Renal vascular reactivity in jaundice

Obstructive jaundice is associated with a predisposition to hypotension and acute renal failure that may be related to changes in renovascular responsiveness, particularly to norepinephrine (NE). This study was undertaken to investigate changes in vascular response to NE and to determine how these changes are related to prostaglandins. Kidneys from bile duct-ligated (BDL) rabbits (n = 5) were perfused with Krebs' solution at 7.65 ml/min, and the response to varying boluses of NE (0.78 to 6.24 micrograms) was measured as changes in perfusion pressure. When compared with sham-operated control kidneys (n = 8), a significantly blunted response was seen at all doses tested. The NE response was further assessed by measuring force development in mounted segments of main renal arteries (MRAs) (n = 8) and interlobar arteries (ILAs) (n = 6) from BDL rabbits and sham-operated controls (MRA, n = 8; ILA, n = 6). The dose-response curves were significantly depressed in both MRAs and ILAs from BDL animals. In addition, MRAs from sham-operated control animals exhibited decreased response to NE after incubation for 1 hour in jaundiced serum. This attenuated response of MRAs to NE was prevented when indomethacin (5 mg/kg) was given to BDL rabbits before death (n = 9) or when 10(-6)mol/L of indomethacin was added to jaundiced serum during incubation (n = 6). These results indicate that obstructive jaundice induces a decreased vascular contractile response in rabbits to NE and that this effect is mediated by prostaglandins.     

Diagnosis and treatment of smoke inhalation

Inhalation remains the most frequent and serious comorbid event that occurs in thermally injured patients. A thorough understanding of the pathophysiology enables individualization of therapy and appropriate triage of patients. We summarize our current knowledge of the pathophysiology, diagnosis, and treatment of inhalation injury, with a focus on newer treatment strategies that are evolving secondary to laboratory research.     

Mechanism of adrenal insufficiency following trauma and severe hemorrhage: role of hepatic 11beta-hydroxysteroid dehydrogenase

BACKGROUND: Although adrenal insufficiency may not occur with moderate hypotension, it does occur with severe hemorrhage. Since hepatocellular function is depressed following severe hemorrhage, it remains unknown whether the liver plays any role in regulating adrenal function after trauma and hemorrhagic shock. HYPOTHESIS: Hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD), a microsomal enzyme responsible for the degradation of bioactive corticosterone, plays a major role in the development of adrenal insufficiency following trauma and severe hemorrhage. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male rats underwent laparotomy to induce trauma before hemorrhage. They were then bled to and maintained at a blood pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer lactate. The rats were then resuscitated with 4 times the volume of maximal bleed-out with Ringer lactate during a 60-minute period. Plasma levels of corticosterone and corticotropin were measured at various intervals. In additional groups, corticotropin-induced corticosterone release, adrenal contents of corticosterone and cyclic adenosine monophosphate (cAMP), hepatic 11beta-HSD activity, and plasma levels of corticosterone-binding globulin were determined at 1.5 hours after resuscitation. Moreover, a model of moderate hypotension (blood pressure, 80 mm Hg) was used to determine whether adrenal function is depressed under such conditions. RESULTS: At the time of maximal bleed-out, plasma corticosterone and corticotropin levels increased by 245% (P<.001) and 293% (P<.001), respectively. Despite corticotropin levels being similar to those of the animals undergoing sham operation after resuscitation, corticosterone levels in hemorrhaged animals remained elevated up to 4 hours after resuscitation (by 158%-207%; P<.001). In addition, corticotropin-induced corticosterone release decreased by 78% at 1.5 hours after resuscitation (P = .009). In contrast, moderate hypotension did not reduce corticotropin-induced corticosterone release. Adrenal corticosterone content and cAMP levels (i.e., the second messenger of corticotropin action) decreased by 55% (P<.001) and 25% (P = .03), respectively. Hepatic 11beta-HSD activity decreased significantly at 1.5 hours after resuscitation (P<.001). CONCLUSIONS: Sustained increase in plasma corticosterone levels following hemorrhage and resuscitation may be, in part, due to the decreased hepatic 11beta-HSD activity. The high level of corticosterone negatively regulates corticotropin release, further reducing adrenal responsiveness to corticotropin stimulation. Thus, the liver appears to play an important role in regulating adrenal function following trauma and severe hemorrhage.     

