An open study of interferon in HIV-antibody-positive men.

Alpha-2a-recombinant interferon (Roferon A) was given subcutaneously in a dose of 3 mega units twice weekly for 15-18 months to 14 HIV-antibody-positive, p24-antigen-negative men with minimal HIV-related disease. Interferon was well-tolerated and safe. Although there was either improvement or lack of deterioration initially in 22 out of 26 HIV disease markers, including lymphadenopathy, thrombocytopenic purpura and nail fungal infection, there were 11 instances of HIV disease indicators appearing during the study. At 15 months, six patients were withdrawn from the study because of clinical and immunological deterioration.

Synthesis and biological activity of a ketomethylene analogue of a tripeptide inhibitor of angiotensin converting enzyme.

An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM, than Bz-Phe-Gly-Pro, I50 = 9.4 microM, or than the orally active D-3-mercapto-2-methylpropanoyl-L-proline (captopril, 1), I50 = 0.30 microM. Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay. In tests for inhibition of angiotensin I induced contractions in the guinea pig ileum, 20 has one-tenth the activity of 1.

Up-regulation of glutathione synthesis in rat kidney by methyl mercury. Relationship to mercury-induced oxidative stress.

Prolonged exposure of rats to methyl mercury hydroxide (MMH) results, during the initial phase of exposure, in the rapid accumulation of mercury as Hg2+ by kidney cortex and in a significant increase in oxidative stress, as characterized by the rate of formation of thiobarbituric acid reactive substances (TBARS) by renal mitochondria. These events are accompanied by a progressive increase in steady-state levels of the mRNA encoding gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in glutathione (GSH) synthesis and a 2- to 3-fold elevation in renal cortical GSH levels. The present study showed that the increase in GSH content was accompanied by a concomitant decrease in the rate of TBARS formation. Subsequent to these initial phase events, continued MMH exposure was characterized by equilibration in the rate of renal Hg2+ accumulation, a sharp decrease in both the TBARS formation rate and GCS mRNA level, but sustained elevation of renal cortical GSH content. Depletion of GSH with buthionine sulfoximine subsequent to the decline in the rate of TBARS formation did not result in a rebound of the TBARS formation rate. These findings suggest that oxidative stress during the initial phase of MMH exposure is derived from the transformation of CH3Hg+ to Hg2+, which, in turn, induces the synthesis of Hg(2+)- and/or oxidant-scavenging GSH molecules via the up-regulation of renal GCS mRNA. The findings also suggest that resistance to Hg(2+)-mediated oxidative stress may be more closely associated with the capacity for up-regulation of GSH synthesis than with elevated GSH levels per se.

The noradrenergic system of the amygdala and aversive information processing.

Water-deprived rats were trained to drink in a passive avoidance apparatus. After reaching a predetermined latency criterion, rats were given a single 3-sec, 3-mA footshock. Immediately or 12 hr after the footshock, rats were given intracranial injections of vehicular saline, norepinephrine (NE), propranolol, or dopamine (DA) into the amygdala, internal capsule, lateral ventricles, or caudate-putamen. Subjects were tested for passive avoidance at 30 min or 24 hr following footshock. No memory deficits were seen as a consequence of short-term retention or because of proactive or toxicity effects. Retention deficits were seen in the 24 hr test only in rats injected with NE in the amygdala, internal capsule, or lateral ventricles. However, qualitative differences in stress-indicative behaviors were noted in the NE groups and in the DA-amygdala animals. The results specifically suggest that the noradrenergic system of the amygdala is involved in the long-term processing of the emotional attributes of aversive information.

Nephrotoxicity of lomustine. A case report and literature review.

A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity.

Amygdala norepinephrine involved in two separate long-term memory retrieval processes.

Noradrenergic manipulation of the rodent amygdala results in time-dependent disruption of long-term memory for a one-trial aversive experience. Findings using both state-dependent and consolidation experimental procedures suggest that the norepinephrine system of the amygdala underlies not only consolidation-like mechanisms. There appear to be specific noradrenergic substrates for two or more memory retrieval processes which may be physiologically similar to either acquisition or later memory development involving aversive information.

Manipulation of the amygdala noradrenergic system impairs extinction of passive avoidance.

