Search PubMed⌕ Search

Biomedical subjects

J R Kirkpatrick

Publications and source records attributed to J R Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed2000

The effects of interleukin-10 in hemorrhagic shock.

BACKGROUND: Interleukin-10 (IL-10) counteracts the effects of the proinflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Experimental data suggest that inhibition of these proinflammatory cytokines improves outcome in sepsis, endotoxemia, necrotizing pancreatitis, and other severe inflammatory states. We hypothesized that the administration of IL-10 would attenuate the release of proinflammatory cytokines after severe hemorrhagic shock. METHODS: To test our hypothesis, male Sprague-Dawley rats (N = 20) were divided into control and experimental groups. We induced hemorrhagic shock by removing a sufficient quantity of blood to maintain a mean arterial pressure of 50 mm Hg or less for 120 min. The animals were then resuscitated with shed blood and an equal volume of 0.9% saline. The experimental group received 10,000 units of IL-10 at the initiation of shock. Serum IL-1, IL-6, TNF, and lactate were measured at baseline, after 120 min of shock, and 60 min after resuscitation. The rats were followed for 72 h to calculate survival. RESULTS: Similar levels of hypoperfusion were obtained in both groups as demonstrated by lactate levels and amount of shed blood. The survival rate (70%) was the same in both groups. Serum levels of IL-1 and IL-6 were not significantly different between the two groups, although there was a trend toward IL-6 suppression. TNF, however, was significantly lower in the IL-10-treated group at the end of shock (Wilcoxon test, P < 0. 025). CONCLUSION: Administration of IL-10 suppresses the TNF surge observed after severe hemorrhagic shock.

Animals↗
PubMed2000

Xenogeneic patch closure of the small intestine: a novel approach to fistula management.

Previous work from our laboratory demonstrated the feasibility of utilizing placental-derived collagen tissue matrix (CTM) as a bowel wall substitute. We reasoned that this technique would also be suitable in managing intestinal fistulae. To test this hypothesis, we created a chronic cecal fistula in rats and randomly managed some with primary repair and others with CTM replacement. Leak rates, mortality, bursting pressures and histologic scores were similar, suggesting that a chronic fistula can be successfully managed with either a CTM or primary repair.

Animals↗
PubMed1999

Polyethylene glycol-superoxide dismutase inhibits lipid peroxidation in hepatic ischemia/reperfusion injury.

BACKGROUND: Hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (OFR)-mediated lipid peroxidation--a process that can be measured through its byproducts, specifically malondialdehyde. The use of free radical scavengers can offer significant protection against OFR-induced liver injury. We hypothesize that a new potent OFR scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD), can inhibit OFR-mediated lipid peroxidation in hepatic ischemia/reperfusion injury. METHODS: Twelve male Sprague-Dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. PEG-SOD (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. Normal saline was given to the remaining six rats to be used as a control group. The right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured. RESULTS: A marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. Treatment with PEG-SOD prevented the rise in tissue malondialdehyde. The mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 +/- 6.35 and 1.70 +/- 3.65 nmol/g in the normal saline (control) and PEG-SOD groups, respectively. This difference was found to be statistically significant (P < 0.005) using Student's t-test. CONCLUSIONS: PEG-SOD can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting OFR-mediated lipid peroxidation.

Animals↗
PubMed1998

Prophylactic jejunostomy: a reappraisal.

BACKGROUND: The effectiveness of enteral feeding in maintaining postoperative nutrition has led some investigators to recommend prophylactic jejunostomy at the time of any high-risk abdominal operation. A failed procedure in this setting weighs heavily on the side of risk without identifiable benefit. METHODS: A benefit/risk analysis comparing complication rate, avoidance of parenteral nutrition, and discontinuation of jejunostomy feeding was performed in 92 patients. These patients were judged retrospectively to be undergoing either a prophylactic jejunostomy placed at the time of operation for another serious condition (group A) or therapeutic jejunostomy alone (group B) during a 3-year period (1993 to 1996). Classification as prophylactic or therapeutic was determined by the surgeon's preoperative intent. RESULTS: Avoidance of parenteral nutritional support, a goal of prophylactic jejunostomy, was not achieved in 39% of the patients. Patients in group A had a 5-fold increase in the risk of premature discontinuation of enteral feeds when compared with group B (P < .03). The complication rate was higher in group A (41%) than in group B (26%). Four life-threatening complications occurred in group A; all required reversal of the feeding jejunostomy. CONCLUSIONS: This study suggests that the benefit/risk ratio of prophylactic jejunostomy is low. This adds weight to the notion that this procedure be abandoned in favor of other forms of nutritional support.

