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Biomedical subjects

N Buchanan

Publications and source records attributed to N Buchanan.

At least 73 records · Page 4Linked to original sources

The effects of genetic exchange on variable antigen expression in Trypanosoma brucei.

The inheritance of variant surface antigens in Trypanosoma brucei has been determined by identifying variable antigen types (VATs) in each of two cloned parental stocks and then examining the presence and abundance of these VATs in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. Nine VATs have been identified from the repertoire of the parental stock STIB 247L and 5 VATs have been identified from the parental stock STIB 386AA; the identified VATs were exclusive to each stock. Their inheritance was elucidated using two assays. In the first, repertoire antisera (RAS) containing antibody specificities to many different VATs were raised in rabbits to the 2 parental stocks and 6 progeny clones. The presence of VAT-specific antibodies in these RAS was then determined by antibody-dependent complement-mediated lysis. In the second assay, the 2 parental stocks and 4 hybrid progeny clones were each independently transmitted through tsetse flies and VATs observed using VAT-specific antisera in indirect immunofluorescence of metacyclic trypanosomes and in bloodstream forms of fly-bitten mice. The results from both assays showed that (1) both metacyclic- and bloodstream-VATs were inherited into the progeny, (2) each hybrid progeny clone contained some VATs from both parents, (3) hybrids did not express all the VATs from either parent, (4) there was little apparent pattern as to which VATs had been inherited and which had not and (5) the VAT repertoires of the hybrid progeny appeared to be larger than those of the parents. In addition, two results indicated that control of VAT expression remains unaltered after genetic exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Paracetamol poisoning in children and hepatotoxicity.

1. Paracetamol is one of the most common drugs that children accidentally ingest. Unlike the situation in adults, death and hepatotoxicity in children from paracetamol poisoning are exceedingly uncommon events. A review of the literature has revealed only seven deaths and fourteen cases of hepatotoxicity in children, with most of the cases resulting from chronic poisoning and not acute poisoning. 2. Children may be less prone to paracetamol hepatotoxicity because of developmental differences in the drug's metabolism and its pathways of detoxification. In the therapeutic setting of treatment of fever and pain in children, paracetamol is regarded as a drug with a higher therapeutic index, and as such, there seems to be little concern with strict adherence to dosage regimes. 3. Scrutiny of the above paediatric cases associated with chronic paracetamol poisoning suggests that the margin of safety of frequent therapeutic doses of paracetamol in infants and young children to be a lot lower than previously appreciated. This review highlights the need to re-evaluate the safety of paracetamol in the context of chronic therapy in infants and young children.

Acetaminophen↗

The normocomplementemic urticarial vasculitis syndrome--report of a case and response to colchicine.

A patient with a 15-year history of urticarial vasculitic rashes and chronic vasculitic skin ulceration has been followed at our Connective Tissue Disease Clinic for the past five years. Serum complement levels have been persistently normal. She has been unresponsive to a variety of medications including steroids, dapsone and hydroxychloroquine. She had a dramatic response to colchicine 500 micrograms daily with total clearing of the urticarial vasculitic rash.

Chronic Disease↗

Methadone levels and neonatal withdrawal.

The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone.

Adult↗

Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis.

The effect of pancreatic enzyme supplementation on the absorption of an oral dose of 250 mg of ciprofloxacin was studied in six patients with cystic fibrosis in a crossover design. The time to achieve maximum serum concentration was slightly reduced upon coadministration of pancreatic enzymes. There were no significant differences in peak concentration, elimination half-life, and area under the concentration-time curve.

Administration, Oral↗

Single-dose concentrations of tinidazole in gingival crevicular fluid, serum, and gingival tissue in adults with periodontitis.

Previous studies have shown that metronidazole is effective in the treatment of subgingival microflora associated with destructive periodontitis. The aim of this study was to determine whether tinidazole, a close analogue of metronidazole, would reach sufficient concentrations in serum, gingival crevicular fluid, and gingival tissue, to inhibit putative periodontopathic bacteria. Ten adult patients with moderate to advanced periodontitis took a single 2-g dose of tinidazole orally. Samples were assayed by high-performance liquid chromatography. The concentrations of tinidazole in serum and GCF were in a similar range (3.2-46.5 micrograms/mL). Tinidazole was not detected in the GCF in three of the patients. The drug was found in gingival tissue obtained at two h (0.17 +/- 0.14 micrograms/mg) and six h (0.15 +/- 0.18 micrograms/mg) after oral administration. The mean concentration of tinidazole in serum at 24 h (13 +/- 3.0 micrograms/mL) is greater than the minimum inhibitory concentration for anaerobic bacteria as reported by others. The present data suggest that a single 2-g oral dose of tinidazole may lead to the presence of potentially bactericidal levels of tinidazole for up to 24 h in the periodontal pockets of some patients with periodontitis.

Administration, Oral↗

Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy.

