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Biomedical subjects

D Harvey

Publications and source records attributed to D Harvey.

At least 73 records · Page 4Linked to original sources
PubMed1995

Metabolism of chloramphenicol by glutathione S-transferase in human fetal and neonatal liver.

The glutathione S-transferases of human fetal and neonatal liver catalyse the conjugation of glutathione with chloramphenicol at a low but measurable rate. The highest rates were 1.30 nmol/min/mg protein in a preterm neonate of 26 weeks of gestation and 1.11 nmol/min/mg in a fetus of 22 weeks of gestation, while the lowest measurable was 0.1 nmol/min/mg in a fetus of 17 weeks of gestation. The activity did not correlate with gestational age, but appeared dependent on the concentration of glutathione in the reaction mixture. The rate rose by a factor of three, from 0.39 nmol/min/mg protein with no added glutathione to 1.24 nmol/min/mg with 2 mumol/ml added to the reaction mixture. Chloramphenicol-aldehyde was detectable in the reaction mixture when a liver extract was incubated with glutathione but the proposed intermediate, glutathione-chloramphenicol, could not be demonstrated. Differences in activity with chloramphenicol or a model substrate, under varying conditions, indicate that different isoenzymes are concerned with the conjugation of glutathione to the two substrates. These data support the hypothesis that when glucuronide conjugation is depressed by immaturity, chloramphenicol is metabolised via other pathways.

Aldehydes↗
PubMed1994

Can expression of CD45RO, a T-cell surface molecule, be used to detect congenital infection?

Exclusion or confirmation of congenital infection can be difficult in newborn infants. The presence of an infective organism in a fetus leads to activation of fetal T lymphocytes. We have examined expression of isoforms of a T-cell surface molecule, CD45RO, in 119 infants, 8 of whom had an intrauterine infection diagnosed antenatally. CD45RO was expressed on fewer than 10% of T cells in control infants and on more than 17% of T cells from infants with known infection (p < 0.006). This method allows screening of infants for infection by a range of organisms as a cause of their infection.

Female↗
PubMed1994

The placental transfer of cefuroxime at parturition.

Maternal and fetal serum concentrations of cefuroxime were determined at birth in 39 women who were given a single intravenous dose of either 750 mg or 1500 mg of cefuroxime before delivery. Mean serum cefuroxime concentrations in maternal venous and umbilical venous blood were dose dependent, being significantly higher after 1500 mg of cefuroxime (55.0 mg/l, 95% CI 33.4-80.9 and 19.5 mg/l, 95% CI 9.5-26.3, respectively) than after 750 mg (14.7 mg/l, 95% CI 10.5-21.1 and 8.8 mg/l 95% CI 5.8-9.4, respectively). Antibiotic concentration in maternal blood correlated with sampling time but a similar relationship was not found in cord blood. Fetal concentrations did not correlate with mode of delivery or initial maternal blood pressure. No relationship could be demonstrated between cefuroxime concentration in maternal or cord blood and maternal weight, maternal weight gain, birthweight of baby or volume of fluid infused prior to epidural anaesthesia. It is concluded that maternal and fetal concentrations likely to be effective for prophylaxis before delivery require a maternal dose of 1500 mg of cefuroxime and are independent of these physiological variables.

Analysis of Variance↗
PubMed1993

The mdm-2 gene is induced in response to UV light in a p53-dependent manner.

Irradiation of mammalian cells with UV light results in a dose-dependent accumulation of the p53 tumor-suppressor gene product that is evident within 2 hr. UV treatment causes a dramatic increase in p53-specific transcriptional transactivation activity and an increase in expression of the p53-responsive gene mdm-2. UV-stimulated mdm-2 expression is not directly correlated with the level of p53 protein in a cell because mdm-2 induction is delayed at high UV doses even though p53 levels rise almost immediately. Cells lacking p53 protein do not respond to UV by increasing their expression of mdm-2. The delayed induction of mdm-2 at high UV doses suggests that, in addition to p53 protein levels, other factors contribute to the regulation of mdm-2 expression following UV treatment. The time of induction of mdm-2 in cells treated with UV light correlates with recovery of normal rates of DNA synthesis, presumably after DNA repair. These data indicate a possible role for mdm-2 in cell cycle progression.

3T3 Cells↗
PubMed1993

Lysogenic phage in Salmonella enterica serovar heidelberg (Salmonella Heidelberg): implications for organism tracing.

A phage typing system using a group of 11 closely related phage (as judged by Southern analysis and restriction fragment length polymorphism analysis) was able to distinguish at least six phage types in Salmonella heidelberg of human and animal origin. Restriction fragment length polymorphism analysis using cosmid probes from S. heidelberg confirmed that most S. heidelberg isolates belong to a single 'clonal' group. Southern analysis using DNA isolated from each of the testing phage group showed that phage types 4, 5 and 6 carry closely related endogenous or lysogenic phage. Induction of a lysogenic phage Hlp-4 (Heidelberg lysogenic phage) from type 4 could become lysogenic and convert phage types 1 and 3 to phage type 4 and phage type 5 to a non-typable phenotype.

Bacteriophage Typing↗
PubMed1993

Production of monoclonal antibodies recognising different epitopes present on insulin-like growth factor 1.

Monoclonal antibodies (MAbs) were generated against recombinant human insulin-like growth factor 1 (IGF-1) by fusion of NS-1 myeloma cells with spleen cells from BALB/c X DBA mice immunised with recombinant IGF-1 and synthetic peptide sequences derived from the published amino acid sequence of IGF-1. MAbs were produced that recognised four distinct epitopes including two defined segments of the C and D domains. All MAbs were IgM mouse immunoglobulins. These results indicate the feasibility of producing MAbs to highly conserved proteins.

