Search PubMed⌕ Search

Biomedical subjects

R Hickman

Publications and source records attributed to R Hickman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Plasma fibronectin levels during acute rejection and acute tubular necrosis in renal transplant patients.

Fibronectin (Fn), an acute phase glycoprotein synthesized by the liver, has an important immunomodulatory role. We have investigated the changes in plasma Fn in patients after renal transplantation in order to determine whether these changes predict graft injury or rejection episodes. Besides normal healthy controls, healthy pregnant controls, and a trauma control group, we used two groups of chronic renal failure patients as controls: group I, patients with end-stage renal failure (ESRF) on peritoneal dialysis; group II, patients with ESRF on hemodialysis. These were compared with two groups of renal transplant patients: group III, patients 3 months after successful renal transplantation; group IV, patients studied sequentially 10 days immediately posttransplantation. The renal transplant patients were treated with low-dose cyclosporine, azathioprine, and steroids. Citrated plasma samples were collected for Fn assay by a sandwich-type ELISA and for SDS-PAGE analysis and Western blotting. The mean plasma Fn levels were as follows: healthy controls 311.6 SEM, 13.5 micrograms/ml; healthy pregnant controls 357 SEM, 5.9 micrograms/ml; trauma controls 262.3 SEM 31.7, micrograms/ml; group I 169 SEM, 25.1 micrograms/ml; group II 199 SEM, 27.2 micrograms/ml; group III 272 SEM, 21.7 micrograms/ml; group IV 212 SEM, 27.4 micrograms/ml (day 3 postop). There was a significant difference in the plasma Fn levels on day 3 posttransplant between the patients with delayed and immediate renal function (P less than 0.03) (group IV). A significant decrease in plasma Fn levels occurred immediately after steroid therapy was stopped (P less than 0.03) in patients treated for acute rejection. Plasma Fn levels were significantly decreased in the presence of delayed graft function but did not predict rejection.

Fibronectins↗
PubMed1992

Presentations to the Surgical Research Society of Southern Africa--the second 10 years (1982-1991).

Over the 10-year period 1982-1991, 594 papers were read at the annual meetings of the Surgical Research Society of Southern Africa. One hundred and thirty-five (23%) reported work performed on experimental animals with a trend to an increase from this base; 152 (26%) were presentations from surgeons-in-training, also with a trend to increase over the decade. The distribution by subspecialty was: upper gastro-intestinal tract 28%; hepatobiliary 12%; vascular 16%; immunology/transplantation 9%; further subspecialties 9%; and miscellaneous 26%. Major observations are that the number of papers has doubled since the first decade, probably due to establishment of the poster session, and that presentations by surgeons-in-training remain in the minority at the Society.

General Surgery↗
PubMed1992

Orthotopic liver transplantation at Groote Schuur Hospital.

We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation.

Adult↗
PubMed1991

Administration of sucralfate prolongs survival of animals with experimental peptic ulceration.

Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation.

Aluminum Hydroxide↗
PubMed1991

Animal models of fulminant hepatic failure.

The six requirements for a satisfactory animal model of fulminant hepatic failure are reversibility, reproducibility, death from liver failure, a therapeutic window, a large animal model, and minimal hazard to personnel. Different models may be required to evaluate the various types of liver failure seen in man. The available models include surgical anheptic and devascularization procedures, as well as hepatotoxic drug administration using agents such as carbon tetrachloride, acetaminophen, or galactosamine. Currently combined surgical and drug models appear to provide the best model but the search for the ideal models continues.

Acetaminophen↗
PubMed1991

Six-hour porcine liver storage without flushing or perfusion.

Livers from normal porcine donors were preserved by surface cooling only, without flushing or perfusion, for periods up to 24 hr. All recipients of livers stored for 6 hr survived until sacrifice at 7 days. In a separate, similar group, survival up to 21 days was noted. Only 2 of 6 recipients survived after 9-hr liver storage, but one of these lived for greater than 120 days. No animals survived longer than 2 days after transplantation of livers stored for 12 or 24 hr. The changes in plasma levels of aspartate aminotransferase of recipients of 6-hr surface-cooled livers were not significantly different from AST levels of recipients of livers stored in University of Wisconsin or Euro-Collins solution as observed in previous studies in this laboratory. At sacrifice after 7 days, there was no histologic evidence of damage after surface cooling. In the light of recent reports of evidence of endothelial and reticuloendothelial damage caused by flushing solutions, it is suggested that surface cooling of the liver may provide adequate preservation for 6 hr in appropriate circumstances. Further studies will be needed to confirm that this method of preservation is applicable to livers removed from brain-dead donors and that it does not cause endothelial damage.

