Search PubMed⌕ Search

Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 253 records · Page 14Linked to original sources
PubMed1991

The red cell distribution width in sickle cell disease--is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.

Adolescent↗
PubMed1991

Treatment of refractory peptic ulcer with omeprazole or continued H2 receptor antagonists: a controlled clinical trial.

We tested the hypothesis that the gastric H+/K+ adenosine triphosphatase inhibitor, omeprazole, because of its different mode of action and pronounced inhibitory effect on gastric acid secretion, may be more effective in peptic ulcer that is refractory to histamine H2 receptor antagonist treatment than continuing the same therapy. Altogether 107 patients (duodenal ulcer, n = 88; prepyloric ulcer, n = 14; gastric ulcer, n = 3; mixed sites, n = 2) with refractory peptic ulcer - that is ulcer unhealed after at least two months' treatment with cimetidine 0.8 g or 1 g daily or with ranitidine 0.3 g daily - were randomly allocated to receive either omeprazole 40 mg daily (n = 54) or to continue treatment with the same H2 receptor antagonist and at the same dose (n = 53) for up to eight weeks. The patients in the two treatment groups were well matched demographically. Healing by 'intent to treat' analysis was as follows: at four weeks, omeprazole 46 of 54 (85%), H2 receptor antagonist 18 of 53 (34%) (p less than 0.0001); and at eight weeks, 52 of 54 (96%) and 30 of 53 (57%) respectively (p less than 0.0001). One patient was lost to follow up but of the 22 patients whose ulcers were shown to be unhealed at endoscopy after receiving continued H2 receptor antagonist treatment, 21 healed in four to eight weeks when changed to omeprazole. Daytime epigastric pain cleared at four weeks in 43 of 47 (91%) patients on omeprazole and in 32 of 46 (70%) on H2 receptor antagonists (p=0.01) and relief of all dyspeptic symptoms occurred in 39 of 47 (83%) and 23 of 45 (51%) (p=0.0009) patients respectively. Adverse events occurred in 11 of 54 (20%) patients on omeprazole and in 12 of 35 (34%) on cimetidine but in none on ranitidine. The events were mild and none required treatment withdrawal. The commonest event in patients on omeprazole was loose stools or diarrhoea (n=5). Omeprazole was significantly better than continued H2 receptor antagonist treatment for the short term management of refractory peptic ulcer as judged by healing rate and pain relief, and it was safe.

Cimetidine↗
PubMed1991

Intracellular signalling in the ovine pars tuberalis: an investigation using aluminium fluoride and melatonin.

The effect of aluminium fluoride (AlF4-) has been studied on inositol phosphate accumulation, calcium mobilization, cyclic AMP production and [2-125I]iodomelatonin binding in ovine pars tuberalis cells. These cells have high-affinity receptors for, and respond to, melatonin through inhibition of forskolin-stimulated adenylate cyclase. In the presence of 10 mM LiCl, AlF4- stimulated the net accumulation of inositol monophosphate and inositol bisphosphate. Consistent with these findings, AlF4- increased intracellular calcium; although this response was attenuated in calcium-depleted medium, indicating that the calcium response comprises both intracellular and extracellular components. Melatonin was ineffective on either basal or AlF4(-)-stimulated turnover of inositol phosphates. In concordance with the inositol phosphate response, melatonin had no effect on either the AlF4(-)-stimulated or the basal calcium levels. AlF4- blocked the increase in cyclic AMP stimulation by 1 microM forskolin, being as effective as melatonin, achieving approximately 90% inhibition. AlF4- also attenuated the binding of [2-125I]iodomelatonin to ovine pars tuberalis membranes by 15%. At the concentration used, these results are consistent with the interpretation that AlF4- activates many G protein-mediated responses, and thus imply that the inhibitory pathway for cyclic AMP predominates over the stimulatory arm, whereas there can only be a stimulatory pathway linked to phosphoinositide metabolism in ovine pars tuberalis cells.

Aluminum↗
PubMed1991

Gastric ulcer healing: a comparison of enprostil versus ranitidine.

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.

Antacids↗
PubMed1991

Proximal cutaneous necrosis associated with small vessel calcification in renal failure.