Impact of coworker involvement with supported employees on wage and integration outcomes

This report is the fourth in a series on positive relations of typical employment features and coworker involvement with higher wage and integration outcomes for persons in supported employment. Imbedded in the discussion about natural supports in recent years has been the extent and value of coworker participation in the work life of employees with disabilities. Previous studies have illustrated the connection between natural supports and meaningful and satisfying employment outcomes. We investigated specific details associated with coworker training and support and their relation to social and economic outcomes that enable persons with disabilities to succeed economically and socially in inclusive employment.     

The influence of ocular pulsatility on scanning laser Doppler flowmetry.

PURPOSE: To determine the effect of the cardiac cycle on scanning laser Doppler flowmeter measurements of retinal capillary blood flow in rhesus monkeys and humans. METHODS: Multiple scanning laser Doppler flowmetry images of rhesus monkey and human retinal capillary blood flow over a range of heart rates were obtained. Average flow values were determined for the 64 scan lines that compose the two-dimensional flow map. Cutaneous blood flow was measured simultaneously with a laser Doppler flowmeter. The temporal relationships between retinal capillary blood flow, peripheral arterial pulse, and cutaneous blood flow were determined. In addition, human retinal capillary blood flow in a 10 x 10-pixel area during different phases of the cardiac cycle was compared. RESULTS: Regular oscillations in human and rhesus monkey retinal capillary blood flow are evident as alternating bright and dark horizontal bands in scanning laser Doppler flowmetry images. These fluctuations are temporally correlated with cutaneous blood flow. Linear regression of actual vs predicted heart rate based on peaks in retinal capillary flow yielded r = 0.999 in a rhesus monkey and 0.938 in a human. Retinal capillary blood flow in a 10 x 10-pixel area fluctuated as much as 50% depending on the phase of the cardiac cycle. CONCLUSIONS: The alternating bright and dark banding pattern observed in scanning laser Doppler flowmetry scans of retinal capillary blood flow is related to the cardiac pulse. The errors introduced by pulse-related fluctuations in retinal capillary blood flow are significant and must be minimized or corrected for accurate and reproducible measurements of ocular hemodynamics.     

Gender differences in supported employment

Questions about gender equity have been asked in many aspects of the disability field and have resulted in findings that women with disabilities have significantly different experiences than do men. We analyzed an existing database of information on supported employment and natural supports to ascertain whether gender plays an important role in the employment of people with mental retardation. The findings suggest that there are several important differences. Although women were perceived as being more socially appropriate on several dimensions, they worked in jobs traditionally stereotyped by gender. Women also typically worked fewer hours than did men and, therefore, earned less money, although not statistically significantly so. The pattern of findings suggests parallels with the broader society.     

Insight into the mechanism by which estradiol improves organ functions after trauma-hemorrhage

BACKGROUND: Recent studies have indicated that female rodents with high levels of estradiol (proestrus) have better organ functions after trauma-hemorrhage than females with low estradiol levels (estrus) or male animals. However, the precise role of estrogens in maintaining organ function after hemorrhage remains unknown. METHODS: Adult female Sprague-Dawley rats were ovariectomized 14 days before the experiment to decrease circulating levels of estradiol. Animals underwent laparotomy to induce tissue trauma and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. Resuscitation was carried out with 4 times the volume of maximal bleed-out with Ringer's lactate during a period of 1 hour. 17beta-Estradiol (E2, 1 mg/kg body weight intravenously) with or without a specific estrogen receptor antagonist ICI 182,780 (3 mg/kg body weight intraperitoneally) was given at the beginning of resuscitation. At 24 hours after hemorrhage and resuscitation, cardiovascular and hepatocellular functions (ie, the maximal velocity and overall efficiency of indocyanine green clearance) were determined. Plasma E2 was also assayed. The effects of ovariectomy and E2 administration on uterine weight were measured in additional groups of animals. RESULTS: The results indicate that cardiovascular and hepatocellular organ functions were significantly depressed after trauma-hemorrhage and were restored in animals receiving E2. However, simultaneous administration of its specific receptor antagonist abolished the salutary effects of E2 treatment despite high circulating levels of E2. Uterine weight decreased at 14 days after ovariectomy, which was partially restored with a single dose of E2. CONCLUSIONS: Administration of 17beta-estradiol should be considered a novel and safe adjunct for ameliorating hemorrhage-induced organ dysfunctions in ovariectomized and postmenopausal women because of their low estradiol levels.     

Antiproliferative oleanane saponins from Meryta denhamii

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.