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Biomedical subjects

I D Watson

Publications and source records attributed to I D Watson.

At least 37 records · Page 2Linked to original sources

Detection of drug use in a methadone maintenance clinic: sweat patches versus urine testing.

AIMS: To evaluate the novel use of sweat patches in outpatients attending a methadone maintenance clinic. DESIGN: Assessment of inter-patch reliability and validity of patch results compared to urine tests at the start and end of the patch period. Semi-structured questionnaire on patients' opinion of the patches. Randomized cross-over trial comparing illicit drug use during the week that the patch was worn with a control period. SETTING: Methadone maintenance outpatient clinic in a deprived urban area. PARTICIPANTS: Forty-eight patients with a diagnosis of opiate addiction prescribed methadone for a median of 5 years. MEASUREMENTS: Analysis of urine and patch tests by standard methods for methadone, opiates, morphine (heroin metabolite) and benzoylecgonine (cocaine metabolite). FINDINGS: There was good inter-patch reliability between arm and side patches for methadone (all positive), opiates (k = 0.8) and morphine (k = 1.0) but only moderate agreement for benzoylecgonine (k = 0.49). There was good agreement between the sweat patches and urine tests for methadone (all positive), opiates (k = 1.00) and morphine (k = 0.8), but again only moderate agreement for benzoylecgonine (k = 0.50). The patches were well tolerated and the main side effect was minor irritation. The majority of men preferred a urine test while more women preferred a sweat patch. There was no evidence of reduced use of illicit drugs the period that the patch was worn. CONCLUSION: Sweat patches are reliable and give valid results for patients on maintenance methadone. There are few side effects and it is practical to use them in busy outpatient clinics. They are preferred by some patients but there was no evidence that they altered behaviour.

Adult↗

An audit of therapeutic drug monitoring service provision by laboratories participating in an external quality assessment scheme.

Therapeutic drug monitoring services were investigated in a questionnaire sent to all subscribers to the United Kingdom National External Quality Assessment Scheme for Therapeutic Drug Assays. Questions were posed on assay availability and use, target ranges, and reporting procedures for digoxin, lithium, phenytoin, phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty-seven laboratories replied and, except for lithium, 45% reported in mass units, 34% in molar units, and 22% a mixture of mass and molar units. Target ranges for lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but ranges for phenytoin, theophylline, and valproic acid were more consistent. Immunoassay was the most popular methodology although high-performance liquid chromatography was commonly used for anticonvulsants. Paper copies of results were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and 28% by computer. Additional data, mainly dose, time of last dose, and duration of therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing results ranged from nurses to senior consultants, and collaboration with pharmacists occurred in 26% of laboratories. Most laboratories provided a daily analytical service and 73% offered a 24-hour emergency service. This audit unexpectedly identified use of a wide range of target concentrations, particularly for digoxin and lithium.

Drug Monitoring↗

Laboratory support for the poisoned patient.

Poisoning often does not require toxicology laboratory analysis, though support is necessary from the departments of hematology and biochemistry. There are some compounds, such as paracetamol (acetaminophen), lithium, and methanol, for which quantitative or qualitative analysis is essential for effective patient management. Standard methods such as immunoassays, chromatography, and spectrophotometry have been extended by mass spectrometry and will be enhanced by nuclear magnetic resonance and by hyphenated techniques (e.g., LC-MS-MS). The new perspectives that can be gained with these techniques may greatly improve our knowledge of toxicokinetics and enable better patient management. Comatose patients and those with suspected brain death comprise a difficult group requiring comprehensive toxicologic screens. Although current immunoassay-chromatography methods are adequate, it is to be hoped that more comprehensive screens are achievable. The author has performed trials on TLC-FABMS-MS as a potential procedure and has obtained satisfactory preliminary results. This and other spectrometric-spectroscopic methods may be the techniques of the future for reference centers.

Clinical Laboratory Techniques↗

Beta-2-transferrin and cerebrospinal fluid rhinorrhoea.

Beta-2-transferrin is a protein produced by neuraminidase activity in the brain which is uniquely found in the cerebrospinal fluid (CSF) and perilymph. Its absence in other body secretions makes its detection invaluable in diagnosing a CSF leak. In this series samples were analysed from 25 patients with suspected CSF rhinorrhoea. The presence of beta-2-transferrin was determined by immuno-fixation electrophoresis. Out of 25 patients 16 were positive for beta-2-transferrin. A dural defect and CSF leak were confirmed during surgery in 13 of the 16 patients. In three patients the rhinorrhoea stopped spontaneously. Out of nine patients who were negative for beta-2-transferrin in the nasal fluids, two underwent a craniotomy and neither had evidence of CSF leak or dural effect. Two of the eight patients had a normal computerized coronal tomography (CT) despite a CSF leak. Seventeen patients underwent CT cisternography (six in the beta-2-transferrin negative group and 11 in the positive group). A leak was shown by CT cisternography in seven patients in the positive beta-2-transferrin group, but a leak could not be confirmed in the other four patients. No leak was demonstrated in the six patients in the negative beta-2-transferrin group. Beta-2-transferrin is a valuable and sensitive means of confirming the diagnosis of CSF leaks. Patients with a suspected CSF leak but no beta-2-transferrin in their nasal discharge can avoid unnecessary invasive investigations.

