C. Ralph Buncher

Ragweed Immunotherapy in Adult Asthma

BACKGROUND Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear. METHODS We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years. RESULTS During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy. CONCLUSIONS Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years.

Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents

BACKGROUND Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS The mean (±SD) baseline age of the participants was 17±1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micronutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.).

DEMONSTRATION TO MEDICAL STUDENTS OF PLACEBO RESPONSES AND NON-DRUG FACTORS

Abstract A class experiment for medical students Summary was devised to demonstrate the influence of the placebo effect and non-drug factors on response to drugs. The subjects were conditioned to expect sedative or stimulant effects, but all received placebo in one or two blue or pink capsules. Predictions about the size and nature of the placebo response and influence of the non-drug factors were made before the experiment and discussed afterwards. Four of six predictions were fully confirmed. Drug- associated changes were reported by 30% of the subjects and were severe in 1 or 2 individuals. Two capsules produced more noticeable changes than one, and blue capsules were associated with more sedative effects than pink capsules. Students rated the experiment highly both as a learning experience and for its relevance to their future practice of medicine.

Prospective Analysis of Strength in Spinal Muscular Atrophy

Spinal muscular atrophy is a genetic disorder of the motor neurons that causes profound hypotonia, severe weakness, and often fatal restrictive lung disease. Patients with spinal muscular atrophy present a spectrum of disease from the most severe infantile-onset type, called Werdnig-Hoffmann disease (type 1), associated with a mortality rate of up to 90%, to a late-onset mild form (type 3), wherein patients remain independently ambulatory throughout adult life. Although many clinicians agree that patients with spinal muscular atrophy lose motor abilities with age, it is unknown whether progressive weakness occurs in all patients with spinal muscular atrophy. We present here results of the first prospective study of muscle strength in patients with spinal muscular atrophy. There was no loss in muscle strength as determined by a quantitative muscle test during the observation period. However, motor function diminished dramatically in some patients with spinal muscular atrophy. Explanations for this loss of function could not be determined from our data. Decrease in motor function could be caused by factors other than loss of strength. Therefore, it is not clear from our results whether spinal muscular atrophy is a neurodegenerative disease. We conclude that treatment trials in spinal muscular atrophy should be designed with consideration of the natural history of strength and motor function in this disorder. (J Child Neurol 2000;15:97-101).

Relationship between socioeconomic factors and severe childhood injuries.

The objective was to examine the relationship between injury rates and socioeconomic factors for children in Hamilton County, Ohio, using small-area analysis. The subjects were county residents less than 15 years old who were hospitalized or died of injuries between January 1, 1993, and December 31, 1995; they were identified through a population-based trauma registry. The census tract was the unit of analysis; the rate of injury per 100,000 population was the dependent variable. Risk factors included median income, level of education, percentage below the poverty level, percentage unemployment, percentage non-Caucasian, and percentage families headed by females. There were 2,437 children meeting the case definition; injuries per census tract ranged from 0 to 2,020.2 per 100,000 per year. Census tracts with higher injury rates had lower median incomes, more people with less than a high school education, more unemployment, more families headed by females, more people living below the poverty level, and more non-Cancasians han those with lower rates. In a regression model, percentage of people living below poverty level, percentage of those who did not graduate from high school, and percentage unemployment were significant risk factors for injuries, P<.001. Since small-area analysis examines associations on an ecological level rather than an individual level, these studies should always be interpreted with caution because an association found at the level of the census tract may not apply at the individual level. Inverventions to reduce injuries should target socioeconomically disadvantaged children living below the poverty level and those in areas with fewer high school graduates and more unemployment.

