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Study Objective: To identify factors responsible in the selection of anesthesiology as a career by Mayo Clinic house staff (i.e., residents and clinical fellows); to evaluate their level of satisfaction with their choice of career and training program, and their perceptions of the future for anesthesiology trainees., Design: Cross-sectional analysis using a questionnaire survey of 67 house staff enrolled in the anesthesiology training program during the 1995-1996 academic year., Setting: Mayo Clinic, Rochester, MN., Measurements and Main Results: Forty-eight (72%) of those surveyed responded to the questionnaire. Data were analyzed using the Chi-square and Mann-Whitney rank sum tests. A p-value less than or equal to 0.05 was considered statistically significant. The most frequently cited reasons for selecting anesthesiology as a career included the following: it is a "hands-on" specialty, it involves clinical application of physiology and pharmacology, and it provides immediate gratification in one's work. The most frequently cited reasons for selecting our training program were the diversity of training experience, prestige associated with Mayo Clinic, and employment opportunities following training. Forty-four (92%) felt downsizing of anesthesiology training programs was a national trend, 26 (54%) anticipated difficulty obtaining a job following training, and 16 (33%) felt they had future job security. Overall, 47 (98%) were happy with their career choice, and 40 (83%) would choose anesthesiology as a career if they were now graduating from medical school. All 1996 graduates found suitable employment without difficulty., Conclusions: Our data indicate that selection of a career in anesthesiology and training program are strongly associated with concerns regarding educational experiences and postgraduate employment opportunities.

Background and Objectives: Preoperative time spent with patients has been abbreviated with the advent of same-day admission requirements and outpatient surgery. This study was conducted to evaluate the effects that materials mailed to the home relating to anesthetic-focused patient education may have on preoperative patient anxiety., Methods: Patients scheduled for a total hip arthroplasty or for a total knee arthroplasty were screened via telephone for inclusion in a prospective, randomized study. Patients were asked about their access to a video cassette recorder/player (VCR) and their limitations regarding hearing or vision. Subjects were randomly assigned to either the intervention group and received two pamphlets and a video describing general and regional anesthesia or to the usual care group. All subjects were mailed a preoperative demographic questionnaire and a State Trait Anxiety Inventory (STAI), as developed by CD Spielberger. Questionnaires were completed at least 96 hours prior to admission and again preoperative on the day of surgery., Results: Of 236 patients screened, 26 had no access to a VCR, 6 were hearing or visually impaired, and 4 declined participation. Of 200 subjects randomized, 134 completed both sets of questionnaires and thus form the basis of this report. A statistically significant difference between the subjects who received the video and pamphlets and the usual care subjects was detected with respect to change in STAI-assessed anxiety from baseline to immediately prior to surgery (P = .035). The intervention subjects experienced a smaller mean increase in anxiety. Forty-nine percent of the usual care subjects expressed interest in having additional information., Conclusions: Increase in preoperative anxiety is diminished when additional anesthesia information in printed and video format is made available. Useful information can be provided to patients to view or read prior to surgery.

Background: The goal of this study was to determine whether airway obstruction determined by preoperative spirometry predicts perioperative complications in smokers undergoing abdominal surgery whose treatment is managed according to current clinical practice., Methods: A pulmonary function database identified patients undergoing abdominal surgery who met the following criteria for airway obstruction (n = 135): a forced expiratory volume less than 40% of predicted normal value, a forced expiratory volume:forced vital capacity ratio less than the lower limit of predicted normal, a smoking history of more than 20 pack-years, and an age older than 35 yr. A group of patients without airway obstruction (n = 135) was matched for gender, surgical site (upper vs. lower abdominal), smoking history, and age. Medical records were reviewed by an abstractor to identify perioperative complications that occurred within 30 days after surgery., Results: The forced expiratory volume values were 0.9+/-0.21 (mean +/- SD) and 2.9+/-0.61 in patients with and without airway obstruction, respectively. When analyzed by conditional logistic regression using the 1:1 matched-pairs feature, including age, pack-year smoking history, site of incision, and current smoking status as covariates, in patients with airway obstruction bronchospasm was more likely to develop (odds ratio, 6.9 [95% confidence interval, 1.2 to 38.4]) but the patients were not more likely to need prolonged endotracheal intubation (odds ratio, 1.1 [95% confidence interval, 0.4 to 3.2]). They were also no more likely to need prolonged intensive care admission or readmission. The frequency of other complications was less than 5%., Conclusion: When other factors were considered, preoperative airway obstruction predicted the occurrence of bronchospasm, but not prolonged endotracheal intubation, in smokers undergoing abdominal surgery who are treated according to current clinical practices.

Background: A past history of major depression or alcoholism has been associated with poorer smoking treatment outcomes., Aim: To evaluate the efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism, and changes in depressive symptoms during smoking abstinence., Method: Data were drawn from a multicentre trial of bupropion for smoking cessation. Smokers (n = 615) received placebo or bupropion sustained-release at 100, 150, or 300 mg/day for six weeks after target quit date (TQD). The primary outcome was the point prevalence smoking abstinence at the end of treatment and at one year. The Beck Depression Inventory (BDI) was used to assess depressive symptoms., Results: A significant dose-response effect of bupropion for smoking cessation was found. This was independent of history of major depression or alcoholism. Among those continuously abstinent from smoking for two weeks following TQD, an increase in BDI score was associated with a return to smoking at end of treatment., Conclusions: Bupropion is efficacious for smoking cessation independently of a former history of major depression or alcoholism. Increases in depressive symptoms during an initial period of abstinence are associated with a return to smoking.

Background: Patients with cirrhosis have a reduced life expectancy. Anesthesia and surgery have been associated with clinical decompensation in patients with cirrhosis., Methods: The authors retrospectively reviewed the records of all patients with the diagnosis of cirrhosis who underwent any surgical procedure under anesthesia at their institution between January 1980 and January 1991 (n = 733). Univariate and multivariate analyses were used to identify the variables associated with perioperative complications and short- and long-term survival., Results: The perioperative mortality rate (within 30 days of surgery) was 11.6%. The perioperative complication rate was 30.1%. Postoperative pneumonia was the most frequent complication. Multivariate factors that were associated with perioperative complications and mortality included male gender, a high Child-Pugh score, the presence of ascites, a diagnosis of cirrhosis other than primary biliary cirrhosis (especially cryptogenic cirrhosis), an elevated creatinine concentration, the diagnosis of chronic obstructive pulmonary disease, preoperative infection, preoperative upper gastrointestinal bleeding, a high American Society of Anesthesiologists physical status rating, a high surgical severity score, surgery on the respiratory system, and the presence of intraoperative hypotension., Conclusion: Risk factors have been identified for patients with cirrhosis who undergo anesthesia and surgery.

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n=29), active 4 mg nicotine gum (n=31), saline placebo nasal spray (n=16) or placebo gum (n=15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1=no withdrawal, 41=extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (+/-SD) age of the subjects was 38.6 (+/-10.1) years, 48% were females, smoking rate was 24.5 (+/-7.8) cigarettes per day, and years of smoking was 19.9 (+/-10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects.

