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1.
Edema develops when lymph does not return to the venous circulation at a rate equal to the rate of capillary filtration. Fetal sheep develop edema as well as an increased central venous pressure while undergoing atrial pacing at 320 beats per min. We hypothesized that the increased central venous pressure augmented the appearance of fetal edema by impairing the return of thoracic duct lymph to the venous circulation. To investigate this hypothesis, we studied the effect of outflow pressure upon thoracic duct lymph flow in 10 unanesthetized fetal sheep who had low resistance lymph catheters placed in the cervical thoracic duct near its junction with the left jugular vein. After the ewe and fetus recovered for 5 d, we altered the outflow pressure of the lymph catheter by adjusting its height with respect to amniotic fluid pressure and measured the resultant change in thoracic duct lymph flow rate. We found that lymph flow rate was constant over the range of outflow pressures (central venous pressures) normally encountered but decreased in a linear fashion at pressures greater than 0.68 kPa (5.1 torr). Lymph flow stopped at an outflow pressure of 2.40 kPa (18 torr). The data points are best fit by two lines obtained by a piecewise linear regression rather than a single line obtained from a linear regression. We conclude that fetal thoracic duct lymph flow is sensitive to elevations in outflow pressure. Lymph flow begins to diminish at outflow pressures corresponding to central venous pressures commonly encountered in pathologic conditions and may augment the appearance of fetal edema. 相似文献
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3.
The eleven top-ranked graduate programs in health services administration, based on a national survey of deans, top administrators, and senior faculty, were linked to one another by hiring one another's graduates. It is suggested that this linkage helps these programs maintain and enhance their prestige. 相似文献
4.
Changes in drug handling activities, revenue, and telephone communications were documented during a conversion from a centralized unit dose system to decentralized pharmacists and unit dose services in a 310-bed university teaching hospital. All decentralized services were mobile; no physical satellites were utilized. Computer programs were used to collect and analyze drug handling and revenue data during a prestudy control period and three equal-length study periods after decentralization of pharmaceutical services for five patient care areas of the hospital. All telephone calls to the central pharmacy were recorded and classified by type during 21 days of the prestudy period and were compared with 21 days of the second postimplementation period. The mean number of doses handled decreased for all patient care areas. After decentralization the number of telephone calls to the central pharmacy requesting clinical drug information, as well as distributive information, decreased sharply. Moving the pharmacist to the patient care unit decreased the time that pharmacists spent handling drugs and improved communication with the medical and nursing staffs. 相似文献
5.
Robert M. Zucker David J. Adams Kenneth W. Bair Kenneth H. Elstein 《Investigational new drugs》1992,10(1):1-15
To investigate the toxicity and mechanism of action of crisnatol (CRS), a new DNA intercalator currently in phase II clinical trials, we analyzed cellular and nuclear flow cytometric (FCM) parameters of murine erythroleukemic cells (MELC) exposed to a range of CRS concentrations over three exposure conditions: short-term (4 h), long-term (24 h), and short-term with recovery (4 h+/19 h–). At 0.5–1.0M CRS, 4 h exposure results in a reversible G2-phase block, while 24 h exposure results in > G2 polyploidy. At 5–10M CRS concentrations, cells exhibit persistent retardation of S-phase progression or irreversible G2 and/or > G2 blocks, depending on duration of exposure. Cells terminally blocked in G2 exhibit increased nuclear/cellular volumes and increased nuclear fluorescein isothiocyanate (protein) staining, suggestive of unbalanced growth. At 25–50M CRS concentrations, MELC exhibit severe membrane perturbation (loss of viability) regardless of exposure. In contrast, following similar exposures to an inactive isomer of CRS, MELC exhibit minimal cell cycle effects, suggesting that cell cycle kinetics may be a useful criterion for assessing potential efficacy. Similar analyses with different classes of chemotherapeutic agents reveal that the range of induced cellular/nuclear perturbations varies with the class of compound used. Taken together, these results suggest that drug toxicity can vary with both concentration and duration of exposure and, as such, a selective multiple-exposure FCM analysis may better represent the spectrum of drug action for drug development and pharmacodynamic studies.Abbreviations
m-AMSA
amsacrine
- ARA-C
cytosine arabinoside
- BrdU
5-bromodeoxyuridine
- CF
5,6-carboxyfluorescein
- CFDA
5,6-carboxyfluorescein diacetate
- CRS
crisnatol
- FCM
flow cytometry
- FITC
fluorescein isothiocyanate
- 5-FU
5-fluorouracil
- DMSO
dimethylsulfoxide
- MELC
Friend murine erythroleukemic cell
- MLP
melphalan
- PBS
phosphate-buffered saline
- PI
propidium iodide
- TAX
taxol
- topo
topoisomerase
- VBL
vinblastine sulfate
-
cis-Pt
cis-platinum 相似文献
6.
