A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and the leading cause of death in patients with the acquired immunodeficiency syndrome. The prevention of the occurrence and recurrence of PCP is a cornerstone in the treatment of patients infected with the human immunodeficiency virus. There are few studies comparing PCP prophylactic regimens. METHODS: The efficacy of three regimens for prophylaxis against PCP was assessed in a retrospective chart review of 211 human immunodeficiency virus-infected patients at risk for the disease. Over the course of the 2-year study period, 133 patients were prescribed trimethoprim-sulfamethoxazole (one double-strength tablet twice a day, thrice weekly) for a mean of 7.4 months (range, 1 to 25 months). Seventy-seven patients received dapsone (50 mg daily) for a mean of 5.7 months (range, 1 to 23 months), and 125 patients received aerosolized pentamidine (300 mg via nebulizer once monthly) for a mean of 9.3 months (range, 1 to 21 months). The majority of patients (62%) received primary prophylaxis; 38% had one or more previous episodes of PCP; and 73% were receiving concomitant antiretroviral therapy. RESULTS: Pneumocystis carinii pneumonia did not develop in any patient receiving trimethoprim-sulfamethoxazole in 981 patient-months. Five patients receiving dapsone for 437 patient-months and 17 patients receiving aerosolized pentamidine for 1166 patient-months developed PCP. Fifty-six percent of the trimethoprim-sulfamethoxazole group and 55% of the dapsone group changed drug due to adverse reactions, while only 2% in the aerosolized pentamidine group required drug change. CONCLUSION: Despite its adverse reaction profile, trimethoprim-sulfamethoxazole is the most effective agent to prevent the occurrence and recurrence of PCP.

Temporal relation of changes in regional coronary flow and myocardial lactate and nucleoside metabolism during pacing-induced ischemia.

The temporal relation between myocardial lactate and hypoxanthine metabolism and regional changes in krypton-81m perfusion during pacing-induced ischemia was studied in 17 patients with coronary artery disease (CAD). During incremental atrial pacing, lactate production and hypoxanthine release occurred early and simultaneously, accompanied by ST-segment changes, but before angina and only few minutes after a significant (17%) reduction in krypton-81m perfusion in areas with more than 90% luminal diameter reduction. During maximal pacing heart rates, krypton-81m distribution decreased to 68 +/- 7% of control in areas with more than 90% diameter reduction and to 80 +/- 4% in 70 to 90% reduction (both p less than 0.05 vs control). Maximal lactate production occurred 15 seconds after pacing (extraction -15 +/- 7% vs 16 +/- 2% during control, p less than 0.05) and peak hypoxanthine release 1 minute after pacing (delta arteriovenous -2.64 +/- 0.8 microM vs 0.08 +/- 0.21 microM during control, p less than 0.05). Krypton-81m perfusion decreased in 20 of the 21 CAD areas. Angina, ST-segment changes, hemodynamic alterations and lactate production occurred in 15, 14, 9 and 15 patients, respectively. In contrast, hypoxanthine release was found in all cases. After pacing, lactate production and all general indexes of ischemia persisted for only 2 to 3 minutes. In contrast, krypton-81m perfusion was still significantly reduced 5 minutes after pacing and was only accompanied by hypoxanthine release (delta arteriovenous -1.41 +/- 0.6 microM, p less than 0.05 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous determination of regional myocardial blood flow with intracoronary krypton-81m in coronary artery disease.