Prospective study of spinal muscular atrophy before age 6 years

Spinal muscular atrophy (SMA) is a common neuromuscular disorder of childhood, associated with a high mortality rate during the first 2 years of life. Most practitioners expect patients with SMA to follow a progressive course with loss of muscle strength and function over 2-10 years. Counselling sessions with parents frequently emphasize the high mortality rate and risk for respiratory failure. The progressive nature of SMA has been attributed to the loss of motor neurons. Fifty-eight children, ages 6 years and younger, were examined between January, 1987, and April, 1992, as part of a large, multicenter collaborative study of SMA. Muscle function was evaluated at regular intervals using a standardized protocol that was demonstrated to be reliable. We determined a prevalence of 56% for tongue fasciculations, a prevalence of 22% for facial weakness, and persistent deep tendon reflexes in one patient. Improved motor function and acquired milestones during the study were documented. This work should contribute toward a better understanding of the natural history of SMA.

Meta-analysis of EEG test performance shows wide variation among studies

Background: EEG results are used for counseling patients with seizures about prognosis and deciding on medications. Published sensitivities of interictal EEG vary widely. Objective: To account for variation in test characteristics between studies. Methods: Meta-analysis. Medline search, 1970 to 2000, of English language studies. Standard methods for meta-analysis of diagnostic test performance were used to determine the ability of EEG results to distinguish between patients who will and will not have seizures. Using linear regression, the authors assessed the influence of readers’ thresholds for classifying the EEG as positive, sample probability of seizure, percent of subjects with prior neurologic impairment, percent treated, and years followed. Results: Twenty-five studies involving 4,912 EEG met inclusion criteria. Specificity (range 0.13 to 0.99) and sensitivity (range 0.20 to 0.91) of epileptiform EEG interpretations varied widely and were heterogeneous by χ2 analysis (p < 0.001 for each). Diagnostic accuracy of EEG and the thresholds for classifying EEG as positive varied widely. In the multivariate model, differences in readers’ thresholds accounted for 37% of the variance in EEG diagnostic accuracy, and no other reported factors were significant. Conclusion: This analysis suggests that there is wide interreader variation in sensitivity and specificity of EEG interpretations, and that this variation influences the ability of EEG to discriminate between those who will and will not have seizure recurrences. In clinical practice, interpreting the degree to which a positive EEG result predicts increased seizure risk in an individual patient is difficult. Interpreting EEG with higher specificity yields more accurate predictions.

Cardiac tamponade: A comparison of right versus left heart compression

It has been postulated that in cardiac tamponade, the hemodynamic effects of compression of the right heart chambers and great veins are more important than are the effects of left heart compression. In 10 anesthetized dogs with surgically compartmented pericardium, the hemodynamic effects of right atrial and right ventricular compression were compared with the hemodynamic effects of left atrial and left ventricular compression. The effects of right heart compression, left heart compression, and then effects of combined right and left heart compression, were compared at three levels of intrapericardial pressure: 10, 15 and 20 mm Hg. Aortic mean pressure decreased significantly at each level of intrapericardial pressure with right-sided tamponade but not with left-sided tamponade. Left atrial mean pressures decreased significantly with right-sided tamponade and increased with left-sided and combined tamponade. Right atrial mean pressures increased significantly with right-sided and combined tamponade, but not with left-sided tamponade. Heart rate increased significantly with each of the three varieties of tamponade. Cardiac output and stroke volume, which decreased with each variety of tamponade, were significantly lower during right-sided than during left-sided tamponade. Combined tamponade lowered stroke volume more than did right-sided tamponade, and lowered cardiac output more at 15 and 20 mm Hg intrapericardial pressure. It is concluded that, in this preparation, right-sided cardiac compression has more important hemodynamic effects than does left-sided compression. However, left-sided tamponade still makes a significant contribution to the total hemodynamic picture of cardiac tamponade.

Radiation-Associated Carcinoma of the Salivary Glands a Controlled Study

Five hundred fifty-four persons were evaluated who had received external radiation therapy for benign diseases of the head and neck in childhood and whose salivary glands were presumably included in the radiation field. A significant excess of salivary gland cancers were noted when they were compared to 958 nonirradiated control subjects.

Therapeutic responses of spontaneous canine malignancies to combinations of radiotherapy and hyperthermia

Abstract The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy ( 60 CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44°C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4–5 hours in the other. Adjuvant hyperthermia resulted in a significant ( p p