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Biomedical subjects

T J Krause

Publications and source records attributed to T J Krause.

13 recordsLinked to original sources
PubMed2001

The effects of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery.

HYPOTHESIS: Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may contribute to prolongation of systemic inflammation after cardiopulmonary bypass. BACKGROUND/OBJECTIVE: Preoperative administration of glucocorticoids has been used ostensibly to attenuate the systemic inflammation associated with cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic signal transduction. DESIGN: Randomized control study. SETTING: Medical school and affiliated tertiary care hospital. PATIENTS: Thirteen patients undergoing coronary artery bypass grafting. INTERVENTION: Patients were randomly assigned to the control group (n = 7) or to receive 1 g of methylprednisolone sodium succinate on anesthetic induction (n = 6). MAIN OUTCOME MEASURES: Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, immediately postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6 hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte apoptosis was measured using propidium iodide-RNAase staining and flow cytometry. Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha, interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2) were measured. RESULTS: In all 13 patients, spontaneous and Fas-mediated PMN apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1. Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1 compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone administration did not modulate PMN apoptosis or immunocyte receptor expression; however, such treatment did decrease postoperative IL-6 secretion (P<.001) and increase postoperative IL-10 secretion (P<.001). CONCLUSIONS: The complications of major surgery include persistent inflammation, which can lead to multisystem organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute to this process. A single preoperative dose of glucocorticoids did not effect PMN apoptosis or receptor phenotype.

Anti-Inflammatory Agents↗
PubMed2001

Dose response to nitric oxide in adult cardiac surgery patients.

STUDY OBJECTIVE: To determine the dose responsiveness to nitric oxide in adult cardiac surgery patients, especially in those patients with pulmonary hypertension. DESIGN: Prospective, randomized, nonblinded study. SETTING: University teaching hospital. PATIENTS: 62 consecutive cardiac surgery patients demonstrating pulmonary hypertension immediately before induction of anesthesia. INTERVENTIONS: Subjects were assigned by random number allocation to receive one of five doses of inhaled nitric oxide on termination of cardiopulmonary bypass (CBP; i.e., restitution of pulmonary artery flow). Subjects in Group 1 (n = 11) received 10 ppm of inhaled nitric oxide, Group 2 subjects (n = 12) received 20 ppm, Group 3 subjects (n = 12) received 30 ppm, and Group 4 subjects (n = 12) received 40 ppm. The fifth group (n = 15) received no nitric oxide. This fifth group served as a control and was treated with milrinone only. Those patients who were randomized to the milrinone group, had milrinone initiated by bolus administration (50 microg/kg) 15 min before separation from CPB. Milrinone was maintained at 0.5 microg/kg/min in the operating room thereafter. The conduct of anesthesia, surgery, and CBP were controlled. A therapeutic algorithm dictated the use of vasoactive substances for all patients. MEASUREMENTS: Heart rate, mean arterial pressure, pulmonary vascular resistance (PVR), peripheral vascular resistance, cardiac index, and right ventricular ejection fraction were monitored throughout the operative experience. MAIN RESULTS: There were no significant differences found in demographic data, baseline hemodynamic data, surgical treatment, conduct of CBP, or the use of inotropic or vasoactive drugs among the five treatment groups. The percentage decrease in PVR on treatment with nitric oxide as compared to baseline values was not significantly different among the groups (10 ppm = 38%, 20 ppm = 50%, 30 ppm = 44%, 40 ppm = 36%, milrinone = 58%, p = 0.86). CONCLUSIONS: Treatment with nitric oxide was associated with significant reductions in PVR in all groups. Dosages higher than 10 ppm were not associated with greater reductions in pulmonary vascular tone. In view of the fact that nitric oxide-related toxicity is dose-related, doses greater than 10 ppm do not appear to be justified in this patient population.

Administration, Inhalation↗
PubMed1997

Mitral valve myxoma.

