Biomedical subjects

R G Tompkins

Publications and source records attributed to R G Tompkins.

At least 73 records · Page 4Linked to original sources

PubMed1996

Quantitative aspects of interorgan relationships among arginine and citrulline metabolism.

The quantitative roles of the splanchnic region and the kidneys in whole body (WB) arginine and citrulline metabolism were assessed in postabsorptive mongrel dogs with primed constant intravenous infusions of [15N2-guanidino, 5,5-2H2]arginine and [13C-ureido]citrulline or [13C-guanidino]arginine and [15N]urea tracers. Isotope and metabolite concentration balances of arginine and citrulline were measured across the gut, liver, splanchnic region, and kidneys, together with WB arginine and citrulline fluxes and urea production rate. The WB citrulline flux and rate of citrulline to arginine (C-A) conversion were 16 and 9.4 mumol.kg-1.h-1, respectively. Concentration balance of citrulline across kidneys was +8.2 mumol.kg-1.h-1, and metabolism of citrulline by kidneys was 8.7 mumol.kg-1.h-1, which was derived about equally from intestine and liver. The appearance rate of citrulline-derived arginine in renal vein was 6.8 mumol.kg-1.h-1. These three separate estimates of C-A conversion within the kidneys were in good agreement, indicating 40% of blood C-A conversion occurring outside kidneys. These findings of interorgan metabolism are discussed in reference to the current knowledge derived largely from studies in laboratory rodents.

Animals↗

PubMed1995

Common virulence factors for bacterial pathogenicity in plants and animals.

A Pseudomonas aeruginosa strain (UCBPP-PA14) is infectious both in an Arabidopsis thaliana leaf infiltration model and in a mouse full-thickness skin burn model. UCBPP-PA14 exhibits ecotype specificity for Arabidopsis, causing a range of symptoms from none to severe in four different ecotypes. In the mouse model, UCBPP-PA14 is as lethal as other well-studied P. aeruginosa strains. Mutations in the UCBPP-PA14 toxA, plcS, and gacA genes resulted in a significant reduction in pathogenicity in both hosts, indicating that these genes encode virulence factors required for the full expression of pathogenicity in both plants and animals.

ADP Ribose Transferases↗

PubMed1995

Effects of hypothermia on the function, membrane integrity, and cytoskeletal structure of hepatocytes.

To increase the storage time of livers for transplantation, a better understanding of hypothermia-induced hepatocyte damage is necessary. To this end, we have characterized the effects of hypothermia on long-term function and cytoskeletal organization of hepatocytes cultured in the collagen sandwich configuration, which maintains the expression of liver-specific functions for several weeks. In these studies, cultured hepatocytes (maintained at 37 degrees C for 7 days) were exposed to 4 degrees C in Leibovitz-15 (L15), University of Wisconsin (UW) solution, or L15 supplemented with 2.5 g% polyethylene glycol (PEG) for various time periods followed by a return to normothermia. When L15 medium was used, the long-term albumin secretion rate of cultured hepatocytes was decreased by 50% after 4 h, and by 95% after 24 h of exposure to 4 degrees C. Amorphous precipitates of F-actin and fragmented short microtubules were also observed after 4 and 12 h of hypothermia, respectively. Similar results were obtained when hepatocytes were stored in UW solution. However, in L15 supplemented with PEG, no significant reduction in long-term albumin secretion rates and intact actin and microtubule morphology was observed even after 24 h of exposure to 4 degrees C. The membrane integrity and long-term albumin secretion of hepatocytes stored in the presence of PEG were decreased to approximately 50% only after 48 h of exposure to 4 degrees C. Thus, PEG may be a useful additive in preservation solutions for hepatocytes in hepatocyte-based liver support systems and for intact tissue as well.

Actins↗

PubMed1995

Intraoperative reflectance oximetry in burn patients.

