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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 937 records · Page 52Linked to original sources

Frequent polymorphism in the 13th exon of the adenomatous polyposis coli gene.

We have studied the DNA from 170 individuals affected with familial adenomatous polyposis and from 20 uneffected individuals. Denaturing gradient gel electrophoresis of polymerase chain reaction amplified DNA from the adenomatous polyposis coli (APC) gene demonstrated three major patterns consistent with the existence of two different sequences in exon 13 of the gene in the human population. Direct sequencing of the amplified product from DNAs producing these three patterns confirmed the presence of a polymorphism in the coding region of the APC gene.

Adenomatous Polyposis Coli↗

Acute renal failure in orthotopic liver transplantation.

Acute renal failure (ARF) is a frequent complication of orthotopic liver transplantation (OLT) and is a major cause of mortality and morbidity. We report the incidence, management and outcome of ARF in OLT patients during the first year of a liver transplant programme.

Acute Kidney Injury↗

2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans.

14 patients with heavy metal poisoning received 2,3-dimercaptosuccinic acid (DMSA). 12 subjects were given 30 mg/kg/day for 5 days; 1 subject was started on a lower dose because of a history of atopy; another subject was treated for 15 days because of very high initial blood lead concentrations. In the 9 subjects who had lead poisoning, DMSA decreased blood lead concentrations by 35 to 81%, and induced a 4.5- to 16.9-fold increase in mean daily urinary excretion of the metal. In the acutely arsenic-poisoned case, the plasma arsenic concentration on day 7 was half the pretreatment value, while no clear decrease was observed in a chronically exposed subject. In 3 mercury cases, DMSA increased daily mercury urinary excretion 1.5-, 2.8- and 8.4-fold, respectively, while blood mercury concentrations remained below detection limits. No serious side effects were observed and 3 weeks after administration of the drug the clinical condition of all subjects was either stable or improved. These results indicate the efficacy of DMSA for lead poisoning in humans and provide a rationale for further investigating its usefulness in mercury and arsenic poisoning cases.

Adolescent↗

Coil embolization of a solitary congenital intrahepatic hepatoportal fistula.

Congenital hepatic artery-to-portal vein fistula, a rare type of arteriovenous malformation that may be intrahepatic or extrahepatic, is an uncommon cause of severe infantile portal hypertension. Many researchers believe that acquired intrahepatic arterioportal fistulas are best treated by embolization and that extrahepatic arterioportal fistulas require surgical intervention. The experience with congenital intrahepatic arterioportal fistulas is very limited and has required both embolization and surgical intervention. We report a case of solitary congenital arterioportal fistula successfully treated with coil embolization.

Angiography, Digital Subtraction↗

The role of Hydrotaea irritans in the transmission of summer mastitis.

A series of experiments to investigate the possible role of the sheep head fly, Hydrotaea irritans, in the transmission of summer mastitis is reported. These showed that the pathogens Actinomyces pyogenes and Peptococcus indolicus may be harboured in the gut of the fly for up to 96 h following a contaminated meal; A. pyogenes survived on the surface of the fly for a similar period. H. irritans fed on the pathogens can contaminate a subsequent meal by regurgitation. However, no infections resulted from repeated exposure of the teats of heifers or cows to H. irritans fed on blood containing A. pyogenes and P. indolicus or on pus from a case of summer mastitis. In these experiments the frequency of feeding of the flies on the teat was high but subsequent bacterial contamination of the teat skin was low. Artificial contamination of the teat skin with greater than 10(6) cfu A. pyogenes led to a low incidence of mastitis even in the absence of cutaneous damage. Repeated applications of lower doses (less than 10(4) cfu) did not produce infection.

Actinomyces↗

Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels.

Transmembrane influx of extracellular calcium through specific calcium channels is now accepted to have an important role in the excitation-contraction coupling of cardiac and smooth muscle. The importance of such slow calcium channels has been underlined by the development of specific calcium channel blocking agents, the 'calcium antagonists', typified by verapamil, nifedipine and diltiazem. These drugs have been used to investigate the properties of slow calcium channels in a variety of tissues. We have found that small modifications to the nifedipine molecule produce other dihydropyridine derivatives (see Fig. 1) with effects diametrically opposite to those of the calcium antagonists: cardiac contractility is stimulated and smooth muscle is contracted. These effects are competitively antagonized by nifedipine. Apparently, nifedipine and the novel compounds bind to the same specific dihydropyridine binding sites in or near the calcium channel. In contrast to nifedipine, however, the new compounds promote--instead of inhibiting--the influx of Ca2+ ions. We report here the properties of BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate), one of the most potent of these novel compounds.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Organization and bidirectional transcription of H2A, H2B and H4 histone genes in rice embryos.

