Search PubMed⌕ Search

Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 451 records · Page 25Linked to original sources
PubMed1985

Creatine kinase and phosphorylase in cardiac lymph: coronary occlusion and reperfusion.

Cardiac lymph, collected from conscious dogs, was monitored for glycogen phosphorylase and creatine kinase (CK) enzymatic activity during control state, circumflex coronary artery (CFX) occlusion, and reperfusion. CFX occlusions, lasting for intervals as short as 10 min, initiated a release of phosphorylase and CK into the cardiac lymph, which was immediately observed during reperfusion of the ischemic tissue. Blood plasma levels did not appear for several hours. In the absence of reperfusion, the appearance of enzymes in cardiac lymph was delayed and peaked later. Glycogen phosphorylase and CK entered the lymph in greater quantities with reperfusion as the length of occlusion was increased. Histological examination of multiple sections of the reperfused hearts showed infarcts in hearts where CFX occlusions lasted 20 min or longer; occlusions of 10-15 min showed evidence of cell injury and death in two hearts and no definable infarct in the majority. Ischemic intervals of short duration release functionally active glycogen phosphorylase and CK, which reflect changes in myocardial cell egress of macromolecules and/or cell death.

Animals↗
PubMed1985

Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia.

Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 +/- 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 +/- 1.2% of the left ventricle in the control group and 26.5 +/- 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 +/- 14.3 vs 12.8 +/- 11.6) and 2 hr of reperfusion (74.2 +/- 8.4 vs 31.6 +/- 9.8, p less than .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia.

Animals↗
PubMed1985

Stable angina as a manifestation of ischemic heart disease: medical management.

Stable angina is the most common form of presentation of ischemic heart disease, being more common in women (65%) than men (37%), while the reverse is true for the prevalence, being present in about 3.5% of men over 55 as opposed to 1.5% of women. The overall 10 year survival for individuals with stable angina at a mean age of 60 years is 58% for men and 68% for women. Prognosis is related to several factors: age, sex, the number of coronary vessels involved, collateral flow, ventricular function, and the extent of myocardium at risk. It is estimated that stable angina of recent onset is associated with single-vessel disease in about 40% of cases. Angina is a clinical diagnosis but, if doubt exists, one should exclude coronary atherosclerosis or spasm by cardiac catheterization and not rely on noninvasive techniques. Therapy for unstable angina or acute infarction receives considerable attention and is reasonably well defined, but such is not the case for stable angina. Conventionally, it consists of secondary prevention and prescription of nitrates, calcium blockers, or beta-blockers. There are several problems: No studies have been performed to assess efficacy in reducing the development of unstable angina. The group of drugs most appropriate for first-line therapy has not been identified. It has not been determined if nitrate tolerance is a major problem. The effect of beta-blockers on prognosis in patients with unstable angina has not been defined. A noninvasive means of identifying high and low risk patients with unstable angina has not been developed.

Adrenergic beta-Antagonists↗
PubMed1985

Anterior thigh pain or tenderness. A diagnostically useful manifestation of bacteremia.

In four patients with putative infectious process, anterior, bilateral proximal thigh pain and tenderness unaccompanied by generalized myalgias developed. This unusual manifestation, observed in these and other patients, was associated with demonstrable bacteremia. Aside from tenderness, no local abnormalities were found and the pain and tenderness disappeared after appropriate therapy. Creatine kinase levels, measured in three of the four patients, were elevated in only one. This manifestation is useful clinically as it strongly suggests bacteremia; attention to this finding can be lifesaving.

Abdomen↗
PubMed1985

Inability of caliper measurement to enhance observer agreement in the interpretation of coronary cineangiograms.

Important clinical decisions are made on the basis of the interpretation of the degree of stenosis in the coronary cineangiogram. Thus, minimization of observer variation (both intra and inter) is crucial. The purpose of this investigation was to determine if measurement of stenotic lesions by caliper (CM) as compared with the usual eyeball method (EM) would reduce observer variation. Five observers, using the AHA scoring system, estimated maximal luminal narrowing in 14 segments on 10 films providing 2 reports on each film by EM and 2 by CM, thus making observations on 2800 segments. This allowed analysis of intraobserver variation for each reporter for method EM and CM, and for interobserver variation by each method. Since chance agreement is an important component in an observational study, a correction for this was made using the Kappa statistic. The results revealed that the mean Kappa by EM was 0.71 compared to 0.63 by CM (1 being perfect agreement and 0 no agreement). Agreement was much greater in proximal rather than distal segments. Interobserver agreement was consistently higher by EM K = 0.62 than CM K = 0.53 (p = 0.0007). A delineation of the types of disagreement and their clinical significance are important considerations in the evaluation of observer variation. It is concluded that the use of a caliper does not enhance either intra or interobserver agreement.

