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Biomedical subjects

R A Braithwaite

Publications and source records attributed to R A Braithwaite.

At least 37 records · Page 2Linked to original sources

Drugs of abuse screening in the West Midlands: a 6 year retrospective survey of results.

We describe the results of urinary drugs of abuse screening performed by the West Midlands Regional Laboratory for Toxicology, Birmingham, UK, on more than 27,800 urine specimens received between January 1988 and December 1993. The number of specimens positive for amphetamine declined from 1988 to 1990, but this was followed by a doubling of specimens testing positive from 5.7% in 1990 to 12.0% in 1993. There is very little evidence of methamphetamine or Ecstasy abuse in the West Midlands. Morphine (assumed to be from heroin abuse) is the most common opiate detected, with 11.7% of all specimens received proving to be positive in 1993. The incidence of cocaine abuse is low, less than 5% when requests are based on clinical judgement, and less than 3% in the overall population monitored.

Amphetamine↗

Binding of lead to a metallothionein-like protein in human erythrocytes.

We have studied the erythrocytes from 24 workers occupationally exposed to inorganic lead, one asymptomatic lead worker showing exceptionally high exposure, and eight control subjects (blood lead 300-750, 1800, and < 100 micrograms/L, respectively). High performance protein chromatography, electrophoresis, and trace metal analysis have identified a low M.Wt., copper, and zinc-containing protein in all cases. This protein (designated protein M) bound lead on in vitro incubation with buffered lead nitrate. Purified samples of protein M were found to show characteristics consistent with metallothionein (M.Wt. approximately 6500, low pI, and greater UV absorbance at 254 nm). Amino acid analysis found a composition of 33% cysteine but no aromatic amino acids. The highly exposed subject showed endogenous lead binding to protein M, which on further purification by ion exchange was found to be associated with one particular constituent (protein M5). Protein M5 was present in much lower quantities in control subjects. These findings suggest the existence of a metallothionein-like protein in erythrocytes which binds lead, sequestering it into a nonbioavailable form and hence protects against lead toxicity.

Adult↗

A pilot study using 99mTc to measure lead and platinum in the human kidney.

A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels.

Cisplatin↗

Monitoring of total chromium in rat fluids and lymphocytes following intratracheal administration of soluble trivalent or hexavalent chromium compounds.

1. Intratracheal instillation of sodium dichromate (CrVI) and chromium acetate hydroxide (CrIII) to male Wistar rats gave rise to increased chromium concentrations in whole blood, plasma and urine up to 72 h post exposure; peak concentrations were reached at 6 h after exposure. 2. The ratio of whole blood chromium to plasma chromium concentrations was significantly different for Cr(VI) and Cr(III) treatments. Both blood chromium and plasma chromium assays should therefore be used for the assessment of chromium exposure. 3. Chromium was also detected in peripheral lymphocytes. Cr(VI), but not Cr(III) accumulated significantly in the lymphocytes after treatment. These cells have potential to be used for biomarkers of the assessment of exposure to chromium compounds.

Acetates↗

Induction of DNA strand breaks in peripheral lymphocytes by soluble chromium compounds.

1. Incubation of human lymphocytes with sodium dichromate (CrVI) at 37 degrees C for 3 h resulted in a dose-dependent increase in DNA strand breaks without concurrent cytotoxicity. In contrast, chromium acetate hydroxide (CrIII) failed to induce DNA strand breaks at sub-cytotoxic concentrations. 2. DNA strand breaks were also detected in the peripheral lymphocytes of Wistar rats, 24 h after intratracheal instillation of sodium dichromate (1.3 and 2.5 mg kg-1). Instillation of chromium acetate hydroxide (up to 21.8 mg kg-1) failed to induce DNA strand breaks in peripheral lymphocytes. In accord with previous studies, hexavalent chromium was found to be more readily absorbed from the lungs into the peripheral blood than chromium in its trivalent form. 3. The results of this study indicate that fluorometric analysis of DNA unwinding (FADU) in peripheral lymphocytes might be a convenient method of measuring an important biological effect of chromium in occupationally-exposed workers.

Animals↗

Disintegration of mercury disc cells in simulated gastric juice: implications for management of disc cell ingestion.

The disintegration of charged alkaline mercury button cells in simulated gastric fluid over a 24 h period has been studied. The integrity of the cells and the amount of mercury that can leak out of them were assessed. The cells raised the pH of the incubating solutions. Disruption was seen in five out of 18 cells tested in 0.1 mol/L hydrochloric acid and one out of nine in 0.9% saline. Five of the six disrupted cells were made by the same manufacturer. Major leakage of mercury only occurred after complete disintegration of the cells. The implications of these findings for the management of patients who have ingested mercury-containing button cells are discussed.