OBJECTIVE: Transmission oximetry sites for intraoperative monitoring are frequently difficult to find in burn patients, as standard transmission oximetry sites are often burned or contained within the operative field. The objective of this study was to determine if reflectance oximetry is of potential value in monitoring this group of patients. METHODS: A total of 16 operative procedures in a group of acutely burned adult and pediatric patients with an average age of 9.7 years (range, 10 months to 37 years), average burn size of 42% of the body surface (range, 15% to 94%), and average weight of 34.2 kg (range, 9 to 100 kg) were done with simultaneous transmission and reflectance oximetry monitoring. RESULTS: During these 16 procedures in a diverse group of acutely burned adult and pediatric patients, there was no significant difference in saturations derived from transmission and reflectance oximetry probes. In smaller children, adequate signal for reflectance probe monitoring was often detected in hyperemic sites, such as healed partial thickness burn. CONCLUSIONS: This is the first published report documenting both the clinical use of the reflectance oximetry in burn patients and the clinical use of the Nellcor Oxisensor II RS-10 reflectance oximetry probe (Nellcor Corporation, Hayward, CA). This technique can facilitate the intraoperative monitoring of acutely burned adult and pediatric patients in whom standard transmission oximetry sites are difficult to find.

Adult↗

PubMed1995

Plasma arginine and leucine kinetics and urea production rates in burn patients.

We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an L-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N.kg-1.d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were L-[guanidino-13C]arginine, L-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, alpha-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Emergency management of major hydrofluoric acid exposures.

Exposures of as little as 2.5 per cent of the body surface to concentrated hydrofluoric acid (HF) may be fatal. Survival after major HF exposures is facilitated by aggressive emergency management which, we feel, includes wound irrigation, subeschar injection of calcium gluconate, monitored supplementation of serum calcium, and prompt wound excision carried out as an emergency procedure. The following case reports and literature review illustrate the important differences between exposures to concentrated HF of as little as 2 per cent of the body surface and smaller exposures to concentrated HF or exposure to dilute HF.

Accidents, Occupational↗

PubMed1995

Central venous catheter sepsis with weekly catheter change in paediatric burn patients: an analysis of 221 catheters.

To document the risk of catheter sepsis associated with central venous catheter changes every 7 days in paediatric burn patients, and analysis of data collected prospectively on 234 such catheters was performed. During an 18-month period there were 301 acutely burned children admitted to a regional paediatric burn facility of whom 53, with an average burn size of 42 per cent TBSA, required 234 central venous catheters. A central venous catheter management protocol was followed which included catheter changes every 7 days. If insertion sites were clean and uninflamed, catheters were replaced by guidewire and the original catheter tip was semiquantitatively cultured. Catheters were replaced to a new site if insertion sites appeared inflamed or catheter tips grew 15 or more colony forming units. Overall, 3.2 per cent (10.9 per cent by Centers for Disease Control definition) of central venous catheters were associated with sepsis. When catheters were replaced by guidewire from one to three times, catheter sites were used for a mean of 15.6 days without an increased rate of line sepsis. There was no difference in sepsis rates between catheters placed at a new site or replaced by guidewire. There were no deaths attributed to catheter-related sepsis. We conclude that a protocol allowing for catheter change to a new site, or replacement by guidewire, every 7 days was associated with a low risk of catheter sepsis in paediatric burn patients.

Acute Disease↗

PubMed1995

Dynamics of photoinduced cell plasma membrane injury.

We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes.

Cell Line↗

PubMed1995

Dynamics of cell membrane permeability changes at supraphysiological temperatures.

A quantitative fluorescent microscopy system was developed to characterize, in real time, the effects of supraphysiological temperatures between 37 degrees and 70 degrees C on the plasma membrane of mouse 3T3 fibroblasts and isolated rat skeletal muscle cells. Membrane permeability was assessed by monitoring the leakage as a function of time of the fluorescent membrane integrity probe calcein. The kinetics of dye leakage increased with increasing temperature in both the 3T3 fibroblasts and the skeletal muscle cells. Analytical solutions derived from a two-compartment transport model showed that, for both cell types, a time-dependent permeability assumption provided a statistically better fit of the model predictions to the data than a constant permeability assumption. This finding suggests that the plasma membrane integrity is continuously being compromised while cells are subjected to supraphysiological temperatures.

