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Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease
312
of meningitis were of bacterial etiology, 13% were granulomatous, and 11% were classed as aseptic. In the younger group, 23% of the cases were bacterial whereas 70% were aseptic. Streptococcal species and Gram-negative bacilli were the predominant bacterial isolates in the more elderly patients; Neisseria meningitidis and Streptococci were more commonly found in the younger group. Presenting symptoms and their duration before diagnosis were similar in the two groups. Older patients with bacterial meningitis more commonly had identificable predisposing factors, including neurosurgical procedures in 28%, sinusitis in 17%, and neoplastic disease or immunosuppressive therapy in 17%. The morbidity rate for bacterial meningitis was 70% in elderly patients as compared to 41% in the younger group; mortality rates were 44% and 13% in the two groups, respectively. The authors conclude that menigitis in the elderly is more likely to be bacterial and is associated with significant morbidity and mortality. [Tom Reinecke, MD]
?E ?MERGENCIES IN RHEUMATOID ARTHRITIS. Weiner SR. Am Fum Physician 1984; 29:127-131. Rheumatoid arthritis may present with extraarticular emergencies that require prompt diagnosis and treatment. These emergencies include rupture of the extensor tendons of the dorsum of the hand, carpal tunnel syndrome, and “pseudothrombophlebitis” syndrome caused by rupture of a Baker’s cyst into the calf. Cervical spine involvement occurs in more than half of all patients with rheumatoid arthritis and can lead to acute or insidious subluxation of the atlantoaxial and subaxial joints. Cricoarytenoid arthritis may present with stridor, and septic arthritis can appear in a joint, with the development of new pain or inflammation. Rheumatoid nodules may cause organ dysfunction, including cardiac involvement with the development of arrythmias and valvular disease. Vasculitis may present with large vessel involvement and tissue or organ infarct. Ocular complications such as keratoconjunctivitis and scleritis occur. Drug reactions to therapy may present with gastrointestinal bleeding, bone marrow suppression, or renal disease. Although rheumatoid arthritis is typically an indolent disease, failure to recognize its urgent complications can lead to significant morbidity and mortality. [Douglas M. Davenport, MD]
The Journal of Emergency Medicine
?D ?IAGNOSIS OF DEEP-VEIN THROMBOSIS: COMPARISON OF CLINICAL EVALUATION, ULTRASOUND, PLETHYSMOGRAPHY, AND VENOSCAN WITH X-RAY VENOGRAM. Sandler DA, Duncan JS, Ward P, et al. Lancet 1984; 2:716-719. In this study of 50 patients with suspected deep vein thrombosis (DVT), the diagnostic accuracy of clinical examination, doppler ultrasound, impedance plethysmography, and venoscan was compared to that of x-ray venography. Venoscan is a relatively new diagnostic procedure for DVT that uses both flow and clot incorporation of technetium-labeled fibrinogen. Twenty-nine patients had deep vein thrombosis demonstrated by venography. Physical examination was the least accurate method of making the diagnosis. Plethysmography, venoscan, and ultrasound had diagnostic accuracies of 655’0, 80%, and 82%, respectively. Sixteen (32%) of the venoscans yielded equivocal results; the remaining 34 scans were reported as either positive or negative. In this latter group, the accuracy was 97%. There were no false negatives. The authors conclude that venoscan may serve as a screening procedure for DVT, to be followed by venography in those patients with equivocal results. Advantages of the venoscan include a completion time of four hours and increased sensitivity for calf vein thrombosis. [Ross Berringer, MD]
?? EFFECTS OF THEOPHYLLINE ON DIAPHRAGMATIC STRENGTH AND FATIGUE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Murciano D, Aubier M, Lecocguic Y, Pariente R. New Eng JMed 1984; 311:349-353. The authors assessed the effect and duration of effect of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease (COPD). Ten patients were randomized to receive oral theophylline 13 mg/kg/d in two divided doses. Theophylline levels were checked at 7 and 30 days, and doses were adjusted to maintain therapeutic levels. Five patients received placebo. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing and was measured. Measurements were
Abstracts
performed before therapy and after 7 and 30 days of theophylline or placebo administration. Mean plasma theophylline concentrations were 12.9 and 13.5 mg/L on days 7 and 30, respectively. Theophylline increased maximal transdiaphragmatic pressure by 16% after 7 days of administration; this increase persisted after 30 days. No significant change was observed in the placebo group. Diaphragmatic fatigue was suppressed in all patients receiving theophylline throughout the study but in no patient receiving placebo. The authors conclude that theophylline has a potent and long-lasting effect on diaphragmatic contractility and fatigue in patients with COPD. [Richard G. Lyons, MD] Editor’s Note: Bronchodilator therapy should theoretically be ineffective in patients with fixed airway obstruction. The authors provide credible evidence for a mechanism by which the bronchodilator theophylline produces clinical improvement in these patients.
