Effect of atrial radiofrequency ablation designed to cure atrial fibrillation on atrial mechanical function.

INTRODUCTION: The effects of linear radiofrequency lesions in the atria for cure of atrial fibrillation on atrial contraction have not previously been quantified. METHODS AND RESULTS: Atrial function was measured before and 30 +/- 24 days after a biatrial ablation procedure designed to cure atrial fibrillation in eight dogs and after a sham procedure in three dogs. Atrial mechanical function was assessed using Doppler diastolic blood flow velocities, atrial systolic pressure wave amplitude, and assessment of atrial contribution to cardiac output estimated by comparison of AV sequential pacing to ventricular pacing at the same heart rate. The mitral Doppler A/E velocity ratio was 1.03 +/- 0.45 before and 0.72 +/- 0.43 after ablation (P = 0.048). The tricuspid A/E ratio was 0.88 +/- 0.17 before and 0.71 +/- 0.12 after ablation (P = 0.04). The estimated atrial contribution to cardiac output was 18% +/- 9% before and 5% +/- 4% after ablation (P < 0.01). The left atrial systolic pressure wave amplitude was 2.8 +/- 1.5 mmHg before and 1.7 +/- 1.0 mmHg after ablation (P = 0.1). These changes were not observed in control dogs. Lesions covered 25% +/- 6% of the atrial endocardial surface. CONCLUSION: Multiple linear radiofrequency lesions in the atria designed to cure atrial fibrillation may impair atrial contractility. Reduced atrial function is partly due to loss of atrial myocardial mass, but regional delays in atrial activation and splinting of the atria by scarring also may contribute.

Mechanism, localization and cure of atrial arrhythmias occurring after a new intraoperative endocardial radiofrequency ablation procedure for atrial fibrillation.

OBJECTIVES: The purpose of this study was to test a new pattern of radiofrequency ablation for atrial fibrillation (AFib) intended to optimize atrial activation, and to demonstrate the usefulness of catheter techniques for mapping and ablation of postoperative atrial arrhythmias. BACKGROUND: Linear radiofrequency lesions have been used to cure AFib, but the optimal pattern of lesions is unknown and postoperative tachyarrhythmias are common. METHODS: A radial pattern of linear radiofrequency lesions (Star) was made using an endocardial open surgical approach in 25 patients. Postoperative arrhythmias were induced and characterized during electrophysiological studies in 15 patients. RESULTS: The AFib was abolished in most patients (91%), but atrial flutter (AFlut) occurred in 96% of patients postoperatively. At postoperative electrophysiological studies, 37 flutter morphologies were studied in 15 patients (46% spontaneous, cycle length [CL] 223 +/- 25 ms). Seven mechanisms (lesions discontinuity, n = 6; focal mechanism, n = 1) of AFlut were characterized in six patients. In these cases, flutter was abolished using further catheter radiofrequency ablation. In the remaining cases, flutter was usually localized to an area involving the interatrial septum, but no critical isthmus was identified for ablation. After 16 +/-10 months, 15 patients (65%) were asymptomatic with (n = 3) or without (n = 12) antiarrhythmic medications. Eight (35%) patients had persistent arrhythmias. Postoperative atrial electrical activation was near physiological. CONCLUSIONS: The AFib maybe abolished using a radial pattern of linear endocardial radiofrequency lesions, but postoperative AFlut is common even when lesions are made under optimal conditions. Endocardial mapping techniques can be used to characterize the flutter mechanisms, thus enabling subsequent successful catheter ablation.

Diagnosis and management of Alzheimer disease.

BACKGROUND: Alzheimer disease afflicts millions of older Americans, with an estimated cost to society approaching $100 million annually. Family physicians will care for an increasing number of patients with Alzheimer disease as well as their caregivers and families. METHODS: A comprehensive and systematic review of the literature published between 1985 and 1998 about diagnosing and treating Alzheimer disease was conducted, using "dementia," "Alzheimer's disease," and "treatment" as search strategy key words. Data and information that reported significant conclusions were critically reviewed. Potentially important new data about new agents that might be of benefit when caring for patients with Alzheimer disease are discussed. RESULTS AND CONCLUSIONS: The primary goals when treating Alzheimer disease patients are enhancing autonomy and functional abilities and maintaining quality of life for patients and caregivers. In addition to diagnostic and pharmacologic treatment, primary care physicians will be called upon to provide nonpharmacologic support to assist with behavioral, social, and living environment problems faced by these patients and their families. The most common pharmacologic treatment is cholinesterase inhibition. Two cholinesterase inhibitors, tacrine and donepezil, are effective in treating cognitive and global function. Newer cholinesterase inhibitors should soon be available that might offer safety advantages as well as efficacy in treating behavioral and psychiatric symptoms related to Alzheimer disease. Other agents, including vitamin E, nonsteroidal anti-inflammatory drugs, estrogen, and Ginkgo biloba, are under investigation. Nonpharmacologic measures are important components in the management of Alzheimer disease. Support groups can help to diminish behavioral problems, maintain the patient's independence, and provide relief for caregivers and families.

