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Biomedical subjects

R Hafner

Publications and source records attributed to R Hafner.

At least 55 records · Page 3Linked to original sources

Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team.

BACKGROUND: In patients with the acquired immunodeficiency syndrome (AIDS), toxoplasmic encephalitis is usually a presumptive diagnosis based on the clinical manifestations, a positive antitoxoplasma-antibody titer, and characteristic neuroradiologic abnormalities. A response to specific therapy helps to confirm the diagnosis, but it is unclear how rapid the response should be. We studied the course of patients treated for acute toxoplasmic encephalitis and evaluated objective clinical criteria for this empirical diagnosis. METHODS: A quantifiable neurologic assessment was used prospectively to evaluate the clinical outcome of patients with AIDS and toxoplasmic encephalitis who were treated with oral clindamycin (600 mg four times a day) and pyrimethamine (75 mg every day) for six weeks. RESULTS: Thirty-five of 49 patients (71 percent) responded to therapy, and 30 of these (86 percent) had improvement by day 7. Thirty-two of those with a response (91 percent) improved with respect to at least half of their base-line abnormalities by day 14. Improvement in neurologic abnormalities within 7 to 14 days after the start of therapy was strongly associated with the neurologic response at 6 weeks. The four patients in whom treatment failed and the two patients with lymphoma had progressing neurologic abnormalities or new abnormalities during the first 12 days of therapy. Nonlocalizing abnormalities (headache and seizure) improved regardless of the clinical outcome. CONCLUSIONS: Oral clindamycin and pyrimethamine are an effective treatment for toxoplasmic encephalitis. Patients who have early neurologic deterioration despite treatment or who do not improve neurologically after 10 to 14 days of appropriate antitoxoplasma therapy should be considered candidates for brain biopsy.

AIDS-Related Opportunistic Infections↗

Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.

AIDS-Related Opportunistic Infections↗

[Risk factors of cerebral toxoplasmosis in patients with HIV infection: data of a primary prevention trial].

To identify risk factors for cerebral toxoplasmosis (CT) in HIV patients (pts) with positive serology for Toxoplasma gondii and CD4 < 200/mm3, data from the placebo group (N = 280) of a primary prophylaxis trial, were analyzed. The probability of onset of CT (n = 46) was, at one year, 13.1%. Three baseline variables were independently associated with a higher risk of CT: group IV non AIDS, AIDS stage and CD4 < 50/mm3. Initial titer of antibodies to Toxoplasma gondii was not.

Double-Blind Method↗

[Primary prevention of cerebral toxoplasmosis in patients with HIV infection: results of a double-blind randomized trial, pyrimethamine versus placebo].

To assess the efficacy of pyrimethamine (Pyr) for primary prophylaxis of cerebral toxoplasmosis (CT) in HIV patients (pts), 554 pts were randomized in a double-blind, placebo-controlled trial (mean follow-up: 14 months). The intent-to-treat analysis found no significant difference in the incidence of ct at 1 year: 12% (Pyr) versus 13% (Pcb) nor in survival. Side-effects leading to stop the study drug were more frequent in Pyr group, especially cutaneous rashes: 8% (Pyr) versus 2% (Pcb).

Double-Blind Method↗

Toxicity of clindamycin as prophylaxis for AIDS-associated toxoplasmic encephalitis. Community Programs for Clinical Research on AIDS.

A double-blind, placebo-controlled trial was set up to compare clindamycin and pyrimethamine as prophylaxis for toxoplasmic encephalitis (TE) in HIV-infected patients at risk of the disorder. Interim analysis showed that clindamycin-treated patients were 4.4 (95% confidence interval 1.3-15.2) times more likely to experience an adverse effect that necessitated withdrawal of the study drug than those who received placebo. Diarrhoea and rash were reported in 16 (31%) and 11 (21%), respectively, of 52 patients treated with clindamycin (300 mg twice daily) compared with 2 (6%; p = 0.06) and none (p = 0.01) of the 32 placebo-treated patients. The clindamycin arm of the trial was prematurely terminated, although recruitment to the pyrimethamine arm continues.

Acquired Immunodeficiency Syndrome↗

A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.

BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine. RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued. CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Acquired Immunodeficiency Syndrome↗

Clinical programs for clinical research on AIDS: description of a randomized prospective study of clindamycin versus pyrimethamine for prevention of Toxoplasma gondii infection.

The risk of toxoplasmic encephalitis complicating AIDS appears largely limited to those HIV-infected patients with serologic evidence of past Toxoplasma gondii infection and low CD4 lymphocyte counts. The Community Programs for Clinical Research on AIDS has initiated a randomized, placebo-controlled trial to determine if clindamycin or pyrimethamine prophylactic regimens are effective and safe in preventing toxoplasmic encephalitis.

Acquired Immunodeficiency Syndrome↗

In vivo additive antiretroviral effect of combined zidovudine and foscarnet therapy for human immunodeficiency virus infection (ACTG Protocol 053).

