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Biomedical subjects

S Maxwell

Publications and source records attributed to S Maxwell.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Exercise metabolism during 1 hour of treadmill walking while taking high and low doses of propranolol, metoprolol, or placebo.

Aerobic exercise and beta-blocking drugs are regularly prescribed as treatment for hypertension and as a prophylactic for patients at risk from coronary heart disease and for those recovering from an infarct. Some beta blockers, particularly non-beta 1-selective drugs, may make exercise more difficult, possibly by interfering with substrate metabolism during exercise. This study examined the effects of low and high doses of a beta 1-selective blocker, metoprolol, and a non-selective beta blocker, propranolol, on exercise metabolism. The study involved 20 healthy subjects (10 men, 10 women) who walked on a treadmill at 50% of their maximal oxygen uptake for 1 h on five occasions, separated by 7 days. On each of the five occasions they received one of the following treatments, given in random order: placebo, metoprolol 50 mg, metoprolol 100 mg, propranolol 40 mg, or propranolol 80 mg, all taken twice daily. Fat oxidation, expressed as a percentage of total energy expenditure, was significantly lower than with placebo for all of the active treatments except metoprolol 50 mg (placebo: 42.7 +/- 11.6%; metoprolol 50 mg: 38.7 +/- 14.1%, p = NS; metoprolol 100 mg: 36.3 +/- 13.7%, p = 0.05; propranolol 40 mg: 31.2 +/- 9.3%, p = 0.01; propranolol 80 mg: 29.5 +/- 10.9%, p = 0.01); and significantly lower with propranolol than with metoprolol (propranolol 40 mg: p = 0.0036; propranolol 80 mg: p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The medical and surgical management of trigeminal neuralgia.

Trigeminal neuralgia is a paroxysmal and severely disabling facial pain. The diagnosis is usually made on the basis of a typical history and the exclusion of secondary causes. Initial management of the pain is medical. Carbamazepine is the drug of choice although some patients respond to other drugs including phenytoin, baclofen, sodium valproate and clonazepam. Surgical therapy should be considered if medical treatment fails or cannot be tolerated. Surgical options include peripheral or central (intracranial) procedures. Central procedures have greater morbidity and a significant mortality rate (approximately 1%) but the success rates are much greater. Physicians should be aware of the potential benefits of surgery but all patients should be advised carefully about the risks before informed consent is given.

Baclofen↗
PubMed1994

Reduced transfer of tetanus antibodies with placental malaria.

Placental malaria may limit antibody transfer to the fetus. We compared concentrations of tetanus antibody in paired maternal-cord sera from 224 women living in a malarious area of Papua New Guinea. With heavy placental infection (> 35 parasites per 200 white cells) the average cold tetanus antibody corresponding to a maternal level of 1 IU/mL was 0.18 (95% CI 0.12-0.26); corresponding figures after light (< 35 parasites per 200 white cells) or no infection were 0.23 (0.14-0.34) and 0.82 (0.57-1.21), respectively. About 10% of babies born to mothers with a placenta heavily infected with Plasmodium falciparum may fail to acquire protective levels of tetanus antibody despite adequate maternal antibody.

Antibodies, Bacterial↗
PubMed1994

Particle size: the key to the atherogenic lipoprotein?

Using different analytical methods, up to 12 low-density lipoprotein (LDL) subfractions can be separated. LDL particle size decreases with increasing density. Smaller, denser LDL particles seem more atherogenic than the larger, lighter particles, based on the experimental findings that smaller LDL particles are more susceptible for oxidation in vitro, have lower binding affinity for the LDL receptors and lower catabolic rate, have a higher concentration of polyunsaturated fatty acids, and potentially interact more easily with proteoglycans of the arterial wall. Clinical studies have shown that a smaller LDL subfraction profile is associated with an increased risk of heart disease, even when total cholesterol level is only slightly raised. There is a strong inverse association between LDL particle size and triglyceride concentrations. Although LDL particle size is genetically determined, its phenotypic expression may also be affected by environmental factors such as drugs, diet, obesity, exercise or disease. Factors that shift the LDL subfractions profile towards larger particles may reduce the risk of heart disease.

Arteries↗
PubMed1994

Exercise metabolism in healthy volunteers taking atenolol, high and low doses of metoprolol CR/Z0K, and placebo.

1. Exercise and beta-adrenoceptor blockade have important roles in the prevention and treatment of cardiovascular disease, but fatigue and a reduced capacity to exercise are commonly reported side effects of beta-adrenoceptor blockers. The reduced capacity to exercise may be partly caused by a reduction in fat metabolism. 2. We investigated the effects of atenolol 50 mg, metoprolol CR/Z0K 50 mg, metoprolol CR/Z0K 100 mg and placebo, on heart rate, energy expenditure, fat oxidation, plasma free fatty acids, glycerol, glucose, lactate, ammonia and perceived exertion during 2 h of treadmill walking at 40% of maximal oxygen uptake in 20 healthy volunteers. 3. Compared with placebo (38.0%), total fat oxidation was significantly lower on atenolol 50 mg (30.1%) and metoprolol CR/Z0K 100 mg (31.0%), but not on metoprolol CR/Z0K 50 mg (33.7%). Reductions in fat oxidation correlated well (r2 = 0.970) with reductions in exercising heart rate, and probably reflected the degree of beta 1-adrenoceptor blockade. Maximum plasma ammonia concentration was reached after 45 min of exercise on atenolol, 60 min on metoprolol CR/Z0K 100, and 75 min on metoprolol CR/Z0K 50, and was higher than placebo on all active drug treatments. 4. The greater reduction in fat oxidation with atenolol may be a reflection of a peak in plasma concentration, which is avoided with a controlled release preparation.

Adipose Tissue↗
PubMed1993

Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise.

This study investigated the effects of antioxidant vitamin supplementation upon muscle contractile function following eccentric exercise and was performed double blind. Twenty-four physically active young subjects ingested either placebo (400 mg; n = 8), vitamin E (400 mg; n = 8) or vitamin C (400 mg; n = 8) for 21 days prior to and for 7 days after performing 60 min of box-stepping exercise. Contractile function of the triceps surae was assessed by the measurement of maximal voluntary contraction (MVC) and the ratio of the force generated at 20 Hz and 50 Hz tetanic stimulation before and after eccentric exercise and for 7 days during recovery. Following eccentric exercise, MVC decreased to 75 (4)% [mean (SE); n = 24; P < 0.05] of the preexercise values and the 20/50 Hz ratio of tetanic tension from 0.76 (0.01) to 0.49 (0.03) [mean (SE); n = 24; P < 0.05). Compared to the placebo group no significant changes in MVC were observed immediately post-exercise, though recovery of MVC in the first 24 h post-exercise was greater in the group supplemented with vitamin C. The decrease in 20/50 Hz ratio of tetanic tension was significantly less (P < 0.05) post-exercise and in the initial phase of recovery in subjects supplemented with vitamin C but not with vitamin E. These data suggest that prior vitamin C supplementation may exert a protective effect against eccentric exercise-induced muscle damage.

Adolescent↗