3T3 Cells↗

PubMed1995

Strategies for success in academic surgery.

BACKGROUND: A growing concern among university surgeons is a perceived threat to the traditional academician role. Factors that have led to this concern include (1) changes in reimbursement and patient referral patterns, both of which have resulted in reduced income; (2) mounting external pressure from the departmental chairperson/dean to generate professional fees; (3) pervasive ambiguity in the criteria for promotion and tenure; (4) intensified competition for research dollars in recent years; and (5) a perception that fellow academicians view surgeons as operating room technicians incapable of laboratory research. These cogent issues have the means to place academic goals in jeopardy. Potentially they lead to dissatisfaction, unhappiness, and eventual departure from academia. A healthy solution to the problem includes departmental recognition and reward for whichever primary role/s the academic surgeon embraces--clinical, educational, research, or administrative. Clear chairperson-faculty communication on the issues of expectation and reward is a key ingredient in the solution. METHODS: A mail survey was conducted with chairpersons of surgical departments and academic surgeons addressing the issues of retention, promotion, and benefits. RESULTS: Results revealed significant differences in perceptions, suggesting the need for improved communication between faculty and chairpersons and a team approach to help maintain academic viability in the future. CONCLUSIONS: When the quadruple threat can be mutually described as a departmental rather than individual quality, the joys and rewards of academic surgery can be considerable for faculty and chairpersons alike.

Academic Medical Centers↗

PubMed1995

Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients.

Plasma fluxes of arginine, citrulline, and leucine, and the rate of conversion of labeled citrulline to arginine (Qcit-->arg) were determined in nine severely burned patients (mean: 56% body surface burn area, mean 10 d postinjury) while they received total parenteral nutrition (TPN) including an L-amino acid mixture that supplied a generous amount of nitrogen (mean: 0.39 +/- 0.02 g.kg-1.d-1). Plasma fluxes were also studied in these patients during a basal state (low-dose intravenous glucose) by using a primed, 4-h constant intravenous tracer-infusion protocol. Stable-nuclide labeled tracers were L-[15N-15N-guanidino,5,5,2H2]arginine; L-[13C-ureido]citrulline; L-[1-13C]leucine; and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, and alpha-ketoisocaproate (KIC; for leucine) in plasma and 13CO2 in breath. Leucine kinetics (flux and disappearance into protein synthesis) confirmed the anticipated higher protein turnover in these burn patients compared with healthy control subjects. The plasma arginine fluxes were correspondingly higher in burn patients than in healthy control subjects. However, the citrulline flux and rate of conversion of citrulline to arginine were not higher than values obtained in our laboratories in healthy adult subjects. We hypothesize that the higher rates of arginine loss from the body after burn injury would need to be balanced by an appropriate exogenous intake of preformed arginine to maintain protein homeostasis and promote recovery from this catabolic condition.

Adult↗

PubMed1995

Postburn pancreatitis.

OBJECTIVE: The authors examined the prevalence and complications of pancreatitis in severely burned patients. Factors predictive for the development of pancreatitis after burns are considered. SUMMARY BACKGROUND DATA: Pancreatitis has been documented at necropsy after burns; however, it is not clinically recognized as a common complication of burn injury. Recent improvements in survival rates could yield previously unrecognized complications, such as pancreatitis, particularly in those patients who previously would have not survived. The hypothesis is that pancreatitis is a frequent complication after major burn injury and causes significant morbidity for patients with large burns. METHODS: This retrospective review of adult patients with large burns examines postburn pancreatitis using stepwise logistic regression analysis. RESULTS: Forty-nine of 121 (40%) patients developed hyperamylasemia or hyperlipasemia well after the admission period (23 +/- 3 days), and all enzyme abnormalities were temporally associated with emerging infections. Most of these patients (40/49, 82%) had symptoms of pancreatitis. Three patients (6%) had pancreatic pseudocysts or abscesses. Inhalation injury (p = 0.0001), associated trauma (p = 0.0311), and escharotomy (p = 0.0415) were risk factors for pancreatitis. Using Fischer's exact test, patients with pancreatitis had increased mortality and length of stay. Patients with high enzyme elevations and > or = 50% body surface area burned were at severe risk of pancreatic pseudocyst or abscess development (43%; 90% confidence interval of 23-77%). CONCLUSIONS: Pancreatitis is a frequent complication after large burn injuries. Patients at high risk for pancreatitis complications should receive surveillance examinations during their acute hospitalization.

