The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep.

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.     

The academic elite in health services administration: linkages among top-ranked graduate programs

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.     

Analysis of dispensing activities before and after decentralization of pharmaceutical services

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.     

An efficient multiple-exposure analysis of the toxicity of crisnatol,a DNA intercalator in phase II clinical trials

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     

Retrospective study of treatment outcome for individuals with aphasia

Abstract

Measurement of outcomes subsequent to treatment and documentation of the efficiency with which outcomes are achieved is critical information for healthcare policy makers and third-party payers. This study employed the ASHA Functional Communication Measure (FCM) scales to retrospectively analyse charts of 20 aphasic patients. By discharge, both severe and moderate groups gained a median (across modalities) of 1 FCM level. The severe group remained dependent for communication, while the moderately impaired group typically achieved independent communication levels. Efficiency (amount of FCM level gain relative to number of treatment sessions) was greater for the moderate group; average number of treatment sessions was 40 for the severe group and 22 for the moderate group.     

Group Relations and 12-Step Recovery

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.     

Cross-validation for nonlinear mixed effects models

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.     

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

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.