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Biomedical subjects

J A Griswold

Publications and source records attributed to J A Griswold.

At least 19 recordsLinked to original sources

The effects of infection of thermal injury by Pseudomonas aeruginosa PAO1 on the murine cytokine response.

Pseudomonas aeruginosa infection, one of the major complications of burn wounds, may lead to sepsis and death. Using the Multi-Probe Template/RNase protection assay, we have compared the expression of different cytokine genes within the skin and livers of thermally injured mice infected with P. aeruginosa PAO1. Thermal injury alone enhanced or up-regulated certain cytokines, including macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1)RI, IL-1 beta, macrophage inflammatory protein (MIP)-1 beta and MIP-2; while PAO1 challenge alone up-regulated tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) expression. The combination of thermal injury plus PAO1 infection enhanced the expression of several pro-inflammatory and haematopoietic cytokines [stem cell factor (SCF), leukocyte inhibitory factor (LIF), IL-6 and TNF-alpha]; induced the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF by 5 h and the expression of additional cytokines, including TGF-beta, TNF-beta, lymphotoxin beta (LT-beta), interferon gamma (IFN-gamma), and IFN-beta by 40 h post-burn/infection. While the most intense cytokine expression occurred in the skin, the majority of cytokines tested were also expressed in the liver by 40 h post-burn/infection. These results suggest that in P. aeruginosa infection of burn wounds: (1) up-regulation of the expression of different cytokines, locally and within the livers of burned mice, is an indication of P. aeruginosa -induced sepsis; and (2) IL-6 and G-CSF play an important role in the host response mechanism.

Animals↗

Adrenal hemorrhage in a pediatric burn patient.

Adrenal hemorrhage with subsequent insufficiency is a rare complication in the burn patient. The case of a previously healthy 3-year-old Latin American male who was a victim of child abuse is presented. He suffered a submersion injury in hot water leading to a 45% total body surface area burn. An acute deterioration on the 7th post burn day was unresponsive to standard inotropic support and cardiopulmonary resuscitation. Post mortem examination revealed bilateral adrenal hemorrhage that had not been present 2 days earlier. To the authors' knowledge, this is the first reported case in a pediatric burn patient. The clinical manifestations of adrenal insufficiency vary widely and can be easily confused with sepsis. High index of suspicion is necessary for early diagnosis and treatment. Serum cortisol level should be checked and steroid therapy implemented if sepsis syndrome is unresponsive to standard therapy in this setting. This early intervention may be the key to improved survival of the burn patient with a sudden unexplained deterioration resistant to well established resuscitation methods.

Adrenal Gland Diseases↗

The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide variety of infections. The cell-density-dependent signaling mechanisms known as quorum sensing play a role in several of these infections including corneal, lung and burn wound infections. In addition, the quorum-sensing systems contribute to the ability of P. aeruginosa to form biofilms on medically important devices. The quorum-sensing systems accomplish their effect by controlling the production of different virulence factors and by manipulating the host immune response.

Animals↗

Analysis of Pseudomonas aeruginosa clinical isolates for possible variations within the virulence genes exotoxin A and exoenzyme S.

We have previously characterized several Pseudomonas aeruginosa isolates that were obtained from patients with tracheal, urinary tract, or wound infections (A. H. Hamood, J. A. Griswold, and C. M. Duhan, 1996, J. Surg. Res. 61: 425). Analysis of additional isolates showed that regardless of the isolation site, some isolates produced significantly higher or significantly lower levels of either exotoxin A or exoenzyme S proteins. These variations did not correlate with the mucoid phenotype of the isolates. One aim of this study was to determine if the variations in the level of exotoxin A or exoenzyme S are due to DNA rearrangements within either the toxA or the exoS gene. This was accomplished by Southern blot hybridization experiments using a toxA internal probe, a toxA upstream probe, or an exoS internal probe. Hybridization with the toxA internal probe produced a 0.8-kb hybridizing fragment, whereas hybridization with the exoS internal probe produced either a 2.0- or a 2.3-kb hybridizing fragment. Hybridization with the toxA upstream probe, however, produced hybridizing fragments of varying sizes, regardless of their isolation site. Isolates that showed a similar hybridization fragment with either the toxA upstream probe or the exoS internal probe produced variable levels of exotoxin A or exoenzyme S. These results suggest that: [1] specific location within the host has no effect on either the mucoid phenotype of the isolate or the level of exotoxin A or exoenzyme S produced by the isolates; [2] although restriction polymorphism exists within the toxA upstream region, both the toxA and the exoS structural genes are relatively conserved; and [3] variations in the level of exoenzyme S and exotoxin A produced by different isolates do not correlate with either the observed heterogeneity within the toxA upstream region or the mucoid phenotype of the isolates.

