Increased central adiposity in morbidly obese patients with obstructive sleep apnoea.

BACKGROUND: With the growing epidemic of obesity, few data are available regarding adipose distribution and the severity of sleep apnoea. Our aim was to measure precisely adipose distribution with dual-energy X-ray absorptiometry (DXA) in a morbidly obese population with and without obstructive sleep apnoea (OSA). METHODS: Morbidly obese female subjects without a history of OSA underwent overnight polysomnography and DXA analysis. Subject demographics, DXA variables, serum laboratory markers and physical exam characteristics were compared between individuals with and without OSA. RESULTS: For the study population (n= 26), mean body mass index (BMI) was 45.9 ± 7.8 kg/m(2); mean age was 47.5 ± 10.2 years and all were female. The central adiposity ratio (CAR) was higher in individuals with OSA (apnoea-hypopnoea index > 5) than those without OSA (1.1 ± 0.05 vs 1.0 ± 0.04; P = 0.004). No difference was observed in Epworth Sleepiness Scale scores, body mass index (BMI) or neck circumference between groups. CONCLUSIONS: OSA is associated with increased central adipose deposition in patients with a BMI of >40 kg/m(2). These data may be helpful in designing future studies regarding the pathophysiology of OSA, and potential treatment options.

Prescription of resistance training for healthy populations.

Although there are well documented protective health benefits conferred by regular physical activity, most individuals of all ages are not physically active at a level for sufficient maintenance of health. Consequently, a major public health goal is to improve the collective health and fitness levels of all individuals. The American College of Sports Medicine (ACSM) and other international organisations have established guidelines for comprehensive exercise programmes composed of aerobic, flexibility and resistance-exercise training. Resistance training is the most effective method available for maintaining and increasing lean body mass and improving muscular strength and endurance. Furthermore, there is an increasing amount of evidence suggesting that resistance training may significantly improve many health factors associated with the prevention of chronic diseases. These health benefits can be safely obtained by most segments of the population when prescribed appropriate resistance-exercise programmes. Resistance-training programmes should be tailored to meet the needs and goals of the individual and should incorporate a variety of exercises performed at a sufficient intensity to enhance the development and maintenance of muscular strength and endurance, and lean body mass. A minimum of 1 set of 8 to 10 exercises (multi-joint and single joint) that involve the major muscle groups should be performed 2 to 3 times a week for healthy participants of all ages. More technical and advanced training including periodised multiple set regimens and/or advanced exercises may be more appropriate for individuals whose goals include maximum gains in strength and lean body mass. However, the existing literature supports the guidelines as outlined in this paper for children and adults of all ages seeking the health and fitness benefits associated with resistance training.

Familial adenomatous polyposis and extracolonic cancer.

Our purpose is to focus attention on the cancer family history, coupled with an understanding of the natural history and extracolonic tumor spectrum of familial adenomatous polyposis (FAP), through a family study. This family report provides an example of how colorectal cancer (CRC) can be prevented by knowledgeable gastroenterologists and colorectal surgeons who educate and compassionately counsel members of high-risk families so that their compliance with diagnostic screening and, ultimately, with protection through prophylactic colectomy, is achieved. A working pedigree of this extended family was constructed through interviews with the proband, followed by questionnaires sent to all primary and secondary relatives. Appropriately signed permission forms enabled us to secure pertinent medical and pathology records in order to ensure accuracy of historical information. Integral extracolonic tumors included medulloblastoma, papillary thyroid carcinoma, hepatoblastoma, and desmoid tumors. We conclude that, due in part to improved longevity as a result of being spared CRC, several family members have developed certain FAP integral extracolonic cancers.

Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.

Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope gene of the primary, dual-tropic HIV89.6. Only post-natal treatment with a similar triple mAb combination was used. One out of 4 mAb-treated infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated controls. Two out of 4 mAb-treated infants maintained normal CD4+ T-cell numbers, in contrast to all controls that had steep declines at 2 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.

Potent neutralization of primary human immunodeficiency virus clade C isolates with a synergistic combination of human monoclonal antibodies raised against clade B.

