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Biomedical subjects

J M Simpson

Publications and source records attributed to J M Simpson.

At least 145 records · Page 8Linked to original sources

A controlled trial of GL enzyme in the treatment of acute myocardial infarction.

GL enzyme (hyaglosidase) is a highly purified component enzyme of hyaluronidase. A therapeutic trial was carried out in the treatment of suspected myocardial infarction among 1,488 patients presenting within 6 h of the onset of symptoms. No significant reduction in mortality at 6 months was observed in the GL group (15.7%) compared with the placebo group (16.4%). Mortality at 2 weeks was also unaffected by treatment (GL 10.3%; placebo 10.9%).

Clinical Trials as Topic↗

Plasma oxalate in patients receiving continuous ambulatory peritoneal dialysis.

Plasma oxalate has been measured in 125 patients maintained on continuous ambulatory peritoneal dialysis using an enzyme/bioluminescent assay. Values ranged between 6 and 134 mumol/l, with a positively skewed distribution. Multiple linear regression analysis with plasma oxalate as the dependent variable showed highly significant associations with the dose of ascorbic acid, dose of alfacalcidol, and plasma creatinine, and weaker associations with serum phosphate, serum calcium, and body weight. When the presence of other potential risk factors was taken into account, no significant relationship could be found between the presence of clinically evident cardiac or vascular disease and plasma oxalate.

Ascorbic Acid↗

A limiting dilution assay to determine the frequency of antigen presenting cells.

A limiting dilution assay to measure the functional frequency of antigen presenting cells (APC) has been developed and used to measure the frequency of mouse lymphoid cells which stimulated the mixed leucocyte response. The experiments utilised measurements of proliferation in 20 microliter hanging drop microcultures of activated T lymphocytes. When the data supported a model of single-hit kinetics, the APC frequency in the titrated stimulating cell population was calculated by the method of maximum likelihood. The assay was validated by measuring the frequency of unpurified spleen cells and enriched spleen dendritic cells which presented alloantigens in mixed leucocyte culture. APC frequency in unpurified spleen cells was 1:7254 (SE +/- 2134, 8 experiments) and was increased markedly to 1:15 (SE +/- 7, 7 experiments) when enriched populations consisting 70-95% of dendritic cells were used as stimulators.

Animals↗

Effects of intradermal bradykinin after inhibition of angiotensin converting enzyme.

Inhibitors of angiotensin converting enzyme may cause angio-oedema. To see if this might be due to potentiation of the tissue effects of bradykinin the thickness of weals raised by intradermal injection of saline or 1, 3, or 10 micrograms bradykinin was measured before and three times after single doses of captopril, enalapril, or placebo. The mean thickness increased with increasing doses of bradykinin. It did not change with time after the administration of placebo or captopril but increased from 0.61 mm before enalapril to 1.12 mm two and a half hours and 1.06 mm five hours after enalapril was given. Five subjects flushed when given bradykinin after captopril and four after enalapril, but none flushed when given bradykinin after placebo. It is concluded that angiotensin converting enzyme inhibitors potentiate the effects of intradermal bradykinin in vivo and that this may partially explain why they cause angio-oedema in susceptible patients.

Adult↗

High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy.

We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophosphamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.

Adult↗

Inhibition of colonization of the chicken alimentary tract with Salmonella typhimurium gram-negative facultatively anaerobic bacteria.

Oral administration of strains of food poisoning salmonellas to day-old chickens produced a profound inhibition in the subsequent colonization of the caeca by a strain of Salmonella typhimurium given one day later. Closely related genera were unable to produce a similar inhibition. The inhibition was not the result of bacteriophages produced by the first strain. Neither was it the result of an immunological response by the host induced by the first strain. In additional experiments in day-old chickens, inhibition of an Escherichia coli Nalr strain and of a Citrobacter sp. Nalr strain was produced by the antibiotic-sensitive forms of the homologous strains while strains from other genera did not produce any inhibition. When an avirulent mutant of S. typhimurium was used for pre-treatment a statistically significant reduction in the excretion of the super-infecting S. typhimurium Nalr strain over several weeks was produced. A genus specific inhibition was reproduced in vitro by mixed culture experiments. Live cultures were necessary for in vitro inhibition. Killed cells or a culture supernatant produced no inhibition.

