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Biomedical subjects

B J Rowlands

Publications and source records attributed to B J Rowlands.

At least 145 records · Page 8Linked to original sources
PubMed1989

Structural and functional alterations in the zona fasciculata of the rat adrenal cortex in obstructive jaundice.

This study investigated the effect of experimentally-induced cholestasis in the rat on the structure and function of the zona fasciculata, the glucocorticoid secretory region of the adrenal cortex. Wistar-Furth rats (200-250g) were assigned to three groups: bile duct ligated (BDL), Sham operated (Sham) and unmodified normal control (NC). On day 14, serum bilirubin and liver histology were performed to confirm cholestasis in BDL animals together with basal 24 hour 17-hydroxycorti-costeroid excretion, adrenal histology and zona fasciculata ultrastructure in all experimental groups. Following this laparotomy, structural and functional studies were repeated on day 15 to evaluate the response of the gland to surgically induced stress. Basal 24 hr, 17-hydroxycorticoid steroid excretion was elevated in BDL animals (26.9 +/- 3.2 micrograms/24 hr) with respect to Sham (10.4 +/- 2.3) and NC groups (13.5 +/- 3.2) (p less than 0.05). Adrenal histology and ultrastructural studies demonstrated excessive accumulation of vesicles laden with glucocorticoid biogenic precursors. Following surgical stress 24 hr 17 OH corticosteroid excretion increased in all groups: BDL (31.0 +/- 3.0 micrograms/24 hr) vs Sham (15.6 +/- 1.8) and NC (14.5 +/- 2.4) Moderate alterations in zona fasciculata architecture were seen following surgery in all groups. Cholestasis induces overactivity of the zona fasciculata of the adrenal cortex, and may modify the normal metabolic responses to surgical and other stresses.

17-Hydroxycorticosteroids↗
PubMed1989

Prophylactic antibiotics in trauma: the hazards of underdosing.

Prophylactic antibiotic regimens in trauma patients may be significantly altered by large fluid shifts and hyperdynamic physiologic responses. We prospectively studied prophylactic amikacin and clindamycin in 150 abdominal trauma patients requiring laparotomy, analyzing the effects of duration of coverage, dosing interval, and dose. No difference in infection rates was noted when 72-hour coverage was compared with 24-hour coverage (19% vs. 21%). Clindamycin dosed at 1,200 mg every 12 hours achieved acceptable serum concentrations; infection rates were not significantly higher than seen with 600 mg every 6 hours (21% vs. 12%, p greater than 0.05). High-dose (11 mg/kg) amikacin reduced infection rates in patients with high blood loss (p less than 0.025), high Injury Severity Scores (p less than 0.025), and no colon penetration (p less than 0.005). These data suggest that high doses are more effective than long courses of antibiotics in reducing infections in trauma patients undergoing laparotomy.

Abdominal Injuries↗
PubMed1988

Urgent thoracotomy for pulmonary or tracheobronchial injury.

Three hundred eighty-eight of 7,283 (5.3%) admitted trauma patients underwent urgent thoracotomy. In 61 patients (15.7%), pulmonary or tracheobronchial injury prompted thoracotomy (11, blunt; 50, penetrating). Pulmonary hemorrhage necessitated thoracotomy in 54 patients (88.5%); tracheobronchial injury in five patients (8.2%). The mortality was 27.9%. Nine patients (14.8%) underwent pneumonectomy: eight died of intractable hemorrhagic shock during thoracotomy despite rapid control of pulmonary hemorrhage: one died of sepsis. Eleven patients (18.0%) underwent lobectomy: six (54.5%) died of concomitant injuries. Thirty-six patients (59.0%) underwent pneumonorrhaphy: one died of concomitant injuries. Five (8.2%) patients underwent tracheobronchial repair: one died of concomitant injuries. Pneumonectomy was uniformly fatal and should be a procedure of last resort in the treatment of pulmonary injury, as lobectomy and pneumonorraphy are better tolerated by these critically ill patients.

Bronchi↗
PubMed1988

The influence of hepatocellular function on NK and T cell tumoricidal activity.

