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J H Matthews

Publications and source records attributed to J H Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1986

A method for performing deoxyuridine suppression tests on microtitre plates.

A method of performing deoxyuridine suppression tests on bone marrow cells using microtitre plates is described. The geometric mean and 95% reference interval derived from 19 patients with normoblastic erythropoiesis and normal levels of serum B12 and folate were, respectively, 5.1 and 2.0-12.8%. In 70 deoxyuridine suppression tests on 60 patients, the correlation between the results from the conventional tube test and the plate method was good, r = 0.9, P less than 0.001, and replicate tests with both techniques showed equal degrees of precision. The microtitre plate method uses fewer cells and is easier to perform than the tube method: thus each test may be performed in triplicate, and additional investigations carried out on cells obtained from a single marrow aspiration. We conclude that the microtitre plate method of performing a deoxyuridine suppression test is useful for both diagnostic and research purposes.

Bone Marrow Cells↗
PubMed1985

Dynamic responses to intravenous urapidil and dihydralazine in normal subjects.

Hemodynamic responses after urapidil were compared with those after dihydralazine in placebo-controlled, double-blind studies after cumulative intravenous doses. We recorded heart rate, blood pressure, systolic time intervals corrected for heart rate (electromechanical systole and preejection period), electrical impedance cardiography [(dZ/dt)/RZ index and mean electrical thorax impedance], and M-mode echocardiogram (end-systolic and -diastolic diameters, end-systolic wall stress, fractional shortening, and cardiac output). Both drugs induced dose-dependent reductions in total peripheral resistance, which resulted in reduction in left ventricular end-systolic wall stress and increases in heart rate (limited at +10 bpm with urapidil), fractional shortening, cardiac output, and the (dZ/dt)/RZ index. With each drug, diastolic blood pressure fell by 5 mm Hg, the corrected preejection period shortened (dihydralazine greater than urapidil), the corrected electromechanical systole did not change, and mean electrical thorax impedance rose with urapidil. The spectrum of effects indicates that both drugs reduce left ventricular afterload, thereby increasing left ventricular pump performance. Urapidil also exerts some preload reduction.

Adult↗
PubMed1985

Importance of low serum vitamin B12 and red cell folate concentrations in elderly hospital inpatients.

To determine the functional importance of the low B12 and red cell folate concentrations repeatedly observed in the elderly 200 consecutive patients admitted to a geriatric unit were studied. Forty six of the patients had low serum concentrations of B12 (15), red cell folate (26), or both (five). Serum B12 and red cell folate concentrations correlated with mean cell volume, and serum B12 correlated with the neutrophil lobe count. Bone marrow deoxyuridine suppression was abnormal in 35% of the patients with low vitamin concentrations, but 55% of those with abnormal deoxyuridine suppression had morphologically normal bone marrow, and 73% had a normal mean cell volume. In patients with low vitamin values the deoxyuridine suppressed value correlated with the haemoglobin concentration and neutrophil lobe count. Thus synthesis of thymidylate was impaired by vitamin B12 or folate deficiency in at least 8% of newly admitted elderly patients, many of whom had normal blood counts despite the biochemical disturbance affecting haemopoiesis. A nutritionally depleted diet may have been responsible for many of the low vitamin values.

Aged↗
PubMed1985

In vitro receptor occupancy allows to establish equieffective doses of beta-blockers with different pharmacodynamic profiles in man. Investigations with propranolol and bufuralol.

The aim of the present study was to establish equieffective doses of propranolol (PROP) and bufuralol (BUF) in man. Both drugs compete for radioligand binding of 3H-CGP 12177 at beta-adrenoceptors of rat reticulocytes with Ki-values of 6.7 (PROP) and 19.6 (BUF) ng/plasma in the mean. In contrast to PROP, which is a pure antagonist, BUF shows partial agonism with an intrinsic activity around 5% (relative to isoprenaline) in vitro. After i.v. injection of cumulative doses of both drugs to 10 healthy volunteers, drug present in plasma occupies beta-adrenoceptors in vitro in a dose-dependent manner up to 80%. In man the full beta-adrenoceptor agonist isoprenaline (8 micrograms/min for 3 min) induces an increase in heart rate by 73%, an increase in stroke volume by 47%, a decrease in total peripheral resistance by 63% and a shortening of the preejection period by 70%. PROP exerts effects in man in the opposite direction of isoprenaline (at resting state), whereas BUF does not influence heart rate and stroke volume to a significant extent. Only the preejection period and total peripheral resistance are influenced in analogy to the isoprenaline effects. A direct comparison of the effects of PROP and BUF at 50% in vitro receptor occupancy by the respective plasma samples shows the clear-cut qualitative differences between the pharmacodynamics of both drugs in man as expected from the comparison of the full agonist isoprenaline and the antagonist propranolol. It is concluded that only on the basis of the respective receptor occupancy one may delineate pharmacodynamic differences of different drugs of the same class in man.

Adult↗
PubMed1985

Kinetic analysis of mechanisms regulating granulopoiesis in cultured human bone marrow.

In the past, in vitro perturbations of granulocytic progenitor cells have been measured by comparing the number of colonies that have grown to a threshold size in a given time. In our hands this method has proven to be both insensitive and unreliable. In this paper kinetic evidence is presented that the number of colonies, however defined, is subject to the influence of unpredictable independent variables which include the age distribution of the clonogenic cells, the proportion of them which are dormant, and the factors which promote their recruitment, their expansion into colonies and the rate at which colonies die. Results are improved by an early analysis of total clonal number (TC) as a measure of recruitment and mean clonal size (MCS) as a measure of clonal expansion rate.

