Renal involvement in relapsing polychondritis

Twenty-nine of the 129 patients with RP seen at the Mayo Clinic between 1943 and 1984 had renal involvement. These patients were older, had arthritis and extrarenal vasculitis more frequently, and had a significantly worse survival rate than those without renal involvement. Renal biopsies were obtained in 11 of these 29 patients. The predominant lesions were mild mesangial expansion and cell proliferation, and segmental necrotizing glomerulonephritis with crescents. Small amounts of electron-dense deposits, predominantly mesangial, were noted on electron microscopy. Immunofluorescence revealed faint deposition of C3 and/or IgG or IgM, predominantly in the mesangium. Autopsies were obtained in 13 of the 47 patients who had died. Information regarding the renal pathology was available in 10 of these 13 autopsies. At the time of the initial evaluation at the Mayo Clinic, 6 of these 10 patients had evidence of renal involvement. At autopsy, none of these 10 patients had evidence of active renal vasculitis or segmental necrotizing glomerulonephritis, but 8 of the 10 patients exhibited variable degrees of vascular and glomerular sclerosis, segmental mesangial proliferation, tubular loss, and interstitial lymphocytic infiltrates. These observations expand the limited information available in the literature, which is based on 11 previously published case reports of renal involvement in RP. In only a few of our patients and previously reported patients were the manifestations of the disease limited to the systems characteristically involved in pure RP. The frequent coexistence of other autoimmune and connective tissue diseases supports the role of immune mechanisms in the pathogenesis of this syndrome. Deposition of immune complexes is likely to play a role in the pathogenesis of the glomerular lesions associated with RP. Administration of corticosteroids alone is sufficient to induce a complete remission in some cases, while in others the addition of a cytotoxic agent is necessary to control the activity of the disease or to spare corticosteroid side effects and maintain a remission. Immunosuppression-related infectious complications and undetected relapses after discontinuation of immunosuppressive therapy are largely responsible for the morbidity and mortality observed in these patients.     

Influence of ventricular morphology on outcome after the Fontan procedure

The modified Fontan procedure has gained wide acceptance in the treatment of various congenital heart defects. Determination of risk factors for mortality remains an important issue for optimizing patient selection for the Fontan procedure. Conflicting results have been reported about whether ventricular morphology is a risk factor in these patients. Survival free of Fontan takedown or cardiac transplantation was assessed in the first 500 patients undergoing the Fontan procedure at our institution. This survival was correlated with ventricular morphology as evaluated by angiography. Both multivariate and univariate analyses indicated ventricular morphology was predictive of early survival free of Fontan takedown or cardiac transplantation following the procedure. However, there was no statistical evidence for ventricular morphology being a risk factor for mortality in patients alive 6 months after the procedure. Ventricular morphology is a risk factor for early survival in patients undergoing a Fontan procedure, with left ventricular morphology associated with a better early survival than right ventricular morphology.     

Bupropion for smoking cessation : predictors of successful outcome

OBJECTIVES: To identify predictors of smoking abstinence at the end of medication use that could assist in the optimal use of a sustained-release (SR) form of bupropion for treating cigarette smokers. DESIGN: A double-blind, placebo-controlled, dose-response trial. SETTING: Multicenter (three sites) study conducted in the United States. PARTICIPANTS: Six hundred fifteen healthy men and women (> or = 18 years of age) who were smoking > or = 15 cigarettes per day and who were motivated to stop smoking. INTERVENTION: Random assignment of patients to placebo or SR bupropion treatment, 100, 150, or 300 mg/d, for 7 weeks (total duration of study was 52 weeks: 7 weeks of treatment and 45 weeks of follow-up). Measurements and results: Logistic regression was used to identify predictors of abstinence at the end of the medication phase. Univariate predictors included the following: bupropion dose (p < 0.001); older age (p = 0.024); lower number of cigarettes smoked per day (cpd) (p < 0.001); lower Fagerstr?m Tolerance Questionnaire score (p = 0.011); longest time previously abstinent that was < 24 h or > 4 weeks (p < 0.001); absence of other smokers in the household (p = 0.021); greater number of previous stop attempts (p = 0.019); and study site (p = 0.004). Multivariate predictors of abstinence at the end of the medication phase were the following: higher bupropion dose (p < 0.001); lower number of cpd (p < 0.001); longest time previously abstinent from smoking (p = 0.002); male gender (p = 0.014); and study site (p = 0.021). CONCLUSION: Bupropion SR therapy was effective in treating cigarette smokers independently of all other characteristics studied. Lower smoking rate, brief periods (ie, < 24 h) or long periods (ie, > 4 weeks) of abstinence with previous attempts to stop smoking, and male gender were predictive of better outcomes, independent of the dose of bupropion that was used.     

