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Biomedical subjects

C W Spearman

Publications and source records attributed to C W Spearman.

17 recordsLinked to original sources

The effect of rapamycin on the healing of the ureteric anastomosis and wound healing.

Rapamycin is a potent immunosuppressive agent that also inhibits fibroblastic activity and therefore may affect the healing of various tissues. The aim of this study was to investigate the effect of rapamycin on wound healing and the healing of the ureteric anastomosis. Large White/Landrace pigs were subjected to a laparotomy and division and immediate anastomosis of the ureter. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on postoperative day 5, and strips of the skin and fascia closure and the ureteric anastomosis excised and used to determine the tensile strength, hydroxyproline levels, and histological changes. The tensile strength and the hydroxyproline levels in the ureter and fascia were lower in the rapamycin-treated animals. There was no difference in the tensile strength in the skin, although the hydroxyproline levels were lower. This study shows that healing of the ureteric anastomosis and fascia and skin closure may be impaired by rapamycin.

Anastomosis, Surgical↗

Effect of rapamycin on the healing of the bile duct.

Besides its potent immunosuppressive properties, rapamycin also has antitumor and antifungal effects. Rapamycin also inhibits the proliferation of fibroblasts and therefore may impair the healing of various tissues. We investigated the effect of rapamycin on the healing of the bile duct anastomosis. The study was undertaken in pigs that were subjected to a laparotomy under general anesthesia. The bile duct was mobilized and divided and immediately reanastomosed. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on the postoperative day 5, then the biliary anastomosis was excised and used to determine the tensile strength, hydroxyproline levels, and the histological changes. The tensile strength and the hydroxyproline levels in the biliary anastomosis were lower in the animals treated with rapamycin. The liver function tests were normal. These studies show that rapamycin may impair the healing of the biliary anastomosis.

Anastomosis, Surgical↗

Restoration of liver mass after partial hepatectomy--implications for living donor liver transplantation.

In living donor liver transplantation, the recipient liver undergoes more rapid regeneration than the remnant liver in the donor. In this study we investigated the factors which may be responsible for the difference in the regenerative response between the donor and the recipient. Long Evans rats were subjected to either partial hepatectomy (PH) or sham operation (SH) and were treated with liver cytosol (C) and cyclosporine (Cy). The rats were sacrificed at 24, 48, 72 and 96 hours and 1 and 2 weeks postoperatively. The livers were removed to determine the liver weight/body weight (LW/BW) ratio and the mitotic index. The mitotic index, serum aspartate transferase (AST) and serum alanine transferase (ALT), although unchanged in the SH groups, were increased in the rats treated with PH + C + Cy, and were greater than after PH only. However LW/BW ratios increased after PH but had returned to preoperative levels by 2 weeks. The changes in LW/BW ratio were not modified by the cytosol or cyclosporine.

Alanine Transaminase↗

Decreasing blood product requirements after orthotopic liver transplantation.

OBJECTIVES: To document the changing blood product transfusion requirements over time during the first 50 orthotopic liver transplantation (OLT) operations performed at Groote Schuur Hospital. DESIGN: The first 50 OLT operations were divided into three groups chronologically and blood transfusion requirements were compared across the three groups. SETTING: Groote Schuur Hospital, Cape Town. SUBJECTS: Forty-seven patients undergoing 50 OLT operations between October 1988 and September 1999. The majority of patients had end-stage chronic liver disease. Patients were divided chronologically into three groups of 16, 17 and 17 patients. OUTCOME MEASURES: The number of units of blood products transfused in each group was quantified. RESULTS: During the study period there was a significant decrease in the number of units of packed red cells, fresh frozen plasma (FFP) and platelets (but not cryoprecipitate) transfused intraoperatively. The median number of units of packed cells decreased from 13.5 in our first 16 patients (group 1) to 5.0 in our last 17 (group 3). The median number of units of platelets transfused was 9 in group 1 and 0 in groups 2 and 3. No platelets were transfused in our last 22 patients. The average cost of blood products transfused intraoperatively per patient in the three groups decreased from R13 034 in group 1 to R11 389 in group 2 to R7 396 in group 3. CONCLUSION: The number of units of blood products transfused during OLT operations has decreased since the programme started 13 years ago. The reasons include increased experience, the use of aprotinin to block fibrinolysis and the selective use of the thromboelastogram to monitor coagulation intraoperatively. OLT need no longer be regarded as wasteful of blood resources. Use of platelets to treat thrombocytopenia need not be empirical.

