Biomedical subjects

M G Jeschke

Publications and source records attributed to M G Jeschke.

46 records · Page 3Linked to original sources

PubMed1999

IGF-I gene transfer in thermally injured rats.

Exogenous insulin-like growth factor-I (IGF-I) is known to improve the pathophysiology of a thermal injury, however, deleterious side-effects have limited its utility. Cholesterol-containing cationic liposomes that encapsulate complementary DNA (cDNA) are nonviral carriers used for in vivo gene transfection. We propose that liposome IGF-I gene transfer will accelerate wound healing in burned rats and attenuate deleterious side-effects associated with high levels of IGF-I. To test this hypothesis IGF-I gene constructs, encapsulated in liposomes, were studied for their efficacy in modulating the thermal injury response. Thirty adult male Sprague-Dawley rats were given a 60% TBSA scald burn and randomly divided into three groups to receive weekly subcutaneous injections of liposomes plus the lacZ gene coding for beta-galactosidase, liposomes plus cDNA for IGF-I and beta-galactosidase or liposomes plus the rhIGF-I protein. Body weights and wound healing were measured. Muscle and liver dry/wet weights and IGF-I concentrations in serum, skin and liver were measured by radioimmunoassay. Transfection was confirmed by histochemical staining for beta-galactosidase. Rats receiving the IGF-I cDNA constructs exhibited the most rapid wound re-epithelialization and greatest increase in body weight and gastrocnemius muscle protein content (P < 0.05). Local IGF-I protein concentrations in the skin were higher when compared to liposomes containing only the lacZ gene (P < 0.05) Transfection was apparent in the cytoplasm of myofibroblasts, endothelial cells and macrophages of the granulation tissue. Liposomes containing the IGF-I gene constructs proved effective in preventing muscle protein wasting and preserving total body weight after a severe thermal injury.

Animals↗

PubMed1999

Acute renal dysfunction in severely burned adults.

BACKGROUND: Factors contributing to mortality in burned children with acute renal failure have been identified; however, they have not been identified in thermally injured adults. METHODS: The records of 1,404 acutely burned adults admitted to the Blocker Burn Unit were reviewed. Seventy-six patients with acute renal dysfunction and burns covering more than 30% of their total body surface area with a full-thickness component greater than 10% total body surface area were identified. These patients were divided into those admitted from 1981 through 1989 (n = 35) and those admitted from 1990 to 1998 (n = 41). RESULTS: No significant differences could be shown in the incidence of acute renal dysfunction (5.4 vs. 5.1%) or mortality (88 vs. 87%) for the two time periods, respectively. Sixty-seven percent of the survivors were younger than 40 years of age, compared with only 25% of nonsurvivors (p < 0.02); sepsis was identified in 44 and 96% of survivors and nonsurvivors, respectively (p < 0.001). Fluid resuscitation was delayed in survivors by 1.7+/-1.0 hours compared with 4.4+/-2.1 hours in nonsurvivors (p < 0.001). CONCLUSION: early fluid resuscitation and the prevention of sepsis may reduce the incidence of acute renal dysfunction and mortality in burned adults.

Acute Kidney Injury↗

PubMed1999

Electrical injuries: a 30-year review.

INTRODUCTION: Electrical injuries currently remain a world-wide problem. This study determines whether electrical injuries at our institution have changed in the past 30 years, and identifies electrical burn complications and any high-risk groups. METHODS: From 1967 to 1997, 185 children admitted to our institute were identified with electrical burns. Fifty-five percent of these electrical burns occurred from 1987 to 1997. RESULTS: During the last 10 years of this study, 43% of the electrical injuries (n = 44) were from low voltage (120-240 V) and 57% (n = 58) from high voltage (>1,000 V). In 17 children, serious low-voltage burns were identified as oral commissure burns. These were treated conservatively with one to two reconstructive procedures within 2 years. High-voltage injuries were mainly identified in male children (age 11 to 18 years). Thirty-three percent of high-voltage burns required amputation, 29% had deep muscle involvement, and 24% required either escharotomy or fasciotomy. No mortalities were reported. CONCLUSION: Although the incidence of low-voltage burns is currently on a steady decline, high-voltage injuries remain a problem, particularly in adolescent males.