Animals↗

Contribution of Salmonella gallinarum large plasmid toward virulence in fowl typhoid.

Four strains of Salmonella gallinarum isolated from independent cases of fowl typhoid all possessed both an 85-kilobase and a 2.5-kilobase plasmid. Each plasmid was eliminated in turn from one of the strains by transposon labeling and curing at 42 degrees C. Elimination of the small plasmid had no effect on the high virulence of the strain for newly hatched and 2-week-old chickens. Whereas oral inoculation of 2-week-old chickens with the parent strain produced 90% mortality with characteristic signs of fowl typhoid, inoculation of the large-plasmid-minus strain produced 0% mortality. A corresponding increase in the 50% lethal dose from log10 1.1 to greater than log10 7.3 was seen with the large-plasmid-minus strain after intramuscular inoculation. Reintroduction of the large plasmid completely restored virulence. A role for the plasmid-linked virulence genes in both invasion and growth in the reticuloendothelial system is suggested by the failure of the large-plasmid-minus strain to penetrate to the liver and spleen after oral inoculation and by its increased clearance from the reticuloendothelial system after intravenous inoculation. These results clearly demonstrate that the large plasmid of S. gallinarum contributes toward virulence in fowl typhoid of chickens.

Animals↗

Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis.

The histopathological characteristic of ankylosing spondylitis (AS) is the presence of chronic enthesitis. Our aim was to develop a clinical measurement of the severity of tenderness over entheses. The scoring system was based on the patients' response to palpation over entheses easily accessible to examination. The enthesis index (EI) correlated with pain (r = 0.67, p less than 0.01) and stiffness (r = 0.46, p less than 0.05) scores. A single, blind, crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability. The index showed significantly lower scores after one week's drug treatment (p less than 0.05). The EI is a convenient, non-invasive measure of disease severity in patients with AS. Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinically between severity of enthesitis and synovitis in different types of polyarthritis.

Adolescent↗

The Memory Clinic. A new approach to the detection of dementia.

Memory impairment is a salient and early feature of developing dementia, but in practice is often not recognised until it has reached an advanced stage. The operation described is of a Memory Clinic opened on an experimental basis at the Geriatric Research Unit, University College London, in 1983, with the aim of identifying the causes of memory impairment in the elderly, with particular reference to the early detection of dementia. It proved possible to identify a group of people with early dementia who had previously been undiagnosed, and also to reveal deficiencies in the utilisation of existing services. Memory clinics would be a valuable addition to geriatric and psychogeriatric services.

Aged↗

Observations on the pathogenesis of experimental Salmonella typhimurium infection in chickens.

The virulence of Salmonella typhimurium strains for day-old chickens was examined. The mortality following oral inoculation varied from 0 to 100 per cent. Some breeds were more susceptible than others. There was no correlation between oral and parenteral virulence. Pathogenesis studies associated with one of the most virulent strains suggested that, after invasion, organisms multiplied in the liver and spleen and spread to other organs producing a systemic infection. The cause of death was probably a combination of anorexia and dehydration resulting from general malaise and diarrhoea. A virulent strain studied in detail spread through the body faster, persisted for a longer period and was more invasive than an avirulent strain. In the system studied invasiveness was the virulence determinant of overriding importance.

Animals↗

A trial of flunarizine in the treatment of Duchenne muscular dystrophy.

Twenty-seven boys with Duchenne muscular dystrophy (DMD) entered a double-blind controlled trial of treatment with the calcium antagonist flunarizine. They were matched for age and disability. At monthly intervals, muscle power, functional ability, locomotor score, contractures, and forced vital capacity were measured by a team not involved in clinical care. Over a period of 1 year, flunarizine in a dose of up to 0.25 mg/kg/day had no effect on the clinical course of the disease.

Adolescent↗

The effect of altering area of application and dose per unit area on sensitization by DNCB.

We have investigated the contributions of dose per unit area and area of application to the degree of sensitivity induced by dinitrochlorobenzene (DNCB). Subjects sensitized with 35.4 micrograms/cm2 showed equal sensitization whether the total dose was 250 micrograms applied to 7.1 cm2 or 62.5 micrograms applied to 1.8 cm2. Three groups of subjects were sensitized with 16.4 micrograms/cm2 applied as 56 micrograms on 3.5 cm2, 116 micrograms on 7.1 cm2 or 232 micrograms on 14.2 cm2. Although the total dose changed by a factor of four, the proportions of subjects sensitized were comparable (66, 50 and 55% respectively), and their degrees of reactivity were similar. This contrasts with previous findings that when the area of sensitization was fixed and the concentration was increased over a similar range, highly significant increases in the proportion of sensitized subjects and degree of reactivity occurred.