In a consolidation paradigm, noradrenergic manipulation of the rat amygdala results in disruption of extinction for passive avoidance. These results are discussed in light of a recent controversy concerning the role of central norepinephrine systems in general extinction behavior. The discussion is cast primarily within the framework of rodent natural life history, the presence of innate behavioral strategies, and the organization of information processing as an integration of experiential attributes.

Memory consolidation: brain region and neurotransmitter specificity.

Post-trial injections of norepinephrine, but not dopamine, into the amygdala produce a long-term retention deficit (amnesia) for a 1-trial footshock experience in rats. In contrast, post-trial injections of dopamine, but not norepinephrine, into the caudate produce long-term facilitation. The data provide evidence for brain region-neurotransmitter specificity which supports a multiple component hypothesis.

Hyperbaric oxygen treatment: 10 years' experience of a Regional Infectious Diseases Unit.

Ten years' experience of a Regional Centre for Infectious Diseases in the use of hyperbaric oxygen in 87 patients have been reviewed. Its efficacy in the treatment of non-infectious cases has been confirmed. Fifty-eight (67 per cent) patients had anaerobic infections associated with peripheral vascular disease, limb trauma, abdominal surgery or occurred spontaneously. All patients had failed to respond to surgery and antimicrobial agents, and were transferred for hyperbaric treatment as the infection was progressive. Marked improvement in general condition, wound infection and limitation of extension of the anaerobic infection occurred following hyperbaric treatment. These improvements had benefits in terms of surgical risk, demarcation and mortality. Symptoms suggestive of oxygen toxicity occurred in up to 24 per cent of all patients, but in many this took the form of anxiety and anxiety-related symptoms. Despite the beneficial effects of hyperbaric oxygen, many surgeons appear to be unaware or sceptical of the facility. A prospective controlled trial is advocated.

An analysis of 12 months admissions to a regional infection unit with an open door admission policy.

All admissions to the Aberdeen Infection Unit over a period of 12 months have been analysed. Forty per cent of the patients proved to have non-infectious conditions although most were referred as having an infectious disease. Those patients with infectious diseases were younger and had a shorter stay in hospital. Also there was seasonal variation in the time of their admission as well as a low mortality rate when compared with older patients with non-infectious disease admitted over the same period. Cross infection did not arise in spite of patients sharing accommodation.

Neutropenia associated with dual antimalarial chemoprophylaxis--use of bone-marrow culture as an aid in further drug management.

Bone-marrow culture in soft agar was used to determine the cause of neutropenia in a visitor to Tanzania who had been taking both amodiaquine and proguanil for antimalarial prophylaxis. Desethyl-amodiaquine, a major metabolite of amodiaquine (but not amodiaquine itself, proguanil, cycloguanil or chloroquine) was implicated. Supplementary studies using amodiaquine binding techniques supported the notion that the parent compound, amodiaquine, was not the cause of the neutropenia. The bone-marrow culture technique proved useful in deciding further anti-malarial prophylaxis and in formulating the choice of curative antimalarial therapy, should this have proved necessary. The procedure may help in the managing other such patients with presumed drug-induced blood dyscrasias when the choice of appropriate and effective antimalarial drugs is limited.

Does isolation of patients with infections induce mental illness?

Forty-one patients admitted into single-bedded isolation cubicles in an infectious diseases unit were assessed for evidence of mental disturbance. By use of the Crown-Crisp Experimental Index as a measure of mental state, the scores for somatic anxiety, free floating anxiety, and the total score were found to be significantly raised on admission, falling towards those found in a control general practice population by the time of discharge from hospital. Higher scores were associated with a past history of mental illness. There was, however, no statistical correlation between the psychological indices and consumption of alcohol, smoking, or patient's sex. Clinically apparent behavioural disturbance, mainly anxiety and agitation, was seen in 12 patients. Overall, patients expressed a preference for single rooms and did not find the isolation rituals disconcerting. The findings indicate that anxiety in patients with acute infections is more related to their illness and referral to hospital than to their imposed isolation. Only those patients with a past psychiatric history are likely to benefit from transfer to an open ward during convalescence.

Brucella peritonitis.

