FDG SPECT in patients with lung masses.

STUDY OBJECTIVES: To determine whether 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) single-photon emission CT (SPECT) is useful in characterizing pulmonary masses. DESIGN: Scans were prospectively acquired and interpreted. Interpretations were performed with CT or chest radiograph but interpreters were blinded to eventual diagnosis. SETTING: University hospital practice and affiliated Veterans Administration medical center. PATIENTS OR PARTICIPANTS: Forty patients participated as part of an institutional review board-approved research protocol, and informed consent was obtained in all. Eight additional patient scans were acquired as part of their clinical evaluation for pulmonary mass. MEASUREMENTS AND RESULTS: There were 26 malignant lesions (12 were 1 to 2 cm in size, the rest were larger) and 17 benign lesions (3 were < 1 cm in size, 9 were 1 to 2 cm in size, and 5 were larger). Averaged sensitivity, specificity, positive predictive value, and negative predictive value were, respectively, 50% (12 of 24), 94% (17 of 18), 92% (12 of 13), and 59% (17 of 29) for lesions 1 to 2 cm in size, 100% (28 of 28), 90% (9 of 10), 97% (28 of 29), and 100% (9 of 9) for lesions > 2 cm in size. There was good correlation between readers (p < 0.0001). CONCLUSION: FDG SPECT is useful in characterizing pulmonary masses > 2 cm in size and appears to be equivalent to positron emission tomography for these lesions. Although currently clinically suboptimal for characterizing lesions < or = 2 cm in size, FDG SPECT appears to be better than current anatomic imaging methods. In addition, the positive predictive value of FDG SPECT for small lesions is also high (92%), and this technique appears potentially useful in the subset of patients in whom a positive result would alter clinical diagnostic pathways or care.

Moving a graveyard: how one school prepared the way for continuous curriculum renewal.

From 1991 to 1996, the faculty at the University of Florida College of Medicine initiated several significant changes in its curriculum. These changes, included the introduction of early clinical experience in primary care settings; the enhancement of active learning experiences in small-group settings; production and use of computer-based interactive learning materials; increased clinical teaching in the ambulatory care training in an interdisciplinary primary care clerkship; effective course and faculty evaluation; establishment and use of an assessment center for instruction and performance-based evaluations utilizing standardized patients; creation of a medical education center as the focal point for logistics support of the teaching faculty and education data handling; creation of a faculty development program; and initiation of mission-based budgeting based on the faculty's teaching effort and quality. Because the faculty were relatively conservative, it was important to identify variables that would facilitate the introduction of changes and those that might hinder it. The following factors were most important: interest and support by the dean and clearly defined delegation of authority to an associate dean; introduction of a mission-based budgeting process that allocates education funds on the basis of faculty teaching effort and its quality; a clear understanding of the empowerment of the curriculum committee; and an identification of the principles that should guide educational planning and implementation. These efforts are considered the beginning of the continuous renewal needed to respond to information networking, scientific and technological innovations, and the fundamental changes in health care delivery. As these changes have taken place, a shift toward greater institutional control of the educational program leading to the MD degree has been evident.

Natural history and course of acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group.

STUDY OBJECTIVE: To determine the pathogenesis and clinical course of lactic acidosis in adults receiving standard medical care. DESIGN: Placebo arm of a 5-year prospective, randomized, blinded study comparing placebo and dichloroacetate as specific lactate-lowering therapy. Each patient received intravenous saline placebo in addition to conventional therapy. SETTING: Intensive care units of 10 tertiary care hospitals in North America. PATIENTS: One hundred twenty-six patients with lactic acidosis, defined as arterial blood lactate greater than or equal to 5 mmol/L and either arterial pH of less than or equal to 7.35 or base deficit greater than 6 mmol/L. Patients were followed for up to 6 months. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD demographic entry data for 126 patients included: age 56 +/- 17 years, lactate 10.4 +/- 5.5 mmol/L, pH 7.24 +/- 0.14, calculated base deficit 14.1 +/- 5.4, arterial systolic blood pressure 103 +/- 29 mm Hg, Glasgow Coma score 7.9 +/- 4.9, and APACHE II score 19.2 +/- 8.1. Despite fluids and pressors, 32% of patients had systolic blood pressures of less than or equal to 90 mm Hg in association with sepsis (59%), cardiac failure (18%), or hemorrhage (18%). The most common causes of lactic acidosis in the absence of shock were sepsis (49%), liver disease (15%), and respiratory failure (12%). The median survival was 38.5 hours. Survival at 24 hours was 59%. Arterial pH predicted 24-hour survival better than base deficit or bicarbonate level. Percent survival was 41% at 3 days and 17% at 30 days. Only 21% of patients survived to leave the intensive care unit, and 17% were discharged from the hospital. In patients receiving sodium bicarbonate, neither acid-base nor hemodynamic status improved. CONCLUSIONS: In this first prospective study of the clinical course of acute lactic acidosis in adults, nearly all subjects had both hemodynamic and nonhemodynamic (metabolic) underlying causes, many of which independently predicted survival and most of which were refractory to standard care.

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.

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.

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.

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.

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.

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.

Treatment of lactic acidosis with dichloroacetate.

We administered dichloroacetate, which prevents or reverses hyperlactatemia in animals and lowers plasma lactate levels in human beings, to 13 patients with lactic acidosis of various causes. All had hypotension, and their acidemia had resisted treatment with sodium bicarbonate. The metabolic effects of dichloroacetate were evaluated in 11 patients. In seven dichloroacetate significantly reduced the level of arterial blood lactate (P less than 0.005) from the base-line value and raised the levels of arterial blood bicarbonate (P less than 0.02) and arterial pH (P less than 0.005). In six of these seven, the acidemia resolved completely with therapy. In 10 of the 13 patients systolic blood pressure increased by 10 to 40 mm Hg, and 4 patients had a 21 per cent increase in cardiac output (P less than 0.02). Despite improvement in their lactic acidemia, all patients but one died of their underlying disease. No serious drug-related toxicity occurred. We conclude that dichloroacetate is a safe and effective adjunct in the treatment of patients with lactic acidosis, although the ultimate prognosis may depend on the underlying disease.

The effect of weight loss on sleep-disordered breathing and oxygen desaturation in morbidly obese men.

Four morbidly obese men who had been found to have significant sleep-disordered breathing and oxygen desaturation were restudied after an average weight loss of 108 kg (range 53-155 kg). In all subjects, weight loss was accompanied by a significant reduction in the number of episodes per hour of sleep-disordered breathing events. In three of the four subjects, there was improvment in the severity of desaturation accompanying abnormal breathing. The two subjects with daytime somnolence and hypercapnia prior to weight loss showed the most dramatic improvement in desaturation. This suggests that obesity is a cause, rather than an effect, of the sleep apnea syndrome.

Investigation of a dosage regimen for intravenous theophylline.

A study was designed to evaluate the validity of the dosage guidelines for theophylline recommended by Hendeles and Weinberger. A total of seven asthmatic smokers and non-smokers were entered and studied. Theophylline serum concentrations were determined prior to the start of therapy and at intervals following initiation of an infusion. The mean theophylline concentration attained for all subjects was 10 micrograms/ml, however, five of the six patients completing the study did not achieve the predicted serum theophylline concentration. Further study of higher dosage designed to achieve a concentration of 12 micrograms/ml is suggested.

Evaluating the patient who claims to be disabled.

The decision to award an individual disability benefits is administrative and involves a review of his education and work history in relation to his medical impairment. The physician evaluating such a patient needs to be sympathetic to the stressful situation yet objective in supplying medical evidence.