Animals↗

The metabolic effects of fatal cyanide poisoning.

Metabolic and toxicological data were obtained during the first 24 hours following severe and eventually fatal cyanide poisoning. Initial blood cyanide concentrations were 804 mumol/l but fell rapidly over 24 hours following cobalt edetate therapy to 15 mumol/l. However, plasma thiocyanate concentrations rose over 24 hours (147-267 mumol/l) suggesting continued tissue detoxification. The major metabolic abnormality was lactic acidosis (initial pH 7.21, blood lactate 17.5 mmol/l) which corrected over 12 hours. Despite high circulating insulin concentrations the responses of blood glucose, plasma non-esterified fatty acid, blood glycerol and 3-hydroxybutyrate suggested marked insulin resistance.

Acidosis, Lactic↗

Blood lead, ethnic origin, and lead exposure.

A survey of blood lead concentrations is reported in a group of 199 young Walsall children (3-6 years of age). The geometric mean blood lead concentration was 0.47 mumol/l (range 0.2-1.6 mumol/l). There were no significant differences in blood lead concentrations between groups of children with different ages, sex, ethnic origin, or environment.

Child↗

Clinical and sub-clinical lead poisoning: a laboratory perspective.

1. The background, scope and limitations of laboratory methods for the diagnosis of inorganic lead poisoning are outlined in the context of the work of a specialist clinical laboratory for trace element analysis. 2. Data for blood lead, haemoglobin and erythrocyte zinc protoporphyrin concentrations are presented in cases of clinical and sub-clinical poisoning due to accidental or occupational exposure. 3. Data from population surveys of children and adults subject to either environmental or occupational exposure are also shown. 4. In general, analysis for lead in an appropriate specimen of blood offers the single most useful index of exposure. 5. The importance of good accuracy control in such measurements is emphasized.

Adult↗

Emergency analysis of paraquat in biological fluids.

A variety of spectrophotometric, gas and liquid chromatographic and radioimmunoassay techniques have been applied to the measurement of paraquat in biological fluids. A brief review of these techniques is presented. The majority of described methods are far from suitable in the provision of an accurate and reliable quantitative result in an emergency situation and the further development of suitable 'rapid' techniques is desirable. The preparation and characterisation of internal accuracy control materials and the introduction of an external quality assessment scheme would be valuable in the improvement of laboratory investigations of paraquat poisoning.

Body Fluids↗

In vitro and in vivo evaluation of two preparations of activated charcoal as adsorbents of aspirin.

1 The adsorptive capacities of two preparations of activated charcoal have been studied both in vitro and in vivo using aspirin as a test compound. 2 The in vitro adsorptive capacities of the charcoal preparations were 477 mg of acetylsalicylic acid/g effervescent charcoal ('Medicoal'); 359 mg/g untreated standard charcoal ('Norit-A') and 482 mg/g reheated charcoal ('Norit A'). 3 In vivo both charcoal preparations significantly reduced peak salicylate concentrations and salicylate availability, to a similar extent (analysis of variance P less than 0.001). 4 Both charcoal preparations have similar capacities for adsorbing aspirin both in vitro and in vivo.

Adsorption↗

Prediction of steady-state plasma concentrations and individual dosage regimens of tricyclic antidepressants from a single test dose.

Inappropriate plasma drug concentrations may be one major reason why many patients fail to show a satisfactory clinical response or experience side-effects to treatment with tricyclic antidepressants. One way of improving the situation is to try to reduce the variability in plasma concentrations by individualising drug dosage regimens as early as possible in treatment. This could be done if it were possible to predict the steady-state plasma concentrations that would be achieved by patients on any given dosage regimen. Our own studies, as well as those of other groups, have demonstrated that it is possible to make such predictions from simple measurements of drug plasma concentrations after administration of a single test dose of antidepressant. The test is best carried out in addition to therapeutic monitoring and is a simple means of selecting the optimum starting dose. The clinical advantages of a simple tolerance test are (1) ensuring that an appropriate dosage is prescribed, (2) reducing the number of dosage alterations, (3) reducing the risk of toxicity, and (4) checking patient compliance when used in combination with routine therapeutic monitoring.

Antidepressive Agents, Tricyclic↗