OBJECTIVES: We investigated the ability of several human neutralizing monoclonal antibodies (mAbs), originally raised against human immunodeficiency virus (HIV) clade B isolates, to neutralize primary clade C isolates as single agents and in combination. STUDY DESIGN/METHODS: HIV clade C isolates from five different countries were tested for susceptibility to neutralization by anti-clade B mAbs in human peripheral blood mononuclear cells. Monoclonal antibody combinations were evaluated for possible synergy. RESULTS: All 20 primary HIV clade C isolates could be neutralized 97.5% to 100% by a quadruple combination of mAbs IgG1b12, 2G12, 2F5, and 4E10. These mAbs recognized conserved epitopes and were highly synergistic, resulting in strong cross-clade neutralization. CONCLUSIONS: In our previous experiment, a synergistic combination of human neutralizing mAbs protected all macaque neonates against oral challenge with a simian-human immunodeficiency virus encoding HIV env. Together, our data suggest that passive immunization with currently available anti-clade B mAbs could play a role in preventing HIV clade C transmission through breastfeeding.

Self-efficacy, psychosocial factors, and exercise behavior in traditional versus modified cardiac rehabilitation.

BACKGROUND: Self-efficacy and social support are established determinants of exercise adherence and have potential usefulness for tailoring independent exercise regimens for cardiac patients. Highly supervised traditional cardiac rehabilitation programs may be a barrier for independent exercise self-efficacy in low - and moderate-risk patients. PURPOSE: The authors evaluated changes in psychosocial measures including self-efficacy and social support in 80 cardiac patients with low to moderate risk randomized to a traditional cardiac rehabilitation protocol (TP) or modified protocol (MP). These measures also were assessed for their potential to predict subsequent exercise behavior. METHODS: The TP (n = 38) emphasized a supervised exercise regimen and included continuous electrocardiogram (ECG) monitoring for 3 months. The lower cost MP (n = 42) emphasized independent exercise and included group education/support meetings, and gradually weaned patients from continuous ECG monitoring and direct medical supervision. RESULTS: Repeated measures analyses of variance indicated that MP patients had higher levels of self-efficacy for independent exercise without continuous ECG monitoring (P < .05). No other protocol differences were found. Multiple regression analyses using the pooled sample (excluding dropouts) indicated that self-efficacy for independent exercise was the only significant predictor of exercise over 6 months (R2=.28 [adjusted R2= .221 P < .01). In contrast to previous reports, social support for exercise was not a significant predictor of exercise behavior. CONCLUSIONS: These findings suggest cardiac rehabilitation programs for low- and moderate-risk patients should emphasize educational and patient monitoring methods that promote patient self-efficacy for independent exercise. Programs that emphasize highly supervised exercise including longer term use of continuous ECG monitoring may impair self-efficacy for independent exercise. Longer-term studies are needed to fully determine the value of using psychosocial measures for designing individualized exercise programs and predicting long-term exercise behavior in cardiac patients.

Physical activity for the chronically ill and disabled.

Exercise prescription principles for persons without chronic disease and/or disability are based on well developed scientific information. While there are varied objectives for being physically active, including enhancing physical fitness, promoting health by reducing the risk for chronic disease and ensuring safety during exercise participation, the essence of the exercise prescription is based on individual interests, health needs and clinical status, and therefore the aforementioned goals do not always carry equal weight. In the same manner, the principles of exercise prescription for persons with chronic disease and/or disability should place more emphasis on the patient's clinical status and, as a result, the exercise mode, intensity, frequency and duration are usually modified according to their clinical condition. Presently, these exercise prescription principles have been scientifically defined for clients with coronary heart disease. However, other diseases and/or disabilities have been studied less (e.g. renal failure, cancer, chronic fatigue syndrome, cerebral palsy). This article reviews these issues with specific reference to persons with chronic diseases and disabilities.

Recurrent ventricular fibrillation in a marathon runner during exercise testing.

We report a case of a marathon runner who presented with chest tightness, ST-segment depression, and ventricular fibrillation following treadmill exercise testing. At cardiac catheterization, the patient was found to have an isolated lesion in the left anterior descending (LAD) artery that was hemodynamically insignificant by accepted angiographic and coronary flow reserve standards. Ventricular fibrillation was thought to be idiopathic, and an implantable cardioverter defibrillator was placed. Chest pain and ST-segment depression followed by ventricular fibrillation was reproduced during follow-up treadmill testing, prompting reconsideration of the original diagnostic hypothesis. A coronary stent was deployed in the LAD artery. The patient has been asymptomatic and arrhythmia free during follow-up treadmill testing and recreational running.