Recent studies by this group have demonstrated that hepatocellular integrity is important in the preservation of host cellular immune function. This study evaluated the effect of experimental hepatocellular dysfunction (EHD) on host antineoplastic defense mechanisms. In nonspecific immune studies, we examined the effect of EHD on Wistar Furth (WF) natural killer (NK) cell cytotoxicity; in specific immune studies, we assessed WF C3H/HeJ lymphocytic responsiveness to both T cell mitogen and unmodified syngeneic fibrosarcoma. In concurrent studies, we evaluated the effect of EHD on interleukin-2 (IL-2) synthesis, an important NK and T cell trophic factor. WF rats and C3H/HeJ mice were assigned to three groups: EHD induced by bile duct ligation, sham, and normal control (NC). At day 21 serum bilirubin, WF NK cytotoxicity to YAC-1 tumor cells, WF and C3H/HeJ lymphocytic responsiveness to phytohemagglutinin (PHA) and syngeneic MCA-fibrosarcoma (MCA-F), and WF T-helper IL-2 production were determined in respective groups. Serum total bilirubin was elevated in EHD rats and mice with respect to controls (p less than 0.01). Wistar Furth cytotoxicity to the YAC-1 tumor cells was depressed in EHD animals with respect to sham and NC groups at 12.5:1 (p less than 0.01), 25:1 (p less than 0.05), 50:1 (p less than 0.05), and 100:1 (p less than 0.05) effector/target cell ratios. WF T cell responsiveness to PHA was depressed in EHD with respect to controls (p less than 0.01). C3H/HeJ lymphoproliferative response to MCA-F tumor antigen was also depressed in EHD animals when compared with control groups with the addition of 12.5 X 10(3) (p less than 0.05) and 50 X 10(3) (p less than 0.05) MCA-F cells. These impairments in NK and T cell function in EHD could not be attributed to diminished IL-2 production (EHD vs sham and NC: 112,141 +/- 5232 vs 106,691 +/- 1419 and 120,759 +/- 3248 cpm, respectively). These results demonstrate that hepatocellular failure compromises NK and T cell tumoricidal function, an effect not resultant on diminished T helper IL-2 production.

Animals↗
PubMed1988

Endotoxemia and cholestasis.

Endotoxemia has been incriminated as a major cause of morbidity and mortality in patients with obstructive jaundice. It has been postulated that absence of gastrointestinal bile salt flow in cholestasis enhances portal absorption of bacterial endotoxin from the intestine, thereby predisposing the host to endotoxemia and its complications. This study re-evaluates this pathologic mechanism, using new quantitative chromogenic and conventional qualitative limulus techniques for the detection of bacterial endotoxin. Female Sprague-Dawley rats underwent either ligation of bile duct or sham operation. Serum total bilirubin, serum bile acid and intestinal bile acid concentrations were determined seven, 14 and 21 days after operation. Chromogenic and conventional qualitative limulus lysate endotoxin determinations were simultaneously performed on post-operative days two, seven, 14 and 21. Serum total bilirubin and bile acid concentrations were elevated and intestinal bile acid levels depressed at days seven, 14 and 21 (p less than 0.05). Results of quantitative and qualitative limulus studies failed to demonstrated the coexisting development of portal or systemic endotoxemia in rats with the bile duct ligated after diminution of flow of gastrointestinal bile salt. These data refute the hypothesis that flow of gastrointestinal bile salt enhances portal absorption of intestinally derived endotoxin and suggest alternative mechanisms are involved in the pathogenesis of endotoxemia in obstructive jaundice.

Animals↗
PubMed1987

The protective effect of hepatic dysfunction on vascularized allograft survival.

Recent studies have demonstrated that hepatic dysfunction, induced by experimental biliary ligation (EBL), impairs lymphocytic responsiveness to PHA stimulation in vitro and to cellular antigens in vivo. This suppression appears to be selective for T-cell mechanisms while B-cell-mediated functions remain intact. The purpose of this study was to determine whether coexisting hepatic insufficiency could exert a protective effect on vascularized or nonvascularized allograft survival in the transplanted recipient. Female Wistar-Furth (Rtlw) 225 g rats were assigned randomly to three groups: EBL, sham operation (Sham) and normal control (NC). Fourteen days following operation animals received heterotopic cardiac or skin allografts from Buffalo (Rtlb) donors. Cardiac and skin graft survival was determined daily, rejection was confirmed histologically, and technical failures were omitted from analysis. Allograft survival was expressed as median survival time +/- SEM. Serum total bilirubin (mean +/- SEM) was significantly elevated at Day 14 in EBL animals compared to Sham and NC groups (15.1 +/- 1.0 vs 0.1 +/- 0 and 0.2 +/- 0.1 mg/dl, respectively, P less than 0.01). Median cardiac allograft survival time by Probit was 10.6 +/- 2.6 vs 5.6 +/- 0.7 and 6.0 +/- 0.9 days, respectively (P less than 0.03). Skin graft survival (mean and range) was similar in all groups. These results demonstrate that EBL in the rat suppresses T-cell function and significantly prolongs vascularized allograft survival, but not skin allograft survival across the Rtl histocompatibility barrier. The mechanism whereby coexisting hepatic dysfunction exerts a protective effect on vascularized allograft survival warrants further investigation.

