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Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 343 records · Page 19Linked to original sources
PubMed1989

Sensitive, rapid assay of subforms of creatine kinase MB in plasma.

The subforms of creatine kinase (CK; EC 2.7.3.2) in plasma have received recent attention as potential markers for the early diagnosis of acute myocardial infarction. Because changes in CK-MM subforms are not specific for myocardial injury, we developed an assay, based on high-voltage electrophoresis, that is sufficiently sensitive to detect the CK-MB subforms at concentrations substantially below the upper limit of normal (14 U/L). The assay can detect 1.25 U of either MB subform per liter with a precision of 0.20 U/L and gives responses that vary linearly with activity concentration from 0.0 through 30.0 U/L, with an identical signal response for both subforms. When both subforms are present in a serum sample, the assay accurately measures both the relative percentage and the absolute quantity of each: assay activity/known activity was 1.03 for each subform at a total MB subform activity of 5.0 U/L (r = 0.98). Assay time is 25 min, and there is no loss of CK during electrophoresis. Thus, this system can be used to rapidly, sensitively, and precisely quantify the two CK-MB subforms at activities well within the normal reference interval.

Biomarkers↗
PubMed1989

Continence issues in acute care.

Urinary incontinence affects up to 43 per cent of acute care patients. Toileting is a function of intact bladder, sphincters, and nervous system. Five types of incontinence are stress, urge, reflex, total, and functional. Problems affecting patients in acute care are: 1. Diagnostic studies 2. Treatments--for example, intravenous fluids, hyperalimentation, medications, catheters 3. Bedrest 4. Restraints 5. Pain 6. Iatrogenic conditions 7. Environment Assessment includes a specific history and physical examination, focused on previous episodes of incontinence, functional ability, and cognitive status. Management includes scheduled fluid intake and toileting, manipulation of the environment, and attention to orientation and psychological factors. The treatment of fecal incontinence in the hospital elderly includes: 1. Assessment of incontinence and contributing factors; 2. Bowel regimen and environmental assists for persons with periodic incontinence; 3. Treatment of diarrhea or constipation; and 4. Protection of perineal skin from stool exposure.

Aged↗
PubMed1988

Ketoconazole inhibition of progesterone oxidation by the rabbit.

Ketoconazole, a known cytochrome P-450 inhibitor, inhibited both progesterone ring hydroxylation and side-chain oxidation to steroidal acids. Progesterone 21 6 beta- and 16 alpha-hydroxylase activities of rabbit liver microsomes were inhibited 50% by ketoconazole at concentrations between 10(-5) and 10(-4) M. Steroid acid formation was similarly inhibited at a 10(-5) M concentration. Ketoconazole administration to rabbits produced a significant reduction in the urinary excretion of acidic metabolites of [3H]deoxycorticosterone and [14C]progesterone by approximately 50 and 75% respectively. The differential effect of ketoconazole in vivo may indicate that more than one acidic metabolite pathway may be operative.

Animals↗
PubMed1988

A clinician's guide for conducting randomized trials in individual patients.

In determining optimal treatment for a patient conventional trials of therapy are susceptible to bias. Large-scale randomized trials can provide only a partial guide and have not been or cannot be carried out for most clinical disorders. However, randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may in some circumstances provide a solution to this dilemma. In an N of 1 RCT a patient undergoes pairs of treatment periods (one period of each pair with the active drug and one with matched placebo, assigned at random); both the patient and the clinician are blind to allocation, and treatment targets are monitored. N of 1 RCTs are useful for chronic, stable conditions for which the proposed treatment, which has a rapid onset of action and ceases to act soon after it is discontinued, has shown promise in an open trial of therapy. The monitoring of treatment targets usually includes quantitative measurement of the patient's symptoms with the use of simple patient diaries or questionnaires. Pairs of treatment periods are continued until effectiveness is proved or refuted. The cooperation of a pharmacy is required for the preparation of matching placebos and conduct of the trial. Formal statistical analysis may be helpful for interpreting the results. The practical approach presented in this paper allows clinicians to conduct their own N of 1 RCTs.

Clinical Trials as Topic↗
PubMed1988

The role of evidence in the consensus process. Results from a Canadian consensus exercise.

As part of a consensus conference on cesarean birth, the ten-member consensus panel rated 224 clinical scenarios on their appropriateness for a cesarean section. Ratings were obtained before and immediately after the consensus conference. The level of agreement (consensus) among panelists was assessed separately for scenarios with good research evidence (evidence scenarios) and for those with conflicting, poor, or no evidence (nonevidence scenarios). For each scenario, consensus between panelists was measured as total agreement, partial agreement, or disagreement on the appropriateness of a cesarean section. Before the conference, total or partial agreement existed for a larger percentage of evidence than nonevidence scenarios (85% vs 30%), with the pattern reversed for disagreements (15% vs 70%). After the conference, possible improvement in the level of consensus actually occurred for 71% of the evidence and only 24% of the nonevidence scenarios. Thus, the consensus process, as structured here, was sensitive to the availability of good evidence and suggests that aspects of both expert and public processes can successfully be combined. However, an improvement could be made in the process by grading final recommendations according to the availability of rigorous research evidence.

