"Staying at Home": A pivotal trial of telemedicine-based internal medicine hospitalization at a nursing home.

Background: In-hospital stay of acutely ill elderlies could be reduced by increasing the availability of community-based hospitalizations. The feasibility of remotely managing these patients by specialized internists, without leaving their nursing homes should be sought. In the current pivotal study, we aimed to evaluate the aforementioned model. Methods: This was a prospective, open-label study at a tertiary medical center and a nursing home. The study aimed at comparing clinical outcomes of patients hospitalized in each location. Results: Over a period of 5.5 months, we recruited 18 patients designated for hospitalization, meeting our inclusion criteria to either in-hospital stay or staying in their nursing home and treated by means of telemedicine from our tertiary medical center. The mean age was 85.3 years. Out of 114 hospitalization days, 44 days (48%) were at the nursing home. No significant difference was noted in terms of age, gender, and length of stay between the patients who were hospitalized in either location. In almost all cases, diagnosis changed during hospitalization. Three patients died during the study, all included in the in-hospital group. No safety breaching events happened in the nursing home-hospitalization group. Conclusions: Remote, telemedicine-based hospitalization of nursing home-dwelling elderlies is safe and feasible, potentially reducing the length of in-hospital stay by almost 50%. Larger studies in this realm are warranted.

Instrumentation and radiopharmaceutical validation.

Although the promise of new positron emission tomography (PET) imaging agents is great, the process of bringing these agents to commercialization remains in its infancy. There are no PET products today that have gone through the full clinical and chemistry development process required to gain marketing approval by the US Food and Drug Administration (FDA). The purpose of this paper was to review validation from the perspective of the chemistry, manufacturing and controls (CMC) section of an FDA filing, as well as the validation requirements described in FDA good manufacturing practice (GMP) regulations, guidance documents and general chapters of the US Pharmacopeia (USP). The review includes discussion of validation from development to commercial production of PET radiopharmaceuticals with a special emphasis on equipment and instrumentation used in production and testing. The goal is to stimulate a dialog that leads to the standardization of industry practices and regulatory requirements for validation practices in PET.

Prion protein expression in mammalian lenses.

PURPOSE: Aging and oxidative stress resulting from over-expression of Alzheimer precursor protein (betaAPP) have been studied as important factors contributing to the major age-related (sporadic), and minor (hereditary) forms of Alzheimer's disease (AD), and muscle inclusion body myositis, (IBM). AD and prion proteins accumulate in plaques linked with AD and scrapie diseases, and in rimmed vacuoles of IBM. Soluble beta-amyloid (Abeta) fibrillar forms are now thought to play a critical role in and outside of cells by producing oxidative stress. In lens, betaAPP and Abeta increase in cultured lenses exposed to oxidative stress, and in areas of lens fiber cell degeneration in thiamine (vitamin B1) deprived mice, a classic model of systemic oxidative stress. The purpose of the present study is to extend our studies of amyloid disease-related protein expression in mammalian lenses. METHODS: Western blot, immunohistochemical detection, and RT-PCR methods were used to identify and quantitate prion protein expression in human, monkey, and guinea pig lenses. RESULTS: We demonstrate for the first time that prion protein gene expression increases with oxidative stress in cultured human lens epithelial cells. In addition, we detected greater prion protein gene expression in fiber cells than epithelial cells in vivo. This is consistent with increases in prion protein expression demonstrated in myoblasts and neuronal cells induced to differentiate. Our initial investigations of prion protein in human lens cataracts identified increased prion protein immunoreactivity in regions of lens fiber cell degeneration. CONCLUSIONS: The present data indicate that prion protein expression increases during lens development, and is substantially increased in cultured human lens epithelial cells exposed to oxidative stress. We also provide evidence that prion protein immunoreactivity can be increased in regions of fiber cell disorganization. These data suggest a potential role for prion protein as a marker for some types of lens pathology, and in the mechanism of oxidative stress-related lens degeneration.

Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer's disease: a pilot double blind transdermal nicotine positron emission tomography study.

Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.

Inhibition of naphthalene cataract in rats by aldose reductase inhibitors.

Naphthalene-induced cataract in rat lenses can be completely prevented by AL01576, an aldose reductase inhibitor (ARI). In an attempt to understand the mechanism of this inhibition, several ARIs were examined to compare their efficacies in preventing naphthalene cataract, using both in vitro and in vivo models. Two classes of ARIs were tested: One group including AL01576, AL04114 (a AL01576 analog) and Sorbinil contained the spirohydantoin group, while Tolrestat contained a carboxylic acid group. Furthermore, to clarify if aldose reductase played a role in naphthalene-induced cataractogenesis in addition to its role in sugar cataract formation, a new dual cataract model was established for ARI evaluations. This was achieved by feeding rats simultaneously with high galactose and naphthalene or incubating rat lenses in culture media containing high galactose and naphthalene dihydrodiol. Under these conditions, both cortical cataract and perinuclear cataract developed in the same lens. It was found that at the same dosage of 10 mg/kg/day, both AL01576 and AL04114 completely prevented all morphological and biochemical changes in the lenses of naphthalene-fed rats. Sorbinil was less efficacious, while Tolrestat was inactive. AL01576 showed a dose-response effect in preventing naphthalene cataract and at 10 mg/kg/day, it was also effective as an intervention agent after cataractogenesis had begun. With the dual cataract model, Tolrestat prevented the high galactose-induced cortical cataract but showed no protection against the naphthalene-induced perinuclear cataract. AL01576, on the other hand, prevented both cataract formations. Results for dulcitol and glutathione levels were in good agreement with the morphological findings. AL04114, and ARI as potent as AL01576 but without its property for cytochrome P-450 inhibition, displayed similar efficacy in preventing naphthalene cataract. Based on these results, it was concluded that the prevention of the naphthalene cataract probably results from inhibition of the conversion of naphthalene dihydrodiol to 1,2-dihydroxynaphthalene and that the effect of the ARIs cannot be explained by their inhibition of the dihydrodiol dehydrogenase activity of aldose reductase.