The purpose of this study was to compare the psychotropic prescribing practices of family physicians and psychiatric physicians, and to assess their satisfaction with education about psychotropic prescribing. A survey was mailed to 461 active members of the Minnesota Psychiatric Society and to a randomized sample of 461 active members of the Minnesota Academy of Family Physicians. Major depression, panic disorder, and dementia with behavioral disturbance were selected for study. For each disorder, we asked for the estimated number of patients seen and treated as well as a list in order of preference of the three medications they most commonly use. Those surveyed were also asked about their level of satisfaction with the training they received in medical school, residency, and continuing medical education (CME) courses on the topic of psychotropic prescribing. The two physician groups reported similar prescribing practices for the single-drug treatment of depression. Family physicians more frequently prescribed minor tranquilizers and older generation psychotropics than did psychiatrists when treating panic disorder and dementia with behavioral disturbance. Patients with depression were the least likely to be referred to other health professionals. Neither physician group was satisfied with medical school education in this area; family physicians were less satisfied with residency training and in related CME courses than were psychiatric physicians. Additional study is needed to better understand interspecialty practice variation for commonly encountered psychiatric disorders. Medical education programs at all levels could better meet the reported needs of their graduates by providing more attention to prescribing psychotropic agents.

Background: The objectives of our study were to determine the frequency of supraventricular tachyarrhythmias (SVTAs) among modifications of the Fontan operation and identify risk factors for developing SVTA., Methods and Results: The population consisted of all patients who had any modification of the Fontan operation at the Mayo Clinic between 1985 and 1993. Clinically significant SVTAs were those requiring initiation or change of antiarrhythmic treatment, and they were divided into early SVTAs (<30 days after the operation) and late SVTAs (>/=30 days after the operation). Clinical histories were reviewed, and health status questionnaires were sent. Four hundred ninety-nine patients had various modifications of the Fontan operation. Frequency of early SVTA was 15%. Risk factors identified by multivariate analysis for early SVTA were AV valve regurgitation, abnormal AV valve, and preoperative SVTA. Frequency of late SVTA was 6% by 1 year, 12% by 3 years, and 17% by 5 years. Risk factors for late SVTA were age at operation (<3 or >/=10 years) and systemic AV valve replacement. By univariate and multivariate analysis, the type of Fontan operation was not a significant risk factor for late SVTA when all 6 modifications were considered. However, when we analyzed the frequency of late SVTA for the 2 recently used modifications, we found a lower frequency of late SVTA in patients with atriopulmonary connection with lateral tunnel compared with those with total cavopulmonary connection., Conclusions: Postoperative SVTA continues to be a significant problem. Risk factors for SVTA are AV valve regurgitation, abnormal AV valve, preoperative SVTA, and age at operation. Frequency of SVTA does not appear to be related to type of Fontan procedure except for slightly lower frequency in patients with atriopulmonary connection with lateral tunnel compared with those with total cavopulmonary connection.

Objective: To assess the outcomes of anesthesia and surgery for men and women 100 years of age and older., Design: Retrospective cohort study in the 20-year time period from 1975 to 1994, with follow-up through 1995., Setting: Mayo-affiliated hospitals and Olmsted Community Hospital, Rochester, Minnesota., Participants: All men and women 100 years of age and older who underwent surgery at a participating hospital., Measurements: Forty-eight-hour and 30-day perioperative morbidity and mortality; long-term survival., Results: Thirty-one men and women aged 100 to 107 years underwent 42 procedures. One major complication (3%) within 48 hours was observed. The 48-hour, 30-day, and 1-year mortality rates were 0%, 16.1%, and 35.5%, respectively. When compared with survival rates for age-, gender-, and calendar year of birth-matched peers from the general population, the survival rate for centenarians who underwent surgery and anesthesia was comparable to the rate expected., Conclusion: These data suggest that people 100 years of age and older who have operable diseases or injuries should not be denied surgical interventions because of perceived risks associated with their advanced age.

Twenty-six symptomatic subjects with clinical evidence plus either high-resolution computed tomography (HRCT, n = 25) or open-lung biopsy (OLB, n = 1) patterns typical for idiopathic usual interstitial pneumonia (idiopathic UIP) were entered into a randomized prospective treatment trial using high-dose prednisone (n = 12) versus colchicine (n = 14). The minimum dose of prednisone used was 60 mg/d for 1 mo, tapered to 40 mg/d over the second month, tapered to 40 mg every other day during the third month, with subsequent doses adjusted as clinically indicated. The dose of colchicine was 0.6-1.2 mg/d, as tolerated. The presence of a rim of subpleural honeycomb change was present in all of the 25 subjects who had HRCT. Subjects treated with high-dose prednisone alone experienced a higher incidence of serious side effects and also exhibited a trend (not statistically significant, p = 0.391) to more rapid decline of pulmonary function and shortened survival than did those treated with colchicine alone. In most subjects with typical clinical and HRCT features of idiopathic UIP, neither prednisone nor colchicine resulted in objective improvement, and the disease continued to progress in the majority. Colchicine appears to be a safer alternative to a trial of high-dose prednisone but may be no different than no therapy.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, urine excretion rates of nicotine and cotinine were measured in 70 subjects while they were actively smoking (baseline) and for 6 consecutive inpatient days while they were receiving transdermal nicotine therapy. Subjects were stratified according to baseline smoking rate as light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30 cigarettes per day) smokers and randomly assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg. Steady-state excretion rates of nicotine and cotinine were attained in 2 and 3 days, respectively, at all doses and were independent of smoking rate. Percentage replacement of nicotine was calculated by dividing steady-state nicotine or cotinine excretion rates by their respective baseline excretion rates. Significant underreplacement occurred with the 11-mg/day dose, particularly in moderate and heavy smokers (<50%). At a dose of 22 mg/day, nicotine replacement was still <100% in the majority of subjects. Only at a dose of 44 mg/day did mean replacement exceed 100% regardless of baseline smoking rate.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30 cigarettes per day). Steady-state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady-state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.

This study describes the current vital, health, and employment status of 249 patients with chronic pain who were treated in a pain management center at the Mayo Clinic, on average, 13 years ago. These patients do not have an increased risk of mortality; their death rate is similar to that of the US white population. However, 68% of the patients reported worse-than-average or an abnormal level of bodily pain, with increased morbidity in their physical health, physical functioning, and social functioning. Emotional and mental health were claimed to be adequate. About half of the patients reported being gainfully employed.

Regression equations are presented for converting the non-K-corrected raw scores on the Minnesota Multiphasic Personality Inventory (MMPI) basic scales to an estimated optimism-pessimism score. This score describes an individual's explanatory style on a continuum from optimistic to pessimistic. These equations will enable clinicians and researchers to estimate an optimism-pessimism score if the MMPI item responses are not accessible or if computer scoring facilities for individual items are unavailable.