Adolescent↗
PubMed1998

Divided gastric bypass: a fifteen-year experience.

In suitable candidates, a reduction in gastric capacity to achieve significant weight loss is life-saving. The number and variety of procedures proposed in the last 15 years suggest that the ideal operation is still in evolution. We present a 15-year experience with a single operation designed to avoid the hazards of staple line dehiscence, achieve maximum weight loss, and maintain physiologic homeostasis. From 1979 through 1994, 212 patients, whose age, weight, and number of medical complications were consistent with the criteria for morbid obesity, underwent divided gastric bypass. All patients lost at least 70 lbs, and 95 per cent of the patients lost greater than 100 lbs in 2 years, with an average loss higher than in most comparable series. There were four post operative deaths and three late deaths. Thirteen anastomotic leaks (6%) were successfully managed. Eight patients received nutritional support and antibiotics, and five patients had operative drainage. Eighteen per cent had one or more minor complications. Divided gastric bypass avoids the problem of staple line dehiscence while providing a safe physiologic approach for maximum weight loss in the morbidly obese patient.

Adult↗
PubMed1996

Acquired immunity to TNF: effects on intestinal wound healing.

Increased concentrations of tumor necrosis factor (TNF) damage normal tissue and produce a shock-like syndrome--changes that can be prevented with anti-body-specific antisera. These findings suggest that TNF-stimulated immunity should protect normal tissue and promote wound healing. To test this hypothesis, 30 Fischer 344 rats (150-200 g) were serially immunized against TNF (20 micrograms/kg). Convalescent sera assayed (micro-ELISA) for circulating antibodies revealed titers (2.54 +/- 0.08 au) significantly higher (P < 0.00001) in immunized animals than in nonimmunized controls (0.11 +/- 0.06 au). Following this, 10 immunized (Group I), 10 nonimmunized (Group II), and 10 control rats underwent partial cecectomy with primary anastomosis. Animals from Groups I and II received TNF (25 micrograms/kg) while controls received saline intravenously on Postoperative Days 1, 3, and 5. Animals were then sacrificed to determine: (1) hydroxyproline content of the anastomosis, (2) mitochondrial respiratory control ratio, and (3) pyruvate dehydrogenase activity of the muscle. We found that (1) exposure to increased concentrations of TNF (Group II) depresses (P < 0.01) biologic markers of wound healing and (2) acquired immunity to TNF (Group I) eliminates this response. In conclusion, acquired immunity to TNF protects the healing intestinal anastomosis from the effects of exposure to increased levels of TNF.

Animals↗
PubMed1995

Peritoneovenous shunt for palliation of gynecologic malignant ascites.

BACKGROUND: Ascites is a common sequela of advanced or recurrent gynecologic malignancies, such as carcinoma of the ovary, fallopian tube, or endometrium. Symptomatic treatment with repeated paracentesis is the initial management after failure of chemotherapy. STUDY DESIGN: This study was done to evaluate the safety and effectiveness of a peritoneovenous shunt (PVS) in the palliation of these patients with recurrent ascites. A retrospective review of 25 patients having a PVS between 1982 and 1992 was performed. RESULTS: The 25 patients consisted of 21 patients with carcinoma of the ovary, two with primary carcinoma of the peritoneum, one with carcinoma of the endometrium, and one patient with carcinoma of the fallopian tube. The mean weight and abdominal girth decreased after shunt insertion (p < 0.001). Gastrointestinal dysfunction and dyspnea also improved with PVS insertion. There was no change in mean Karnofsky score after placement of a PVS. Two patients died within ten days postoperatively. The median survival period was 80 days and shunt occlusion occurred in four patients. CONCLUSIONS: The insertion of a PVS is effective in relieving refractory malignant ascites in gynecologic malignancies. The impact on quality of life requires further study.

Ascites↗
PubMed1995

Contaminated wounds: the effect of initial management on outcome.

Delayed primary closure has been advocated as the optimal method of management in the presence of wound contamination. The present study was performed to determine whether surgeons have accepted this standard. A total of 918 surgical wounds were evaluated and classified according to the level of contamination and type of wound management used. We found that 150 patients had a Class III or Class IV contaminated wound; however, only 21 per cent were treated with delayed primary closure. The 118 patients treated with primary closure and antibiotics had an aggregate wound infection rate of 27 per cent (Class III-29%; Class IV-24%). Only one (3%) of the wounds managed by delayed primary closure developed an infection. If infection did not occur, there was no difference in the length of stay between patients managed with primary closure and delayed primary closure. However, there was a significantly longer length of stay in the primary closure group if infection occurred. Benefit risk analysis of the patients with contaminated wounds confirmed that in this clinical setting, delayed primary closure remains the optimal method of management for the wound.

