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Biomedical subjects

R G Murray

Publications and source records attributed to R G Murray.

At least 73 records · Page 4Linked to original sources

Felodipine in patients with chronic heart failure: discrepant haemodynamic and clinical effects.

Previous open studies have suggested that felodipine, a selective calcium antagonist and vasodilator, may be useful in the treatment of heart failure. A double blind placebo controlled crossover trial was therefore conducted to investigate the clinical and haemodynamic effects of felodipine in 15 patients with chronic ischaemic heart failure in New York Heart Association symptom class III. Felodipine significantly increased resting and exercise (25W bicycle ergometry) cardiac output without producing concomitant changes in resting or exercise heart rate or right and left ventricular filling pressures. Felodipine did not significantly improve symptom scores or exercise capacity in the group as a whole. It also resulted in significant fluid retention as shown by a rise in ankle circumference, body weight, and a fall in haematocrit. Further research is required to elucidate the mechanism that is responsible for the discrepancy between the haemodynamic and clinical effects of felodipine in patients with moderately severe heart failure.

Aged↗

Urease activity related to the growth and differentiation of swarmer cells of Proteus mirabilis.

Urease activity was measured using whole cells of both long (swarming) and short (nonswarming) populations of Proteus mirabilis from casein hydrolysate agar (CHA) and broth (CHB) cultures, and from brain heart infusion broth (BHIB) cultures. Urease is a constitutive enzyme for both long and short cells, but its activity was tremendously increased when urea was incorporated into the media. Urease production was also affected by culture age and media used. Before exponential phase, urease activity was very low, and it increased to its highest point after about 4 h in BHIB and 8 h in both CHA and CHB cultures at 37 degrees C. Long cells had higher urease activity than did short cells when grown on CHA, and was also expressed by two different strains cultured in BHIB. Strain PM23, in BHIB, was able to form long cells (swarming cells) to a maximum proportion after about 4 h, but strain IM47 could not differentiate in any of the liquid media. The former had more urease when swarming differentiation was initiated. PM23 grew relatively faster than IM47 when the former began to differentiate, but this fast growth could not be observed when nutrient broth or minimal medium was used. These observations suggest that long or swarming cells are "faster growing" rather than "nongrowing bacteria".

Kinetics↗

Minicell formation by Campylobacter jejuni.

Campylobacter jejuni sheds its flagella and varying proportions of the poles of the cell late in the growth cycle, resulting in the production of very small flagellated structures 0.1 to 0.3 microM in diameter. Electron microscopy revealed that these structures were minicells possessing outer membrane, cytoplasmic membrane, flagellar basal complex, and polar membrane; nucleoplasms were not seen. The initial event in the formation of these minicells involved a constriction of the cytoplasmic membrane, segregating the polar regions of the cell. The peptidoglycan layer of the cell wall was not visible, but was presumed to lyse at the separation site of minicell formation, and to reform or remain intact along the main length of the cell because the rods did not spheroplast. Finally, rupture and resealing of the outer membrane component of the wall resulted in the release of fully enclosed minicells and nonflagellated rods.

Campylobacter fetus↗

Myocardial salvage following elective angioplasty for total coronary occlusion.

A 65-year-old man with unstable angina had a critical left anterior descending coronary artery stenosis which progressed to total occlusion, without evidence of acute myocardial infarction. Thallium imaging revealed defects in the distribution of the left anterior descending coronary artery on exercise and redistribution, 4 h later. 99mTc radionuclide angiography showed a fall in left ventricular ejection fraction on exercise, and contrast cineangiography showed an extensive area of akinesia. Percutaneous transluminal coronary angioplasty was successful without any complications. Repeat radionuclide studies demonstrated improvement of both myocardial perfusion and function. Angiography at 1 year showed normal left ventricular contraction and no evidence of recurrent stenosis. The patient is free of angina, on no medication 2 years after angioplasty. This case illustrates the feasibility of myocardial salvage by elective coronary angioplasty in patients with unstable angina total coronary occlusion.

Aged↗

Prognostic investigations after myocardial infarction: a comparison of radionuclide angiography and 201Tl scintigraphy.

