平贝碱乙的分离和鉴定

本文报道了自东北平贝母(Fritillaria ussuriensis Maxim)中分得一种新的甾体生物碱,经光谱(IR,MS,¹HNMR及¹³CNMR)解析和衍生物制备,推定其结构为5α,17β,22α-cevanine-3 β,6α,12α,14α,16β,20β-hexol,定名为平贝碱乙。     

The effects of continuous superfusion of L-aspartate and L-glutamate on horizontal cells of the turtle retina

We have studied the effects of prolonged superfusion with L-aspartate and L-glutamate on the membrane potential and photoresponses recorded in luminosity type horizontal cells in the turtle retina using an everted eyecup preparation. These acidic amino acids produce effects which are a function of the past history of the impaled cell. Initial prolonged superfusions with 30 mM of either drug has no pronounced effect on the membrane potential and photoresponses of horizontal cells. Subsequent superfusions with either agent eventually produce depolarizations with reductions in the amplitudes of the light evoked responses. These effects, however, are transient; the horizontal cell rehyperpolarizes and the light evoked response grows with time. In a retina which had been stored at 4 degrees centrigrade for 20 hours, an initial superfusion with L-aspartate solution produced an immediate depolarization of the horizontal cell and complete suppression of the light evoked response for as long as the amino acid was present. The data are consistent with the existence of powerful amino acid uptake mechanisms operating at a number of sites within the inner and outer retina but also raise questions about the role of acidic amino acids in the outer plexiform layer of the turtle retina.     

Flow cytometry in hairy cell leukemia before and during interferon alfa-2b therapy

Mononuclear cells from 15 patients with hairy cell leukemia were studied before and during therapy with interferon alfa-2b (IFN) by regular peripheral blood differential counts and flow cytometry, using a panel of monoclonal antibodies (Moab). Seven leukemic phase patients (Group 1) had a mean leukocyte count of 48,870/microliter at entry with a mean absolute hairy cell (HC) count of 40,100/microliter. After 3 months on IFN, both parameters decreased significantly (WBC 3,500/microliter; HC count 130/microliter). In eight patients with a cytopenic form of the disease (Group 2) the mean leukocyte count rose from 2950/microliter to 3890/microliter while the mean absolute HC count decreased from 300/microliter to 120/microliter. The morphologic shifts correlated well with changes in the Moab reaction pattern. In Group 1 the activity of all Moab decreased significantly. In Group 2, only cells expressing Leu 3a and Leu 11a (a marker of natural killer cells) showed a significant shift, the latter increasing from 170/microliter to 360/microliter. This increase in natural killer cell antigen expression was not obvious based on routine morphologic observations alone. We show that flow cytometry may be a useful adjunct in monitoring the response of HCL to therapy. Changes in populations of cells that may be difficult to discriminate on morphologic grounds alone may be observed.     

Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers

Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan–Meier analyses. Use of RRSO was 45 % for BRCA1 and 34 % for BRCA2 by age 40, and 86 % for BRCA1 and 71 % for BRCA2 by age 50. RRM usage was estimated to be 46 % by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.     

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre‐ and post‐transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter‐associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species‐level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long‐term multidrug regimens, and consideration of complex drug‐drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.     

Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men

Introduction It remains uncertain whether long-term participation in regular weight-bearing exercise confers an advantage to bone structure and strength in old age. The aim of this study was to investigate the relationship between lifetime sport and leisure activity participation on bone material and structural properties at the axial and appendicular skeleton in older men (>50 years).Methods We used dual-energy X-ray absorptiometry (DXA) to assess hip, spine and ultradistal (UD) radius areal bone mineral density (aBMD) (n=161), quantitative ultrasound (QUS) to measure heel bone quality (n=161), and quantitative computed tomography (QCT) to assess volumetric BMD, bone geometry and strength at the spine (L₁–L₃) and mid-femur (n=111). Current (>50+ years) and past hours of sport and leisure activity participation during adolescence (13–18 years) and adulthood (19–50 years) were assessed by questionnaire. This information was used to calculate the total time (min) spent participating in sport and leisure activities and an osteogenic index (OI) score for each participant, which provides a measure of participation in weight-bearing activities.Results Regression analysis revealed that a greater lifetime (13–50+ years) and mid-adulthood (19–50 years) OI, but not total time (min), was associated with a greater mid-femur total and cortical area, cortical bone mineral content (BMC), and the polar moment of inertia (I _p) and heel VOS (p ranging from <0.05 to <0.01). These results were independent of age, height (or femoral length) and weight (or muscle cross-sectional area). Adolescent OI scores were not found to be significant predictors of bone structure or strength. Furthermore, no significant relationships were detected with areal or volumetric BMD at any site. Subjects were then categorized into either a high (H) or low/non-impact (L) group during adolescence (13–18 years) and adulthood (19–50+ years) according to their OI scores during each of these periods. Three groups were subsequently formed to reflect weight-bearing impact categories during adolescence and then adulthood: LL, HL and HH. Compared to the LL group, mid-femur total and cortical area, cortical BMC and I _p were 6.5–14.2% higher in the HH group. No differences were detected between the LL and HL groups.Conclusions In conclusion, these findings indicate that long-term regular participation in sport and leisure activities categorized according to an osteogenic index [but not the total time (min) spent participating in all sport and leisure activities] was an important determinant of bone size, quality and strength, but not BMD, at loaded sites in older men. Furthermore, continued participation in weight-bearing exercise in early to mid-adulthood appears to be important for reducing the risk of low bone strength in old age.     

Rates of admission to six Northern Ireland psychiatric hospitals of patients with primary alcohol-related diagnoses

The rate of admissions to psychiatric hospitals of patients with primary alcohol-related diagnoses (PARD) has increased from 1971 to 1983 and they now account for 19.7% of all admissions. There is a wide variation in admission rates between hospitals, and the use of the Mental Health (NI) Act 1961 to admit these patients formally varies up to twelvefold.