Biomedical subjects
R Roberts
Publications and source records attributed to R Roberts.
Will that IM needle reach the muscle?
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Comparison of left ventricular diastolic function as determined by nuclear cardiac probe, radionuclide angiography, and contrast cineangiography.
In this investigation, determinations of peak diastolic filling rate (PDFR) and ejection fraction (EF) by two distinct nuclear techniques--gated radionuclide angiography (RNA) and nuclear cardiac probe (NCP)--were compared with contrast ventriculography in 44 patients with coronary artery disease (CAD). In addition, PDFR was tested as a potential index of the severity of disease. Good agreement in PDFR was found between NCP and contrast ventriculography (r = 0.83, p less than 0.001), but there was poor correlation between RNA and contrast ventriculography. Ejection fraction measured by either RNA or NCP correlated well with contrast ventriculography (r = 0.96 and r = 0.73, respectively). A positive correlation was found between PDFR and the EF measured by the NCP (r = 0.79) and by contrast ventriculography (r = 0.64), but poor correlation was found between these parameters by RNA. Patients with multivessel CAD had lower PDFR than patients with single vessel disease when studied by the NCP (1.6 +/- 0.4 versus 2.5 versus 0.6 EDV/sec [mean +/- s.d.], p less than 0.0001), but not by RNA. Thus, compared with contrast ventriculography, determination of PDFR is more accurate by NCP than by RNA. Furthermore, the PDFR measured by NCP, but not by RNA, may be a potentially useful index of the extent of CAD.
Reevaluation of cytochrome b and flavin adenine dinucleotide in neutrophils from patients with chronic granulomatous disease and description of a family with probable autosomal recessive inheritance of cytochrome b deficiency.
Chronic granulomatous disease (CGD) is a genetically heterogeneous syndrome characterized by a microbial killing defect of polymorphonuclear leukocytes (PMNs) due to lack of superoxide O2-. 2 generation. Recent studies indicate that the neutrophil O2-.-generating system consists of at least two components, flavoprotein--flavin adenine dinucleotide (FAD)--and cytochrome b. We evaluate the cytochrome b and FAD content in PMN from 30 CGD patients. The method for quantitating cytochrome b was modified by using PMN sonicates incubated with azide plus hydrogen peroxide. With this approach, several absorption peaks corresponding to myeloperoxidase and eosinophil peroxidase, which overlap with peaks of cytochrome b, were obliterated from reduced-minus-oxidized spectra, whereas the peaks of cytochrome b were not and could be readily quantitated. Cytochrome b was detected in PMNs from all 24 normal adults (47.4 +/- 2.9 pmol/7.5 X 10(6) cells), was absent in PMNs from 11 male CGD patients and one female CGD patient but was present in normal amounts in PMNs from nine male and nine female CGD patients. Stimulated nitroblue tetrazolium (NBT) tests performed on PMNs from mothers of CGD patients indicated that cytochrome b deficiency was associated with X-linked inheritance, except in one case in which probable autosomal recessive inheritance was demonstrated. The PMN NBT test of the mother of another male patient without cytochrome b deficiency suggested an X-linked form of inheritance. In related studies, the FAD content in PMN particulate fractions was reduced in 4 of 28 CGD patients studied. All four CGD patients with reduced FAD lacked cytochrome b. However, three patients with cytochrome b deficiency had normal FAD. Thus, the results indicate that PMN cytochrome b deficiency is observed in most X-linked and in some autosomal recessive CGD, that cytochrome b deficiency may be associated with FAD deficiency, and that cytochrome b and FAD are normal in most patients with non-X-linked CGD.
The changing base line of complex ventricular arrhythmias. A new consideration in assessing long-term antiarrhythmic drug therapy.