Cutaneous necrosis with microvascular calcification is a rare and serious complication of chronic renal failure and has been given the sobriquet of 'calciphylaxis'. We describe four dialysis-dependent patients with proximal cutaneous necrosis who presented with this distinctive clinical syndrome. All of the patients were women aged between 40 and 68, and all developed widespread livedo reticularis followed by painful subcutaneous nodules which progressed to eschar-like lesions of the skin. Microvascular calcification was seen on radiographs of the limbs, especially at the sites of the cutaneous lesions. Serum phosphorus concentrations were increased in all the patients (maximally to between 2 and 3.6 mmol/l), but serum calcium concentrations were mildly increased in only two patients and only one patient had hyperparathyroidism. Histological examinations of skin biopsies in two patients showed cutaneous infarcts. Three patients died despite a reduction in serum phosphorus concentration and one patient improved. The proximal form of 'calciphylaxis' constitutes a distinct syndrome which can be recognized clinically.

Adult↗
PubMed1990

An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory.

We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22,512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10,000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10,000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Organ-specific hematopoietic changes induced by a recombinant human interferon-alpha in mice.

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine that mediates numerous biological activities and has demonstrated therapeutic potential in a variety of malignancies. Encouraging activity against HIV-1 replication has also been observed with IFN-alpha in the treatment of AIDS, although hematotoxicity has been a frequently observed side effect. In addition, in vitro studies have suggested that IFN-alpha may function as a down-regulator of myelopoiesis. A recombinant hybrid of subtypes of human IFN-alpha, rHuIFN-alpha A/D, has antiviral activity in murine cells in vitro and in vivo. This study examines the effect of acute and subchronic exposure to rHuIFN-alpha A/D on hemopoietic and immune parameters in C57Bl/6 mice. IFN-alpha was administered ip at 0, 1000, 10,000, and 100,000 units/day for either 1 or 10 consecutive days. Many of the known effects of IFN-alpha in humans such as anemia, leukopenia, and thrombocytopenia were observed in mice following subchronic exposure, with the latter two effects also manifested following acute exposure. Further analysis showed that this leukopenia was not selective. Both splenic and bone marrow cells were examined following 10 days of dosing with the high dose of IFN-alpha. Lymphocytes were reduced in both compartments, while granulocytes were increased in both compartments. Bone marrow cells programmed to differentiate into granulocytes (CFU-G) were suppressed, while macrophage progenitors (CFU-M) were stimulated. Erythroid cells decreased in the marrow but increased in the spleen, suggesting that the microenvironment may play a significant role in the effect of IFN-alpha. The proliferative capacity of both B and T splenic lymphocytes was significantly suppressed in a dose-related fashion following multiple exposure to IFN-alpha. Clinically, IFN-alpha is most often given in multiple doses and the present data suggest that such a regimen is toxic to both erythroid and myeloid cells, as well as being immunotoxic to splenic B and T lymphocytes.

Alanine Transaminase↗
PubMed1990

Toxicity of p-chloroaniline in rats and mice.

p-Chloroaniline (PCA) was administered as PCA hydrochloride in water by gavage to groups of ten Fischer 344 rats and ten B6C3F1 mice of each sex for 13 wk. The doses, calculated as PCA rather than the hydrochloride salt, were 0, 5, 10, 20, 40 or 80 mg PCA/kg body weight/day for rats and 0, 7.5, 15, 30, 60 or 120 mg/kg body weight/day for mice. The vehicle controls were given deionized water by gavage. All male rats survived to the end of the studies. One of the ten female rats that received 80 mg PCA/kg died from unknown causes. The final body weights of rats that received 80 mg/kg were 16% lower than those of vehicle controls in the case of males and 4% lower in females. In mice, there was no mortality related to PCA administration. The final body weights of treated mice were similar to those of vehicle controls. In both rats and mice, no treatment-related effects on organ weights were observed at autopsy, except for a dose-related increase in spleen weight. The proportion of haemoglobin in the form of methaemoglobin was increased in dosed groups in both species and resulted in a secondary anaemia, the severity of which was dose related. Compound-related lesions observed histologically in rats and mice, included pigmentation (haemosiderin) in the kidney, spleen and liver and increased haematopoiesis in the liver and spleen and in the bone marrow (in rats but not mice), reflecting the response to the haemolytic anaemia and methaemoglobinaemia induced by PCA. It is concluded that the haematopoietic system is a target of PCA toxicity.