Colony-Forming Units Assay↗
PubMed1985

The generation of colony stimulating activity by lectin stimulated human peripheral blood mononuclear leucocytes.

In order to clarify the role of T-lymphocytes and monocytes in the regulation of granulopoiesis, we have examined the production of colony stimulating activity by human peripheral blood mononuclear cells in response to phytohemagglutinin. T-cells prepared by adherence and sheep erythrocyte rosettes synthesized appreciable quantities of colony stimulating activity, but after further depletion using a monoclonal antibody against monocytes, this synthesis was much reduced, and DNA synthesis abolished. It was possible to restore DNA synthesis by adding back small numbers of monocytes, without restoring the production of colony stimulating activity. Similarly, depleting monocytes from unfractionated mononuclear leucocytes with monoclonal antibody caused a marked reduction in the amount of colony stimulating activity generated. In contrast, depleting T-cells from whole mononuclear cells, or from a sheep cell rosette negative fraction, had little effect on colony stimulating activity production. Mononuclear leucocytes were also depleted of helper and suppressor T-cell subsets. Colony stimulating activity production following these procedures was highly variable, and no clear pattern emerged. We postulate that monocytes are the major source of the colony stimulating activity measured by our assay. We have failed to establish a clear role for T-lymphocytes in either producing or regulating colony stimulating activity, although the difficulties inherent in depletion experiments do not allow such a role to be excluded.

Antibodies, Monoclonal↗
PubMed1984

Megaloblastic anaemia in vegetarian Asians.

Of 27 Asians with a megaloblastic bone marrow, 22 (81%) had nutritional deficiency of vitamin B12 (NMA), while five (19%) had true pernicious anaemia (PA). All the patients were Hindu vegetarians except for a single Muslim who had PA. Dietary intakes of calories, protein, iron, vitamin B12 and folate were below the recommended level in both groups. The PA group had lower levels of serum B12 and higher levels of serum folate than the NMA group. Despite low levels of red cell folate (RCF) in the NMA patients, the abnormality in deoxyuridine (dU) suppression was always corrected by vitamin B12. The dU suppressed value showed a significant inverse relationship to the RCF level. Nutritional deficiency of vitamin B12 is the most common cause of megaloblastic anaemia in Hindu vegetarians but the incidence of true PA is higher than previously thought and may approximate to that of the white population.

Adolescent↗
PubMed1984

Pulmonary disease due to Mycobacterium malmoense.

A case of pulmonary disease due to Mycobacterium malmoense was recently diagnosed in a 43-year-old man from Virginia. This organism was isolated from sputum and bronchial washings. This is the first case of documented human infection due to this organism in the United States

Adult↗
PubMed1984

Influence of dihydralazine induced afterload reduction on systolic time intervals and echocardiography in healthy subjects.

The influence of a pure afterload reduction on systolic time intervals and various echocardiographic indices was assessed in six healthy volunteers, who underwent a single blind placebo controlled trial of three regimens of intravenous dihydralazine (6.25, 12.5, and 25.0 mg). Subsequently autonomic blockade (propranolol and atropine) was used to eliminate the influence of the autonomic reflex action during dosage with dihydralazine 6.25 mg. Dihydralazine increased heart rate to an extent depending on dose, decreased diastolic blood pressure, end systolic diameter, and end systolic wall stress, and enhanced fractional shortening and cardiac output. Heart rate corrected pre-ejection period was shortened and left ventricular ejection time was prolonged, whereas electromechanical systole remained virtually unchanged. Autonomic blockade eliminated dihydralazine's effect on heart rate and cardiac output; blood pressure and systolic wall stress fell appreciably, whereas dihydralazine-induced changes in the systolic time intervals were virtually unaffected. Thus the present study indicates that regardless of the autonomic reflexes heart rate corrected pre-ejection period and left ventricular ejection time, but not electromechanical systole, are highly dependent on afterload, and this effect should be considered when systolic time intervals are evaluated.

Autonomic Nerve Block↗
PubMed1981

Homozygous G gamma delta beta thalassaemia.

This report describes the clinical and haematological findings in three siblings homozygous for G gamma delta beta thalassaemia in an Indian family. There was a mild to moderate anaemia and markedly abnormal red cell morphology. Haemoglobin analysis showed 100% Hb F, solely of the G gamma type, with a pancellular but uneven distribution. Considerable chain imbalance was detectable in globin synthesis studies. In contrast to five previously reported cases, these children were essentially asymptomatic and have never required transfusions.

Adolescent↗
PubMed1979

Beta thromboglobulin and glycosylated haemoglobin in diabetes mellitus.

No correlation has been demonstrated between the elevated levels of plasma beta-thromboglobulin and glycosylated haemoglobin found in a group of 97 diabetic patients. The abnormality in diabetic platelets which is reflected by beta-thromboglobulin levels may not therefore be a direct result of poor metabolic control. The highest levels of beta-thromboglobulin were found in those patients with a raised blood urea. Glycosylated haemoglobin levels correlated with prevailing blood glucose and with the type of therapy employed, and were highest in the insulin dependent diabetics, intermediate in those on tablets and lowest in those on diet alone.

Adolescent↗
PubMed1976

'Oblongata' crises in tabes dorsalis.

A patient in the pre-ataxic stage of tabes dorsalis suffered from gastric crises, but in addition had numerous episodes of apnoea and coma which in the older literature have been described as 'oblongata crises'--the presumption being that the crises are due to a brain stem disturbance.

Abdomen↗