We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.

If a cause-effect relationship exists between the first economical crisis in the ferry alloy plant and the concomitant rise in blood pressure, job strain had a powerful but time-limited effect on blood pressure. Since the same phenomenon was not reproduced 5 years later, the marked difference in job control (high vs low) may constitute the difference. Alternatively, age-related effects or adaptive coping mechanisms may have prevented a similar second blood pressure rise despite exposure to a job strain of similar severity. However, there was also a high 19-year total mortality in the study population, which could be related to long-term health consequences of the first or both economic crises. This study provides some support for the notion that increased job strain elevates blood pressure and deteriorates outcome.

The purpose of this study was to compare the histological characteristics of an autogenous fascia lata graft alone and a fascia lata graft combined with a deltoid flap in the reconstruction of rotator cuff tears. Ten New Zealand white rabbits were divided into two groups. Infraspinatus tendon defects (1 x 1 cm) were created in each animal. Reconstruction consisted of either a fascia lata graft alone or a fascia lata graft combined with a distally based deltoid flap. At 3 months, tissue harvest and histological analysis was performed. Compared to the fascia lata graft alone, there was significantly increased remodeling activity and neovascularization in the group that included a deltoid flap. Also, there was pronounced interdigitation at the graft/flap interface in the latter group. A mutually beneficial relationship may exist when an autogenous fascial graft is combined with a functional deltoid flap for reconstructing large rotator cuff defects.

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