Adult↗

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.

Adolescent↗

History of liver transplantation at the University of Cape Town and Groote Schuur Hospital.

The liver transplant programme at Groote Schuur Hospital was born out of a rich history of experimental liver transplantation and an active liver clinic. Professor John Terblanche has played a key role in the initiation and success of the programme. In the first 10 years since October 1988, 41 adults have undergone liver transplantation. The cumulative graft survival rates at 1 and 5 years were 74% and 62% respectively.

History, 20th Century↗

Liver transplantation in children--the Red Cross War Memorial Children's Hospital experience.

Liver transplantation for infants and children has been available in South Africa for more than a decade. Current concerns have shifted from an initial target of early post-transplant survival to quality of life in the long term. Since 1985, 175 infants and children have been assessed, with 104 accepted for transplantation. Fifty have had orthotopic liver transplants (OLTx), 48 (3 retransplants) in Cape Town and 2 abroad. Biliary atresia was the most frequent diagnosis (52%) followed by acute liver failure (ALF) (16%). Waiting list mortality has remained high (15%), particularly for the ALF group (50%). Thirty-four patients survive 1 month--14 years post-transplant. Early post OLTx mortality was low (7%) but late morbidity and mortality (23%) were mainly due to viral infection: de novo hepatitis B (5 patients, 2 deaths), EBV-related post-transplantation lymphoproliferative disease (PTLPD) (6 patients, 4 deaths) and CMV disease (9 patients, 4 deaths). Tuberculosis prophylaxis, required in 6 cases, resulted in major morbidity in 1. Hypertension requiring medication along with some compromise of renal function has been present in all but 2 patients. However, all those of school-going age (20) attend school normally and remain in good health and only 3 of the survivors have abnormal liver function tests. Successful liver transplantation is possible in a developing country with limited resources. Scarcity of virus-free donors (HBV and HIV) leading to waiting list mortality and infrequent retransplantation along with long-term consequences of immunosuppression (infection, lymphoma and renal toxicity) remain problems.

Child↗

A novel high molecular weight fibrinogenase from the venom of Bitis arietans.

A fibrinogenase (Ba100) with an apparent molecular mass of 100 kDa under non-reducing conditions and a pI of 5.4 was purified from the venom of the African puff adder (Bitis arietans) by fibrinogen affinity chromatography. Under reducing conditions the protease dissociates into subunits of 21 kDa and 16 kDa. N-Terminal amino acid sequencing showed these two chains to have 66.7% homology and homology to C-type lectins. The fibrinogenase activity of Ba100 cleaves the Aalpha and Bbeta chain of fibrinogen rendering the molecule unable to polymerise into fibrin clots. Ba100 inhibited platelet aggregation in platelet rich plasma, and clot formation in whole blood, in a concentration dependent manner.

Amino Acid Sequence↗

The management of biliary complications following orthotopic liver transplantation.

OBJECTIVE: Review of the biliary complications following orthotopic liver transplantation (OLT) at our institution, and their management and outcome. DESIGN: Retrospective study of medical records of 63 patients who underwent 68 transplant operations. SETTING: The Liver Transplant Unit, Groote Schuur Hospital and Red Cross War Memorial Children's Hospital, Cape Town PATIENTS: Six patients treated for 9 biliary complications. INTERVENTIONS: Reoperation with biliary reconstruction, or non-operative measures by either endoscopic retrograde pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). OUTCOME MEASURES: Clinical outcome and survival following treatment for biliary complications. RESULTS: Biliary complications occurred in 8.8% of patients who underwent transplantation at our institution. These consisted of strictures in 4 patients (with leak in 2), bile leak in 1 patient, and unsuspected primary sclerosing cholangitis (PSC) of the recipient duct in 1 patient. The mean time interval of biliary complications following OLT was 8 weeks (range 3-16). Biliary reconstruction was required in 4 patients while 2 patients were treated by endoscopic stenting. After a mean follow-up period of 30 months (range 1-64), 4 patients remained stable, 1 patient developed progressive stricturing of the intrahepatic ducts requiring repeated PTC dilatations, and 1 patient experienced stent blockages requiring endoscopic stent changes (died of unrelated causes). CONCLUSIONS: The rate of biliary complications following OLT at our institution compares favourably with literature reports. While biliary reconstruction is usually needed, endoscopic stenting appears effective in selected cases of biliary stricture and leak. PSC should be excluded prior to transplantation in young patients with cryptogenic cirrhosis.

Adolescent↗

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↗