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Biomedical subjects

R Hurley

Publications and source records attributed to R Hurley.

At least 73 records · Page 4Linked to original sources

Cytomegalovirus infection in pregnancy: preliminary findings from a prospective study.

8278 (56%) of 14 789 pregnant women who were screened for cytomegalovirus (CMV) antibodies at their first antenatal visit were seropositive. 42 (3 per 1000) infants screened were congenitally infected. 3 (7%) have serious handicaps, 14 (33%) have minor or transient problems, and 25 (60%) have so far had no problems. In 26 of the 42 mothers with infected infants CMV antibodies were present in the first antenatal blood sample. 28 (67%) of the infected infants were born to mothers who had experienced a primary infection in pregnancy and 7 (17%) to mothers who had experienced recurrent infection. In the remaining 7 (17%) it was not possible to determine the type of maternal infection. One handicapped infant was born after a probable recurrent CMV infection during pregnancy. These preliminary findings suggest that routine screening of pregnant women to detect evidence of primary CMV infection is not helpful.

Antibodies, Viral↗

Efficacy of chloramphenicol in the treatment of neonatal and infantile meningitis: a study of 70 cases.

The efficacy of chloramphenicol in the treatment of 21 neonates and 9 infants with proven meningitis and 37 neonates and 3 infants with suspected meningitis was evaluated from mortality and morbidity data, and by assay of the drug in serum and cerebrospinal fluid. Minimum inhibitory concentrations (MICs) were established for ten isolates. 25% of neonates and 50% of infants had subtherapeutic concentrations of chloramphenicol in serum or cerebrospinal fluid. Dosage was less than that currently recommended in over half of these subjects. Mild toxicity (reversible thrombocytopenia) was observed in only 1 of 20 babies being treated at the recommended dose. Toxic reactions, including the grey-baby syndrome, occurred in 10 babies receiving higher doses. In 4 cases, doses up to ten times that prescribed had been given, and death of 1 baby was attributable in part to chloramphenicol toxicity. 5 of 21 neonates and 1 of 9 infants with bacteriologically proven meningitis died, an overall mortality of 20%. Those infected with gram-negative bacteria had a higher mortality than those infected with gram-positive bacteria (p less than 0 . 05). 21% of the survivors had neurological sequelae. Therapeutic concentrations of chloramphenicol will be achieved in serum and cerebrospinal fluid with daily doses of 25 mg/kg in preterm and term infants during the first week of life and 37 . 5-50 mg/kg for older term babies. The drug should be assayed at 48-hour intervals, to maintain concentrations in the therapeutic, non-toxic range. Dosage should be increased when the peak serum concentration falls below 20 mg/l and decreased when the trough serum concentration exceeds 15 mg/l or the peak concentration exceeds 30 mg/l.

Administration, Oral↗

The pharmacokinetics of chloramphenicol in the neonate and young infant.

The peak and trough serum concentrations and total body clearance of chloramphenicol were determined by microbiological assay in a multicentre investigation of 90 babies. Chloramphenicol was administered by the intravenous, intramuscular or oral route and dosage ranged between 12 and 210 mg/kg/day. A wide variation in both serum levels and clearance amongst babies receiving the same dose was observed. Neonates (64) had significantly higher serum concentrations (P less than 0.001) and slower clearance (P less than 0.0001) than infants (26). Oral administration in neonates resulted in lower steady state serum levels (P less than 0.02) than those following intravenous administration. Term neonates cleared chloramphenicol more rapidly than their preterm contemporaries (P less than 0.005). Forty-one per cent of subjects had potentially toxic serum levels; subtherapeutic peak serum levels (less than 15 mg/l) were recorded in 39/90 babies. Concomitant penicillin therapy resulted in higher serum concentrations (P less than 0.05); phenobarbitone was not associated with increased clearance or lower steady state serum levels of chloramphenicol. Postnatal age and gestational age accounted for some of the variability in pharmacokinetic response to chloramphenicol. Although many babies receiving the recommended dose had serum levels within the accepted range (15-25 mg/l), others did not. Routine monitoring of chloramphenicol in every baby receiving this antibiotic is essential: the regimens of 18% babies in the present study were altered after assay.

Administration, Oral↗

Evaluation of a course on medical microbiology for non-medical graduate scientists from medical microbiological laboratories.

