Biomedical subjects
Publications and source records attributed to R Marshall.
A review of the use of manual handling aids in two hospitals found equipment was employed on a multi-patient basis with inadequate cleaning. Sampling with a Casella slit sampler demonstrated frequent contamination by methicillin-resistant Staphylococcus aureus and Clostridium difficile of fabric aids. Recommendations for care of equipment are made.
The presence of metalloproteinase activity in endometrial flushings obtained from premenopausal women, during the proliferative and secretory phases of the menstrual cycle, control post-menopausal women and women with post-menopausal bleeding (PMB) with or without adenocarcinoma was analysed by zymography. In addition, quantitative measurements of matrix metalloproteinase 2 (MMP-2), MMP-3, MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) in the flushings were obtained by ELISA. The zymography results showed eight bands of activity, with molecular weights ranging from 51 to 208 kDa in the flushings from pre-menopausal women and post-menopausal women, particularly those with adenocarcinoma. Both zymography and ELISA showed that MMP-2 and MMP-9 were the major metalloproteinases found in the flushings and only low concentrations of MMP-3 were found. Concentrations of MMP-2 in pre-menopausal women were higher in flushings obtained during the secretory phase of the menstrual cycle than those obtained in the proliferative phase (P < 0.05), suggesting that it may play a role in embryo implantation. Concentrations of MMP-2 (P < 0.001), MMP-9 (P < 0.05) and TIMP-1 (P < 0.001) in the flushings from post-menopausal control women were lower than those from pre-menopausal women. Concentrations of MMP-2 (P < 0.05) and TIMP-1 (P < 0.05) were higher in flushings from women with PMB without carcinoma compared with post-menopausal controls and concentrations of MMP-9 (P < 0.01) and TIMP-1 (P < 0.05) in flushings from women with adenocarcinoma were higher than in post-menopausal controls. Among subjects with PMB, concentrations of MMP-9 in women with adenocarcinoma were higher than those without carcinoma (P < 0.05). Our results show that concentrations of MMP-2, MMP-9 and TIMP-1, but not MMP-3, are associated with endometrial activity and, therefore, may have a role in the breakdown of endometrial tissue. In addition, the increased concentrations of MMP-9 in flushings of women with adenocarcinoma indicate that this particular proteinase is associated with the presence of endometrial neoplastic cells.
A study population of 1850 children resident in East Lancashire born between 2 July and 1 October 1994 was obtained from local child health information systems (CHIS) and family health service (FHS) general practitioner registration data in March 1997 to determine the accuracy of reported measles, mumps, and rubella (MMR) vaccine coverage in 2 year old children registered with East Lancashire general practitioners. The reported MMR immunisation coverage was 89.7%, but the observed coverage was higher at 95.5% (95% confidence interval (CI) 93.9-97.3%). Small practices (3 Pounds GPs) achieved significantly higher MMR coverage (97.1%; 95% CI 95.8-98.0%) than large practices (93.5%; 95% CI 91.5-95.1%). Significantly higher MMR coverage was found in practices that used CHIS recall systems (96.2%; 95% CI 95.1-97.1%) than those using their own recall methods (91.2%; 95% CI 87.0-94.4%). Logistic regression showed that MMR vaccine coverage was independently predicted by practice size (odds ratio (OR) 2.5; 95% CI 1.5-4.0), recall method (OR 2.3; 95% CI 1.4-3.8), and relative deprivation (OR 1.7; 95% CI 1.0-2.6). Actual MMR coverage in 2 year old children in East Lancashire was significantly higher than reported, mainly because of inaccuracies in the CHIS database. Methods to improve the transfer of data on immunisation from practices to population databases should be explored.
The factor V Leiden mutation, a G-->A transition at position 1691 in exon 10 of the gene that codes for factor V, produces an Arg506Gln substitution and is the most common genetic risk factor for venous thrombosis. We have developed a rapid, sensitive, and specific method to detect the factor V Leiden mutation in genomic DNA from whole blood by PCR amplification and microparticle enzyme immunoassay detection using the Abbott LCx instrument. We compared this automated method with the standard procedure using restriction endonuclease digestion of PCR products followed by gel electrophoresis in blinded experiments. In 130 patients (from Veterans Affairs medical centers) with deep venous thromboses, including 24 heterozygotes with the factor V Leiden mutation, there was complete agreement between the two methods. The assay was also able to distinguish heterozygotes from homozygotes. This method, which carries a low potential for cross-contamination of samples, should be a useful routine test for the factor V Leiden mutation in clinical laboratories with sufficient demand for molecular diagnostic assays using the LCx instrument.
