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Biomedical subjects

R Davison

Publications and source records attributed to R Davison.

At least 19 recordsLinked to original sources
PubMed1995

Drug eruptions and isotypic antibody responses to streptokinase after infusions of anisoylated plasminogen-streptokinase complex (APSAC, anistreplase).

BACKGROUND: Anisoylated plasminogen-streptokinase complex (APSAC, anistreplase) is a thrombolytic agent (131 kd) used for treatment of myocardial infarction. Like its principal antigenic determinant, streptokinase, APSAC has been reported to cause a variety of allergic reactions. OBJECTIVE: This study was intended to determine any association between isotypic antibody responses to streptokinase and observed allergic reactions to APSAC. METHODS: We measured sequential IgM, IgG, IgA, and IgE antistreptokinase serum levels in 21 patients who received APSAC or tissue-type plasminogen activator in a prospective, double-blind study. RESULTS: Of 11 patients who received APSAC, four had maculopapular rashes and one had urticaria; those with maculopapular rashes had significantly higher rises in serum IgM, IgG, IgA, and IgE antistreptokinase levels. We could not, however, define a temporal relationship between rises in antistreptokinase levels of a particular isotype and the onset of maculopapular rashes. The patient who had urticaria had no antistreptokinase responses but had also received several other potentially causal drugs. None of 10 patients who received tissue-type plasminogen activator had allergic reactions or significant rises in serum antistreptokinase levels. CONCLUSION: The more vigorous panisotypic antistreptokinase responses observed in patients who received APSAC and had maculopapular rashes may reflect generalized immune system activation that included other immune responses (such as cell-mediated hypersensitivity) that were responsible for these reactions.

Aged↗
PubMed1992

Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II.

BACKGROUND: Thrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate. METHODS AND RESULTS: Clinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p less than 0.001); in the invasive strategy, the mortality rates were similar (6.0% and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conservative strategy (14.8% versus 4.2%, p less than 0.001). Reinfarction was not independently correlated with baseline characteristics except with history of angina (relative risk, 1.9). Mortality was lower in current smokers and ex-smokers versus never-smokers (3.6% and 4.8% versus 8.0%, p less than 0.001). Current smokers had a lower risk profile (p less than 0.001), including age, pulmonary edema/cardiogenic shock, history of hypertension, and diabetes. The rate of reinfarction was lower in current smokers versus ex-smokers and never-smokers (4.6% versus 8.3% and 8.8%, p less than 0.001). "Not current smoker" was an independent correlate with reinfarction (relative risk, 1.9). The coronary anatomy did not differ among the current smokers, ex-smokers, and never-smokers. CONCLUSIONS: The strong independent correlation of pulmonary edema/cardiogenic shock with death suggests that thrombolysis is not sufficient to improve survival in these patients. The higher mortality in patients with versus without prior AMI in the conservative strategy suggests that early catheterization and revascularization of these patients might be beneficial. Conversely, the higher mortality in diabetes without prior AMI in the invasive than in the conservative strategy suggests that early aggressive management might not be suitable in this subgroup except for clinical indications. Reinfarction was not predictable by clinical variables except by history of angina. The finding that "not current smoker" was an independent correlate with reinfarction was unexpected.

Female↗
PubMed1988

The use of epinephrine in the treatment of older adult asthmatics.

Three subcutaneous doses of 0.3 mL 1:1,000 epinephrine were given 20 minutes apart to 95 adult asthmatics 15 to 96 years old during 108 asthma exacerbations. Patients with a history of recent myocardial infarction or of angina were excluded from our study. Heart rhythm and rate, blood pressure, respiratory rate, and clinical response were prospectively evaluated before, during, and after the administration of epinephrine. There was no significant difference in the occurrence of ventricular arrhythmias between patients less than 40 and more than 40 years old. The mean systolic and diastolic blood pressures, mean heart rate, and mean respiratory rate decreased with treatment in the older population. Our results suggest that epinephrine is safe to use in acute asthmatics of any age.

Acute Disease↗
PubMed1988

The effect of clonidine on the cessation of cigarette smoking.

The effect of clonidine on smoking cessation was studied by randomly assigning 186 smokers in a double-blind fashion to either placebo or clonidine. Abstinence from smoking was reported more frequently by subjects receiving clonidine, but the difference was statistically significant only at the end of the first week (34.4% vs 21.5%; p less than 0.05). Bothersome side effects were common and resulted in the early discontinuation of the study medication by 23 of the subjects taking clonidine and eight taking placebo (p less than 0.05). Although this study did not demonstrate a significant effect of clonidine on smoking cessation, a beneficial trend was detected and therefore further trials with transcutaneous delivery of this agent in combination with behavior modification techniques are warranted.

Adult↗
PubMed1987

Role of heparin after intravenous thrombolytic therapy for acute myocardial infarction.

