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Biomedical subjects

W Martin

Publications and source records attributed to W Martin.

At least 235 records · Page 13Linked to original sources

Familial Parkinson's disease: possible role of environmental factors.

We report here six families with Parkinson's disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinson's disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system.

Adult↗

Gated thallium scintigraphy in patients with coronary artery disease: an improved planar imaging technique.

The use of thallium scanning in the assessment of myocardial perfusion is well established. However, myocardial contraction leads to significant blurring of standard static images. By using electrocardiographic gating and a high sensitivity collimator, multiple view gated scans can be acquired prior to thallium redistribution. Reporting of these images on cine loop display in 100 consecutive patients undergoing coronary arteriography and 14 volunteers results in improved visual assessment of regional myocardial perfusion (with reduced interobserver variability) and, in addition, yields useful and accurate information on left ventricular function. The combination of better assessment of perfusion and information on wall motion results in improved detection of patients with significant coronary disease with no loss of specificity when compared with static images. Predictive accuracy improves from 85% to 94% with gated imaging. Gated thallium scanning could be readily applied in most centres using thallium at no extra cost and with improved predictive accuracy in the non-invasive detection of significant coronary disease.

Coronary Disease↗

A comparison of intravenous elantan and frusemide in patients with chronic cardiac failure.

Opiates and loop diuretics are the mainstay of treatment of acute pulmonary oedema, but it is now recognized that immediate response to intravenous loop diuretics is acute vasoconstriction with impaired cardiac performance. It therefore seemed appropriate to compare the effects of intravenous isosorbide 5-mononitrate and frusemide on systemic and coronary haemodynamics in a group of patients with chronic cardiac failure at cardiac catheterization. Intra-arterial blood pressure was recorded from the ascending aorta, pulmonary capillary wedge pressure and cardiac output were measured using a Swan-Ganz thermodilution catheter. Coronary venous blood flow was measured using a thermodilution technique and A-V oxygen difference across the myocardium was obtained from simultaneous blood sampling in the aorta and coronary sinus. Absolute myocardial nutrient blood flow was measured using a 133Xe clearance technique. Frusemide in a dosage of 0.5 mg/kg given intravenously provoked acute vasoconstriction with falls in cardiac output and stroke volume. Pulmonary capillary wedge pressure was unchanged in the first 60 min after administration of frusemide. Isosorbide 5-mononitrate in a dosage of 15 mg intravenously, significantly reduced the pulmonary capillary wedge pressure within 5 min, and with the subsequent fall in systolic arterial blood pressure, cardiac output was maintained. These results suggest that intravenous isosorbide 5-mononitrate could well be of value in the immediate management of the patient with acute pulmonary oedema.

Blood Pressure↗

Calcium channel blocker and isosorbide 5-mononitrate in the management of chronic cardiac failure.

In the management of the patient with chronic cardiac failure, the combination of an arteriolar vasodilator and venodilator should be beneficial. 8 patients with NYHA grade III-IV chronic cardiac failure were studied following placebo, after 4 weeks' therapy with the arteriolar vasodilator felodipine, and with the combination of felodipine and oral isosorbide 5-mononitrate. Haemodynamic measurements were made at rest and during dynamic exercise at an individual, fixed, near maximal workload. Ejection fraction (EF) was obtained by gated radionuclide ventriculography. At rest, heart rate was unchanged 73 +/- 6 at control, 72 +/- 4 with felodipine and 74 +/- 4 beats/min with the addition of isosorbide 5-mononitrate. Mean arterial pressure fell from 98 +/- 5 to 84 +/- 4 (p less than 0.02) and 84 +/- 3 mm Hg (p less than 0.02) with nitrate. Cardiac index increased from 2.2 +/- 0.1 to 2.5 +/- 0.2 litres/min/m2 with felodipine and further to 2.6 +/- 0.2 litres/min/m2 (p less than 0.02) with nitrate. Exercise tachycardia and mean arterial pressure were not significantly affected by therapy. Cardiac index increased on exercise from 4.4 +/- 0.3 to 4.8 +/- 0.3 litres/min/m2 with felodipine and 4.9 +/- 0.3 litres/min/m2 (p less than 0.05) with the addition of nitrate. Stroke volume index increased from 35.4 +/- 4 to 40.8 +/- 4 beats/min/m2 and further to 41.0 +/- 4 beats/min/m2 (p less than 0.05) and EF from 14 +/- 3 to 18 +/- 3% with nitrate. In conclusion, in patients with chronic cardiac failure, treatment with a calcium channel blocker produced sustained haemodynamic improvement, particularly on exercise, and combination with nitrate produced further benefit.

