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Biomedical subjects

H Masur

Publications and source records attributed to H Masur.

At least 109 records · Page 6Linked to original sources
PubMed1993

Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697,661.

L-697,661 is a non-nucleoside analogue with potent, selective inhibitory activity against the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1). The present study evaluated the potential role of this compound in the treatment of HIV-1-infected patients in a double-blinded, placebo- and zidovudine-controlled trial using plasma viremia as a marker of antiviral activity and real-time phenotypic evaluation of viral isolates for the emergence of resistance. Participants received 12 weeks of either placebo, 25 mg twice a day, 100 mg three times a day, or 500 mg twice a day of L-697,661, or zidovudine, 100 mg five times a day. Mean logarithmic reciprocal titers of plasma virus in patients taking either L-697,661 or zidovudine decreased by week 4 of therapy; for L-697,661 recipients these changes were dose-dependent and, at the highest dose tested, were comparable in magnitude to those seen with zidovudine. Viral suppression induced by L-697,661 persisted through 8 weeks of treatment but decreased by week 12. This rebound paralleled emergence of viral isolates showing resistance to L-697,661. We conclude that although L-697,661 has potent antiretroviral activity in vivo, its utility may be compromised by rapid emergence of L-697,661-resistant virus. Plasma viremia is a highly sensitive technique affording considerable utility in the early testing of such agents.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗
PubMed1993

Lack of clinical utility of cytomegalovirus blood and urine cultures in patients with HIV infection.

OBJECTIVE: To determine the clinical significance of cytomegalovirus (CMV) blood and urine cultures in patients with human immunodeficiency virus (HIV) infection. DESIGN: Inception cohort of patients with HIV infection and CMV culture data. SETTING: Government referral-based research hospital. PATIENTS: A total of 322 HIV-infected patients who had a CMV blood culture and 293 HIV-infected patients who had a CMV urine culture within 7 days of a CD4 determination. MEASUREMENTS: Cytomegalovirus blood and urine culture results; circulating CD4 lymphocyte counts; pathologic or retinopathic findings of CMV disease. RESULTS: Nine of 26 patients (34.6%) with CMV viremia subsequently developed CMV end-organ disease compared with 11 of 74 (14.9%) patients without viremia, (difference, 19.7%; 95% CI, -0.3% to 39.7%). Fifteen of 47 patients (31.9%) with CMV viruria developed end-organ disease compared with 4 of 43 (9.3%) patients without viruria, (difference, 22.6%; CI, 6.7% to 38.5%). Cytomegalovirus culture positivity had poor predictive value for the subsequent development of end-organ disease (35% for viremia and 28% for viruria). Further, patients with proven end-organ disease were often not viremic (45%), but most were viruric (88%). Cytomegalovirus viremia did not correlate with the presence of either fever or weight loss in this patient group. Both blood culture positivity and urine culture positivity varied inversely with the CD4 count (P = 0.0001 for both associations). CONCLUSIONS: The likelihood that a blood or urine culture will be positive in a patient with HIV infection correlates better with immunologic status than with current or future clinical status. Although the absence of CMV viruria may suggest that CMV disease is not present, CMV blood and urine cultures have poor diagnostic and predictive value and therefore should be used primarily for research purposes or drug susceptibility testing and not for making clinical decisions.

Adult↗
PubMed1993

Increased survival of a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis who received sodium phosphonoformate (foscarnet).

PURPOSE: To evaluate the impact of foscarnet on the longevity of persons with human immunodeficiency virus, type 1 (HIV-1) infection and cytomegalovirus (CMV) retinitis. PATIENTS AND METHODS: A cohort of 24 patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis received sodium phosphonoformate (foscarnet) as part of a controlled efficacy trial at the National Institutes of Health. Foscarnet was continued for as long as it was tolerated. Antiretroviral therapy was given to the patients as tolerated. Long-term follow-up was available on all patients. RESULTS: Seventeen patients received zidovudine during or after receiving foscarnet, 2 patients received dideoxyinosine, 2 patients zidovudine and dideoxyinosine, and 3 patients received no specific antiretroviral agent. Patients received foscarnet for a mean of 6.2 months (median, 4 months; range, 10 days to 22 months). Ten patients required a change to ganciclovir therapy at some time after receiving foscarnet. The median time from the diagnosis of CMV retinitis until death was 13.5 months (range, 3 to 34 months). Patients lived longer than untreated or ganciclovir-treated historical controls with AIDS and CMV retinitis. There was no difference in the survival of patients treated with foscarnet at the time of diagnosis and those patients treated with foscarnet only after progression of their CMV retinitis. CONCLUSIONS: These data suggest that foscarnet may prolong the survival of persons with AIDS and CMV retinitis and should be the initial treatment of choice in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Suppression of visual perception by transcranial magnetic stimulation--experimental findings in healthy subjects and patients with optic neuritis.

