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Biomedical subjects

S Maxwell

Publications and source records attributed to S Maxwell.

At least 19 recordsLinked to original sources
PubMed1999

Is routine synovial fluid analysis necessary? Lessons and recommendations from an audit.

This audit of 408 synovial fluid samples, analysed for cell counts and crystals, revealed that crystals were present in only 25 samples (6.1%). Of these, in only three patients was the diagnosis uncertain and therefore the analysis helpful. Cell counts and types generally reflected known underlying diagnoses of inflammatory arthritis or osteoarthritis. Routine synovial fluid analysis does not contribute to diagnosis or management in established rheumatic disorders and should be performed only when the underlying cause is uncertain or in newly presenting patients. Major savings can be made by abandoning routine synovial fluid analysis.

Diagnostic Tests, Routine↗
PubMed1999

Food coping strategies: a century on from Rowntree.

The objectives of this study were to update Rowntree's food estimates to bring them into line with contemporary food habits and changing lifestyles; to determine whether food budgeting/ coping strategies of low income households observed by Rowntree at the turn of the century were still prevalent in low income groups today: and to evaluate whether expenditure by low income households on food was sufficient to meet minimum dietary recommendations. Two hundred questionnaires were completed face to face with the interviewer within the Merseyside boundary and included only those households who were in the Post code area. Many low income households are unable to access a healthier diet due to income limitations. Many used a variety of coping strategies to stretch their incomes and were also found to rely on help from outside the immediate family such as extended family and friends and voluntary agencies. Households with children were found to be spending slightly more on food than the reconstructed Rowntree minimum dietary. There are thus two issues; firstly that there are households spending slightly more than the minimum yet that are unable to achieve a healthy diet. Secondly all the low income households are spending much less per person than the average person in the United Kingdom. It is concluded that whilst sterling work is being achieved within health promotion departments and within community health settings there is still a great deal to be undertaken. The value of Home Economics teaching in schools should be better recognised, and Home Economics should be reinstated in the National Curriculum. Secondly it is recommended that a standard approach be adopted to inform both welfare benefit payments and in-work top up payments, thus allowing households on low incomes to make informed choices within a budget that will accommodate healthier eating strategies.

Adult↗
PubMed1998

Sorting mechanisms regulating membrane protein traffic in the apical transcytotic pathway of polarized MDCK cells.

The transcytotic pathway followed by the polymeric IgA receptor (pIgR) carrying its bound ligand (dIgA) from the basolateral to the apical surface of polarized MDCK cells has been mapped using morphological tracers. At 20 degreesC dIgA-pIgR internalize to interconnected groups of vacuoles and tubules that comprise the endosomal compartment and in which they codistribute with internalized transferrin receptors (TR) and epidermal growth factor receptors (EGFR). Upon transfer to 37 degreesC the endosome vacuoles develop long tubules that give rise to a distinctive population of 100-nm-diam cup-shaped vesicles containing pIgR. At the same time, the endosome gives rise to multivesicular endosomes (MVB) enriched in EGFR and to 60-nm-diam basolateral vesicles. The cup-shaped vesicles carry the dIgA/pIgR complexes to the apical surface where they exocytose. Using video microscopy and correlative electron microscopy to study cells grown thin and flat we show that endosome vacuoles tubulate in response to dIgA/pIgR but that the tubules contain TR as well as pIgR. However, we show that TR are removed from these dIgA-induced tubules via clathrin-coated buds and, as a result, the cup-shaped vesicles to which the tubules give rise become enriched in dIgA/pIgR. Taken together with the published information available on pIgR trafficking signals, our observations suggest that the steady-state concentrations of TR and unoccupied pIgR on the basolateral surface of polarized MDCK cells are maintained by a signal-dependent, clathrin-based sorting mechanism that operates along the length of the transcytotic pathway. We propose that the differential sorting of occupied receptors within the MDCK endosome is achieved by this clathrin-based mechanism continuously retrieving receptors like TR from the pathways that deliver pIgR to the apical surface and EGFR to the lysosome.

Animals↗
PubMed1998

In polarized MDCK cells basolateral vesicles arise from clathrin-gamma-adaptin-coated domains on endosomal tubules.