?? LABETALOL FOR HYPERTENSION. Abramowicz M (ed). Med Lett 1984; 26:83-85. Labetalol (Trandate, Glaxo; Normodyne, Schering) is a nonselective cr- and @blocking agent recently approved by the U.S. Food and Drug Administration for the treatment of hypertension. It is available as an oral agent for the treatment of essential hypertension and as an intravenous (IV) agent for the treatment of severe hypertension and hypertensive crises. This drug’s mechanism of action couples the usual /3blocking effects of bradycardia and depressed myocardial contractility with vasodilatation and decreased peripheral vascular resistance from (Yblockade. It is the a-blocking effect that brings a decrease in blood pressure within one to two hours after oral ingestion and in five minutes after intravenous administration. Clinical trials show no clear advantage to this agent over previously available P-blocking drugs in the treatment of essential hypertension. It may be effective in some patients who have failed to respond to other P-blockers. Intravenous administration lowers the blood pressure of most patients, but it may fail if the patient is currently receiving Pblockers. The oral dose is initiated at 200 mg b.i.d. and may be increased slowly. The usual maintenance dose is 200 to 400 mg b.i.d. Intravenous labetalol may be given by continuous infusion at 2 mg/min or intermittently in doses of
313
20 mg given over a two-minute period at lominute intervals. Major adverse effects include all those previously associated with fl-blockers, with an increased incidence of postural hypotension and impotence. The drug is contraindicated in patients with congestive heart failure and bronchospastic disease. [Paul W. Snider, MD]
?? DESMOPRESSIN FOR HEMOPHILIA AND OTHER COAGULATION DISORDERS. Abramowicz M (ed). Med Lett 1984; 26:82. Desmopressin is a synthetic analog of arginine vasopressin. It has been available as DDAVP for intranasal use since 1978 for the treatment of diabetes insipidus. Desmopressin can also temporarily increase factor VIII: C concentration and von Willebrand’s factor in the blood. The intravenous (IV) formula of desmopressin is now available for the treatment of patients with moderate hemophilia A, type I von Willebrand’s disease, and uremia. Parenteral administration can temporarily decrease bleeding time sufficiently to stop bleeding from trauma or to permit minor surgical procedures to be performed. The use of this drug may thus help to avoid the risk of hepatitis and AIDS from the use of blood products. Patients must have at least 5% of normal factor VIII activity for treatment to be successful. Rarely encountered side effects include headache, nausea, facial flush, mild abdominal pain, and local pain at the injection site, most of which respond to a decrease in the infusion rate. The dose of IV desmopressin is 0.3 mg/kg diluted in saline given slowly over 30 minutes; maximum effect is usually obtained in 15 to 30 minutes. Intravenous desmopressin is safe and effective for the temporary correction of coagulation defects in patients with hemophilia A, von Willebrand’s disease, or [Jan M. Kief, MD] uremia.