Animals↗
PubMed1987

Biochemical consequences of protein depletion in the rabbit heart.

We showed previously that cardiac function was depressed in rabbits subjected to 6 weeks of protein depletion and was restored after 4 weeks of protein refeeding. To identify nutritional or metabolic factors that underlie cardiac dysfunction, we assessed the nutritional status and myocardial content of energy-providing substrates in three groups of rabbits: group I served as control; group II was fed a protein-free diet; and group III was fed a protein-free diet and then repleted. Animal weights were 2.73 +/- 0.22 kg in group I, 1.92 +/- 0.28 kg in group II, and 2.78 +/- 0.12 kg in group III. Serum albumin concentrations decreased from 3.70 +/- 0.12 g/dl in group I to 2.81 +/- 0.10 g/dl in group II, and returned to normal (3.71 +/- 0.11 g/dl) in group III. The heart weights; myocardial contents of water, nitrogen (N), total fat, and glycogen; skeletal muscle N concentrations; and liver N contents were measured. Protein depletion produced a reduction in total cardiac mass due to decreased nitrogen and glycogen contents, but there was an increased fat content. Comparison with other organs suggests that cardiac muscle plays a role in energy homeostasis, undergoing glycogenolysis and proteolysis similar to those of liver and skeletal muscle. Protein repletion restored normal mass of the heart, but not of the liver. We conclude that adequate nutrition may be important in maintaining cardiac function.

Animals↗
PubMed1987

Postoperative alterations in interorgan glutamine exchange in enterectomized dogs.

The effect of enterectomy on postoperative visceral organ glutamine exchange was studied in order to gain further understanding of the role of the intestinal tract in the altered glutamine metabolism that occurs following catabolic illness. In addition to studying glutamine, which transports 1/3 of whole blood amino acid nitrogen, we determined the fluxes of glutamate and alanine across the gastrointestinal tract, liver, and kidneys in 18 postoperative dogs. Arterial glutamine and glutamate were significantly higher in enterectomized animals than in controls. With enterectomy the gut became an organ of glutamine balance while in control dogs the GI tract consumed glutamine (0.11 +/- 0.04 vs 1.67 +/- 0.14 mumole/kg X min, P less than 0.001). The gut switched from an organ of glutamate release to one of net glutamate uptake following enterectomy and intestinal alanine release simultaneously fell by 50%. Simultaneously, the liver reduced its uptake of alanine and became an organ of glutamine release. Renal glutamine consumption was also diminished in enterectomy animals. The interorgan exchange of glutamine and other amino acids is altered by enterectomy. The increase in circulating glutamine levels in enterectomized animals suggests that the accelerated intestinal glutamine consumption that characterizes catabolic illnesses contributes to the low glutamine levels in these stress states. In addition, it becomes apparent that the gut is an important supplier of alanine to the liver, which supports gluconeogenesis. Metabolic adaptation and cooperation between organs is essential during organ absence or dysfunction if the organism is to survive critical illness.

Alanine↗
PubMed1987

Impaired nonspecific cellular immunity in experimental cholestasis.

The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice.

Animals↗
PubMed1987

General metabolism in head injury.

Seventy-six patients with closed head injuries alone were studied to define the relation between the severity of the head injury and secondary alterations of general metabolism. The effect of metabolic changes on neurological outcome and the importance of nutritional support on nutritional status and neurological outcome were also evaluated. Using a powerful statistical tool, convergence analysis, it was possible to take into consideration the effects of a number of confounding factors that obviously affected general metabolism. Most of the patients were hypermetabolic for prolonged periods. In addition, many did not receive even basal requirements of calories or protein for many days. Despite this, their outcomes were determined by their initial neurological status and the amounts that they were fed, admittedly relatively modest, did not influence their courses. Despite such feedings, their visceral protein levels, which often dropped initially, rose toward normal levels, indicating effective adaptation. Indeed, it could not be shown that these patients developed complications of malnutrition such as infections. However, it will require a sophisticated randomized clinical trial of vigorous intravenous hyperalimentation to determine whether this complex, dangerous, and expensive therapy is helpful for severely head-injured patients.

Craniocerebral Trauma↗
PubMed1987

Infected aortic aneurysm after intraabdominal abscess.

