Frederick H. Lovejoy

Value of the QRS Duration versus the Serum Drug Level in Predicting Seizures and Ventricular Arrhythmias after an Acute Overdose of Tricyclic Antidepressants

There is a need for a rapid predictor of potential clinical severity to guide therapy in patients with an acute overdose of tricyclic antidepressant drugs. We performed a prospective study of 49 such patients to observe the associations among serum drug levels, maximal limb-lead QRS duration, and the incidence of seizures and ventricular arrhythmias. Patients were divided into two groups on the basis of maximal limb-lead QRS duration. Group A (13 patients) had a duration of less than 0.10 second, and Group B (36 patients) had a QRS duration of 0.10 second or longer. No seizures or ventricular arrhythmias occurred in Group A. In Group B there was a 34 per cent incidence of seizures and a 14 per cent incidence of ventricular arrhythmias. All patients survived. Serum drug levels failed to predict the risk of seizures or ventricular arrhythmias accurately. Seizures occurred at any QRS duration of 0.10 second or longer (P less than 0.05), but ventricular arrhythmias were seen only with a QRS duration of 0.16 second or longer (P less than 0.0005). We conclude that determination of the maximal limb-lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants. Serum drug levels are not of predictive value.

Acute isopropyl alcohol intoxication: Diagnosis and management

Alcohol intoxication (methyl, ethyl, isopropyl, and ethylene glycol) is treated frequently in emergency room and intensive care units. Although high morbidity and mortality rates exist, effective therapies for methyl alcohol and ethylene glycol (ethyl alcohol blocking and hemodialysis) and ethyl and isopropyl alcohol (hemodialysis) are available. Prompt and accurate clinical and laboratory differentiation is needed to optimize these therapies. This review presents clinical, pharmacologic, and management data, contrasts important aspects in differential diagnosis, and suggests an appropriate approach to management of isopropyl alcohol intoxication.

A Promotion Ladder for Teachers at Harvard Medical School: Experience and Challenges

The authors describe the development, implementation, and institutionalization at Harvard Medical School of a promotion ladder that recognizes the teaching and scholarly contributions of full-time clinical faculty. They also discuss the challenges that arose during this process, for example, how to make the new track creditable and attractive to both the appointed faculty and the faculty at large. The criteria developed for promotion focus on a candidates skills and accomplishments in teaching, scholarship, clinical work, and departmental service. The authors present the elements of these criteria for the three professional levels of the ladder and outline the appointment process, including the steps for consideration of a given promotion. The development of this teacher–clinician ladder has had a positive influence on faculty who are committed to teaching by allowing recognition of their contributions in a track held to be the equal of the other full-time tracks in a medical faculty traditionally committed to research and patient care. Data are given for the 70 faculty who were promoted over the five years from 1989 to 1994. The true success of this promotion ladder will be measured only over time through its impact on the educational enterprise within the medical school and its hospitals, and its capacity to both successfully advance the careers of qualified medical educators and further the development of the field of medical education.

Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin.

Three children developed extensive extrapulmonary disease in the course of fatal adenovirus type 7 pneumonia. Several clinical features, including the unexpected onset of coma, suggested the development of Reye syndrome, but biochemical and histopathologic findings were inconsistent with this diagnosis. Virologic and pathologic studies did not reveal evidence of extrapulmonary adenovirus infection, despite clinical involvement of the liver, skeletal muscle, and central nervous system. The detection in premortem sera from all three patients of adenovirus penton antigen, known to be cytotoxic in vitro, suggests a possible mechanism for the production of extrapulmonary pathology in the absence of extrapulmonary virus infection.

Efficacy and toxicity of d-penicillamine in low-level lead poisoning

In a retrospective cohort study we reviewed our experience using D-penicillamine in children with low-level lead poisoning (whole blood lead levels 25 to 40 micrograms/dL) to determine its efficacy and the incidence of side effects. Two groups were compared: treated subjects (n = 84) were treated with penicillamine at a mean daily dose of 27.5 mg/kg; control subjects (n = 37) received no chelation therapy. Over a prechelation observation period of 60 days, lead levels (PbB) did not change in either group. With a mean period of 76 days of D-penicillamine therapy, PbB fell in treated patients by 33% (P less than 0.001). In 64 patients (76%), PbB was reduced to a currently acceptable range (less than or equal to 25 micrograms/dL). There were eight treatment failures (10%). In control subjects, mean PbB did not change significantly over 119 days of observation. Fourteen control subjects eventually required conventional chelation with calcium disodium ethylene-diaminetetraacetic acid, and 17 were lost to follow-up. Use of D-penicillamine was associated with an adverse reaction in 28 cases (33%); transient leukopenia occurred in eight, rash in seven, transient platelet count depression in seven, enuresis in three, and abdominal pain in two. Treatment was terminated prematurely in eight cases (10%) because of an adverse reaction. We conclude that D-penicillamine is effective therapy for selected children with low-level plumbism, but adverse effects can complicate or prevent its use in some patients.

Scholarly activities recorded in the portfolios of teacher-clinician faculty.

