Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 55 records · Page 3Linked to original sources

PubMed1996

Effect of transfusion on oxygen transport in critically ill patients.

The role of isolated blood transfusion as a means toward improving oxygen transport was evaluated in 19 critically ill patients having sepsis syndrome as defined by standard criteria. ICU therapies were unchanged during transfusion and hemodynamic profiles with serum lactate levels were obtained before and after packed red blood cells were given. Blood transfusions in these patients did not cause a change in hemodynamic status. Arterial lactate determination was normal before and after transfusion was administered. Oxygen uptake failed to increase with transfusion, corresponding to increased arterial and mixed venous oxygen content. In the presence of sepsis, patients having oxygen delivery and uptake above normal without evidence of ischemia (normal lactate) will not increase oxygen consumption by raising the hemoglobin.

Adult↗

PubMed1996

Partial hepatectomy reduces the endotoxin-induced peak circulating level of tumor necrosis factor in rats.

The pro-inflammatory cytokine tumor necrosis factor (TNF) is dramatically and transiently elevated in the circulation during endotoxic and septic shock and is a primary mediator in the pathogenesis of the sepsis syndrome. TNF peaks in the circulation 90 min after endotoxin administration with little variation, even among species. The specific cells, tissues, or organs that produce the high circulating level of TNF in septic shock remain unknown. The most likely sources are macrophage-laden tissues such as the liver and the spleen and circulating blood leukocytes. This study evaluated whether the liver is an important source producing the TNF spike 90 min after endotoxin. To test this hypothesis, we measured the peak circulating level of TNF following an endotoxin injection in rats subjected to a two-thirds hepatectomy versus sham-operated controls. Hepatechectomized rats produced 64% less TNF after endotoxin than controls (857 + or - 143 pg/mL plasma vs. 2410 + or - 491, respectively; p < .01). In contrast, splenectomy did not significantly after peak TNF levels versus sham-operated controls following an endotoxin injection (1380 + or - 148 pg/mL plasma vs. 1710 + or - 291). Furthermore, incubation of rat blood with endotoxin for 90 min did not significantly increase TNF above controls. These experiments demonstrate an important role for the liver in producing the high circulating levels of TNF after an endotoxin injection and suggest that hepatic-specific cytokine modulation deserves study for a therapeutic benefit in septic shock.

Animals↗

PubMed1996

Thrombospondin 1 synthesis and function in wound repair.

Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix molecule that belongs to a family of homologous glycoproteins. TSP1 can be produced by many cell types that are involved in wound repair, including keratinocytes, fibroblasts, endothelial cells, and macrophages. To investigate the kinetics of TSP1 synthesis in wounds, mRNA from murine full thickness excisional dermal wounds was analyzed. TSP1 mRNA was undetectable in normal skin but was present in early wounds. After day 1, TSP1 mRNA levels within wounds slowly decreased, returning to undectable day 10. In situ hybridization revealed that the primary source of the TSP1 mRNA within wounds was macrophage-like cells in the inflammatory infiltrate. To explore the function of TSP1 production in sites of injury, wounds were treated with antisense TSP1 oligomers. Antisense-treated wounds contained 55 to 66% less TSP1-positive macrophages than control and exhibited a marked delay in repair. This delay included a decreased rate of re-epithelialization as well as a delay in dermal reorganization. The results suggest that TSP1 production by macrophages facilitates the repair process and provide evidence that TSP1 production is an important component of optimal wound healing.

Animals↗

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

Differential effects of 21-aminosteroids on wound healing.