An assessment of the educational value of a series of courses intended to improve the clinical awareness of non-medical graduate microbiologists has been made. Objective and subjective data were collected by means of questionnaires, pre- and post-course multiple choice tests and informal discussion. The format of the courses are described. The increase in cognitive knowledge acquired during three of the courses is comparable with results from another study in clinical students. The anomalous results from one of the four courses may be explained in terms of the composition of that course. The data presented contribute to the information required for the evaluation and assessment of educational courses.

Curriculum↗

Incidence of potentially toxic concentrations of gentamicin in the neonate.

The incidence of putatively toxic serum concentrations and the factors influencing their occurrence were investigated in a study of 91 neonates receiving parenteral gentamicin twice daily at a dose of mean (SD) 5.5 (0.1) mg/kg/day. Most neonates were preterm and of low birthweight. Serum concentrations, area under the curve (AUC), and clearance were calculated. Potentially toxic trough concentrations (greater than 2 mg/l) were recorded in 57 of 91 (63%) neonates; 24 of these had trough concentrations greater than 3 mg/l. These babies were of a significantly lower gestational age and were younger than the remainder of the population. Toxic trough concentrations were not accompanied by raised peak serum values. A wide variation in all pharmacokinetic variables was observed. Peak serum concentration was most highly correlated with dose, while trough concentration, AUC, and clearance were more dependent on postnatal age. Clearance of gentamicin decreased significantly with increasing serum urea and creatinine concentrations. Preterm neonates in the first week of life are likely to develop potentially toxic serum concentrations when receiving the currently recommended dose of gentamicin (5-6 mg/kg/day). To prevent accumulation the dosage interval may need to be increased to 18 hours in these babies.

Female↗

The safety and pharmacokinetics of cefotaxime in the treatment of neonates.

Seventeen neonates with clinical signs of infection who would otherwise have received gentamicin with penicillin were treated with cefotaxime (50 mg/kg bd) for a period of 5 days. One hundred eleven bacteriological cultures were collected and those from 6/17 neonates yielded pathogenic or potentially pathogenic bacteria. Biochemical investigations undertaken before, during, and after the treatment revealed no adverse effects on renal or hepatic function associated with cefotaxime therapy. In addition to manual methods, a computer program was used to determine six pharmacokinetic variables. The mean peak serum level was 87.4 +/- 36.2 mg/liter, the mean trough level 8.0 +/- 6.9 mg/liter and the serum half life 3.1 +/- 0.8 hours. All the neonates showed clinical improvement following cefotaxime treatment with no adverse clinical signs and were discharged well from hospital. It is concluded that cefotaxime may be safely used in neonates and is a suitable alternative to gentamicin and penicillin for primary treatment in units that do not have a persistent and serious problem with infections due to Pseudomonas aeruginosa.

Bacterial Infections↗

Cefuroxime in the treatment of neonates.

The new broad spectrum cephalosporin, cefuroxime, was used to treat 28 neonates with suspected or proved infection. All of them had had complications at birth or in early neonatal life which were known to predispose to infection. The treatment regimen consisted of intramuscular or intravenous cefuroxime (50 mg/kg twice a day) for 5 days. Previously, such infants would have received gentamicin with penicillin or ampicillin. Pathogenic or potentially pathogenic bacteria were isolated from 7 (25%) of them. All of these organisms were sensitive to cefuroxime. None of the babies had meningitis, but blood cultures from 2 gave positive results. There was significant clinical improvement in 27 of them after 5 days of treatment and each was well on discharge from hospital. Serum urea, total protein, albumin, and alanine transaminase levels were estimated before, during, and after cefuroxime treatment. There were no changes attributable to cefuroxime nor were any changes in haemoglobin, packed cell volume, or total differential white cell counts observed. There were no adverse clinical side effects. One hundred and ninety-four samples of serum were assayed for cefuroxime. The mean peak level after intramuscular injection (42.7 mg/l) was reached in 0.8 hours, and the mean trough level was 10.5 mg/l. The mean half-life of cefuroxime in infants aged less than 4 days was 5.8 hours. In 4 infants older than 8 days, it ranged from 1.6-3.8 hours. Half-life was not associated with birthweight. Cefuroxime is a safe, well-tolerated, and rapidly absorbed drug for the treatment of neonates with suspected or proved infections; it is a useful alternative to gentamicin, if the use of an aminoglycoside is not clearly indicated.

Bacterial Infections↗

Bloodstream infections and perinatal mortality.

