α-Synuclein in motor neuron disease: an immunohistologic study

-Synuclein (ASN) has been implicated in neurodegenerative disorders characterized by Lewy body inclusions such as Parkinsons disease and dementia with Lewy bodies. Lewy body-like inclusions have also been observed in spinal neurons of patients with amyotrophic lateral sclerosis (ALS) and reports suggest possible ASN abnormalities in ALS patients. We assessed ASN immunoreactivity in spinal and brain tissues of subjects who had died of progressive motor neuron disorders (MND). Clinical records of subjects with MND and a comparison group were reviewed to determine the diagnosis according to El-Escariol Criteria of ALS. Cervical, thoracic and lumbar cord sections were stained with an antibody to ASN. A blinded, semiquantitative review of sections from both groups included examination for evidence of spheroids, neuronal staining, cytoplasmic inclusions, anterior horn granules, white and gray matter glial staining, corticospinal tract axonal fiber and myelin changes. MND cases, including ALS and progressive muscular atrophy, displayed significantly increased ASN staining of spheroids (P0.001), and glial staining in gray and white matter (P0.05). Significant abnormal staining of corticospinal axon tract fibers and myelin was also observed (P0.05 and 0.01). Detection of possible ASN-positive neuronal inclusions did not differ between groups. Significant ASN abnormalities were observed in MND. These findings suggest a possible role for ASN in MND; however, the precise nature of this association is unclear.     

Hypertonic hyperglycemia progresses to diabetes faster than normotonic

To explore whether elevated plasma glucose might progress to diabetes via a mechanism that involves plasma hypertonicity, we evaluated the independent and joint effects of these variables on diabetes risk. Community-dwelling older adults (70+years), who reported no previous diagnosis of diabetes and had glucose levels below 200 mg/dl in the 1992 Duke EPESE survey, were re-interviewed in 1996 for diabetes status (n=979). Plasma tonicity at baseline was estimated from serum glucose, sodium, and potassium measures. In logistic regression models that controlled for glucose, as well as age, sex, race, weight status, activity level, serum creatinine, history of heart disease, stroke and cancer, plasma hypertonicity (300 mOsm/l) was independently associated with increased odds of developing diabetes (OR=2.0, 95% CI: 0.9–4.2). Hypertonicity magnified the effects of elevated glucose (125 mg/dl), such that individuals with both exposures were over four times more likely to develop diabetes than those with elevated glucose only (OR=4.9, 95%CI: 1.7–14.3), adjusting for all covariates. When tonicity was replaced by its determinant variables, glucose, sodium and potassium, in the multivariable models, independent effects of sodium were also observed. Further work is needed to pursue plasma hypertonicity as a factor in the progression of elevated plasma glucose to diabetes.     

Testosterone and behavior

In older men and women testosterone clearly improves libido and perhaps sexual activity. A number of authors have tried to describe a set of behavioral symptoms associated with the andropause. In older women testosterone seems to decrease dysphoria. In men the effects of testosterone on mood are less clear. In older men testosterone enhances spatial memory and possibly verbal and working memory. Table 2 summarizes the putative behavioral effects of testosterone. [Table: see text] There is a clear need for better designed large-scale behavioral studies to determine the effects of testosterone in older men and women.     

Brain membrane cholesterol domains,aging and amyloid beta-peptides

Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. These domains consist of the exofacial and cytofacial leaflets, cholesterol pools, annular lipids, and lipid rafts. Membrane lipid domains have been proposed to be involved in a variety of different functions including e.g. signal transduction, lipid transport and metabolism, and cell growth. Membrane lipid domains have been identified in brain and can be modified by different experimental conditions, aging and certain neurodegenerative diseases. Recent data reveal the very interesting possibility that membrane lipid domains may be a target of Alzheimer's disease. There is a growing body of evidence showing an association between cholesterol and Alzheimer's disease, and cholesterol is a major component of membrane lipid domains. Here we discuss recent data on brain membrane lipid domains emphasizing the structural and functional role of cholesterol. In addition, lipid domains and aging, and the potential interaction of lipid domains and amyloid beta-peptides (Abeta) that are a major component of senile plaques in brains of Alzheimer's patients are considered. We propose that age changes in the asymmetric distribution of cholesterol in contrast to total or bulk cholesterol in neuronal plasma membranes provides a cooperative environment for accumulation of Abeta in plasma membranes and the accumulation of Abeta is due in part to a direct physico-chemical interaction with cholesterol in the membrane exofacial or outer leaflet.     

Financial effect of a hospital outpatient senior clinic on an academic medical center

OBJECTIVES: To estimate the billed charges generated for the university hospital (UH) by patients seen in a UH outpatient senior clinic over a 6-month period. To estimate the average billed charges per geriatric patient generated for the UH over the same 6-month period. DESIGN: Retrospective analysis. SETTING: Hospital-based outpatient senior clinic at a university medical center. PARTICIPANTS: Outpatients aged 65 and older. MEASUREMENTS: The total inpatient, outpatient, and professional fee charges generated for the UH by the senior health center (SHC) patients were estimated for a 6-month period, with the use of billing data from the professional and hospital billing systems. To estimate the multiplier effect and average charges per SHC patient per year, our analysis focused on professional charges generated directly in the SHC and professional fees and hospital charges generated by secondary referral (inpatient and outpatient). RESULTS: One thousand nine hundred ninety-eight patients were seen in the SHC during the 6-month period. For every $1 billed in professional charges in the SHC, $17 was billed elsewhere in the hospital system. Geriatric medicine professional charges generated by the 1,998 SHC patients over the 6-month period totaled $546,691. The 6-month charges by the rest of the hospital system for the same 1,998 patients included hospital inpatient charges of $4,684,195 for all departments; hospital outpatient charges (ancillary plus technical, including facility fees for the SHC) of $3,027,212; and professional fees of $1,606,287 for other departments, thereby producing a multiplier factor of 17. The average overall charges per geriatric patient per 6 months totaled $4,937, which included hospital inpatient, hospital outpatient, and professional fees. The UH generated an average of $3,860 in hospital charges per SHC patient per 6 months. The average hospital charges generated per established SHC patient per 6 months were $2,936. The average hospital charges for a new SHC patient were $7,187 per 6 months. The average professional charges were $1,078 per patient per 6 months. CONCLUSIONS: This study provides a reasonable estimate of the substantial multiplier, or "flow-through," effect of a senior clinic on its parent medical center. Although senior clinics may be a cost center when viewed in isolation, these clinics are actually revenue generators when viewed from the perspective of the entire health system.     

Anxiety disorders. Helping patients regain stability and calm

Anxiety disorders affect more than 19 million American adults and are prevalent in the geriatric population. Generalized anxiety disorder, panic disorder, and other anxiety types can affect quality of life, precipitate social withdrawal, interfere with self-care, and exacerbate health problems. Anxiety disorders also may be associated with physical or mental disorders such as heart disease and depression. Patients may volunteer information about some anxiety disorders and be guarded about others. A proactive patient work-up can help reveal anxiety disorders in the primary care setting. Effective symptom management involves a combination of psychotherapy (cognitive behavioral) and pharmacotherapy.