Risk factors for foot fracture among individuals aged 45 years and older

A case-control study undertaken among members of five Northern California Kaiser Permanente medical centers sought to identify risk factors for foot fractures among persons aged 45 years and older. Foot fracture cases (n=920) and frequency matched controls (n=2366) were interviewed between October 1996 and May 2001 using a standardized questionnaire. Foot fractures occurred most often while walking or climbing stairs. While 60% of foot fractures resulted from falls, 20% were attributed to other causes, such as hitting the foot or tripping on sidewalks and curbs. Having a self-reported history of physician-diagnosed diabetes [adjusted odds ratio (OR)=1.45, 95% confidence interval (CI)=1.10–1.91] or cataracts (OR=1.40, 95% CI=1.07–1.83), having a self-reported foot problem (OR=1.38, 95% CI=1.06–1.78 for two or more foot problem versus no foot problems), having difficulty walking in minimum light (OR=1.86, 95% CI=1.14–3.05) and having had a prior fracture (OR=1.20, 95% CI=1.05–1.37) were associated with increased risk. Putative protective factors for osteoporotic fractures, such as menopausal hormone therapy use, thiazide or water pill use, high calcium intake, and high body mass index were not associated with foot fracture risk. These findings suggest that risk factors for foot fractures among older people differ in part from risk factors for other fracture sites generally considered to be osteoporotic, such as the hip, vertebrae, and forearm.     

In vitro blood-brain barrier permeability and cerebral endothelial cell uptake of the neuroprotective nitrone compound NXY-059 in normoxic,hypoxic and ischemic conditions

The free radical trapping nitrone compounds alpha-phenyl-N-tert-butylnitrone (PBN), 2-sulfophenyl-N-tert-butylnitrone (S-PBN) and disodium 2,4-disulfophenyl-N-tert-butyl nitrone (NXY-059) are effective neuroprotective agents in experimental models of both transient and permanent focal ischemia. A recent in vivo study suggested that NXY-059 had poor brain uptake in a transient ischemia model. We have now examined its blood-brain barrier permeability and cerebral endothelial uptake during hypoxic and ischemic conditions using an in vitro model of the blood-brain barrier. The in vitro blood-brain barrier permeability and cerebral endothelial uptake of NXY-059 and S-PBN were low during normoxic conditions. In contrast, PBN had very high blood-brain barrier penetration in vitro which confirmed earlier in vivo results. The permeability of [14C]NXY-059 increased 3.5 times after 9 h of hypoxia or 3 h of ischemia. There was, respectively, a 5-fold and more than 10-fold increase, after 6 and 9 h of ischemia. The control molecule [3H]inulin (M(r) approximately 5000) showed a similar increase in permeability under the same experimental conditions indicating a major change in the transport properties of the endothelium. There was a 60% reduction in the ATP levels of astrocytes after 3 h of ischemia and a 90% reduction after 9 h. The reduction in ATP levels in endothelial cells was somewhat lower. The uptake of NXY-059 in cerebral endothelial cells under normoxic, hypoxic or 9 h of ischemic conditions was negligible. NXY-059, S-PBN and PBN showed no effects on vesicular transport or the integrity of the blood-brain barrier in normoxic or ischemic conditions, nor did the compounds induce any change in the ATP levels of the cells. In conclusion, it is possible that the increase in blood-brain barrier permeability of [14C]NXY-059 which occurs during prolonged ischemia in vitro reflects a change which may be of importance to the neuroprotective effects of this nitrone free radical trapping agent.     

Brain and ventricle instability during psychotic episodes of the schizophrenias

Recent reports from serial brain scans suggest that the rate of ventricular expansion and/or brain atrophy may be accelerated in at least some schizophrenics. The authors assessed the effect of state changes upon such findings.Within-subject 3D MRIs were assessed for ventricular and brain volumes during periods of [partial] remission and of exacerbation of psychosis. Additional scans at comparable within-subject SAPS were used to assess rates of change in volumes that were independent of SAPS changes.Correlations of changes of ventricle and brain volumes vs. change of SAPS cores between scans revealed that ventricle volumes decreased during a period of psychotic exacerbation and increased at a time of [partial] remission (r(p)=-0.666; P<0.0005); conversely, brain volumes increased during psychotic exacerbation and decreased at [partial] remission (r(p)=+0.448; P=0.032). Scans at comparable SAPS scores suggested that the majority of patients had rates of ventricular expansion comparable to controls (0.9+/-0.6 cc/year), though two patients appeared to have rates of ventricular increase of 4.5+/-2. 1 cc/year (Lilliefores P=0.036; K-means clustering F=17.75). Exacerbation of psychosis in schizophrenia is accompanied by evidence of brain swelling, especially of periventricular brain, with encroachment of brain substance upon ventricular volumes. Controlled for state changes, the majority of schizophrenics show rates of ventricular expansion or brain atrophy indistinguishable from controls.     

An intervention program to reduce the number of hospitalizations of elderly patients in a primary care clinic

Background  

The elderly population consumes a large share of medical resources in the western world. A significant portion of the expense is related to hospitalizations.     

Postnatal repeated maternal deprivation produces age-dependent changes of brain-derived neurotrophic factor expression in selected rat brain regions.

BACKGROUND: Adverse life events occurring early in development may alter the correct program of brain maturation and render the organism more vulnerable to psychiatric disorders. Identification of persistent changes associated with these events is crucial for the development of novel therapeutic strategies. METHODS: We used postnatal repeated maternal deprivation (MD) from postnatal day (PND) 2-14 to investigate changes in brain-derived neurotrophic factor (BDNF) levels. RNase protection assay and enzyme linked immunosorbent assay were employed to determine the anatomic profile of neurotrophin expression at different ages following MD. RESULTS: We found that MD produces a short-term up-regulation of neurotrophin expression in hippocampus and prefrontal cortex, as measured on PND 17, whereas at adulthood, a selective reduction of BDNF expression was observed in prefrontal cortex. When adult animals were challenged with a chronic swim stress paradigm, both a reduced expression of BDNF in prefrontal cortex and a significant reduction in striatal protein levels were found only in control subjects, whereas levels in the MD group were not further decreased. CONCLUSIONS: Our data suggest that MD produces a significant reduction of BDNF expression within prefrontal cortex and striatum, which may render these structures less plastic and more vulnerable under challenging conditions.