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Biomedical subjects

R A Braithwaite

Publications and source records attributed to R A Braithwaite.

At least 19 recordsLinked to original sources
PubMed2001

Drug absorption may be delayed after stroke: results of the paracetamol absorption test.

BACKGROUND: Autonomic changes are frequent after stroke but it is not known whether gastric emptying is altered. We have investigated this using the paracetamol absorption test. METHODS: 12 acute stroke patients and 13 healthy controls of similar age received 1 g oral paracetamol tablets. We studied all patients within 24 h of the stroke and 5 days later. Standard pharmacokinetic measurements were derived from the plasma paracetamol-time curve. RESULTS: In acute stroke patients, mean plasma T(max) was delayed compared with that in controls (96.3 vs 46.2 min, P=0.015). The C(max) of paracetamol was also lower (16.1 vs 23.9 mg l(-1), P=0.028). The area under the curve of paracetamol did not differ significantly in acute stroke patients and controls. CONCLUSIONS: Gastric emptying appears to be delayed in acute stroke patients, and this may result in delayed pharmacological action of orally administered drugs.

Acetaminophen↗
PubMed2000

Using amphetamine isomer ratios to determine the compliance of amphetamine abusers prescribed dexedrine.

The amphetamine isomer ratios (l-amphetamine/d-amphetamine) in 373 urine specimens submitted for analysis over a two-year period have been determined using a chiral derivatizing agent in conjunction with a gas chromatograph fitted with a nitrogen-specific detector. All of the specimens were collected from known or suspected amphetamine abusers, some of which were prescribed dexedrine for maintenance and detoxification. The mean (+/- 1 standard deviation [SD]) l/d-amphetamine isomer ratio for 147 specimens from compliant subjects prescribed dexedrine was 15.0% (+/- 4.9%). The mean (+/- 1 SD) l/d-amphetamine isomer ratio from 165 subjects abusing illicit amphetamine was 98.5 (+/- 27.5%). The calculation of l/d-amphetamine isomer ratios in urine has been found to be a rapid method for determining the compliance of subjects prescribed dexedrine and is therefore a useful technique for the continued management of amphetamine abusers. In addition, 17 specimens of illicit amphetamine powder (assumed to be a racemic mixture) were submitted to the laboratory for analysis. Using a combination of gas chromatography with and without chiral derivatization, the powders were found to have a mean l/d-amphetamine isomer ratio of 89.2% (range 72.2% to 98.3%) and mean purity (w/w) of 21.5% (range 3.4% to 71.0%) relative to pure dl-amphetamine substance.

Amphetamine-Related Disorders↗
PubMed2000

Estimating antemortem drug concentrations from postmortem blood samples: the influence of postmortem redistribution.

AIMS: To compare blood drug concentrations during life with postmortem drug concentrations measured from a peripheral site and a central site. METHODS: Coroner's cases from October 1990 to July 1997 were reviewed. Six cases had data on both antemortem and postmortem blood drug concentrations. The postmortem to antemortem ratio was compared with the postmortem central to peripheral ratio, using cardiac blood as a central site and femoral blood as a peripheral site. RESULTS: Drugs that have a high postmortem central to peripheral ratio; that is, drugs that exhibit considerable postmortem redistribution, also have high postmortem to antemortem ratios. CONCLUSIONS: A large degree of error can arise from attempting to estimate antemortem drug concentrations and the ingested dose from postmortem measurements. The chosen site and technique for postmortem blood sampling can greatly influence the concentration of drug measured.

Adolescent↗
PubMed2000

Simple high-performance liquid chromatographic method to monitor vigabatrin, and preliminary review of concentrations determined in epileptic patients.

