A new approach to the development of assessment guidelines for osteoporosis.
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Biomedical subjects
Publications and source records attributed to L Melton.
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The volatile anaesthetic sevoflurane is degraded to fluoride (F-) and a vinyl ether (Compound A), which have the potential to harm kidney and liver. Whether renal and hepatic injuries can occur in horses is unknown. Cardiopulmonary, biochemical and histopathological changes were studied in six healthy thoroughbred horses undergoing 18 h of low-flow sevoflurane anaesthesia. Serum F- concentrations were measured and clinical laboratory tests performed to assess hepatic and renal function before and during anaesthesia. Necropsy specimens of kidney and liver were harvested for microscopic examination and compared to pre-experimental needle biopsies. Cardiopulmonary parameters were maintained at clinically acceptable levels throughout anaesthesia. Immediately after initiation of sevoflurane inhalation, serum F- levels began to rise, reaching an ongoing 38-45 micromol 1(-1) plateau at 8 h of anaesthesia. Serum biochemical analysis revealed only mild increases in glucose and creatinine kinase and a decrease in total calcium. Beyond 10 h of anaesthesia mild, time-related changes in urine included increased volume, glucosuria and enzymuria. Histological examination revealed mild microscopic changes in the kidney involving mainly the distal tubule, but no remarkable alterations in liver tissue. These results indicate that horses can be maintained in a systemically healthy state during unusually prolonged sevoflurane anaesthesia with minimal risk of hepatocellular damage from this anaesthetic. Furthermore, changes in renal function and morphology observed after sevoflurane inhalation are judged minimal and appear to be clinically irrelevant; they may be the result of anaesthetic duration, physiological stressors, sevoflurane (or its degradation products) or other unkown factors associated with these animals and study conditions.
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PURPOSE: To present guidelines for a community needs assessment for a Sexual Assault Nurse Examiner (SANE) program using Neuman's Systems Model. The guidelines provide advanced practice nurses with a holistic, systematic means to conduct an assessment prior to the implementation of a SANE program and facilitate collaborative work with other disciplines and agencies. DATA SOURCES: Selected research-based articles on sexual assault, classic texts and writings on Neuman's Systems Model, and community assessment models and programs. CONCLUSIONS: Sexual assault is a problem faced by almost every community. A thorough community assessment is an important first step in establishing programs that adequately meet a community's needs. Guidelines for conducting such an assessment related to implementation of a SANE program are rare, and guidelines using a nursing model were not found in the literature. IMPLICATIONS FOR PRACTICE: One program that has been successful in meeting community needs is the SANE program. A concise and organized assessment guide can reduce the necessary time and money allocated for a community assessment and can provide a basis for evaluation and research.
BACKGROUND: We previously reported that N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) treatment caused large increases of ceramide levels in neuroblastoma cell lines and induced cell death by a combination of apoptosis and necrosis through p53 (also known as TP53)-independent and caspase-independent pathways. Our goal was to determine if several molecules that inhibit enzymes involved in ceramide metabolism-L-threo-dihydrosphingosine (safingol), d, l-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP), and tamoxifen-enhanced 4-HPR-mediated cytotoxicity and/or affected ceramide levels. METHODS: Cellular lipids were quantified by radiolabeling and thin-layer chromatography. Cytotoxicity and cytotoxic synergy (expressed as combination index, where combination index <1 indicates synergy and >1 indicates antagonism) were measured in cultured cancer cell lines with the use of a fluorescence-based assay of cell viability employing digital imaging microscopy. Statistical tests were two-sided. RESULTS: 4-HPR increased ceramide levels by de novo synthesis. Safingol (1-4 microM) was incorporated into a stereochemical variant of ceramide and synergized with a 3:1 molar ratio of 4-HPR (3-12 microM), to produce a 100-fold to 10 000-fold (2 to 4 logs) increase in cytotoxicity relative to 4-HPR alone in neuroblastoma (combination index <0.1), lung (combination index <0.1-0.2), melanoma (combination index <0.1-0.2), prostate (combination index <0.1-1.0), colon (combination index 0.1-0.3), breast (combination index = 0.1-0.5), and pancreas (combination index = 0.2) cell lines, including p53 mutant and alkylator-resistant cell lines. The 4-HPR and safingol combination was cytotoxic in low-oxygen conditions and was minimally toxic to normal fibroblasts and bone marrow myeloid progenitor cells. Addition of agents that retard ceramide glucosylation and/or acylation, such as PPMP or tamoxifen, to 4-HPR or to the combination of 4-HPR and safingol further increased cytotoxicity to tumor cells. CONCLUSIONS: Combinations of 4-HPR and modulators of ceramide metabolism may form the basis for a novel chemotherapy that is functional under hypoxic conditions (e.g., such as those within tumors) and is p53 independent and caspase independent.
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Suspicions of the impact of oestrogen beyond its traditional role in sex maturation were confirmed with the discovery of oestrogen receptors in a great variety of tissues other than just in sex organs. Recently, research findings have indicated the central nervous system as one of the prime target organs--not only does oestrogen modulate the production and actions of serotonin, acetylcholine, dopamine and norepinephrine, but it also encourages the growth of new synapses and enhances neuronal survival. Whether the many effects of oestrogen operate through classical oestrogen receptors or alternative channels remains under intense investigation. During this three-day symposium, researchers and clinicians discussed a wide-range of oestrogen-related subjects from novel mechanisms of action to the influence of oestrogen on cognition and behaviour, and results from clinical studies that suggest oestrogen therapy after menopause may protect from Alzheimer's disease.
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A global assessment of hemostasis can be determined by the perfusion of unanti-coagulated whole blood through a hollow fiber at a nominal shear rate of 300 sec(-1). Once the pressure across the hollow fiber is stable, uniform holes are punched through the top and bottom of the fiber, resulting in an optically detectable leakage of blood from the hollow fiber and a pressure drop throughout the system. Changes in the shear rate and flow profile at the puncture site are sufficient to activate platelets mechanically, resulting in a platelet plug observable by electron microscopy. Fibrin is the principal component of the luminal surface adjacent to the puncture site and a prominent fibrin tail extends downstream from this site. The time from the introduction of the punch site to 90% recovery of the baseline pressure defines the in vitro bleeding time (IVBT). The rate of the pressure recovery appears to be related to the efficiency of the thrombin-mediated recruitment of additional platelets to the plug. Pressure recovery can be delayed by either platelet or thrombin inhibitors.