Search PubMed⌕ Search

Biomedical subjects

R G Williams

Publications and source records attributed to R G Williams.

At least 145 records · Page 8Linked to original sources
PubMed1983

Temperature-induced changes in dissociation constants (KA) of agonists at cardiac beta-adrenoceptors determined by use of the irreversible antagonist Ro 03-7894.

The positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 38 degrees and 30 degrees C. At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10(-5)M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10(-4)M) as inhibitors of extraneuronal uptake and catechol-O-methyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (greater than 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible beta-adrenoceptor antagonism. Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope-1)/intercept). KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 38 degrees and 30 degrees C and indicates that the beta-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. The KA values of both agonists were, however, consistently and significantly lower at 30 degrees than at 38 degrees C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the B-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1982

Responses mediated via beta 1, but not beta 2-adrenoceptors, exhibit hypothermia-induced supersensitivity.

The beta-adrenoceptor-mediated responses of various isolated tissues from the guinea-pig were examined at bath temperatures of 38 and 30 degrees C. The positive inotropic responses to orciprenaline of paced left atria and papillary muscles were potentiated at the lower bath temperature, as indicated by a significant shift of the dose-response curve to the left. A similar hypothermia-induced supersensitivity was observed for the positive chronotropic response of right atria. The beta-adrenoceptor-mediated inhibition of coaxially stimulated ileum in response to orciprenaline also exhibited supersensitivity at 30 degrees C. In contrast, the relaxation of lung strips was not altered at the lower bath temperature. The relaxant responses of potassium-contracted uterine strips from untreated guinea-pigs or progesterone-dominated guinea-pigs and rats also failed to reveal any hypothermia-induced supersensitivity. The responses of lung and uterine strips are mediated via beta-adrenoceptors of the beta 2-type, whereas they are of the beta 1-type in the cardiac preparations and ileum. Therefore, these results suggest that hypothermia-induced supersensitivity occurs only at the beta 1-adrenoceptors, indicating a fundamental temperature-dependent difference between the two receptor types.

Animals↗
PubMed1982

Differential distribution in rat basal ganglia of Met-enkephalin- and Met-enkephalin Arg6 Phe7-like peptides revealed by immunohistochemistry.

Antisera to Met-enkephalin and its heptapeptide variant Met-enkephalin Arg6Phe7 were used in immunohistochemistry to study distribution of immunoreactive material in rat basal ganglia. In the pallidum, the Met-enkephalin antiserum, but not the Met-enkephalin Arg6Phe7 antiserum, revealed abundant nerve terminals, whereas in the caudate-putamen the heptapeptide antiserum demonstrated numerous immunoreactive cell bodies that were not shown by the Met-enkephalin antiserum. The differential distribution of immunoreactivity is compatible with distinct physiological roles for the two peptides in basal ganglia.

Animals↗
PubMed1982

Capsaicin depletes CCK-like immunoreactivity detected by immunohistochemistry, but not that measured by radioimmunoassay in rat dorsal spinal cord.

In rats treated neonatally with capsaicin there were significant reductions in substance P measured by radioimmunoassay in dorsal spinal cord, spinal ganglia, and coeliac ganglia, but concentrations of cholecystokinin octapeptide (CCK8) measured by radioimmunoassay were not decreased. However, immunohistochemical studies using antisera to both substance P and CCK8, respectively, demonstrated decreased immunoreactive material in the dorsal horn of the spinal cord. The nature of the material localized by CCK8 antiserum in immunohistochemistry remains to be resolved.

Animals↗
PubMed1982

Conotruncal malformations: diagnosis in infancy using subxiphoid 2-dimensional echocardiography.

Subxiphoid 2-dimensional echocardiography was performed and interpreted before the first cardiac catheterization of 109 of 113 infants less than 1 year of age with conotruncal malformations, situs solitus of the atria, and d-ventricular loop. The 4 remaining infants could not be examined using this technique for technical reasons. In 104 of 109 patients successfully examined a correct diagnosis was obtained with the use of subxiphoid 2-dimensional echocardiography. All patients with d-transposition of the great arteries had a correct diagnosis, and in 10 of 11 patients various types of double-outlet right ventricle were recognized by direct visualization of ventriculoarterial connection. Tetralogy of Fallot was correctly diagnosed in 34 of 36 patients and tetralogy of Fallot and pulmonary atresia were correctly diagnosed in 8 of 9 patients, on the basis of the position of the infundibular septum and presence or absence of continuity between the main pulmonary artery and the right ventricular. Five of 6 patients with truncus arteriosus communis were correctly diagnosed by demonstrating a connection between the pulmonary arteries and the ascending portion of the single large semilunar root. Subxiphoid 2-dimensional echocardiography proved to be a sensitive and specific technique for diagnosing conotruncal malformations in infancy.

Cardiac Catheterization↗
PubMed1982

Early assessment of hemodynamic status after repair of tetralogy of Fallot: a comparison of 24 hour (intensive care unit) and 1 year postoperative data in 98 patients.