Administration, Cutaneous↗

Anatomical variations in the first extensor compartment of the wrist. A clinical and anatomical study.

We studied 300 wrists from cadavera and the wrists of forty patients with de Quervain disease to determine the variation in the pattern of the tendons and septa in the first extensor compartment. In 75 per cent of the wrists from cadavera, we found that the number of tendons within the compartment differed from what is considered standard; there was complete or partial septation in 40 per cent. In about a third of the specimens from cadavera, the first extensor compartment was divided by a septum and two tendons or more were present within the major subcompartment. These features might readily result in inadequate decompression of the compartment in the treatment of de Quervain disease. In our prospective study of forty patients with de Quervain disease, septation was found in twenty-seven. There was no significant difference between the number of patients and the number of specimens from cadavera that had no, one, or two accessory abductor tendons.

Cadaver↗

Extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom.

The epidemiology of extrapyramidal reactions to prochlorperazine and haloperidol in the United Kingdom has been studied using reports in the Adverse Reactions Register of the Committee on the Safety of Medicines (CSM) and from general practitioner prescribing data. Between 1967 and 1982 there were an estimated 37.0 million prescriptions for prochlorperazine and 3.2 million for haloperidol; in this time there were 104 reports of adverse reactions to prochlorperazine and 62 to haloperidol. The predominant extrapyramidal reaction reported was dystonia-dyskinesia (99 reports for prochlorperazine and 47 for haloperidol). The remaining reactions reported were of Parkinsonism. Dystonia-dyskinesia usually occurred within three days of commencing treatment, and for both drugs the incidence, expressed per million prescriptions, varied significantly with age, the highest incidence being in patients under 20 years. Thus young patients appear at particular risk of acute extrapyramidal reactions to dopamine receptor antagonists.

Adolescent↗

Extrapyramidal reactions with metoclopramide.

The epidemiology of extrapyramidal reactions to metoclopramide was studied by examining reports in the Adverse Reactions Register of the Committee on the Safety of Medicines and comparing these with prescribing figures by general practitioners in the United Kingdom for metoclopramide (Maxolon). In the period 1967-82 there were an estimated 15.9 million prescriptions and 479 reports of extrapyramidal reactions (455 of dystonia-dyskinesia, 20 of parkinsonism, and four of tardive dyskinesia). When corrected for prescribing rates the relative risk of dystonia and dyskinesia was 1.8 in female compared with male patients (95% confidence interval 1.4-2.2). The overall reporting rate for dystonia and dyskinesia was 28.6/million prescriptions but was significantly more common in young adults (p less than 0.0001) and especially girls and women aged 12-19 (190.7 reports/million prescriptions). By contrast parkinsonian reactions were significantly more common in the elderly (p less than 0.0001).

Adolescent↗

Susceptibility and amplification of sensitivity in contact dermatitis.

We have examined the hypothesis that people who develop contact allergies to environmental substances do so because they have heightened susceptibility. Analysis of data from 2200 consecutive patients tested with the 20 commonest antigens in a patch-test clinic showed that more people developed multiple contact allergies than would be predicted from the frequency of single allergies; the excess was too great to be explained by chance and increased with number and rarity of the combinations of sensitizers. The possibility that this was due to enhanced individual susceptibility to sensitization rather than concomitant exposure to several sensitizers was confirmed by showing that patients with multiple allergies are more readily sensitized experimentally, and to a greater degree than normal, by dinitrochlorobenzene (DNCB), an unrelated antigen. The defect involves induction rather than expression of sensitivity. Amplification of the response to DNCB is proportional to susceptibility (calculated from the ratio of observed prevalence of multiple allergies to that predicted from the prevalence of single allergies) throughout the range from normal subjects, through those with a single sensitivity, to those with rare, multiple allergies. Therefore, we conclude that individual susceptibility is an important factor in the development of contact dermatitis, and occurs by a non-antigen-specific amplification of immune sensitization.

Adult↗