OBJECTIVE: The aim of this study was to examine the effects of the 21-aminosteroid U74389F on wound healing, compared with corticosteroids using a murine incisional wound model. BACKGROUND DATA: The 21-aminosteroids are extremely potent inhibitors of iron-dependent lipid peroxidation and peroxyl radical formation, and have proven significantly beneficial in reducing neurologic sequelae following head and spinal cord trauma in experimental models. The detrimental effects of currently administered corticosteroids on wound healing are well-documented; however, the effects of the 21-aminosteroids on wound healing are poorly defined to date. METHODS: Male BDF1 mice (n = 28/group) given a left paraspinous wound received daily intraperitoneal injection of vehicle or U74389F (1 to 100 mg/kg/day) for 10 days. Wound disruption strengths (WDSs) in grams were determined on freshly harvested (F) and 36-hour formalin-fixed (FF) wounds. In addition, U74389F (3 mg/kg/day) was compared with equipotent doses of methylprednisolone, dexamethasone, and hydrocortisone (n = 12/group) for alterations in wound healing. RESULTS: The WDSs of the U74389F animals F or following FF were not significantly different from controls. In the comparison study, no significant difference in F or FF WDS was found for U74389F (3 mg/kg/day) or methylprednisolone animals when compared with controls. Dexamethasone-treated and hydrocortisone-treated animals had F and FF WDSs that were 50% of control and U74389F values (p < 0.001; ANOVA). Wounds harvested from both the control and U74389F-treated animals demonstrated the greatest extent of wound cleft contraction, collagen deposition, and neovascularity, with no obvious internal differences detectable under light microscopy. CONCLUSIONS: These results show that the 21-aminosteroid U74389F did not impair wound healing, as determined by WDS and light microscopy. Furthermore, given their greater efficacy in cell membrane stabilization and potent ability to scavenge peroxyl radicals, the 21-aminosteroids may prove beneficial in treating a variety of clinical conditions, wherein ischemia-reperfusion injury plays a major component.

Animals↗

PubMed1995

The impact of substance use on mortality and morbidity from thermal injury.

Alcohol and drug use have been associated with increased mortality and morbidity from thermal injury. To determine whether substance users (SUs) differed from controls, 398 burn patients were studied, of whom, 161 had a positive drug screen for either ethanol, cannabinoids, cocaine metabolites, amphetamines, phencyclidine, or benzodiazepines. SUs versus controls showed no difference in age, but had a significantly greater percentage of total burn surface area (TBSA) (25 vs. 17%), inhalation injury (29 vs. 7%), and mortality (14 vs. 3%). The alcohol users (AUs) and drug users (DUs) were similar in relation to sex, age, inhalation injury, percentage of TBSA, and type of burn. DU patients experienced the same increase in inhalation injury as the AU group compared to controls. The mortality of AU patients was twice that of DU patients and six times that of controls. The best independent predictors of death were age, inhalation injury, percentage of TBSA (p < 0.001), and ethanol use (p < 0.02).

Adolescent↗

PubMed1995

Burn-induced nitric oxide release in humans.

Nitric oxide (NO) generation in a series of 20 burn patients was studied with a novel anion exchange high-performance liquid chromatographic method for the simultaneous determination of nitrite (NO2-) and nitrate (NO3-), the stable metabolic endproducts of NO. The NO values within our survivor group (n = 17) were significantly altered at days 1, 6, and 12 postburn in contrast to controls (n = 23) (p < or = 0.03). NO2- values were significantly depressed in both plasma and urine, whereas NO3- values were significantly elevated in contrast to control values (p < or = 0.03). The ratio of NO2-:NO3- was significantly lower for burn patients versus controls in both plasma and urine (p < 0.01). The NO generation seemed in part to be dependent on the percentage of total body surface area burn, most dramatically elevated in patients with burns of 10 to 40% total body surface area. In subjects who did not survive beyond 36 hours postinjury because of irreversible shock (n = 3), the production of NO was significantly depressed in contrast to survivors and controls (p < 0.0001). However, the NO2-:NO3- ratio (0.001) was relatively unchanged, with reflection of a global depression in NO formation with no change in the individual component release. Burn injury resulted in an increased release/production of NO that in the first postburn week is maximally elevated immediately postinjury. NO release, although decreased at day 6 relative to the day 1 values, remained elevated into the second week postinjury when there was evidence for a further increase in NO production. The enhanced NO3- formation may well result from NO reacting with oxygen-free radicals counteracting superoxide anion-induced destruction of tissue, thereby potentially functioning as a protectant molecule.

Anion Exchange Resins↗

PubMed1995

General surgeons and the Advanced Trauma Life Support course: is it time to refocus?

OBJECTIVE: The aim of this study was to assess Advanced Trauma Life Support (ATLS) training status of general surgeons, its perceived utility, and its relation to clinical trauma practice. METHODS: A national sample of 1300 general surgeons was surveyed by mail about trauma training, ATLS status, trauma call, and confidence in clinical trauma care abilities. RESULTS: Response rate was 61%. Respondents most commonly (67%) felt they learned a great deal about trauma care in residency training; 13% responded similarly regarding ATLS. Course participation within 4 years of the survey was reported by 33% of respondents. Nearly 75% of those not taking the course cited primary reasons related to relevance (30%), redundancy (29%), and credentialing (15%). Inaccessibility, inconvenience, and cost were lesser factors. Of those expressing extreme confidence with trauma resuscitation, 40% had taken ATLS; 15% of those expressing a lesser degree of confidence had taken ATLS. CONCLUSIONS: The ATLS course represents a standard of initial trauma care education in which only one-third of surgeons report current participation. Many view ATLS as not relevant or useful, yet take trauma call. To ensure standard education and patient care, an ATLS course curriculum specifically geared to the general surgeon should be developed and made a mandatory component of residency training or a requirement for board certification and trauma call credentialing.