We report the case of a patient with peritonitis caused by Brucella melitensis who also had chronic liver disease. At first the patient was treated for bacterial peritonitis but when a lymphocytic ascites was aspirated antituberculosis chemotherapy was given. However, the serological tests for brucellosis were strongly positive and subsequently B. melitensis was isolated from ascitic fluid.

A double-masked, placebo-controlled trial of acyclovir cream in immunocompetent patients with herpes zoster.

Sixty-four patients with herpes zoster were entered into a randomised double-masked, placebo-controlled trial of 5% acyclovir cream applied five times daily for 5 days. Of these patients, 56 were included in the final analysis (26 acyclovir, 30 placebo). Significant and objective differences in either progression of the rash, severity of acute pain or incidence of post-herpetic neuralgia were not observed. Although significantly more rashes involuted in the acyclovir group, this isolated finding cannot be explained. Twenty-two patients (12 acyclovir, 10 placebo) experienced erythema or desquamation or both during treatment with the cream. The similar incidence of skin reactions in both groups suggests that they were related to the cream base rather than the acyclovir.

Once-weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS-related complex: a double-blind placebo-controlled study.

Fluconazole 50 mg daily for 14-28 days was effective in the treatment of patients with AIDS and AIDS-related complex with severe oropharyngeal and oesophageal candidiasis. Of 24 patients entered, 17 (81%), including seven with oesophageal candidiasis, were clinically cured and two (9.5%) improved at the end of treatment. Following clinical cure, 14 patients were entered into the double-blind phase of the study, where fluconazole (150 mg) or placebo capsules were given once weekly. Treatment was double blind. Fluconazole 150 mg once weekly was found to be effective in maintaining patients both clinically and mycologically free of oropharyngeal candidiasis.

Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever--preliminary observations from a pilot, exploratory study.

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytomegalovirus cholecystitis and colitis associated with the acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) is an important cause of acalculous gangrenous cholecystitis in immunocompromised persons. We report a case of acalculous acute cholecystitis and active colitis associated with CMV in a patient suffering from the acquired immune deficiency syndrome. The condition was treated successfully with surgery and 9-(1,3,-dihydroxy-2-propoxymethyl)guanine intravenously.

Amnesia attenuation specificity: propranolol reverses norepinephrine but not cycloheximide-induced amnesia.

Post-trial injections of norepinephrine (NE) or cycloheximide (CHX) into the amygdala produces a long-term retention deficity (amnesia) for a 1-trial footshock experience in rats. concomitant post-trial injections of the adrenergic antagonist, propranolol, prevents NE-, but not CHX-induced amnesia. These results indicate separate mechanisms of action for amnesia produced by intracranial CHX and NE injections.

Hyperglycemic complications associated with adjuvant chemotherapy of breast cancer. A cancer and leukemia group B (CALGB) study.

Many adjuvant chemotherapy regimens used for breast cancer include prednisone, which has the potential to cause hyperglycemia. We reviewed the results of three CALGB studies employing prednisone as part of adjuvant therapy to determine the incidence and severity of hyperglycemic complications. All treatment regimens included cyclophosphamide, methotrexate or doxorubicin, 5-fluorouracil, and vincristine in addition to prednisone. Among 1,237 evaluable patients receiving a five-drug regimen including prednisone, there were 98 patients (7.9%) who experienced any degree of hyperglycemia. Thirty patients (2.4% overall; 30.6% of those having any hyperglycemia) had severe or life-threatening degrees of hyperglycemia, including two patients whose hyperglycemia contributed directly to death. We conclude that prednisone administration as part of adjuvant chemotherapy regimens in breast cancer produces an appreciable incidence of hyperglycemia. Serum glucose levels should be monitored during therapy to help prevent the occasional severe or life-threatening episode of hyperglycemia in these patients.

Localized pulmonary disease due to Trichosporon beigelii.

A case of pulmonary infection caused by Trichosporon beigelii is reported. The infection occurred in a neutropenic patient with acute lymphoblastic leukemia. His chest radiograph showed a 6-cm pulmonary infiltrate in the right midzone and an apical infiltrate on the left. Repeated cultures of bronchoalveolar lavage grew budding yeast that was identified as T beigelii on the basis of morphological, cultural, and biochemical characteristics. He responded to amphotericin-B therapy. Systemic infections caused by this yeast are rare and its causal relationship in localized lung disease has been reported only seven times previously.