Pacing-induced changes in regional coronary flow were studied continuously with krypton-81m by intracoronary infusion in 25 patients: 21 with 50% or greater diameter narrowing of 1 or more left coronary arteries (group I) and 4 with less than 50% diameter reduction of a left coronary artery (group II). No changes occurred in group II. In group I, krypton-81m perfusion decreased progressively in all areas with more than 70% diameter narrowing, with a simultaneous increase in normal regions. At the end of pacing during angina, krypton-81m perfusion was reduced to 81 +/- 4% of control in areas with 71 to 90% diameter reduction (n = 8) and to 69 +/- 6% in areas with more than 90% diameter narrowing (n = 15). In contrast, in regions with 50 to 70% diameter reduction changes were variable (decrease in 4 regions, increase in 2 and an unchanged distribution in 1 region). Krypton-81m perfusion decreased early, before general signs of ischemia in areas with more than 90% diameter reduction, whereas this decrease occurred later in regions with 71 to 90% diameter narrowing, concurrently with ST-segment changes but before anginal pain. Although all signs of ischemia had disappeared between 2 and 5 minutes after pacing, changes in krypton-81m distribution persisted in most areas for 5 to 15 minutes after pacing. It is concluded that the functional significance of coronary arterial narrowing can be assessed with a continuous intracoronary infusion of krypton-81m. Changes in regional distribution persisted after cessation of pacing-induced ischemia, indicating an ongoing decrease in regional myocardial blood flow.

125Iodinated fibrinogen uptake in inflammatory joint disease as a complicating factor in the detection of deep vein thrombosis.

An enhanced uptake of 125I-fibrinogen observed in the arthritic knee joint of a patient suspected of deep vein thrombosis was confirmed in a number of patients with inflammatory joint disease in the absence of thrombosis. Whilst this is a potentially serious source of false positive diagnoses, the possibility also exists that this phenomenon could be used to evaluate the degree to which active disease is present in the joints of patients suffering from inflammatory disease.

Technetium-99m-labelled diethyl-acetanilido-iminodiacetate: a new hepatobiliary agent. A preliminary report.

A new hepatobiliary reagent 99Tcm diethyl-acetanilido-iminodiacetate has been examined in a small group of patients to evaluate its potential as a clinical reagent. The radiopharmaceutical accumulated readily in the hepatocytes and was rapidly excreted via the biliary system. It would appear possible to develop a dynamic test of hepatocyte function coupled with an evaluation of the patency of the biliary system. No adverse reactions were observed.

Thallium 201 chloride uptake in tumours, a possible complication in heart scintigraphy.

An abnormal uptake pattern of 201Tl thallous chloride observed during myocardial scintigraphy of a patient with known thoracic tumour localization suggested the possibility that thallous chloride may also accumulate in tumours. This was confirmed by observing 201thallous chloride accumulation in rhabdomyosarcoma implants in rats. Thallium 201 accumulation in tumour cells should be borne in mind as a possible complicating factor when using this reagent for the evaluation of cardiac conditions in oncological patients.

A quantitative index derived from 99mTc-pertechnetate scintigraphy to assist in the diagnosis of primary Sjögren's syndrome.

A safe and simple technique is reported by which primary Sjögren's syndrome can be detected with a relatively high specificity and sensitivity. The method of serial scintigraphy has been used with reasonable success; however, the application of the linearity index as described here produced superior results. In 71 patients investigated, a sensitivity of 87% and specificity of 93% were recorded and make this the method of choice for evaluating patients suspected of having primary Sjögren's syndrome.

Criteria for the use of monoclonal antibodies, legislation and ethical considerations.

The criteria governing the in vivo use of monoclonal antibodies in humans are based upon a number of legal requirements with respect to radiation hygiene, pharmaceutical legislation, radiopharmaceutical legislation and regulations with respect to products arising from biotechnology. This in itself has led to a complicated situation which has undoubtedly restricted the development of valuable diagnostic and potential therapeutic agents. From the ethical point of view there are also important considerations, firstly with respect to the methods of producing antibodies, which has resulted in the discontinuation of the raising of antibodies in murine ascites, and secondly in consideration of the ethics of administering labelled antibodies to healthy volunteers and to patients who may not necessarily benefit personally from the procedure. These factors must be evaluated in the light of the EEC document 'Good clinical practice for trials in medicinal products in the European Community from the CPMP working party on Efficacy of Medicinal Products'.

Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection.

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.