ADP Ribose Transferases↗

Pseudomonas aeruginosa strains obtained from patients with tracheal, urinary tract and wound infection: variations in virulence factors and virulence genes.

Pseudomonas aeruginosa produces several virulence factors including exotoxin A, exoenzyme S and elastase. In previous reports we have analysed several clinical isolates for the production of these three virulence factors and for possible heterogeneity within the genes that code for these factors (toxA, lasB and the exoS genes). The isolates were obtained from three specific sites (trachea, urinary tract and wounds). Although the isolates produced variable levels of these factors, isolates that were obtained specifically from urinary tract and wound infections produced increased levels of exotoxin A and exoenzyme S. In addition, a prolonged infection with P. aeruginosa appears to enhance exoenzyme S production. Restriction site polymorphism was very limited within the toxA, lasB, and exoS structural genes; however, the upstream region of toxA showed restriction site polymorphisms between the different isolates. The observed polymorphisms did not correlate with any variations in the levels of the virulence factors. In this article, we provide a short review of these studies.

ADP Ribose Transferases↗

Bradykinin metabolism in perfused rat kidney.

The purpose of this study was to assess the capacity of perfused rat kidney to inactivate bradykinin (BK), and to compare the BK degrading capacity of rat kidney with the BK degrading capacities of rat lung, liver, and skeletal muscle, which was approximated by perfusion of rat hind limbs. Radioactively labeled BK, with the Pro2 and Pro3 residues having been tritiated, in an asanguinous salt solution was perfused through the kidney of the rat, over a concentration range of .0028-33 microM. Rat kidney had a large capacity to degrade BK and the system did not appear to approach saturation until perfusate BK concentrations reached 24 microM. A least-squares linear regression analysis and extrapolation to zero concentration was used to obtain values for amounts of BK degraded and BK fragments formed. The amount of BK cleaved was 99.9% of the administered dose. The major tritiated BK fragments formed, and the amount of each expressed as a percentage of the amount of BK degraded during transrenal passage, were the amino acid proline derived from the Pro2 and/or Pro3 residues of BK (Pro2,3), 60%; Pro-Pro (BK 2-3), 12%; Arg-Pro-Pro-Gly-Phe (BK 1-5), 14%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro (BK 1-7), 14%. The formation of BK 2-3 is indicative of initial aminopeptidase-P cleavage of BK to yield Arg, and des-Arg1-BK. Thus in rat kidney the aminopeptidase-P pathway is the major route for BK degradation, as is the case in rat liver.

Animals↗

Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections.