Initial base-line electrocardiograms are used to assess the efficacy of treatment for ventricular arrhythmias. This approach assumes that in the absence of treatment the frequency of arrhythmia would remain constant. To test the validity of this assumption, we studied 26 clinically stable patients with symptomatic but not life-threatening ventricular arrhythmias, during two periods of placebo treatment separated by a mean of 17 months. As compared with the initial placebo period, there were significant reductions in ventricular premature depolarizations (50 per cent), pairs (65 per cent), and ventricular tachycardia (83 per cent) during the second period of placebo administration (P less than or equal to 0.05 for all comparisons). Over one third of the patients gave the appearance of receiving successful therapy during the second placebo period, even when the reported spontaneous variability of ventricular arrhythmia was taken into consideration. If unrecognized, these long-term spontaneous changes in the frequency of arrhythmia could result in continuation of unnecessary and potentially toxic therapy and lead to incorrect conclusions regarding the efficacy of antiarrhythmic drugs in clinical trials. We therefore recommend that the frequency of arrhythmia be reassessed annually in the absence of treatment in patients similar to those in our study. These recommendations should not be applied to patients with life-threatening ventricular arrhythmias.
Beta-adrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent functional deterioration.
The prolonged myocardial dysfunction observed after reversible ischemia (stunned myocardium) has been postulated to result from an inability of the myocytes to replenish ATP stores. Accordingly, one would expect inotropic stimulation to result in minimal increase in contractile function, or possibly even further deterioration. To test this hypothesis, studies were performed in open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery (LAD) followed by 4 hours of reperfusion. Systolic wall thickening, an index of regional myocardial function, was measured in the LAD-dependent territory with ultrasonic crystals. Thickening fraction was 20.8 +/- 3.0% (mean +/- standard error of the mean) under baseline conditions, decreased to -18.6 +/- 1.6% during LAD occlusion, and was still severely depressed after 3 hours of reperfusion (2.6 +/- 3.4%). Thickening fraction remained stable between 3 and 4 hours of reperfusion in 5 untreated control dogs. In 9 treated dogs, isoproterenol (0.1 microgram/kg/min intravenously for 30 minutes starting 3 hours after reperfusion) increased thickening fraction to values (24.8 +/- 4.5%) that were similar to those at baseline. Thirty minutes after discontinuation of isoproterenol administration, thickening fraction had returned to pre-isoproterenol levels. Thus, reperfused, severely depressed myocardium responds dramatically to beta-adrenergic stimulation without subsequent adverse effects on function in the short-term. These findings imply that the stunned myocardium can generate ATP, and therefore do not support the view that an inability to replenish ATP stores is the cause of postischemic dysfunction. More important, this study suggests that postischemic dysfunction in humans may be effectively reversed with inotropic therapy without short-term deleterious sequelae.
Circadian variation in the frequency of onset of acute myocardial infarction.
To determine whether the onset of myocardial infarction occurs randomly throughout the day, we analyzed the time of onset of pain in 2999 patients admitted with myocardial infarction. A marked circadian rhythm in the frequency of onset was detected, with a peak from 6 a.m. to noon (P less than 0.01). In 703 of the patients, the time of the first elevation in the plasma creatine kinase MB (CK-MB) level could be used to time the onset of myocardial infarction objectively. CK-MB-estimated timing confirmed the existence of a circadian rhythm, with a three-fold increase in the frequency of onset of myocardial infarction at peak (9 a.m.) as compared with trough (11 p.m.) periods. The circadian rhythm was not detected in patients receiving beta-adrenergic blocking agents before myocardial infarction but was present in those not receiving such therapy. If coronary arteries become vulnerable to occlusion when the intima covering an atherosclerotic plaque is disrupted, the circadian timing of myocardial infarction may result from a variation in the tendency to thrombosis. If the rhythmic processes that drive the circadian rhythm of myocardial-infarction onset can be identified, their modification may delay or prevent the occurrence of infarction.
Where, oh where has the MB gone?
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Progress in the surgical treatment of cardiac arrhythmias. Initial experience of 90 patients.
