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Biomedical subjects

L Booth

Publications and source records attributed to L Booth.

At least 19 recordsLinked to original sources
PubMed1999

Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals.

Thiopurine methyltransferase (TPMT) degrades 6-mercaptopurine, azathioprine and 6-thioguanine which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Heterozygous individuals have an increased risk of haematological toxicity after thiopurine medication, while homozygous mutant individuals suffer life threatening complications. Previous population studies have identified ethnic variations in both phenotype and genotype, but limited information is available within African populations. This study determined the frequency of common TPMT variant alleles in 101 Kenyan individuals and 199 Caucasians. The frequency of mutant alleles was similar between the Caucasian (10.1%) and Kenyan (10.9%) populations. However, all mutant alleles in the Kenyan population were TPMT*3C compared with 4.8% in Caucasians. In contrast TPMT*3A was the most common mutant allele in the Caucasian individuals. This study confirms ethnic differences in the predominant mutant TPMT allele and the findings will be useful for the development of polymerase chain reaction-based strategies to prevent toxicity with thiopurine medications.

Alleles↗
PubMed1996

The admission of Asian patients to intensive therapy units and its implications for kidney donation: a preliminary report from Coventry, UK.

OBJECTIVE: To determine the relative admission rates of Asian and non-Asian patients to intensive therapy units (ITUs) in Coventry and to explore the implications of these rates for the transplantation of organs to Asian people. DESIGN: Examination of 1991 census data and a retrospective review of ITU admissions books. Data were collected on ethnic background, presenting diagnosis, and clinical outcome for each admission. SETTING: The three ITUs in Coventry. PATIENTS: All admissions to the ITUs from 1990-93 inclusive. RESULTS: Asian patients were admitted to ITUs disproportionately to their numbers in the Coventry population. Members of the Asian community were less than half as likely to be admitted to an ITU (p < 0.001) and more likely to die while there (p = 0.007) than members of the non-Asian population in Coventry. The proportions of patients referred to the transplant unit and the rates of subsequent donation do not seem to differ significantly for Asian and non-Asian patients (p = 0.26 in both cases). CONCLUSIONS: There are clear implications for the availability of cadaveric kidney transplantation to Asian patients, given that few kidneys from non-Asian donors are histocompatible with Asian recipients. Indeed, in Asians, promotion of living related donation may be more effective in countering the organ shortfall than efforts to increase consent to cadaveric transplantation. However, it may be valuable to investigate any patterns of morbidity or social or cultural factors that might explain the initial low admissions rates to ITUs for Asian patients.

Asia↗
PubMed1992

Syntax PAL: a system to improve the written syntax of language-impaired users.

In our work with children who have difficulty with spelling or with the physical action of writing, we have found a number of children who also have difficulty with written grammar. As an extension of PAL, an existing predictive spelling and typing aid, we have developed a writing aid to help these children with sentence construction. The enhanced system uses the syntax of the initial part of a sentence to enhance the position in the prediction list of syntactically correct words. It was postulated that this would discourage the use of incorrect syntax and encourage the use of correct syntax. In two case studies, the use of Syntax PAL significantly improved the quality and quantity of one child's written output, but had little effect on the other child's work.

Adolescent↗
PubMed1992

Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine.

A primed-constant infusion of deuterated leucine was used in humans to determine the maximal level of enrichment at plateau of apolipoprotein (apo)B-48 and apoB-100 which are synthesized in the intestine and liver, respectively, and to compare the kinetics of these two proteins under identical conditions. Eight normal subjects (four post-menopausal females and four males) over the age of 40 were studied in the constantly fed state over a 20-h period by providing small hourly feedings of identical composition. [5,5,5-2H3]Leucine (10 mumol/kg body weight followed by 10 mumol/kg body weight per hour) was infused over 15 h intravenously. The enrichment of deuterated leucine in apoB-48 and apoB-100 triglyceride-rich lipoproteins isolated by ultracentrifugation (d less than 1.006 g/ml) was determined during the entire infusion period. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-48 was 3.96 +/- 1.41 tracer/tracee ratio (%) which was 39.7% of the plasma leucine enrichment level. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-100 was 7.23 +/- 1.17 tracer/tracee ratio (%) which was 72.5% of the plasma leucine enrichment level. Mean fractional secretion rates of triglyceride-rich lipoprotein apoB-48 and apoB-100 were 4.39 +/- 2.00 and 5.39 +/- 1.98 pools per day, respectively, with estimated residence times of 5.47 and 4.45 hours, respectively. The data indicate that in the fed state there is about a twofold difference in the plateau enrichment of an intestinally derived protein, as compared to one of hepatic origin, most likely attributable to differences in the enrichment of the intracellular leucine in the two organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Production of prostaglandin E2 by human amnion in vitro in response to addition of media conditioned by microorganisms associated with chorioamnionitis and preterm labor.