Adolescent↗

PubMed1999

Effects of recombinant human growth hormone on the development of burn scarring.

Anabolic agents, such as recombinant human growth hormone (rhGH), have been used effectively to ameliorate the catabolic response to burn injury and to improve wound-healing. However, in experimental animal models, growth hormone has also been associated with increased renal scarring. The effect of rhGH on the development of human scarring is unknown. Therefore, the purpose of this study was to assess the effect of rhGH on the scarring of human skin after burn injury. A series of 94 patients was studied in a prospective randomized double-blind clinical trial. Patients receiving 0.2 mg/kg/day subcutaneous rhGH during their acute hospital stays presented with the same quality and intensity of scarring as patients receiving a placebo. Similar reconstructive needs also resulted. The treatment of severely burned children with recombinant human growth hormone during the acute-phase hospital course did not increase scarring of the burn wound.

Burns↗

PubMed1999

The combination of growth hormone with hepatocyte growth factor alters the acute phase response.

Recombinant human growth hormone (rhGH) and hepatocyte growth factor (HGF) have both been shown to individually modulate hepatic acute phase reactant proteins and cytokine expression following trauma through different pathways. Recombinant hGH has also been shown to decrease serum and hepatic HGF concentrations after a thermal injury. We hypothesized that the combination of rhGH plus HGF improves the burn-induced acute phase response. Fifty-six male Sprague-Dawley rats received a 60% TBSA third-degree scald burn and were randomly divided to receive either rhGH (2.5 mg/kg/day sc.) plus HGF (200 microg/kg i.v. every 12 h) or placebo (saline). Rats were sacrificed on post-burn days 1, 2, 5, or 7 and serum constitutive and acute phase proteins, TNF-alpha, IL-1beta, IL-6 and liver total protein measured. Hepatic cytokine gene expression, triglyceride concentration, and hepatocyte proliferation were also measured. In rats receiving rhGH/HGF, serum albumin increased on days 5 and 7 and transferrin on day 7 after burn compared to placebo (P<0.05). Haptoglobin decreased 5 days after burn compared to placebo (P<0.05). RhGH/HGF increased serum TNF-alpha on day 2 after burn, while it decreased serum IL-1beta on day 1 after burn compared with placebo (P<0.05). RhGH/HGF had no effect on hepatic cytokine gene expression compared with placebo. Liver total protein content and hepatocyte proliferation increased on days 1, 2, 5, and 7 after burn with rhGH/HGF treatment (P<0.05). These findings indicate that rhGH in combination with HGF exert additive effects on constitutive hepatic proteins and partial inhibitory effects on acute phase protein and cytokine expression. RhGH/HGF has a strong mitogenic effect on hepatocytes.

Acute-Phase Reaction↗

PubMed1998

Mortality in burned children with acute renal failure.

BACKGROUND: During the past 13 years, mortality from acute renal failure in burned children has been on the decline. OBJECTIVE: To determine which new burn therapies contributed to the decrease in mortality. DESIGN: The medical records of burned children admitted from February 1966 to January 1997 were reviewed, and the outcome of changes in the treatment of burned children were compared. PATIENTS AND METHODS: Sixty children with acute renal failure were identified. These children were divided into those admitted from 1966 to 1983 (n=24) and those admitted from 1984 to 1997 (n=36). They were compared with matched control subjects from the same period without renal failure. Values are presented as means+/-SEMs. Statistical analysis was by the Student t test or chi2 analysis. RESULTS: Mortality rates in burned children with acute renal failure decreased from 100% before 1983 to 56% after 1984 (P<.001). The time between a burn injury and the initiation of intravenous fluid resuscitation was 8.6+/-1.7 hours before 1983 compared with 3.0+/-0.5 hours after 1984 (P<.005). The time between a burn injury and complete early wound excision decreased from 228+/-37 hours before 1983 to 40+/-7 hours after 1984 (P<.001). The incidence of sepsis decreased from 71% to 44% in these periods (P<.05). After 1984, survivors had a shorter time delay for fluid resuscitation than nonsurvivors (1.7+/-0.5 hours vs 4.8+/-0.9 hours; P<.005) and a lower incidence of sepsis (19% vs 60%; P<.05). From 1984 to 1997, burned children with acute renal failure who did not require dialysis had significantly shorter delays for fluid resuscitation (2.2+/-0.5 hours vs 4.4+/-0.9 hours) and complete wound excision (29+/-6 hours vs 49+/-7 hours) compared with those requiring dialysis (P<.05 for both). CONCLUSION: Early adequate fluid resuscitation, early wound excision, and better infection control may reduce mortality in burned children with acute renal failure.