The ability of pre-discharge thallium Tl201 scintigraphy and radionuclide angiography (RNA) to predict subsequent cardiac events was investigated in 46 apparently low-risk survivors of a first acute myocardial infarction. All patients underwent selective coronary arteriography at 3 months post-discharge. At the time of the initial investigation, half were beta-blocked, and thereafter, all patients were given prophylactic beta-blockade. During a mean follow-up period of 12 +/- 4 months, 14 patients (30%) experienced cardiac events, i.e. recurrent myocardial infarction (3 patients), angina pectoris (13 patients) and coronary surgery (8 patients). No patient died during the follow-up period. Of the 14 with subsequent cardiac events, 11 were identified by the presence of a reversible perfusion defect at 201Tl scintigraphy, while 7 exhibited abnormal left ventricular exercise reserve on RNA. The predictive accuracy of 201Tl (85%) for subsequent cardiac events exceeded that of RNA (56%; P less than 0.01) and of arteriographic multi-vessel disease (65%; P less than 0.05). The sensitivity of the non-invasive techniques was not influenced by beta-blockade at the time of investigation. Thus, 201Tl scintigraphy appears to be the more accurate technique for the assessment of the prognosis of apparently low-risk patients following myocardial infarction. The accuracy of the technique was not reduced by beta-adrenergic blockade.

Adult↗

Isosorbide-5-mononitrate in the treatment of acute left ventricular failure following acute myocardial infarction.

Eleven patients with acute left ventricular failure following acute myocardial infarction (mean pulmonary capillary wedge pressure [PCW] greater than 20 mmHg) were entered into an open, haemodynamic study of oral isosorbide-5-mononitrate (ISMN). Left ventricular failure was resistant to intravenous diuretic therapy. No patient received concurrent cardioactive drugs nor further diuretic therapy during the study period. Haemodynamic data were acquired via a flow-directed thermodilution catheter placed in the pulmonary artery. Baseline data were acquired prior to the intravenous administration of an ISMN challenge. Thereafter, oral ISMN (20 mg, 8 hourly) was administered over 48 h. Following intravenous ISMN challenge, mean PCW fell from 26.2 to 17.5 mmHg. Cardiac index fell from 2.4 to 2.3 l/min/m2 due to a fall in heart rate (103 to 96.8 beats/min) as stroke volume and blood pressure were unchanged. At 8 h following ISMN, two patients were withdrawn due to hypotension (systolic pressure less than 85 mmHg). In the remainder, PCW remained acceptable throughout 48 h (13.1 mmHg at 48 h), cardiac output, systemic blood pressure and heart rate showed no further significant change. These data suggest that ISMN is effective in the treatment of acute left ventricular failure following acute myocardial infarction.

Adult↗

The effects of metoprolol given early in acute myocardial infarction on ventricular arrhythmias.

The effects of metoprolol, administered in the early stages of acute myocardial infarction was studied in 126 patients. Patients were treated in a double-blind randomized fashion, with metoprolol -15 mg, intravenously followed by 100 mg twice daily for 15 days or placebo, with a mean delay of 8.1 hours from onset of symptoms. All patients underwent 24 hour Holter monitoring on days 1, 5 and 15 after randomization. Although there was no antiarrhythmic effect on day 1, metoprolol reduced the number of hours with warning arrhythmias (greater than 30 ventricular ectopics/hour, any R/T ectopics or ventricular tachycardia) on both days 5 (35 +/- 16% vs 8 +/- 11%; P less than 0.05) and day 15 (13 +/- 37% vs 4 +/- 13%; P less than 0.05). Metoprolol also reduced the incidence of ventricular fibrillation and ventricular tachycardia requiring cardioversion -6% vs 0%; P = 0.058. Metoprolol, administered in the early stages of acute myocardial infarction, had an antiarrhythmic effect which was evident only in the later phase of the study.

Administration, Oral↗

The clinical role of thallium-201 scintigraphy in the management and prognosis of coronary artery disease.

The clinical impact of thallium-201 (Tl-201) scintigraphy in coronary artery disease was reviewed in 162 consecutive patients referred for routine investigation. Normal Tl-201 images were obtained in 86 of the 102 studies undertaken for diagnostic purposes. Eighty-one (94%) of the 86 were spared diagnostic coronary arteriography; 5 proceeded to coronary arteriography for persistent symptoms (1 had double vessel disease, 2 had single vessel disease only, 2 had normal arteriograms). Conversely, coronary arteriography was normal in 2 of 16 patients (12.5%) with unequivocal image defects. Tl-201 scintigraphy was performed as a functional complement to coronary arteriography in 60 patients, influencing the decision for surgery in 36 and determining the presence or absence of myocardial ischaemia in 24 patients with equivocal coronary arteriograms. Normal data were obtained in 9 patients. Of the 95 patients with normal Tl-201 scintigrams, only 5 (5.2%) required further investigations or intervention (4 arteriograms, 1 coronary angioplasty) over a follow-up period of 18 +/- 1 months, none suffered myocardial infarction and none died. There were no deaths in either the diagnostic or complementary group, irrespective of the result of the Tl-201 scintigram, during the mean follow-up period of 18 months. These data confirm both the valuable role of Tl-201 scintigraphy in the management of patients with suspected or proven coronary artery disease and the excellent prognostic value of a normal Tl-201 scintigram.