Purpose To explore what contributions to scholarship teacher-clinician faculty list in the portfolios that they use as evidence for promotion. Method In 1998, the authors randomly selected 15 Harvard Medical School teacher-clinicians (five from each rank of assistant, associate, and full professor) from among 120 such faculty members who had been successfully promoted between 1990 and 1997. Using a descriptive research study design, the authors counted and categorized the contributions to scholarship, teaching, and committee service that the faculty listed in their portfolios. They did not assess the quality or weighting of the contributions. Results According to the portfolios, the faculty members had contributed to both teaching and scholarships at local, regional, and national levels. They listed not only peer-reviewed original journal articles, but also works that integrated and synthesized knowledge: specifically, chapters, textbooks, editorials, syllabi, newsletters, computer resources, and videotapes. Faculty generally had published in multiple areas of scholarship, which fell in two domains: the faculty members subspecialty and medical education. The number of publications increased at each promotion level. The faculty also participated in broad-based teaching and education at the student, resident, fellow, and continuing medical education levels. Leadership contributions in education had occurred not only locally and regionally but also at a national level. Finally, faculty participated actively in service to the medical school, hospital, and national organizations, with leadership roles at the associate and full professor levels. Conclusion The academic culture at Harvard Medical School has shifted from promotion based solely on original scholarship to promotion based on a broad array of educational contributions. The faculty, as they seek promotion, create portfolios that list written scholarship, teaching, and service at the local, regional, and national levels and at all ranks of promotion.

Repetitive Oral Activated Charcoal and Control of Emesis in Severe Theophylline Toxicity

Excerpt Treatment with multiple doses of oral activated charcoal increases theophylline clearance in patients receiving theophylline therapy and in patients with mild theophylline toxicity (1-3). H...

Results of multicenter studies of digoxin-specific antibody fragments in managing digitalis intoxication in the pediatric population

Digitalis toxicity continues to be a problem for pediatric patients undergoing therapy with cardiac glycosides for heart failure or arrhythmias, as well as in accidental ingestions. In this article the previous use of digoxin-specific antibody Fab fragments to treat digitalis overdose or intoxication in children is reviewed. The case reports cited in the medical literature and the 57 pediatric cases gathered as a result of the multicenter clinical trial and postmarketing surveillance study reported here indicate that digoxin-specific antibody Fab fragments are effective in ameliorating signs of digitalis poisoning in children. Not only can Fab fragments rapidly eradicate potentially life-threatening arrhythmias and conduction defects, but they are also effective in treating hyperkalemia and other noncardiac manifestations of digitalis toxicity. In the small samples of patients studied to date, complications have been minimal and no allergic reactions to digoxin-specific Fab fragments have been observed. Recommendations for the management of digitalis intoxication in children are outlined.

Hypotension in severe tricyclic antidepressant overdose

Sixty four patients who presented to the emergency department following severe acute tricyclic antidepressant (TCA) overdose (defined as an antidepressant ingestion associated with a QRS interval greater than or equal to 0.10 seconds, TCA level greater than or equal to 500 ng/mL, or grade IV coma) were prospectively evaluated to determine the incidence of hypotension and the factors associated with its development. Among these patients, the mean antidepressant level was 1,094 ng/mL. The overall frequency of admission hypotension (systolic BP less than 95 mmHg) was 34% (22 of 64 patients). Using regression analysis, systolic BP showed poor correlation with TCA level (r = -.37) and maximal QRS interval (r = -.17) following severe TCA overdose. Using multivariate analysis with a logistic regression model, the influence of BP (as well as TCA level, QRS interval, and coingestion of another drug) was evaluated on four clinical outcomes: seizures, arrhythmias, aspiration pneumonia, and pulmonary edema. The occurrence of arrhythmias and pulmonary edema was significantly associated (inversely) with hypotension (P less than .01). Seizures and aspiration pneumonia were unrelated to admission BP. These results suggest that hypotension is common after severe TCA overdose and occurs independently of TCA level and prolongation of the QRS interval. Hypotension is strongly associated with the development of arrhythmias and pulmonary edema. Seizures and aspiration pneumonia may occur regardless of initial BP.

Pulmonary consequences of severe tricyclic antidepressant ingestion

We prospectively studied 56 consecutive patients with severe tricyclic antidepressant ingestion to determine the incidence of associated pulmonary complications. Among the patients meeting the entrance criteria, the mean antidepressant level was 1136 ng/ml. Other characteristics were a QRS duration of greater than or equal to 0.1 seconds in 35 (63%) and seizures in 19 (34%). Seventeen patients (30%) developed 18 abnormal chest X-ray findings which included pulmonary edema in 8 cases and aspiration pneumonia in 10. Using logistic regression, we evaluated the influence of tricyclic antidepressant level, blood pressure, QRS interval, seizures, drug co-ingestion and the use of gastric lavage vs. ipecac-induced emesis on pulmonary complications. For patients with pulmonary edema, the only significantly associated factor was hypotension on emergency department presentation. For aspiration pneumonia, no significant associations were found. Co-ingestion of another drug had no apparent influence on the development of pulmonary abnormalities. Our findings suggest that pulmonary edema and aspiration pneumonia are frequent complications of severe ingestions of tricyclic antidepressants. Pulmonary edema appears to result from hypotension or its treatment. The etiology of aspiration pneumonia is unclear. A chest X-ray should be obtained in all victims of tricyclic antidepressant overdose.