Myocardial single-photon emission computed tomographic imaging with technetium 99m tetrofosmin: stress-rest imaging with same-day and separate-day rest imaging.

BACKGROUND: Technetium 99m tetrofosmin is a new ethylene diphosphine ligand for myocardial perfusion imaging and has unique properties. We have compared stress-rest single-photon emission computed tomographic (SPECT) imaging with 99mTc tetrofosmin with same-day and separate-day rest imaging to detect myocardial perfusion defects. METHODS AND RESULTS: Myocardial SPECT imaging was performed in 22 patients with coronary artery disease who had undergone planar thallium 201 imaging and coronary angiography. Single-day (stress-rest) and separate-day rest 99mTc tetrofosmin SPECT protocols were compared in the same patient. Images were assessed by a blinded panel to identify myocardial infarction, ischemia, or normal scans. Overall sensitivity for identification of patients with coronary artery disease was 86% (19/22) by both same-day stress-rest and separate-day rest protocols with 99mTc tetrofosmin (p = NS). Of a total of 396 segments studied, 107 abnormal segments were identified at exercise and 76 and 81 at the same-day and separate-day rest tests, respectively (p = NS). Same-day stress-rest and separate-day rest 99mTc tetrofosmin SPECT protocols were also useful for detecting individual coronary stenosis with a greater than 50% lesion: 80% of the left anterior descending, 93% of the right coronary, and 75% of the left circumflex coronary arteries were detected. CONCLUSION: Excellent images were obtained with 99mTc tetrofosmin during both stress and rest. 99mTc tetrofosmin imaging with the same-day stress-rest and separate-day rest imaging protocols have similar diagnostic sensitivities for detection of coronary heart disease.

Comparison of myocardial perfusion imaging with technetium-99m tetrofosmin versus thallium-201 in coronary artery disease.

Technetium-99m (Tc-99m) tetrofosmin, a new myocardial perfusion imaging agent, was evaluated at exercise and rest in 50 patients with documented coronary artery disease to determine myocardial kinetics, redistribution and ideal imaging time. Planar imaging was performed at 5, 30, 60, 90, 120 and 240 minutes after an injection of Tc-99m tetrofosmin (8 to 10 mCi) at peak graded ergometric exercise. Reinjection (24 to 30 mCi) was performed at rest, 4 hours after the stress injection and also on a separate day, and imaging was repeated. All patients underwent thallium-201 (Tl-201) exercise and redistribution (4-hour) imaging. Perfusion defect to normal, and heart to lung ratios were calculated for exercise Tc-99m tetrofosmin images at each time point. The mean +/- SD defect to normal ratios were 0.75 +/- 0.10, 0.75 +/- 0.10, 0.74 +/- 0.09, 0.73 +/- 0.10, 0.73 +/- 0.10 and 0.72 +/- 0.10 at 5, 30, 60, 90, 120 and 240 minutes, respectively (p = NS), suggesting absence of redistribution. There was a significant increase in lung uptake of Tl-201 during exercise (p < 0.05), but not with Tc-99m tetrofosmin (p = NS). Washout of Tc-99m tetrofosmin was calculated in a subset of patients (n = 23). Rapid background clearance enabled postexercise diagnostic imaging as early as 5 minutes after injection. Myocardial retention curves after rest injection suggested that the optimal time for imaging was approximately 30 minutes later. Slow myocardial washout (4%/hour after exercise and 0.6%/hour after rest injection) enabled diagnostic images to be obtained up to 4 hours after each study.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term zidovudine treatment of asymptomatic HIV-1-infected subjects.