The Pseudomonas aeruginosa quorum-sensing systems, las and rhl, control the production of numerous virulence factors. In this study, we have used the burned-mouse model to examine the contribution of quorum-sensing systems to the pathogenesis of P. aeruginosa infections in burn wounds. Different quorum-sensing mutants of P. aeruginosa PAO1 that were defective in the lasR, lasI, or rhlI gene or both the lasI and rhlI genes were utilized. The following parameters of the P. aeruginosa infection were examined: (i) lethality to the burned mouse, (ii) dissemination of the P. aeruginosa strain within the body of the infected mouse (by determining the numbers of CFU of P. aeruginosa within the liver and spleen), and (iii) spread of the P. aeruginosa strain within the burned skin (by determining the numbers of CFU of P. aeruginosa at the inoculation site and at a site about 15 mm from the inoculation site [distant site]). In comparison with that of PAO1, the in vivo virulence of lasI, lasR, and rhlI mutants was significantly reduced. However, the most significant reduction in in vivo virulence was seen with the lasI rhlI mutant. The numbers of CFU that were recovered from the livers, spleens, and skin of mice infected with different mutants were significantly lower than those of PAO1. At 8 and 16 h post burn infection, comparable numbers of CFU of PAO1 and lasI and rhlI mutants were obtained from both the inoculation and distant sites of the burned skin of infected mice. In contrast, CFU of the lasR mutant and the lasI rhlI double mutant were recovered only from the inoculation site of infected mice at 8 and 16 h post burn infection. The ability of a plasmid carrying either the lasI or rhlI gene or the lasI and rhlI genes to complement the defect of the lasI rhlI double mutant was also examined. The presence of any of these plasmids within the lasI rhlI double mutant significantly enhanced its in vivo virulence, as well as its ability to spread within the burned skin. These results suggest that the quorum-sensing systems play an important role in the horizontal spread of P. aeruginosa within burned skin and in the dissemination of P. aeruginosa within the bodies of burned-and-infected mice and contributed to the overall virulence of P. aeruginosa in this animal model.

Animals↗

Bradykinin metabolism in rat hind limbs.

The purpose of this study was to assess the capacity of perfused rat hind limbs, the majority of which is skeletal muscle, to inactivate bradykinin (BK), and to compare the BK degrading capacity of rat hind limbs with the BK degrading capacities of rat lung and liver. BK, with tritiated Pro2 and Pro3 residues, in an asanguinous salt solution was perfused for a single passage through skeletal muscle and other tissues in the hind legs of the rat over a concentration range of .0029 to 49.3 microM. Rat hind limbs had a large capacity to degrade BK and the system did not approach saturation, even at 49.3 microM. A least-squares linear regression analysis and extrapolation to zero concentration was used to obtain values for amounts of BK degraded and BK fragments formed. The amount of BK cleaved was 95% of the administered dose. The major BK fragments formed, and the amount of each expressed as a percentage of the amount of BK degraded were Pro-Pro (BK 2-3), 8.6%; Arg-Pro-Pro-Gly-Phe (BK 1-5), 82%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro (BK 1-7), 6%. The BK 1-5 yield was reduced from 82% to one-fourth of that by angiotensin converting enzyme (ACE) inhibitors. BK 2-3 formation is indicative of initial aminopeptidase-P cleavage of BK to yield Arg, and des-Arg1-BK. ACE inhibitor sensitive formation of BK 1-5 is indicative of initial kininase-II, also known as ACE, cleavage of BK. Thus in rat hind limbs, the ACE pathway is the preponderant mechanism for BK degradation, which is in contrast to our previously published reports that in rat liver the amino-peptidase-P pathway predominates, and that in rat lung both the aminopeptidase-P pathway and the ACE pathway exhibit nearly equal capacities to degrade BK.

Animals↗

Production of extracellular virulence factors by Pseudomonas aeruginosa isolates obtained from tracheal, urinary tract, and wound infections.

This study was conducted to determine the effect of the local environment within the host on the ability of P. aeruginosa to produce different extracellular virulence factors (elastase, phospholipase C, toxin A, and exoenzyme S). A total of 105 P. aeruginosa isolates was obtained from patients with tracheal, urinary tract, and wound infections. Quantitative analysis of the virulence factors was done by growing the isolates in vitro in different defined media. Single colonies of each isolate were inoculated from the primary isolation plates into the defined medium. All four virulence factors were produced by most isolates. However, depending on the location of their isolation, the isolates varied in the level of virulence factors they produced. High levels of elastase and phospholipase C were produced by most isolates obtained from trachea, urinary tract, and wounds. A significantly higher level of toxin A was produced by wound isolates, while a significantly higher level of exoenzyme S was produced by wound and urinary tract isolates. Some P. aeruginosa strains were frequently isolated from the same site of infection (persistent infection isolates). Comparative analysis of virulence factors produced by these isolates showed that, regardless of the isolation site, subsequent isolates produced higher levels of exoenzyme S. These results suggest that: (1) elastase, phospholipase C, toxin A, and exoenzyme S are produced by P. aeruginosa isolates from different sites of infection; (2) the production of higher levels of elastase and phospholipase C is important in all types of infections, while the production of toxin A and exoenzyme S is important in wound infection; (3) persistent infection with P.aeruginosa may enhance exoenzyme S production.

