Biomedical subjects
Publications and source records attributed to P E Mitchell.
Heavy chain diseases (HCD) are uncommon. We report the first use of recently developed analytical techniques for the assay of immunoglobulin heavy and light chains in the diagnosis and monitoring of a patient with gamma-HCD.
Monoclonal gammopathy of uncertain significance (MGUS) may present the clinician with diagnostic difficulties. This paper reviews the literature relating to MGUS, presents findings of a local prevalence study, and provides advice on monitoring.
Calculation of osmolal gap in plasma and urine samples from patients after acute myocardial infarction was carried out to see whether changes in these variables support the concept of a "sick-cell" mechanism being responsible for the hyponatremia associated with acute myocardial infarction. Some supportive evidence was found on the first day after admission but, overall, the evidence was not convincing.
A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic beta adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3.35 MJ diet that was low in fat and high in fibre. Weight loss was 15.4 (SD 6.6) kg in subjects given BRL 26830A compared with 10.0 (5.9) kg in those given placebo (p = 0.02). The relative weight loss was 0.93 (0.39%) a week with BRL 26830A and 0.61 (0.38)% with placebo (p = 0.02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4.1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11.6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically. BRL 26830A may be a useful drug in the treatment of obesity.
Using automated assays of IgG, IgA, and IgM, and kappa (kappa) and lambda (lambda) light-chains, we assessed the analytical, intra-individual, and interindividual components of variation in a cohort of 12 apparently healthy subjects to examine the utility of the Kallestad Immunochemical Evaluation system. The immunoglobulins and light-chains had small intra-individual variation, and, in consequence, good analytical precisions (CV) of 2.3%, 2.5%, 3.0%, 2.4%, and 2.4% are required for IgG, IgA, IgM, kappa, and lambda assays, respectively. All of these analytes, and the derived kappa/lambda and heavy-/light-chain ratios, have marked individuality. Conventional population-based reference values are of limited utility; therefore, the assays are unlikely to have high diagnostic sensitivity but will be very useful for monitoring individuals. The kappa/lambda ratio may be of particular value in monitoring because a change exceeding 4% does imply a significant (P less than or equal to 0.05) difference in serial results.
The thermic response to noradrenaline infusion was measured by indirect calorimetry in 40 newly referred obese subjects and 19 lean controls. A marked variation in response was found, more so in the obese than in the lean. In the lean group the lowest noradrenergic thermic response was 12.8 kJ but in the obese group 26 per cent had a thermic response less than this. When the thermic response to noradrenaline is expressed as a percentage of the resting metabolic rate the response was significantly (P less than 0.002) lower in the obese, 8.5 (s.d. 6.0) per cent compared with 13.8 (s.d. 5.1) per cent in the lean. The lowest value in the lean group was 7.8 and 42 per cent of the obese group had lower values. The thermic responses in the obese group did not correlate with glucose:insulin ratios measured both fasting and in response to oral glucose, or with the cumulative rises of either free fatty acids or glycerol during the noradrenaline infusion. Hence the majority of obese subjects have a 'normal' response to infused noradrenaline, but there is a subgroup who do have a blunted response. This may explain to some extent the conflicting reports in the literature regarding the presence of otherwise of a thermic defect in obesity.
Parenteral nutrition is a well-established technique for feeding patients with intestinal failure and other conditions which render enteral feeding impossible. Biochemical tests are required in the initial assessment of these patients, for monitoring their response to treatment and for the detection and management of complications. The use of these tests is discussed critically and guidelines are provided for the frequency with which they should be performed. Chemical pathologists and clinical biochemists have an important role in the provision of parenteral nutrition as members of multi-disciplinary nutrition teams.
A patient is reported who developed lactic acidosis, hyponatraemia and features of the Wernicke-Korsakoff syndrome following long term excessive ingestion of beer and lager. Intramuscular thiamine caused a rapid correction of the lactic acidosis, and the hyponatraemia was corrected by intravenous therapy. On discharge after six weeks of intramuscular Parentrovite the patient still retained some chronic features of the Wernicke-Korsakoff syndrome.
Ten tumor markers were measured in serum or urine at approximately three month intervals in patients with breast cancer following mastectomy but before development of overt metastatic disease. In 23 patients who later had metastases, only three markers, alkaline phosphatase, carcinoembryonic antigen (CEA), and gamma-glutamyl transpeptidase (gamma-GT) were consistently abnormal prior to the development of detectable metastases in more than one patient. In half the patients, a "lead interval" of three months or more was obtained using these three markers and little advantage was obtained by the addition of any other biochemical marker. The value of these three measurements was then assessed in a larger group of patients and compared with other tests for metastases. Alkaline phosphatase, CEA, gamma-GT, clinical examination, and chest x-ray were the best indices of the metastatic state in breast cancer, being collectively abnormal in 98% of patients at first presentation with metastases. The authors recommend screening patients postoperatively with these five tests for metastases; more detailed tests should only be carried out if results of one or more these are abnormal.
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