Objective - To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection.Design - Randomised, double blind, parallel group multicentre study.Setting - Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland.Subjects - 474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts.Interventions - Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily.Main outcome measures - Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects.Results - 460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related.Conclusion - Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.
The influence of pH, dye concentration and sample storage on the histochemical nitroblue tetrazolium (NBT) test in 45 patients with acute bacterial infections and 51 healthy individuals has been examined. Even minor deviations in pH and NBT dye concentration markedly influenced the reduction of NBT to formazan by patient and control neutrophils, and the differentiation between results in these groups was optimal at pH 7.2 and a concentration of 0.05% NBT in the final blood-NBT mixture. Storage of heparinized blood samples for more than 2 hours at 21 degrees C and for more than 6 hours at 4 degrees C is not recommended due to overlap between results in patients and controls. The error involved in counting of NBT-positive neutrophils accounted for the major discrepancies tests in patients and controls and in tests performed on different days. The reproducibility of the endotoxin stimulated test was inferior to that of the unstimulated test.
The reduction of nitroblue tetrazolium (NBT) dye by neutrophils from 379 patients with infectious diseases and 268 controls has been examined. The mean NBT score was 29.8% (72.3% positive tests) in the 231 patients with non-tuberculous bacterial infections, 9.7% (28.1% positive tests) in the 135 patients with viral infections 5.3% (1.5% positive tests) in the controls. Positive tests were demonstrated in 1 of 7 patients with tuberculosis and in 4 of 6 with mycoplasma pneumonia. Patients with urinary tract infections or septicemia had the highest percentage of positive tests, particularly when the infections were caused by gram-negative bacteria. In acute bacterial infection, the 176 patients who had not received any antibacterial therapy prior to testing had a significantly higher mean NBT score and proportion (77.8%) of positive tests than the remaining 55 pretreated patients (54.5%). Recent antibiotic treatment seriously invalidates the NBT test results. In acute viral infection, 29 of the 38 positive tests were obtained from patients with acute hepatitis (mean score 20.0%) or infectious mononucleosis (mean score 9.3%). When evaluating the test results, special attention should be paid to patients with hepatitis. Endotoxin stimulated NBT tests disclosed normal enhancement of NBT reduction by neutrophils from the patients and the controls. Cautiously interpreted, the NBT reduction by neutrophils from the patients and the controls. Cautiously interpreted, the NBT test results may be useful as an adjunct in the differential diagnosis of major bacterial and viral infections.