Cineangiography↗
PubMed1985

Monitoring at the National Hospital, Queen Square, London.

At the National Hospital, video-EEG telemetry is performed on about 100 patients per year and ambulatory EEG recordings on about 40 patients per year. For clarification of the diagnosis of odd attacks of uncertain cause 55% of the patients are selected, and 35% for the investigation of established epilepsy. The equipment employed for the long-term EEG monitoring is described. The results obtained during 1983 are discussed in detail; clinically useful results are obtained in over 50% of the patients.

Ambulatory Care↗
PubMed1985

The presence and distribution of gap junctions in the oocyte-follicle cell complex of the zebrafish, Brachydanio rerio.

Membranes of teleost female gametes and investing layer of follicle cells characteristically exhibit a prolonged, close spatial relationship. This relationship is manifested, in part, by numerous folds of the plasma membrane of both oocyte and follicle cells that extend through channels called pore canals within a thick, laminated extracellular coat, the vitelline membrane. During oogenesis the folded oocyte processes, or microvilli, increase in number and length, but decrease in width. Follicle cell processes are frequently wider and less numerous than oocyte microvilli, but do not usually touch the unfolded portion of the oocyte surface. Throughout development, distal portions of oocyte microvilli contact either the proximal portion of follicle cell processes or unfolded parts of the follicle cell plasma membrane where many membranous specializations characteristic of gap junctions are present, especially during intermediate and later stages of oogenesis. Freeze-fracture replicas of the oocyte-follicle complexes revealed numerous localized aggregations of discrete intramembranous particles approximately 9-15 nm diameter that are characteristic of gap junctions. Gap junctions were located in the region of contact between the terminals of oocyte microvilli in relation to the different areas of the follicle cell plasma membrane. In ultrathin sections, the apposed plasma membranes of oocyte microvilli and follicle cells, in places, take the form of a seven-layered membrane approximately 18 nm thick which is bisected by a 2 nm gap that appears somewhat electron dense due to uranyl acetate stain. The location of gap junctions in the zebrafish oocyte-follicle is different from the situation in mammals where gap junctions are associated with cumulus cell processes as they make contact with the oocyte. The entire oocyte-follicle cell complex in the zebrafish contains the structural pathways for the transfer of small molecules between these cells.

Age Factors↗
PubMed1985

Comparative molecular pharmacology in leukemic L1210 cells of the anthracene anticancer drugs mitoxantrone and bisantrene.

1,4-Dihydroxy-5,8-bis(2-[(2-hydroxyethyl)aminoethyl]amino)-9, 10-anthracenedione (mitoxantrone) and 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2y)hydrazone] dihydrochloride (bisantrene) were evaluated for their abilities to cause cytotoxicity and interact with cellular DNA using leukemic L1210 cells. On a molar basis mitoxantrone has been found to be 7-fold more toxic than bisantrene. Using a nucleoid sedimentation technique, bisantrene caused changes in DNA supercoiling which were characteristic of an intercalating drug, but mitoxantrone did not induce these changes. Both drugs were found to interact with cellular DNA with tight but noncovalent binding. Both drugs also induced protein-associated double- and single-strand DNA breaks, but with mitoxantrone only some of the DNA single-strand breaks were protein associated, whereas with bisantrene all the DNA single-strand breaks were protein associated. The cytotoxicity produced by bisantrene at a given frequency of protein-associated DNA strand breaks was low. However, with mitoxantrone at an equivalent DNA strand break frequency, the cytotoxicity was high. Treatment of isolated L1210 nuclei with either drug did not result in DNA single-strand breaks. It can be concluded that bisantrene binds DNA in whole cells by an intercalative mechanism, whereas mitoxantrone binds DNA by a nonintercalative, electrostatic interaction and induces non-protein-associated DNA strand breaks.

Animals↗
PubMed1985

Validation of left ventricular volume measurements by radionuclide angiography.