Breech Presentation↗
PubMed1988

Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis.

The proliferation and development of haemopoietic stem cells takes place in close association with marrow stromal cells. This intimate cell contact presumably enables the stem cells and their progeny to respond to stimuli present on the stromal cell surface. While the nature of these stimuli has not been determined, it is likely that growth factors play some role. Recently, it was demonstrated that the natural and the recombinant haemopoietic growth factor, granulocyte/macrophage colony stimulating factor (GM-CSF), could be adsorbed out of solution by an extract of human marrow stromal extracellular matrix (ECM) with retention of biological activity. However, the precise ECM molecules involved were not identified. Here, we clearly demonstrate that the major sulphated glycosaminoglycan of mouse marrow stroma, heparan sulphate, possesses the ability to adsorb both GM-CSF and the multilineage haemopoietic growth factor, Interleukin 3 (IL-3). Furthermore, these growth factors, once bound, can be presented in the biologically active form to haemopoietic cells.

Adsorption↗
PubMed1988

Editorial.

Explore the source record for details and available documents.

Journal Article↗
PubMed1988

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location.

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.

Cardiac Volume↗
PubMed1988

Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block.

Whether myocardial infarction (MI) can be diagnosed electrocardiographically in the presence of left bundle branch block (LBBB) is controversial. Our study sought to test the reliability of ECG criteria for diagnosing MI in patients with LBBB. Among 985 patients presenting within 18 hours of the onset of ischemic chest pain, 35 had complete LBBB. Acute MI was identified by serial MB-creatine kinase (CK) elevations and prior MI was determined by previously documented ECG and/or enzyme changes. Among those with LBBB, 24 patients had acute and/or prior MI, while 11 had neither. Eleven ECG criteria previously proposed for detecting MI in the presence of LBBB were evaluated. In patients presenting with ischemic chest pain and complete LBBB, presence of any one of the following ECG criteria was highly specific (90% to 100%) and predictive (85% to 100%) for acute or prior MI: Q waves in at least two of leads I, aVL, V5, or V6; R wave regression from V1 to V4; notching of the upstroke of the S wave in at least two of leads V3, V4, or V5, and primary ST-T wave changes in two or more adjacent leads.

Bundle-Branch Block↗
PubMed1988

Intravenous fenoldopam in heart failure: comparing the hemodynamic effects of dopamine1 receptor agonism with nitroprusside.

Dopamine1 receptors mediate hemodynamic effects that may be beneficial in patients with congestive heart failure. We infused the selective dopamine1 receptor agonist, fenoldopam mesylate (SKF 82526 J), to evaluate hemodynamic and neurohumoral changes during continuous intravenous infusion in patients with congestive heart failure and compared them with the effects of nitroprusside, a traditional vasodilator that works by a distinctly different mechanism. In 15 patients with a mean radionuclide ejection fraction of 17%, the agents were infused in a random-ordered, double-blinded, crossover, active drug-controlled protocol after optimal dosing was determined during a titration period. Hemodynamic changes were induced in minutes with both drugs during a mean (+/- standard deviation) infusion dose of 1.45 +/- 1.66 micrograms/kg/min for fenoldopam and 2.99 +/- 1.59 micrograms/kg/min for nitroprusside. At 1 hour, mean blood pressure decreased and cardiac index rose with both drugs, and the effect lasted throughout the 6-hour infusion period. Nitroprusside, but not fenoldopam, reduced right heart filling pressures (including mean pulmonary capillary wedge, mean right atrial, and mean pulmonary artery pressures) during the infusion period. Both drugs caused significant reduction in systemic vascular and pulmonary arteriolar resistances. No significant change occurred in plasma norepinephrine levels. Fenoldopam ameliorates some of the adverse hemodynamic changes that occur during heart failure but does not reduce right heart filling pressures as does nitroprusside. Because of fenoldopam's unique characteristics, it may benefit certain patients with heart failure.

Adult↗
PubMed1988

Rate of disappearance of creatine kinase-MB after acute myocardial infarction: clinical determinants of variability.