Adult↗

Cigarette smoking and free radical activity in young adults with insulin-dependent diabetes.

Cigarette smoke is potentially capable of generating a high free radical load in the body and many patients with diabetes are smokers. This study was designed to investigate the relationship between long-term smoking and free radical activity in young adult insulin-dependent diabetic patients with no evidence of macrovascular disease. Eight-five patients (48 male) aged 17-40 years were studied. Mean duration of diabetes was 10.5 years (0.08-33) and 39 were cigarette smokers. All had normal serum creatinine levels. The free radical markers measured were: thiobarbituric acid reactive substances, glutathione peroxidase, and superoxide dismutase. No significant differences in thiobarbituric acid reactive substances, glutathione peroxidase, or superoxide dismutase, were found between the diabetic smokers and non-smokers. Also no difference was found comparing the diabetic patients with 40 non-diabetic control subjects (20 smokers). Persistent albuminuria was present in 16 patients (10 microalbuminuria) and free radical marker concentrations in these subjects were similar to the normoalbuminuric patients. This data suggests that any increase in free radical activity due to cigarette smoke is adequately scavenged in young adults with diabetes who are free of significant macrovascular disease.

Adolescent↗

Free radical activity in young adult cigarette smokers.

Cigarette smoke is capable of generating free radicals. In this study markers of free radical activity (thiobarbituric acid reactivity, superoxide dismutase and glutathione peroxidase) were measured in young adult smoking and non-smoking volunteers. No significant differences were found in any of the free radical markers between the two groups. The number of leucocytes was elevated and a positive correlation was found between the number of leucocytes and thiobarbituric acid reactivity in the smokers. The results from this study suggest that any free radical activity generated from long term cigarette smoking in young adults is adequately scavenged.

Adolescent↗

External quality assessment of techniques for the detection of drugs of abuse in urine.

Five chromatographic and six immunoassay techniques were compared using data reported by 131 participants in the UK National External Quality Assessment Scheme for Drugs of Abuse in Urine. Twenty five samples were studied containing none or one of three concentrations of amphetamine, barbiturates, benzodiazepines, benzoylecgonine, methadone and morphine. Technique sensitivity and specificity achieved with realistic clinical samples of 25 mL vol were assessed as the percentage of true positive and true negative tests, respectively. Thin-layer chromatography was inadequate for the detection of several analytes, the sensitivity for 0.5 mg/L of benzoylecgonine being < 30%, and for 1.5 mg/L of amphetamine < 86%. Gas chromatography with mass spectrometry was significantly less sensitive than other techniques for the detection of 0.5 mg/L of benzoylecgonine (71%) and 1.5 mg/L of morphine (88%). High-performance liquid chromatography was the most sensitive for amphetamine. Immunoassays performed well when operating above their specified cut-off concentrations but, because they are directed to quinalbarbitone showed reduced cross-reactivity with amylobarbitone, the barbiturate more commonly prescribed in the UK.

Chromatography↗

Assessment of theophylline compliance in general practice using a 'compliance index' based on apparent drug clearance.

The monitoring of compliance in outpatients using serum drug levels suffers from the difficulty of relating concentrations to changes in dosage. Clearance is independent of dose for most drugs, and may be predicted using a Bayesian based forecasting program. This paper describes how the apparent clearance obtained following a single drug analysis can be compared with the Bayesian population value to derive a Compliance Index. In compliant individuals with stable hepatic and renal function this index should remain constant. We evaluated the usefulness of the Compliance Index in general practice with patients prescribed theophylline. Of 54 patients examined on up to five occasions, only 12% were deemed to be fully compliant at all times. Compliance improved during the study, but worsened again once regular consultation ceased. The results indicate that such a Compliance Index is a viable method of assessing compliance with the aid of concentration measurements.

Adolescent↗

The effect of doxorubicin on the glutathione content and viability of cultured human lung cancer cell lines A549 and GLC4 210.

Glutathione was measured in doxorubicin-sensitive cells from small cell carcinoma of lung (GLC4 210), and the levels compared with those of cells with acquired resistance and a line of resistant non-small-cell adenocarcinoma A549 (Alveolar type 2). The effect of different doxorubicin concentrations on glutathione were measured by HPLC. The effect of doxorubicin on the viability of the cell lines was studied using thiazole blue dye reduction. An increase in A549 sensitivity to doxorubicin was produced using buthionine-S,R-sulfoximine at a non-toxic dose.

Adenocarcinoma↗