Zidovudine and foscarnet each have antiretroviral activity against human immunodeficiency virus (HIV) and, when combined in vitro, inhibit HIV replication in an additive or synergistic fashion. To determine if an in vivo additive or synergistic antiretroviral effect might result from combined therapy, six symptomatic HIV-infected patients were studied who had persistently quantifiable serum HIV p24 antigen despite 9-27 weeks of full-dose oral zidovudine therapy (1200 mg/day). These patients were given intravenous foscarnet (30 mg/kg every 8h) for 2 weeks with continued oral zidovudine for 14 days, followed by zidovudine alone for 6 months. Serum p24 antigen concentrations decreased in all six patients during the period of combined therapy by a mean 53% (P = .005). Subsequently, serum p24 antigen levels rose to the baseline value in four patients after 4-14 weeks. As predicted from in vitro studies, combined treatment with zidovudine and foscarnet resulted in an additive in vivo effect, but the effect was transient.

Administration, Oral↗

[Male subfertility and oral bacterial diseases].

More than 70% of the husbands consulting the Dept. of Gynecology and Obstetrics of the RWTH Aachen for sterility since June 1987 needed treatment for bacteriospermia with germ concentrations greater than 10(4) cfu/ml ejaculate. In 23% of the treated men however, no convincing reduction of germ concentration were achieved. 36 patients with therapy-resistant bacteriospermia were sent to the Dept. of Dentistry of the RWTH Aachen. A lot of intra-oral foci were found, which got eliminated. Intra-operational bacterial specimens were taken and evaluated by a special diagnostic technique in the Dept. of Microbiology. It was shown that the bacterial spectrum of the intraoral specimens and the spermiograms were identical. Six months after completion of the dental therapy a new andrological examination was performed. Two thirds of the spermiograms now were already sterile. There was an improvement of the spermparameters as well as motility, morphology and density. It can be concluded from these results that there is a direct causal relationship between a symptomatic dental primary disease and bacteriospermia which probably leads to subfertility.

Bacteria↗

Ulnar variance in children--standard measurements for evaluation of ulnar shortening in juvenile rheumatoid arthritis, hereditary multiple exostosis and other bone or joint disorders in childhood.

Measurements for radioulnar variance in adults cannot be used in children because the epiphyses are not fully ossified. We describe a method of determining ulnar variance in children by using the distance from the distal metaphysis of the radius to the distal metaphysis of the ulna. Standards for this measurement are presented for ages 1.5 to 15.5 years in boys and girls. These measurements change little with age and may be helpful in establishing shortening of the ulna which may been seen in juvenile rheumatoid arthritis, hereditary multiple exostosis, or other bone and joint diseases with childhood onset.

Adolescent↗

[Predictive potential of positive values in the latex agglutination test for Candida antigen (Cand-Tec)].

The correlation of Cand-Tec (candida antigen detection) with clinical findings and results in passive hemagglutination and immunoelectrophoresis (antibody detection) has been evaluated retrospectively. Based on mycological findings, 33 patients with a Cand-Tec titer were classified into five groups. Systemic antimycotic therapy was another criterion. Using a titer of greater than or equal to 1:8 as diagnostic of systemic or local candidal infection, the positive predictive value was 33% and 55% respectively. However, a titer of greater than or equal to 1:8 correlated significantly (p less than 0.05) with infection (systemic, presumably systemic and local candidiasis, n = 3). The combined findings of an antigen titer of greater than or equal to 1:8 and antibodies to cytoplasmatic protein antigens of candida correlated even better with infection (p less than 0.02) and had a positive predictive value of 100%. Antigen and antibody determination may be useful adjunctive procedures in the diagnosis of candida infections.

Aged↗

[Removal of tattoos with the Nd:YAG laser].

Irradiation of 20 tattoos using the Q-switched Nd:YAG laser (energy density 3-5 J/cm2, asymmetrical pulse shape with 50% energy output in 18 ns, spot size 3 mm in diameter) gave the impression that black ink tattoos can be completely removed without scarring. Some patients needed several treatments. The results continued to improve even some months after the irradiation. In preliminary experiments on excised tattooed and untattooed skin the non-Q-switched Nd:YAG laser had distinct burning effects. It was therefore not tested in patients. The results of chemical, physical, and histological examinations are discussed with special reference to toxic side-effects that might be induced by laser irradiation.

Humans↗

Acute fulminant toxoplasma meningoencephalitis in a homosexual man.

A homosexual man with a history of sexually transmitted infections including recent giardiasis and high cytomegalovirus (CMV) titer was admitted with generalized weakness, headache, and depression. He rapidly became comatose and developed signs of increased intracranial pressure. CT scan revealed a right cerebral lesion. Pathologic examination disclosed an acute necrotizing granulomatous toxoplasmosis involving the cerebrum. This case represents an example of an opportunistic infection in a male homosexual associated with fulminant clinical course, probably on the basis of immune deficiency.

Acute Disease↗