To examine the potential role of bacterial infection in the cause of spontaneous preterm labor, human amnion cells in tissue culture were exposed to medium conditioned by culturing each of 21 microorganisms previously found in association with chorioamnionitis and preterm labor. At a final concentration of 0.1% bacterial conditioned medium, a significant stimulation of prostaglandin E2 production from amnion cells was observed for this range of microorganisms. Conditioned medium obtained from culturing Bacteroides fragilis caused a dose-related increase in prostaglandin production, final concentrations of 0.02% to 0.1% being stimulatory but greater concentrations (0.1% to 10%) causing a progressive inhibition of prostaglandin synthesis. A similar concentration-related response in which stimulation was followed by inhibition occurred on addition of increasing concentrations of phospholipase A2 to amnion cells. These data suggest that bacterial phospholipase may release arachidonic acid from amnion leading to prostaglandin E2 synthesis, but excessive addition of phospholipase and consequent increased arachidonic acid availability may give rise to substrate inhibition of cyclooxygenase enzyme and inhibit prostaglandin E2 synthesis. Overall it appears that a wide variety of microorganisms associated with preterm labor may secrete phospholipase, which liberates amnion arachidonic acid for conversion to the oxytocic agent prostaglandin E2.

Amnion↗
PubMed1990

The role of image size and retinal motion in the computation of absolute distance by the Mongolian gerbil (Meriones unguiculatus).

In a series of experiments in which Mongolian gerbils were trained to jump over a variable gap, it was demonstrated that computation of the distance to be jumped was dependent on both image size and retinal motion, the latter cue being generated by the production of vertical translation movements of the head (head bobs). When image size was not a reliable cue, the animals produced more head bobs, thereby increasing the availability of retinal motion cues. The performance of the gerbils on various probe trials strongly suggested that they computed absolute distance by combining information about the velocity (or amplitude) of their head bobs with information about the velocity (or displacement) of the moving image of the landing platform.

Animals↗
PubMed1986

Clinical importance of Campylobacter pyloridis and associated serum IgG and IgA antibody responses in patients undergoing upper gastrointestinal endoscopy.

Campylobacter pyloridis was isolated from 77% of 220 (35%) unselected adults undergoing gastroscopy. Isolation was significantly associated with histological gastritis (p less than 0.0001), duodenal ulcer (p less than 0.0001), and to a much lesser extent, with gastric ulcer (p less than 0.05). The relation between the isolation of C pyloridis and peptic ulcer seemed to be independent of coexisting gastritis. In those with no endoscopic or histological evidence of disease there was no relation between isolation and increasing age. Antibody responses to a whole cell sonicate of a strain of C pyloridis were measured by means of an enzyme linked immunosorbent assay (ELISA). Increased IgA (p less than 0.0001) and IgG (p less than 0.0001) antibody titres were found in patients with C pyloridis. Peptic ulceration or gastritis were present in 78% and 100% of patients with a high concentration of IgG and IgA, respectively, but in only 9% and 18% of those with low titres. These results provide further evidence for a possible pathogenic role of these organisms in gastric disease and suggest that immunological markers of their presence might be useful non-invasive indicators of disease.

Adult↗
PubMed1986

Ceftazidime in the treatment of serious Pseudomonas aeruginosa sepsis.

28 patients with serious Pseudomonas aeruginosa sepsis were enrolled into a prospective open study using ceftazidime (CAZ). 10 patients had rapidly fatal underlying pathology, including 5 neutropenic (neutrophils less than 1.0 X 10(9)/l) patients with malignancy. 9 patients including all those with neutropenia also received concomitant therapy with other active antipseudomonal antibiotics (mainly aminoglycosides). All isolates were initially sensitive to CAZ. A favourable response was seen in 18/27 (67%) evaluable cases. Genitourinary infection and osteomyelitis responded well with 100% and 83% favourable responses respectively. Soft tissue and respiratory tract infection responded less well. Results with biliary sepsis were disappointing (all 3 failed therapy). Of the 9 patients failing treatment 5 responded to alternative antibiotics (usually combination therapy of ureidopenicillin plus aminoglycoside). 2 died primarily from underlying pathology and 2 as a direct result of Ps. aeruginosa sepsis. Toxicity was minimal. In the few cases observed other agents and underlying pathology possibly contributed. The most disturbing feature of the study was the emergence of multiple beta-lactam resistance in organisms whilst treated with CAZ. 5 cases occurred, 4 in the infected strain and 1 in a superinfecting strain, occurring in 4 patients within 10 days of starting therapy. 2 cases occurred in patients receiving concomitant aminoglycosides.

Adolescent↗