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Biomedical subjects

P Dineen

Publications and source records attributed to P Dineen.

At least 19 recordsLinked to original sources

Elevated production of neutrophil leukotriene B4 precedes pulmonary failure in critically ill surgical patients.

Leukotriene B4, a potent neutrophil chemotactic factor, is also made by the neutrophil. Neutrophil function was studied in 12 patients at risk for the development of adult respiratory distress syndrome (ARDS) after admission to the surgical intensive care unit (ICU) to test the hypothesis that increased generation by the neutrophil generation of this mediator precedes the development of pulmonary failure. Peripheral blood neutrophils were tested for chemotaxis to f-met-leu-phe (fMLP) and leukotriene B4 (LTB4) and the generation of LTB4. Plasma was collected simultaneously for assay of C3a desArg levels. Five patients had ARDS a mean of 2.2 +/- 0.25 days after admission to the ICU. Neutrophil generation of LTB4 was significantly enhanced on ICU day 1 in these patients as compared with patients at risk for ARDS but not developing the syndrome (119.4 +/- 6.1 versus 101.0 +/- 5.1, per cent control, p less than 0.05). Chemotaxis to fMLP and LTB4 was significantly reduced in both groups of patients. However, neutrophil chemotaxis improved in patients who did not have pulmonary failure during the time in the ICU, whereas neutrophil chemotactic responsiveness worsened in patients who did have pulmonary failure. Plasma C3a desArg levels were significantly elevated over normal laboratory values on ICU day 1 in the ARDS patients (317.2 +/- 74.0 versus 132.0 +/- 16.0 milligrams per milliliter, p less than 0.01). These data indicate that LTB4 production by the neutrophil occurs concomitantly with complement activation, is a predictor of subsequent ARDS and may play a significant role in the development of pulmonary failure in critically ill surgical patients.

Chemotaxis, Leukocyte

Leukotriene B4 generation in patients with established pulmonary failure.

We investigated the cause of the reduced leukotriene B4 (LTB4) production seen in neutrophils from patients with established adult respiratory distress syndrome compared with control neutrophils. Lymphocytes/monocytes from controls were found to synergistically enhance the amount of LTB4 produced when incubated with neutrophils. This synergistic effect was not seen in cells from patients with adult respiratory distress syndrome. Fatty-acid analysis of neutrophils from patients with adult respiratory distress syndrome and controls showed remarkable similarity in all quantities of fatty acids measured except for arachidonic acid, where there was a 22% reduction in patients' cells compared with controls. Assay of the rate of generation of LTB4 and its degradation product, 20-hydroxy LTB4, revealed that reduced LTB4 generation in patients' neutrophils was not due to increased degradation of LTB4 by hydroxylase enzymes. When the amount of LTB4 being generated per milliliter of whole blood was analyzed in the patients with adult respiratory distress syndrome and compared with controls, it was determined that the potential to generate LTB4 in patients in the intensive care unit was three to five times greater than in controls.

Fatty Acids

Tumor necrosis factor-enhanced leukotriene B4 generation and chemotaxis in human neutrophils.

In an in vivo study of five normal volunteers infused with endotoxin (20 U/kg of US reference endotoxin lot EC-5), increased neutrophil (PMN) generation of leukotriene B4 and chemotaxis to leukotriene B4 were found concomitantly with elevated plasma tumor necrosis factor (TNF) levels. To clarify the role of TNF in PMN activation, neutrophil responsiveness after in vitro treatment with TNF was examined. Neutrophils from seven normal subjects were incubated with TNF for 30 minutes and tested for chemotaxis to leukotriene B4, formyl-methionyl-leucyl-phenylalanine and zymosan-activated serum, or the calcium ionophore A23187 to assess leukotriene B4 generation. A range of 10(-13) to 10(-9) mol/L of TNF was used for these assays. When 10(-9) mol/L of TNF was used, the amount of leukotriene B4 that was produced was significantly greater than in control cells. The effect of TNF on PMN chemotaxis was uniformly inhibitory for the three stimuli at 10(-10) mol/L compared with untreated cells. At a picomolar range, PMN migration to leukotriene B4, but not to zymosan-activated serum or formyl-methionyl-leucyl-phenylalanine, was significantly increased over that of PMNs not exposed to TNF. This suggests that TNF has a specific facilitatory effect on PMN responsiveness for both leukotriene B4 production and chemotaxis to leukotriene B4 and may be the same signal for this phenomenon in endotoxemic patients.

Calcimycin

Differential neutrophil activation before and after endotoxin infusion in enterally versus parenterally fed volunteers.

This study was done to determine whether or not increased susceptibility to infection seen in enterally versus parenterally fed patients was caused by altered neutrophil (PMN) responsiveness. To determine the differential effects of route of feeding on human PMN activation, plasma C3a levels, circulating PMN counts, PMN migration to leukotriene B4 (LTB4), the peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and zymosan activated serum (ZAS) and generation of LTB4 were assayed before and after and infusion of endotoxin. Nine normal volunteers were enterally (n=4) or parenterally (n=5) fed a diet sufficient to maintain body weight for seven days prior to a standard challenge of endotoxin. Samples were taken prior to the infusion and hourly thereafter for six hours. Prior to the injection of endotoxin, significant differences were seen in the two feeding groups. Plasma C3a levels, absolute circulating PMN counts and chemotaxis to LTB4 were all significantly (p less than 0.02) elevated in the enterally fed group. Generation of LTB4 was higher in the intravenously fed group at base line than the orally fed group (p less than 0.05). Plasma C3a levels rose in the enterally fed group, but not in the intravenously fed group, at two hours after infusion. Neutrophil counts rose in both feeding groups after endotoxin infusion; but the change in percentage was greater in the enterally fed group than in the intravenously fed group. Chemotaxis to FMLP and ZAS was not different during the study and did not differ between the two feeding can have significant impact on neutrophil function and that parenteral nutrition may impair host responsiveness.