A simple and rapid high-performance liquid chromatographic method has been developed for the determination of vigabatrin concentrations in plasma or serum. The assay uses only 100 microL of specimen and has been found to be linear over a concentration range of 1 to 50 mg/L. The limit of detection has been determined as 1 mg/L, and the between-batch coefficient of variation for the two internal quality controls routinely analysed (n = 33) has been found to be less than 5%. There was no evidence of interferences in the assay from other commonly prescribed anti-epileptic drugs. This method has been applied to routine clinical specimens to determine the concentration of vigabatrin in 47 patient specimens over a 12-month period. It was found that only 63% of the male group and 53% of the female group were within the proposed target concentration of 5 to 35 mg/L. In addition, it was found that 26% of the male group and 36% of the female group were found to have concentrations below 5 mg/L, which may indicate lack of compliance and/or lack of therapeutic efficacy of treatment.

Adolescent↗
PubMed2000

Application and validation of a urinary methadone metabolite (EDDP) immunoassay to monitor methadone compliance.

A total of 1381 urine specimens were screened using a Microgenics CEDIA urinary primary methadone metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EDDP) immunoassay (cut-off calibrator concentration of 100 microg/L) in combination with a Dade Behring EMIT urinary methadone immunoassay (cut-off calibrator concentration of 300 microg/L). Of these, 642 (46%) were found to be positive using the EDDP assay but only 541 (39%) were found to be positive by the methadone assay. Out of the 108 specimens which were EDDP-positive but negative by the methadone assay, 47 (7%) could not be confirmed as positive using the routine in-house method of gas chromatography incorporating nitrogen-specific detection. Of these 47 results, 38 were re-screened using a more sensitive gas chromatography-mass spectrometry (GC-MS) technique, which demonstrated the presence of EDDP in every case. There was insufficient specimen to analyse the remaining nine samples. There were seven specimens which gave negative results by the EDDP and GC-MS assays but which had methadone concentrations ranging from 4000 to 37,500 microg/L. These were therefore presumed to be 'spiked' with methadone, i.e. to have had methadone added to the specimen to yield positive screening results and simulate compliance. It is concluded that the Microgenics CEDIA EDDP assay is a sensitive and reliable technique to determine the compliance of subjects prescribed methadone for opiate detoxification and maintenance.

Calibration↗
PubMed1997

The measurement of morphine in the hair of heroin abusers.

Several techniques have been described for the determination of morphine in hair as a method of monitoring past heroin use. However, although some of the techniques [notably radioimmunoassay (RIA)] may appear relatively simple to perform, any results obtained must be interpreted with caution. In this study, hair specimens from four known heroin abusers were sectionally analysed by a specific RIA for morphine. Prior to analysis, all hair sections were cleaned to remove any possible surface contamination. Five different hair digestion procedures were evaluated to determine the most effective method that could be used to liberate morphine from hair. The greatest analytical recovery was obtained by incubation with 1.0 M sodium hydroxide for 18 h at 55 degrees C, neutralization with 1.0 M hydrochloric acid, and pH adjustment with 0.1 M phosphate buffer (pH 7.0). The morphine concentrations detected in the hair specimens ranged from 0.5 to 13.2 ng/mg of hair. It was also found that the use of shorter length segments (e.g. 1 cm length) gave a clearer, more detailed picture of the historic pattern of heroin use in the four subjects studied.

Acetone↗
PubMed1997

Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs.

Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to the manufacture of more designer drugs. Production of substituted phenethylamines was facilitated by the drug makers' cook book, 'PIHKAL' (Phenethylamines I Have Known And Loved) by Dr Alexander Shulgin and Ann Shulgin, and production of substituted tryptamines is promised in their next book, TIHKAL. Looking to the future, laboratories will need to ensure that they can detect and quantitate an ever-increasing number of drugs and related substances. The question of confidence in results of drugs of abuse testing raised in 1993 by Watson has assumed even greater importance as a result of attention focused on the OJ Simpson trial in Los Angeles. Toxicological investigations are likely to be challenged more frequently in the future. Even if analyses have been performed by GC-MS, there is a need to establish the level of match between the spectrum of the unknown substance and a library spectrum which is considered acceptable for legal purposes. It will also be essential to ensure that computer libraries contain spectra for all substances likely to be encountered in drugs of abuse screening.

Barbiturates↗
PubMed1996

Elemental mercury-induced skin granuloma: a case report and review of the literature.