Anti-Bacterial Agents↗
PubMed1991

Prevention of central venous catheter sepsis: a prospective randomized trial.

A prospective randomized trial was undertaken to evaluate the influence of routine 72-hour catheter exchange and the use of an implantable collagen cuff in preventing central venous catheter infection in critically ill patients requiring multiple lumen central venous access. Patients were randomized to one of four groups, which determined whether the central venous catheter placed would be removed at 3 or 7 days and whether an implantable collagen cuff would be used or not. Upon removal, cultures of the central line tip, the insertion site, and peripheral blood were obtained. One hundred and fifty-nine catheters were studied in 85 patients during a 14-month period. There were 26 (16.4%) episodes of catheter colonization and four (2.5%) episodes of catheter infection in the entire population. Catheter colonization rates (same organisms cultured from catheter tip and skin site) were 14.5 per cent at 3 days and 18.4 per cent at 7 days. Infection rates (same organism cultured from catheter tip and peripheral blood culture) were 2.4 per cent at 3 days and 2.6 per cent at 7 days. With regard to the use of the collagen cuff, colonization rates were 14.5 per cent with the use of the cuff and 18.1 per cent without the use of the cuff. Infection rates were 5.3 per cent with the use of the cuff and 0 per cent without the use of the cuff. None of these differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗
PubMed1990

Endotoxin and calcium effect on metabolism.

The effects of calcium and endotoxin were investigated in vivo and in vitro using the A/J, retired white male breeder mouse model. Intravenous administration of increasing calcium doses (3.75, 4.37, and 4.75 mg Ca/g-BW) resulted in increasing serum calcium levels (11.4, 14.4, 15.2, respectively vs. animals not injected, 9.5 mg/dl). Mice injected with E. coli bacterial endotoxin after injection of calcium demonstrated significantly (P less than 0.05) lowered serum calcium concentrations (10.5, 12.1, 12.5, respectively). The magnitude of serum calcium reduction was related to the level just prior to endotoxin administration. Mitochondria were incubated using a Percoll purification step. The effect of pretreating the animal in vivo with calcium, endotoxin or calcium plus endotoxin versus control was investigated in both liver and skeletal muscle. When mitochondria were incubated in medium containing EGTA (free Ca less than 1 X 10(-9)). no significant difference between groups was observed in either (RCR) or mitochondrial calcium content. When mitochondria were incubated in EGTA buffers containing calcium (free Ca approximately 7 X 10(-7) liver, 1 X 10(-7) muscle) significant differences in RCR and mitochondrial calcium content were observed. Liver RCR increased significantly with calcium or endotoxin pretreatment (2.20, 2.43 vs. 1.86). Muscle mitochondrial RCR significantly decreased with calcium administration (5.02 vs. 6.79). Both liver and muscle mitochondrial calcium content significantly decreased (2.54 vs. 27.32, and 6.46 vs. 25.82 nMole Ca/mg mitochondrial protein). Preloading with calcium prevented the decline in mitochondrial calcium content. Findings suggest that the reduction in intramitochondrial calcium content during endotoxemia could be an effector of metabolic derangement specifically through calcium-dependent intramitochondrial enzymes.

Animals↗
PubMed1988

Enhancement of mitochondrial function in sepsis.

Recent reports from our laboratory have challenged the concept that sepsis selectively damages or interferes with mitochondrial function. To address the lingering skepticism that mitochondrial assays in surviving animals might not detect this "injury," we injected rats with a lethal dose of Escherichia coli endotoxin and compared hepatic, cardiac, and skeletal muscle mitochondrial function in these animals with that of control rats. Mitochondrial function was serially determined during a four-hour postmortem period by measuring the respiratory control ratio, the adenosine diphosphate-oxygen ratio, and protein levels. Hepatic mitochondria ceased to function within 30 minutes of the time of death. Cardiac and skeletal muscle mitochondria functioned normally up to four hours after death in both septic and control animals. Mitochondria from septic animals had a significantly higher respiratory control ratio than those from control rats. Thus, sepsis appears to enhance rather than damage mitochondrial function up to four hours after death.

Animals↗
PubMed1987

Jejunoileal bypass. A legacy of late complications.