Chronic Disease↗

Lack of direct coronary vascular effects of Escherichia coli endotoxin in dogs.

This study explored the hypothesis that coronary vascular injury and dysfunction result from intracoronary administration of Escherichia coli endotoxin (0.025 to 0.025 to 0.4 mg/kg) in dogs. Peak hyperemic coronary flow following a 15-sec period of stopped flow and the maximum flow in response to adenosine were used to estimate coronary vascular reserve. The wet-to-dry ratio of myocardial tissue was used to estimate extravascular water content as an indicator of vascular leak due to endothelial injury. Intracoronary saline was used as a control. Peak reactive hyperemia and maximum flow at constant coronary pressure were not different in the animals receiving intracoronary endotoxin (n = 6) and the animals receiving saline (n = 5) during 4 hr following treatment. In addition, wet-to-dry ratios were similar in these two groups. These data fail to support the hypothesis that endotoxin, per se, produces coronary vascular injury of sufficient magnitude to produce myocardial dysfunction.

Animals↗

On the prevention of viral transmitted infections in plasma products.

A short review is given on screening tests and regulatory requirements of viral inactivation for plasma products in the Federal Republic of Germany. Guidelines for blood group determination and blood transfusion and guidelines for plasmapheresis contain the particular directions for blood and plasma donations. The licensing of drugs is regulated by the Drugs Act of 1976. To prevent virus infections the following screening tests are advised: HBs antigen, ALT, and LAV/HTLV-III antibody determination.

Antibodies, Viral↗

Gated blood-pool imaging in mechanical left ventricular assistance following myocardial infarction in dogs.

Gated blood-pool scanning has been used to assess the physiological effects of left ventricular assistance following acute myocardial infarction in dogs. Both left atrial-aortic and left ventricular-aortic bypass improve survival up to 6 hr after acute coronary occlusion, compared with control animals. The initial measurement of left ventricular ejection fraction (LVEF) following occlusion appears predictive of the need for ventricular assistance. Assisted animals maintain their level of left ventricular function until 6 hr in contrast with control animals, whose function steadily deteriorates over this period. There was no demonstrable recovery in regional ventricular function in the infarcted territory over this period, and in all assisted animals the right ventricular function deteriorated more rapidly than in controls. These results demonstrate the efficacy of left ventricular assistance in terms of improved survival and preserved left ventricular function. Gated blood-pool ventriculography has also been shown to be a suitable technique for monitoring the physiological changes during left ventricular assistance.

Animals↗

Prokaryotic features of a nucleus-encoded enzyme. cDNA sequences for chloroplast and cytosolic glyceraldehyde-3-phosphate dehydrogenases from mustard (Sinapis alba).

Two cDNA clones, encoding cytosolic and chloroplast glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from mustard (Sinapis alba), have been identified and sequenced. Comparison of the deduced amino acid sequences with one another and with the GAPDH sequences from animals, yeast and bacteria demonstrates that nucleus-encoded subunit A of chloroplast GAPDH is distinct from its cytosolic counterpart and the other eukaryotic sequences and relatively similar to the GAPDHs of thermophilic bacteria. These results are compatible with the hypothesis that the nuclear gene for subunit A of chloroplast GAPDH is of prokaryotic origin. They are in puzzling contrast with a previous publication demonstrating that Escherichia coli GAPDH is relatively similar to the eukaryotic enzymes [Eur. J. Biochem. 150, 61-66 (1985)].

Amino Acid Sequence↗

[Ventricular arrhythmias in cor pulmonale. The effect of oxygen treatment].

Long-term ECG monitoring was carried out on 36 patients with chronic obstructive airway disease and cor pulmonale. Ventricular extrasystoles were detectable in all patients with greater than 30/h occurring in 13. Multifocal ventricular extrasystoles were seen in 29 patients, couplets in 16, runs in 6 and early (R-on-T) extrasystoles in 8 patients. When the ventricular extrasystoles exceeded 30 per hour the average oxygen partial pressure (paO2), determined in capillary blood, was 59.5 mm Hg, whereas it was higher, 66.4 mm Hg (P less than 0.0125), when there were less than or equal to 30/h. Oxygen (2 l/min) was administered to 13 patients between 20.00 h and 08.00 h and then room-air the following night via a nasal tube. After the administration of oxygen mean paO2 was 72.3 mm Hg and after breathing room-air 62.6 mm Hg (P less than 0.01). During the administration of oxygen, extrasystoles appeared less frequently than after breathing room-air (927 vs 1211; P less than 0.05). These results show that ventricular extrasystoles appear more often with decreasing paO2 and that oxygen therapy can reduce their frequency.