A pilot study of adjunctive family psychoeducation in adolescent major depression: feasibility and treatment effect

OBJECTIVE: To obtain preliminary evidence of the feasibility and effectiveness of adjunctive family psychoeducation in adolescent major depressive disorder. METHOD: Participants were from outpatient clinics in Hamilton and London, Ontario. Over 24 months, 41 adolescents ages 13 through 18 years meeting major depressive disorder criteria were recruited (31 in Hamilton, 10 in London). Participants were randomized to usual treatment or usual treatment plus family psychoeducation. Outcome measures were readministered at 2 weeks, mid-treatment, posttreatment, and 3-month follow-up. Intent-to-treat analyses used chi2 and t tests and growth curve analysis. Standardized effects based on growth curve estimates were calculated for continuous outcomes. RESULTS: The London site was withdrawn because of poor participant retention. In Hamilton, no participant missed more than one assessment and there was good family psychoeducation adherence. Compared to controls, participants in the experimental group showed greater improvement in social functioning and adolescent-parent relationships (with medium standardized effect size > 0.5), and parents reported greater satisfaction with treatment. CONCLUSIONS: There were positive treatment effects on family and social functioning processes postulated to mediate the clinical course of major depressive disorder. The study provides support for further evaluation of family psychoeducation in this clinical population.     

The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms

OBJECTIVE: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. BACKGROUND: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. METHODS: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. RESULTS: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. CONCLUSIONS: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.     

Reported willingness among adolescent nonsmokers to help parents, peers, and others to stop smoking

BACKGROUND: This study of 1025 adolescent nonsmokers aged 11-19 years examined level of interest and factors associated with reported willingness to help someone stop smoking. METHODS: Data were collected from a survey distributed primarily in the schools at four geographic and ethnically diverse study sites. RESULTS: A total of 692 adolescents identified someone close to them who smokes whom they thought should quit. Of these, 90% reported that they would be willing to help this person stop smoking. Multivariate predictors of willingness to help were female gender, less difficulty reading English, and greater level of comfort with talking to the smoker about their smoking. The smoker that the adolescents were willing to help was most often a parent or same age friend. CONCLUSIONS: If this strong interest among adolescents could be tapped, engaging teens as support persons could be a novel public health approach to reaching parents, adolescents, and other smokers in the population.     

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study

Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, 1 male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1 of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.     

Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species

BACKGROUND: Duchenne muscular dystrophy is a severe X-linked congenital disorder characterized by lethal muscle wasting caused by the absence of the structural protein dystrophin. OBJECTIVE: Because generation of reactive oxygen species appears to play an important role in the pathogenesis of this disease, we tested whether antioxidant green tea extract could diminish muscle necrosis in the mdx mouse dystrophy model. DESIGN: A diet supplemented with 0.01% or 0.05% green tea extract was fed to dams and neonates for 4 wk beginning on the day of birth. Muscle necrosis and regeneration were determined in stained cryosections of soleus and elongator digitorum longus muscles. Radical scavenging by green tea extract was determined in differentiated cultured C2C12 cells treated with tert-butylhydroperoxide, with the use of 2',7'-dichlorofluorescin diacetate as a radical detector. RESULTS: This feeding regimen significantly and dose-dependently reduced necrosis in the fast-twitch muscle elongator digitorum longus but at the doses tested had no effect on the slow-twitch soleus muscle. Green tea extract concentration-dependently decreased oxidative stress induced by tert-butylhydroperoxide treatment of cultured mouse C2C12 myotubes. The lower effective dose tested in mdx mice corresponds to approximately equal to 1.4 L (7 cups) green tea/d in humans. CONCLUSION: Green tea extract may improve muscle health by reducing or delaying necrosis in mdx mice by an antioxidant mechanism.     

The aftermath of orbital radiotherapy for graves' ophthalmopathy

OBJECTIVE: To determine whether long-term improvement could be observed after orbital radiotherapy for Graves' disease; in addition, to evaluate ancillary treatments needed for those who have received radiotherapy, to search for late-emerging adverse consequences of radiotherapy, and to relate orbital changes to serum levels of thyroid-stimulating immunoglobulin (TSI). DESIGN: Three-year follow-up of noncomparative interventional case series. PARTICIPANTS: Forty-two patients. INTERVENTION: All patients had received orbital radiotherapy within 6 months of study entry. Twelve months after study entry, patients were free to select any additional treatment for their ophthalmopathy. MAIN OUTCOME MEASURES: Need for surgery, steroid therapy, volume of extraocular muscles and fat, proptosis, area of diplopia fields and range of extraocular muscle motion, volume changes after decompression and correlations of eye findings with serum TSI levels, retinal status. RESULTS: Half of the patients elected to have a surgical procedure on their eyes or orbits. Among patients who were not decompressed, we found only slight improvement in some of the main outcome measures. TSI did not positively correlate with baseline status or with any observed change in major outcome measures. After orbital decompression, the volumes of both muscle and fat increase, but bony orbital volume increases more and proptosis diminishes. Retinal microvascular abnormalities consistent with radiation retinopathy developed de novo in five eyes of three patients within 3 years of radiation therapy. CONCLUSIONS: In this 3-year uncontrolled follow-up phase, limited evidence for a clinically significant improvement was observed, which may be the result of treatment or of natural remission. In either case, the changes are of little clinical significance. Because it is neither effective nor innocuous, radiotherapy does not seem to be indicated for treatment of mild to moderate ophthalmopathy.