Cardiac myxomas arising from the mitral valve are extremely rare. We describe the case of an asymptomatic 49-year-old woman who was found to have a 3.6 x 4.0-cm myxoma originating from the atrial side of the anterior mitral leaflet. The lesion was successfully treated by surgical excision and mitral valve replacement. A review of the literature regarding this rare lesion is presented.

Female↗
PubMed1996

Mycotic aneurysm of the thoracic aorta caused by Clostridium septicum.

We describe a case-of a 78-year-old man who presented with a mycotic aneurysm of the thoracic aorta caused by Clostridium septicum and underwent successful resection. There are only 3 cases of mycotic aneurysms caused by Clostridium septicum reported in the literature. Clostridium septicum infections have been shown to have a high association with gastrointestinal and hematologic malignancies. All patients with Clostridium septicum infections, therefore, require a search for gastrointestinal lesions, as they may represent a source of persistent bacteremia. This patient had no malignant lesions but did have multiple benign sigmoid polyps.

Aged↗
PubMed1993

Measurement of intracellular hydrogen peroxide induced by biomaterials implanted in a rodent air pouch.

Biomaterials elicit an inflammatory response that is undoubtedly a factor in their healing and in the complications associated with their use. Herein, we report the modification of a rat air pouch in which we measured the production of intracellular hydrogen peroxide by inflammatory cells adherent to the surfaces of silicone elastomer (SE) and expanded polytetrafluoroethylene (ePTFE). We used the fluorescent probe dichlorofluorescein diacetate (DCFH-DA) to measure the intracellular production of hydrogen peroxide 2 and 7 days after implantation. After 2 days, host cells adherent to ePTFE produced almost 3.5 times more hydrogen peroxide than did cells adherent to SE (P < .001). By 7 days, the H2O2 production of cells adherent to ePTFE had decreased while that on cells adherent to SE was unchanged. These data indicate that the air pouch is a good alternative to other in vivo models for studies of the biological reactions induced by biomaterials.

Air↗
PubMed1990

Differential production of interleukin 1 on the surface of biomaterials.

The production of cytokines on the surface of surgical biomaterials plays a major role in their biocompatibility. Membrane-associated interleukin 1 (mIL-1) is a cytokine found on the surface of macrophages activated by biomaterials. To better understand the host-foreign body interaction, we quantitated the production of mIL-1 on the surface of two materials commonly used in surgery, expanded polytef (ePTFE) and silicon elastomer (SE). The mean (+/- SD) level of mIL-1 produced by adherent cells to ePTFE significantly decreased from day 2 (13,746 +/- 3630 cpm per disk) compared with day 7 (2828 +/- 1304 cpm per disk). However, the level of mIL-1 produced by ePTFE-adherent cells was still markedly greater than the level of mIL-1 produced by cells adherent to SE (1877 +/- 1028 vs 1595 +/- 822 cpm per disk). These results indicate that ePTFE and SE elicit a differential host response in terms of cytokine production. This study may enhance our understanding of the cellular events on the surface of biomaterials that underlie clinical observations.

Animals↗
PubMedDate not supplied

Prevention of postoperative adhesions with the chitin derivative N-O-carboxymethylchitosan.

The ideal barrier agent for the prevention of surgical adhesions has remained elusive. We have examined the ability of a new hydrogel N-O-carboxymethylchitosan, a derivative of chitin with properties similar to the extracellular matrix, to prevent adhesions when applied topically to traumatized mesothelial surfaces. In two rodent adhesion models (pericardial and peritoneal), the application of N-O-carboxymethylchitosan significantly prevented or minimized the formation of scar and fibrosis. According to a scoring system from 0 to 3 (0 = no adhesions and 3 = severe dense adhesions), control groups in each model consistently produced severe dense adhesions (2.9 +/- 0.2, 2.7 +/- 0.3). All treated groups consistently scored less than 1.0, indicating minimal or no fibrosis. The differences between the control and treated groups were statistically significant (p < 0.05). Thus, the application of N-O-carboxymethylchitosan to traumatized mesothelial surfaces may have significant potential in the prevention of postoperative adhesion formation.