Aged↗

Atriopeptin II-induced relaxation of rabbit aorta is potentiated by M&B 22,948 but not blocked by haemoglobin.

We examined the effects of haemoglobin (which inhibits the vascular responses to stimulation of soluble guanylate cyclase) and of M&B 22,948 (which selectively inhibits cyclic GMP phosphodiesterase) on the relaxation induced in rabbit aorta by the atrial natriuretic peptide, atriopeptin II (which stimulates particulate guanylate cyclase). Pretreatment with M&B 22,948 (100 microM) produced a 2.3 fold potentiation of atriopeptin II-induced relaxation of endothelium-denuded rings of rabbit aorta. Pretreatment with haemoglobin (10 microM) had no effect on the relaxation or the 10.9 fold increase in cyclic GMP content induced by atriopeptin II in endothelium-denuded rings of rabbit aorta. The potentiation by M&B 22,948 suggests a causal role for cyclic GMP in mediating atriopeptin II-induced vasodilatation of rabbit aorta. The inability of haemoglobin to block the atriopeptin II-induced rise in cyclic GMP suggests that it does not block stimulation of particulate guanylate cyclase. Thus, it is unlikely that a ferrous haem-containing receptor site is involved in the activation of the particulate form of guanylate cyclase as it is with soluble guanylate cyclase.

Animals↗

The mechanisms by which haemoglobin inhibits the relaxation of rabbit aorta induced by nitrovasodilators, nitric oxide, or bovine retractor penis inhibitory factor.

The mechanisms by which haemoglobin and methaemoglobin inhibit the vasodilator actions of glyceryl trinitrate, sodium azide, nitric oxide, and the bovine retractor penis inhibitory factor (IF) were studied on rabbit endothelium-denuded aortic rings. Methaemoglobin was less effective than haemoglobin against each vasodilator, it was more effective at inhibiting the relaxation to azide than that to glyceryl trinitrate. Glyceryl trinitrate was neither bound nor inactivated when passed through columns of haemoglobin-agarose or methaemoglobin-agarose. Azide was reversibly bound but less by haemoglobin-agarose than by methaemoglobin-agarose. Inhibition of the vasodilator actions of glyceryl trinitrate is not attributable therefore to a direct interaction with the haemoproteins, although a small part of the inhibition of azide-induced relaxation by methaemoglobin is likely to be due to a direct interaction. Columns of haemoglobin-agarose were more effective than columns of methaemoglobin-agarose in removing nitric oxide from solution. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by nitrovasodilators may therefore reflect the greater ability of haemoglobin to bind nitric oxide which is the active principle of the nitrovasodilators. Neither the acid-activated nor the inactive forms of IF were bound or inactivated when passed through columns of methaemoglobin-agarose. Neither form of IF was retained on passage through columns of haemoglobin-agarose, but the resulting activity in the eluates was less than control, was unstable and, unlike the original activity, decayed rapidly on ice. The greater ability of haemoglobin, compared to methaemoglobin, to inhibit vasodilatation induced by IF might therefore reflect the greater ability of haemoglobin to interact with this vasodilator and inactivate it.

Animals↗

Action of citrinin on bacterial chromosomal and plasmid DNA in vivo and in vitro.

Citrinin, a mycotoxin of Penicillium citrinum and other species of the genera Penicillium and Aspergillus, caused the following effects at different concentrations in Escherichia coli. In vivo at 100 micrograms/ml single-strand breaks were caused in the chromosomal DNA. In the presence of 100 micrograms/ml, UV (254 nm)-induced DNA damage was repaired in the bacterial cells without need for a complete growth medium. At 300 micrograms/ml lambda ts prophage was induced in a lysogenic E. coli strain. In an E. coli strain carrying a F' lac plasmid, 4.7% of the cells displayed the Lac- phenotype after treatment with 200 micrograms of citrinin per ml, suggesting elimination of the F' factor. In vitro, DNA repair synthesis was observed at 5 micrograms of citrinin per ml in permeabilized cells, and replicative DNA synthesis was inhibited at 200 micrograms/ml. In these systems synthesis of stable RNAs was slightly diminished at 300 micrograms/ml, and protein synthesis was not affected at concentrations up to 450 micrograms/ml. Lambda and ColE1 plasmid DNA were cleaved in vitro when small amounts of copper ions were present. This DNA-attacking activity was prevented by NADPH, catalase, and superoxide dismutase and by higher concentrations of hydroxyl radical scavengers, suggesting the involvement of free radicals in the mechanism of action of citrinin on DNA.

Bacteriocin Plasmids↗

Phosphodiesterase inhibitors induce endothelium-dependent relaxation of rat and rabbit aorta by potentiating the effects of spontaneously released endothelium-derived relaxing factor.