ADP Ribose Transferases↗

Bradykinin metabolism in the liver and lung of the rat.

Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat liver. The perfusate was delivered through the portal vein and was collected from the inferior vena cava. BK concentrations varied from 0.0030 to 38.0 microm. The liver had a large capacity to degrade BK and the system did not approach saturation until perfusate BK concentrations reached 60 microm. The quantitatively predominant BK fragments formed and the amount of each formed, expressed as a percentage of the BK degraded during a single transhepatic passage, were Pro-Pro, 74%; Arg-Pro-Pro-Gly-Phe, 15%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro, 7%; the first is indicative of initial aminopeptidase-P cleavage of BK to yield Arg and des-Arg1-BK and the latter two are indicative of initial angiotension converting enzyme (ACE) cleavage of BK. On the other hand, while the perfused rat lung also had a large capacity to degrade BK, the quantitatively predominant BK fragments formed and the amount of each formed, again expressed as a percentage of BK metabolized during a single transpulmonary passage, were Pro-Pro, 47%; Arg-Pro-Pro-Gly-Phe, 35%; and Arg-Pro-Pro-Gly-Phe-Ser-Pro, 7%. Thus in rat liver the aminopeptidase-P pathway is the major route for BK degradation, whereas in rat lung the aminopeptidase-P and the ACE pathways exhibit nearly equal capacities to degrade BK.

Angiotensin-Converting Enzyme Inhibitors↗

Trauma in pregnancy: the role of interpersonal violence.

OBJECTIVE: Our purpose was to determine what role interpersonal violence as intentional injury plays in the pregnant trauma victim. STUDY DESIGN: We performed a retrospective review of medical records. RESULTS: During a 9-year period in a single university medical and trauma center, 203 pregnant women were treated for a physically traumatic event. Sixty-four women (31.5%) were victims of intentional injury, in most cases by the husband or boyfriend. Although the mean Injury Severity Score was higher in women with fetal death than in women with successful pregnancy outcomes (7.25 vs 1.74, respectively; p < 0.01), 5 of the 8 women with fetal losses incurred these despite an apparent absence of physical injury (maternal Injury Severity Score = 0). CONCLUSIONS: Interpersonal violence during pregnancy is a frequent and increasingly common cause of maternal injury. The inconsistent relationship between Injury Severity Score and serious fetal injury or death is underscored by the loss of 5 fetuses despite an Injury Severity Score of 0.

Accidents, Traffic↗

The mangled lower extremity: can salvage be predicted?

The ability to predict amputation following combined orthopedic, vascular and soft tissue trauma to an extremity could eliminate prolonged attempts at salvage of a doomed limb. We reviewed our experience with 48 mangled lower extremities in 46 patients. Twenty-one penetrating wounds and 25 blunt injuries occurred in 37 men and nine women ranging in age from 3 to 59 years. Severity of injuries to muscle, skin, and major nerves were strongly interrelated (r = 0.49 to 0.74, P < 0.001), but there were no correlations between injuries to these tissues and severity of bone injury (r < 0.19, P > 0.20). Twenty-four limbs were salvaged, and 24 were amputated. Increased severity of soft tissue injury was associated with a greater probability of limb loss (P < 0.001), but limb salvage or amputation could not be predicted accurately by any variable or group of variables such as age, mechanism of injury, Injury Severity Score, presence of shock, level of injury, venous injury or repair, sequence of repair (vascular vs skeletal), time of fasciotomy, arteriography, blood requirement, or duration of ischemia. Amputation was best predicted by severity of injury to the sciatic or tibial nerves (P < 0.001), and by failure of arterial repair (P < 0.01). Severe extremity injuries require a coordinated approach and decisions regarding amputation require careful judgement. These decisions cannot always be made at the time of presentation or during the initial operation. If after revascularization and skeletal stabilization the extremity is clearly nonviable or remains insensate, then delayed amputation can be performed under more controlled circumstances.