Objective: To determine the extent of side effects during the initial use of nicotine nasal spray for smoking cessation., Design: We performed a one-sample, noncomparative, open-label evaluation of the pattern of use, side effects, relief of withdrawal symptoms, and cotinine levels with nicotine nasal spray., Material and Methods: Adult smokers were recruited to use the nicotine nasal spray for smoking cessation at a dosage of 1 to 2 mg/h. Subjects completed daily diaries, which included an assessment of nicotine withdrawal symptoms, previously reported irritant effects of the nicotine nasal spray, and symptoms of nicotine toxicity. A plasma cotinine level was measured at baseline and at day 7 for calculation of percentage replacement., Results: The mean age of the 50 study subjects was 43.7 years, 46% were women, and the mean baseline smoking rate was 28.5 cigarettes per day. We found an increase in five symptoms (runny nose, nasal irritation, throat irritation, watering eyes, and sneezing) that had been essentially absent before initiation of use of the nicotine nasal spray. All but throat irritation decreased significantly during days 0 through 7 of the study. The mean daily frequency of nicotine nasal spray use for the first week was 15.0 doses. Use of the nasal spray decreased significantly (P<0.001) during the initial 8 weeks of treatment. The mean percentage cotinine replacement for those subjects who were abstinent at day 7 was 38.6%., Conclusion: Although nicotine nasal spray causes substantial irritant side effects during the first few days of use, these adverse effects decrease significantly within the first week. Despite these side effects, subjects continued to use the nicotine nasal spray and experienced a high rate of initial abstinence from smoking.

Background: Inhaled corticosteroids and oral theophylline are effective treatments for moderate asthma., Objective: We sought to compare the benefits and adverse reactions of theophylline and aerosol beclomethasone spray., Methods: A multicenter, double-blind, double-placebo, randomized, controlled trial of 1-year duration was performed. Seven hundred forty-seven patients with asthma received either beclomethasone dipropionate aerosol spray (84 microg four times per day) or sustained-release theophylline twice per day in doses adjusted for optimum control of the disease. The main outcome measures were daily diary of symptoms and peak flow rates (recorded on a mark-sense computer-readable form); supplemental bronchodilator use; doctor's office or hospital visits and absence from work or school; spirometry; methacholine testing; adverse experiences; and cortisol blood measurements., Results: Both treatment strategies reduced symptoms promptly and achieved low absenteeism from work or school and low rates of emergency treatment for asthma. Both maintained nearly normal pulmonary function. Beclomethasone was statistically significantly more effective in reducing symptoms, supplemental bronchodilator and systemic glucocorticoid doses, bronchial hyperresponsiveness, and eosinophilia. However, the magnitude of these differences was small. Theophylline caused more headache, nervousness, insomnia, and gastrointestinal distress, and more patients discontinued treatment because of side effects. Beclomethasone caused more oropharyngeal candidiases and hoarseness and reduced morning plasma cortisol levels before and after cosyntropin. It reduced the rate of growth in children. No new cataracts or glaucoma developed., Conclusion: Theophylline effectively controlled symptoms at lower than the customarily recommended blood level. The risk/ benefit profiles of these agents suggest that inhaled corticosteroids may be the preferred agent for most adult patients and for some children.

Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance. The study group consisted of 54 men and 50 women with a median age of 63 yr. Median survival was 3.8 yr after diagnosis by OLB with an estimated 10 yr survival of 27%. Current histopathologic review showed a heterogeneous group including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia/fibrosis (NSIP), acute interstitial pneumonia (AIP), bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), and others. Median survival of the UIP group was 2.8 yr which is significantly worse (p < 0.001) than for other subgroups of chronic interstitial pneumonias. IPF includes several histopathologic subgroups with significantly different survival rates. Patients with UIP have worse survival than patients with other types of idiopathic chronic interstitial pneumonias including NSIP. Accurate histopathologic classification is essential for prognostication in patients with IPF.

Nicotine may affect cardiovascular function through release of neurotransmitters from autonomic nerves or release of vasoactive substances from the vascular endothelium. Nitric oxide is a neurotransmitter and endothelium-derived factor that reduces tone of vascular smooth muscle. Experiments were designed to determine whether or not use of nicotine nasal spray for smoking cessation affects plasma levels of nitric oxide. Forty smokers self-administered nicotine by nasal spray (one 0.5 mg spray to each nostril). Blood samples were taken before the use of the nasal spray and at treatment day 7 for the measurement of cotinine by high pressure liquid chromatography and nitric oxide (NOx) by chemiluminescence. Age-comparable controls were never-smokers nonnicotine users recruited from laboratory personnel. Mean plasma concentrations of NOx from smokers before treatment were significantly greater compared with nonsmokers (23 +/- 10, n = 40 and 15 +/- 6, n = 13 nmoles/mL [mean +/- SD], respectively, P < 0.01). Plasma NOx in smokers was not significantly correlated with the average daily number of cigarettes smoked (r2 = 0.02, P > 0.05) but was positively and linearly correlated with plasma cotinine (r2 = 0.13, P < 0.02). In 32 self-reported abstinent smokers (confirmed by expired carbon monoxide < 9 ppm) using nicotine nasal spray, cotinine decreased by 64% from pretreatment levels of 284 +/- 103 to posttreatment levels of 90 +/- 58 ng/mL. Plasma NOx was unchanged and went from 23.0 +/- 10.1 at pretreatment to 21 +/- 12 nmoles/mL with nicotine treatment. These results suggest that nicotine-use, independent of cigarette smoking, affects plasma NOx.

Objective: Examine weight change in subjects receiving variable doses of transdermal nicotine replacement for smoking cessation., Design: Randomized, double-blind clinical trial., Setting: One-week inpatient treatment with outpatient follow-up through 1 year., Intervention: This report examines weight change after smoking cessation for 70 subjects randomized to placebo or to 11, 22, or 44 mg/d doses of transdermal nicotine. The study included 1 week of intensive inpatient treatment for nicotine dependence with active patch therapy continuing for another 7 weeks. Counseling sessions were provided weekly for the 8 weeks of patch therapy and with long-term follow-up visits at 3, 6, 9, and 12 months., Measurements and Main Results: Forty-two subjects were confirmed biochemically (i.e., by expired carbon monoxide) to be nonsmokers at all weekly visits during patch therapy. Their 8-week weight change from baseline was 3.0 +/- 2.0 kg. For these subjects, 8-week weight change was found to be negatively correlated with percentage of cotinine replacement (r = -.38, p = .012) and positively correlated with baseline weight (r = .48, p = .001), and age (r = .35, p = .025). Men had higher (p = .003) 8-week weight gain (4.0 +/- 1.8 kg) than women (2.1 +/- 1.7 kg). Of the 21 subjects who abstained continuously for the entire year, 20 had their weight measured at 1-year follow-up. Among these 20 subjects, 1-year weight change was not found to be associated with gender, baseline weight, baseline smoking rate, total dose of transdermal nicotine, or average percentage of cotinine replacement during the 8 weeks of patch therapy., Conclusions: This study suggests that higher replacement levels of nicotine may delay postcessation weight gain. This effect is consistent for both men and women. We could not identify any factors that predict weight change with long-term abstinence from smoking.