Between 1981 and 1985, ninety patients were treated surgically for cardiac arrhythmias and have been followed for a mean interval of 21 months (range, one to 49 months). Follow-up is 100% complete. Fifty accessory pathways were divided in 35 patients (25 male and ten female; mean age, 35.2 years; range, 10 to 72 years), with no deaths. Five females, aged 10 to 35 years, were treated for focal atrial tachycardia, three for an atrial focus alone, and two with other arrhythmia procedures; four were cured and one was improved. Two patients (one man and one woman, both aged 33 years) had ablation of the atrioventricular node. Forty-one patients (32 male and nine female; average age, 56.9 years; range, 15 to 74 years) had ablation of ventricular tachycardia. Kent bundle division and focal atrial tachycardia ablation were also performed in two of these patients. More than 80% of patients had coronary disease. Mean preoperative ejection fraction was 33.9% with a range of 14% to 65%. Aneurysmectomy, endocardial resection, cryoablation, and coronary artery bypass were the procedures used. The perioperative mortality rate was 9.8% but there were no deaths in the last 23 patients. Ventricular tachycardia was abolished in all but three survivors in whom medical treatment is now effective. The automatic implantable defibrillator was implanted in 11 patients, with no surgical deaths. These results confirm the feasibility of relieving a variety of serious arrhythmias by surgical intervention.
Identification of a 43-kDa polypeptide associated with acetylcholine receptor-enriched membranes as MM creatine kinase.
Creatine kinase isoenzymes from Torpedo californica electric organ, skeletal muscle, and brain were purified and characterized. Torpedo electric organ and skeletal muscle creatine kinase have identical apparent Mr, electrophoretic mobility, and cyanogen bromide fragments. The electrophoretic mobility of the Torpedo creatine kinase was anodal as compared to mammalian MM creatine kinase. No creatine kinase isoenzyme with an electrophoretic mobility similar to mammalian BB creatine kinase was seen in any of the Torpedo tissues examined. Hybridization studies demonstrate the Torpedo electric organ creatine kinase to be composed of identical subunits and capable of producing an enzymatically active heterodimer when combined with canine BB creatine kinase. Creatine kinase from sucrose gradient-purified Torpedo electric organ acetylcholine receptor-rich membranes has an electrophoretic mobility identical with the cytoplasmic isoenzyme and an apparent Mr identical with mammalian MM creatine kinase. Western blot analysis showed Torpedo electric organ skeletal muscle creatine kinase and acetylcholine receptor-enriched membrane creatine kinase reacted with antiserum specific for canine MM creatine kinase. NH2-terminal amino acid sequence determinations show considerable sequence homology between human MM, Torpedo electric organ, chicken MM, and porcine MM creatine kinase. The acetylcholine receptor-associated creatine kinase is, therefore, identical with the cytoplasmic form from the electric organ and is composed of M-subunits.
Analysis of the spontaneous variability of ventricular arrhythmias: consecutive ambulatory electrocardiographic recordings of ventricular tachycardia.
Results are reported of analysis of the variability of complex ventricular arrhythmias in a cohort of 110 patients selected for the presence of ventricular tachycardia (VT). All patients were enrolled in investigational antiarrhythmic drug trials and had an average of 4 consecutive days of placebo ambulatory electrocardiographic recording to serve as the database for this study. Using a statistical approach incorporating analysis of variance, the minimum percent reductions of ventricular premature complexes, couplets and VT were calculated to establish "drug effect" rather than variability at a significance level of 0.05. The relative variability of ventricular arrhythmias in prognostically important groups was also analyzed: (1) coronary artery disease (CAD) (n = 57) vs no CAD (n = 53); (2) patients with a left ventricular ejection fraction of 40% or less (n = 52) vs those with an ejection fraction greater than 40% (n = 58); and (3) patients with frequent runs of VT (10 or more runs/day, n = 63) vs infrequent VT (n = 47). Multiple regression analysis revealed that patients with CAD have significantly greater premature ventricular complex variability than patients without CAD (p less than 0.01). Also, patients with frequent VT runs have greater VT variability than that previously reported in smaller studies, thus requiring greater VT reductions to establish drug effect. Whether the variability of ventricular arrhythmia is itself an independent risk factor for sudden cardiac death is unknown.
Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (A MILIS Study).
Methods for detecting acute myocardial infarction (AMI) were compared in a prospective study of 726 patients with pain presumed to be caused by ischemia that lasted 30 minutes or longer and was associated with electrocardiographic changes (ST-segment deviation greater than or equal to 0.1 mV and/or new Q waves or left bundle branch block). Using MB-CK values of more than 12 IU/liter as the standard criterion for detection of AMI, 639 patients (88%) were judged to have AMI. Total plasma CK values, technetium-99m stannous pyrophosphate images 48 to 72 hours after admission, and serial 12-lead electrocardiograms over 10 days were analyzed by investigators blinded to other clinical and laboratory data. For detection of AMI, total CK, electrocardiograms (ECGs) and pyrophosphate imaging were all highly accurate and sensitive (total CK accuracy 97%, ECG 92%, pyrophosphate 88%; total CK sensitivity 98%, ECG 96% and pyrophosphate 91%). However, both pyrophosphate and ECG were less specific than total CK (p less than 0.01) (total CK specificity 89%, pyrophosphate 64% and ECG 59%). The sensitivity (p less than 0.05) and accuracy (p less than 0.01) of total CK and pyrophosphate for those patients with Q-wave development were slightly greater than for those in whom Q waves did not evolve. The ECG was less accurate (p less than 0.02) and pyrophosphate was less specific (p less than 0.04) in patients with prior MI compared with those with initial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Filipin-sterol complexes in the plasma membrane of zebrafish spermatozoa.
The presence and distribution of filipin-sterol complexes in the plasma membrane of zebrafish (Brachydanio rerio) sperm was investigated. The zebrafish sperm plasma membrane, treated with freeze-fracture techniques, is seen to contain a multitude of intramembranous particles that, in a specific region of the posterior part of the sperm head, are organized into unusual particle arrays that appear as simple hexagons or parallelograms. The polyene antibiotic filipin forms complexes with 3-beta-OH sterols to produce characteristic protrusions and pits in membranes that are readily observable in freeze-fracture replicas. Numerous filipin-sterol complexes were found to populate the sperm plasma membrane, and the complexes exhibited variability in their distribution in different sperm. This appears to be the first illustrated example of an acrosomeless sperm that exhibits a high concentration of filipin-sterol complexes. In contrast, the unique grating formed by the intramembranous particles as well as variable amounts of membrane surrounding the unusual particle arrays were always free of the filipin-sterol complexes. Thus, while cholesterol appears to be present in the plasma membrane of the zebrafish sperm, it is not apparent in the highly differentiated region of the membrane based on the observed distribution of the filipin-sterol complexes.
Enzyme kinetics of a highly purified mitochondrial creatine kinase in comparison with cytosolic forms.
Mitochondrial creatine kinase (CK) purified from canine myocardium showed a single protein band on SDS-PAGE and was free of MMCK. Its amino acid composition was different than MMCK or BBCK and did not react to antiserum to MMCK or BBCK. Using purified mitochondrial, MM and BBCK, the velocity of reaction (V) was estimated for creatine phosphate (CP), creatine (C), adenosine triphosphate (ATP) and adenosine diphosphate (ADP) over a wide range of concentrations including those at Vmax. The values for Km (mM/L) derived from Lineweaver-Burke plots are shown: (Table: see text). The affinity of mitochondrial CK for C is much greater than MMCK which is compatible with the energy shuttle hypothesis, namely ATP is converted by mitochondrial CK to CP, and then diffuses to the myofibril for conversion to ATP for utilization.
