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Biomedical subjects

B J Harris

Publications and source records attributed to B J Harris.

At least 19 recordsLinked to original sources

Quantification of HIV-1 group M (subtypes A-G) and group O by the LCx HIV RNA quantitative assay.

Human immunodeficiency virus type 1 (HIV-1) genetic diversity presents a challenge to nucleic acid-based assays with regard to sensitivity of detection and accuracy of quantification. The Abbott LCx HIV RNA Quantitative assay (LCx(R) HIV assay), a competitive RT-PCR targeting the pol integrase region, was evaluated using a panel of 297 HIV-1 seropositive plasma samples from Cameroon, Uganda, Brazil, Thailand, Spain, Argentina and South Africa. The panel included group M subtypes A-G, mosaics, and group O based on sequence analysis of gag p24, pol integrase, and env gp41. The LCx HIV assay quantified 290 (97.6%) of the samples, including all the group O samples tested. In comparison, the Roche AMPLICOR HIV-1 MONITOR test versions 1.0 and 1.5 quantified 67.3 and 94.6% of the samples, respectively. No group O specimens were quantified by either version of AMPLICOR HIV-1 MONITOR. Seven specimens were below the detectable limits of all the three assays. The LCx HIV assay had fewer nucleotide mismatches at primer/probe binding sites as compared with both AMPLICOR HIV-1 MONITOR tests. The high degree of nucleotide conservation within the pol target region enables the LCx HIV assay to efficiently quantify the HIV-1 subtypes A-G and the most genetically diverse HIV-1, group O.

Genes, Viral↗

Is vaginal delivery preferable to elective cesarean delivery in fetuses with a known ventral wall defect?

OBJECTIVE: We sought to test the hypothesis that vaginal delivery compared with elective cesarean delivery results in improved neonatal outcome in fetuses with a known isolated ventral wall defect. STUDY DESIGN: We performed a retrospective chart review. RESULTS: Between 1989 and 1999, we identified 102 infants with a confirmed antenatal diagnosis of an isolated ventral wall defect with either the diagnosis of an omphalocele or gastroschisis. Sixty-six infants were delivered by cesarean and 36 were delivered vaginally. There were no significant demographic differences between the study groups or between the two sites except that one center (Cincinnati) usually delivered these fetuses by cesarean whereas the other (Louisville) usually delivered such fetuses vaginally. Overall, there were a greater number of infants with gastroschisis than omphalocele (gastroschisis, n = 71; omphalocele, n = 31). After we controlled for primary versus staged closure of ventral wall defect and gestational age at delivery; the medians and interquartile ranges for cesarean and vaginal delivery were 39 (25, 63) days versus 42 (26, 75) days, respectively (P =.32), for neonatal length of stay and 13 (9, 18) days versus 13 (9, 26) days, respectively (P =.16), for days to enteral feeding. After we controlled for the size of the defect and the amount of bowel resected, the odds of primary closure given a vaginal delivery was about half that given a cesarean delivery (odds ratio, 0.56; 95% confidence interval, 0.18-1. 69), but this was not statistically significant. There was no statistically significant difference in the rates of neonatal death (2 [3%] vs 2 [6%]; P =.61) and neonatal sepsis (2 [3%] vs 4 [11%]; P =.18) for cesarean versus vaginal delivery. Maternal length of stay after delivery was found to be 1 day less after vaginal delivery [vaginal, 2 (2, 2) days; cesarean, 3 (2, 3) days; P =.0001]. There were 5 instances of maternal complications, and all 5 pregnancies were delivered by cesarean (P =.16). CONCLUSION: Fetuses with an antenatal diagnosis of an isolated ventral wall defect may safely be delivered vaginally, and cesarean delivery should be performed for obstetric indications only.

Adult↗

Antibiotic overkill of trauma victims?

Antibiotic usage was assessed in a prospective, randomized trial of recombinant interferon-gamma (rIFN-gamma) versus placebo for 212 severely injured trauma patients in four university hospitals. All patients were observed until death or discharge from the hospital. We found the number of antibiotics used and their associated costs staggering and difficult to justify, although serious antibiotic-related complications were infrequent. Regular antibiotic administration following severe trauma should be re-evaluated since clinical evidence supports the use of shorter courses for these patients, with presumed similar outcomes and much-reduced expenses.

Adolescent↗

Effects of polyaspartic acid on pharmacokinetics of tobramycin in two strains of rat.

To provide insight into polyaspartic acid nephroprotection and differences in aminoglycoside renal toxicity between two rat strains, the single-dose pharmacokinetics of tobramycin was examined in the presence and absence of polyaspartic acid. Following a single subcutaneous 6.5-mg/kg dose of tobramycin alone, higher aminoglycoside concentrations were measured in Sprague-Dawley rats than in Fischer rats (P < 0.05). Simultaneous administration of polyaspartic acid (50 mg/kg) and tobramycin did not alter the concentrations of tobramycin in serum. The amount of tobramycin in renal tissue and the amount recovered in urine over a 24-h period were greater in both rat strains when tobramycin and polyaspartic acid were given concomitantly. In summary, polyaspartic acid did not alter the concentrations in serum achieved after a single dose of tobramycin in two different rat strains but did result in higher renal concentrations and greater urinary excretion of tobramycin.

Animals↗

An open-trial evaluation of mitoxantrone in the treatment of progressive MS.