Predictors of functional ability in geriatric rehabilitation patients.

This study explored the impact that motivation, cognitive status, depression, age, and physical status have on the functional ability of older adults in a rehabilitation program. The study was based on a hypothesized model and was conducted with 200 patients on a geriatric rehabilitation unit. Structural equation modeling was done to test the hypothesized model. The average age of participants was 78 years, and the majority were female, Caucasian, unmarried, and had been admitted for rehabilitation after an orthopedic event. The data fit the hypothesized model; however, only five paths were significant. Mental status was a significant predictor of function on admission and a direct and indirect predictor of function at discharge, and diagnosis and age directly predicted function at discharge.

Patient-caregiver functional unit scale: a new scale to assess the patient-caregiver dyad.

BACKGROUND AND OBJECTIVES: This study evaluated the reliability and validity of the Patient-Caregiver Functional Unit Scale (PCFUS), a new instrument to assess the stability or endurance of patient-caregiver dyads. METHODS: Patient-caregiver dyads were recruited from a nursing home (NH) (n = 38), a comprehensive geriatric assessment program (CGA) (n = 20), and an ambulatory medical clinic (controls) (n = 85). Caregivers were eligible if they assisted, or were available to assist, the patient with personal and instrumental activities of daily living, without pay. Data were collected by interviewer-administered questionnaires. Inter-rater and test-retest reliability were evaluated among the CGA sample. Validity was assessed by comparing PCFUS scores among the NH, CGA, and control groups and by correlation of PCFUS scores with other standardized caregiver burden measures. RESULTS: The PCFUS had excellent inter-rater and test-retest reliability. Mean PCFUS scores were significantly lower (ie, less stable patient-caregiver dyad) in NH than CGA and control caregivers. PCFUS scores were significantly associated with Burden Interview, Perceived Stress Scale, and Geriatric Depression Scale scores and risk factors for caregiver stress (eg, patient's cognitive impairment, disruptive behaviors). CONCLUSIONS: The PCFUS is a short, easily administered measure with good reliability and validity and is applicable to clinical and research settings.

The effect of cognitive status on outcomes following rehabilitation.

BACKGROUND AND OBJECTIVES: Impaired cognition is a determinant of poor recovery following a hip fracture. Because of the risk of poorer outcomes, individuals with impaired cognitive function may be refused admission into a rehabilitation program. This study considered the impact of cognitive status on functional ability over time for older adults who participate in a rehabilitation program. METHODS: We studied a convenience sample of 200 consecutive patients who participated in an inpatient rehabilitation program following an orthopedic event. We obtained complete follow-up data on 181 participants. Baseline data were collected within 48 hours of admission and included demographics, rehabilitation diagnosis, living location prior to admission, the Mini-mental State Examination, and the Barthel Index (BI). Telephone follow-up was made at 3, 6, and 12 months after discharge from rehabilitation, and we obtained information about demographic data and functional status (BI). RESULTS: There were no differences in the demographic characteristics of the two groups except for race; a larger percentage of African-Americans were in the impaired group. There was a statistically significant main effect of time with functional ability of all participants, increasing over the 12-month follow-up period. CONCLUSIONS: This study suggests that rehabilitation of the older adult, both with and without cognitive impairment, can result in improvement in functional ability that is sustained over a 12-month period. Although the findings indicate that those with cognitive impairment have lower functional performance at each testing period, these individuals improved functionally during the course of rehabilitation and maintained their discharge level of functioning for 1 year after discharge.

Weight change: an indicator of caregiver stress.