A nongeometric, attenuation-corrected technique to quantitate left ventricular volumes using equilibrium radionuclide angiography was validated in vitro and in vivo. In vitro experiments were performed to derive a linear attenuation coefficient, which was then employed in the volume determinations using balloons in a water bath. Good in vitro correlation was found between radionuclide and actual volumes (r = 0.99, p less than 0.0001), over a wide range (5 to 400 ml). In vivo validation was done by comparing the nuclear technique to contrast angiography in 29 patients: Good correlations were found for end-diastolic volume (r = 0.98), end-systolic volume (r = 0.95), stroke volume (r = 0.96), and ejection fraction (r = 0.85). When the conventional linear attenuation coefficient was used, the radionuclide technique consistently overestimated volumes in vitro and in vivo. Although high intraobserver and interobserver correlation coefficients were found (r from 0.88 to 0.93), significant individual variability existed, particularly in the interobserver data. Our data provide unique validation of radionuclide volume determinations, using an experimentally determined attenuation coefficient, which results in improved accuracy.

Adult↗
PubMed1984

Molecular mechanism for the production of multiple forms of MM creatine kinase.

Incubation of human, canine or rabbit MM creatine kinase with carboxypeptidase-N or B resulted in the production of 2 additional enzyme forms with increased anodal migration on polyacrylamide gels. The C-terminal amino acid of tissue MM creatine kinase from all 3 species was shown to be lysine, a specific substrate for carboxypeptidase-N and B.

Amino Acids↗
PubMed1984

Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial.

A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were similar in the two groups. The primary end point evaluated--infarct size as estimated from plasma MB creatine kinase activity--was virtually identical in the two groups, averaging 13.3 and 13.6 gram-equivalents of MB creatine kinase per square meter of body-surface area. Peak plasma levels of the enzyme were also similar in the two groups. No significant difference was observed between the propranolol and placebo groups in the change in left ventricular ejection fraction, extent of area involved in pyrophosphate uptake, R-wave loss on electrocardiograms, or mortality (after three years). These results do not support the use of propranolol administered four or more hours after the onset of symptoms to limit infarct size.

Administration, Oral↗
PubMed1984

Risk factors for sudden death after acute myocardial infarction: two-year follow-up.

The risk of sudden coronary death after myocardial infarction (MI) was assessed in 533 patients who survived 10 days after MI and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of multiple clinical and laboratory variables determined before hospital discharge revealed that frequent ventricular premature beats (VPBs) (greater than or equal to 10/hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction less than or equal to 0.40) were independently significant markers of risk for subsequent sudden death believed to be the result of a primary ventricular arrhythmia. The incidence of sudden death was 18% in patients with both LV dysfunction and frequent VPBs (11 times that of patients with neither of these findings). Seventy-nine percent of all sudden deaths occurred within 7 months after the index MI. In 280 survivors reclassified 6 months after MI with regard to the presence or absence of frequent VPBs and LV dysfunction, these risk factors could not be associated with sudden coronary death over a further follow-up period of up to 18 months; the overall incidence of sudden cardiac death was low (1.4%) after 6 months. Thus, the presence of frequent VPBs in association with LV dysfunction early after MI identifies patients at high risk for sudden death over the next 7 months.

Aged↗
PubMed1984

Specialized delivery systems for intravenous nitroglycerin. Are they necessary?

Nitroglycerin is absorbed in vitro into polyvinyl chloride tubing, and it has been recommended that nitroglycerin be administered intravenously through specialized polyethylene infusion sets. To determine if tubing type is essential to achieve physiologic effectiveness, we studied dose responses to intravenous nitroglycerin in 15 patients with heart failure using standard polyvinyl chloride tubing in seven (group 2) and special polyethylene infusion sets in seven (group 1) (one patient was excluded from analysis because of technical difficulties). We monitored heart rate, blood pressure, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output. Cardiac index, systemic and pulmonary vascular resistance, triple index, rate pressure product, stroke volume, stroke volume index, and stroke work index were calculated. Baseline and treatment measurements were obtained from five to 15 minutes after the infusion of 10, 20, 40, and 80 micrograms of nitroglycerin per minute. Over-all, systolic blood pressure decreased (p less than 0.05) about 8 percent and mean blood pressure approximately 12 percent, mean pulmonary artery pressure and mean pulmonary capillary wedge pressure decreased 30 to 40 percent, and the decline in mean right atrial pressure was 35 percent of baseline (all p less than 0.05). Heart rate and cardiac index did not change (p greater than 0.05). Pulmonary vascular resistance decreased slightly (p = 0.07) and systemic vascular resistance significantly (p less than 0.05). When the two groups were compared physiologic changes were virtually identical (p less than 0.05). Two-way analysis of variance for baseline corrected data proved no differences between tubing sets (p less than 0.05), but the infusion concentration rate was highly related to response (p = 0.0001). A significant (p less than 0.05) decrease in mean blood pressure and mean right atrial pressure was noted at lower dose rates (20 micrograms per minute and 40 micrograms per minute, respectively) in group 1. Beneficial hemodynamic effects in heart failure patients can, then, be predicted to occur at 80 micrograms per minute infusion rates; these responses seem independent of the type of infusion tubing system employed. Additionally, when patients given intravenous nitroglycerin for various reasons were followed for 48 hours, the majority receiving infusions via polyvinyl chloride tubing (group 2) did not require dosage adjustments. Also, at lower flow rates, more solution than calculated may be delivered when polyethylene tubing infusion sets are employed with volumetric infusion pumps.