Human transferrin receptors (TR) and receptors for polymeric immunoglobulins (pIgR) expressed in polarized MDCK cells maintain steady-state, asymmetric distributions on the separate basolateral and apical surfaces even though they are trafficking continuously into and across these cells. The intracellular mechanisms required to maintain these asymmetric distributions have not been located. Here we show that TR and pIgR internalize from both surfaces to a common interconnected endosome compartment that includes tubules with buds coated with clathrin lattices. These buds generate vesicles that carry TR to the basolateral border. The lattices contain gamma-adaptin and are dispersed by treatment with brefeldin A (BFA). Since BFA treatment abrogates the vectorial trafficking of TR in polarized MDCK cells, we propose that the clathrin-coated domains of the endosome tubules contain the polarized sorting mechanism responsible for their preferential basolateral distribution.

Adaptor Protein Complex gamma Subunits↗
PubMed1997

Comparison of antioxidant activity in lipoprotein fractions from insulin-dependent diabetics and healthy controls.

The insulin-dependent diabetic patient is at greatly increased risk of premature atherosclerosis. Oxidative damage to lipoproteins has been implicated as an important factor in the atherogenic process. Diabetic patients are exposed to excessive oxidative stress because of non-enzymatic glycation of proteins and a variety of defects in antioxidant systems. We have previously described an enhanced chemiluminescent method for measuring protective 'chain-breaking' antioxidant activity in plasma lipoprotein fractions. In this study we compare the lipid content and antioxidant activity of plasma lipoproteins in 22 young insulin-dependent diabetics without vascular complications and 20 age- and sex-matched controls. Mean levels of haemoglobin A 1c in the diabetic group were 8.8 +/- 0.2%. There were no significant differences in serum total cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein(a) levels between the study groups. Serum total triglyceride levels (1.32 +/- 0.11 versus 1.01 +/- 0.08 mmol/l; P < 0.05) and LDL-associated triglyceride (0.28 +/- 0.04 versus 0.15 +/- 0.02 mmol/l; P < 0.05) were significantly elevated in the diabetic group. Total plasma antioxidant activity was significantly reduced in the diabetic group (272.0 +/- 15.4 versus 338.3 +/- 20.7 micromol/l; P < 0.05). Antioxidant activity measured in five lipoprotein fractions isolated by density gradient ultracentrifugation (VLDL1. VLDL2, LDL1, LDL2 and HDL) showed no significant differences between groups when corrected for protein, total lipid or cholesterol content. When corrected for triglyceride content significantly lower antioxidant values were found in the diabetic HDL fraction only. The results of this study imply that the susceptibility of the insulin-dependent diabetic to the development of premature atherosclerosis cannot be attributed to reduced antioxidant activity in circulating plasma lipoproteins.

Adult↗
PubMed1997

Routine synovial fluid culture: is it necessary? Lessons from an audit.

An estimated third of rheumatologists send aspirated synovial fluid samples for culture routinely during the course of management of their patients irrespective of the underlying diagnosis. This is done apparently even when sepsis is not suspected. This audit of 507 synovial fluid culture requests revealed that positive bacterial growth was rare even when sepsis was queried on the request forms but none was positive in any of the routine samples. Our findings throw doubt on the value of routine synovial fluid culture. We recommend that such cultures are undertaken when infection is a possibility and in immuno-compromised patients. An average health district would save pounds 3000 per annum if such a policy was adopted, but across the National Health Service as a whole the total expenditure saved on this unnecessary investigation would be considerable.

Adolescent↗
PubMed1997

Exercise metabolism in healthy volunteers taking celiprolol, atenolol, and placebo.

