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Biomedical subjects

N Clumeck

Publications and source records attributed to N Clumeck.

At least 19 recordsLinked to original sources

Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group.

OBJECTIVE: To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen. SETTING: University hospitals. PATIENTS: Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable. INTERVENTIONS: Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks. MEASUREMENTS AND MAIN RESULTS: There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover. CONCLUSIONS: The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.

Acquired Immunodeficiency Syndrome

Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion.

The pharmacokinetics of oral administration of R 82913, or tetrahydroimidazol [4,5,1-jk]-benzodiazepin-2(1H)-one or -thione (TIBO), was compared with those of intravenous administration in five AIDS patients. TIBO was administered as a single daily 1-h infusion of 100 mg for 29 days and orally as a single daily dose for 14 days with three consecutive regimens of 100, 200, and 100 mg with probenecid (1 g) daily. Each cycle was followed by a wash-out period. Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid. Trough levels obtained with oral administration systematically remained far below the 90% inhibitory concentration of TIBO against human immunodeficiency virus type 1 (HIV-1). Tolerance of TIBO was excellent. No clinical efficacy could be demonstrated. p24 antigenemia decreased significantly in one patient under intravenous therapy. TIBO derivatives are promising anti-HIV-1 agents in vitro, but improvement of oral bioavailability is needed before implementation of long-term efficacy and tolerability studies. Moreover, rapid emergence of resistance, which has been recently documented, constitutes a major problem with most nonnucleoside reverse transcriptase inhibitors.

Acquired Immunodeficiency Syndrome

Anticardiolipin antibodies (ACA) are most often not associated with lupus-like anticoagulant (LLAC) in human immunodeficiency virus (HIV) infection.

Anticardiolipin antibodies (ACA) and lupus-like anticoagulant (LLAC) have been studied in a group of 142 non-hospitalized and a group of 72 hospitalized HIV infected patients. We observed a variable frequency of ACA positivity ranging from 7.7% to 30.3% according to the groups of patients and the isotype of immunoglobulin fraction containing ACA activity. None of the patients investigated presented a prolongation of the activated partial thromboplastin time (APTT) compatible with the presence of a LLAC. Some patients presented a weak anticoagulant activity only detected by the tissue thromboplastin inhibition (TTI) test. No positive correlation was found between this latter test and ACA. We conclude that, like in syphilitic patients, ACA present in HIV infected patients are most often not associated with LLAC.

Antibodies

Efficacy of oral fluconazole in the treatment of AIDS associated oesophageal candidiasis.

To assess the efficacy and tolerance of fluconazole in the treatment of oesophageal candidiasis, 47 AIDS patients with this infection were enrolled in an open prospective study using fluconazole 100 mg given orally once daily. Clinical cure was obtained in all of 41 evaluable patients, with confirmation of cure in all of 31 patients who underwent post-treatment oesophagoscopy. Forty patients were followed up for at least 30 days; none suffered a relapse of oesophagitis but seven had a recurrence of stomatitis which was effectively treated with fluconazole. Fluconazole was well tolerated. Nausea was noted in three patients one of whom interrupted therapy. Transient mild elevation of ALT/AST was noted in five of 41 patients (12%). Fluconazole appears to be a safe and effective agent for oral therapy of oesophageal candidiasis associated with AIDS.

Acquired Immunodeficiency Syndrome

Biochemical thyroid profile in patients infected with the human immunodeficiency virus.

Over a 2-year period, thyroid function was studied in 102 patients infected with the human immunodeficiency virus (HIV) and in 102 age- and sex-matched controls with various infectious diseases. Biochemical abnormalities were observed in 1-20% of the patients, depending on thyroid indices, but thyroid disease (hypothyroidism) was diagnosed in only 1. Compared to controls, patients, especially those with the acquired immunodeficiency syndrome (AIDS), had a significant increase in serum thyroxine-binding globulin, a lower T3 and free thyroxine index, and a higher frequency of thyroglobulin antibodies.

Adult

The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

AIDS-Related Complex

Pancreatic disturbances and typhoid fever.