Multiple, single-dose naltrexone administrations fail to effect overall cognitive functioning and plasma cortisol in individuals with probable Alzheimer's disease.
A double-blind placebo-controlled study was conducted in 10 individuals with probable Alzheimer's disease to assess the effects of varying doses of Naltrexone (0, 25, 50 and 100 mg) on cognitive functioning and on plasma cortisol. Each individual participated in four separate sessions at least three days apart. Naltrexone was found to improve performance in only one of the six psychometric tasks employed (Token Test). However, enhancement of Token Test performance was limited to the 25 mg Naltrexone dose and was mainly the result of an improvement on the part of the two most severely impaired patients. In contrast to the previous reports of elevations of plasma cortisol following administration of opiate antagonists to younger, non-demented subjects, Naltrexone administration failed to produce any significant increase in plasma cortisol in Alzheimer's patients.
Psychosocial adjustment of burn survivors.
The purpose of this study was to assess the magnitude and predictors of psychosocial adjustment in burn victims. It was postulated that once individuals sustain a burn, their long-term psychosocial adjustment is a function of their present coping responses, social resources, burn severity and time since burn. It was expected that these variables could also be used to identify individuals at risk for psychosocial maladjustment. A historical cohort analytical survey of 340 randomly selected adults and the mothers of 145 children who had sustained either major or minor burns during the past 12 years were administered the Coping Scale, Participation in Social and Recreational Activities Index, Social Support and the Psychosocial Adjustment to Illness Scale. The children's mothers also completed the Family Environment Scale and the Child Behaviour Checklist. In summary, the variance in psychosocial adjustment among adults was related to unemployment, loss of occupational status, avoidance coping, and little involvement in recreational activities. Together, these variables explained 40 per cent of the variance in psychosocial adjustment. Severity of the burn and time since the burn were not related to psychosocial adjustment. The prevalence of psychosocial maladjustment among the adults was 10 per cent and 15.7 per cent among children. Psychosocial adjustment among children was not related to the severity of the burn. The less adjusted children could be distinguished from adjusted children on the basis of their mothers' adjustment and methods of coping. The findings tended to refute the commonly held view that post-burn adjustment is associated with burn severity and suggests psychosocial adjustment is a function of both coping responses and social resources.
Community pharmacy residency program: a contemporary perspective.
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Hemodynamic effects of an oral dopamine receptor agonist (fenoldopam) in patients with congestive heart failure.
Dopamine receptor stimulation causes vascular and neurohumoral responses that may be beneficial in patients with heart failure. Oral inactivity, emesis and adrenergic-induced arrhythmias have limited the use of currently available compounds. Fenoldopam (SKF-82526-J) is a new, orally available, selective, dopamine-receptor agonist with potent renal vasodilating properties (six times that of dopamine) without positive inotropic or adrenergic activity. Drug efficacy was clinically evaluated in 10 patients with heart failure after single oral doses of placebo and 50, 100 and 200 mg of medication. Placebo produced no changes. Peak efficacy was noted 30 minutes to 1 hour after the 200 mg dose with mean blood pressure decreasing from 96 +/- 15 (mean +/- SD) to 83 +/- 8 mm Hg (p less than 0.05), pulmonary capillary wedge pressure decreasing from 23 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05) and mean pulmonary artery pressure decreasing from 32 +/- 9 to 29 +/- 8 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1,987 +/- 887 to 1,191 +/- 559 dynes.s.cm-5 (p less than 0.05) with a subsequent 55% increase in cardiac index from 2.2 +/- 1.1 to 3.1 +/- 1.3 liters/min per m2 (p less than 0.05). Heart rate and right atrial pressure did not change (p greater than 0.05). No emesis or new tachycardia was noted at any dose. Baseline hemodynamics generally returned within 3 to 4 hours. Fenoldopam, therefore, is a short-acting, orally effective drug that decreases systemic vascular resistance and increases cardiac index in patients with heart failure and represents a new class of oral compounds that may be useful in treating such patients.