Inhibition of leukotriene biosynthesis by quinolone alkaloids from the fruits of Evodia rutaecarpa

The n-hexane extract of the fruits of Evodia rutaecarpa showed a considerable inhibiting effect on leukotriene biosynthesis in human granulocytes. Bioassay-guided fractionation of the extract led to the isolation of the 5 quinolone alkaloids: 1-methyl-2-nonyl-4(1H)-quinolinone, 1-methyl-2-(6Z)-6-undecenyl-4(1H)-quinolinone, 1-methyl-2-(4Z,7Z)-4,7-tridecadienyl-4(1H)-quinolinone, evocarpine and 1-methyl-2-(6Z,9Z)-6,9-pentadecadienyl-4(1H)-quinolinone. The compounds exhibited inhibitory activity on leukotriene biosynthesis in a bioassay using human polymorphonuclear granulocytes, with IC50 values of 12.1, 10.0, 10.1, 14,6 and 12.3 microM, respectively. Structure elucidation of the compounds was achieved by 1D and 2D NMR experiments and comparison of spectral data with literature data.     

Negotiation as relationship-building in healthcare organizations: a case study exercise

A key skill needed by healthcare managers is an ability to simultaneously maintain and enhance relationships with multiple stakeholders, most notably clinical professionals, through the process of decision-making and negotiation. Additionally, healthcare managers need to be able to actively integrate various components of functional areas into their decision-making process. This article presents two exercises that serve the following purposes: (1) it can help raise students' awareness of the complexity involved in decision-making and negotiating, (2) it can create an understanding that decision-making and negotiations are embedded in a larger context involving multiple relationships between parties, and (3) it can be used as a means to measure the student's integrative ability within the traditional curriculum of an MHA program.     

Patterns of intra-cluster correlation from primary care research to inform study design and analysis

OBJECTIVE: To provide information concerning the magnitude of the intraclass correlation coefficient (ICC) for cluster-based studies set in primary care. STUDY DESIGN AND SETTING: Reanalysis of data from 31 cluster-based studies in primary care to estimate intraclass correlation coefficients from random effects models using maximum likelihood estimation. RESULTS: ICCs were estimated for 1,039 variables. The median ICC was 0.010 (interquartile range [IQR] 0 to 0.032, range 0 to 0.840). After adjusting for individual- and cluster-level characteristics, the median ICC was 0.005 (IQR 0 to 0.021). A given measure showed widely varying ICC estimates in different datasets. In six datasets, the ICCs for SF-36 physical functioning scale ranged from 0.001 to 0.055 and for SF-36 general health from 0 to 0.072. In four datasets, the ICC for systolic blood pressure ranged from 0 to 0.052 and for diastolic blood pressure from 0 to 0.108. CONCLUSION: The precise magnitude of between-cluster variation for a given measure can rarely be estimated in advance. Studies should be designed with reference to the overall distribution of ICCs and with attention to features that increase efficiency.     

Age-related variations in progression of cancer at diagnosis and completeness of cancer registry data

There is some evidence that stage and grade at diagnosis of cancer decreases with age and that the availability of data on stage and grade of cancer decreases with age. This may be because older people tend to receive less intensive investigation of cancer but this has not been confirmed. We investigated the relationship between age at diagnosis of cancer and both stage and grade at diagnosis, and the chances of data on stage or grade at diagnosis being unavailable, in people with colorectal cancer (n=12,419) and women with breast cancer (n=12,793) using 2 years of cancer registry data from the north of England. Stage and grade decreased with increasing age in colorectal cancer. Grade decreased but stage increased with increasing age in women with breast cancer. The chances of data on stage and grade at diagnosis being unavailable increased with age in all cases.     