The apparent rate of disappearance (Kd) of creatine kinase (CK)-MB is used in the calculation of the size of acute myocardial infarction (AMI), but little is known about the determinants of variability of this parameter. We therefore evaluated the relationship between clinical characteristics and apparent Kd in 328 patients with AMI without evidence of recurrent infarction. Patients with a history of cigarette smoking within 6 months had higher rates of disappearance of CK-MB, but no relationship was found between renal function and apparent Kd. Slower rates of disappearance of CK-MB were correlated with longer times from the onset of symptoms to peak CK-MB value (p less than 0.001), while higher peak CK-MB levels were not correlated with apparent rates of enzyme clearance. Decreased rates of disappearance of CK-MB were found in patients who had congestive heart failure during or after the hospitalization (both p less than 0.05), and who died during the hospitalization or during study follow-up (both p less than 0.05). Slower rates of disappearance were also significantly correlated with lower ejection fractions on radionuclide ventriculography at 10 days (p less than 0.001) and at 3 months (p less than 0.05) after AMI. These data suggest that patients with slower rates of disappearance of CK-MB may have poorer prognoses, perhaps reflecting continuing necrosis and enzyme release from jeopardized myocardium.

Creatine Kinase↗
PubMed1988

Assessment of myocardial perfusion in humans by contrast echocardiography. I. Evaluation of regional coronary reserve by peak contrast intensity.

Myocardial contrast echocardiography was performed during coronary angiography with 2 ml of sonicated meglumine diatrizoate sodium 76% (meglumine) in 40 patients (ranging in age from 25 to 79 years) before and 10 to 15 s after intracoronary injection of papaverine, 8 mg into the right coronary artery (n = 43) and 10 mg into the left (n = 46). The same protocol was repeated in 17 patients 5 to 10 min after completion of coronary angioplasty. In 13 patients with normal coronary angiograms, peak contrast intensity corrected for background myocardial intensity was measured in 36 regions and was found to increase after papaverine from 36 +/- 16 to 55 +/- 22 U (p less than 0.001). In contrast, in the 27 patients with angiographic evidence of coronary artery disease, peak intensity in 64 regions remained unchanged after papaverine (35 +/- 22 versus 36 +/- 23 U). An increase in peak intensity greater than or equal to 10 U was 80% sensitive and 92% specific for coronary artery disease. After successful coronary angioplasty, peak intensity in the involved regions improved significantly (p less than 0.001) during baseline contrast injections (from 32 +/- 16 to 50 +/- 25 U) as well as in the postpapaverine contrast injections (from 30 +/- 12 to 60 +/- 26 U). In conclusion, measurement of peak contrast intensity after intracoronary injections of sonicated meglumine provides a relative index of myocardial perfusion that allows assessment of regional coronary reserve in patients with coronary artery disease. This may be of particular value in evaluating the immediate effects of coronary angioplasty on myocardial perfusion.

Adult↗
PubMed1988

Thrombolytic therapy in acute myocardial infarction: Part I.

Thrombolytic therapy with pharmacologic agents is an exciting approach to the treatment of myocardial infarction. The results of several clinical studies indicate that perfusion can be restored with intravenous therapy and may be associated with a reduction in infarct size and improved left ventricular function. In a trial involving more than 11,000 patients, thrombolytic therapy reduced acute and long term mortality. Pharmacologic thrombolysis, however, is not without problems. When administered intravenously, the agents currently available, streptokinase and urokinase, are associated with a relatively low recanalization rate as well as a risk of adverse effects, most commonly a systemic lytic state and risk of bleeding complications. Although intracoronary administration is associated with a higher rate of recanalization, the need for cardiac catheterization limits its applicability and results in a delay in the initiation of thrombolytic therapy (which diminishes salvage of myocardium). The trials assessing the existing agents have shown that time is a critical variable in the success of thrombolytic therapy. This had led investigators to focus more attention on intravenous agents that can be administered rapidly. The newer agents now under investigation, acylated streptokinase and single-chain urokinase, may represent improvements of currently available products and may offer potentially increased benefits. A fibrinogen-sparing agent, such as t-PA, in addition to being highly effective, may offer advantages through minimizing the systemic lytic effect. Additional randomized, controlled clinical trials currently are underway to determine the effect on mortality of this "fibrinolytic" therapy as part of a total treatment regimen. The current status of our knowledge concerning thrombolytic therapy in acute myocardial infarction can be summarized as follows: 1. Transmural (that is, Q wave) myocardial infarction usually is caused by an obstructing coronary thrombus. 2. The thrombus can be lysed with intravenous therapy in the majority of cases, particularly with newer, well-tolerated fibrin-specific agents. 3. There is considerable evidence suggesting that reperfusion reduces the acute morbidity and mortality when therapy is administered successfully within the initial 3 to 4 hours (and possibly up to 6 hours) after onset of symptoms. 4. Data on long term prognosis after thrombolysis are very encouraging, although limited. 5. Conventional agents lead to significant fibrinogen depletion and therefore an increased risk of bleeding; the new fibrin-selected agents cause less fibrinogen degradation and may reduce the risk of hemorrhagic complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiomyopathies↗