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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

A comparison of three nucleoside analogs with anti-retroviral activity on immune and hematopoietic functions in mice: in vitro toxicity to precursor cells and microstromal environment.

A number of 2'3'-dideoxynucleosides have been reported to markedly inhibit the in vitro growth of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that the continued therapeutic use of these nucleoside derivatives can be associated with adverse side effects. Since these side effects include myelotoxicity, as occurs in many patients treated with zidovudine (AZT; 3'-azido'3-deoxythymidine), and AIDS patients already represent an immunologically compromised population, we examined the immunological effects of three nucleoside inhibitors, including zidovudine, 2'3'-dideoxycytidine, and 2'3'-dideoxyadenosine (DDA) in a mouse model. Additional studies were conducted to further determine and characterize the potential toxic effects associated with these drugs on the hematopoietic system. Of the three dideoxynucleosides examined, only DDA altered immune functions following a 30-day subchronic exposure in mice. This was evidenced by a marked suppression of the antibody plaque-forming cell response and a slight alteration in macrophage function. None of the nucleoside derivatives affected bone marrow function following in vivo exposure, although AZT produced a mild macrocytic anemia in vivo and was myelotoxic when added in vitro to bone marrow cell cultures. In vitro studies indicated that AZT was capable of affecting both proliferating stem cells as well as the stromal cell microenvironment, both of which play a role in hematopoiesis. These data indicate that, although the mice may not develop the identical toxicities associated with nucleoside therapy in humans, certain adverse immunological and hematological effects were readily discerned which could have relevance to humans.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Molecular receptors and their potential for artificial transduction.

The thesis is presented that molecular receptor physical chemistry offers an interesting model for the design of biosensors with respect to chemical recognition and transduction. In order to appreciate the desirable features of this system and the inherent difficulties, the structures and binding state energetics of molecular receptors are considered via a direct comparison with enzyme chemistry. Detailed analyses of the candidate species nicotinic and beta-adrenergic receptors are provided to illustrate the complexity of molecular receptor binding properties. A revised ternary-complex model, which combines enzymatic and receptor energetics, is proposed to explain the free-energy changes which drive ligand-binding reactions of coupled systems. Throughout this discussion the relevance of the various arguments to applications in biosensor development is highlighted. Finally, a brief appraisal of attempts to produce devices ready for marriage to molecular receptor material is presented.

Animals↗
PubMed1989

The regulation of immunoglobulin production by B cells in patients with endometriosis.

Nineteen patients with endometriosis and 26 control infertile patients were included in the study. All patients were undergoing laparoscopy as part of their infertility evaluations. The study was conducted on sterile heparinized peripheral blood and peritoneal fluid. The age range was 20 to 37 years for both groups. Mononuclear cells were isolated on Ficoll-hypaque density gradients. T cells, B cells, and T cell subsets were identified by the specific immunobead rosette technique. Mononuclear cells 1 x 10(6) were cultured in Roswell Park Memorial Institute medium and stimulated in the presence or absence of pokeweed mitogen. Immunoglobulin production was measured by an enzyme-linked immunosorbent assay. Increased amounts of immunoglobulin (Ig) IgG and IgA were demonstrated in the peritoneal cell cultures (P less than 0.05), whereas peripheral blood cell cultures showed only an increase in IgG in patients with endometriosis (P less than 0.05). There was an increase in the number of T cells, B cells, and the ratio of CD4/CD8 lymphocytes in endometriosis compared with control patients (P less than 0.005) in both peritoneal fluid and peripheral blood. This study suggests that immunoglobulin production by the "activated" B cells may be regulated by the increased presence of T cells, specifically the helper cells (CD4) in endometriosis.

Adult↗
PubMed1989

A comparison of audiometric test methods for 2-year-old children.

Visual reinforcement audiometry (VRA), visual reinforcement operant conditioning audiometry (VROCA), and play audiometry were compared in terms of conditionability and number of responses obtained prior to habituation on normal 2-year-old (24-27 months) children. Results indicated that a higher percentage of children could be conditioned to VRA than to either VROCA or play audiometry. Results also indicated that for children who could be conditioned, the play audiometry group showed more responses prior to habituation than were obtained from the other two groups.

Age Factors↗