Frequency and timing of symptoms in infants screened for sepsis: effectiveness of a sepsis-screening pathway

To determine the frequency and timing of symptoms and to evaluate the effectiveness of a sepsis-screening pathway in term and near-term infants, data were collected prospectively for a period of 1 year from December 1, 2000, to November 30, 2001. Results confirmed that a sepsis-screening pathway using a combination of at least 2 serial complete blood cell count and C-reactive protein measurements in both symptomatic and asymptomatic infants is a safe, simple strategy that prevents unnecessary treatment of infants with risk factors with antibiotics. However, most infants with presumed or suspected early-onset sepsis are symptomatic. Routine treatment of asymptomatic infants with risk factors or prior treatment with intrapartum antibiotics is unnecessary. A combined approach of screening in the presence of risk factors and /or symptoms of sepsis and adequate follow-up for infants discharged at less than 72 hours of age may help reduce unnecessary treatment of infants with antibiotics.     

Future challenges in analysis and treatment of human immune senescence

Immune functions decline with age; immunorestorative approaches have been explored in laboratory animals and humans with definite, but limited success. In the clinical setting, the age-associated immune deficiency (immunesenescence) is compounded by the presence of comorbidities that are associated with a functional decline in immunity. Thus, any successful immune reconstitution strategy for humans must involve treatment of the underlying diseases. Furthermore, general health measures such as nutrition and exercises may have powerful effects on restoring immunity, to the extent that malnutrition and a sedentary lifestyle have contributed to existing immune deficiency. More selective approaches, such as with specific cytokines or organ transplantation are of experimental interest but are quite distant from achieving clinical applicability as interventions to restore immunity in the frail elderly.     

Serial analysis of gene expression provides new insights into regulatory T cells

It is now possible to induce donor-specific transplantation tolerance in adult rodents using a number of therapeutic strategies. Such peripheral tolerance is maintained by regulatory CD4+ T cells, not only in transplantation models, but also in autoimmunity. Differential gene expression analyses have been used to identify potential new markers for regulatory T cells, aiming to reveal new insights into their mechanisms of action, and to find novel targets for therapeutic manipulation of the immune system.     

Sequence analysis demonstrates that <Emphasis Type="Italic">Onion yellow dwarf virus</Emphasis> isolates from China contain a P3 region much larger than other potyviruses

Summary.  The complete sequence of an isolate of Onion yellow dwarf virus (OYDV) from Yuhang, Zhejiang province, China, was determined. It was 10538 nts in length and was predicted to encode a polyprotein 3403 amino acids (aa) long with a calculated M_r of 385.1 kDa. The predicted P3 protein (530 aa) was larger than that of any of the potyviruses sequenced to date (344–378 aa). The additional sequence occurs at the N-terminus of the protein, does not represent a duplication from elsewhere in the OYDV genome and could not be matched to any other sequences in the databases. Similar sequences were found in 4 other Chinese OYDV isolates. Phylogenetic analysis of the amino acid sequences of the polyprotein showed that OYDV is distantly related to Pea seed-borne mosaic virus and the potyviruses of grasses and cereals. Received November 26, 2002; accepted February 4, 2003 Published online April 2, 2003     

Prevalence of Mycoplasma bacteria in amniotic fluid at the time of genetic amniocentesis using the polymerase chain reaction

OBJECTIVE: To use the polymerase chain reaction (PCR) to detect the presence of bacteria and Mycoplasma in amniotic fluid at the time of genetic amniocentesis and to assess their relationship to amniotic fluid interleukin-6 (IL-6) concentration and preterm delivery. STUDY DESIGN: A prospective study was performed on 78 asymptomatic pregnancies presenting for genetic amniocentesis. Amniotic fluid samples were analyzed by PCR for the detection of bacterial 16S ribosomal RNA, by PCR/enzyme-linked immunosorbent assay (ELISA) for Mycoplasma and by ELISA analysis for IL-6 concentration. RESULTS: All 78 samples were analyzed, and bacterial RNA was detected in 18% of them. However, no sample tested positive for Mycoplasma. The mean IL-6 concentration was 435 pg/mL. There was no difference in IL-6 levels or gestational age between bacteria-positive and -negative groups. CONCLUSION: Amniotic fluid may not be sterile in the midtrimester, yet the presence of bacteria, as detected by PCR, does not always result in an inflammatory response or adverse perinatal outcome.