Journal Article↗
PubMedDate not supplied

Prevention of pericardial adhesions with N-O carboxymethylchitosan in the rabbit model.

The presence of mediastinal adhesions significantly increases the morbidity and mortality of reoperative cardiac surgical procedures. Previous investigations have reported on the therapeutic utility of topical hydrogels in reducing the formation of postsurgical adhesions. The goal of the present study is to evaluate the ability of N-O carboxymethylchitosan (a glycosaminoglycan hydrogel derivative) to reduce the formation ofpostsurgical pericardial adhesions in a large-animal model. Sixteen adult New Zealand white rabbits were randomly assigned to one of two treatment groups. Group 1 subjects (n = 8) had N-O carboxymethylchitosan directly applied to the heart and retrosternal surfaces after sternotomy was performed, while subjects in group 2 (n = 8) had saline applied to these areas. After a period of 14 days the animals were sacrificed under anesthesia, and independent observers, blinded to treatment, graded the formation of pericardial adhesions. The severity of adhesion formation was significantly less in the group treated with N-O carboxymethylchitosan (p < .01). This study demonstrates that N-O carboxymethylchitosan markedly decreases the formation of poststernotomy adhesions in a large-animal model without untoward cardiac side effects. This hydrogel derivative may prove to be of great therapeutic value when used prophylactically in the setting of cardiac surgery.

Animals↗
PubMedDate not supplied

Increased levels of surgical adhesions in TGFbeta1 heterozygous mice.

Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-beta1 (TGFbeta1) have been associated with inflammation and adhesion production, we investigated the requirement of TGFbeta1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGFbeta1 allele. Mice that were either wild-type (+/+), containing two normal alleles of TGFbeta1, or heterozygous (+/-) for the TGFbeta1 null allele received injections of magnesium silicate (talc), and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more TGFbeta1 protein in peritoneal fluids at 2 h posttrauma compared to heterozygous (+/-) mice (727 vs. 243 pg TGFbeta1/mg protein by enzyme-linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had significantly less scar and adhesion formation (p < .05) at 7 days posttrauma (1.8 +/- 0.8 vs. 3.4 +/- 1.4, graded from 0 to 5, in +/+ and +/- mice, respectively). These results demonstrate that haploid insufficiency in TGFbeta1 levels can lead to inappropriate matrix and adhesion production during inflammation, and together with previous studies suggest that any perturbation of normal TGFbeta1 levels can modulate the injury response that regulates the extent of adhesion formation.

Animals↗
PubMedDate not supplied

An inhibitor of cell proliferation associated with adhesion formation is suppressed by N,O-carboxymethyl chitosan.

Surgical adhesions are a major cause of morbidity and mortality. The ideal barrier agent will both minimize adhesions and provide a milieu for the regeneration of the mesothelium lining of the abdominal and thoracic cavities. N,O-Carboxymethylchitosan (NOCC), a derivation of chitin that markedly reduces adhesions, may function to modulate intracellular signals such as growth factors and cytokines in the inflammatory exudate. Since transforming growth factor-beta is implicated in the fibrotic process, we investigated the possibility that NOCC's effects on adhesion formation reflects a modulation of TGF-beta activity. Using a biological assay for inhibition of cell proliferation to detect TGF-beta activity, we demonstrate that NOCC suppresses the levels of an inhibitor of cell proliferation released into serum and peritoneal exudates after cecal abrasion in the rat. However, this activity was distinct from known forms of TGF-beta as determined using both TGF-beta-neutralizing antisera and a TGF-beta-resistant cell proliferation assay. Thus at least one potential effect of NOCC involves a mechanism distinct from TGF-beta inhibition.

Animals↗