Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Graded responses of human neutrophils induced by serum-treated zymosan

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3'- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.     

Salivary secretion and connective tissue disease in man.

Parotid and submandibular gland secretions collected from patients with rheumatoid arthritis or systemic sclerosis have been analysed and the results compared with those obtained from a matched group of healthy individuals. Flow rates were measured and the saliva samples assayed for amylase, kallikrein, protein, and salivary IgA concentration. The results showed that only patients with rheumatoid arthritis had a reduced salivary flow, especially parotid flow, with a significantly increased concentration of salivary IgA in both parotid and submandibular saliva. Patients with systemic sclerosis did not show significantly altered salivary flow rates, but there was a marked depletion of salivary IgA content in both parotid and submandibular saliva. Neither disease states appeared to alter the kallikrein or amylase content of saliva. The possible clinical value of these findings is discussed.     

Adolescents' relationships with grandparents: an empirical contribution to conceptual clarification

Findings from research in which a sample of 132 late adolescents completed questionnaires about their relationships with each of their living grandparents are reported. The grandchildren were most likely to describe their relationships with their maternal grandmothers as close and least likely to describe their bonds with the paternal grandparents in this way. Grandchildren's current evaluations of relationships with their grandparents were affected by access to the particular grandparent in childhood and their perceptions of each of their parents' relationships with the specific grandparent. The findings demonstrate empirically the importance for future research of conceptualizing the grandparent-grandchild tie as both particularistic and mediated through a biological and an in-law-child.     

Surgical Management of Pancreaticobiliary Disease associated with Juxtapapillary Duodenal Diverticula: Case Series and Review of the Literature

Introduction

Juxtapapillary duodenal diverticula (DD), although usually asymptomatic, are occasionally associated with pancreaticobiliary conditions such as recurrent bile duct stones, cholangitis, and pancreatitis.

Materials and methods

An unusual case of DD associated with a dorsal duct stricture in a patient with recurrent pancreatitis and pancreas divisum is presented along with three additional instances of surgically treated DD and a review of the literature.

Results

The role of surgical intervention depends upon the specific nature of the presentation and the anatomical relationship of the diverticulum to the ampullary and pancreaticobiliary ductal system.

Conclusion

Operations that divert bile and the food stream from DD are preferred over diverticulectomy.     

Laparoscopic Dor versus Toupet fundoplication following Heller myotomy for achalasia: results of a multicenter, prospective, randomized-controlled trial

Background

The type of fundoplication that should be performed in conjunction with Heller myotomy for esophageal achalasia is controversial. We prospectively compared anterior fundoplication (Dor) with partial posterior fundoplication (Toupet) in patients undergoing laparoscopic Heller myotomy.

Methods

A multicenter, prospective, randomized-controlled trial was initiated to compare Dor versus Toupet fundoplication after laparoscopic Heller myotomy. Outcome measures were symptomatic GERD scores (0?C4, five-point Likert scale questionnaire) and 24-h pH testing at 6?C12?months after surgery. Data are mean?±?SD. Statistical analysis was by Mann?CWhitney U test, Wilcoxon signed rank test, and Freidman??s test.

Results

Sixty of 85 originally enrolled and randomized patients who underwent 36 Dor and 24 Toupet fundoplications had follow-up data per protocol for analysis. Dor and Toupet groups were similar in age (46.8 vs. 51.7?years) and gender (52.8 vs. 62.5% male). pH studies at 6?C12?months in 43 patients (72%: Dor n?=?24 and Toupet n?=?19) showed total DeMeester scores and % time pH?p?=?0.152). Dysphagia and regurgitation symptom scores improved significantly in both groups compared to preoperative scores. No significant differences in any esophageal symptoms were noted between the two groups preoperatively or at follow-up. SF-36 quality-of-life measures changed significantly from pre- to postoperative for five of ten domains in the Dor group and seven of ten in the Toupet patients (not significant between groups).

Conclusion

Laparoscopic Heller myotomy provides significant improvement in dysphagia and regurgitation symptoms in achalasia patients regardless of the type of partial fundoplication. Although a higher percentage of patients in the Dor group had abnormal 24-h pH test results compared to those of patients who underwent Toupet, the differences were not statistically significant.     

Increased biliary fistulas after liver resection with the harmonic scalpel

The Harmonic Scalpel (HS) is frequently used for hepatic resection. Yet, no current study addresses its utility compared to conventional methods. We reviewed our experience with this device to determine if it decreased perioperative complications when compared to the traditional clamp crushing technique. One hundred forty-nine anatomic hepatic resections were performed at our institution from September 1992 to February 2002. Patients were divided into two groups based on the technique of resection: HS [53% (n = 79)] versus clamp crushing [47% (n = 70)]. Use of the HS was associated with a shorter mean operative time (357 +/- 15.0 vs. 404 +/- 19.1 min; p = 0.05) and a trend toward decreased blood loss (1211 +/- 125.5 vs. 1411 +/- 180.7 mL; P = NS) and transfusion requirements (2.6 +/- 0.5 vs. 1.7 +/- 0.3 units; P = 0.10). However, use of the HS was associated with a significant increase in biliary fistulas [24% (n = 19) vs. 7% (n = 5); P = 0.01]. Use of the Harmonic Scalpel was associated with decreased operative time and a trend toward decreased blood loss and transfusion requirements. Its use was also associated with a significant increase in the incidence of postoperative bile leaks, and, therefore, surgeons must be vigilant during liver parenchymal transection when using this device.