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G Thomas

Publications and source records attributed to G Thomas.

967 records · Page 54Linked to original sources
PubMedDate not supplied

Calcium channel modulation: ability to inhibit or promote calcium influx resides in the same dihydropyridine molecule.

BAY K 8644, a dihydropyridine of the nifedipine type, was shown to increase coronary resistance and to enhance myocardial contractility (Schramm et al., Nature 1983;303:535-7), in contrast to the well-known vasodilating and negative inotropic effects of the "classical" calcium channel blockers. In the isolated perfused guinea pig heart at high concentrations (greater than 3 microM), however, the coronary constricting and positive inotropic effects of BAY K 8644 progressively reverse until the drug has a negative inotropic effect and decreases coronary resistance, thus mimicking the effects of the "classical" calcium antagonists. On the other hand, in the same experimental model, calcium antagonists like nifedipine, nitrendipine, and nicardipine are shown to exert a small but definite positive inotropic effect at low concentrations, indicating a calcium agonistic action at those concentrations. To explain the pharmacological effects of BAY K 8644 and the calcium channel blockers of the dihydropyridine type, a model is proposed that suggests the existence of two dihydropyridine binding sites per channel. According to this model, it depends on the chemical structure of the respective dihydropyridine whether, after occupation of the first site, which increases the calcium influx through the channel, the occupation of the second site is unimpaired, turning the channel to one with low calcium permeability; or whether occupation of the second site is hindered, leaving the channel in the high conductance state.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

The development of a valveless cardiac assist device attached to the ventricular apex.

Konstantinov et al, in October, 1991, published a novel way to bridge a patient for heart transplantation. They proposed to cut off both ventricles high under the atrioventricular groove, leaving the atria, aorta, and pulmonary artery and their valves intact and to attach pneumatically driven, valveless pulsating pouches to assist the heart until a donor could be found. The removal of the ventricles just below the atrioventricular groove is called the "high cut"; it, however, destroys the chordae tendineae rendering the mitral and tricuspid valves insufficient. These have to be replaced by tissue inflow valves. We chose to cut off the ventricles at a lower level (the "low cut") to leave the papillary muscles on both sides intact, thereby saving the integrity of the mitral and tricuspid valves. Pulsating pouches were made to fit the heart at this lower level. They can be easily connected to the remaining heart after a specially disigned cuff has been sutured over the ventricular stumps. The pouches were pumped during the systole of the natural heart, but the myocardium may have to be electrically stimulated during systole to prevent undue distension. If the turgor is too weak to prevent distension, a sleeve over the ventricles is provided. To find the best location for these pouches, human cadaver implantations were done and the pre peritoneal cavity was found to be the most suitable. In vitro testing to determine how much flow could be pumped was done by attaching the pouches to fresh pig hearts and connecting them to a double sided mock circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗
PubMedDate not supplied

Multi-facial anomalies in mandibulofacial dysostosis. A report of three cases.

Mandibulofacial dysostosis is readily recognized on the basis of a characteristic facial appearance caused by hard and soft tissue abnormalities of the face, including malformations of the ear. Generally, the abnormality is symmetrical. The psychological and social stigma associated with severe facial deformity makes this syndrome one of the most challenging reconstructive problems presented to the craniomaxillofacial surgeon.

Abnormalities, Multiple↗
PubMedDate not supplied

[Analysis of genetic disorders of cancer of the rectum: differences in relation to cancer of the colon].

AIMS AND METHODS: We studied the mechanisms of colon and rectal carcinogenesis by analysing in a series of 83 rectal tumors the prevalence of the two tumor types characteristic of colon cancer, i.e., the LOH+ type, defined by p53 and APC mutations (studied by DGGE and protein truncation assay), and the RER+ type, which is characterized by the instability of some mononucleotide repeat microsatellites (Bat 25 and Bat 26). Additionally, we analyzed the occurrence of Ki-Ras mutations (direct sequencing). RESULTS: Only one tumor turned out to be RER+. Moreover, in 59% of the tumor cases mutations were found in p53, essentially affecting codon 175. The APC and Ki-Ras genes were found to be mutated in 40 and 26% of the rectal tumors, respectively. In 18 tumors (21%) none of the genes studied were mutated. CONCLUSIONS: The RER+ phenotype is rare among rectal tumors, which are essentially LOH+. In these LOH+ tumors the p53 gene is more frequently mutated than in colorectal tumors with the same phenotype. Mutations in the APC and Ki-Ras genes, on the other hand, are less frequent in rectal tumors. Tumors with the RER- and LOH- phenotype may develop as a result of a third carcinogenesis model which must be defined.

Aged↗