Since 1977, we have managed 56 patients (36 Payne and 20 Scott bypasses) with late (one to 18 years) complications resulting from a jejunoileal bypass. All patients underwent a one-stage conversion of the jejunoileal bypass to a gastric bypass. Patients were classified according to postbypass weight, the need for nutritional support, the type and severity of complication, and the time interval between jejunoileal bypass and the onset of the complication and correction of the complication. There were no operative deaths; one patient died 18 months after surgery of cirrhosis. The complication rate was 34%; however, most complications were minor. Our experience with this procedure has shown it to be highly effective in correcting complications other than polyarthritis. When coupled with nutritional support, it is safe even in malnourished patients.

Adult↗
PubMed1985

The relationship of insulin production to glucose metabolism in severe sepsis.

Basal glucose metabolism was evaluated in eight stable, infected patients by measuring hepatic glucose production rates in relation to stress endocrine profile and by comparing these data to five injured, noninfected patients. All patients exhibited normal total-body oxygen consumptions and cardiac indices. Fasting basal insulin values were similar in both groups (6 microU/cc) despite a significantly higher plasma glucose level in septic patients (106 +/- 14 mg/dL) compared to nonseptic patients (88 +/- 10 mg/dL). Septic patients exhibited splanchnic glucose production and calculated glucose clearance rates, 53% and 34% higher, than injured nonseptic patients, respectively. In addition, septic patients exhibited a decreased pancreatic insulin secretory response to an intravenous glucose tolerance test as evidenced by a significantly depressed peak insulin value (17 microU/cc) relative to injured patients (77 microU/cc). These findings indicate that insulin suppression is evident in sepsis even in the absence of shock and suggest that sepsis-related basal hyperglycemia does not appear to be associated with peripheral insulin resistance.

Aged↗
PubMed1985

The significance of hypoalbuminemia following injury and infection.

Serum albumin and absolute hepatic albumin synthetic rates were measured in ten seriously ill injured and septic patients using the (14C) carbonate technique. Although it is commonly believed that serum albumin levels (SAL) reflect hepatic function and visceral protein status in hospitalized patients, no relationship was found between these two measured parameters in this patient population. A depressed mean serum albumin level of 1.98 +/- 0.50 gm/dl (range: 1.25-2.69 gm/dl) was associated with a supranormal mean albumin synthetic rate of 215 +/- 121 mg/kg/day (range: 21-447 mg/kg/d). No significant mean SAL and albumin synthetic rate differences were noted between injured nonseptic and septic patient populations. Since albumin synthesis was elevated in most of these stressed patients these findings support the view that extravascular protein redistribution and/or increased peripheral catabolism are the major factors responsible for hypoalbuminemia in critically ill patients.

Aged↗
PubMed1984

Gastrojejunal disruptions. Changing concepts in management.

From 1973 through 1983, 197 patients were treated at Harper-Grace Hospital, Detroit, according to a protocol designed to minimize the effects of possible gastrojejunal disruption. All had high-risk resections or bypasses of the stomach reconstructed with an end-to-end Roux-en-Y anastomosis using a long (100-cm) jejunal limb. Eighteen anastomoses leaked, producing fever, pain, and mild respiratory distress in 14 patients and peritonitis with shock in four. Nine of the 14 patients without shock avoided surgery, requiring only antibiotics and nutritional support. The other five had a subphrenic abscess, necessitating drainage. The four patients with shock were treated with staged intestinal discontinuity, nutritional support, and reestablishment of gastrointestinal continuity at a later date. Seventeen patients (94%) survived this serious complication, a significant improvement compared with the mortality of historical controls.

Humans↗
PubMed1983

Substrate composition and sepsis. Effects on immunity.

A randomized prospective study was performed to determine the effects of substrate composition on immunity in septic malnourished patients. A balanced substrate formula was administered to 11 patients with sepsis and 11 nonseptic patients. This provided 40 kcal/kg/day and 1 to 1.5 g of protein per kilogram each day with a carbohydrate-nitrogen ratio of 50:1. A 25% dextrose and 4.25% protein solution that provided 50 kcal/kg/day and 1 to 1.5 g of protein per kilogram each day with a carbohydrate-nitrogen ratio of 150:1 was provided to ten patients with sepsis and 11 without. Skin test conversion rates were not affected by substrate composition; however, the absolute lymphocyte count was significantly improved in septic patients who achieved positive nitrogen balance, regardless of the nutritional support regimen used. These findings suggest that substrate composition per se has no effect on immunologic responsiveness.

Amino Acids↗