Chemotaxis

Hand-washing degerming: a comparison of povidone-iodine and chlorhexidine.

Two antiseptic preparations for hand washing were compared by the glove-juice method in a crossover study on 10 volunteers. The reference preparation was 7.5% povidone-iodine (Betadine Surgical Scrub); the test agent was 4% chlorhexidine gluconate combined with 4% isopropyl alcohol (Hibiclens). The experimental model included inoculation of the hands with a mixture of Serratia marcescens, Escherichia coli, Providentia stuartii, and Pseudomonas aeruginosa. The reference preparation achieved a reduction ratio in colony counts of 695 to 1 under the conditions of this study. The average postwash colony count after use of 7.5% povidone-iodine was significantly less than the preinoculation colony count. Logarithmic values, and the paired t test applied to them, showed a highly significant difference (p = less than 0.001) in favor of the degerming ability of the reference agent compared to the test agent. These data are of value in the selection of preparations for hand washing and may point the way to quantitative methods for other degerming studies.

Anti-Infective Agents, Local

The role of splenectomy in the treatment of thrombocytopenic purpura due to systemic lupus erythematosus.

Splenectomy in the treatment of thrombocytopenic purpura associated with lupus erythematosus has afforded satisfactory overall results in a group of ten patients. Postoperative deaths occurred in two patients, each of whom had significant underlying problems. Clinical manifestations of SLE-induced thrombocytopenic purpura included ecchymoses, petechiae, menorrhagia, epistaxis, and hematuria. Splenectomy in this disorder should be reserved for cases in whom corticosteroids do not produce satisfactory results, or in whom unacceptably high doses are required. Follow-up indicates long term control of thrombocytopenic purpura following splenectomy.

Adolescent

Comparison of the results of resection, bypass, and bypass with exclusion for ileocecal Crohn's disease.

Controversy continues regarding the optimal surgical treatment of Crohn's disease involving the ileum and cecum. Over 43-years, 161 patients underwent primary surgery for this disease at The New York Hospital-Cornell Medical Center. Resection was performed in 115 patients, bypass with exclusion in 25, and side-to-side ileotranverse colostomy in 21. Overall recurrence rates were 25% for resection, 63% for bypass with exclusion, and 75% for simple bypass. Expressed as 15 year follow-up, recurrence rate were 65% for resection, 82% for bypass with exclusion, and 94% for simple bypass. Much of the difference in final outcome was accounted for by early recurrence or by persistent disease in the two bypass groups. This amounted to 21% for the bypass with exclusion and 45% for simple bypass as compared to 3% for patients who had resection. Conclusions from this review are that 1) resection can be performed with a morbidity and mortality equivalent to either of the bypass procedures; 2) the recurrence rat following resection is significantly lower than bypass with exclusion or simple bypass, and amounts to about 4% per year; 3) continuing disease in the bypassed loop accounts for a high percentage of reoperations in the bypass groups, while appearance of new disease is the usual problem following resection; 4) resection is the surgical treatment of choice for ileocecal Crohn's disease.

Adult

The effect of oxidized regenerated cellulose on experimental intravascular infection.

Two groups of dogs had aortotomies and insertion of a Teflon patch. One group had the area of the aorta with the patch wrapped with oxidized regenerated cellulose (ORC); the other group served as a control. Both groups of animals were infected with S. aureus intravenously immediately after removal of the aortic clamps. The animals which had ORC wrapping of the aorta had significantly lower bacterial counts at the time of death than did the untreated group. This was measured from an hour after challenge up to 30 days.

Animals

The role of surgery in primary syphilis of the anus.

Surgery has no role in the treatment of primary (infectious) syphilis of the anorectum. In this paper, we describe four patients who presented directly to the surgeon complaining of localized anal lesions. In three patients, the chancre was excised and in one patient the correct diagnosis was made prior to surgery. Rectal pain, which we attributed to secondary infection, was the chief complaint in three patients. Two patients also complained of tender lymphadenopathy. Darkfield examination is the most important diagnostic technique and penicillin remains the drug of choice. When treating diseases of the anorectum, the surgeon must maintain a high index of suspicion and a constant awareness of the manifold presentations of primary syphilis.

Adult

Antibacterial activity of oxidized regenerated cellulose.

It has been demonstrated that oxidized regenerated cellulose promptly and markedly reduces the bacterial census of ten different strains of common pathogens when exposed to them in vitro. This was not true of two other hemostatic agents tested, namely, absorbable gelatin sponge and topical thrombin. Wounds in guinea pigs in which oxidized regenerated cellulose was placed and infected with one of three pathogens had healing per primum in 39 of 40 instances. In similar control wounds and incisions in which absorbable gelatin sponge was placed, sepsis of the wound developed in 19 of 20 of the control group and in 39 of 40 guinea pigs in the absorbable gelatin sponge group.

Animals