A pilot, two-year longitudinal study of the interrelationship between trabecular bone and articular cartilage in the osteoarthritic knee

OBJECTIVE: To examine the relationship between structural changes of trabecular bone and cartilage, in patients with varying degrees of osteoarthritis (OA) over 2 years, using magnetic resonance imaging. METHODS: High-resolution, axial images were acquired for assessing trabecular bone structure, using a 3-D fast gradient-echo sequence. High-resolution, fat-suppressed, sagittal images were acquired for assessing cartilage structure, using a 3-D spoiled gradient-echo sequence. In a subset of the patients, sagittal images were acquired for measuring T(2) relaxation time, using a 2-D dual-echo spin echo sequence. RESULTS: A large variation in bone and cartilage parameters is evident among individual subjects in each group, however, group-specific means demonstrate decreasing trends (in bone and cartilage parameters) in osteoarthritic subjects (especially in mild OA subjects). The mean T(2) increased significantly (P<0.05) between the baseline and follow-up exams for all cartilage compartments except the lateral tibia. A positive relationship was established between cartilage changes and localized bone changes closest to the joint line, while a negative relationship was established between cartilage changes and global bone changes farthest from the joint line. CONCLUSION: This study quantifies the changes in bone and cartilage structural parameters over time, and demonstrates a longitudinal relationship between the morphological changes in bone and cartilage structure in patients with varying degrees of OA. Although a large variation of bone and cartilage changes is apparent among subjects, significant trends are evident in a relatively small sample size, with a short follow-up duration.     

Donepezil for Alzheimer's disease in clinical practice--The DONALD Study. A multicenter 24-week clinical trial in Germany

This multicenter open-label clinical trial was designed to investigate the safety and efficacy of donepezil, a selective acetylcholinesterase inhibitor, in the treatment of Alzheimer's disease (AD) in routine clinical practice in Germany. A total of 237 patients with mild-to-moderate AD were treated with donepezil for 24 weeks, 186 completed the study according to the protocol. In the completer group, mean MMSE score for efficacy showed an improvement from baseline of +1.6 points at week 12 (95% CI +1.1 to +2.1) and of +1.1 points at week 24 (95% CI +0.5 to +1.7). In more than 80% of the patients, global tolerability was rated to be very good or good. There were only insignificant effects on ECG parameters. This study confirms the results obtained in previous double-blind trials, which showed that donepezil is effective and well tolerated in patients with mild-to-moderately severe AD.     

Barriers to identification and treatment of hazardous drinkers as assessed by urban/rural primary care doctors

This pilot study analyzed three types of barriers encountered by forty family physicians when identifying and treating patients with hazardous drinking and alcohol dependence. The Patient Centered category included patient denial and lack of motivation to change. The Physician Centered category included lack of physician time and lack of addiction medicine training. The System Centered category included lack of community resources and distance to treatment programs. The Patient Centered barriers were rated significantly greater (p < .001) than the Physician Centered or the System Centered barriers. There was also a significant negative correlation (r = -0.49, p < .001) between the Physician Centered and the Patient Centered categories, meaning that the more problematic the patients were rated, the less problematic the physicians rated their time or training. The types of barriers that were rated as most problematic varied depending on rural/urban practice location and how current the physician's training was.     

The prognostic value of polymorphonuclear leukocyte elastase in patients with primary breast cancer