Levodopa (LD) is the most effective drug for symptomatic control of Parkinsonism (PS). As prolonged LD therapy leads to response failure; is associated with adverse effects; may accelerate disease process, and its impact on life expectancy is controversial, delaying LD use has been recommended. We studied 934 PS cases including 859 Parkinson's disease (PD) patients over twenty-two years (1968-1990) to identify: (i) survival change coincident with widespread LD use and (ii) the critical level of disease severity when LD influences survival. Survival was measured from the date of first assessment until the last evaluation for a cumulative 3563 person-years of follow-up and compared with that expected in the general population of the same age, sex and year of birth. A Cox regression model was used to identify independent clinical predictors of survival. The observed to expected survival was reduced significantly in PS. Dementia and advanced disability at initial assessment and the final non-PD diagnosis, each was independently associated with poor survival. Survival improved significantly coincident with the widespread unrestricted access to LD (p = 0.024 - < 0.001) compared to pre-levodopa era cases. Life expectancy was longest in the more recent non-demented PD cases. When the major disease and treatment related factors were considered the timely use of levodopa in the recent cases resulted in improved survival compared to the earlier cases who received LD later in the course of illness. When LD naive cases were considered, survival was significantly reduced if the drug was delayed until Stage 3 Hoehn and Yahr, but not so if the patients remained untreated during Stages 1 and 2 Hoehn andYahr[1]. Life expectancy in PD has increased significantly since the widespread use of LD. This benefit is evident only if LD therapy is initiated before the patient reaches Stage 2.5 disability [2].

Background and Methods: Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or "target quit date") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less., Results: At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups., Conclusions: A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.

Background: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine tartrate as a liquid enema decreases systemic nicotine absorption and may be effective for treatment of active distal ulcerative colitis. Ileocolonic delivery of nicotine tartrate via a delayed release oral capsule would be the preferred route to deliver nicotine to the colon., Aim: To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine., Methods: Twenty healthy human subjects received delayed-release oral nicotine tartrate at one of two doses (each group n = 10): 3 mg and 6 mg nicotine. All subjects also received intravenous nicotine tartrate (at a dose of 15 micrograms nicotine base/kg) during a separate study period. Serum nicotine concentrations were determined by gas chromatography-mass spectrometry. In addition, concentrations of serum cotinine (major nicotine metabolite) were determined by high-performance liquid chromatography in all samples for two subjects (both given 6 mg nicotine). Adverse reactions were determined by questionnaire., Results: The mean bioavailabilities of nicotine after ileocolonic nicotine tartrate administration via delayed-release oral capsules at doses 3 mg and 6 mg nicotine were 41% and 42%, respectively. The ratios (after adjusting for nicotine dose) of cotinine area under the curve (AUC) for delayed-release oral nicotine to cotinine AUC for intravenous nicotine were 1.5 and 1.6 for the two subjects undergoing cotinine pharmacokinetics, demonstrating significant first-pass metabolism. Serum nicotine concentrations did not predict adverse reactions., Conclusions: Nicotine tartrate delivered to the ileocolon as a delayed-release oral capsule at doses of 3 mg and 6 mg nicotine considerably reduced systemic nicotine bioavailability. This reduction in bioavailability appears to be a result of first-pass hepatic metabolism rather than poor mucosal absorption of nicotine. The therapeutic potential of an ileocolonic delivery formulation of nicotine tartrate, which can potentially limit toxicity by local delivery of high doses of nicotine, should be investigated in patients with ulcerative colitis.

Objective: To estimate the cost-effectiveness of treating nicotine dependence, expressed as cost per net year of life gained by smoking cessation., Design: A cost-effectiveness analysis was conducted of a cohort of consecutive adult patients treated for nicotine dependence from April 1988 through December 1992 at the Mayo Clinic Nicotine Dependence Center (NDC)., Material and Methods: The study cohort consisted of 5,544 patients (50.8% female; mean age, 47.8 years) with a mean baseline smoking rate of 25.4 cigarettes per day. After an initial consultation, a nonphysician counselor developed an individual nicotine dependence treatment plan, which could include follow-up counseling, nicotine replacement therapy (patches or gum), group therapy, or an inpatient program. A relapse-prevention program included telephone calls and a series of letters to the patient. We computed the years of life gained for each person specific to age, gender, smoking rate at entry, and 6-month smoking status by using published mortality rates for current and former cigarette smokers. The 6-month smoking status was assumed to be applicable at 1 year. For subsequent determinations, we modeled by computer simulation the year-by-year (to age 100) smoking status by using published relapse and late cessation rates. Coupled with treatment costs, this information allowed the expression of cost per net year of life gained by stopping smoking. Net years of life gained, discounted 0, 3, and 5%, were computed with use of cessation and relapse rates expected for patients not seen in the NDC. Treatment costs were based on 1993 rates for the intervention services but did not include any tobacco product cost savings associated with smoking cessation., Results: The 1-year smoking-cessation rate was 22.2%. With all NDC patients included, the estimated net years of life gained, with use of a 5% rate of discount for benefits, was 0.058, and the corresponding cost was $6,828 per net year of life gained., Conclusion: In comparison with the cost-effectiveness of other medical services, the cost of $6,828 per net year of life gained by treatment of nicotine dependence is relatively inexpensive. Such cost-outcome data are important as economic considerations are applied for optimal allocation of limited health-care resources. Nonphysician health-care professionals can assume a key role in the provision of cost-effective nicotine dependence intervention.

Objective: To assess whether patients with pancreatic cancer-associated pain living near a pain control center were more likely to undergo neurolytic celiac plexus block (NCPB) than those living at a distance and to determine the rationale of physicians at our institution for referring patients for NCPB., Design: We retrospectively reviewed the frequency of use of NCPB in patients with pancreatic cancer and conducted an anonymous physician survey of referral patterns for NCPB for such patients., Material and Methods: A prospective database of medical diagnoses and a clinical database at our institution were used to identify patients with pancreatic cancer within three geographic regions who were assessed during the inclusive years 1980 through 1989: group I ("local") = all patient with pancreatic cancer in Olmsted County, Minnesota; group II ("surrounding") and group III ("distant") = patients referred for pancreatic cancer evaluation who lived within 100 miles of our institution (excluding Olmsted County) or more than 100 miles from our institution, respectively. Medical records were retrospectively reviewed to assess the use of NCPB at any time during the course of pancreatic cancer. For the physician survey component, all medical oncologists, gastroenterologists, and general surgeons at our institution who might be responsible for the care of patients with pancreatic cancer were sent a questionnaire about their referral patterns for NCPB among patients with pancreatic cancer., Results: Overall, approximately 15% of the 292 patients with pancreatic cancer studied underwent NCPB. Distance from our pain control center was not found to be associated with frequency of use of NCPB. Of the 78 physicians surveyed, 59 (76%) responded, and 35 of the responders (59%) had encountered at least 1 patient with pancreatic cancer during the preceding 12 months. In that subset of physicians, perceived barriers for referral for NCPB were limited appointment availability and need for repeating the procedure., Conclusion: On the basis of this study, referral patterns for NCPB in patients with pancreatic cancer do not seem to be associated with the geographic distance of a patient's residence from a pain control center. Improving appointment availability for NCPB might increase the number of patients offered this technique for control of pain.