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BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine. METHODS: Fifty-four patients with oral clomipramine-refractory OCD were randomized to receive 14 infusions of either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 patients. Response was based on a Clinical Global Impressions rating of at least "much improved." RESULTS: Six (21%) of 29 patients randomized to receive intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were responders after 14 infusions (df = 1, P<.02). Dimensional ratings after infusion 14 revealed significant (P = .007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week later, all dimensional measures of OCD showed significant improvement. At 1 week post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and treated subsequently with oral clomipramine were responders, whereas 0 of 18 patients initially randomized to receive i.v. placebo and treated subsequently with several days of open-label i.v. clomipramine responded (df = 1, P<.002). Of the 31 patients assessed 1 month after i.v. infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences. CONCLUSIONS: Intravenous clomipramine is more effective than i.v. placebo for patients with OCD with a history of inadequate response or intolerance to oral clomipramine. Further study of this promising treatment for refractory OCD is needed.
To maximise sensitivity, protocols for testing chemicals in chromosomal aberration assays in vitro are designed so that cells are sampled when the peak frequency of aberrations might be expected to occur. They are not designed to measure the frequency of aberrations in cells which survive. Only chromosomal aberrations which are heritable, however, can have any relevance to human health, but the detection of those aberrations most likely to be tolerated (inversions, reciprocal translocations) is notoriously difficult with conventional light microscopy. Current protocol design is justified by arguing that the presence of structural aberrations of any type at early times after treatment indicates a risk that a proportion of aberrations will persist and be maintained in the population. Chromosome painting allows reciprocal exchanges to be relatively easily measured and permits the validity of these assumptions to be tested. To date, the kinetics of induction and dose-response relationships of reciprocal translocations induced by chemicals have been little investigated. We compared the frequency of chromosome-type aberrations in human lymphocytes following treatment with two powerful clastogens, streptonigrin and Trenimon, using conventional staining techniques and chromosome painting. The results show that although reciprocal translocations can be shown to arise and persist in treated populations of human lymphocytes for several days following treatment, their frequency is very low, even at concentrations where large amounts of chromosomal damage are induced, indicating that, at present, the value of using chromosome painting as an adjunct to traditional clastogenicity testing is limited.
The research literature on the psychiatric consequences of the Vietnam War focuses primarily on the construct of Posttraumatic Stress Disorder (PTSD), after an initial focus in the 1970s on depression and alcohol and substance abuse. The present paper examines the hypothesis that among men without current PTSD, those with higher combat in Vietnam will be more likely to have current DSM-III-R illnesses. The Australian Vietnam Veterans' Health Study (AVVHS) collected a broad range of interview data on 641 Vietnam veterans throughout 1990-1993. Measures of combat exposure, age at embarkation to Vietnam, enlistment IQ and pre-Army personality problems were drawn from Army records of the era. Retrospective measures of combat were obtained at interview. The interview also involved the administration by trained lay interviewers of the DSM-III-R based Diagnostic Interview Schedule (DIS). This epidemiological instrument provides current psychiatric diagnoses as well as temporal (retrospective) symptom and diagnosis onset data. The results of this study show that current disorders (without PTSD comorbidity) with onsets within 5 years of embarkation to Vietnam are more likely among men who saw higher combat, as indexed by combat-exposure measures drawn from Army records of the era as well as retrospective self-report. This combat relatedness remains when age at embarkation. IQ at enlistment and pre-Army personality measures are used as covariates. No more than 11.4% of sampled Vietnam veterans currently meet DSM-III-R diagnostic criteria for PTSD, while a further 7.8% do not have current PTSD but do have some other current DIS diagnosis with onset in the 5-year period following (first) emabarkation to Vietnam. Our data support the hypothesis that the current illnesses of many of these men without PTSD are combat-related DSM-III-R illnesses.