0 ISOLATED SIXTH-NERVE PALSIES IN YOUNGER ADULTS. Moster ML, Savino PJ, Sergott RC, et al. Arch Ophthalmol1984; 102: 1328-1330. Isolated sixth-nerve palsy usually occurs in adults over 50 years of age and is associated with hypertension, diabetes, and atherosclerosis. Because this condition is less common in younger adults, the authors reviewed their experience with 49 patients, aged 15 to 50 years, with isolated sixth-nerve palsy. The following causes for
of meningitis were of bacterial etiology, 13% were granulomatous, and 11% were classed as aseptic. In the younger group, 23% of the cases were bacterial whereas 70% were aseptic. Streptococcal species and Gram-negative bacilli were the predominant bacterial isolates in the more elderly patients; Neisseria meningitidis and Streptococci were more commonly found in the younger group. Presenting symptoms and their duration before diagnosis were similar in the two groups. Older patients with bacterial meningitis more commonly had identificable predisposing factors, including neurosurgical procedures in 28%, sinusitis in 17%, and neoplastic disease or immunosuppressive therapy in 17%. The morbidity rate for bacterial meningitis was 70% in elderly patients as compared to 41% in the younger group; mortality rates were 44% and 13% in the two groups, respectively. The authors conclude that menigitis in the elderly is more likely to be bacterial and is associated with significant morbidity and mortality. [Tom Reinecke, MD]
?E ?MERGENCIES IN RHEUMATOID ARTHRITIS. Weiner SR. Am Fum Physician 1984; 29:127-131. Rheumatoid arthritis may present with extraarticular emergencies that require prompt diagnosis and treatment. These emergencies include rupture of the extensor tendons of the dorsum of the hand, carpal tunnel syndrome, and “pseudothrombophlebitis” syndrome caused by rupture of a Baker’s cyst into the calf. Cervical spine involvement occurs in more than half of all patients with rheumatoid arthritis and can lead to acute or insidious subluxation of the atlantoaxial and subaxial joints. Cricoarytenoid arthritis may present with stridor, and septic arthritis can appear in a joint, with the development of new pain or inflammation. Rheumatoid nodules may cause organ dysfunction, including cardiac involvement with the development of arrythmias and valvular disease. Vasculitis may present with large vessel involvement and tissue or organ infarct. Ocular complications such as keratoconjunctivitis and scleritis occur. Drug reactions to therapy may present with gastrointestinal bleeding, bone marrow suppression, or renal disease. Although rheumatoid arthritis is typically an indolent disease, failure to recognize its urgent complications can lead to significant morbidity and mortality. [Douglas M. Davenport, MD]
The Journal of Emergency Medicine
?D ?IAGNOSIS OF DEEP-VEIN THROMBOSIS: COMPARISON OF CLINICAL EVALUATION, ULTRASOUND, PLETHYSMOGRAPHY, AND VENOSCAN WITH X-RAY VENOGRAM. Sandler DA, Duncan JS, Ward P, et al. Lancet 1984; 2:716-719. In this study of 50 patients with suspected deep vein thrombosis (DVT), the diagnostic accuracy of clinical examination, doppler ultrasound, impedance plethysmography, and venoscan was compared to that of x-ray venography. Venoscan is a relatively new diagnostic procedure for DVT that uses both flow and clot incorporation of technetium-labeled fibrinogen. Twenty-nine patients had deep vein thrombosis demonstrated by venography. Physical examination was the least accurate method of making the diagnosis. Plethysmography, venoscan, and ultrasound had diagnostic accuracies of 655’0, 80%, and 82%, respectively. Sixteen (32%) of the venoscans yielded equivocal results; the remaining 34 scans were reported as either positive or negative. In this latter group, the accuracy was 97%. There were no false negatives. The authors conclude that venoscan may serve as a screening procedure for DVT, to be followed by venography in those patients with equivocal results. Advantages of the venoscan include a completion time of four hours and increased sensitivity for calf vein thrombosis. [Ross Berringer, MD]
?? EFFECTS OF THEOPHYLLINE ON DIAPHRAGMATIC STRENGTH AND FATIGUE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Murciano D, Aubier M, Lecocguic Y, Pariente R. New Eng JMed 1984; 311:349-353. The authors assessed the effect and duration of effect of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease (COPD). Ten patients were randomized to receive oral theophylline 13 mg/kg/d in two divided doses. Theophylline levels were checked at 7 and 30 days, and doses were adjusted to maintain therapeutic levels. Five patients received placebo. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing and was measured. Measurements were
Abstracts
performed before therapy and after 7 and 30 days of theophylline or placebo administration. Mean plasma theophylline concentrations were 12.9 and 13.5 mg/L on days 7 and 30, respectively. Theophylline increased maximal transdiaphragmatic pressure by 16% after 7 days of administration; this increase persisted after 30 days. No significant change was observed in the placebo group. Diaphragmatic fatigue was suppressed in all patients receiving theophylline throughout the study but in no patient receiving placebo. The authors conclude that theophylline has a potent and long-lasting effect on diaphragmatic contractility and fatigue in patients with COPD. [Richard G. Lyons, MD] Editor’s Note: Bronchodilator therapy should theoretically be ineffective in patients with fixed airway obstruction. The authors provide credible evidence for a mechanism by which the bronchodilator theophylline produces clinical improvement in these patients.