BACKGROUND: Injection of elemental mercury is rare and only some 72 cases have been reported in the literature over the period 1923-1995. Direct subcutaneous injection or extravasation of mercury injected into blood vessels can produce local granulomata and abscesses. Unless intravascular mercury injection has occurred, clinical signs of mercury toxicity are usually absent though four cases of systemic toxicity have been reported following isolated subcutaneous injection without evidence of elemental mercury dissemination. CASE REPORT: We report a further case of subcutaneous injection by gunshot of elemental mercury, with subsequent granuloma formation, in a 19-year old man who was admitted with an eight month history of a tender enlarging mass in his left antecubital fossa, while on active military service. Surgical removal of mercury from a presumed mercury-tipped bullet was undertaken but was incomplete and the patient declined further operative intervention as he remained asymptomatic. Chelation therapy was not instituted. Serum and urine mercury concentrations were measured for six years after presentation. CONCLUSIONS: We recommend that cases of subcutaneous metallic mercury injection should be managed by complete surgical excision of the granuloma under X ray control and serial monitoring of blood and urine mercury concentrations.

Adult↗
PubMed1995

Screening for drugs of abuse. I: Opiates, amphetamines and cocaine.

(1) In order to provide an efficient and reliable service for drugs of abuse screening in urine, the laboratory should analyse 20-30 samples per week, and the staff should include a scientist with special expertise in the subject. (2) Turnaround times should be between 2-3 days of sample collection. To achieve this aim it may be necessary to make special arrangements for the delivery of samples to the laboratory. Results should preferably be transmitted by electronic mail or facsimile with the necessary precautions for security and confidentiality: hardcopy reports may also be required. (3) Good communications between the requesting clinician and the laboratory are essential. An advisory service should be provided by the laboratory and clinicians should be encouraged to discuss requests and results with laboratory staff. It is important that the laboratory inform doctors of the range of substances detected and the sensitivity and specificity of laboratory assays. (4) Assays should be performed according to the manufacturer's protocols, or by modified methods that have been rigorously validated. Quality control samples should be included in each analytical run and participation in an external quality assessment scheme, e.g. UKNEQAS, is essential to provide independent confirmation and confidence that results compare with those from other laboratories. Other requirements include adequate training and supervision of staff, and careful recording of samples and results. (5) Drugs to be tested will depend on the drug 'scene' in the area but should include those drugs regularly prescribed for maintenance therapy (e.g. methadone, dihydrocodeine, benzodiazepines), and drugs frequently misused (e.g. heroin, buprenorphine, amphetamines, cocaine). (6) Positive results obtained by preliminary screening methods e.g. EMIT, should be confirmed by another analytical technique, e.g. TLC, GC or GC-MS. If there are potentially serious or legal implications, and in employment and preemployment testing, confirmation of positive results is mandatory. In some cases, e.g. checking for methadone or benzodiazepine compliance, it may be considered unnecessary to confirm positive results although possible spiking of samples cannot be excluded without checking for the presence of metabolites by a chromatographic procedure.

Amphetamines↗
PubMed1995

Routine therapeutic monitoring of lamotrigine in epileptic patients using a simple and rapid high performance liquid chromatographic technique.

We have developed a simple and rapid high performance liquid chromatographic technique to determine lamotrigine concentrations in epileptic patients and validated it using external quality control material. The method has been used to monitor the lamotrigine concentration in 70 specimens from 61 patients. Only 50% of the specimens had concentrations within the proposed target range of 1 mg/L to 4 mg/L, and there was no relationship between lamotrigine concentration and age, sex, other anti-epileptic treatments, or dose, although this could in part be explained by concomitant anti-epileptic therapy. We suggest that lamotrigine should be monitored therapeutically in order to assess its efficacy and audit its use as an anti-epileptic treatment, especially with the introduction of this relatively new drug as monotherapy.

Adolescent↗
PubMed1995

Lead poisoning from Asian traditional remedies in the West Midlands--report of a series of five cases.

