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Biomedical subjects

A E Barber

Publications and source records attributed to A E Barber.

27 records · Page 2Linked to original sources
PubMed1991

Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates.

Interleukin (IL)-1 is an early mediator of host response to inflammation, although its contribution to individual components of the acute phase reaction is still unclear. To evaluate how the hemodynamic, metabolic, and hormonal responses to sublethal endotoxemia compare with IL-1 administration, baboons received intravenously either lipopolysaccharide (LPS) or 0.1, 10, or 100 micrograms/kg IL-1 alpha. LPS induced an early tachycardia and a fall in mean arterial pressure, as well as lacticacidemia and hypoaminoacidemia. Similar hemodynamic and metabolic changes were seen with 10 or 100 micrograms/kg of IL-1 alpha. An increase in adrenocorticotropic hormone and fall in serum iron were induced by IL-1 alpha but not by LPS. Plasma tumor necrosis factor-alpha (TNF-alpha) was not measurable after IL-1 alpha administration, whereas LPS induced a monophasic TNF-alpha response. IL-6 levels were significantly greater after LPS than IL-1 alpha administration. Histopathological lesions, similar in LPS- and 100 micrograms/kg IL-1 alpha-treated groups, were present only in the adrenal cortex. We conclude that many, but not all, of the effects of sublethal endotoxemia can be replicated by IL-1 alpha administration, and these responses are dose dependent.

Amino Acids↗
PubMed1990

Unknown primary squamous cell carcinoma metastatic to the neck.

We analyzed retrospectively 157 cases of metastatic neck squamous cell carcinoma from unknown primary sites, treated with surgery, radiotherapy, excisional biopsy, and combined modalities. Median follow-up was 74 months, and overall actuarial survival was 55% at 5 years. The surgery-treated group, despite a higher rate of manifesting primary tumors, had significantly better survival at 5 years compared with those receiving radiation therapy, of whom 23% had residual disease after treatment. Primary tumors were discovered during follow-up in 16% overall. Different treatments yielded comparable results in lower-staged neck disease (NX, N1, N2a), while surgery appeared more effective in controlling advanced disease (N2b, N3a). Factors that affected survival include neck stage, connective tissue invasion, and presence of recurrent or residual disease after treatment.

Carcinoma, Squamous Cell↗
PubMed1990

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.

Animals↗
PubMed1990

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis.

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.

Ampicillin↗
PubMed1990

Additive effects of thermal injury and infection on the small bowel.

Thermal injury is associated with functional alterations of multiple organ systems, including the gastrointestinal tract. To study the effects of ongoing infection after thermal injury on bowel mass, composition, and blood flow, male Wistar rats were randomized to receive either 30% scald burn, 30% scald burn with Pseudomonas aeruginosa wound inoculation, sham burn, or sham burn with pair feeding to burned and infected animals. On days 3 and 7 after injury, intestinal blood flow was measured with 51Cr-labeled microspheres, and intestinal mass and composition were analyzed. Burned and infected animals demonstrated a chronic loss of small bowel mass not seen in burned animals without infection by day 7 after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to but occurring earlier than that seen with anorexia alone and significantly decreased deoxyribonucleic acid and ribonucleic acid content, whereas tissue water content remained unchanged. These chronic intestinal alterations in the burned and infected group could not be explained by ongoing ischemia because intestinal blood flow in these animals was not significantly altered at either time point, implying mediation by other pathophysiologic mechanisms.

Animals↗
PubMedDate not supplied

Matrix metalloproteinase inhibition protects hepatic integrity in hemorrhagic shock.

Hemorrhagic shock increases cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), and compromises hepatic function and integrity. The production of TNF-alpha involves a cascade reaction regulated by the enzyme TNF-alpha convertase. The purpose of this study was to examine the effects of matrix metalloproteinase inhibitor (MMPI) (British Biotech 1101) in vivo on hepatic integrity in a rat model of hemorrhagic shock. Sprague-Dawley rats (n = 26) were divided as follows: hemorrhagic shock (group 1) and hemorrhagic shock plus MMPI (group 2). TNF-alpha, IL-6, and hepatic membrane potentials (Em) were obtained. The administration of MMPI significantly decreased TNF-alpha levels (P <0.001) and stabilized the membrane potential at -30 mV as compared to the depolarized membrane potential at -20 mV for hemorrhagic shock without MMPI. IL-6 levels were not affected by the MMPI. This study demonstrates that MMPI decreases TNF-alpha levels and protects hepatic integrity in hemorrhagic shock, as evidenced by the stabilization of the membrane potential, independent of the mean arterial pressure. The hepatic protection is closely related to the decrease in TNF-alpha levels seen in the portal circulation.

Animals↗
PubMedDate not supplied

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters.

BACKGROUND: Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. METHODS: Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day. RESULTS: Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p < .05) when compared with placebo-supplemented subjects. Blood creatinine levels were not changed. However, blood urea nitrogen increased (p = .01) with HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation. CONCLUSION: These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Harry M. Vars award. Glutamine or fiber supplementation of a defined formula diet: impact on bacterial translocation, tissue composition, and response to endotoxin.

Despite provision of adequate calories, defined formula diets in rats lead to bacterial translocation (BT), fatty infiltration of the liver, and an increased susceptibility to endotoxin. These deleterious effects may be due in part to a loss of intestinal barrier integrity resulting from bowel atrophy. Defined formula diets lack both glutamine and fiber, substances which may help maintain intestinal mass. To determine whether supplementation of defined formula diets with either glutamine or fiber might prevent bowel atrophy and, thus, BT, hepatic steatosis, and the altered response to endotoxin, Wistar rats were fed (1) defined formula diet ad libitum (DFD), (2) (DFD + 2% (w/v) glutamine, (GLUT), or (3) DFD + 2% (w/v) psyllium (FIBER). Rats given standard food isocalorically pair-fed to DFD were used as controls. Nutritional status was assessed by daily weight gain, as well as the ability to maintain serum albumin, hematocrit and white blood counts. After 2 weeks of these feeding regimens, animals were sacrificed, and organ weights and composition were determined, with rates of bacterial translocation determined by mesenteric lymph node, abdominal viscera, and cecal cultures. Additional animals receiving the same experimental diets were subsequently challenged with endotoxin and observed for mortality with rates of post-endotoxin BT and the responses of acute phase proteins and cytokines measured. All dietary regimens resulted in equivalent weight gain and other nutritional parameters. Both glutamine and fiber supplementation maintained small bowel mass, but only GLUT preserved normal jejunal mucosal architecture. Neither fiber nor glutamine supplementation prevented cecal bacterial overgrowth or BT, resulting from the DFD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