Bloodstream infection is demonstrable at necropsy in 21.1% of perinatal death but is almost invariably a secondary event, often terminal, contributing to death as a secondary cause. In only 3.8% is infection recorded as the primary cause of death. Escherichia coli predominates, and postmortem and antemortem studies alike confirm the tendency of this and other microbes to involve the meninges in the course of bloodstream infection. Fatal viral and fungal infections are rare, and life-threatening disease is overwhelmingly of bacterial origin. A separate, prospective study of septicaemia in the newborn is reported, and the data are tabulated. The overall incidence in inborn and outborn populations, together with the incidence of specific infections, is stated, and the relationship to birthweight is analysed. The overall mortality for treated cases is 40.7% the mortality being inversely proportional to birthweight, and highest at 62.5% in those born weighting less than 1000 g. The advent of meningitis (1 in 5 cases of septicaemia) aggravates the mortality (83%). The potential hazard of nursing seriously infected babies is emphasised.

Bacteria↗

Screening for toxoplasmosis in pregnancy.

The prevalence of antibody against Toxoplasma gondi in a population of 715 pregnant women has been evaluated by two methods: indirect haemagglutination antibody (IHA) and indirect fluorescent antibody (IFA) test and all positive sera were checked by the dye test. Five hundred of the study population were questioned on diet and on animal contact to elucidate a possible relation to the prevalence of antibody. Results are expressed in international units (IU) of antibody against T gondi. Of the 715 sera, 171 were positive by IHA and 173 by IFA. One hundred and sixty-seven sera were positive by both tests, ninety-eight (58%) correlating exactly, as to the concentration of antibody. The ten sera which were not positive by both tests all had detectable antibody at the minimum concentration only (12 IU). The dye test confirmed all sera positive by both tests with the exception of three. It also confirmed one of four sera positive by IHA antibody alone and two of six positive by IFA alone. All sera that proved dye test-negative had low antibody concentrations (12 IU) by IHA or IFA. The IHA test, which is commercially available in kit form, would be suitable for use as a screening test during pregnancy. The estimated annual rate of antibody acquisition over the age range 16-40 years is 1.2% per annum with the highest rate in the 36-40 age group (2.5% per annum) and the lowest in the 26-30 age group (0.4% per annum). The clinical history was not significantly different between those with and those without antibody against T gondi but significantly more women in the 36-40 age group had a history of animal contact than those in the 26-30 age group. No conclusive evidence of recent or current infection was found.

Adolescent↗

Intrapartum and postpartum pyrexia and infection after induction with extra-amniotic prostaglandin E2 in tylose.

One hundred and twenty-four women, bearing 127 children, in whom labour was induced with extra-amniotic prostaglandin E2 in tylose were studied. High vaginal swabs taken from 111 patients immediately before insertion of prostaglandin E2 were examined, specific identification of microbes being restricted to those present in the amniotic fluid, to haemolytic streptococci, and to other specific microbes. Lancefield group B streptococci were isolated from nine patients, and in eight of these the microbes were isolated from the amniotic fluid. Amniotic fluid was examined from 86 patients and was shown to be contaminated with microbes potentially pathogenic for mother or baby in 11 out of 86 (13 per cent) of the patients examined; in eight patients, the contaminating pathogen was the group B streptococcus. All 127 blood cultures taken during or just after delivery were negative. Six out of nine patients with a group B streptococcus in the vagina developed fever and proven streptococcal endometritis; one child developed fever and another streptococcal septicaemia.

Adult↗

Susceptibility to rubella in a pregnant population after the introduction of vaccination.

The results of testing for the presence of rubella antibody by haemagglutination inhibition in pregnant women are presented for a number of years, together with an analysis of results for the year 1977. Levels of immunity are correlated with age and British nationality. The influence of vaccine availability on numbers with antibody cannot be demonstrated nor can any evidence for the boosting of antibody levels by natural infection can be discerned.

Adolescent↗

Comparison of methods available for assay of chloramphenicol in clinical specimens.

Eight methods for the assay of chloramphenicol in clinical samples were compared with our own modification of a plate diffusion technique using Sarcina lutea and yeast extract agar. Six of the eight methods were less sensitive than originally reported, and five of them were considered unsuitable for use in clinical microbiology practice. The remaining three methods together with the S. lutea/yeast extract modification were used to assay chloramphenicol in 20 samples of serum. Twenty samples of cerebrospinal fluid were also assayed by the S. lutea/yeast extract method. Our results indicate that only the Bacillus subtilis (sensitivity 6x0 mg/l) and the S. lutea (sensitivity 2x5 mg/l) diffusion methods are suitable for use with clinical samples in routine practice. The problems of chloramphenicol toxicity, appropriate dosage regimens, and the need for assay of the drugs are considered.

Bacillus subtilis↗