OBJECTIVE: Previous studies have shown that beta 1 selective agents have fewer adverse effects on exercise metabolism than nonselective beta blockers, and this has been attributed to their reduced blockade of beta 2 receptors. This study aimed at determining whether a beta blocker with partial agonist activity at beta 1 and beta 2 receptors (celiprolol) was better than a conventional beta 1 receptor-blocker (atenolol) in prolonging exercise capabilities. METHODS: After four days of treatment with celiprolol 200 mg, atenolol 50 mg, or placebo, 22 healthy volunteers exercised on a treadmill for two hours at 50% of their maximal oxygen uptake. Resting heart rate and blood pressure were recorded before and after exercise. During exercise, fat oxidation, plasma free fatty acids, glycerol, glucose, and ammonia were measured together with heart rate and perceived exertion. RESULTS: Mean exercising heart rate was significantly lower in those taking either of the beta blockers than in those taking placebo, and significantly lower for those taking atenolol rather than celiprolol. Fat oxidation was significantly lower for those taking celiprolol (38.8 (SD 12.2)%, P < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6 (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than celiprolol (29.6 (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was also significantly attenuated by both beta blockers in comparison with the rise in those taking placebo (P < 0.01). CONCLUSIONS: Both celiprolol and atenolol reduced fat oxidation compared with placebo. For the first 15 minutes of exercise fat oxidation was preserved by celiprolol, but not atenolol. This preservation of fat oxidation during the early part of exercise may confer some small benefit to patients who take beta blockers and intend to exercise regularly. However, we did not detect significant differences between atenolol and celiprolol in overall mean fat oxidation or perceived exertion in this study.

Administration, Oral↗
PubMed1997

Underdiagnosis of PTSD and substance use disorders in hospitalized female veterans.

Discharge diagnoses of 31 female veterans and 31 male veterans hospitalized at a large urban VA medical center were examined to elucidate possible biases in clinicians' diagnostic practices. Only one woman in the sample was diagnosed as having posttraumatic stress disorder, compared with seven men. All men given this diagnosis were combat veterans. Although about half of each group had a drug-positive urine screen on admission, only 11 women received a diagnosis of a substance use disorder, compared with 24 men. VA clinicians may need further training and experience assessing the presentation of PTSD and substance use disorders in women.

Adult↗
PubMed1997

Substance abuse as a risk factor for tardive dyskinesia: a retrospective analysis of 1,027 patients.

Tardive dyskinesia (TD) affects between 10 and 50 percent of all patients on long-term antipsychotic therapy, depending on the population studied. Various risk factors for TD have been reported; a correlation between TD and substance abuse has been suggested in some reports and not found in others. This study analyzes the association of substance abuse with the incidence of tardive dyskinesia in a schizophrenic population. All patients at the West Side Veterans Affairs Medical Center are evaluated prior to the initiation of neuroleptic therapy with the Dyskinesia identification System: Condensed User Scale (DISCUS); those with a diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder during the years 1986 through 1993 were included in this analysis. History of substance abuse was considered positive if there was clinician report or diagnosis of substance abuse. These data were collected and analyzed using ANOVA. In a sample of 1,027 subjects (97% male), 83.2 percent had a neuroleptic exposure of 10 or more years, and slightly more than half (50.8 percent) had a positive history of substance abuse. Using research diagnostic criteria, 28.9 percent of the sample had tardive dyskinesia. Analysis of variance showed history of substance abuse (p < .000) and years on neuroleptics (p < .000) to be strongly correlated to a diagnosis of TD. Age was less strongly correlated to the DISCUS score (p < .01), and there was no association of TD with diagnosis (p = .237). This study therefore demonstrates a robust correlation between TD and substance abuse. A mechanism of action involving N-methyl-D-aspartate (NMDA)-mediated excitotoxicity is proposed.

Adult↗
PubMed1996

Physicochemical and metabolic basis for the differing neurotoxicity of the pyrrolizidine alkaloids, trichodesmine and monocrotaline.