During an 8-year period, 14 adult patients were hospitalized with typhoid fever confirmed by positive blood cultures for Salmonella typhi. Among these patients, we have retrospectively (n = 7) and prospectively (n = 7) evaluated pancreatic disturbance by serum amylase and lipase measurements at the time of admission. In 7 (50%) biological signs of pancreatitis were noted: mean amylase level 81 IU (range 30-201 IU, normal value less than 40 IU), mean lipase level 949 IU (range 468-2,000 IU, normal value less than 300 IU). Clinical signs of pancreatitis were observed in 4 cases, one of whom had a concomitant salmonella biliary tract infection and gall stones demonstrated by laparotomy and the others a normal biliary ultrasonographic examination with a swelling of the pancreas. No alcohol or drug use or other infection were noted before admission. This study suggests that biological or clinical pancreatitis should be considered as a frequent complication of typhoid fever. S. typhi should therefore be added to the list of pathogens implicated in the pathogenesis of non-alcoholic or non-lithiasic pancreatitis.

Acute Disease

[Current aspects of AIDS].

HIV epidemic is still expanding all over the world. Heterosexual transmission into the general population is of particular concern mostly in Africa and Western countries. So far, pathogenesis of the syndrome is best explained by the likely role of co-factors that interfere with the latency phase of the virus. In this setting early treatment by specific antiviral therapy such as zidovudine, will probably slow down the evolution of HIV infection.

Acquired Immunodeficiency Syndrome

[Current aspects of AIDS].

HIV epidemic is still expanding all over the world. Heterosexual transmission into the general population is of particular concern mostly in Africa and Western countries. So far, pathogenesis of the syndrome is best explained by the likely role of co-factors that interfere with the latency phase of the virus. In this setting early treatment by specific antiviral therapy such as zidovudine, will probably slow down the evolution of HIV infection.

Acquired Immunodeficiency Syndrome

[Computed tomography aspects of cerebral toxoplasmosis in AIDS].

We followed by CT 19 AIDS patients with cerebral toxoplasmosis. Diagnosis of cerebral toxoplasmosis was assessed on radiological and clinical basis, including the therapeutic response. CT allowed to confirm brain lesions (40 lesions in 19 patients) and to follow the evolution with treatment. Analysis of the CT features of these brain lesions permits to define some characteristic findings, though not pathognomonic. These lesions share common characteristics with other granulomatous diseases or with brain abscesses. The most frequently observed features are: target lesions (74%) with contrast enhancement (95%), frequently multiple (53%), associated with a hypodense area of oedema (100%), and responsible for a mass effect (79%). Under treatment, we observed improvement in 89%, resulting either in complete disappearance of the lesions (16%), disappearance of one or more contrast enhancing (46%) or hypodense (6%) areas, or volumetric regression of the hypodensities (50%). We conclude that CT is a good first-step examination for the detection and follow-up of cerebral toxoplasmosis in AIDS patients. MRI, a method with a higher sensitivity but still less accessible, may be considered at the present time as a second-step examination for those patients with solitary lesions on CT, or for symptomatic patients with normal CT.

Acquired Immunodeficiency Syndrome

Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS.

In a randomised, double-blind study the efficacy and toxicity of oral fluconazole 50 mg daily and ketoconazole 200 mg daily were compared for the treatment of oropharyngeal candidiasis in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). 20 episodes (18 patients) were treated with fluconazole and 20 episodes (19 patients) with ketoconazole. Pretreatment clinical features and laboratory test results were similar in both groups. 17 episodes (85%) in the fluconazole group and 16 (80%) in the ketoconazole group could be evaluated. There was clinical cure at the end of therapy in all fluconazole-treated and 12 of 16 (75%) ketoconazole-treated episodes. Cultures were negative at the end of therapy in 87% of the fluconazole group and 69% of the ketoconazole group. 1 patients stopped taking fluconazole because of severe nausea. 1 of 18 fluconazole-treated and 4 of 19 ketoconazole-treated patients had transient rises in alanine or aspartate aminotransferase. Fluconazole seemed more effective than ketoconazole in the treatment of oral thrush among AIDS and ARC patients.

AIDS-Related Complex

Preliminary results on clinical and immunological effects of thymus hormone preparations in AIDS.

The human immunodeficiency virus (HIV) is the newly recognized agent of the acquired immunodeficiency syndrome (AIDS). Global defects of the immune functions, including T- and B-cell immunity, macrophage functions and cytokine production, are commonly observed among patients with HIV infection. Many studies have shown thymus involvement and endocrine function impairments among these patients. Clinical trials with thymic compounds aiming at restoring the immune dysfunctions will be reviewed.

Acquired Immunodeficiency Syndrome

AIDS in Africa.

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Acquired Immunodeficiency Syndrome