Aniline Compounds↗
PubMed1990

Synthesis and evaluation of a series of aryl[e]fused pyrazolo[4,3-c]pyridines with potential anxiolytic activity.

A series of pyrazolo[4,3-c]pyridines has been synthesized and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different from that of diazepam. A number of the compounds possess higher affinity for central benzodiazepine receptors than diazepam, yet show less anticonvulsant activity and are less sedative. The structure-activity relationships of these potential anxiolytic agents are discussed.

Animals↗
PubMed1990

Insight of first-year medical students into their future working conditions.

In the light of recent publicity in the media, and a Private Members Bill in the Houses of Parliament, a multiple choice questionnaire was designed to ascertain the insight of first-year medical students at Leicester Medical School into their career structure and future working conditions. The results obtained were surprising in that they indicated an almost total lack of knowledge among the medical students about the profession into which they had just entered, and to which they had made a lifelong commitment.

Adolescent↗
PubMed1990

Emotional Stroop performance and the manic defence.

Undergraduate subjects were selected on the basis of high, low and medium scores on Eckblad & Chapman's Hypomanic Personality Scale and were given an emotional Stroop test. Hypomanic traits were associated with interference of colour naming for depressive but not euphoria-related words.

Adult↗
PubMed1990

Omeprazole in the treatment of erosive oesophagitis refractory to high dose cimetidine and ranitidine.

Forty five patients with refractory oesophagitis, defined as persisting erosive changes or ulceration despite a minimum of three months' treatment with cimetidine 3.2 g daily or ranitidine 0.9 g daily, were treated in an open trial with omeprazole 40 mg daily for up to eight weeks. Endoscopically defined healing was observed in 73% of patients after four weeks' treatment and in 91% after eight weeks' treatment. Symptoms were completely relieved in 60% of patients, improved in 34%, unchanged in 4%, and worsened in 2%. After healing patients returned to maintenance treatment with cimetidine 1.6-3.2 g daily, depending on the severity of their illness before treatment with omeprazole. By six months and 12 months only 55% and 33% of patients respectively were still in remission. This study suggests that when erosive oesophagitis is refractory to treatment with high dose cimetidine or ranitidine, treatment with omeprazole 40 mg daily for up to eight weeks is effective in inducing healing and relieving symptoms.

Adult↗
PubMed1990

Gastric endocrine cells share a clonal origin with other gut cell lineages.

There has been considerable debate about the ontological origin of gut endocrine cells as being either from the neural crest (or primitive epiblast) or from the endodermal stem cell. We have attempted to define the ontological origin of endocrine cells by applying an experimental system that uses a marker to identify one of the two phenotypes present in chimaeric mice as suggested by Ponder et al. (1985). This study involved two separate experiments. The first made use of the unique staining properties of Dolichos biflorus agglutinin (DBA), a lectin that binds to the N-acetyl galactosamine sugar residues present on the surface of C57Bl mouse gut, but absent from RoRIII mouse gut, in C57Bl----RoIII mouse chimaeras at the ultrastructural level. A four-stage procedure for staining at the EM level was developed. Although mature villous endocrine cells stained for DBA, immature endocrine cells did not, either in the positive crypts of chimaeric mouse gut or in gut from C57Bl positive controls. Thus a second marker was chosen. This experiment combined immunocytochemistry (to identify gastric antral gastrin cells chosen as a representative neuroendocrine cell) with in situ DNA hybridization for the mouse male chromosome repeat sequence PY 353 (to identify XY cells) in XX----XY chimaeric mice. This study showed that the sex chromosomal pattern in the gastrin cells parallels that of other cells in the same gastric gland and therefore are clonal with them. This suggests that gut endocrine cells share a common stem cell with other epithelial cell lineages in the antrum and are endodermally derived.

Animals↗