Monocrotaline and trichodesmine are structurally closely related pyrrolizidine alkaloids (PAs) exhibiting different extrahepatic toxicities, trichodesmine being neurotoxic (LD(50) 57 mu mol/kg) and monocrotaline pneumotoxic (LD(50) 335 mu mol/kg). We have compared certain physicochemical properties and metabolic activities of these two PAs in order to understand the quantitative and qualitative differences in toxicity. Both PAs were metabolized in the isolated, perfused rat liver to highly reactive pyrrolic dehydroalkaloids that appear to be responsible for the toxicity of PAs. More dehydrotrichodesmine (468 nmol/g liver) than dehydromonocrotaline (116 nmol/g liver) was released from liver into perfusate on perfusion for 1 hr with 0.5 mM of the parent PA. Dehydrotrichodesmine had a significantly longer aqueous half-life (5.4 sec) than that of dehydromonocrotaline (3.4 sec). In vivo, significantly higher levels of bound pyrroles were found in the brain 18 hr after injection of trichodesmine (25 mg/kg; i.p.) than were seen following either an equal dose (25 mg/kg; i.p.) or an equitoxic dose (90 mg/kg; i.p.) of monocrotaline. Trichodesmine had a higher partition coefficient than monocrotaline for both chloroform and heptane, indicating its greater lipophilicity. The pK(a) of trichodesmine (7.07) was only slightly higher than that of monocrotaline (pK(a¿ 6.83), suggesting that a difference in degree of ionization was not a major factor affecting the relative ability of the dehydroalkaloids to cross the blood-brain barrier. We conclude that the greater lethality and neurotoxicity of trichodesmine compared to monocrotaline is due to two structural characteristics: (i) steric hindrance at position 14 of dehydrotrichodesmine results in greater resistance to hydrolysis, allowing more to be released from the liver and to be delivered to the brain; (ii) the larger isopropyl substituent at position 14 of dehydrotrichodesmine renders the molecule more lipophilic, leading to greater penetration of the brain.

Alkaloids↗
PubMed1996

A comparison of the effects of fluvastatin and bezafibrate on exercise metabolism: a placebo-controlled study in healthy normolipidaemic subjects.

1. We have examined the interaction between aerobic exercise and lipid-lowering drugs in a crossover study of 16 healthy normolipidaemic volunteers who each received 21 days' treatment with bezafibrate (400 mg), fluvastatin (40 mg), and placebo, in random order. 2. Fluvastatin treatment reduced pre-exercise total cholesterol (TC) by 23% (P < 0.0001), low-density lipoprotein cholesterol (LDL-C) by 33% (P < 0.0001), and plasma triglycerides by 11%, compared with pre-treatment values. Bezafibrate reduced TC by 11% (P < 0.01); LDL-C by 9%; and plasma triglycerides by 40% (P < 0.01), compared with pre-treatment values. 3. During exercise, in comparison with placebo, and fluvastatin treatment, respectively, bezafibrate significantly reduced mean fat oxidation: 31% vs 39%, P = 0.035, 31% vs 39%, P = 0.002, plasma free fatty acid (FFA) availability, e.g. after 90 min of exercise: (t90) 520 vs 662 mumol 1(-1), P = 0.054, 520 vs 725 mumol 1(-1), P = 0.016, and plasma levels of glycerol (t90): 59 vs 74 mumol 1(-1), P = 0.037, 59 vs 73 mumol 1(-1), P = 0.016. Fluvastatin had no impact on fat metabolism in comparison with placebo. 4. Reduced plasma FFA concentration and lower fat oxidation during prolonged exercise on bezafibrate treatment may be due to an inhibition of hepatic acetyl coenzyme A carboxylase, resulting in reduced FFA release from adipose tissue. 5. The possibility that impaired fat metabolism on fibrates could induce premature fatigue during exercise of moderate duration and intensity should be examined in hyperlipidaemic patients.

Adult↗
PubMed1996

The causes and management of atrial fibrillation.

Atrial fibrillation is present in approximately 10% of the population aged over 65 years, in whom its presence is associated with a significantly increased morbidity and mortality. Principal complications include reduced cardiac output and the precipitation of heart failure and thromboembolic phenomena, including strokes and peripheral emboli. In the majority of cases atrial fibrillation is associated with ischaemic heart-disease and hypertension. Other important causes are thyrotoxicosis, valvular heart-disease and atrial septal defect. The primary aims of treatment in atrial fibrillation are to terminate the arrhythmia (cardioversion) with either drugs or direct current (DC) shock and to prevent its recurrence. Effective cardioversion may necessitate the treatment of underlying pathology. If these primary aims cannot be achieved then an attempt must be made to effectively control the ventricular rate with drugs such as digoxin. Recently, further strong evidence has been provided to support the role of anticoagulants and antiplatelet drugs in preventing the major problem of systemic thromboembolic complications. Some of the special difficulties relating to the treatment of atrial fibrillation associated with thyrotoxicosis as well as paroxysmal atrial fibrillation will also be considered.

Anti-Arrhythmia Agents↗