The optimal approach to management of patients after thrombolytic therapy for acute myocardial infarction (AMI) is unclear. The role of anticoagulation with heparin was evaluated in 75 consecutive patients who received intravenous streptokinase for AMI. Heparin therapy was titrated to keep the partial thromboplastin time (PTT) between 90 and 120 seconds. Seventeen episodes of definite myocardial ischemia (associated with reversible electrocardiographic changes) were observed in 13 patients. When episodes of probable myocardial ischemia are included (typical chest pain relieved by nitroglycerin or associated with more than a 15-mm Hg change in blood pressure but without electrocardiographic changes), 52 episodes occurred in 28 patients. Four episodes of definite and 4 of probable myocardial ischemia occurred within 24 hours of discontinuation of heparin. Analysis of the level of anticoagulation as assessed by PTT at the time of the ischemic events shows that ischemia occurred more often at lower PTTs. Nine hemorrhagic complications occurred, all within 24 hours of streptokinase infusion. In 4 patients bleeding was believed to be major and heparin administration was discontinued; 2 patients with gastrointestinal bleeding required blood transfusions. Our data suggest that after thrombolytic therapy for AMI, the level of anticoagulation is inversely related to the frequency of recurrent ischemic events; that discontinuation of heparin is frequently associated with ischemia; and that administration of heparin is associated with a low incidence of hemorrhagic complications.

Female↗
PubMed1986

Release of unassembled rat cardiac myosin light chain 1 following the calcium paradox.

To determine the intracellular source and release kinetics of myosin light chain 1 immediately following irreversible myocytic injury, we perfused rat hearts in a Langendorff apparatus under control conditions (20 minutes), or during global cellular injury produced by oxygenated, calcium-free perfusion (5 minutes), followed by reperfusion with buffer containing 2.5 mM calcium (15 minutes). Light chain 1 concentration (double antibody radioimmunoassay) and creatine kinase activity were measured in both the coronary effluent and the 140,000 g supernatant extract of perfused ventricular tissue (after homogenization and ultracentrifugation). Calcium reperfusion caused the rapid release of both light chain 1 and creatine kinase activity (peak light chain 1 = 1.09 +/- 0.19 micrograms/g; peak creatine kinase = 74.9 +/- 10.7 IU/ g at 1 minute, mean +/- SD, n = 3); 28.5 +/- 13.5% of total light chain 1 and 86.5 +/- 0.6% of total creatine kinase activity were depleted from the tissue extract during the 15-minute reperfusion. No light chain 1 or creatine kinase was detected in the effluents of control-perfused hearts. Dodecyl sulfate polyacrylamide gel electrophoresis and immunodetection with specific antibody to myosin heavy chain and light chain 1 showed that the effluent light chain 1 was of similar molecular weight (mol wt = 27,000) to the subunit bound to myofibrils. In addition, light chain 1 was released in the absence of myosin heavy chain. Thus, a small soluble pool of unassembled myosin light chain 1 subunits exists in the cytoplasm of cardiac myocytes that is released from irreversibly injured cells. This pool demonstrates initial washout kinetics similar to creatine kinase.

Animals↗
PubMed1986

Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions.

Thallium 201 (201Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial 201Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

Adult↗
PubMed1986

Identification of patients at risk for anaphylaxis due to streptokinase.

To identify patients at risk for immediate-type allergic reactions to streptokinase, we performed streptokinase skin tests on patients immediately before planned administration of intravenous streptokinase for treatment of acute myocardial infarction. Forty-five patients had negative skin tests and received streptokinase without allergic reaction. One patient had a positive skin test and was given urokinase instead, without incident. Positive skin tests were also present in a patient who had recently had an anaphylactic reaction to streptokinase, and in two physician volunteers who had been sensitized to streptokinase during initial determination of the optimal skin testing dose. Immunoassays for IgE to streptokinase were performed on serum samples from skin-tested patients and volunteers, and on 16 other patients who had not been skin tested but had previously received streptokinase without allergic reactions. The skin test was a sensitive and specific indicator of elevated levels of IgE to streptokinase. We propose that skin testing immediately before streptokinase administration is a practical approach for identifying patients at risk for immediate-type allergic reactions to streptokinase, and its use may possibly prevent anaphylaxis and death.

Anaphylaxis↗
PubMed1985

Frequency of pericardial effusion as determined by M-mode echocardiography in acute myocardial infarction.

A pericardial friction rub occurs in 6 to 16% of patients after acute myocardial infarction (AMI), but the incidence of pericardial effusion (PE) is not known. M-mode echocardiography was done 1, 3 and 5 days after AMI in 43 consecutive patients admitted within 24 hours of AMI, and PE was detected in 16 (37%). The PE was small in 7 patients, moderate in 6 and large in 3. A pericardial friction rub developed in 8 (19%), of whom only 4 had PE. Pleuritic chest pain diminished by sitting up and relieved by antiinflammatory agents developed in 12 (28%), of whom only 5 had PE. The peak creatine kinase level was significantly higher in patients with PE (1,769 +/- 1,003 U) than in those without (1,181 +/- 838 units). More patients with PE were in Killip classification II, III or IV (11 of 16 [69%] vs 9 of 27 [33%]). The presence of PE was not associated with age, site of AMI, development of Q waves, use of heparin or previous AMI. In conclusion, PE as detected by M-mode echocardiography is frequently present after AMI, and its presence is not closely associated with the occurrence of a pericardial friction rub or typical pericardial pain.