Clinical Competence↗

PubMed1995

Recombinant human granulocyte colony-stimulating factor treatment improves macrophage suppression of granulocyte and macrophage growth after burn and burn wound infection.

Granulocyte and macrophage production after burn injury or burn wound infection is significantly reduced and further compromised by endotoxin (ET). Moreover, the macrophage seems to be the major source of this bone marrow suppression. We sought to determine if recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that is capable of improving survival after experimental burn wound sepsis, altered postburn macrophage-mediated marrow suppression. Groups of male BDF1 mice (n = 6 to 10) receiving a 15% total body surface area burn +/- infection (B or B + I) with Pseudomonas aeruginosa were injected with 100 ng rhG-CSF twice daily. On day 3, peritoneal-elicited macrophages (5 x 10(6) cells/mL) from either rhG-CSF-treated or control (5% dextrose in water) mice were incubated +/- ET (300 ng/mL). The resultant macrophage supernatant was added to cultures of target marrow granulocyte-macrophage progenitor cells (GM-CFC) at a volume of 1:10. The GM-CFC growth as a percentage of cultures not containing macrophage supernatant were compared and reductions in the number of GM-CFC taken as an index of marrow suppression. Macrophages obtained from B and B + I animals reduced target GM-CFC growth, compared with macrophages from normal animals (B vs. normal animals p < 0.05). In addition, ET-stimulated macrophages induced further bone marrow suppression for all three groups (p < 0.01). Macrophages from granulocyte colony-stimulating factor-treated animals caused significantly less bone marrow suppression, compared with untreated animals for all groups (p < 0.05 to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Systemic administration of interferon-gamma impairs wound healing.

Interferon-gamma (IFN-gamma), a cytokine that has been shown to upregulate macrophage function, has recently been demonstrated to improve outcome when exogenously administered in several animal models of injury. Because the macrophage is also important in the events that govern wound healing, we evaluated the effects of IFN-gamma upon wound healing in a murine model. IFN-gamma was administered in doses of 937.5-22,500 u synchronous with the creation of a left paraspinous wound and then daily. At Day 10, wounds were harvested, evaluated for wound disruption strength (WDS), and subjected to morphometric analysis. Wounds were also subjected to 36-hr formalin fixation to maximally cross-link collagen fibrils and retested for WDS. We found that IFN-gamma impaired wound healing at all doses relative to control, and WDS was impaired in a dose-dependent fashion. Our highest dose of IFN-gamma (22,500 u) produced a WDS only 65% of the control. Morphometric studies demonstrated less collagen deposition and a lower degree of neovascularity in IFN-gamma-treated animals. In addition, formalin fixation studies suggested that IFN-gamma may impair collagen cross-linking. The potential benefits of IFN-gamma in the multiply injured patient must be weighed against the possibility that IFN-gamma might deleteriously effect events fundamental to wound healing.

Animals↗

PubMed1994

Dose dependency of granulocyte-macrophage colony stimulating factor for improving survival following burn wound infection.

Infections remain a serious problem following injury. Immune modulation offers an additional strategy for the treatment of infections. We evaluated the ability of a multilineage hematopoietic growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), to improve survival following burn injury with a superimposed burn wound infection. Groups of 12 BDF1 mice received a 15% total body surface area (TBSA) thermal injury by immersion in 100 degrees C water; 6 x 10(3) Pseudomonas was then applied to the burn wound. The GM-CSF was injected subcutaneously B.I.D. for 7 days. Mice receiving the 10-ng dose of GM-CSF had significantly improved survival compared with the controls; other doses had no significant effect on survival. Clinical trials to assess the ability of GM-CSF to reduce infectious complications following burn injury are underway and these data suggest selecting a specific dose may be critical in achieving maximal benefit.

Animals↗

PubMed1994

Interferon-gamma increases mortality following cecal ligation and puncture.