Animals↗
PubMed1991

Comparison of the effects of semi-occlusive polyurethane dressings and hydrocolloid dressings on dermal repair: 1. Cellular changes.

The effects on dermal repair of two wound dressings, one the semi-occlusive polyurethane sheet Opsite, the other the hydrocolloid Granuflex, were compared in full-thickness excised lesions on porcine skin during the period from 5 d to 6 months after injury. Quantitative studies were made of changes in the populations of polymorphonuclear leucocytes, macrophages, fibroblasts, and endothelial cells. The progress of repair in the wounds covered with the semi-occlusive dressing showed a decrease in the number of inflammatory cells (polymorphonuclear leukocytes and macrophages) from 5 to 60 d, whereas the number of proliferative phase cells (fibroblasts and endothelial cells) increased from 5 to 7 d. The total cellularity per unit area showed an increase between 5 and 7 d, that is, during the proliferative phase of repair, and then progressively decreased as the proliferative phase was succeeded by the remodeling phase. In contrast, the repair process in the hydrocolloid-dressed wounds was more complex. The number of inflammatory cells remained relatively high throughout and there were consistently fewer endothelial cells present throughout. Fibroblast number showed an initial fall from 5 to 14 d but then started to increase in number from 21 to 60 d. This chronic inflammatory reaction appeared to be in response to particulate matter that had been incorporated into the wound bed and hypodermis, and was still apparent 6 months after injury, when hydrocolloid particles were detectable microscopically in the hypodermis.

Animals↗
PubMed1991

Heparin as the cause of coagulopathy which may complicate grafting of the liver.

Disposal of heparin is accomplished rapidly by the normal liver, but the effects of ischemia, flushing and hypothermia during hepatic transplantation have not been investigated before. The results of the present study showed that neither laparotomy, hypothermia nor insertion of the portosystemic bypass seemed markedly to affect the coagulation profile, but autograft associated with 30 to 45 minutes of warm ischemia resulted in a twofold prolongation of the t1/2 heparin as calculated from sequential measurements of the activated clotting time. Unexpectedly, the storage of livers for four hours in EuroCollins solutions seemed to result in more rapid disappearance of heparin than in animals after laparotomy. After hepatectomy, the clearance of heparin was delayed for two hours but, thereafter, the slope of the disappearance resembled that in sham operated animals. Autograft and allograft of livers in normal pigs that did not receive transfusion were also associated with changes in fibrinolysis and declining levels of fibrinogen together with severe intraoperative bleeding problems and rapid death on the operating table in 30 per cent of the pigs. While administration of heparin alone did not appear to precipitate these changes, use of the drug after dissection, mobilization and storage of the liver may release other tissue factors that activate fibrinolysis.

Animals↗
PubMed1990

The relevance of the order of revascularization in liver grafting.

A study was conducted comparing the effects of initial arterialization vs. initial portal revascularization in unstored warm ischemic (for 30 min) livers, livers stored for 4 hr at 0 degrees C in Collins solution and livers rendered warm ischemic for 1 hr before removal and replacement as autografts. All livers that received initial arterialization showed uniform diffuse perfusion, whereas those with initial portal perfusion were patchy and well perfused only in the right lobe. In the experimental animal, initial arterialization using an end-to-end method was much easier and required less retraction. The energy charge and ATP levels dropped sharply during brief warm ischemia but returned rapidly to normal on revascularization. Although the decline in energy charge was less in stored livers, the return to normal was slower and incomplete. Plasma levels of AST indicated much greater damage in the stored livers and were lowest in recipients in unstored livers that were arterialized first. After longer warm ischemia, energy charge values declined and only completely returned to 60% of preoperative values within 2 hr of grafting. Despite this, the survival rate of these animals was very poor and only one survived overnight. Seven of the 12 survived the procedure, but in five death occurred within 30 min of full revascularization. In this group, AST levels rose sharply after revascularization to a mean level of 1,000 U.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1990

Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose.

Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods.

Animals↗
PubMed1990

Function of kidney grafts from brain-dead donor pigs. The influence of dopamine and triiodothyronine.