Our current understanding of the evolution of the histone gene family suffers from a lack of information on plant histone genes. With a view to gathering some much needed information on these genes, we studied a rice genomic clone in pBR322 carrying H2A, H2B and H4 histone genes on a DNA fragment of 6.64 kilobases (kb). A restriction map of the insert was constructed and the organization of the three genes on this insert was determined. H2A and H2B histone genes were located at one end of the insert and H4 gene at the other with a 3.1 kb spacer in between. This cluster of three histone genes was found to be transcribed in a bidirectional fashion with H2A and H2B genes being encoded by one strand and the H4 gene by the other. These results indicate that plant histone gene organization differs from that of the sea urchin, but shows many similarities to the systems in other animals.

Genetic Linkage↗

Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice.

Insulin controls glucose homeostasis by regulating glucose use in peripheral tissues, and its own production and secretion in pancreatic beta cells. These responses are largely mediated downstream of the insulin receptor substrates, IRS-1 and IRS-2 (refs 4-8), through distinct signalling pathways. Although a number of effectors of these pathways have been identified, their roles in mediating glucose homeostasis are poorly defined. Here we show that mice deficient for S6 kinase 1, an effector of the phosphatidylinositide-3-OH kinase signalling pathway, are hypoinsulinaemic and glucose intolerant. Whereas insulin resistance is not observed in isolated muscle, such mice exhibit a sharp reduction in glucose-induced insulin secretion and in pancreatic insulin content. This is not due to a lesion in glucose sensing or insulin production, but to a reduction in pancreatic endocrine mass, which is accounted for by a selective decrease in beta-cell size. The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance.

Animals↗

Squamous cell carcinoma of the tongue among young Indian adults.

Oral cancer is one of the commonest cancers among males in India. This study was carried out to evaluate the demographics, risk profile, clinicopathologic features, and treatment outcome in young patients with squamous cell carcinoma (SCC) of the tongue. Patients under the age of 35 years with SCC of the tongue presenting between 1982 and 1996 were identified using institutions centralized electronic database. Demographic, clinical, and pathologic characteristics were abstracted from the case records. Survival was calculated by Kaplan-Meier method. One hundred and fifteen patients with histologically confirmed SCC of the tongue were analyzed. The mean age at presentation was 30.5 years with a 1.7:1 male to female ratio. Prior exposure to tobacco and alcohol was noted in 58 (50.5%) patients. At presentation, 70 (60.9%) were in stages III and IV, and 59 (51.3%) patients had regional lymph node involvement. The overall disease-free survival (DFS) at 3 and 5 years were 63% and 54.9%, respectively. A statistically significant difference in DFS was seen between patients with N(0) and N(1) disease compared to N(2) or N(3) disease. Various other factors like age, sex, habits, and stage of the disease were found to have no significant effect on DFS. Results of the present study suggest that contrary to the belief, the survival among young patients is almost similar to that in older patients.

Adult↗

Is concurrent chemotherapy and radiotherapy the new standard of care for locally advanced cervical cancer?

The results of five multi-institutional randomized controlled trials demonstrating a survival advantage for the concurrent administration of chemotherapy and radiotherapy in the management of cervix cancer represented the first major advance in the management of this malignancy in many years and prompted many practitioners to alter their pattern of practice. More recently, the results of the National Cancer Institute of Canada (NCIC) trial demonstrating no survival benefit when combined modality therapy is compared with optimally delivered radiotherapy, has led many to question the strength of the evidence supporting the adoption of combined modality therapy as the standard therapy for cervix cancer and in particular the magnitude of the benefit derived from the addition of chemotherapy to an optimally delivered radiotherapy regimen. This review paper will critically examine the evidence presented in the literature indicating a benefit for the use of combined modality therapy, discuss possible reasons why the conclusions of negative trials such as the NCIC study differ from those of the other studies and highlight those aspects of the use of combined modality therapy that require further evaluation.

Adult↗

Mechanisms of chemical carcinogenesis: recent advances.

The carcinogenetic risk assessment of veterinary drugs has to be envisaged as part of food toxicology. The authors review the recent discoveries which have proved significant for the toxicologist. Tumours arise from an inherited transformation of normal cells through genotoxic, perigenetic and epigenetic processes. Genotoxic mechanisms are best understood and have led to the development of short-term reference tests. The biochemistry of DNA alterations is being unravelled and permits quantitative estimation of carcinogenetic potencies. Work on the role of oncogenes is providing new clues to the understanding the mechanisms of chemical carcinogenesis. Perigenetic processes deal mainly with DNA repair systems and emphasize the complexity of human genome dynamics. Experimental findings about epigenetic mechanisms are still inconclusive as to their practical implications. Abnormal expression of HLA-antigens at the surface of neoplastic cells has been reported, but its significance is still unknown. In conclusion, the main source of progress in toxicology undoubtedly comes from molecular biology, but experimental results must be interpreted with caution if practical issues are to be derived from them.

Animals↗

Asthma and growth--cause for concern? Asthma & Growth in Tayside Children.

