest that acute ACE inhibition may be an useful tool in predicting postoperative blood pressure of patients with renovascular disease.

Angiotensin-converting enzyme inhibitors in hypertension: a review.

Angiotensin-converting enzyme (ACE) inhibitors are a new class of drugs, whose main indications are the treatment of hypertension and of heart failure. Data obtained with captopril, the first orally active ACE inhibitor, affords an understanding of the rationale of their therapeutic use based on the knowledge of their mechanisms of action, efficacy, contraindications and precautions, dosage and frequency of administration, side-effects, interactions and advantages. ACE inhibitors appear to exert their haemodynamic effect mainly by inhibiting the renin-angiotensin-aldosterone system, but also by modulating sympathetic nervous system activity and by increasing prostaglandin synthesis. Therefore they act both on vasoconstrictor and volume factors, since they cause vasodilation (the main effect) and mild natriuresis without affecting the heart rate and contractility and, probably, favourably influencing renal, coronary and cerebral circulation. So far it appears that ACE inhibitors can be usefully employed in the treatment of heart failure, in which they reduce both pre- and after-load, and mainly of hypertension. In the past captopril has been used to treat only severe and or resistant hypertension and some secondary forms, like renal parenchymal and renovascular hypertension, but now it seems that captopril is useful also to treat mild to moderate essential hypertension. Their efficacy in reducing blood pressure is similar to that of thiazide diuretics and of beta-blockers, the two drugs now considered of first choice and they exert their hypotensive action without the development of pseudotolerance or tolerance. ACE inhibitors seem, at the moment, contraindicated in pregnancy and in hyperkalaemic syndromes and must be used with caution in patients with collagen disease (mainly associated with renal failure), with severe bilateral renal artery stenosis (and with severe artery stenosis of a solitary kidney) and with severe sodium depletion. It is now established that captopril has a flat dose response curve and that it must be given (twice daily) at a dose not exceeding 150 mg/day. The same pharmacological approach must be used with future ACE inhibitors in order to establish the right posology and the frequency of administration. In this respect enalapril seems to be a promising ACE inhibitor with a prolonged action (at least 24 hours). The exact posology of ACE inhibitors might be crucial, since it has been shown that the side-effects of captopril (skin rashes, fever, taste disturbances, proteinuria and neutropenia) are dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)