Objective: To examine outcomes and predictors of smoking cessation among elderly patients treated for nicotine dependence., Design: Retrospective analysis of patients aged 65-82 who received a nicotine dependence consultation at the Mayo Medical Center between 1 April 1988 and 30 May 1992. Patients were contacted by telephone by a trained interviewer six months after the consultation and were sent a follow-up survey in August 1993., Setting: Mayo Medical Center, Rochester, Minnesota, United States., Subjects: A total of 613 patients (310 men, 303 women) with a mean age of 69.0 (SD 3.5) years were seen during the study period., Main Outcome Measures: Point prevalence self-reported smoking status. Patients were considered abstinent if they self-reported not smoking (not even a puff) during the seven days before contact., Results: At six-month follow up, 24.8% of the 613 patients reported abstinence from smoking. On multivariate analysis, smoking abstinence was more likely if patients were hospitalised at the time of the consultation, married to a non-smoking spouse, very motivated to stop smoking, and reported their longest time of previous abstinence to be less than a day or more than a month. The response rate to the mailed follow-up survey was 69.9% (429 of 613). The mean duration of follow up was 40.0 +/- 13.2 months following the consultation. Of the 429 patients, 103 (24.0%) reported abstinence from smoking and 326 (76.0%) were smoking at six-month follow up. Patients who reported abstinence at six months had a higher cessation rate at the last follow up (76.0%) compared with patients who were smoking at six-month follow up (33.0%, P < 0.001). For patients who were not smoking at six months, no factors were found to significantly predict abstinence at last follow up. For patients who were smoking at six months, factors associated with smoking cessation at last follow up were: more than a year as the longest time off cigarettes before the consultation; counsellor rating of less severe nicotine dependence; and older age at first regular smoking., Conclusions: Several predictors of smoking cessation were identified in this study which may be useful for tailoring smoking interventions for the elderly.

Background: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption., Aim: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study., Methods: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively., Results: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 +/- 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas., Conclusions: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.

Logistic regression has probably been underutilized in clinical investigations of personality because of its relatively recent development (dictated by the need for computer programs to obtain maximum likelihood estimates), and the fact that use has been largely confined to the fields of biostatistics, epidemiology, and economics Its use should be given serious consideration when the outcome of interest is dichotomous (or polychotomous) in nature and the predictors of interest may be categorical or continuous. The logit transformation is quite tractable mathematically, and it embodies the notion of threshold, which may have relevance for many of the variables that are of interest to investigators in the field of personality. Furthermore, investigators with experience in multiple linear regression or contingency table analysis should have little trouble in transitioning to logistic regression. Logistic regression programs are readily available in the major statistical packages, all of which provide fairly standard output.

Ulcerative colitis is predominantly a disease of nonsmokers, and transdermal nicotine is therapeutic but often results in adverse reactions. Colonic administration of nicotine tartrate as a liquid enema could decrease systemic nicotine absorption and adverse reactions. The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 micrograms nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 micrograms nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 +/- 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. The therapeutic potential of nicotine tartrate liquid enemas, which can potentially limit toxicity by local (colonic) delivery of high doses of nicotine should be investigated in patients with left-sided ulcerative colitis.

Background: Ulcerative colitis is predominantly a disease of nonsmokers. Transdermal nicotine may help control clinical manifestations of this condition., Objective: To determine the efficacy of transdermal nicotine for controlling clinical disease activity in active ulcerative colitis., Design: Randomized, double-blind, placebo-controlled, single-center clinical trial., Setting: Multispecialty group serving as an academic tertiary referral center., Patients: 64 nonsmoking patients with mildly to moderately active ulcerative colitis despite the use of medication., Intervention: Patients were stratified on the basis of smoking history, extent of disease, and concomitant medical therapy. After stratification, patients were randomly assigned to daily treatment with transdermal nicotine (n = 31) at the highest tolerated dose (11 mg for 1 week and then < or = 22 mg for 3 weeks) or placebo (n = 33)., Measurements: Clinical features were assessed at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Serum concentrations of nicotine were determined by using gas chromatography and mass spectrometry, and plasma concentrations of cotinine were measured by using high-performance liquid chromatography., Results: At 4 weeks, 12 of 31 patients (39%) who received nicotine showed clinical improvement compared with 3 of 33 patients (9%) who received placebo (P = 0.007). Four patients receiving nicotine discontinued therapy because of side effects (contact dermatitis [n = 2], nausea [n = 1], and acute pancreatitis [n = 1]). At week 4, the nicotine group had a mean (+/-SD) trough serum nicotine concentration of 11.3 +/- 8.4 ng/mL and a mean trough plasma cotinine concentration of 192 +/- 95 ng/mL., Conclusions: Transdermal nicotine administered at the highest tolerated dosage (< or = 22 mg/d) for 4 weeks is efficacious for controlling clinical manifestations of mildly to moderately active ulcerative colitis.

Linking data from a case-control study of Alzheimer's disease with data from a Minnesota Multiphasic Personality Inventory (MMPI) outpatient study, we identified 13 Alzheimer's disease cases and 16 controls for case-control comparison. The mean time between personality testing and onset of Alzheimer's disease (or corresponding age for controls) was 13 years in cases and 14 years in controls. Alzheimer's disease cases, but not the controls, had scores significantly greater than the normative reference on MMPI scales measuring Social Introversion (p = 0.05), and Pessimism (p = 0.01). When compared to controls, Alzheimer's disease cases had significantly greater scores on the Social Introversion scale (p = 0.03). Despite the small sample size and some design limitations of this exploratory study, our findings may suggest that subjects who score higher on these personality scales have a greater risk of Alzheimer's disease.

Objective: To assess overall perioperative and anesthetic care-specific patient satisfaction., Design: We mailed questionnaires postoperatively to three groups of surgical patients (those who underwent anesthesia without complications, those who experienced airway management difficulties, and those who had cardiovascular perturbations) and analyzed the responses., Material and Methods: All patients 18 to 75 years of age who underwent hospital-based surgical procedures in our acute-care hospitals during the interval from January to September 1993 were eligible for this investigation. We asked a total of 315 patients--105 in each of the three study groups--about their satisfaction with perioperative care. Specific positive or negative comments that the patients returned in their questionnaires were tabulated into the following sub-categories: physician, nurse, technique, time, and institution concerns., Results: Of the 315 questionnaires sent to patients, 239 (75.9%) were returned. No difference in overall patient satisfaction (defined as very satisfied or a combination of very satisfied and satisfied) was noted among the groups. No patients identified themselves as dissatisfied or very dissatisfied with their overall care, although a small percentage expressed dissatisfaction because of time delays. The specific patient comments suggested that the positive interactions with physicians and nurses outweighed the concerns about time delays., Conclusion: This study showed that intraoperative anesthetic events did not affect patient satisfaction. Interactions with physicians and nurses dominated the decision about patient satisfaction, and time delays were the most frequently cited negative comment.