?? LABETALOL FOR HYPERTENSION. Abramowicz M (ed). Med Lett 1984; 26:83-85. Labetalol (Trandate, Glaxo; Normodyne, Schering) is a nonselective cr- and @blocking agent recently approved by the U.S. Food and Drug Administration for the treatment of hypertension. It is available as an oral agent for the treatment of essential hypertension and as an intravenous (IV) agent for the treatment of severe hypertension and hypertensive crises. This drug’s mechanism of action couples the usual /3blocking effects of bradycardia and depressed myocardial contractility with vasodilatation and decreased peripheral vascular resistance from (Yblockade. It is the a-blocking effect that brings a decrease in blood pressure within one to two hours after oral ingestion and in five minutes after intravenous administration. Clinical trials show no clear advantage to this agent over previously available P-blocking drugs in the treatment of essential hypertension. It may be effective in some patients who have failed to respond to other P-blockers. Intravenous administration lowers the blood pressure of most patients, but it may fail if the patient is currently receiving Pblockers. The oral dose is initiated at 200 mg b.i.d. and may be increased slowly. The usual maintenance dose is 200 to 400 mg b.i.d. Intravenous labetalol may be given by continuous infusion at 2 mg/min or intermittently in doses of
313
20 mg given over a two-minute period at lominute intervals. Major adverse effects include all those previously associated with fl-blockers, with an increased incidence of postural hypotension and impotence. The drug is contraindicated in patients with congestive heart failure and bronchospastic disease. [Paul W. Snider, MD]
?? DESMOPRESSIN FOR HEMOPHILIA AND OTHER COAGULATION DISORDERS. Abramowicz M (ed). Med Lett 1984; 26:82. Desmopressin is a synthetic analog of arginine vasopressin. It has been available as DDAVP for intranasal use since 1978 for the treatment of diabetes insipidus. Desmopressin can also temporarily increase factor VIII: C concentration and von Willebrand’s factor in the blood. The intravenous (IV) formula of desmopressin is now available for the treatment of patients with moderate hemophilia A, type I von Willebrand’s disease, and uremia. Parenteral administration can temporarily decrease bleeding time sufficiently to stop bleeding from trauma or to permit minor surgical procedures to be performed. The use of this drug may thus help to avoid the risk of hepatitis and AIDS from the use of blood products. Patients must have at least 5% of normal factor VIII activity for treatment to be successful. Rarely encountered side effects include headache, nausea, facial flush, mild abdominal pain, and local pain at the injection site, most of which respond to a decrease in the infusion rate. The dose of IV desmopressin is 0.3 mg/kg diluted in saline given slowly over 30 minutes; maximum effect is usually obtained in 15 to 30 minutes. Intravenous desmopressin is safe and effective for the temporary correction of coagulation defects in patients with hemophilia A, von Willebrand’s disease, or [Jan M. Kief, MD] uremia.
0 ISOLATED SIXTH-NERVE PALSIES IN YOUNGER ADULTS. Moster ML, Savino PJ, Sergott RC, et al. Arch Ophthalmol1984; 102: 1328-1330. Isolated sixth-nerve palsy usually occurs in adults over 50 years of age and is associated with hypertension, diabetes, and atherosclerosis. Because this condition is less common in younger adults, the authors reviewed their experience with 49 patients, aged 15 to 50 years, with isolated sixth-nerve palsy. The following causes for