Recombinant human gamma interferon in human immunodeficiency virus-infected children: safety, CD4(+)-lymphocyte count, viral load, and neutrophil function (AIDS Clinical Trials Group Protocol 211)

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.     

Chemoattraction of male gametes by a pheromone produced by female gametes of Chlamydomonas

In isogamous species of Chlamydomonas, such as Chlamydomonas reinhardtii and Chlamydomonas eugametos, the sexual process involves the use of flagella agglutinins by which the gametes of compatible strains adhere through chance encounter and ultimately pair and fuse to form zygotes. In a newly described heterogamous species, Chlamydomonas allensworthii, the sexual process is initiated by the chemoattraction of small sperm to a sexually competent female gamete, which continues to secrete the pheromone until it has fused with one of the sperm so attracted. From bacteria-free female strains of C. allensworthii, the chemoat-tractant has been isolated and identified as a pentosylated hydroquinone (Mr = 532) whose spectral, chemical, and physical properties are in accord with the structure of a 2,3-dimethyl-5-(triprenylcarboxymethyl)-1,4-benzohydroquinone-1-(beta-xyloside). A rapid bioassay of the pheromone uses DEAE-Toyopearl 650M beads to which the pheromone adsorbs. When such activated beads are placed in a suspension of sperm, they act as surrogate females and attract the small motile sperm. The purified pheromone shows activity at a concentration as low as 1 pM.     

Reliability of self-reported behavioural health risk factors in a South Australian telephone survey

OBJECTIVE: To test the reliability of telephone health survey questions. METHOD: A telephone survey on mental health of South Australians in 1997 was re-administered to a random sub-sample of 102 respondents between 32 and 79 days after the original survey. RESULTS: Demographic questions (age, gender, number of adults and children in the household) showed the highest reproducibility and were almost perfect. Questions regarding health risk factors, such as smoking and drinking behaviour, showed substantial to almost perfect agreement. Co-morbidity variables were substantially reproducible where prevalence estimates were not close to zero. CONCLUSIONS: The results were comparable to findings from similar studies associated with the Behavioral Risk Factor Surveillance System (BRFSS) in the United States. The study suggests that the telephone health survey instrument used in South Australia is reliable for estimating health conditions and behaviours in the population.     

Random digit dialling and Electronic White Pages samples compared: demographic profiles and health estimates

OBJECTIVE: To compare the methodologies of and health estimates derived from two telephone household survey methods. In particular, to establish if White Pages telephone listings provide a relatively unbiased sampling frame for population health surveys. METHOD: In South Australia in 1998, a health survey questionnaire was administered by telephone to two randomly selected population samples. The first method used EWP (Electronic White Pages, n = 6,012), which contains all listed residential telephone numbers as the sampling frame. The results were compared to a RDD (random digit dialling, n = 3,080) sample where all listed and unlisted telephone numbers were included in the sampling frame. Demographic variables and health estimates were compared between the surveys, and then compared to a 'gold standard' door-to-door household survey conducted concurrently. RESULTS: The response rate for EWP (83.8%) exceeded that of RDD (65.4%). More than four times as many calls were required per completed interview in RDD. Demographic profiles and health estimates were substantially similar. CONCLUSIONS: EWP requires fewer telephone calls and enables approach letters establishing the bona fides of the survey to be sent to each selected address before calling, increasing the response rate. RDD is a more inclusive sampling frame but also includes non-connected and business numbers, and offers no significant advantages in providing health estimates. IMPLICATIONS: There are substantial methodological and cost advantages in using EWP over RDD as the sampling, frame for population health surveys, without introducing significant bias into health estimates.     

Opposite effects of glutamate antagonists and antiparkinsonian drugs on the activities of DOPA decarboxylase and 5-HTP decarboxylase in the rat brain

This study measured the activities of L-DOPA and 5-HTP decarboxylase (DDC and 5-HTPDC) in the substantia nigra and corpus striatum of reserpine-treated rats. Acute injection of the NMDA receptor antagonists CGP 40116 (5 mg/kg) and HA 966 (5 mg/kg), and to a lesser extent eliprodil (10 mg/kg), greatly elevated DDC in both structures, whilst having no effect on (nigra) or inhibiting (striatum) 5-HTPDC. L-DOPA (25 mg/kg) on its own inhibited both enzymes in either brain region. The weak NMDA receptor-channel blockers (and antiparkinsonian drugs) budipine (10 mg/kg), memantine (40 mg/kg) and amantadine (40 mg/kg) strongly increased DDC, whilst not affecting or decreasing 5-HTPDC activity in nigra and striatum. The L-DOPA-induced suppression of DDC was mostly reversed by all three antiparkinsonian drugs, whilst L-DOPA-induced inhibition of 5-HTPDC was only reversed by CGP 40116 (striatum only). It is concluded that glutamate exerts a differential physiological influence on the biosynthesis of dopamine and 5-HT in the brain, by tonically suppressing DDC and tonically stimulating 5-HTPDC. The L-DOPA-induced reduction in DDC may help to explain the eventual loss of efficacy of L-DOPA therapy in parkinsonian patients. It is suggested, however, that it may be possible to extend the lifetime of L-DOPA therapy with drugs which potentiate the activity of DDC, such as budipine and the 1-aminoadamantanes.     

Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery

BACKGROUND: Corticosteroids have been recommended to facilitate rapid recovery after cardiac surgery. We previously reported that dexamethasone given after induction of anesthesia decreases the incidence of postoperative shivering. We performed a post hoc analysis of the data obtained during that study, focusing on secondary outcomes. METHODS: A total of 235 adult patients undergoing elective coronary or valvular heart surgery were randomized to receive dexamethasone 0.6 mg/kg or placebo after induction of anesthesia. Patients who had pharmacologically treated diabetes mellitus, had hypersensitivity to dexamethasone, or were receiving treatment with corticosteroids were excluded. RESULTS: We found that, compared with placebo, patients receiving dexamethasone were more likely to remain tracheally intubated for 6 hours or less (26.4% vs 10.0%, p = 0.020) and had a lower incidence of early postoperative fever (20.2% vs 36.8%, p = 0.009) and new-onset atrial fibrillation during the first 3 days postoperatively (18.9% vs 32.3%, p = 0.027). However, we could not demonstrate a statistical difference in the intensive care unit or hospital length of stay, or in overall morbidity and mortality. The dexamethasone-treated patients were also more likely to have a higher blood glucose on admission to the intensive care unit (186 mg/dL vs 143 mg/dL, p = 0.012). CONCLUSIONS: Dexamethasone facilitates early tracheal extubation and is associated with a lower incidence of early postoperative fever and new-onset atrial fibrillation. Apart from a treatable decreased glucose tolerance, dexamethasone treatment was not shown to affect morbidity or mortality significantly.