Adolescent↗

Surgical approach of choice for penetrating cardiac wounds.

One hundred nineteen patients suffered penetrating cardiac trauma over a 15-year period: 59 had gunshot wounds, 49 had stab wounds, and 11 had shotgun wounds. The overall survival rate was 58%. The most commonly injured structures were the ventricles. Twenty-seven patients had injuries to more than one cardiac chamber. Thirty patients had associated pulmonary injuries. Emergency thoracotomy was performed in 47 patients with 15% survival. Median sternotomy was used in 30 patients with 90% survival. Seventeen of the 83 patients with thoracotomies required extension across the sternum for improved cardiac exposure or access to the contralateral hemithorax. Only one patient with sternotomy also required a thoracotomy. All pulmonary injuries were easily managed when sternotomy was used. We conclude that sternotomy provides superior exposure for cardiac repair in patients with penetrating anterior chest trauma. We feel it is the incision of choice in hemodynamically stable patients. Thoracotomy should be reserved for unstable patients requiring aortic cross-clamping, or when posterior mediastinal injury is highly suspected.

Adult↗

Essential fatty acids influence survival in sepsis.

Metabolites of arachidonic acid, formed from omega-6 essential fatty acids (n-6), play a pathologic role in mortality from sepsis. Metabolites of eicosapentaenoic acid, formed from omega-3 essential fatty acids (n-3), are less potent inflammatory mediators. Dietary restriction of n-6 fatty acids or supplementation with n-3 fatty acids in the form of fish oil have been shown to decrease the production of n-6 metabolites. Male Sprague-Dawley rats (350-400 g) were divided to receive either rat chow (CHOW) or essential-fatty-acid-deficient chow (EFAD) and subdivided to receive 1 mL daily of either fish oil (N3), linoleic acid (N6), or normal saline (NS), via gastric gavage. Two weeks later, half of the animals in each group underwent cecal ligation and puncture (CLP) to induce peritonitis or sham (SHAM) celiotomy. Survival was tabulated for 7 days. Survival was significantly decreased for animals undergoing CLP for both the N6 and NS groups but not for the N3 group. Omega-3 fatty acids as the sole essential fatty acids or as a supplement to a "routine" diet, when fed to rats for 2 weeks before a septic challenge, improved survival in this peritonitis model.

Animals↗

Computed tomography in the management of blunt thoracic trauma.

Computed tomographic (CT) scanning has proved to be valuable in evaluating the head and abdomen of victims of blunt trauma; CT scans of the thorax often are obtained on patients with blunt torso trauma, but their value for this purpose is unclear. We conducted a prospective study to evaluate the role of chest CT scanning in thoracic trauma. Hemodynamically stable patients at least 18 years old with an estimated Abbreviated Injury Scale--Thorax score of 2 or greater underwent a contrast-enhanced CT scan of the chest, usually in conjunction with CT scans of the head, abdomen, or both. Thirteen patients were dead on arrival, 14 required emergency surgical procedures, and 13 were too unstable to undergo chest CT scan. Thirty-three patients were not included because they refused to participate or the protocol was not followed. Forty-six men (69%) and 21 women with a mean age of 42.7 years completed the study. Sixty-one were injured in motor vehicle crashes, four were injured in falls, and one each was injured by assault and by crushing forces. Injury Severity Scores ranged from 4 to 45, with a mean of 20.5. Four patients died (6%), three from head injury and one from multiple organ dysfunction. Chest roentgenography (CXR) was superior to CT scanning in identifying rib fractures, but CT scanning was more sensitive than CXR for pneumothorax, fluid collections, and infiltrates (p < 0.001); CT scanning also was more specific for aortic injury. Despite this quantitative superiority, the abnormalities missed by CXR but identified by CT scanning infrequently led to a change in management.(ABSTRACT TRUNCATED AT 250 WORDS)

Abbreviated Injury Scale↗

The role of infection in outcome of Multiple Organ Failure.