All pairwise combinations of three cloned stocks of Trypanosoma brucei (STIB 247L, STIB 386AA and TREU 927/4) were co-transmitted through tsetse flies (Glossina morsitans) and screened for the production of hybrid trypanosomes. Clones of metacyclic and bloodstream trypanosomes from flies harbouring mature infections containing hybrid trypanosomes were established and screened for several isoenzyme and restriction fragment length polymorphisms. For each of the three combinations of parents, some progeny clones were observed to be of a phenotype and genotype indicating that genetic exchange had occurred during development of the trypanosomes in flies. These hybrid clones shared three salient features: (1) where the parents were homozygous variants the progeny were heterozygous, (2) where one of the parents was heterozygous, allelic segregation was observed and (3) the progeny clones were shown to be recombinant when two or more markers for which one of the parents was heterozygous were examined. These results are consistent with the progeny being an F1 in a diploid mendelian genetic system involving meiosis and syngamy. Our observations show that all possible combinations of the three stocks may undergo genetic exchange. A marker analysis of a series of clones each derived from single metacyclic trypanosomes showed that individual flies transmit a mixture of trypanosome genotypes corresponding to F1 progeny and to parental types, indicating that genetic exchange was a non-obligatory event in the life-cycle of the trypanosome. In addition, a preliminary analysis of the phenotype of procyclic stage trypanosomes derived from flies infected with two stocks, indicates that genetic exchange is unlikely to occur at this stage.

Alleles↗

Can maximal cardiopulmonary capacity be recognized by a plateau in oxygen uptake?

The failure of oxygen uptake to increase with increasing work has been considered a marker of the limits of the cardiopulmonary system for many years. However, the concept has suffered from inconsistencies in definition, criteria, and data sampling, all of which affect the interpretation of the relation between changes in work and oxygen uptake. To evaluate the response and reproducibility of the slope in oxygen uptake at peak exercise, six subjects (mean age, 33 +/- 6 years) performed two individualized ramp treadmill tests on separate days. During exercise, oxygen uptake (for a given sample of 30 eight-breath running averages) was regressed with time and the slope was calculated. Maximal oxygen uptake, maximal heart rate and maximal perceived exertion were reproducible from day 1 to day 2 (mean difference, 0.4 ml/kg/min, 1.0 beats per minute, and 0.2 for maximal oxygen uptake, heart rate, and maximal perceived exertion, respectively [not significant]). Considerable variability in the slopes was observed during each test and from day to day. This occurred despite the use of large gas exchange samples, averaging techniques, and constant, consistent changes in external work. A plateau, defined as the slope of an oxygen uptake sample at peak exercise that did not differ significantly from a slope of zero, was not a consistent finding within subjects between days. We conclude that marked variability in the slope of the change in oxygen uptake occurs throughout progressive exercise, despite the use of large samples and a linear change in external work. These findings appear to preclude the determination of a plateau by common definitions.

Exercise Test↗

Munchausen syndrome by proxy: a family anthology.

While the Munchausen-by-proxy syndrome is well recognized, the story of one family has been related to describe some remarkable features. These include the psychopathology of the mother, the involvement of both children in the family, the great difficulty in obtaining proof of child abuse and, finally, the prosecution of the mother in the criminal court.

Adult↗

Social aspects of epilepsy in childhood and adolescence.

Epilepsy differs from other chronic conditions because of the unpredictability of the seizures, the absence of an absolute diagnostic test other than video-telemetry and the stigma associated with the condition. Working from a hospital base with a biased population, one might be forgiven for thinking that most people with epilepsy have major problems either of seizure control or socially. This is naturally not the case, but the social problems of epilepsy are sufficiently frequent and/or severe to warrant comment. Simply making the diagnosis may produce parental anxiety and guilt. This is often compounded by societal misunderstanding of epilepsy and the incorrect association with mental illness. Furthermore, it is those children or adults who have severe epilepsy who stand out in society, with the tacit implication that all epileptics (people with epilepsy) are like them. There is a societal generalization that all epileptics are the same. It is not appreciated that there are many types of epilepsy (convulsive and non-convulsive) and that epilepsy varies from being very mild to intractable. Treatment also has implications: children and adolescents may not like to take, or be seen to be taking, medication. It is desirable where possible to recommend twice daily dosage with breakfast and dinner. This avoids the need to take medication to school, or in the case of adolescents, to work. In addition, compliance is enhanced with a twice daily dosage. There is without doubt a stigma associated with epilepsy which persists despite being to a less degree than in the past.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The management of epilepsy: patients' perceptions and expectations.

An anonymous questionnaire, which was designed to obtain information on satisfaction with medical management, personal attitudes and experiences, and patients' knowledge about epilepsy, was sent to a systematic sample of persons on the membership lists of various Epilepsy Associations across Australia. Comments regarding doctors' attitudes towards persons with epilepsy and the inadequacy of informational exchanges between doctors and patients reflected many respondents' dissatisfaction with their medical management. The problems that are perceived by patients in regard to the management of their epilepsy may be addressed through improved education of these patients and of the community in general. Continuing education of medical practitioners, especially in relation to current management trends, patient education skills and the importance of a positive attitude towards epilepsy, may help to improve patients' perceptions of their medical treatment.

Adolescent↗