Acute Kidney Injury↗

PubMed1998

Recombinant human growth hormone (rhGH) downregulates hepatocyte growth factor (HGF) in burns.

INTRODUCTION: Hepatocyte growth factor (HGF) and recombinant human growth hormone (rhGH) have both been shown to increase albumin serum concentrations after major injury. However, the effect of rhGH on HGF production after injury is unknown. We postulated that rhGH effects constitutive protein concentrations by inducing HGF expression. METHODS: In order to determine a dose response, 20 male Sprague-Dawley rats received three different concentrations of rhGH 1, 2.5, and 5 mg/kg and a saline treatment. Rats were sacrificed 10 days after burn and serum albumin and HGF plasma concentrations were measured. Eighty male Sprague-Dawley rats received a 60% TBSA third-degree scald burn injury and were randomly divided into three groups, control, burn plus saline treatment, or burn plus rhGH treatment (2.5 mg/kg SQ qD). Rats were sacrificed 2, 5, 7, and 14 days after burn, and serum albumin, plasma, and hepatic tissue HGF concentrations were determined (ELISA, Institute of Immunology, Tokyo, Japan). RESULTS: At 10 days postburn serum albumin levels were significantly increased with rhGH 2.5 mg/kg treatment (P < 0.05); however, HGF plasma concentrations were significantly decreased with a dose of 5 mg/kg of rhGH compared to control and rhGH 1.0 mg/kg (P < 0.05). Serum albumin concentrations decreased immediately after burn and remained low until at least the 14th day after injury. RhGH-treated animals had higher levels of albumin on Day 7 after burn (P < 0.05). Plasma HGF levels decreased immediately after burn, but increased after the second day postburn. Beginning on the 5th day after injury, HGF levels in non-rhGH-treated rats were significantly higher compared to those in rhGH-treated rats (P < 0.05). Hepatic tissue HGF concentrations were higher in non-rhGH-treated rats compared to rhGH treated animals 7 days after burn (P < 0.01). CONCLUSION: Although rhGH treatment improves constitutive protein synthesis, rhGH decreases HGF concentration in a dose-dependent manner. The improvements in constitutive protein concentrations do not occur via a HGF dependent pathway.

Acute-Phase Reaction↗

PubMed1998

Nutritional hepatic steatosis and mortality after burn injury in rats.

AIMS: To investigate the effects of diet composition and starvation on hepatic steatosis and mortality after severe burn injury in rats. METHODS: Experiment 1: rats received either normal chow (55 cent of energy carbohydrates, 14 cent fat, 31 cent protein), a high-fat (40 cent carbohydrates, 40 cent fat, 20 cent protein), or a high-carbohydrate diet (81 cent carbohydrates, 4 cent fat, 15 cent protein) ad libitum for 6 days. Another three groups received these diets ad libitum for 6 days after 48|h starvation. Experiment 2: mortality after 60 cent total body surface area scald burn was determined in a control group of rats and a group with nutritionally induced hepatic steatosis. Hepatic steatosis was induced by feeding the rats a high-fat diet (40 cent carbohydrates, 4 cent fat, 15 cent protein) ad libitum for 6 days. RESULTS: Without starvation, liver triglyceride content (mg/g liver) increased in response to the high-fat diet (25.6'6.9) compared to normal chow (9.4'3.8; P < 0. 05); the high-carbohydrate diet had no influence on liver triglyceride content (12.4'3.7). Refeeding after starvation resulted in elevated (P < 0.05) liver triglyceride content in the high-fat (18.8'8.3) and the high-carbohydrate group (28.7'14.4 vs control 6. 7'3.7). Liver triglyceride content correlated (R2=0.72; P < 0.05) to non-protein energy intake but not to total energy intake. Burn caused 33 cent mortality in the hepatic steatosis group and no deaths in the control group (P < 0.05). CONCLUSIONS: Diet composition and preceding starvation independently manipulate hepatic fat content in rats. Hepatic steatosis increases mortality after burn injury. Thus, nutritional interventions to reduce hepatic fat accumulation may be beneficial.