It is widely assumed that infections are the principal cause and primary outcome determinant of the syndrome of Multiple Organ Failure (MOF) in critically ill patients. Infections are frequent in these patients, but the prevention and treatment of infections may not influence the course of MOF. This study tested the hypothesis that infections play a decisive role in the outcome of MOF. Data were gathered concurrently on all adult patients admitted over an 18-month period to a non-cardiac surgical ICU at a university hospital and recorded in a computer database. Sepsis was defined as a state characterized by at least three of the following: fever, tachycardia, leukocytosis or leukopenia, increased cardiac index, reduced systemic vascular resistance, and hypercatabolism manifested by nitrogen-wasting. The presence of an infection was not required for the diagnosis of sepsis. Mild sepsis was defined as the presence of three or four parameters. Severe sepsis was defined as the presence of five or six parameters. MOF was defined as the development of dysfunction of at least two of the following major organ systems: cardiac, gut, pulmonary, renal, cerebral, and hepatic. Of 749 admissions, 73 patients developed MOF. Thirty four (47%) had a documented source of infection, 37 (51%) had positive blood cultures, and all had sepsis. Hospital mortality was 66 percent (48 of 73 patients). Death could not be predicted by bacteremia (P > 0.25), nor by the presence of an infectious source (P = 1.0), but was strongly associated with severe sepsis (P < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

White blood cell response to burn injury.

Multiple sites of decreased immune response have been discovered, but the instigation of this diffuse immunosuppression remains a matter of much debate. Several investigators have observed immunosuppressive affects of low-molecular weight peptides found in the serum of burn and trauma patients. These substances have been termed suppressive active peptides (SAP). Current research is also focusing on the intricate connection between stress hormones and neurotransmitters, in which there exist a complex information channel between the immune, endocrine, and central nervous systems. It is becoming clear that immune homeostasis may require regulatory influence via immunocompetent cells, along with influences from the central nervous system and a balanced endocrine environment. In fact, macrophages, lymphocytes, and neutrophils contain receptors for many hormones including corticosteroids, insulin, growth hormone, catecholamines, acetylcholine, and endorphins. The dramatic alteration in the hormonal milieu after injury may play a significant role in immunocompetence. Attempts to modulate specific defects in the immune system have been unsuccessful to date. Our goal, to decrease the risk of infection in burn patients, therefore, is meticulous supportive care. This includes not only reducing the risk of invading bacteria, but also increasing the patient's resistance to overall infection. The cornerstone of this support is to restore mechanical barrier function to as near normal as possible. Immediately after injury, vigorous wound management includes several daily debridements combined with wound protection using an appropriate topical antimicrobial substance.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

Injury severity dictates individualized antibiotic therapy in penetrating abdominal trauma.

Antibiotics play a crucial role in reducing the risk of postoperative infection in patients suffering penetrating abdominal trauma. The infection rate for patients with these injuries ranges from 7% to 16%. Single agents with broad-spectrum activity have proven efficacy, but dosage and duration are still controversial. A prospective, double-blinded study was performed on 102 patients randomized to receive one of three antibiotics for a total of 12 hours: cefoxitin (3 doses, 31 patients); ceftizoxime (2 doses, 36 patients); or mezlocillin (3 doses, 35 patients). Two distinct groups at risk for postoperative infection were evident depending on the severity of injury: Group A were those with no colon injury or a colon injury that could be repaired, no evidence of shock, or fewer than 3 organs injured; Group B were those requiring a colostomy, evidence of shock on presentation, or three or more organs injured. All comparisons of the patient populations receiving the different antibiotics showed the two groups to be equivalent. The mean penetrating abdominal trauma index for Group A was 8.8 and 28.2 for Group B. The overall infection rate for Group A was 10.3% and 42.3% for Group B. There was a significant increase in infection rate for all antibiotics except ceftizoxime in Group B compared with group A. The penetrating abdominal trauma index was significantly higher in all patients who developed infection for all antibiotics. In addition, if the surgical wound was closed primarily, patients with colon injuries developed wound infections 71% of the time, and those with small-bowel injuries did so 30% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