Interferon-gamma (IFN-gamma) has been demonstrated to improve outcome following localized infection and hemorrhagic shock in experimental studies. We sought to determine the effects of IFN-gamma in a clinically relevant murine model of intra-abdominal polymicrobial sepsis. Fifty male BDF1 mice, each weighing 23-28 g, underwent cecal ligation and puncture (CLP) followed by administration of subcutaneous injections of IFN-gamma 100-22,500 U or vehicle control immediately post-CLP and then daily. In a second set of experiments, 60 mice underwent daily injections of vehicle control or 100 U IFN-gamma 24, 48, or 72 hours prior to CLP. Interferon-gamma administered following CLP led to increased mortality and earlier deaths in a dose-dependent fashion (p < 0.05). Interferon-gamma given 24, 48, or 72 hours prior to CLP resulted in no demonstrable benefit when compared with animals that did not receive IFN-gamma (p = 0.14, p = 0.94, and p = 0.97, respectively). While IFN-gamma has been reported to be of value in selected clinical situations by improving resistance to infection, it may not be capable of conferring protection following surgery or trauma with intra-abdominal sepsis, and in fact may be detrimental.

Animals↗

PubMed1994

Marrow granulocyte-macrophage progenitor cell response to burn injury as modified by endotoxin and indomethacin.

The production and release of granulocytes and macrophages are significantly impaired following burn injury and infection. In an attempt to determine the factors responsible for these adverse effects and their potential treatments, we performed a series of studies in mice analyzing the bone marrow response to burn wound infection. The proliferative response of the marrow granulocyte-macrophage progenitor cell (GM-CFC) in male BDF1 mice undergoing a dorsal scald burn or burn wound seeding with 1000 colony forming units of Pseudomonas aeruginosa was determined on day 3 postburn using a clonal culture of GM-CFC. Mice with infected burn wounds had a rate of GM-CFC proliferation that was 50% that of noninfected animals and levels of circulating colony stimulating activity (CSA) 30% those of controls (p = 0.006). Similar suppression of marrow proliferative status could be replicated with the administration of endotoxin to normal or burned animals as had been observed for burn-infected animals. The administration of indomethacin (5 mg/kg.day) substantially restored the GM-CFC proliferation in mice with infected burns as well as in animals given endotoxin. Indomethacin-treated animals had CSA values 244% those of untreated burn-infected animals (p = 0.016). We take these observations to suggest that suppression of myelopoiesis in burn-infected animals is related in part to endotoxin-stimulated production of prostaglandin mediators that altered myeloid proliferation and was responsive to cyclooxygenase blockade.

Animals↗

PubMed1994

Macrophage suppression of granulocyte and macrophage growth following burn wound infection.

Burn injury results in alterations in granulocyte and macrophage production. Since macrophages may mediate these alterations we determined the effects of macrophages obtained from animals with burn injury with and without infection on the growth of marrow granulocyte macrophage progenitor cells (GM-CFCs). The in vitro GM-CFC growth response for maximally stimulated cultures was reduced by 25% to 30% (p < 0.01) for burned and infected (B + I) animal macrophages compared with burned (B) or sham (S) animals. Macrophages stimulated with endotoxin caused a further reduction for all groups in GM-CFC growth, most notably so for B + I macrophages. Burned + infected animal macrophages or all-endotoxin macrophages cocultured with indomethacin did not suppress GM-CFC growth. Following burn injury and infection, macrophages spontaneously elaborate negative regulators of myeloid growth that is further increased by endotoxin. It is likely that PGE2, a known negative regulator of granulocyte macrophage growth, is largely responsible for this suppressive effect.

Animals↗

PubMed1994

Perception of differences between trauma care and other surgical emergencies: results from a national survey of surgeons.

A national sample of 2500 surgeons was surveyed. Thirteen variables were analyzed to ascertain perceived differences between trauma care and other surgical emergencies, as well as to identify factors contributing to a preferential reluctance to treat trauma. The response rate was 60%. Trauma was perceived as most likely to occur at inconvenient times by 67% of respondents, more often complex (44%), and more demanding of specialized knowledge (39%). Trauma was viewed as less likely to be reimbursed by 35% and most often litigious by 30%. Fewer respondents perceived differences for risk of exposure to lethal pathogens and violence (26% and 9%) and personal or professional rewards (25%). Surgeons who prefer to treat trauma view it as more often demanding of specialized knowledge and more complex than other surgical emergencies. Surgeons who prefer not to treat trauma or take trauma call perceive it as never personally or professionally rewarding, more often disruptive to personal life, emotionally taxing, litigious, and inconvenient compared with other emergencies. Perception of dissimilar reimbursement and personal health risk are less often associated factors. Perceived differences in the litigious nature of cases are not based on fact. We conclude that the individual degree of reluctance or enthusiasm for trauma care in comparison with other emergencies is influenced by perception, personality, and myth rather than by logic and facts.