This project aimed to investigate the height and weight of children with asthma in the community. The Tayside Childhood Asthma Project examined medical records of 3143 children drawn from 12 general practices, for details of asthma morbidity and management. Concurrently, but independent from it, the Tayside Growth Study measured heights and weights of children aged 3-5, 5, 7, 9, 11 and 14 years. This paper reports on a cross-sectional analysis of 699 children who were known to be receiving some form of asthma medication during the school years 1990-91 and 1991-92 when a growth measurement was recorded. A standard deviation score (SDS) was calculated from height measurements for this cohort of children and from weight and body mass index (BMI = weight/height2) measurements for 559 of these children. The mean and standard deviation of these SDS values were calculated, and the distribution of the scores plotted. The results showed no difference in height, weight or BMI between the general population and the cohort receiving asthma medication. However, further analysis showed the distribution of height for children with severe asthma receiving high doses of inhaled corticosteroids (mean -0.38, SD 0.95) was significantly different from the general population (mean 0, SD 1). This group of children appeared to be shorter, by as much as 2 cm on average for a 5-year-old boy. In general, children receiving treatment for asthma within the community have a similar distribution of height and weight to normal children. Children receiving high-dose inhaled corticosteroids are shorter than their contemporaries, and deserve long-term follow-up.

Adolescent↗

An improved technique for allogeneic hip joint implantations.

A new technique which has been developed for the allogeneic hip-joint transplantation to enable minutely accurate processing of donor and recipient femoral head, neck, and hip-joints is dependent upon the manual skill of the surgeon. The donor and recipient parts had to be made congruent by free hand fitting. Even the most experienced surgeon cannot produce perfect form congruity of the whole contact surface between donor and recipient parts. The foregoing article presents new instruments and the techniques for 0.5 mm precision fit. An ideal fit of donor and recipient parts represents an important prerequisite for successful allogeneic joint implantations and accounts for improvement in previous results from such operations. Obviously, the cell-devitalized cold-conserved joints cannot produce optimum or permanent results, but can be implanted as an alternative to arthrosis in patients in vary young age groups. Further research on viable cartilage and bone in joint implantations await new advances in immunology and tissue typing.

Acetabulum↗

Modulation of calcium ion influx by the 1,4-dihydropyridines nifedipine and BAY K 8644.

We examined the effects of the new dihydropyridine calcium agonist BAY K 8644 on calcium influx and mechanical activity in rabbit aortic rings and compared them with those of the classical calcium antagonist nifedipine. The vasodilating effects of nifedipine and the vasoconstricting effects of BAY K 8644 can be explained by the calcium influx modulating activity of these two dihydropyridines. Only at the high concentration of 3 X 10(-6) mol/L BAY K 8644 is there a marked difference between increased calcium influx and reduced contraction.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

The effect of callus removal on dynamic plantar foot pressures in diabetic patients.

Clinical observation suggests that neuropathic foot ulceration frequently occurs beneath plantar callosities and in areas of high dynamic shear and vertical stress underneath the foot during walking. Seventeen diabetic patients had dynamic foot pressure measurements made before and after the removal of a total of 43 forefoot plantar callosities. Peak pressures (mean +/- SE) in the treated areas were reduced by 26% from 14.2 +/- 1.0 to 10.3 +/- 0.9 kg cm-2 (p less than 0.001), with reductions at 37 of the 43 sites and in all patients. Mean heel pressures were not significantly different (5.0 +/- 0.6 vs 4.9 +/- 0.6 kg cm-2). These results suggest that callus may act as a foreign body elevating plantar pressures and that a significant reduction in pressure is achieved by local chiropody treatment.

Analysis of Variance↗

Genome-wide scanning in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are multifactorial traits involving both environmental and genetic factors. In order to identify the IBD susceptibility genes, two groups of strategies have been developed. In the candidate gene approach, a specific hypothesis is tested by usually investigating the prevalence of specific alleles in groups of affected and control individuals with no familial relationship. Such association studies are powerful and straightforward. However, they are limited by possible recruitment biases and a multitesting problem due to the large number of possible candidate genes. Furthermore, they rely on the existence of a founder effect. In the genome scanning searches, no prior assumption is made on the susceptibility genes. The studies are based on cosegregation (or linkage) analyses performed on families with several affected members. Their drawbacks are the lack of statistical power and the low resolution of the localization. Nonetheless, using genome-wide screens, two IBD loci have been localized by several independent groups on chromosomes 12 and 16. Additional IBD loci have been proposed by individual groups on chromosomes 1, 3, 4, 7, 11, 15 and X. In order to gain wide acceptance, the latter localizations are to be confirmed by additional independent studies. Identification of IBD susceptibility genes would represent a key step in the understanding of the pathogenic mechanism of these diseases. However, in complex disorders, genes are only a part of the risk factors. Epidemiological studies looking for environmental factors are thus complementary of the genetic approach.

Chromosomes, Human, Pair 12↗