There are conflicting reports about the effects of administration of dopamine to brain-dead donors upon posttransplant organ function. This study compared the survival and serum creatinine levels in pigs that received renal grafts from untreated controls, from controls in which either the donor or donor and recipient received dopamine or from animals rendered brain dead for 16 hr by acute elevation of intracranial pressure, and given standard supportive treatment. In two additional groups, brain-dead donors were given dopamine or dopamine with triiodothyronine. Recipients of grafts from control animals or from brain-dead donors survived the 7-day period of study and showed minimal changes in serum creatinine. Recipients of grafts from brain-dead donors given dopamine however showed reduced survival and progressive increase in serum creatinine. This did not occur in the group given triiodothyronine concurrently with dopamine. It is suggested that if administration of dopamine is essential to treat donor hypotension, concurrent use of triiodothyronine may preserve posttransplant renal function.

Animals↗
PubMed1990

Ileocolectomy enhances the regenerative response after partial hepatectomy in the pig.

Although portal blood has been shown to be more hepatotrophic than peripheral venous blood, the origin and nature of the factors responsible remain obscure. In this study the effect of partial ileocolectomy (IC) or partial ileal resection (I) on the regenerative response after 50% partial hepatectomy (PH) in the pig was investigated using thymidine kinase activity and mitotic figures as indices of regeneration. IC with 50% partial hepatectomy resulted in a significantly greater regenerative response on the 3rd day than hepatectomy alone or hepatectomy plus partial I. Levels of plasma insulin were elevated after PH and I but not after IC, although there were no significant differences in levels of plasma glucagon or plasma glucose. Levels of aspartate amino-transferase were similar in all groups. These results extend previous data and suggest that the proximal colon may be the source of a regeneration inhibitory factor.

Animals↗
PubMed1989

Sucralfate in the prevention of porcine experimental peptic ulceration.

Sucralfate is the first drug to be shown to prevent ulceration in bile duct-ligated pigs. Usually such ulceration is uniformly fatal. Seven pigs in each of four groups in this study received only saline, or sucralfate (1 g every six hours), famotidine (40 mg per day), or misoprostol (200 micrograms every six hours). A Foley catheter was placed into a gastrectomy after bile duct ligation. Similar groups of sham-operated pigs were also prepared. After 48 hours, all saline-, famotidine-, or misoprostol-treated pigs showed severe macroscopic ulceration, whereas only two of those treated with sucralfate showed minimal macroscopic ulceration. Until now, only highly selective vagotomy has reduced ulceration caused by bile duct ligation. The present results suggest that acid inhibition is not the only important factor in healing bile duct ligation-induced peptic ulceration.

Alprostadil↗
PubMed1989

The aminopyrine breath test predicts the outcome of hepatic transplantation in pigs.

The aminopyrine breath test has been performed on Day 1 and Day 7 in pigs following experimental liver allografting. The results show that at 24 hr after surgery there was a significant reduction in liver function in all animals as measured by the elimination rate constant of 14CO2 in the breath. This was very profound in the group that died within 5 days (0.09 +/- 0.01 hr-1) and was significantly different from the group that survived (0.16 +/- 0.01 hr-1). There appears to be a critical value of the elimination rate constant (= 0.12 hr-1) which predicts death within 5 days. These results would justify a trial of the aminopyrine breath test in patients after liver transplantation.

Aminopyrine↗
PubMed1989

Reticuloendothelial function and plasma fibronectin in a murine model of intra-abdominal sepsis.

The lung is the target organ most frequently involved in the early phase of multiple organ failure. Microembolisation of the pulmonary vasculature by bacterial and non-bacterial particles and debris with failure of the clearance mechanism of the reticuloendothelial system (RES) and depletion of plasma fibronectin have been implicated in the pathogenesis. The present study examined the concurrent changes in plasma fibronectin, RES phagocytic function, organ localisation of bacterial and non-bacterial particles and the levels of circulating endotoxin and fibrin degradation products in a clinically relevant murine model of severe intra-abdominal infection. Progressive sepsis was associated with deteriorating RES phagocytic function to 45% of control values within 48 h of sepsis induction. There was decreased hepatosplenic uptake and increased pulmonary localisation of bacterial and lipid emulsion particles. Plasma fibronectin increased in septic animals within 48 h suggesting increased fibronectin production. These changes would support the hypothesis that altered RES function may facilitate pulmonary microembolisation in the pathogenesis of septic multiple organ failure.

Abdomen↗