Adult↗

Bacterial chromosomal restriction endonuclease analysis of the homology of Bacteroides species.

Chromosomal DNAs of selected Bacteroides organisms whose relatedness had been previously determined by "conventional" filter-annealing studies (J. L. Johnson, Int. J. Syst. Bacteriol. 28:245, 1978) were further analyzed by restriction endonuclease analysis coupled with the Southern hybridization procedure (E. M. Southern, J. Mol. Biol. 98:503, 1975). By comparing their EcoRI restriction fragment patterns in agarose gel electrophoresis, each Bacteroides strain could be clearly differentiated. As a simple and direct means for comparison purposes this method was particularly useful for differentiating genetically similar organisms such as Bacteroides strains of the same species which shared greater than 75% homology. In contrast, bacterial chromosomal restriction endonuclease analysis in conjunction with Southern hybridizations was most effectively used to determine the significance of low levels of homology (less than 24%) as this technique provided additional information on the nature and relative distribution of that homology when the areas of homology were displayed as reproducible bands in autoradiograms.

Bacteroides↗

Are the clinical benefits of oral prenalterol in ischaemic heart failure due to beta blockade? A six month randomised double blind comparison with placebo.

The clinical effects of the oral beta 1 partial agonist, prenalterol, were investigated in 37 patients (29 male, eight female; mean age 57 years) with chronic ischaemic left ventricular failure using a placebo controlled randomised double blind protocol over six months. All patients were limited by dyspnoea (New York Heart Association class III) despite treatment with digoxin and diuretics. Twenty eight patients completed the protocol. Moderate clinical improvement was seen in the prenalterol group, whereas there was little change in the placebo group. Bicycle exercise capacity increased over six months in the prenalterol and placebo groups but only achieved statistical significance for prenalterol when compared with baseline values. Maximum exercise heart rate was significantly reduced in the prenalterol group compared with placebo. Radionuclide left ventricular ejection fraction at rest and during exercise and cardiothoracic ratio showed no significant improvement in either group over six months. Prenalterol was well tolerated and produced no increase in frequency of angina or ventricular arrhythmias. Prenalterol produced clinical benefits and improved exercise tolerance while reducing exercise heart rate. A moderate placebo response was noted. The apparent beta blocking effect of prenalterol may be as important as the beta 1 agonist effect in producing these benefits. Prenalterol has, however, been withdrawn because of side effects in animals.

Adrenergic beta-Agonists↗

Swarmer cell differentiation of Proteus mirabilis in fluid media.

After 3-4 h in a rich fluid medium such as brain--heart infusion broth, motile nonseptate filaments developed from normal short rods and formed about 80% of the cell mass of Proteus mirabilis PM23. This developmental pattern was not observed in any of the other nine representatives of the species. These filaments were considered to be equivalent to swarmer cells formed on agar media because these cells ceased tumbling (i.e., chemotaxis was repressed), they developed large numbers of flagella (i.e., flagella synthesis and insertion was derepressed), and the distribution of nuclei in the filaments indicated that there was normal segregation. The population of cells grown in a minimal medium supplemented with amino acids and nicotinic acid consisted only of short cells with tumbling motility, despite the production of long cells and swarming on the same medium solidified with ordinary agar (refined agar was not effective). These short cells differentiated in 1-1.5 h in brain--heart infusion broth at 37 degrees C after an initial division. The requirements for initiation of differentiation were good basal nutrition, suitable cations (probably Ca2+ and Na+, or K+), and unknown heat-stable organic factors (molecular weight less than 10 000) present in crude agar and yeast extract. Other components of media promoted swarmer differentiation if it was initiated and these included organic acids (lactate), amino acids (proline or serine), phosphate, and an appropriate ionic environment. Comparison of the observed sequence of length classes in brain--heart infusion broth culture with computer generated growth models suggested that, at the outset of growth, 50% of the products of each short cell division ceased septation but grew in length for about five doubling periods and then divided cells from each end at a faster rate (3-5 times per hour) for return to the short cell pool.