Blood Pressure↗
PubMed1984

Purification and characterization of naturally occurring and in vitro induced multiple forms of MM creatine kinase.

MM creatine kinase purified from tissue exists as a single form but upon release into the plasma exhibits three forms which, based on increasing anodal migration on polyacrylamide gel electrophoresis, are referred to as MM1, MM2, and MM3. The three forms were isolated in pure form from plasma in sufficient quantities for biochemical and physiological studies. Chromatofocusing results show that MM1, MM2, and MM3 have distinct isoelectric points of 7.58, 7.43, and 7.30, respectively. Analysis on high pressure liquid chromatography showed MM1 and tissue creatine kinase (MMt) to have identical peptide maps, but MM2 and MM3 were different in at least one amino acid. Tissue MM creatine kinase was converted in vitro to MM2 and MM3 after incubation in plasma. Conversion was unaffected by nonspecific proteases but inhibited by benzoylarginine, epsilon-amino caproic acid, and guanidinoethylmercaptosuccinic acid, specific inhibitors of carboxypeptidase N. Digestion of purified tissue MM creatine kinase with carboxypeptidases N and B produced MM2 and MM3 which were identical with the forms produced in vivo. Hybridization experiments with MM1 plus MM3 produced all three forms, as did tissue MM creatine kinase plus MM2. MM2 was also able to produce all three forms in the experiments. The plasma half-life of tissue MM creatine kinase or MM1 was shown to be about one-half that of MM3. The results suggest that hydrolytic cleavage of a basic amino acid, presumably by carboxypeptidase N, is responsible for conversion of MMt to MM2 and MM3. COOH-terminal amino acid analysis demonstrated the COOH-terminal amino acid of canine and rabbit MM1 to be lysine. Thus, we conclude that cleavage of the COOH-terminal lysine from MMt by serum carboxypeptidase N generates two additional MM creatine kinase isoforms with prolonged plasma clearance rates.

Animals↗
PubMed1984

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients.

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗
PubMed1984

The outpatient treatment of schizophrenia: an integrated and comprehensive management-oriented approach.

In this era of de-institutionalization, it is incumbent on the mental health profession to develop techniques to treat disorders of the schizophrenic spectrum that are as effective as possible and cost efficient. Such techniques are most likely to be useful to the degree that they can be constructed on a critical analysis of research relevant to the nature of the schizophrenic disorder and the efficacy of past treatment modalities. The past two decades have seen a wealth of research in these areas. A review of this work suggests that an integrated strategy of management is the treatment approach most indicated for this disorder. Details of one such comprehensive approach are presented for two symptoms-subgroups of schizophrenic outpatients.

Adaptation, Psychological↗
PubMed1984

Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus.

To elucidate the factors involved in the reduced survival rate of diabetic patients after acute myocardial infarction (AMI), we prospectively evaluated 100 patients with well-documented diabetes and 426 control patients. We characterized infarct size and analyzed the incidence and severity of congestive heart failure (CHF) and subsequent death with respect to infarct size. The extent of the index infarct was less in diabetic compared to nondiabetic patients, 16.2 +/- 2.2 CK-gm-eq/m2 compared with 19.2 +/- 0.9 (p less than 0.02). However, CHF was more prevalent in diabetic patients (31.2% of the diabetic patients compared to 15.7%). The difference was most prominent in diabetic patients who had sustained prior infarction (50% compared to 16%), but was evident also in diabetic patients with initial infarction (26% compared to 16%). The mortality rate was greater in diabetic patients (p less than 0.04). When diabetic and nondiabetic patients were stratified with respect to the presence or absence of CHF, survival curves were comparable. The increased incidence of CHF despite a smaller infarct size suggests that additional factors must contribute to myocardial dysfunction and the resultant excess in mortality.

Diabetes Complications↗