To assess the long-term outcome in patients who underwent surgical treatment of intractable epilepsy, we retrospectively reviewed the medical records of 291 consecutive Mayo patients treated between July 1972 and March 1985. We also evaluated the responses to a follow-up mailed questionnaire or telephone interview completed in 1992. Of the 291 patients, 245 (94% of the 261 patients known to be alive at the time of the survey) responded to the follow-up questioning. Information on the patients' neurologic status (including frequency of seizures, use of antiepileptic drugs, and self-reported assessment of functional capacity) and their overall satisfaction with the operative procedure and postoperative outcome were evaluated. Two hundred ninety patients survived the operation and were dismissed from the hospital. Of the 245 patients who responded to the follow-up survey, 41% and 58% had been free of seizures since surgical treatment and for 3 years preceding the follow-up survey, respectively. In addition, of the respondent cohort, 36% were successfully weaned off all antiepileptic drugs. Patients reported improvement in their daily functional capacity and quality of life after surgical treatment. For example, in comparison with the preoperative assessment, the patients' ability to obtain a driver's license was significantly increased, and seizure-related driving accidents, falls, and bodily injury significantly decreased. Furthermore, on the basis of current knowledge of the operation and its outcome, 85% reported that they would repeat the operative procedure. Thus, surgical treatment of intractable epilepsy is an effective option that is met with patient satisfaction.

Patients were observed after the Fontan operation to determine the frequency and severity of protein-losing enteropathy. A total of 427 patients who survived for 30 days after the Fontan operation, performed between 1973 and January 1987, were analyzed and, thus far, protein-losing enteropathy has developed in 47 of 427. The cumulative risk for the development of protein-losing enteropathy by 10 years was 13.4% among 30-day survivors, and 5-year survival after the diagnosis was 46%. Hemodynamic studies done coincident with the diagnosis of protein-losing enteropathy have shown increased systemic venous pressure, decreased cardiac index, increased pulmonary vascular resistance, and increased ventricular end-diastolic pressure. Medical management of protein-losing enteropathy was only partially successful. Statistical analysis has shown that factors related to protein-losing enteropathy were ventricular anatomy, increased preoperative ventricular end-diastolic pressure, longer operative bypass time, increased length of hospital stay, and postoperative renal failure. This study suggests that scrupulous selection of cases for the Fontan operation is mandatory and that certain perioperative factors may predispose to this serious complication of the Fontan procedure.

Background: This study uses wrist actigrapy to assess the effects of 24-hr transdermal nicotine replacement on the sleep and daytime activity of smokers during smoking cessation., Methods: Seventy-one subjects grouped as light (n = 23), moderate (n = 24), or heavy (n = 24) smokers were randomly assigned to placebo or 11, 22, or 44 mg/day doses of transdermal nicotine for 1 week of intensive inpatient treatment of nicotine dependence. Outpatient patch therapy continued for 7 weeks following the inpatient stay. Those initially on placebo were randomly assigned to 11 or 22 mg/day, and those initially on 44 mg/day were reduced to 22 mg/day at Week 4., Results: There was a significant decrease in daytime wrist activity during patch therapy and the 1st week off patch therapy. These changes in daytime wrist activity were positively correlated with percentage of nicotine and cotinine replacement. No changes from baseline in sleep (sleep efficiency or wrist activity) were detected, nor were there differences in sleep among the four patch doses., Conclusions: Using wrist actigraphy, this study failed to show any disturbing effects of 24-hr high-dose nicotine replacement on sleep. Lower levels of nicotine replacement were associated with a decrease from baseline in daytime wrist activity.

Objective: To examine the psychometric properties, acceptance, and screening efficacy of the Mini-Mental State Examination (MMSE) in an internal medicine practice., Material and Methods: The MMSE was administered more than 4,000 times by 27 internists to 3,513 elderly patients (2,299 women and 1,214 men, 60 to 102 years old) who underwent general medical examinations. The efficacy of the MMSE for screening was measured in a subsample of age- and sex-matched patients with dementia (N = 185) and control subjects (N = 227). MMSE scores were correlated with age and education in the community sample. The attitudes of physicians about the MMSE were assessed with a 12-question survey. Sensitivity, specificity, and predictive values were calculated., Results: Performance on the MMSE among persons older than 59 years was influenced by age and education but not by sex. During an interval of 1 to 4 years, a change of 4 or more points in the total MMSE score is needed to indicate substantial cognitive deterioration. Participating physicians considered the MMSE of little value for routine screening in unselected populations but wanted it available for use as a clinical test. The traditional MMSE cutoff score of 23 or less had a sensitivity of 69% and a specificity of 99%. Use of age- and education-specific cutoff scores improved the sensitivity to 82% with no loss of specificity. With use of typical base rates for dementia in a general medical practice, the positive predictive value was less than 35%., Conclusion: The clinical utility of the MMSE and acceptance by physicians may be improved through awareness of the influences of age and education on the MMSE and by its application in settings with a high base rate of dementia. The MMSE is ineffective when used to screen unselected populations; it should be used for persons at risk of cognitive compromise.

Background: Patients with asthma are thought to be at high risk for pulmonary complications to develop during the perioperative period, and these complications may lead to serious morbidity. Existing medical records were reviewed to determine the frequency of and risk factors for perioperative pulmonary complications in a cohort of residents of Rochester, Minnesota, who had asthma and who underwent anesthesia and surgery at the Mayo Clinic in Rochester., Methods: Medical records were reviewed for all residents of Rochester, Minnesota, who were initially diagnosed as having definite asthma according to strict criteria from 1 January 1964 through 31 December 1983 who subsequently had at least one surgical procedure involving a general anesthetic or central neuroaxis block at the Mayo Clinic (n = 706)., Results: Bronchospasm was documented in the perioperative records of 12 patients (1.7% [exact 95% confidence interval, 0.9 to 3%]). Postoperative respiratory failure developed in one of these patients. Laryngospasm developed in two additional patients during operation. All episodes of bronchospasm and laryngospasm in the immediate perioperative period were treated successfully. No episodes of pneumothorax, pneumonia, or death in the hospital were noted. For univariate analysis, characteristics associated with complications included the recent use of antiasthmatic drugs, recent asthma symptoms, and recent therapy in a medical facility for asthma. Patients in whom complications developed were significantly older at diagnosis and at surgery., Conclusions: The frequency of perioperative bronchospasm and laryngospasm was surprisingly low in this cohort of persons with asthma. These complications did not lead to severe respiratory outcomes in most patients. The frequency of complications was increased in older patients and in those with active asthma.

The objectives of this study were to evaluate (1) the effect of spinal muscle strengthening by loading exercises on the bone mineral density (BMD) of the spine, and (2) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy, premenopausal women. The study design was a randomized, controlled trial of 3 years' duration. Ninety-six healthy, premenopausal, white women aged 30-40 years participated; 67 completed the study. All subjects were in good health (normal menses) and were active, but not athletic (that is, not involved in a regular sport activity). Subjects were randomized to an exercise or control group. The exercise group performed a supervised, non-strenuous, weight-lifting exercise program. Exercise performance was supervised once a week at the medical facility. In addition, the subjects performed the exercises twice a week on their own. Dietary calcium intake was to be maintained at 1,500 mg/day in both groups. Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0, 1, and 3 years. BMD of the midradius was measured with single photon absorptiometry. Measurements of muscle strength were obtained at baseline and every 3 months for 3 years. Maximal oxygen uptake was measured, and the level of physical activity was recorded. Compliance with the exercise program was excellent during the first year of the study, but decreased thereafter. At the end of 3 years, subject withdrawal was about 34% from the exercise group and about 22% from the control group (total subject withdrawal was about 30%). Muscle strength in the exercise group increased significantly at all involved skeletal sites (p values all < 0.001). There was a modest positive correlation between the BMD of Ward's triangle with spinal flexor strength (r = 0.32, p = 0.008) and with grip strength (r = 0.38, p = 0.001). Comparing study groups, we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group (our control group) on BMD at the spine, hip, or midradius measurement sites. In active, but not athletic premenopausal women, additional moderate weight-lifting exercises showed no significant effect on BMD.