The influence of noninvasive magnetic brain stimulation by a magnetic coil (MC) placed over the occiput on perception and correct reporting of a briefly presented set of 3 letters of the alphabet was examined in 15 patients with prolonged VEP latencies due to neuritis of the optic nerve. The results derived from observing these patients were compared to the results obtained from an age-matched control group of 20 healthy voluntary subjects examined under the same experimental conditions. In both groups it was possible to demonstrate that transcranial magnetic stimulation is able to suppress recognition of the letters if applied with a certain delay time after a brief presentation of the visual stimulus. The groups were compared to each other with regard to the delay with which it was possible to demonstrate the most effective suppression. In the healthy subjects, this delay was found between 60 and 100 msec. In the patients, it was prolonged to 80-140 msec. This prolongation was closely related to the VEP latency (P100). Furthermore, visual suppression and the influence on it by different parameters were studied in detail in healthy subjects; the visual suppression depends on visual (e.g., brightness, duration) and magnetic (e.g., intensity) stimulus conditions. The method described seems to be of considerable value in the investigation of basic mechanisms of visual perception. This includes pathophysiological changes caused by optic neuritis and possibly other disorders affecting the visual system.

Adult↗
PubMed1993

Esophageal disease in AIDS is associated with pathologic processes rather than mucosal human immunodeficiency virus type 1.

Twenty-five patients with AIDS and esophageal symptoms were evaluated for the presence of esophageal disease and human immunodeficiency virus type 1 (HIV-1) in the esophageal mucosa. A single infectious process caused by Candida albicans, cytomegalovirus, herpes simplex virus, varicella-zoster virus, or Mycobacterium avium-intracellulare complex or a single noninfectious process caused by Kaposi's sarcoma or reflux esophagitis was identified in 20 patients. Two processes were identified in 5 patients. HIV-1 mRNA was detected by in situ hybridization in mononuclear cells in esophageal lamina propria in 36% of patients. The presence of HIV-1 in the esophageal mucosa was not associated with a specific esophageal symptom, mucosal inflammation or ulceration, Kaposi's sarcoma, specific opportunistic infection, or response of the infection(s) to therapy. Esophageal disease in patients with AIDS appears to be associated with specific pathologic processes rather than the presence of HIV-1 in esophageal mucosa.

AIDS-Related Opportunistic Infections↗
PubMed1993

Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS.

The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Complete bilateral oculomotor palsy: the only clinical sign of subarachnoid hemorrhage in leukemia.

We report the original case of a patient with acute myelogenous leukemia who presented with a painless, complete bilateral oculomotor palsy during induction chemotherapy. Headache, signs of meningeal irritation or further neurological symptoms were absent throughout the course of illness. The CT revealed a subarachnoid hemorrhage (SAH). Within a day of the onset of symptoms, the oculomotor palsy subsided completely with no residual damage. To our knowledge, this is the first described case of SAH in leukemia with complete bilateral oculomotor palsy being the only clinical symptom. Furthermore, the spontaneous remission of this pathological condition is an extremely rare event.

Aged↗
PubMed1992

NIH conference. Respiratory disease in the immunosuppressed patient.

Pulmonary complications, both infectious and noninfectious, are an important cause of morbidity in patients with various types of immunosuppression. The appropriate response to these clinical problems requires an understanding of pulmonary host defense and of the various types of systemic immunosuppression. Infectious and noninfectious pulmonary complications may vary according to the type of immunosuppression as well as to the degree and duration of immunosuppression. Appropriate clinical management also requires an understanding of the clinical problems commonly seen in specific groups of immunosuppressed patients and an understanding of the sensitivity, specificity, and potential complications associated with the available diagnostic approaches to those patients. Because respiratory disease in these patient groups may progress rapidly to respiratory failure, an expeditious evaluation based on the knowledge of likely causes of respiratory disease and prompt specific or empiric therapy are indicated. Specific sets of algorithms for the evaluation of both focal and diffuse pulmonary disease may facilitate such an evaluation. In addition, an aggressive approach to the prevention of pulmonary disease including immunization, prophylaxis, and immunomodulation (for example, colony stimulating factors) may be warranted in specific subgroups at risk.

Algorithms↗
PubMed1992

NIH conference. Gastrointestinal infections in AIDS.

As the largest lymphoid organ in the body, the gastrointestinal tract is a potential reservoir for human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), and it is an important site for HIV-induced immunodeficiency. The resulting defects in cellular and humoral defense mechanisms predispose the gastrointestinal tract to a spectrum of viral, fungal, bacterial, and protozoan pathogens that cause relentless morbidity and, in some cases, death. With a thorough diagnostic evaluation, physicians can identify one or more of these pathogens in a majority of patients with AIDS who have gastrointestinal symptoms. The identification of enteric pathogens in patients with AIDS is important because an increasing array of therapeutic regimens is becoming available to treat many of these infections.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The relation between functional deficits, motor and sensory conduction times and MRI findings in syringomyelia.

Opinions about the relation between the dimensions of the syrinx and the severity and distribution of symptoms in patients with syringomyelia are controversial. Therefore, this study investigates the relation of clinical symptoms, a disability score, quantified (1- and 2-dimensional) radiological findings (magnetic resonance imaging, MRI) and electrophysiological data (somatosensory and motor evoked potentials) in 22 patients with syringomyelia. There was a close relation between clinical symptoms and electrophysiological data. By both electrophysiological methods subclinical deficits could be detected. Furthermore, the results disclosed that the clinical symptoms, the degree of disability and the duration of the disease are not related to the dimensions of the syrinx or the electrophysiological results obtained by investigating the long ascending and descending spinal tracts of the lower limbs. Our findings suggest that, besides the syrinx, other factors not directly visible in the MRI are responsible for the development and progress of clinical symptoms.

Adolescent↗