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.     

无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

Postmenopausal HRT is not independent risk factor for dural sinus thrombosis

While a dural sinus thrombosis (DST), is a well-known consequence of the use of oral contraceptives, the role of hormone replacement therapy (HRT) in DST was not previously evaluated. We report two postmenopausal women, presenting with DST under HRT. Antiphospholipid antibodies in one case and borderline protein S deficiency in another were diagnosed. Only five cases of DST under HRT were previously reported and in two of them additional prothrombotic risk factors were found. According to these and previous cases, HRT is not an independent risk factor for DST.     

Coemployed spouses: differences,strategies, and discrimination

The authors explore linkages between family and work roles. They examine patterns of apparent economic strategies of spouses working at a southern university located in a rural area. Their research focuses on spousal economic behavior and specifically addresses the effects of spouses' dual employment on the job status of women, differences between spouses in the timing of education and 1st hire at the university, status consistencies in husband and wife employment levels, and sexual discrimination in job levels and income of coemployed spouses. The study uses data extracted from a personnel data set. Cases from a computerized file were identified in 1980-1981, analyzed with 1981-1982 data, and compared with total work force data for 1982-1983. Slightly more than 1/2, or 123 identified cases, were analyzed. Some study findings follow. 1) Marriage to a coemployed spouse is associated with high occupational levels for female employees. 2) It is the husband's career that generally dictates the entry of a couple into the university's internal labor market. 3) There seems to be a strain toward consistency in the status levels of married pairs. 4) Collaborative strategies are being used to secure economic advances for the family unit. Major efforts regarding education and job selection are directed toward advancing the husband's career preference. However, some exceptions suggest that the pattern is flexible and that economic factors will take precedence over stereotyped sex roles when family needs come into consideration. 5) There is employment discrimination by sex at all levels of the internal labor market being studied. Status and income differentials still exist between males and females. Males in the same occupational statuses are paid more than their female counterparts. Females are concentrated at the lower levels of occupational ranks, males toward the top. Although this study is preliminary, it provides partial support for previous research on coemployed spouses' patterns of educational and occupational attainment, and the persistence of sex discrimination in earnings and occupational prestige.     

Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.     

MKK4 and metastasis suppression: a marriage of signal transduction and metastasis research

MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed.     

Communication on end-of-life decisions with patients wishing to die at home: the making of a guideline for GPs in Flanders, Belgium

BACKGROUND: Communication with patients on end-of-life decisions is a delicate topic for which there is little guidance.AIM: To describe the development of a guideline for GPs on end-of-life communication with patients who wish to die at home, in a context where patient autonomy and euthanasia are legally regulated. DESIGN OF STUDY: A three-phase process (generation, elaboration and validation). In the generation phase, literature findings were structured and then prioritised in a focus group with GPs of a palliative care consultation network. In the elaboration phase, qualitative data on patients' and caregivers' perspectives were gathered through a focus group with next-of-kin, in-depth interviews with terminal patients, and four quality circle sessions with representatives of all constituencies. In the validation phase, the acceptability of the draft guideline was reviewed in bipolar focus groups (GPs-nurses and GPs-specialists). Finally, comments were solicited from experts by mail. SETTING: Primary home care in Belgium. SUBJECTS: Participants in this study were terminal patients (n = 17), next-of-kin of terminal patients (n = 17), GPs (n = 25), specialists (n = 3), nurses (n = 8), other caregivers (n = 2) and experts (n = 41). RESULTS: Caregivers and patients expressed a need for a comprehensive guideline on communication in end-of-life decisions. Four major communication themes were prioritised: truth telling; exploration of the patient's wishes regarding the end of life; dealing with disproportionate interventions; and dealing with requests for euthanasia in the terminal phase of life. Additional themes required special attention in the guideline: continuity of care by the GP; communication on foregoing food and fluid; and technical aspects of euthanasia. CONCLUSION: It was feasible to develop a guideline by combining the three cornerstones of evidence-based medicine: literature search, patient values and professional experience.