1. Traditional remedies are an unusual, but recognised cause of lead poisoning. Only two cases have previously been reported in this country. 2. We report a series of five cases of lead poisoning due to traditional remedies in the West Midlands. All developed typical clinical features. 3. Blood lead and zinc protoporphyrin (ZPP) concentrations were elevated 2-10 times the upper limit of normal. The remedies contained up to 60% lead by weight. One also contained traces of mercury, another arsenic, and a third aluminium and tin. 4. Confirmation of the medicines as the cause of the poisoning was made in one patient by measurement of lead isotopic ratios. 5. The present morbidity from traditional remedies may be far greater than is realised, and will continue until such time as the supply of harmful preparations can be effectively limited. There needs to be increased awareness of their dangers amongst doctors and the communities at risk. This will best be achieved by appropriately targeted education.

Adult↗
PubMed1995

An investigation into the extent of possible dilution of specimens received for urinary drugs of abuse screening.

Recent American and Swedish studies have shown an increase in "false" negative results when analysing dilute urine specimens for drugs of abuse. In the light of these studies, it was decided to perform a pilot study to determine the extent of possible specimen adulteration and dilution in a random batch of 50 urine specimens presented to this laboratory, using creatinine, osmolality, pH and relative density. It was found that 20% of the specimens were outside the pH range associated with the optimum working of Syva EMIT Drugs of Abuse in Urine (DAU) immunoassay screening techniques, and that if the National Institute on Drug Abuse (NIDA) recognized dilution cut-off of 1.8 mmol/L for urine creatinine concentration is applied, 84% of the specimens surveyed here would need to be repeated to ensure accurate results. Because of these findings, it is recommended that routine creatinine and pH estimations should be performed on all specimens submitted for urinary drugs of abuse screening, or at least when unexpectedly negative results are obtained.

Creatinine↗
PubMed1995

A preliminary evaluation of five rapid detection kits for on site drugs of abuse screening.

There are now several rapid drugs of abuse testing kits that have been designed for near-patient testing and on-site clinic screening for drug abuse. These kits are sold on the basis of their cost and rapid generation of accurate results. Five such kits have been evaluated by comparison with recognized and established methodologies. All of the kits evaluated were found to lack both sensitivity and specificity. An unacceptable proportion of false negative and false positive results were observed for most kits. This raises the question of their usefulness in the near-patient and clinic situation.

Cost-Benefit Analysis↗
PubMed1994

Use of molecular epidemiological techniques in a pilot study on workers exposed to chromium.

OBJECTIVES: Molecular epidemiological techniques, capable of detecting damage to DNA, were used to see if such damage occurred in the lymphocytes of a group of workers exposed to chromium. The two aims of this pilot study were to see if these new techniques might make useful biological monitoring tools for workers exposed to chromium and also, to help assess whether the current occupational exposure limit for chromium (VI) was sufficiently protective in this specific working situation. METHODS: Volunteer groups of 10 workers exposed to chromium and 10 non-exposed workers provided urine and blood samples towards the end of the working week. Chromium concentrations were measured in whole blood, plasma, lymphocytes, and urine. Lymphocytes were used to examine two forms of DNA damage in the two groups; these were the level of DNA strand breakage and, the production of 8-hydroxydeoxyguanosine. RESULTS: Chromium concentration in whole blood, plasma, and urine of workers exposed to chromium was significantly raised (P < 0.01) compared with non-exposed controls, but in isolated lymphocytes, there was only a modest but significant (P < 0.05) increase in chromium in the group exposed to chromium. There was no difference in the levels of DNA strand breaks or 8-hydroxydeoxyguanosine between the groups. Air monitoring for chromium was not undertaken but current levels for the group exposed to chromium were reported to be around 0.01 mg/m3, which is 20% of the current United Kingdom occupational exposure limit. CONCLUSIONS: We were unable to detect any damage in lymphocytic DNA due to exposure to chromium. This may have been due to the low chromium exposure (< 20% of the United Kingdom occupational exposure limit), the ability of plasma to detoxify chromium (VI) to chromium (III) before it reached the lymphocytes, or perhaps the insensitivity of the molecular techniques used. It is now important to test these and other such techniques on groups exposed to levels closer to the United Kingdom occupational exposure limit.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

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↗