Eighteen asymptomatic men with persistent human immunodeficiency virus type 1 (HIV-1) p24 antigenemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and thereafter with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 92 weeks. Six additional HIV-1 p24 antigenemic subjects were treated with zidovudine 500 mg 12-hourly for 76 weeks. Disease progression occurred in 4 subjects, despite sustained reduction of serum HIV-1 p24 antigen levels: Pneumocystis carinii pneumonia was diagnosed after 60, 80, 90 and 93 weeks, respectively. The median CD4+ cell count of these 4 men at study entry was 0.2 x 10(9)/l, and it declined to 0.07 x 10(9)/l at the moment AIDS was diagnosed. In 20 subjects no disease progression occurred. The median CD4+ cell count of these 20 men at study entry was 0.4 x 10(9)/l and it was 0.45 x 10(9)/l at the end of the study period. Median serum HIV-1 p24 antigen levels at the end of the study period were 42% lower than at study entry in these 20 subjects. In 5/20 men, an initial decline was followed by a rise in antigen levels to above pretreatment value. Treatment with zidovudine was well tolerated. Anemia caused symptoms in 3/24 men, but prolonged leucopenia or neutropenia did not occur. None developed clinical or convincing biochemical evidence of zidovudine-associated myopathy.

A review of the pharmacokinetics of zidovudine in man.

Initial pharmacokinetic and bioavailability data in man were obtained from a phase I, open-label, dose-escalating, multiple-dose study of intravenously and orally administered zidovudine. Dose-independent kinetics were observed over the dose-range 2.0 to 10 mg/kg (oral). Zidovudine is rapidly and extensively absorbed following oral administration. The mean half-life is approximately 1 h. The drug is capable of crossing the blood-brain barrier resulting in antiviral concentrations within the cerebrospinal fluid. The major route of elimination is by hepatic glucuronidation followed by rapid excretion of the metabolite in the urine. Consequently, factors affecting liver or kidney function may alter the pharmacokinetic profile. Although no systematic studies of potential drug interactions have been reported, data are accumulating on the concomitant use of zidovudine with other medications.

Decline of HIV antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine.

Six HIV-antigenaemic patients with AIDS or AIDS-related complex were studied to assess the effect of treatment with low-dose zidovudine (250 mg) in 6-hourly doses on HIV antigen (HIV-Ag) levels in cerebrospinal fluid (CSF). HIV-Ag was detected in CSF of three patients before treatment. These patients became CSF HIV-Ag-negative within 8 weeks of treatment. One initially CSF HIV-Ag-negative patient became strongly CSF HIV-Ag-positive during interruption of zidovudine treatment; CSF HIV-Ag disappeared again after treatment was restarted. None of our patients showed a significant neurological improvement during the study. These results show that low-dose zidovudine can suppress viral expression in CSF. Whether suppression of viral replication can prevent future HIV-related neurological disease remains to be investigated.

Effect of zidovudine on serum human immunodeficiency virus antigen levels in symptom-free subjects.

18 men with longstanding human immunodeficiency virus (HIV) antigenaemia but no symptoms received zidovudine in low-dose regimens (250 mg 6-hourly, 500 mg 6-hourly, or 500 mg 12-hourly) with or without acyclovir. Serum HIV antigen rose in only 1 patient and declined significantly in 13 (to below cut-off values in 9). In the 1 subject from whom HIV antigen positive cerebrospinal fluid was obtained, the fluid was antigen negative after 12 weeks of treatment. Acyclovir treatment alone or in addition did not seem to influence serum antigen levels. In 7 untreated men serum antigen levels rose or remained stable during follow-up. CD4+ cell counts increased in 14/18 treated subjects and 1/7 untreated subjects. No disease progression was observed in either group. Regression of enlarged lymph nodes was seen in the zidovudine-treated subjects. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in 2, but serious leucopenia or neutropenia was not observed.

The inhibition of the RNA polymerase activity of influenza virus A by pyrophosphate analogues.

Substituted methylene diphosphonates are effective inhibitors of the RNA polymerase of influenza A virus causing 50% inhibition of the polymerase activity when they are present in the concentration range 10-85 microM. The inhibitory power of the methylene diphosphonates appears to be related to their ability to chelate with metal ions.