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Biomedical subjects

H Masur

Publications and source records attributed to H Masur.

At least 73 records · Page 4Linked to original sources
PubMed1996

Drug interactions in patients infected with human immunodeficiency virus.

Patients with AIDS who are receiving optimal medical care, including combination therapy with antiretroviral agents and more effective prophylaxis and therapy for opportunistic infections and neoplasms, are surviving longer. However, the potential for drug interactions in these patients is increased because many of the currently used antibiotics and antiviral agents have profound effects on the hepatic cytochrome P-450 enzyme system, on renal tubular function, and on bone marrow function. In this AIDS Commentary, Dr. Piscitelli and colleagues have succinctly reviewed the current state of our knowledge regarding the potential for additive or synergistic drug interactions that can result in enhanced toxicity or, alternatively, augmented therapeutic benefit. Information on these interactions will become more important as more intensive and effective therapy becomes available for persons with far-advanced infection due to human immunodeficiency virus type 1.

Absorption↗
PubMed1996

Combination therapy with didanosine and interferon-alpha in human immunodeficiency virus-infected patients: results of a phase I/II trial.

A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (INF-alpha) in human immunodeficiency virus (HIV)-infected patients. Thirty-six volunteers with >200 x 10(6) CD4 cells/L received didanosine (one 100-, 250-, or 375-mg sachet twice daily) for at least 6 weeks, following which IFN-alpha (1, 5, 10, or 15 MU/day) was begun. Didanosine (one 375-mg sachet twice daily) was substituted for zidovudine in 14 additional patients who had received IFN-alpha and zidovudine for 7-45 months. Thirty-five patients completed the 34-week study. Clinical or chemical pancreatitis was the most common (6 patients) dose-limiting toxicity. CD4 cell counts increased with didanosine but declined following the addition of IFN-alpha; CD4 cell percents tended to increase and remain elevated. Thus, combination therapy with didanosine and IFN-alpha can be safely administered to patients with HIV infection. The clinical benefit of this combination therapy will require further evaluation.

Antiviral Agents↗
PubMed1996

Inhibition of immunoreactive tumor necrosis factor-alpha by a chimeric antibody in patients infected with human immunodeficiency virus type 1.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to stimulate human immunodeficiency virus type 1 (HIV-1) replication, has been implicated in the pathogenesis of HIV-1 infection. Inhibition of TNF-alpha by a chimeric humanized monoclonal antibody, cA2, was investigated in 6 HIV-1-infected patients with CD4 cell counts < 200/mm3. Two consecutive infusions of 10 mg/kg 14 days apart were well tolerated, and a prolonged serum half-life for cA2 (mean, 257 +/- 70 h) was demonstrated. Serum immunoreactive TNF-alpha concentrations fell from a mean prestudy value of 6.4 pg/mL (range, 4.2-7.9) to 1.1 pg/mL (range, 0.5-2.2) 24 h after the first infusion and returned to baseline within 7-14 days. A similar response was seen after the second infusion. No consistent changes in CD4 cell counts or plasma HIV RNA levels were observed over 42 days. Future studies evaluating the therapeutic utility of long-term TNF-alpha suppression using anti-TNF-alpha antibodies are feasible and warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Randomized, controlled phase I/II, trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients.

Delavirdine mesylate (DLV) is a potent nonnucleoside reverse transcriptase inhibitor with activity specific for human immunodeficiency virus type 1. In the present phase I/II study we evaluated the safety, toxicity, pharmacokinetics, and antiretroviral activities of two-drug and three-drug combinations of DLV and conventional doses of nucleoside analogs compared with those of both DLV monotherapy and two-drug nucleoside analog therapy. A total of 85 human immunodeficiency virus type 1 infected patients with CD4 counts of 100 to 300 cells per mm3 were enrolled in two periods: in the first period patients were randomized to receive either zidovudine (ZDV) plus didanosine (group 1) or ZDV plus didanosine plus escalating doses (400 to 1,200 mg/day) of DLV (group 2). In the second period, patients were randomized to receive either 1,200 mg of DLV alone per day (group 3) or ZDV plus 1,200 mg of DLV per day (group 4). DLV demonstrated good oral bioavailability at all five doses tested. The major toxicity was a transient mild rash which appeared in 44% of all DLV recipients. Overall, group 2 patients demonstrated more sustained improvements in CD4 counts, percent CD4 cells, branched DNA levels, p24 antigen levels, and virus titers in plasma than group 1, 3, or 4 patients. The magnitude of the response correlated with the intensity of prior nucleoside analog treatment, the non-syncytium-inducing or syncytium-inducing viral phenotype at baseline, and the presence of a wild-type codon at amino acid position 215 in the baseline reverse transcriptase genotype. Despite a transient rash, DLV therapy was well tolerated. Combination therapy with DLV and nucleoside analogs appears promising, with the three-drug combination appearing to be more potent that either two-drug combinations or monotherapy.