Abscess↗

PubMed1995

Effects of malignancy and interleukin-2 infusion on gut macromolecular permeability.

OBJECTIVE: Enhanced gut permeability has been shown in patients with advanced malignancy. The dramatic inflammatory shock syndrome produced by high-dose interleukin-2 immune therapy could further change gut barrier function. This study measured the effect of advanced renal cell carcinoma and malignant melanoma, and interleukin-2 treatment on gut permeability. DESIGN: Nonrandomized, controlled study. SETTING: University hospital. PATIENTS: Adults with metastatic, unresectable renal cell carcinoma or metastatic, malignant melanoma, and normal volunteers. INTERVENTIONS: Gut permeability was measured in patients with renal cell carcinoma or malignant melanoma before and during interleukin-2 infusions, using polyethylene glycol 3350 and polyethylene glycol 400. The polyethylene glycols were administered orally within 48 hrs of interleukin-2 therapy and the 24-hr urine excretions were measured. MEASUREMENTS AND MAIN RESULTS: Increased permeability was seen in the baseline state of these patients (ratio of polyethylene glycol 3350 to polyethylene glycol 400 = 1.1 +/- 0.7 x 10(-2)) when compared with normal volunteers (ratio = 0.48 +/- 0.2 x 10(-2); p < .05). However, after interleukin-2 treatment, no further increase in permeability was seen (ratio = 1.4 +/- 0.8 x 10(-2)). CONCLUSIONS: Gut permeability to polyethylene glycol 3350 is enhanced in advanced malignancy. High-dose interleukin-2 therapy does not further increase permeability of the gut.

Adult↗

PubMed1995

Cultured autologous epithelium in patients with burns of ninety percent or more of the body surface.

OBJECTIVE: The increasing survival of patients with very large burns has driven an interest in innovative permanent wound closure techniques, one of which is the use of cultured autologous epithelium (CAE). To document our ability to achieve wound closure with CAE in patients with very large burns, we report our 19-month experience with this technology in five patients with burns of 90% or more of the body surface. DESIGN: A retrospective review. MATERIALS AND METHODS: Over a 19-month period five patients with burns in excess of 90% of the body surface had skin biopsies taken for epithelial culture. The clinical course of these five patients was reviewed in detail. MEASUREMENTS AND MAIN RESULTS: These five patients had an average age of 11.5 years (range 7 months to 37 years), and an average total body surface area burn of 94% (range 90%-96%). Four of the five patients had inhalation injury. All wounds had vascularized allograft present at the time of CAE engraftment. Forty-five percent of the CAE was placed on vascularized allodermis and 55% on fascia (range on allodermis 20%-75%). Initial take of CAE was 51% (range 20%-80%). Delayed loss in percent of initial take averaged 60% (range 20%-100%). Delayed loss averaged 33% (range 20%-50%) when two patients who lost all of their CAE were excluded. Three patients had gram-negative bacteremia within 7 days of CAE placement, and two of these had 100% graft loss. Definitive closure rates with CAE averaged 7.5% (range 0%-15%) of the body surface, increasing to 12.5% (range 11.2%-15%) when two patients who lost all of their CAE are excluded. CONCLUSIONS: The initial enthusiasm for CAE has been tempered by demonstrations of low-initial engraftment rates, graft fragility, delayed graft loss, and cost. Such liabilities become more tolerable as usable donor site decreases below 5% to 10% of the body surface. CAE can materially contribute to wound closure in patients with very extensive burns, but gram-negative sepsis is associated with complete graft loss.