Antibodies, Bacterial↗

Cold pressor induced changes in regional left ventricular wall motion: specific but insensitive for coronary artery disease.

The incidence of new regional abnormalities of left ventricular wall motion induced by a peripheral cold stimulus has been examined in 75 patients who all underwent coronary arteriography. When analysis was carried out from a cine loop display a new wall motion abnormality had a sensitivity of 12% and a specificity of 100% for coronary artery disease. From stroke volume images the sensitivity was 35% and the specificity 87%. It is concluded that cold pressor induced wall motion changes are too insensitive to be a useful method of screening for coronary artery disease.

Adult↗

Diagnostic exercise testing in 104 patients over 65 years of age.

Since 1979 we have carried out symptom limited exercise stress tests for the diagnosis of chest pain in 104 patients, 61 male, 43 female, over 65 years of age; mean age 68 +/- 3 years. An upright bicycle ergometer was used for 64 tests, a treadmill for 38 tests and a supervised walk for 2 patients unable to undergo formal exercise testing. A positive result of greater than or equal to 1 mm of ST depression was recorded in 45% of patients; males 57%, females 28% (P less than 0.01). Bicycle and treadmill tests were equally likely to produce a positive result; bicycle 43%, treadmill 50% (NS). The limiting symptom was chest pain in 43%, dyspnoea in 26% and fatigue in 30% of patients. No serious arrhythmias or collapses occurred. During a mean follow up to 24 +/- 18 months 13 patients died. A positive exercise test was associated with a significantly increased risk of cardiac death; 8 of 47 patients with positive tests died compared with 1 of 57 patients with negative or equivocal tests (P less than 0.02). The remaining 4 deaths were due to malignancy. Exercise testing can thus be safely performed in elderly subjects with the expectation of a high diagnostic yield. A positive result confers a poor prognosis.

Aged↗

Components of the regular surface array of Aquaspirillum serpens MW5 and their assembly in vitro.

The two-layered regular surface array of Aquaspirillum serpens MW5 was removed from cell envelopes and dissociated into subunits by treatment with 6 M urea. The surface components reassembled onto an outer membrane surface and self-assembled into planar sheets in vitro in the presence of Ca2+ or Sr2+. The two layers were removed sequentially from cell envelopes by a two-step extraction procedure involving initial treatment with a high-pH buffer to remove the outermost surface layer and subsequent treatment with 6 M urea to remove the innermost layer. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the outer and inner layers of the array were composed of two proteins with molecular weights of 125,000 and 150,000, respectively. The two layers assembled sequentially; the 150,000-molecular-weight protein formed an array on an outer membrane surface, and the 125,000-molecular-weight protein required that array as a template for its in vitro assembly.

Cell Membrane↗

Cell wall and phospholipid composition and their contribution to the salt tolerance of Halomonas elongata.

The salt-tolerant bacterium Halomonas elongata makes a variety of physiological adaptations in response to increases in the salt concentration of its growth medium. The cell walls become more compact and internally coherent. The overall lipid pattern shows an increased amount of negatively charged lipids. In addition, the peptidoglycan composition of H. elongata, although not changing in response to increased NaCl, contains the hydrophobic amino acid leucine which is unique among bacterial species. The results suggest that H. elongata is able to live in a wide variety of salt concentrations because it alters its cell physiology in ways which increase both structural integrity and the amount of less-mobile, "structured" cell water, making the cells less susceptible to NaCl-induced dehydration.

Acclimatization↗

The isolation of surface array proteins from bacteria.

The methods used for the isolation of regularly structured (RS) surface array proteins of a range of prokaryotes are described. Most RS proteins can be selectively solubilized from envelope preparations with low concentrations of urea or guanidine hydrochloride. Sodium dodecyl sulfate - polyacrylamide gel electrophoresis analysis of the protein extracts shows that most RS arrays are composed of a single polypeptide that may contain carbohydrate. The molecular weight of the proteins varies from 41 000 to 200 000. Possible reasons for the presence of more than one polypeptide in RS protein preparations are discussed, as well as the evidence for proteolytic degradation of some RS proteins during isolation. Structural features of the RS proteins are described and the importance of protein conformation to assembly of the arrays is indicated.

Bacteria↗