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Biomedical subjects

E M Harman

Publications and source records attributed to E M Harman.

9 recordsLinked to original sources

A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group.

BACKGROUND: Mortality is very high in lactic acidosis, and there is no satisfactory treatment other than treatment of the underlying cause. Uncontrolled studies have suggested that dichloroacetate, which stimulates the oxidation of lactate to acetyl-coenzyme A and carbon dioxide, might reduce morbidity and improve survival among patients with this condition. METHODS: We conducted a placebo-controlled, randomized trial of intravenous sodium dichloroacetate therapy in 252 patients with lactic acidosis; 126 were assigned to receive dichloroacetate and 126 to receive placebo. The entry criteria included an arterial-blood lactate concentration of > or = 5.0 mmol per liter and either an arterial-blood pH of < or = 7.35 or a base deficit of > or = 6 mmol per liter. The mean (+/- SD) arterial-blood lactate concentrations before treatment were 11.6 +/- 7.0 mmol per liter in the dichloroacetate-treated patients and 10.4 +/- 5.5 mmol per liter in the placebo group, and the mean initial arterial-blood pH values were 7.24 +/- 0.12 and 7.24 +/- 0.13, respectively. Eighty-six percent of the patients required mechanical ventilation, and 74 percent required pressor agents, inotropic drugs, or both because of hypotension. RESULTS: The arterial-blood lactate concentration decreased 20 percent or more in 83 (66 percent) of the 126 patients who received dichloroacetate and 45 (36 percent) of the 126 patients who received placebo (P = 0.001). The arterial-blood pH also increased more in the dichloroacetate-treated patients (P = 0.005). The absolute magnitude of the differences was small, however, and they were not associated with improvement in hemodynamics or survival. Only 12 percent of the dichloroacetate-treated patients and 17 percent of the placebo patients survived to be discharged from the hospital. CONCLUSIONS: Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival.

Acidosis, Lactic

Pulmonary problems in pregnancy.

Pregnant women with asthma and pulmonary infections should be treated essentially the same as nonpregnant women with similar disease severity. Definitive diagnosis and prompt treatment with heparin should be used for patients with pulmonary thromboembolism.

Asthma

Systemic absorption of topical lidocaine in elderly and young adults undergoing bronchoscopy.

This study compared the systemic absorption of topically administered lidocaine in elderly and young adult patients who were undergoing fiberoptic bronchoscopy. Fourteen elderly subjects aged 60-72 years (mean 67 years) and five young subjects age 31-48 years (mean 42 years) were compared with respect to dosage requirements to achieve satisfactory local anesthesia, rate and extent of lidocaine systemic absorption, plasma drug levels, elimination half-life, and drug side effects. Blood samples were drawn prior to, during, and for an average of 3 hours after the completion of bronchoscopy. Lidocaine plasma concentrations averaged in the range of 3.04-0.88 micrograms/ml from the beginning of the procedure to the end of blood sampling. Despite high cumulative amounts of 19 mg/kg (1200 mg) of lidocaine administered topically, the regimen proved relatively safe and achieved satisfactory anesthesia. In patients without known risk factors either for delayed hepatic lidocaine clearance or for enhanced mucosal absorption, the regimen is suitable for both young and old individuals.

Administration, Topical

Rapid mucosal absorption of topical lidocaine during bronchoscopy in the presence of oral candidiasis.

Local anesthetic agents are topically applied during diagnostic procedures such as bronchoscopy. These routine procedures are associated with only rare reports of drug toxicity or extensive systemic drug absorption. We report a case of rapid systemic absorption and elevated plasma lidocaine concentrations following a fiberoptic bronchoscopy procedure in a man with oral candidiasis and lung cancer.

Absorption

Dichloroacetate in the treatment of lactic acidosis.

An open, prospective evaluation of the effects of dichloroacetate on morbidity and survival time was done in 29 pediatric and adult patients with lactic acidosis. Dichloroacetate was administered intravenously over 30 minutes as two 50 mg/kg body weight doses separated by 2 hours. Five patients underwent retreatment with two additional drug doses and were considered new cases when analyzing for treatment response. Survival, however, was determined from the time of initial entry into the study. Patients were considered to respond to treatment if arterial lactate concentration decreased at least 20% from the pretreatment level within 6 hours of beginning the first dichloroacetate infusion. Using this criterion, 26 cases responded to therapy with dichloroacetate. For all cases, patients' mean arterial lactate concentration decreased 52% (P = 0.0009), arterial bicarbonate concentration increased 35% (P = 0.0003), and arterial pH increased (P = 0.024) to normal, defined as the range 7.35 to 7.45. Among responders, however, arterial lactate concentration decreased 74% (P = 0.0001), arterial bicarbonate level increased 47% (P = 0.0001), and arterial pH increased (P = 0.0004) to the normal range. Median survival time among responders was 60 hours, compared to 26 hours among nonresponders (P less than 0.001). There was no evidence of toxicity to dichloroacetate.

Acetates

Immunologic lung disease.

The term "immunologic lung disease" comprises a broad spectrum of disease. I have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies.

Alveolitis, Extrinsic Allergic