A variety of serine proteases, including urokinase-type plasminogen activator (uPA), plasmin,and polymorphonuclear leukocyte elastase (PMN-E), have been implicated in the processes of tumor cell invasion and metastasis. Besides degrading of matrix proteins, PMN-E has been shown to be able to cleave and inactivate plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of uPA, and alpha2-antiplasmin, the natural inhibitor of plasmin, thus enabling an uncontrolled matrix degradation by the fibrinolytic enzymes. Because only limited data are available on a relationship between the tumor level of PMN-E and prognosis in primary breast cancer patients, in the present study we have measured with an ELISA the levels of PMN-E (in complex with alpha1-proteinase inhibitor) in cytosolic extracts of 1143 primary breast tumors. Levels of complexed PMN-E have been correlated with the lengths of metastasis-free survival (MFS), relapse-free survival, and overall survival, and a comparison was made with data previously obtained for uPA and PAI-1. Our results show that patients with a high PMN-E level in their primary tumor had a rapid relapse and an early death compared with patients with a low tumor level of PMN-E. This held true for node-negative and node-positive subgroups of patients as well. The relationship of PMN-E with a poor prognosis was especially obvious during short-term follow-up (0-60 months). In Cox multivariate regression analysis, corrected for the traditional prognostic factors, PMN-E was an independent prognostic factor, and high levels of PMN-E were associated with a poor MFS [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.23-2.16; P < 0.001], relapse-free survival (HR, 1.45; 95% CI, 1.10-1.89; P = 0.01), and overall survival (HR, 1.64; 95% CI, 1.20-2.23; P = 0.003). Furthermore, in all three multivariate models, PMN-E still added significantly to the model after the additional inclusion of the uPA. PMN-E was an independent prognostic factor for MFS even in the multivariate analysis including the traditional clinical prognostic factors and the strong established biochemical prognostic factors uPA and PAI-1. Our present study suggests that PMN-E is associated with breast cancer metastasis, and knowledge of the tumor PMN-E status might be helpful in selecting the appropriate individualized (adjuvant) treatment for patients with breast cancer.     

Predicting rehospitalization and outpatient services from administration and clinical databases

The study tests whether psychiatric services utilization may be predicted from administrative databases without clinical variables equally as well as from databases with clinical variables. Persons with a psychiatric hospitalization at an urban medical center were followed for 1 year postdischarge (N=1384.) Dependent variables included statewide rehospitalization and the number of hours of outpatient services received. Three linear and logistic regression models were developed and cross-validated: a basic model with limited administrative independent variables, an intermediate model with diagnostic and limited clinical indicators, and a full model containing additional clinical predictors. For rehospitalization, the clinical cross-validated model accounted for twice the variance accounted by the basic model (adjusted R²=.13 and .06, respectively). For outpatient hours, the basic cross-validated model performed as well as the clinical model (adjusted R²=.36 and .34, respectively.) Clinical indicators such as assessment of functioning and co-occurring substance use disorder should be considered for inclusion in predicting rehospitalization.     

Frontal dysfunctions in Huntington's disease -- neuropsychology and therapy

Huntington's disease is a hereditary and progressive disease of the central nervous system. Sudden and irregular hyperkinesias are prominent. Psychopathological findings are very frequent and often proceed the decline of motor functions for years. Almost all the patients develop a dementia in later stages of the illness. This case study shows the treatment of a patient with Huntington's disease, verified by genetic analysis, with the atypical antipsychotic drug amisulpride. In this case the psychiatric disturbances and cognitive impairments were the only signs of the disease. The treatment showed an impressive improvement. Neuropsychological aspects of the disease are discussed.     

Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality.

BACKGROUND: During the 1980s, the incidence of primary malignant brain and other central nervous system tumors (hereafter called brain cancer) was reported to be increasing among all age groups in the United States, while mortality was declining for persons younger than 65 years. We analyzed these data to provide updates on incidence and mortality trends for brain cancer in the United States and to examine these patterns in search of their causes. METHODS: Data on incidence, overall and according to histology and anatomic site, and on relative survival were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for 1975 through 1995. Mortality data were obtained from the National Center for Health Statistics. Medicare procedure claims from the National Cancer Institute's SEER-Medicare database were used for imaging trends. Statistically significant changes in incidence trends were identified, and annual percent changes were computed for log linear models. RESULTS/CONCLUSIONS: Rates stabilized for all age groups during the most recent period for which SEER data were available, except for the group containing individuals 85 years of age or older. Mortality trends continued to decline for the younger age groups, and the steep increases in mortality seen in the past for the elderly slowed substantially. Patterns differed by age group according to the site and grade of tumors between younger and older patients. During the last decade, use of computed tomography scans was relatively stable for those 65-74 years old but increased among those 85 years old or older. IMPLICATIONS: Improvements in diagnosis and changes in the diagnosis and treatment of elderly patients provide likely explanations for the observed patterns in brain cancer trends.     

Midlife predictors of Alzheimer's disease

Factors contributing to increased risk for Alzheimer's disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however, accumulating evidence implicates modifiable risk factors in the pathogenesis of AD. Although the continued task of identifying new genes will be critical to learning more about the disease, several research findings suggest that potentially alterable environmental factors influence genetic contributions, providing targets for disease prevention and treatment. Here, we review midlife risk factors for AD, and address the potential for therapeutic intervention in midlife.