The selective cyclic GMP phosphodiesterase inhibitor M&B 22948 and the less selective phosphodiesterase inhibitors papaverine and isobutylmethylxanthine (IBMX) each induced a component of relaxation of rat aortic rings that was endothelium-dependent. The most selective agent at inducing endothelium-dependent relaxation was M&B 22948, which caused little relaxation of endothelium-denuded rings at concentrations that produced almost complete relaxation of endothelium-containing rings. Although endothelium-dependent components of relaxation induced by papaverine and IBMX were clearly present, they were less well separated from the endothelium-independent components of relaxation. In the aorta of the rabbit, M&B 22948 and papaverine were less affective at inducing an endothelium-dependent component of relaxation than in the aorta of the rat, and IBMX produced no discernible endothelium-dependent component. The endothelium-dependent components of relaxation induced by M&B 22948, papaverine and IBMX on rat and rabbit aorta were probably dependent on endothelium-derived relaxing factor (EDRF), because they were associated with concomitant endothelium-dependent rises in cyclic GMP, and these components of relaxation as well as the rises in cyclic GMP were completely blocked by the EDRF-blocking agent hemoglobin. The action of hemoglobin was entirely specific, as none of the endothelium-independent components of relaxation induced by any of the phosphodiesterase inhibitors was affected by this hemoprotein. It is likely that the phosphodiesterase inhibitors induce their endothelium-dependent components of relaxation by inhibiting the hydrolysis of cyclic GMP formed in response to EDRF released spontaneously from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Dorsal dislocation of the radiocarpal joint with associated dorsal perilunar dislocation.

Radiocarpal dislocations are uncommon injuries that occur even more rarely in association with intercarpal dislocations. All the reported examples of such intercarpal dislocations are volar. We here describe a patient with a unique dorsal radiocarpal dislocation with an additional dorsal perilunar dislocation. Radiographic identification of this injury has important implications for its successful treatment.

Adult↗

Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor.

Removal of endothelial cells on rings of rat aorta increased the sensitivity to the selective alpha-1 adrenoceptor agonist phenylephrine, to the nonselective alpha adrenoceptor agonist norepinephrine and to the selective alpha-2 adrenoceptor agonist clonidine. In the case of the first two, which are strong agonists for the alpha-1 adrenoceptor-mediating contraction, removal of endothelium increased sensitivity 4- and 6-fold at the EC30 level, but produced little or no increase in maximum. In the case of clonidine, a partial agonist for the alpha-1 adrenoceptor, which gave only about 15% of the maximum given by phenylephrine on endothelium-containing rings, removal of the endothelium not only shifted the curve to the left but also increased the maximum to about 50% of that given by phenylephrine. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium-derived relaxing factor (EDRF), as hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent depression was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in precontracted rings even when its contractile action was blocked by the alpha-1 adrenoceptor antagonist prazosin. Further evidence against alpha adrenoceptor agents stimulating release of EDRF was that neither phenylephrine nor clonidine induced a rise in cyclic GMP in aortic rings, whereas acetylcholine, which does release EDRF, caused a large rise in cyclic GMP content. The possibility that the muscle cells of intact rat aortic rings were under the tonic influence of released EDRF was supported by the finding that, in the absence of any contractile agent, hemoglobin induced a fall in the basal level of cyclic GMP in endothelium-containing rings. Also consistent with EDRF being released spontaneously was the finding that contraction induced by 5-hydroxytryptamine, like that by alpha-adrenergic agonists, was also depressed in endothelium-containing rings of aorta. When the efficacy of phenylephrine as an alpha-1 agonist was reduced to about the initial efficacy of clonidine by irreversible inactivation of a very large fraction of alpha-1 adrenoceptors of the smooth muscle cells by pretreatment with dibenamine, the concentration-contraction curves for phenylephrine for both endothelium-containing rings and for endothelium-denuded rings now became very similar to the corresponding curves obtained for clonidine before receptor inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Gated xenon scans for right ventricular function.

The complex geometry of the right ventricle makes the use of radionuclides an attractive method for assessing right ventricular function. The use of the gated 133Xe technique for this purpose offers several advantages. A short i.v. infusion over 20 sec of 133Xe permits scans to be obtained, gated to the electrocardiogram at rest and during maximal exercise using a standard gamma camera. The method is both reproducible (3.5%) and repeatable (2.8%), and because of the short half-life within the patient with most of the radioisotope being excreted by the lungs, scans may be repeated within a few minutes and the radiation dose to the patient is small. Right ventricular ejection fraction obtained from gated xenon scans is shown to correlate well with measurements obtained from both standard gated technetium scans and first-pass studies.

Female↗