Infected abdominal aortic aneurysm is rarely associated with an antecedent history of a localized suppurative process. This report describes a case in which an infected aortic aneurysm occurred after surgical treatment of an appendiceal abscess. Diagnosis and management of infected aneurysms are discussed, together with a review of the literature.

Journal Article↗
PubMed1987

Energy sources for intravenous nutrition.

Controversy exists concerning the appropriate use of carbohydrate solutions and fat emulsions as energy sources in intravenous nutritional regimens. Current evidence suggests that glucose is the carbohydrate energy source of choice and that when infused with appropriate quantities of protein it provides cheap and effective nutritional support in the majority of patients and clinical circumstances. During glucose infusion, blood glucose and acid-base balance should be closely monitored and, when indicated, exogenous insulin should be added to the regimen to combat hyperglycaemia and improve protein anabolism. Fat emulsions, although expensive, may justifiably be used in patients with moderate or severe stress to provide up to 50% of non-protein energy, especially in circumstances where attempts to satisfy energy requirements exclusively with glucose would impose an additional metabolic stress.

Energy Metabolism↗
PubMed1987

Penetrating abdominal trauma: the use of operative findings to determine length of antibiotic therapy.

Penetrating abdominal trauma is associated with a high incidence of postinjury infection which can be reduced by appropriate surgical management and short-term antibiotic therapy. Patients at high risk for developing infectious complications may be identified on the basis of operative findings and the duration of the postinjury antibiotic regimen determined. Colonic injury is the most important determinant of infectious complications. Number of other organs injured, age, and mode of injury have little or no additional impact on infection rates. Low-risk patients can be successfully managed with three perioperative doses of antibiotics. Nontrauma related nosocomial infections appear to be associated with trauma related infections in high-risk patients. Intravenous clindamycin plus tobramycin and metronidazole plus tobramycin for 72 hours postinjury are equally effective in reducing postinjury infections in "high-risk" patients.

Abdominal Injuries↗
PubMed1986

Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage.

Little is known of the effect of cholestasis on host immunity. This study evaluates lymphocytic responsiveness to PHA and LPS mitogen and to allogeneic F344 antigen in Sprague-Dawley rats 21 days following bile duct ligation and 31 days following relief of jaundice by internal biliary drainage. Serum bilirubin level was significantly elevated in the bile duct ligated animals at Day 21 (P less than 0.001) and thereafter returned to preoperative levels following internal biliary drainage. Results demonstrate depressed responsiveness to PHA (P less than 0.001) and allogeneic F344 antigen in vivo (P less than 0.04) and in vitro (P less than 0.02) in bile duct ligated animals as compared to sham, sham pair-fed, and normal control rats. The observed deficiency in responsiveness to T-cell-dependent mitogen and antigen cannot be explained on the basis of complicating nutritional, renal, or infective factors. Subsequent internal biliary drainage results in some improvement in T-cell responsiveness in the bile duct ligated group although recovery is not complete. B-Lymphocytic response to LPS mitogen is not affected by bile duct ligation. We conclude that cholestasis subsequent to extrahepatic biliary obstruction per se results in impairment of cell-mediated immunity in vivo. This impairment is partly reversible by internal biliary drainage. In vitro B-cell function does not appear to be affected in this model. Further study of impaired cell-mediated immunity in extrahepatic biliary obstruction will improve our understanding of the immunological status of patients with obstructive jaundice and cholestatic liver diseases.

Animals↗
PubMed1986

Changes in nutritional status associated with obstructive jaundice and biliary drainage in rats.

Effect of bile duct ligation (BDL) and internal biliary drainage on food intake and nutritional status was studied in rats and compared with sham and pair-fed animals. During week 1, food intake of BDL animals was reduced (p less than 0.05), resulting in weight loss (p less than 0.05). In weeks 2 and 3, food intake, nitrogen balance, and weight gain were similar in all groups. Internal biliary drainage or sham operation after 3 wk produced transient changes in food intake and N2 balance. Serum albumin fell in all groups, returned to normal in sham (3.2 +/- 0.1 g/dl) and pair-fed (3.1 +/- 0.1 g/dl), but persisted in BDL rats (2.4 +/- 0.2 g/dl, p less than 0.001). Jaundice was associated with anemia. Although BDL produces transient changes in food intake, weight gain, and N2 balance, anorexia and malnutrition are not features of this animal model. Nutritional risk factors associated with hyperbilirubinemia are probably due to changes in intermediary metabolism.

Animals↗