Sleep disordered breathing is common in patients with tetraplegia. Nocturnal arterial hypoxemia and sleep fragmentation due to sleep apnoea may be associated with cognitive dysfunction. We therefore studied the influence of sleep disordered breathing on neuropsychological function in 37 representative tetraplegic patients (mean age 34 +/- 9.7 years). Thirty percent (11 of 37 patients) had clinically significant sleep disordered breathing, defined as apnoea plus hypopnoea index (AHI) greater than 15 per hour of sleep. Most apnoeas were obstructive in type. Seven patients (19%) desaturated to < 80% during the night. Neuropsychological variables were significantly correlated with measures of sleep hypoxia, but not with the AHI and the frequency of sleep arousals. The neuropsychological functions most affected by nocturnal desaturation were: verbal attention and concentration, immediate and short-term memory, cognitive flexibility, internal scanning and working memory. There appeared to be a weak association between the presence of severe sleep hypoxia and visual perception, attention and concentration but no association was found between sleep variables and depression scores. We concluded that sleep disordered breathing is common in patients with tetraplegia and may be accompanied with significant oxygen desaturation. The latter impairs daytime cognitive function in these patients, particularly attention, concentration, memory and learning skills. Cognitive disturbances resulting from sleep apnoea might adversely affect rehabilitation in patients with tetraplegia.
Pressure ulcers are an important complication of spinal cord injury which place an enormous burden on society due to their financial, psychosocial, and vocational implications. Although they are now rarely fatal, they can still have devastating consequences, often needing prolonged hospitalisation to be properly managed. This study reviews the use of electrical stimulation to overcome increasing debility due to sacral pressure ulcers and saddle soreness in a man with tetraplegia. After 24 months of regular cyclic stimulation he had increased circumferential dimensions across his buttocks by up to 21%, and increased his sitting tolerance.
GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.
A new method for the rapid assessment of neonatal withdrawal was tested. Three studies with 80 newborns compared the reliability, sensitivity and specificity of the Neonatal Withdrawal Inventory (NWI) with that of the Neonatal Abstinence Scoring System (NASS), a widely used neonatal withdrawal scale. Interrater reliability for raters assessing neonatal withdrawal with the NWI (range, 0.89-0.98) was superior to that demonstrated by the same raters using the NASS (range, 0.70-0.88). With the NASS as the standard, the sensitivity and specificity of the NWI were 100% at syndrome detection and treatment threshold levels. With use of the NWI, the severity of neonatal withdrawal could be accurately assessed in 10 minutes under case-blinded conditions. The NWI's advantages include brevity, ease of administration, and flexibility. The NWI's simplicity and accuracy commend its wider use as a clinical and experimental tool.
Minocycline can cause various types of hepatotoxicity. We report an 18-year-old male who developed a delayed onset of minocycline-induced cholestatic hepatitis with autoimmune features and neutropenia. He responded to withdrawal of the drug and a short course of corticosteroids. If minocycline is to be administered, then periodic monitoring for hepatoxicity is recommended.
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BACKGROUND: Moclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia. METHOD: Seventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks. RESULTS: Intention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated. CONCLUSIONS: Moclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.
Aromatic L-amino acid decarboxylase (AADC) is rate limiting in the production of 2-phenylethylamine (2PE). AADC activity and 2PE serum concentrations have been found to be increased in schizophrenic patients. Both antipsychotic and psychotogenic drugs, including amphetamine, affect the activity and encoding mRNA levels of AADC. Amphetamine is an analogue of 2PE and has a similar physiological effect. We have looked at the effects of chronic (32 day) treatment of rats with LSD (0.12 microg/kg/day) and phencyclidine (PCP; 10 mg/kg/day) on AADC mRNA levels. Both drugs up-regulated AADC mRNA levels in striatum, nucleus accumbens, hippocampus and cerebellum by between 50% and 150%. A splicing variant of AADC, present in human brain, which lacks the 3rd exon does not appear to be present in rat brain. These results are consistent with the hypothesis that over activity of AADC leading to increased production of 2PE is involved in endogenous psychosis such as schizophrenia.
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