This study evaluated weight change and caregiver stress in 200 informal caregivers to elderly patients discharged from a rehabilitation hospital. Previous laboratory and epidemiologic studies have shown that stress predisposes to weight change. Nineteen percent of the caregivers had gained or lost at least 10 pounds since becoming caregivers. Weight change was significantly associated with higher scores on standardized measures of burden and stress (e.g., Burden Interview, Perceived Stress Scale, Geriatric Depression Scale) and with lower education, poorer self-rated health, more psychotropic medication use, and caring for patients with more ADL limitations who had been hospitalized for stroke or a frail elderly condition. Caregivers to patients with a stroke or frail elderly condition reported 2.8 times more weight change than caregivers to patients with a rehabilitation problem. These results suggest that weight change is a valid indicator of stress in caregivers, and they have public health, clinical, and research applications.

Mapping of a gene for type 2 diabetes associated with an insulin secretion defect by a genome scan in Finnish families.

Non-insulin dependent diabetes mellitus (NIDDM) affects more than 100 million people worldwide and is associated with severe metabolic defects, including peripheral insulin resistance, elevated hepatic glucose production, and inappropriate insulin secretion. Family studies point to a major genetic component, but specific susceptibility genes have not yet been identified-except for rare early-onset forms with monogenic or mitochondrial inheritance. We have screened over 4,000 individuals from a population isolate in western Finland, identified 26 families (comprising 217 individuals) enriched for NIDDM and performed a genome-wide scan using non-parametric linkage analysis. We found no significant evidence for linkage when the families were analysed together, but strong evidence for linkage when families were classified according to mean insulin levels in affecteds (in oral glucose tolerance tests). Specifically, families with the lowest insulin levels showed linkage (P = 2 x 10(-6)) to chromosome 12 near D12S1349. Interestingly, this region contains the gene causing the rare, dominant, early-onset form of diabetes MODY3. Unlike MODY3 families, the Finnish families with low insulin have an age-of-onset typical for NIDDM (mean = 58 years). We infer the existence of a gene NIDDM2 causing NIDDM associated with low insulin secretion, and suggest that NIDDM2 and MODY3 may represent different alleles of the same gene.

Parametric and nonparametric linkage analysis: a unified multipoint approach.

In complex disease studies, it is crucial to perform multipoint linkage analysis with many markers and to use robust nonparametric methods that take account of all pedigree information. Currently available methods fall short in both regards. In this paper, we describe how to extract complete multipoint inheritance information from general pedigrees of moderate size. This information is captured in the multipoint inheritance distribution, which provides a framework for a unified approach to both parametric and nonparametric methods of linkage analysis. Specifically, the approach includes the following: (1) Rapid exact computation of multipoint LOD scores involving dozens of highly polymorphic markers, even in the presence of loops and missing data. (2) Non-parametric linkage (NPL) analysis, a powerful new approach to pedigree analysis. We show that NPL is robust to uncertainty about mode of inheritance, is much more powerful than commonly used nonparametric methods, and loses little power relative to parametric linkage analysis. NPL thus appears to be the method of choice for pedigree studies of complex traits. (3) Information-content mapping, which measures the fraction of the total inheritance information extracted by the available marker data and points out the regions in which typing additional markers is most useful. (4) Maximum-likelihood reconstruction of many-marker haplotypes, even in pedigrees with missing data. We have implemented NPL analysis, LOD-score computation, information-content mapping, and haplotype reconstruction in a new computer package, GENEHUNTER. The package allows efficient multipoint analysis of pedigree data to be performed rapidly in a single user-friendly environment.

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Burden among white and black caregivers to elderly adults.

Racial differences in caregiver burden were evaluated among 1,062 White and 159 Black caregivers from the 1982 National Long-term Care Survey and its supplement, the National Survey of Informal Caregivers. Black caregivers performed more caregiving activities and cared for persons with greater functional and cognitive impairment. However, White caregivers reported significantly more burden in linear regression analyses, controlling for covariates. Results of separate, race-specific regression models showed that caregiver demographics (being female, spouse of the care recipient, and poorer self-rated health), caregiving activities (helps with ADLs, extra time spent caregiving, unable to leave care recipient alone), and care recipient needs (IADL limitations, cognitive impairment or proxy interview, recent hospitalization) were significantly associated with burden among White caregivers. When this model was replicated in Black caregivers, the only statistically significant variables were poorer self-rated health, caregiving activities (helps with ADLs, extra time caregiving, unable to leave care recipient alone), and cognitive impairment of the care recipient. These results underscore the importance of caregiving activities in assessments of burden among White and Black caregivers.