We treated 13 patients with progressive MS with mitoxantrone. All patients received a standard IV dose of mitoxantrone (8 mg/m2) every 3 weeks for a total of seven infusions, with dosage adjustments depending on the hematologic profile at the nadir. The treatment was well tolerated, with the most common side effect being mild nausea. Four of seven women developed transient secondary amenorrhea. The postenrollment clinical behavior of these patients was generally more favorable than during the 18 months prior to enrollment (only three of 13 patients developed an increase in the Expanded Disability Status Scale of more than 0.5 points), suggesting a possible treatment effect, but comparison with two historical control groups (both the active and placebo groups from the Canadian Cooperative Trial of Cyclophosphamide and Plasma Exchange) does not suggest that mitoxantrone was efficacious. Eight of 12 patients had evidence of MRI activity on 13 of 29 follow-up visits. This small, open-labeled pilot study did not provide strong support for proceeding with a randomized, controlled trial of this dosage regimen of mitoxantrone in patients with progressive MS.

Adult↗

Methionine metabolism in mammals. The methionine-sparing effect of cystine.

Cystine can replace approximately 70% of the dietary requirement for methionine. We used standard enzyme assays, determinations of the hepatic concentrations of metabolites and an in vitro system which simulates the regulatory site formed by the enzymes which utilize homocysteine in this study of the mechanism for this adaptation. A significant alteration in the pattern of hepatic homocysteine metabolism occurs following the substitution of cystine for methionine. The major change is a marked reduction in the synthesis of cystathionine. Decreases in both the level of cystathionine synthase and in the concentration of adenosyl-methionine, a positive effector of the enzyme, explain this finding. Despite significant increases in the hepatic levels of betaine-homocysteine methyltransferase and methyltetrahydrofolate-homocysteine methyltransferase, flow through these reactions remains relatively constant. The betaine enzyme may be essential for efficient methionine conservation. In the absence of choline, cystine cannot replace methionine in an adequate diet limited in the latter amino acid.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Effect of dietary cystine on methionine metabolism in rat liver.

Cystine supplementation of adequate diets resulted in significantly higher hepatic levels of betaine-homocysteine methyltransferase. Other changes occurred but were a function of the basal diet. When the latter contained 0.25% methionine + 0.5% cystine, the additional cystine caused a markedly lower hepatic cystathionine synthase activity and lower levels of both adenosylmethionine and serine. The metabolic effect of these changes may be enhanced methionine retention and diminished transsulfuration.

Animals↗

The effect of personal characteristics on response levels in a health survey.

In a survey of everyday health in South Auckland, 207 mothers kept a diary of their families' health episodes and influences. Besides noting the problems of obtaining and maintaining respondent compliance, we found considerable variations in reporting levels between the main ethnic groups and between those willing to keep diaries for shorter or longer periods. The number of reports recorded varied on different days of the week and as time progressed. We quantified these variations and suggest correction processes which may be applied to research findings in multi-cultural areas.

Adult↗

Audiometry and tympanometry in children throughout one school year.

One hundred children had audiometry and tympanometry testing every two to three weeks throughout 38 weeks of a school year. The results showed an average prevalence of some abnormality in 62% and that the abnormal group was constantly changing. Abnormal episodes had a median duration of three to four weeks and a mean of six weeks. Thirty-nine percent of the children had more than one episode. Comparisons were made between the different measures of hearing and middle-ear function and between these and educational tests of intelligence, language and school achievement. Educational deficit was related most closely to total decibel loss. Four screening models were designed to allow economical use of testers' time. Resultant test patterns were related to two to three week testing and to educational test results. The closest correlation with educational test results proved to be an audiogram pass/fail screen each school term.

Acoustic Impedance Tests↗

Everyday health, South Auckland, 1980-81.

A morbidity diary was kept by 207 families in South Auckland. The subjects were known to the investigators from a previous study and much information about the families was already recorded. During two weeks records were requested on everyday health practices, disabilities, symptoms, health activities, upsets, and opinions on whether days were "good" or "bad". One hundred and fifty families gave information for two weeks and fifty-seven for one week. Data showed many significant relationships between demographic and socio-economic characteristics and health experiences and activities. These relationships are reported, and the importance of obtaining such information about communities and individuals discussed.

Adolescent↗

Regulation of hepatic betaine-homocysteine methyltransferase by dietary betaine.

The level of betaine-homocysteine methyltransferase increases in the livers of rats fed diets supplemented with betaine or choline. The increase occurs within 3 days following the change in diet. When we administered betaine by intraperitoneal injection to rats fed choline-free diets, we observed a similar increase within 24 hours. Since betaine-homocysteine methyltransferase catalyzes a reaction which is essential for the catabolism of betaine, these changes provide a means for adaptation to excessive levels of dietary choline and betaine.

Animals↗

Methionine metabolism in mammals: concentration of metabolites in rat tissues.

We have evaluated factors which regulate the content of methionine, adenosylmethionine, adenosylhomocysteine, cystine, cysteine and acid-soluble thiols in rat tissues. In liver the concentration of methionine appears relatively insensitive to changes in dietary protein intake. In contrast the hepatic levels of adenosylmethionine, adenosylhomocysteine, cystine, cysteine and soluble thiols increased with augmented dietary protein. The ratio of adenosylmethionine: adenosylhomocysteine approximated 6.0 in livers, brains, kidneys and skeletal muscles from rats fed the stock diet. Independent variation in the concentrations of these two metabolites did occur. However, the ratios in livers of animals maintained on diets with varying casein content equaled or exceeded a value of 5.0. We conclude that the maintenance of the concentration of methionine is the primary result of the various homeostatic mechanisms. In addition, most previous reports have overestimated the tissue content of adenosylhomocysteine.

Amino Acids, Sulfur↗