Adult↗
PubMed1996

Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.

More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

AIDS-Related Opportunistic Infections↗
PubMed1996

Variation of reaction time can be reduced by the time locked application of magnetic stimulation of the motor cortex.

It was the aim of this study to determine the influence of non-invasive magnetic stimulation on the performance of a visually induced reaction task. The experiment was performed in 8 healthy volunteers. After a visual stimulus subjects had to move their thumbs as soon as possible. The muscular reaction was recorded with surface EMG on both sides. After the visual go-signal a magnetic stimulus (Fig. 8 coil) was applied above the right or left motor cortex at varying time intervals (30 and 110 ms). The magnetic stimulus was randomly given or not. Short time intervals between visual and magnetic stimulus induced a shortening, long intervals induced a prolongation of the reaction time. The contralateral reaction time was always longer than the ipsilateral one. Compared with the reaction times without magnetic stimulation, the intraindividual standard deviation of the reaction times was markedly reduced by the application of the magnetic stimulation. This reduction was greater in ipsilateral than in contralateral recordings. The kind of the instruction had additional modifying effects.

Evoked Potentials↗
PubMed1995

Localized proton NMR spectroscopy in the striatum of patients with idiopathic Parkinson's disease: a multicenter pilot study.

Single voxel proton MRS was used to study brain metabolism in the striatum of patients diagnosed with idiopathic Parkinson's disease (PD). Peak metabolite ratios in long echo time spectra were evaluated in 151 patient spectra and 97 age-matched control spectra collected at four participating institutions using identical hardware and clinical protocols. Combining data from all ages (27-83 years old) showed no significant difference between patient and control ratios. However, in an elderly subset of patients (51-70 years old), a significant decrease in striatal N-acetylaspartate (NAA)/choline (Cho) was observed. Also, a significant decrease in the mean NAA/Cho ratio was observed in patients versus controls for patients not being treated with Sinemet (Du Pont Pharm, Wilmington, DE) (hereafter referred to as levodopa/carbidopa). This result is consistent with the hypothesis that NAA may provide a reversible spectroscopic marker for neuronal dysfunction, although a prospective follow-up study will be needed to confirm this. Quantitation of MRS would be useful to exclude the possibility that a change in Cho levels affected the NAA/Cho ratios.

Adult↗
PubMed1995

The significance of three-dimensional MR-defined neurovascular compression for the pathogenesis of trigeminal neuralgia.

Three-dimensional MR tomography was used to examine the relationship between symptoms of trigeminal neuralgia and neurovascular compression of the nerve in 18 patients. The intensity of neurovascular interaction was classified according to neuroradiological criteria. We found that a radiologically defined compression or dislocation of the nerve by an artery was always associated with symptoms of trigeminal neuralgia. A simple contact between vessel and nerve, however, was also observed on the asymptomatic sides of 10 out of 18 patients. In 6 of 18 patients, in contrast, trigeminal neuralgia was present in spite of the absence of neurovascular contact. In accordance with a cited study based on autopsy and intraoperative findings, our findings indicate that, in a certain proportion of cases, trigeminal neuralgia may be caused by neurovascular compression alone, whereas in other cases, other pathogenetic factors may be involved to a varying degree or be even exclusively responsible for the development of trigeminal neuralgia. The possible significance of the method for a preoperative estimation of the success of microvascular decompression of the trigeminal nerve is discussed.

Adult↗
PubMed1995

Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy.

A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS--measured by magnetic resonance spectroscopy--no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities. CONCLUSION. DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.

Adolescent↗