Objectives: This study sought to evaluate changes in early morbidity and mortality as well as predictors of outcome in our most recent 339 patients undergoing modified Fontan operations., Background: The Fontan operation is the preferred definitive palliation for patients with functional single ventricles. Previously reported early mortality rates after Fontan operation have been substantial., Methods: Records of 339 consecutive patients who had a Fontan operation at the Mayo Clinic between 1987 and 1992 (recent cohort) were reviewed. This cohort was compared with the previous 500 patients who had Fontan operations performed between 1973 and 1986 (early cohort)., Results: Recently, overall early mortality after Fontan has decreased significantly compared with that for the early cohort (from 16% to 9%, p = 0.002). This decline occurred despite increased anatomic complexity of patients. Short-term posthospital survival has also improved significantly in recent patients. One-year survival improved to 88% from 79%, and 5-year survival to 81% from 73% (p = 0.006). Patients with common atrioventricular valves and those who took daily preoperative diuretic medication or had either postoperative renal failure or elevated postbypass right atrial pressure were at increased risk for early mortality. Young age was not found to be a risk factor for early mortality. Early mortality for patients with heterotaxia decreased dramatically: recent 30-day mortality was 15% compared with 41% in the early heterotaxy cohort., Conclusions: Many factors may have contributed to decreased early mortality after Fontan. Improved patient selection, younger age at time of operation, refinements in surgical techniques and postoperative management may all have had important roles. Proposed technical modifications of the Fontan operation must be evaluated in light of these improved results.

Amantadine has been used for more than 20 years in the symptomatic treatment of Parkinson's disease (PD). Several recent discoveries suggest that amantadine could also have a neuroprotective effect in PD. We studied survival in all parkinsonism (including PD and other parkinsonian syndromes) patients attending a single clinic, employing standard survival curves and a Cox regression model, to identify independent predictive variables for survival (while taking into account factors potentially associated with both outcome and treatment selection). Amantadine-treated patients (n = 250) were similar to the patients not treated with amantadine (n = 586) in terms of age, gender, type of parkinsonism, Hoehn and Yahr stage and dementia status at initial neurological visit. Amantadine use was an independent predictor of improved survival (p < 0.01). Improved survival was also associated with a higher 10-year expected survival (based on age, gender, and birth year), absence of dementia, type of parkinsonism = PD, and low Hoehn and Yahr stage (I or II) at initial neurologic visit (all p < 0.01); these additional factors occurred in statistically similar proportions in the groups that were and were not treated with amantadine. The association of improved survival with amantadine use may stem from symptomatic benefit or may reflect a "neuroprotective" effect, mediated through N-methyl-D-aspartate (NMDA) receptor antagonism, dopamine uptake blockade activity, or other mechanisms. Our preliminary findings suggest that a prospective, controlled, randomized trial of amantadine's effects on PD progression is warranted.

This article reports adolescent norms for the Optimism-Pessimism (PSM) scale of the Minnesota Multiphasic Personality Inventory (MMPI). The PSM scale measures explanatory style on a continuum from optimistic to pessimistic by using 298 MMPI items. It is based on Seligman's theory of explanatory style and was constructed by applying the Content Analysis of Verbatim Explanations (CAVE) technique to the MMPI item pool. The normative equations are based on a random sample of 624 normal boys and 691 normal girls ages 13 through 17 years. Reliability estimates of .94 demonstrate that the PSM scale can accurately assess explanatory style in adolescents. These norms may identify a personality factor associated with poorer physical and mental health and lower levels of achievement.

Transdermal nicotine has been shown to relieve nicotine withdrawal and to double smoking cessation rates compared to placebo in clinical trials. A 21 or 22 mg/day dose provides a steady state serum nicotine that is less than obtained from smoking. Limited information is available about higher nicotine patch doses. To define better the optimal dosing of nicotine patch therapy, we undertook an open-label study to determine the safety and tolerability of 44 mg/day dose for smoking cessation in subjects smoking > or = 20 cigarettes per day. Forty smokers received 44 mg/day of transdermal nicotine for 4 weeks followed by 4 weeks of 22 mg/day. Of the 40 subjects enrolled, 38 (95%) completed the 4 weeks of 44 mg patch therapy and 36 (90%) completed the entire 8 weeks of patch therapy. Non-smokers at week 4 had a mean serum nicotine level of 23.4 +/- 11.7 ng/ml and cotinine of 152.2 +/- 87.3 ng/ml. Percent replacement was calculated by dividing the steady state level at week 4 by the baseline level while the subjects were smoking their usual number of cigarettes. Percent nicotine replacement for non-smokers at week 4 (while on 44 mg nicotine patch) averaged 158% +/- 108.4, and for cotinine was 112.0 +/- 73.8. For nicotine, 33% of non-smokers at week 4 had < or = 100% nicotine replacement and for cotinine 63% < or = 100% replacement. Biochemically confirmed point prevalence smoking cessation rates were 65% and 55% at weeks 4 and 8 of patch therapy, respectively, and self-reported smoking cessation at 3 months was 50%. The most common effect was skin irritation at the patch site. A single subject was admitted for myocardial infarction following step-down from 44 to 22 mg of replacement nicotine. The subject was not smoking and the adverse event was deemed to be not related to the patch therapy. Sleep complaints were reported in 33% of subjects during the 44 mg phase. Other complaints were infrequent. We conclude that 44 mg per 24-h nicotine patch therapy in heavy smokers is safe, tolerable, and without significant adverse events.