Adult↗

PubMed1994

Alterations of glucose transporter mRNA and protein levels in brain following thermal injury and sepsis in mice.

Since glucose transport and utilization are profoundly influenced by injury and infection, and the brain is an organ which primarily utilizes glucose as its energy source, we examined the status of the facilitative glucose transporters GLUT1 and GLUT3 in brain following thermal injury and infection. BDF1 mice underwent a 15% total body surface area burn with or without Pseudomonas aeruginosa infection. At 4 and 72 h post injury +/- infection, GLUT1 and GLUT3 mRNA abundance was measured by Northern blotting, and the correlative proteins determined using Western blotting. At 4 h, both brain GLUT1 mRNA and protein abundance were significantly increased in burned (mRNA 150 +/- 12%, protein 122 +/- 6%) and burn/infected (mRNA 165 +/- 11%, protein 119 +/- 5%) animals. At 72 h, GLUT1 mRNA and protein levels were also significantly increased in burn (mRNA: 139 +/- 11%, protein: 120 +/- 7%) and burn/infected (mRNA: 145 +/- 14%, protein: 138 +/- 8%) animals. Our studies suggest that alterations of GLUT1 mRNA and protein abundance were primary responses to the burn injury and were not further altered by burn wound infection.

Animals↗

PubMed1994

Pseudoepitheliomatous hyperplasia in chronic cutaneous wounds. A flow cytometric study.

Cutaneous squamous cell carcinomas (SCC) arising in a setting of chronic regeneration and repair tend to be highly aggressive lesions prognostically distinct from SCC arising in solar-damaged skin. Full thickness thermal injury and chronic nonhealing ulcers are predisposing conditions in up to 2% of SCC. A significant association has been suggested to exist between pseudoepitheliomatous hyperplasia (PH) and SCC. Three-hundred-eighty-six surgical cases of skin excised secondary to severe burns (n = 254) or chronic ulcers (n = 132) were reviewed, yielding 43 (11%) with PH. Flow cytometric DNA analysis was performed on paraffin-embedded sections. Thirty cases without PH were studied in addition to the 43 cases with PH. The majority (39/43) of the PH cases showed a single diploid population with a mean S-phase of 13.7%. Four cases (9.3%) showed an aneuploid peak. All cases without PH were diploid with a mean S-phase of 9.0%. In this study, PH was present in 11% of cases reviewed, and showed a 50% mean higher S-phase than comparable cases without PH. Aneuploidy was present in 9.3% of the PH cases studied. SCC may arise from a subgroup of PH in a background of rapidly proliferating keratinocytes.

Carcinoma↗

PubMed1994

Interleukin-2 and interleukin-6 in relation to burn wound size in the acute phase of thermal injury.

Thermal injury induces significant physiologic responses of acute inflammation, acute phase reaction and cell repair and growth, mediated by interleukins, cytokines and growth factors. To determine the relative role of interleukin-2 (IL-2) and interleukin-6 (IL-6) in the acute phase of thermal injury, 60 patients (47 men and 13 women, with average age of 37 years [1.5 to 70.0 years]) were analyzed within the first 36 hours and at five to seven days postoperatively. The patient population was categorized by percent burn (2 or 3, or both, degrees): less than 20 percent, n = 22; 20 to 40 percent, n = 18, and greater than 40 percent, n = 20. The average percent burn was 32 percent (range 4 to 95 percent). The mechanism of injury was by flame (25 instances), explosion and flame (19 instances), scald (12 instances), electric (three instances) or chemical (one instance). Twelve patients had an associated inhalation injury; 14 patients had sepsis syndrome. The overall mortality rate was 13 percent. Within 36 hours of onset of injury, IL-6 and IL-2 levels increased in proportion to the severity of the burn wound size. IL-2 levels were significantly elevated in the 20 to 40 percent burn group as compared with the greater than 40 percent group and patients in a control group (p < 0.0001). IL-6 levels increased with burn wound size and were significant only in the greater than 40 percent group (p < 0.0007). Any physiologic modulation of the thermal injury by biologic modifiers must be adapted to the extent of burn wound size and phase of injury: acute, recovery or reparative for optimal benefit and results.

Acute Disease↗