Program participation, exercise adherence, cardiovascular outcomes, and program cost of traditional versus modified cardiac rehabilitation.

Common concerns with the traditional protocol (TP) for cardiac rehabilitation include suboptimal program participation, poor facilitation of independent exercise, the use of costly continuous electrocardiographic (ECG) monitoring, and lack of insurance reimbursement. To address these concerns, a reduced cost-modified protocol (MP) was developed to promote independent exercise. Eighty low- to moderate-risk cardiac patients were randomized to a TP (n = 42) or a MP (n = 38) and were compared over 6 months on program participation, exercise adherence, cardiovascular outcomes, and program costs. During month 1, patients followed identical regimens, including 3 ECG-monitored exercise sessions/week, with encouragement to achieve >/=5 thirty-minute sessions/week. In week 5, the TP continued with a facility-based regimen including 3 exercise sessions/week for 6 months and used ECG monitoring the initial 3 months. The MP discontinued ECG monitoring in week 5 and were gradually weaned to an off-site exercise regimen that was complemented with educational support meetings and telephone follow-up. Compared with TP patients, MP patients had higher rates of off-site exercise over 6 months (p = 0.05), and total exercise (on site + off site) during the final 3 months (p = 0.03). Also, MP patients were less likely to drop out (p = 0.05). Both protocols promoted comparable improvements in maximal oxygen uptake (p <0.05), blood lipids (p <0.001), and hemodynamic measurements (p <0.002). The MP cost $738 less/patient than the TP and required 30% less staff (full-time equivalents). These results suggest that a reduced cost MP was as effective as an established TP in improving physiologic outcomes while demonstrating higher rates of exercise adherence and program participation. Thus, the MP or a similar protocol has applicability to hospitals with large capitated or managed care populations to provide cost-effective cardiovascular risk reduction to patients.

Hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay.

PURPOSE: We updated an Uruguayan family with hereditary nonpolyposis colorectal cancer first described in 1977, incorporating knowledge of how the hMLH1 germline mutation has been established and shown to segregate in accord with the expected autosomal dominant mode of genetic transmission. METHODS: DNA-based molecular genetic testing was performed in conjunction with genetic counseling. Individuals were provided with their genetic test results, so that at-risk family members would be able to benefit from targeted management programs. RESULTS: We counseled 19 members of this kindred, 13 of whom were positive for the hMLH1 germline mutation. Specific recommendations for surveillance and management were provided. We were able to describe follow-up, including anecdotal cancer survival and pathology findings extending from the initial 1977 report of this family to the present. A remarkable sibship within this kindred was comprised of eight siblings, six of whom underwent resections for colorectal carcinoma between 1963 and 1971. Colon carcinomas before 1977 in this sibship were treated with classic hemicolectomies. Of those who had hemicolectomies for their first primary colorectal cancers, two had a second colon cancer primary, and two had a third colon cancer primary. CONCLUSIONS: Attention given to this extended family with hereditary nonpolyposis colorectal cancer has had a positive impact on the physician community in Uruguay, leading to the identification of additional families with hereditary nonpolyposis colorectal cancer.

How much exercise is enough for the coronary patient?

Prescribing exercise for cardiac patients is comparable in many ways to prescribing medications; that is, one recommends an optimal dosage according to individual needs and limitations. For in-patients, simple exposure to orthostatic or gravitational stress can obviate much of the deterioration in exercise tolerance that normally follows a cardiovascular event or intervention. On the other hand, the continuum of exercise therapy for outpatients may range from brisk walking to marathon running. Upper body and resistance training also have been shown to be safe and effective for clinically stable patients. Moderate intensity exercise training can produce beneficial changes in functional capacity, cardiac function, coronary risk factors, psychosocial well being, and possibly improve survival in patients with coronary artery disease. These findings may be especially relevant for the previously sedentary patient, in whom the subjective discomfort of vigorous exercise may serve as a deterrent to long-term compliance with physical training. (c) 2000 by CHF, Inc.

