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1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man. 2. Oral doses of the 14C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity. 3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25 mg/kg in rats, 0.1 and 50 mg/kg in dogs, and 1-160 mg in man. In rhesus monkeys given a 0.5 mg/kg oral dose, the Cmax and AUC of I were similar to values obtained following a corresponding dose in dogs. 4. After i.v. administration of a 1.0 mg/kg dose the terminal elimination half-life (t1/2 beta) of I was 4 h in mice and 9-10 h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2 beta of I was decreased to 2.4 h. In rodents the serum clearance and apparent volume of distribution of I were 0.04-0.2 l/kg.h and 0.5-0.8 l/kg, respectively, and 0.6 l/kg.h and 9.8 l/kg in dogs. 5. In rodents and dogs dosed with 14C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug.  相似文献   
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Scabies     
Scabies is an ectoparasite caused by the mite Sarcoptes scabiei var hominis , an obligate human parasite. There are about 300 million cases of scabies in the world each year. Common predisposing factors are overcrowding, immigration, poor hygiene, poor nutritional status, homelessness, dementia, and sexual contact. Direct skin-to-skin contact between 15 and 20 minutes is needed to transfer the mites from one person to another. The diagnosis suspected with a clinical history of itch, worse at night, affecting other family members, clinical distribution, and appearance. Definite diagnosis relies on microscopic identification of the mites, eggs, or fecal pellets with 10% potassium hydroxide, ink enhancement, tetracycline fluorescence tests, or mineral oil; other methods include: epiluminescence light microscopy and S. scabiei DNA. The most commonly used treatment modalities are permethrin and ivermectin. Persistence of symptoms for 2–6 weeks after successful treatment is common. Most recurrences are because of reinfection from untreated contacts.  相似文献   
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PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.  相似文献   
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Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.  相似文献   
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This study investigates functional disability among some of the nation's most vulnerable older adults: rural Medicaid recipients. Data were provided by 221 older adults (mean age = 75.9 years; 82% women) who were receiving community-based long-term care services through Medicaid. Participants self-reported functional ability involving the completion of six basic activities of daily living (BADLs), three cognitive instrumental activities of daily living (IADLS), and four physical IADLs. Self-reports of depressed affect and the number of physical health conditions were also obtained. Path analysis was used to examine all of the associations among age, gender, number of chronic health conditions, depressed affect and functional disability. The tested model was significant [chi2 (DF = 3, n = 221) = 5.052, p = 0.168; TLI = 0.945; CFI = 0.992; RMSEA = 0.056] and explained 45.1% of the variance in BADL disability. Depressed affect significantly predicted disability in cognitive IADLs and physical IADLs, which predicted disability in BADLs. Age and gender had indirect effects on BADL, through their association with cognitive IADLs and physical IADLs. The number of chronic health conditions exerted both indirect and direct effects on BADL disability. Results are discussed within the context of the growing literature that suggests the importance of psychological variables as predictors of functional disability. Moreover, we discuss whether community-based long-term care is appropriate for older adults with high levels of functional disability.  相似文献   
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Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.  相似文献   
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Alcohol and the adolescent trauma population   总被引:4,自引:0,他引:4  
Trauma is the leading killer of children and adolescents between 1 and 21 years of age. Alcohol-impaired driving represents the single greatest cause of mortality and morbidity of children over the age of 6. We retrospectively reviewed 878 consecutive adolescent (age range, 16 to 20 years) trauma admissions for blood alcohol concentration (BAC). Four hundred sixty-seven patients had BAC drawn, 258 were BAC-negative (group I), 209 (48%) were BAC-positive (group II). The adolescent drinkers were then compared with a group of 748 adult drinkers (group III). Groups I and II differ in sex, age, time of day of the accident, Injury Severity Score, Glasgow Coma Score, and Revised Trauma Score, whereas group II and III differ by type of accident, type of injury, socioeconomic factors (bad debt), time of day of the injury, and BAC. There were no significant differences in TRISS predicted survival, actual survival, nor mean length of stay. We conclude that (1) alcohol is a significant contributor to injury during adolescence, and (2) adolescent drinkers differ from adult drinkers in their habits, demographics, and socioeconomic status. These socioeconomic differences have implications for the access to and cost-effectiveness of interventions.  相似文献   
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