Hemodynamic data obtained in the intensive care unit, immediately after repair of tetralogy of Fallot, were compared with measurements obtained at 1 year postoperative catheterization in 98 infants and children. Eight of 12 patients who had pulmonary artery oxygen saturation of 80% or greater in the intensive care unit had a pulmonary to systemic flow ratio greater than 1.5 at catheterization; all 79 patients who had a pulmonary artery oxygen saturation of ess than 80% in the intensive care unit had a pulmonary to systemic flow ratio of 1.5 or less at catheterization. Five of six patients who had a right ventricular outflow tract pressure gradient greater than 40 mm Hg in the intensive care unit had a gradient greater than 40 mm Hg at catheterization; 7 of 61 patients who had a right ventricular outflow tract gradient of 40 mm Hg or less in the intensive care unit had a gradient greater than 40 mm Hg at catheterization. The addition of measurements of right ventricular pressure and the right ventricular to systemic arterial pressure ratio in the intensive care unit did not improve sensitivity in identifying patients with a right ventricular outflow tract gradient greater than 40 mm Hg at catheterization. Intensive care unit measurement of pulmonary artery oxygen saturation is valuable for determining the presence or absence of a significant left to right shunt after repair of tetralogy of Fallot and should be considered an adjunct to patient management. Intensive care unit measurement of the right ventricular outflow tract gradient identifies patients with a significant right ventricular outflow tract gradient at catheterization but is not highly sensitive.

Blood Pressure↗
PubMed1982

A comparative trial of Mefloquine and Fansidar in the treatment of falciparum malaria: failure of Fansidar.

Falciparum malaria in 104 Thai patients was treated with either Mefloquine or Fansidar and patients were examined for parasitaemia for the next 28 days. All but one of the 40 patients treated with Mefloquine were cured, but the cure rates for Fansidar were only 9 . 1% for the two-tablet regimen and 19 . 4% for the three-tablet regimen. Most failures were classified as RII. Serum sulpha levels indicated that the Fansidar was being absorbed. Immediate steps should be taken to eliminate this focus of resistance and to protect against further resistance to Fansidar by using it in combination with another effective anti-malarial and by vigorous vector control measures.

Antimalarials↗
PubMed1982

Medical teachers' perspectives on development and use of objectives.

Experienced medical teachers were interviewed regarding creation and use of objectives for instruction. This paper summarizes reported advantages and disadvantages of objectives, describes reported changes in strategy with experience, and provides advice on the creation and use of objectives. Medical teachers agree that the process of writing objectives leads to clarification of intuitively held teaching goals and thus leads to better teaching and testing decisions. To achieve this benefit, an instructor must invest considerable time, effort and creativity in the process. The path of least resistance in writing objectives often leads to goals which serve no useful function and may be harmful to the teaching-learning process.

Education, Medical↗
PubMed1981

Congestive heart failure due to adriamycin cardiotoxicity: its natural history in children.

The congestive heart failure (CHF) associated with Adriamycin cardiotoxicity is frequently fatal. To investigate the course of Adriamycin-induced congestive heart failure, all Adriamycin-treated children who developed congestive heart failure at the Children's Hospital Medical Center and Sidney Farber Cancer Institute were studied. Criteria for Adriamycin-induced congestive heart failure included clinical evidence of left ventricular (LV) failure and echocardiographic evidence of abnormal left ventricular function. Fifteen children fulfilled these criteria. Eleven patients received between 400 and 500 mg/m2 of Adriamycin; four patients received cumulative doses over 500 mg/m2. Twelve of 15 (80%) children survived their acute episode of congestive heart failure. At follow-up, three patients had normalized their echocardiographic parameters of left ventricular function, three had died of their malignancies with compensated cardiac function until death, and six were clinically asymptomatic despite persistence of abnormal LV function on echocardiogram. Only three patients died of Adriamycin cardiomyopathy. In children treated with aggressive medical therapy, congestive heart failure secondary to Adriamycin cardiotoxicity may be reversible in certain cases.

Adolescent↗
PubMed1981

Vertebrate brain-gut peptides related to FMRFamide and Met-enkephalin Arg6Phe7.

Many mammalian brain-gut peptides are known to be represented in invertebrate nervous systems; we have now examined the possibility that an invertebrate neuropeptide occurs in vertebrates. Antisera were raised in rabbits to the molluscan neuropeptide. Phe-Met-Arg-Phe-NH2 (FMRFamide). The antiserum used for radioimmunoassay and immunocytochemistry is highly specific for the C-terminus of the tetrapeptide. In radioimmunoassays of tissue extracts of brain, gut and pancreas of various vertebrates (chicken, frog, dog, rat) concentrations of immunoreactive material up to about 200 pmol/g have been recorded. The immunoreactive material in chicken pancreas behaves on gel filtration and ion exchange chromatography as a molecule that is larger and less basic peptide that FMRFamide. Immunocytochemical studies have demonstrated an endocrine cell origin for FMRFamide-like material in chicken pancreas, and in dog ileum. In brain, FMRFamide can be localised to nerve cell bodies (frog) and nerve fibres (frog and rat). Synthetic FMRFamide has been shown to have excitatory actions on brain stem neurons in the rat. It is suggested that neurons in the rat central nervous system have receptors for FMRFamide that normally bind endogenous material with FMRFamide immunoreactivity.

Animals↗
PubMed1981

The early diagnosis of carcinoma of the mouth.

A survey of all known cases of carcinoma of the mouth in a population of half a million shows that late diagnosis in the majority of cases is inevitable. With this neoplasm symptoms are minimal during the early stages and there is no correlation between the duration of symptoms and the stage of the tumour when first diagnosed. There was no evidence of undue delay by the patient or the medical (or dental) practitioner or by the hospital. Consequently an improvement in results in this disease can only be achieved by more effective treatment of the advanced lesion.

Adult↗