Aged↗
PubMed1985

Association of methemoglobinemia and intravenous nitroglycerin administration.

Significant elevation of arterial methemoglobin levels has been reported with the administration of intravenous (i.v.) nitroglycerin (NTG). To determine the incidence and clinical significance of this side effect of i.v. NTG, serial arterial methemoglobin levels were determined in 50 consecutive patients receiving i.v. NTG for 48 hours or longer. The mean i.v. NTG infusion rate was 290 +/- 13 micrograms/min (4.1 +/- 0.2 micrograms/kg/min) and the mean duration of infusion was 7.1 +/- 0.5 days. The mean methemoglobin level for the 141 samples was 1.57 +/- 0.08%, which differs from the control mean value in our laboratory of 0.44 +/- 0.01%. Although no patient had clinical symptoms from methemoglobin, 20 patients had elevated (greater than 1%) levels on at least 1 measurement. Seventy-eight of the 141 samples analyzed were in the normal range; 63 determinations were between 2 and 5%. Patients with normal methemoglobin levels differed from those with abnormal levels in the dose of i.v. NTG (mean infusion rate 244 +/- 16 vs 351 +/- 17 micrograms/min; total cumulative dose 1,612 +/- 153 vs 3,398 +/- 308 mg). Age, weight, renal and hepatic function, and arterial oxygen saturation were not different between the groups. In conclusion, clinically significant methemoglobinemia is uncommon with i.v. NTG infusion; however, when large doses of NTG are administered, this complication is more likely.

Aged↗
PubMed1985

Prophylaxis of supraventricular tachyarrhythmia after coronary bypass surgery with oral verapamil: a randomized, double-blind trial.

This study investigated the efficacy of oral administration of verapamil, started 24 hours after coronary artery bypass grafting (CABG), in reducing the incidence of postoperative supraventricular tachyarrhythmia (SVT). Two hundred patients were randomly assigned in a double-blind fashion to receive a one-week course of either a placebo or 80 mg of verapamil every 6 hours. Overall, SVT developed in 23 control and 14 verapamil-treated patients, a 39% reduction in incidence (p less than 0.10). Of the patients who received at least four doses and continued to receive the study drug, 17 in the control and 7 in the verapamil group experienced SVT, a 53% decrease in incidence (p less than 0.06). Atrial fibrillation constituted 34 of the 37 SVT episodes and was associated with a slower ventricular response in the group given verapamil (115 +/- 8 versus 156 +/- 4 beats per minute; p less than 0.001). No evidence was found linking postoperative SVT with the withdrawal of beta-blocking drugs. Adverse effects required that 20 patients in the verapamil and 6 in the placebo group be removed from the study. Hypotension or pulmonary edema or both developed in 13 of the patients receiving verapamil, but in only 1 of the control patients (p less than 0.001). We conclude that although verapamil has potential merit for the prophylaxis of SVT after CABG, its use in this setting is associated with a high incidence of unacceptable hemodynamic side effects.

Administration, Oral↗
PubMed1985

Myocardial necrosis in a patient with mixed connective tissue disease.

A 23-year-old black woman with mixed connective tissue disease developed acute onset of shortness of breath and evidence of pulmonary edema. Cardiac isoenzymes, electrocardiograms and radionuclide myocardial scintigraphy were consistent with focal myocardial necrosis. The patient has had no further myocardial complication since initiation of therapy with steroids.

Adult↗
PubMed1983

Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy.

Thirty-five patients who had angina at rest that was unresponsive to standard therapy comprised of oral or topical nitrates and beta-blocking drugs were treated with a continuous infusion of intravenous nitroglycerin (IVNTG). The infusion was started at 10 micrograms/min and increased by 10 micrograms/min increments every 5 minutes until an infusion rate of 50 micrograms/min was reached. After each episode of rest angina, the infusion was increased by 50 micrograms/min in the same stepwise manner. Data from a 24-hour baseline control period were compared with those from a 24-hour IVNTG endpoint period at which time the highest IVNTG infusion rate was administered. The average IVNTG infusion rate was 140 +/- 15 micrograms/min. With IVNTG therapy, the number of episodes of angina at rest decreased from 3.5 +/- 0.4 to 0.3 +/- 0.1, sublingual nitroglycerin use decreased from 1.9 +/- 0.3 to 0.4 +/- 0.1 mg/day, and morphine sulfate administration decreased from 5.5 +/- 1.3 to 0.4 +/- 0.2 mg/day (all p less than 0.001). When each patient's response on the endpoint day was analyzed, 25 were defined as complete (no rest angina), 8 as partial (greater than 50% decrease in the number of episodes/day from control values), and 2 as nonresponders. No significant drug-induced adverse effects occurred. IVNTG appears to be effective therapy for angina at rest refractory to standard oral and topical medications.

Adult↗