Biomedical subjects
Publications and source records attributed to S C Mitchell.
Trimethylamine N-oxide, a common food component, has been identified as a major source of urinary dimethylamine in man. The potential pathophysiological consequences of exposure to dietary derived dimethylamine are raised.
The difficulties of 24-hour urine collection are well recognized, especially for elderly people for whom a means of estimating protein excretion from a single casual unit sample would be preferable. We compared measurement of total urinary protein estimated by the protein/creatinine ratio with 24-h urine collection and examined the role of the ratio in discriminating between clinically important levels of proteinuria. Although the protein/creatinine ratio appeared to have an excellent correlation with the 24-h collection, the absolute agreement between the two methods was poor. However, the clinical role of the protein/creatinine ratio as a semi-quantitative test of proteinuria remained, provided adjustment for expected creatinine excretion was made.
A rapid and simple assay procedure employing head-space gas chromatography has been developed for the routine quantification of volatile methylamines and stable trimethylamine N-oxide present in human urine. This assay will enable the rapid screening of patients and aid the diagnosis of fish odour syndrome.
OBJECTIVE: To assess the quality of toilet facilities available for disabled people in a large provincial teaching hospital. DESIGN: Survey of toilet facilities for patients on the wards and in the outpatient department. SETTING: Teaching hospital in Leeds. RESULTS: Although the quality of toilet facilities varied, none met the standards recommended by the British Standards Institution. The worst facilities were found on a ward accommodating elderly patients, where the toilets were unsuitable for use by disabled people and bedside commodes had to be used instead. CONCLUSION: Toilet provision within a major hospital failed to meet standards required for disabled people. Admission to hospital may therefore result in loss of independence and dignity. If hospitals are to be centres of excellence, greater consideration must be given to the requirements of disabled people in the design of new wards, and current inadequate facilities should be upgraded.
Although it is now generally regarded that the origin of urinary trimethylamine (TMA) is via the action of intestinal microflora on precursors such as choline, little direct evidence exists. The normal production of urinary TMA was shown to be absent in germ-free mice and greatly reduced in antibiotic-pretreated animals. Cohabitation of germ-free mice with conventional animals restored their ability to excrete TMA. This study invokes a fundamental role for the intestinal microflora in the provision of TMA from precursors within the food.
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The fate of the three isomeric benzoic acid-substituted monochlorobenzanilides has been studied in the rat after their oral administration. The excretory profile of all three isomers was similar with over half of the dose being excreted in the 0-24 hour urine and between 83-87% being recovered during the three days following administration. The most prominent route of metabolism was that of 4'-hydroxylation on the unsubstituted aniline moiety followed by glucuronic acid conjugation.
The metabolism and excretion of [14C]-trimethylamine has been investigated in seven strains of rat. Over 75% of the administered radioactivity was excreted via the urine within the first day, with up to 9% in the faeces. At this dose level (15 mg/kg body wt) N-oxidation was the major metabolic pathway encountered (45% excreted dose) whilst demethylation was only of minor importance (3%). The remaining compound was excreted unchanged. No significant differences were observed between the strains studied.
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We describe two cases of spontaneous sternal fracture with no underlying pathology other than a severe dorsal kyphosis resulting from osteoporosis. Both patients complained of chest pain. Sternal fractures are particularly likely to occur in the elderly when the costal cartilages become ossified and there is an associated thoracic kyphosis. In elderly patients with a kyphosis the lateral thoracic radiograph should include the sternum to ensure recognition of this complication.
A cDNA that expresses a mRNA restricted to cytotoxic T lymphocytes (CTL) and mammary tissue has been isolated and characterized. The deduced amino acid sequence from this cDNA shows extensive homology with the previously reported amino acid sequence for rat alpha-casein. Indeed, the presence of a six-residue-repeated motif that is specific for rodent alpha-caseins strongly supports the identification of this cDNA as mouse alpha-casein. Northern (RNA) blot analysis of many hematopoietic cell types revealed that this gene is restricted to CTL, being expressed in four of six CTL lines examined. Furthermore, CTL that express this gene were also found to express other members of the casein gene family, such as beta- and kappa-casein. These results suggest that caseins may be important in CTL function, and their potential role in CTL-mediated lysis is discussed.
A method potentially of value for investigating putative heterozygotes or carriers of trimethylaminuria by using a single oral dose of trimethylamine (TMA) is described. For healthy volunteers under normal dietary condition and following oral challenge with 300 mg and 600 mg TMA-base, over 90% of the urinary TMA was excreted in the form of TMA (93.6 +/- 1.6%). However, at a dose level of 900 mg TMA-base, there was clear evidence of saturation of the N-oxidation reaction as urinary TMA excretion declined to 77.2% (range 74.8-78.9) of the total dose of TMA. By contrast, in pedigree studies based upon propositi with trimethylaminuria, several parents were identified who showed clear evidence of saturation of the N-oxidation of TMA at the 600 mg TMA-base dose level, but not at 300 mg TMA-base or under normal dietary condition. In these individuals, the proportion of urinary TMA as trimethylamine N-oxide (TMAO) declined to (77.3 +/- 1.7%). Accordingly we propose that the oral administration of 600 mg TMA-base and the analysis of the following 0-8-h urine collection may be useful for the investigation of possible carriers of trimethylaminuria.
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