Group relations conferences and 12-Step recovery thrive on the participants working in groups. This article is an inquiry into the integration of these traditions, in the Loyola Group Relations Conference, January 14–16, 2011. This conference recruited staff and members from the recovery community. 12-Step meetings were integrated into the conference design. The authors discuss the similarities and differences of the two models and examine the learning of conference staff and members. The authors conclude that Group Relations Conferences focusing on leadership, authority, and recovery from addiction can bring important group relations learning to the recovery community and vice versa. 相似文献
7.
Cross-validation is frequently used for model selection in a variety of applications. However, it is difficult to apply cross-validation to mixed effects models (including nonlinear mixed effects models or NLME models) due to the fact that cross-validation requires “out-of-sample” predictions of the outcome variable, which cannot be easily calculated when random effects are present. We describe two novel variants of cross-validation that can be applied to NLME models. One variant, where out-of-sample predictions are based on post hoc estimates of the random effects, can be used to select the overall structural model. Another variant, where cross-validation seeks to minimize the estimated random effects rather than the estimated residuals, can be used to select covariates to include in the model. We show that these methods produce accurate results in a variety of simulated data sets and apply them to two publicly available population pharmacokinetic data sets. 相似文献
8.
Coyle TE Bair AK Stein C Vajpayee N Mehdi S Wright J 《American journal of hematology》2005,78(4):256-260
Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. 相似文献
9.
Kolek MJ Carlquist JF Muhlestein JB Whiting BM Horne BD Bair TL Anderson JL 《American heart journal》2004,148(6):1034-1040
Background
Coronary artery disease (CAD) and, increasingly, diabetes are recognized as having an inflammatory basis. Membrane toll-like receptors (TLRs) activate signaling pathways that up-regulate inflammation. We evaluated whether the Asp299Gly polymorphism in the TLR4 gene, which impairs inflammatory responses, is associated with reduced vascular inflammation (assessed by C-reactive protein [CRP]) and a decreased risk for CAD and diabetes.Methods
1894 patients without acute myocardial infarction undergoing coronary angiography were studied. Genotyping was performed by real-time polymerase chain reaction. CAD was defined as ≥70% stenosis. Diabetes was diagnosed by patients' referring physicians. CRP was measured by fluorescence polarization immunoassay. Regression analyses adjusted for traditional cardiac risk factors.Results
Patients averaged 64 ± 11 years of age, and 69% were male. Asp299Gly genotype frequencies were: AA = 0.911 (n = 1725), AG = 0.086 (n = 164), and GG = 0.003 (n = 5), in keeping with Hardy-Weinberg equilibrium. CRP was lower among G-allele carriers (median = 1.11 mg/dL) than wild-type (AA) subjects (1.23 mg/dL, adjusted P = .044). G-allele carriers also had a lower prevalence of CAD (65% vs. 73%, OR = 0.67, CI = 0.46-0.99, adjusted P = .048) and diabetes (11% vs. 18%, OR = 0.63, CI = 0.42-0.95, adjusted P = .029), which persisted in multivariate logistic regression analyses. 299Gly carriage did not affect clinical outcomes nor interact with statin therapy.Conclusions
The TLR4 299Gly allele was associated with reduced CRP levels and, in parallel, a decreased risk of angiographic CAD and clinical diabetes. These findings suggest that down-regulation of innate immune responsiveness could beneficially modify CAD and diabetes risk and might provide a novel basis for genetic risk stratification and therapeutic targeting. 相似文献10.
Bair YA García JA Romano PS Siefkin AD Kravitz RL 《Journal of general internal medicine》2001,16(7):475-481
OBJECTIVE: Recent reforms in the federal Medicaid program have attempted to integrate beneficiaries into the mainstream by providing them with managed care options. However, the effects of mainstreaming have not been systematically evaluated. DESIGN: Cross-sectional survey. SETTING/PARTICIPANTS: A sample of 478 adult, nonelderly asthmatics followed by a large Northern California medical group. MEASUREMENTS AND MAIN RESULTS: We examined differences in self-reported access by insurance status. Compared to patients with other forms of insurance, patients covered by the state's Medicaid program (Medi-Cal) were more likely to report access problems for asthma-related care, including difficulties in reaching a health care provider by telephone, obtaining a clinic appointment, and obtaining asthma medication. Adjusting for relevant clinical and sociodemographic variables, Medi-Cal patients were more likely to report at least one access problem compared to non-Medi-Cal patients (adjusted odds ratio [AOR], 3.34; 95% confidence interval [CI], 1.43 to 7.80). Patients reporting at least one access problem were also more likely to have made at least one asthma-related emergency department visit within the past year (AOR, 4.84; 95% CI, 2.41 to 9.72). Reported barriers to care did not translate into reduced patient satisfaction. CONCLUSIONS: Within this population of Medicaid patients, the provision of health insurance and care within the mainstream of an integrated health system was no guarantee of equal access as perceived by the patients themselves. 相似文献