Reducing the risk of heart disease and stroke.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, responsible for almost 50% of all deaths. Compelling scientific evidence, including data from recent studies in patients with coronary artery disease (CAD), demonstrates that comprehensive risk factor interventions-including regular physical activity-augment physical work capacity, increase overall survival, improve quality of life, decrease the need for coronary revascularization procedures, and reduce the incidence of subsequent cardiovascular events ((1)). The rationale for this approach extends to patients with other documented atherosclerotic disease, (eg, transient ischemic attack, stroke ((2)), or aortic or peripheral vascular disease) because CAD is a leading cause of death and disability in these patient subsets. Not only do stroke and CAD share common risk factors (eg, hypertension, hypercholesterolemia, and diabetes mellitus), but 32% to 65% of stroke patients have CAD ((3)).

Avoiding Repeat Cardiac Events: The ABCDESs of Tertiary Prevention.

Multifactorial risk-factor modification-especially intensive ways to manage hyperlipidemia-may slow, halt, or even reverse the progression of coronary artery disease. The American Heart Association recently published comprehensive risk-reduction strategies in patients with coronary heart and vascular disease. These recommendations, endorsed by the American College of Cardiology, have been expanded and can be easily remembered as the ABCDESs of tertiary prevention: 'A': aspirin, alpha-tocopherol, and ACE inhibitors; 'B': beta-blockers, B-vitamins, and blood pressure control; 'C': cholesterol management; 'D': diabetes management and diet; 'E': exercise and estrogen therapy; and 'S': social support, smoking cessation, and stress management.

Genetic testing in families with hereditary nonpolyposis colon cancer.

CONTEXT: Genetic testing for hereditary nonpolyposis colon cancer (HNPCC) is available, but the rates of acceptance of testing or barriers to participation are not known. OBJECTIVE: To investigate rates and predictors of utilization of genetic testing for HNPCC. DESIGN: Cohort study conducted between July 1996 and July 1998. SETTING: Hereditary nonpolyposis colon cancer family registry. PARTICIPANTS: Adult male and female members (n = 208) of 4 extended HNPCC families contacted for a baseline telephone interview. INTERVENTIONS: Family education and individual genetic counseling. MAIN OUTCOME MEASURE: Participant acceptance of HNPCC test results. RESULTS: Of the 208 family members, 90 (43%) received test results and 118 (57%) declined. Of 139 subjects (67%) who completed a baseline telephone interview, 84 (60%) received test results and 55 (40%) declined. Of the 84 subjects who received test results, 35 (42%) received information indicating that they had HNPCC-associated mutations and 49 (58%) that they did not. Test acceptors had higher education levels (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.49-5.61) and were more likely to have participated in a previous genetic linkage study (OR, 4.30; 95% CI, 1.84-10.10). The presence of depression symptoms significantly reduced rates of HNPCC test use (OR, 0.34; 95% CI, 0.17-0.66). Although rates of test use were identical among men and women, the presence of depression symptoms resulted in a 4-fold decrease in test use among women (OR, 0.25; 95% CI, 0.08-0.80) and a smaller, nonsignificant reduction among men (OR, 0.49; 95% CI, 0.19-1.27). CONCLUSIONS: Despite having significantly elevated risks of developing colon cancer, a relatively small proportion of HNPCC family members are likely to use genetic testing. Barriers to test acceptance may include less formal education and the presence of depression symptoms, especially among women. Additional research is needed to generalize these findings to different clinical settings and racially diverse populations.

Clinical impact of molecular genetic diagnosis, genetic counseling, and management of hereditary cancer. Part II: Hereditary nonpolyposis colorectal carcinoma as a model.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common hereditary form of colorectal carcinoma (CRC) and may account for 5-10% of the total CRC burden. The discovery of DNA mismatch repair (MMR) genes, inclusive of hMSH2, hMLH1, hPMS2, and hMSH6, has enabled the identification of who has and who does not have inordinately increased susceptibility to CRC as well as a litany of extracolonic cancers. Mutation testing has focused on hMSH2 and hMLH1, the most common mutations in HNPCC. The protocol for DNA testing and DNA-based genetic counseling is described in Part I of this study. One hundred ninety-nine bloodline relatives were tested and counseled from five hMLH1 and two hMSH2 families. Their major reason for seeking genetic counseling and DNA testing was to inform their children and other loved ones of their mutation status. Those who sought counseling overestimated their risk for inheriting the mutation and showed a high rate of interest in prophylactic surgery, and many were greatly concerned about insurance discrimination. Knowledge about HNPCC, its molecular genetic diagnosis, surveillance and management opportunities, and genetic counseling implications are still emerging, all in the face of a greater need for physician education regarding all facets of hereditary cancer.