Adolescent↗

PubMed1995

Detection of acute bacterial infection within soft tissue injuries using a 99mTc-labeled chemotactic peptide.

OBJECTIVE: Infection imaging with a 99mTc-labeled chemotactic peptide was evaluated in a rabbit model of Escherichia coli infections in burned tissue. MATERIALS AND METHODS: The peptide was radiolabeled with 99mTc via the hydrazino nicotinamide derivative. Three groups of six animals were studied: (group A) unilateral infected burns; (group B) bilateral burns with unilateral infection; and (group C) uninfected burns. Twenty-four hours after injury, groups A and B were infected, and 8 hours later, all animals were injected with approximately 0.50 mCi of 99mTc-peptide. MEASUREMENTS AND MAIN RESULTS: In groups A and B, excellent images of the infections were obtained at 3 to 4 and 16 to 18 hours after injection of the peptide. At 3 to 4 hours after injection, the target-to-background ratios (T/B) were 3.12 +/- 0.28 for group A and 4.33 +/- 0.61 for group B (p = n.s.). At 16 to 18 hours, the T/B ratios increased significantly (p < 0.01): group A = 8.10 +/- 1.03 and B = 7.70 +/- 1.25. The T/B ratio for group C was only slightly greater than unity. CONCLUSIONS: These results indicate that 99mTc-labeled chemotactic peptides are effective radiopharmaceuticals for the rapid detection of focal sites of infection within thermally injured tissues.

Animals↗

PubMed1995

Percutaneous cholecystostomy in the critically ill burn patient.

OBJECTIVE: We desired to demonstrate the utility of percutaneous cholecystostomy in the evaluation and management of critically ill burn patients with fever and rising cholestatic chemistries. DESIGN: Retrospective review. MATERIALS AND METHODS: Over a 2 1/2-year period there were 411 admissions to a regional adult burn until of whom six patients (1.5%) were strongly suspected of having developed acute cholecystitis. Five were managed with percutaneous cholecystostomy. MEASUREMENTS AND MAIN RESULTS: All patients had sonographic signs consistent with acute cholecystitis. One was managed with immediate laparotomy and the remaining five patients underwent ultrasound-guided percutaneous transhepatic cholecystostomy at the bedside (n = 4) or in the ultrasonography suite (n = 1) without complication. One patient died of multiple organ failure 3 days after catheter placement despite good catheter position and function. Two of the surviving patients responded promptly to drainage of the gallbladder with resolution of fever and normalization of liver function tests. Two patients did not respond despite catheters that were properly placed and functioning, reliably eliminating the diagnosis of acute cholecystitis. One patient underwent interval cholecystectomy after wound closure and the remaining patients were discharged after catheters were removed. CONCLUSIONS: Bedside percutaneous cholecystostomy is a minimally invasive procedure that can facilitate the evaluation and management of the critically ill burn patient with fever and rising cholestatic chemistries in whom a diagnosis of acute cholecystitis is suspected.

Acute Disease↗

PubMed1995

The acutely burned hand: management and outcome based on a ten-year experience with 1047 acute hand burns.

Optimal hand function has a very positive impact on the quality of survival after burn injury. Over a 10-year period, 659 patients with 1047 acutely burned hands were managed at the Sumner Redstone Burn Center of the Massachusetts General Hospital. Our approach to acutely burned hands emphasizes ranging and splinting throughout hospitalization, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. This approach is associated with normal function in 97% of those with superficial injuries and 81% of those with deep dermal and full-thickness injuries requiring surgery. Although only 9% of those with injuries involving the extensor mechanism, joint capsule, or bone had normal functional outcomes, 90% were able to independently perform activities of daily living.

Acute Disease↗

PubMed1995

Solid organ procurement from burn patients.

With the increasing success or organ transplantation and the consequent increasing scarcity of suitable organs, many traditional contraindications to organ procurement are being reconsidered. One such traditional contraindication to organ procurement is burn injury. We report a case of successful multiorgan procurement from a child with an extensive burn and propose guidelines for solid organ harvest from burn patients.

Burns↗