Alkaline Phosphatase↗

PubMed1997

Growth hormone attenuates the acute-phase response to thermal injury.

OBJECTIVE: To determine the effects of growth hormone (GH) on the hepatic acute-phase response (APR) in a burned rat model. SETTING: Laboratory. MATERIAL: Male Sprague-Dawley rats (weight, 300-350 g). INTERVENTIONS: Rats underwent a 40% total body surface area burn injury and received GH or saline solution daily by subcutaneous injection. Unburned rats served as controls. MAIN OUTCOME MEASURES: Hepatic messenger RNA (mRNA) expression and serum levels of alpha 1-acid glycoprotein and albumin were determined 2, 7, and 14 days after injury. RESULTS: The serum alpha 1-acid glycoprotein levels in GH-treated animals did not increase on days 2 and 7, whereas saline-treated animals showed a major increase. Hepatic mRNA expression increased dramatically on day 2 for burned groups; however, the mRNA pool levels of GH-treated animals showed a faster rate of decline to control levels on days 7 and 14. The albumin mRNA pool levels of GH-treated and control animals did not show significant differences, whereas the negative APR, indicated by loss of albumin mRNA, was more pronounced on day 7 in the saline-treated animals. By day 14, mRNA levels were comparable in all 3 groups. CONCLUSION: Growth hormone attenuated the positive APR, as indicated by a decrease in alpha 1-acid glycoprotein expression and production, and prevented the negative APR, as seen by an absence of a decline of albumin mRNA pool levels and serum concentration. We conclude that the beneficial effects of GH on thermal injury may be due in part to a modification of the APR.

Acute-Phase Reaction↗

PubMed1997

Enteral feeding intolerance: an indicator of sepsis-associated mortality in burned children.

OBJECTIVE: To determine if enteral feeding intolerance (EFI) is associated with sepsis and increased mortality in children with severe burns. DESIGN: A survey. SETTING: A pediatric burn unit. PATIENTS: Ninety-one children surviving longer than 5 days with greater than 80% total body surface area burns. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Enteral feeding intolerance indicated by high gastric residuals (> 150 mL/h) or uncontrollable diarrhea (> 2500 mL/d); thrombocytopenia (platelet count < 100 x 10(9)/L); hyperglycemia (glucose level > 11.1 mmol/L [> 200 mg/dL]); sepsis (pathogenic bacteremia or fungemia noted on blood culture results); and mortality. RESULTS: Neither EFI nor sepsis developed in 71 patients, EFI alone developed in 2 patients, sepsis alone developed in 5 patients, and EFI and sepsis developed in 13 patients. Enteral feeding intolerance and sepsis were associated by contingency table analysis (P<.001). Mortality was 8% (6 patients) in those with neither EFI nor sepsis, 50% (1 patient) in those with EFI alone, 60% (3 patients) in those with sepsis alone, and 77% (10 patients) in those with EFI-associated sepsis. The 2 latter groups were different from the group with neither EFI nor sepsis (P<.05). Enteral feeding intolerance was identified in 70% of patients before sepsis; thrombocytopenia, 64%; and hyperglycemia, 66%. When compared with thrombocytopenia and hyperthermia, no variables were found to be superior to others for predicting sepsis. CONCLUSIONS: Enteral feeding intolerance was associated with the development of sepsis and increased mortality in children with greater than 80% total body surface area burns. This sign was identified in 70% of the cases before pathogens were found in the blood; no difference could be shown between the identification of EFI, thrombocytopenia, and hyperglycemia before sepsis. These data indicate that the development of EFI should be used as an indicator of infection and should prompt a search for an inciting focus.

Burns↗