Amino Acid Sequence↗
PubMed1993

Transplacental transfer of cefuroxime in uncomplicated pregnancies and those complicated by hydrops or changes in amniotic fluid volume.

The transplacental transfer of cefuroxime was determined at antenatal fetal blood sampling in a cross sectional study of 78 patients between 15-35 weeks' gestation, 8-138 minutes after a maternal intravenous dose of 750 mg. Mean serum cefuroxime concentration, measured by high performance liquid chromatography, was 7.4 (95% confidence interval (CI) 6.8 to 8.1) mg/l in control fetuses; concentrations in hydropic fetuses were similar (6.2 mg/l, CI 4.7 to 7.7) but in fetuses with oligohydramnios they were significantly lower, (4.9 mg/l, CI 3.6 to 6.2). Antibiotic concentration did not correlate with gestational age and remained unchanged by transfusion of packed red cells. We conclude that (i) fetal serum concentrations of cefuroxime obtained after a maternal dose of 750 mg are only adequate for prophylaxis against organisms with a minimum inhibitory concentration of < 4 mg/l and (ii) transplacental passage of cefuroxime is significantly reduced in the presence of oligohydramnios.

Amniotic Fluid↗
PubMed1993

Chloramphenicol toxicity.

Although high serum concentrations of chloramphenicol are related to toxicity, as shown experimentally and during treatment, the mechanism of toxicity remains unclear. Published work suggests that relatively minor metabolites may be causally related to toxic reactions in vitro and some of these metabolites have been detected in sera from treated patients. It is possible that all the major toxic manifestations of chloramphenicol may be explained by attack by free radicals. Depletion in compounds acting as cellular antioxidants, such as glutathione and vitamin E, may conceivably increase the vulnerability of an individual to chloramphenicol toxicity, while supplementation with an antioxidant might protect against it. Research into the metabolism of chloramphenicol and into the mechanism of its toxicity has declined since early work in the 1950s and 1960s, but its continuing use worldwide means that there is justification for renewed interest in the toxicology of this useful antibiotic.

Animals↗
PubMed1992

The development and interpretation of the summating potential response.

The development of cochlear responses in the mouse was investigated, recording from the round window. Positive summating potentials (SP) could be detected as early as 7 days after birth in some individuals, the first signs of negative SP occurred in mice aged 10 days, and compound action potentials were first detected at 11 days of age. These early responses were obtained with relatively low frequency stimuli (usually 6 kHz). All waveforms recorded from 20 day old mice could be interpreted as simple additions of positive and negative SP and compound action potentials, each with different amplitudes and latencies. Positive SP showed both fast and slow components. Our observations are consistent with the positive SP with only a fast component arising from the basal turn inner hair cells, the positive SP with fast and slow components being generated by both inner and outer hair cells in the basal turn, and the negative SP seen at low frequencies of stimulation originating from depolarisation of hair cells in the apical turn. Summating potentials may thus be useful for investigating inner and outer hair cell function separately in abnormal cochleas in which it is not known which cell type primarily is affected.

Acoustic Stimulation↗
PubMed1992

The growth of low-birth-weight children.

The growth of 171 seven-year-old children, free from major disability, with a birth weight of 2000 g or less was examined and compared with that of their own parents and of normal-birth-weight peers. Measurements included height, weight, occipitofrontal circumference, biparietal, occipitofrontal and bi-iliac diameters, triceps and subscapular skinfold thickness. Low-birth-weight children were shorter than their parents whereas those of normal birth weight were taller. For all parameters, particularly weight, the low-birth-weight children were significantly less well grown. There was no significant relationship between occipitofrontal circumference and intellectual ability.

Anthropometry↗
PubMed1991

Infantile meningitis in England and Wales: a two year study.

A two year prospective study identified 1922 cases of meningitis in children under 1 year of age. A further 201 cases were identified from other sources. The annual incidence of meningitis during the first year of life was 1.6/1000; during the first 28 days of life it was 0.32/1000, and among postneonatal infants it was 1.22/1000. The male:female ratio was 1.4:1. The overall case fatality rate was 19.8% for neonates and 5.4% for postneonatal infants. Two thirds of deaths identified in the study, 50% of all deaths, were not attributed to meningitis by the Office of Population Censuses and Surveys. Group B beta haemolytic streptococci (28%), Escherichia coli (18%), and Listeria monocytogenes (5%) were most frequently isolated from neonates and Neisseria meningitidis (31%), Haemophilus influenzae (30%), and Streptococcus pneumoniae (10%) from postneonatal infants. At 2-6 months of age N meningitidis meningitis was most common, and at 7-12 months H influenzae predominated. Meningitis caused by group B beta haemolytic streptococci occurred up to 6 months of age and had a consistent mortality of 25%. Neonatal meningitis due to Gram negative enteric rods had a mortality of 32%. Low birth weight was a significant predisposing factor for both neonates and postneonatal infants. In both groups mortality was significantly higher among children admitted in coma. There was no seasonal variation in incidence in either group. Neonates were treated with either group. Neonates were treated with either chloramphenicol (50%) or gentamicin (48%) usually in combination with a penicillin; 40% received a third generation cephalosporin. Of the 1472 postneonatal infants treated 84% received chloramphenicol with a penicillin and 10% received a third generation cephalosporin. Relapse occurred in 49 patients and three died. Eighteen babies coned as a result of raised intracranial pressure, including four neonates, and four died. Mortality among the 133 (7%) children who received steroids was significantly higher than in the rest of the study group.

Chloramphenicol↗