Objective: To assess the level of nicotine replacement, evidence of nicotine toxicity, and withdrawal symptom relief with placebo and 11-, 22-, and 44-mg/d doses of transdermal nicotine. A secondary objective was to assess short- and long-term smoking cessation rates., Design: Randomized, double-blind, placebo-controlled inpatient/outpatient trial., Subjects: Seventy-one cigarette smokers stratified according to light (n = 23), moderate (n = 24), and heavy (n = 24) smoking rates., Interventions: After baseline measures were obtained, subjects were randomly assigned to placebo or an 11-, 22-, or 44-mg/d dose of transdermal nicotine and admitted to a special hospital unit for intensive inpatient treatment of nicotine dependence. During the 6-day inpatient stay, daily nicotine and cotinine levels were determined from trough and peak blood samples. Outpatient patch therapy continued for 7 weeks following the hospital stay, and those initially assigned to placebo were randomly assigned to 11 or 22 mg/d. At week 4, the dosage of those initially assigned to 44 mg/d was reduced to 22 mg/d., Main Outcome Measures: Percentage of replacement of cotinine was calculated by dividing the steady-state levels attained during patch therapy by the corresponding baseline levels. Abstinence from smoking was verified by expired air carbon monoxide. Withdrawal symptoms and nicotine toxicity were assessed daily through questionnaires during the inpatient stay. Follow-up visits were at 3, 6, 9, and 12 months., Results: There was a statistically significant relationship between baseline smoking rate and baseline trough and peak blood cotinine levels (rs = 0.39, rs = 0.45; P < .001 in both instances). A dose-response relationship was observed with higher patch doses, which produced a higher percentage of cotinine replacement and better withdrawal symptom relief. Only one subject (a light smoker assigned to the 44-mg dose) developed signs of nicotine toxicity. There was a positive association between the week 2 patch dose and the biochemically confirmed abstinence at the end of patch therapy (P = .007) but not for subsequent follow-up times. A higher percentage of cotinine replacement was associated with the higher 8-week smoking abstinence rate (P = .03), an association not found at long-term follow-up., Conclusion: A 44-mg/d dose of nicotine patch therapy appears to be safe for use in heavy smokers. Cigarette smoking rates can be used to estimate the initial nicotine patch dose. Monitoring blood cotinine levels at baseline and steady state can be used for assessing the adequacy of nicotine replacement. Withdrawal symptom relief can be improved with more complete nicotine replacement. Achieving a greater percentage of nicotine replacement may increase the efficacy of nicotine patch therapy.

To test whether eosinophil recruitment after pulmonary allergen challenge is associated with interleukin (IL)-5 in patients with asthma, we performed segmental bronchoprovocation (SBP) with saline, and with low and high dosages of ragweed extract in six patients with allergic asthma. Bronchoalveolar lavage (BAL) of the challenged segments was performed 5 min after challenge (immediate BAL fluid) and repeated 24 h later (late BAL fluid). Allergen challenge resulted in recruitment of eosinophils, and increased levels of eosinophil-active cytokines. A bioassay showed the predominant eosinophil-active cytokine in the late BAL fluids to be IL-5. Analysis of the late BAL fluids revealed that IL-5 levels correlated with the numbers of eosinophils and lymphocytes. This study provides evidence that IL-5 is a critical cytokine associated with eosinophil and lymphocyte recruitment into the airways of patients with asthma following exposure to allergen.

After thoracotomy some patients have discomfort, primarily in the rostral portion of their incisions. In this prospective, randomized study in 66 patients after lateral thoracotomy we evaluated whether, for equal fentanyl dosage in micrograms per kilogram, epidural infusion (lumbar catheter) of fentanyl 5 micrograms/mL provided better segmental analgesia (including the rostral portion of the incision) than a 10-micrograms/mL concentration infused at a rate half that used in the 5-micrograms/mL group. Ketorolac was used as an analgesic adjunct for nonincisional pain. Postoperative epidural fentanyl infusion included a 1-microgram/kg initial dose and an initial infusion rate of 1 microgram.kg-1.h-1 in both the 5-micrograms/mL and 10-micrograms/mL groups. Patients were evaluated for comfort level and pain relief while resting, taking a deep breath, coughing, and ambulating at eight times over 3 days using two visual analog scales for overall comfort and a verbal rating score (VRS) for segmental analgesia. There were no significant differences in demographics, surgical procedure, intraoperative fentanyl dose, side effects, rates of epidural fentanyl infusion, or total epidural fentanyl doses at 12, 24, 36, 48, and 60 h postbolus. Analgesia was effective in both groups. Although overall comfort levels were lower (i.e., indicated greater comfort) in the 5-micrograms/mL group in 6 of 8 visual analog scores (VASs) for comfort level and 20 of 24 VRSs for comfort level scores, and mean VRSs for the rostral portion of the incision were lower (i.e., indicated greater comfort) in the 5-micrograms/mL group at 21 of 24 evaluation subsets (one statistically significant), statistical significance was achieved in only six evaluation subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal, individual, or group counseling to improve smoking cessation rates., Design: An 8-week clinical trial (4 weeks double-blind followed by 4 weeks open label) using random assignment of participants to both dose (22 or 44 mg) and counseling (minimal, individual, or group) conditions., Participants: Daily cigarette smokers (> or = 15 cigarettes per day for at least 1 year) who volunteered to participate in a study of smoking cessation treatment. A total of 504 participants were enrolled at two sites., Intervention: Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction (2 weeks of 22 mg followed by 2 weeks of 11 mg). Counseling consisted of a self-help pamphlet (minimal); a self-help pamphlet, a brief physician motivational message, and three brief (< 15 minutes) follow-up visits with a nurse (individual); or the pamphlet, the motivational message, and eight weekly 1-hour group smoking cessation counseling visits (group). All participants returned weekly to turn in questionnaires and for assessment of their smoking status., Main Outcome Measures: Abstinence from smoking was based on self-report, confirmed by an expired carbon monoxide concentration lower than 10 ppm. Withdrawal severity was assessed by means of an eight-item self-report questionnaire completed daily., Results: Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date. Among those receiving minimal contact, the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose (68% vs 45%; P < .01). Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling (56% vs 67%; P < .05). The 44-mg dose decreased desire to smoke more than the 22-mg dose, but this effect was not related to success in quitting smoking. Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea (28%), vomiting (10%), and erythema with edema at the patch site (30%) than did a 22-mg dose (10%, 2%, and 13%, respectively; P < .01 for each adverse effect). Three serious adverse events occurred during use of the 44-mg patch dose., Conclusions: There does not appear to be any general, sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment. The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up, and the higher patch dose produced more adverse effects. Higher-dose (44-mg) nicotine replacement does not appear to be indicated for general clinical populations, although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment.

In a post hoc analysis of prior nicotine patch studies, we analysed findings in 357 subjects (43 recovering alcoholics, 314 non-alcoholics) to determine if recovering alcoholic smokers were more nicotine dependent than non-alcoholics and whether the efficacy of nicotine patch therapy was comparable. The Self-Administered Alcoholism Screening Test was used to identify recovering alcoholics. Recovering alcoholics had significantly higher mean smoking rates (cigarettes per day), Fagerström scores and baseline serum nicotine and cotinine than non-alcoholics. Among a subset of 240 subjects with a comparable treatment protocol, smoking cessation rates at the end of nicotine patch therapy were similar in recovering alcoholics (46%) and non-alcoholics (47%) receiving active 22 mg patches but higher than the respective placebo groups (17% and 19%). The 1-year rate was significantly (p = 0.005) higher in the non-alcoholic group assigned to an active patch (31%) compared to placebo (14%). For recovering alcoholics, the rates were lower and not significantly different (active 0%, placebo 11%). Recovering alcoholic smokers are likely to be more nicotine dependent than non-alcoholic smokers but can achieve comparable short-term cessation rates with nicotine patch therapy. Use of an objective, validated measure of alcohol dependence is indicated in clinical trials when it is desirable to know whether the subjects are active or recovering alcoholics.

We conclude that echocardiographically detected cardiac rhabdomyomata are common in patients with tuberous sclerosis complex, and are more prevalent and prominent in the younger patient. Tumors regress in size or number, or both, in most patients aged < 4 years, and less so in older patients. Cardiac rhabdomyomata are associated with a higher incidence of preexcitation and may increase the risk for arrhythmia.