The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.

Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by fine-structure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning.

Avoiding polypharmacy and iatrogenesis in the nursing home.

The vast majority of nursing home patients over age 65 take at least one prescription medicine, and, on average, seven drugs are concurrently prescribed for each of these patients. One result of this polypharmacy is an increased risk of iatrogenic disease. The authors discuss traditional prescribing patterns in nursing homes and how these patterns contribute to drug-drug and drug-disease interactions in nursing home patients, as well as strategies to reduce polypharmacy and iatrogenesis.

Rehabilitation of the elderly patient with arthritis.

The rehabilitation of an elderly patient with arthritis involves a cooperative effort on the part of patients and their caregivers, therapists, and physicians. If treatment is begun early in the course of the disease, the onset of functional decline and disability may be delayed or prevented. It may be useful for patients to contact the American Arthritis Foundation for further information and referral to support groups. Older people with arthritis must be included at a societal decision-making level in helping plan, design, and monitor community projects where handicap access questions arise. A major problem for people with disability is often the barriers they encounter in the environment and the attitudes of society. Treatment goals should be discussed and agreed on, and education and psychologic support should be provided for patients and their families. Each case must be individually assessed and a set of tailor-made rehabilitation interventions prescribed. Rest, exercise (active or passive), joint splinting, massage, heat (moist or dry heat), cold, pharmacotherapy, joint injection, surgery, and complementary treatment modalities such as homeopathy, acupuncture, education, and psychosocial support all have their role in the rehabilitation of the elderly patient with arthritis. For most patients, the course and prognosis are excellent. In general strength, ROM, and joint function can be preserved or improved to the point that participation in normal activities of daily living is possible.

Geriatric education and practice of family practice graduates: an alumni survey.

BACKGROUND: The goal of this research was to study the relationship between family practice residency training in geriatrics and subsequent postresidency geriatric practice patterns. METHODS: We surveyed all graduates of the University of Maryland Family Practice Residency Program through 1990 to determine their attitudes toward their geriatric training and the extent of their geriatric practice. Logistic regression analysis was used to identify factors associated with 1) making house calls, 2) making weekly nursing home visits, and 3) having a practice in which more than 25% of patients were older than age 65. RESULTS: The responses of 143 graduates were analyzed. Most respondents (58.8%) made house calls, and the majority (51%) saw nursing home patients weekly. Older respondents and those possessing Certificates of Added Qualifications in Geriatric Medicine (CAQGMs) were more likely to treat patients older than age 65. Respondents with larger nursing home practices rated their geriatric training more favorably. Multivariate logistic regression analysis found that the following factors were associated with making house calls: working in a group family practice (odds ratio [OR] = 3.88, 95% confidence interval [CI] = 2.58-5.84) and a rural practice location (OR = 2.71, 95% CI = 1.77-4.17). Physicians who had additional training after residency (OR = 0.16, 95% CI = 0.10-0.25) were less likely to make house calls. Factors associated with making weekly nursing home visits were: additional training after residency (OR = 0.31, 95% CI = 0.19-0.50) and working in a group family practice (OR = 2.43, 95% CI = 1.63-3.65). Attainment of a CAQGM was the only factor associated with having more than 25% geriatric patients in the office practice (OR = 6.00, 95% CI = 2.72-13.24). CONCLUSIONS: Most graduates of the University of Maryland Family Practice Residency Program maintain significant geriatric practices and value geriatric training, but whether favorable training experiences influence graduates' practices is unknown. Prospective studies of family practice residents are needed to clarify the influence of geriatric curricula on residents' future clinical practices.

A case of neurofibromatosis associated with a coronary artery aneurysm and myocardial infarction.

Aneurysms of the aorta, vertebral arteries, carotid artery, thyrocervical trunk, and mesenteric and celiac arteries have been described in patients with neurofibromatosis. These aneurysms may have part of the vessel wall replaced by neurofibromatosis tissue. One previous case reports a coronary artery aneurysm in a patient with neurofibromatosis who suffered a myocardial infarction due to thrombosis formation within the aneurysm. We document a second case of aneurysmal dilatation of a coronary artery in a patient with neurofibromatosis. This patient also had a myocardial infarction in a vascular distribution not involved by the aneurysm. The vascular changes associated with neurofibromatosis are reviewed. Aneurysmal dilatation of the coronary arteries may be a further vascular manifestation of this condition.