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Biomedical subjects

B W Shaw

Publications and source records attributed to B W Shaw.

At least 73 records · Page 4Linked to original sources

Orthotopic hepatic transplantation in patients with type I diabetes mellitus.

Six transplantations of the liver were performed over a period of six years in five adult patients with Type I diabetes mellitus (DM). The diabetic group included two males and three females with a mean age of 36 years and a mean duration of DM of 20 years. Primary diseases of the liver included two instances of primary biliary cirrhosis, two instances of sclerosing cholangitis and one instance of autoimmune chronic hepatitis. Three patients also received a simultaneous whole organ pancreatic transplant. All patients were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. Patient and hepatic allograft survival rates were 80 and 67 percent, respectively, after a mean follow-up period of 4.7 years. One of the three pancreatic grafts was successful and resulted in euglycemia for two years. Three patients have subsequently undergone successful renal transplantation at one, two and one-half, and six and one-half years after hepatic transplantation. Although transplantation of the liver can be performed safely in carefully selected patients with Type I DM, these patients are still at risk for the development of progressive nephropathy. Renal transplantation is an acceptable therapeutic alternative when this occurs.

Adult↗

Transplantation in the elderly patient.

In summary, as our protocols of immunosuppression improve in selectivity and, more importantly, as we become more adept at tailoring the degree of immunosuppression to the needs of individual patients, both our enthusiasm and our success with organ transplantation in the elderly will improve. This has particular relevance as the average age of our population increases. Arbitrary age limits, largely the products of the 1970s and early 1980s, have now been abandoned. Nevertheless, the enthusiasm to demonstrate skill in treating the older patient must be tempered by an understanding of the extreme shortage of available donor organs. In terms of life-years saved, the older patient offers much less potential than younger patients. At some point, the co-existence of other life-threatening illnesses in older patients must influence our desire to save older lives. One cannot overlook the probability that Medicare coverage of kidney transplantation since 1972 and heart and liver transplantation since the end of the last decade has served as a tremendous stimulus to the enthusiasm for treating older patients. In anticipation of further limits being placed on the availability of dollars for health care, the need for responsible stewardship of our precious donor and health care dollar resources becomes ever more important.

Aged↗

Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

Antigen-Antibody Complex↗

Selective use of Sandostatin in vascularized pancreas transplantation.

Despite improving results, the management of exocrine complications after pancreas transplantation remains problematic. During a 30-month period, we performed 65 pancreas transplants with bladder drainage. A total of 23 patients (35%) were managed with a long-acting somatostatin analogue (Sandostatin) for persistent hyperamylasemia or allograft pancreatitis. Sandostatin was begun at a mean of 29 days after transplant with a mean duration of therapy of 13 days. Sandostatin therapy was associated with significant reductions in the serum, urine, and peritoneal fluid amylase levels (p < 0.05). Sandostatin also caused a decrease in cyclosporine levels during oral cyclosporine use. In patients receiving Sandostatin, pancreas allograft survival was 83%. We conclude that pancreatitis remains a major cause of morbidity after pancreas transplantation. The selective use of Sandostatin can result in excellent graft salvage with low morbidity. Sandostatin appears to be safe and effective in reducing the exocrine output of the denervated pancreas allograft but also reduces cyclosporine levels.

Adult↗

Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection.

Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 1/2-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis A endemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to > 20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

Fulminant hepatic failure after methotrexate and PUVA therapy for psoriasis.

Acute hepatic failure developed after 8-methoxypsoralen and ultraviolet irradiation for psoriasis in a patient with prior methotrexate-induced cirrhosis. Review of the literature and the temporal relationship between 8-methoxypsoralen and hepatic injury in our patient suggests it may be a direct hepatotoxin. In our report, submassive necrosis superimposed on cirrhosis appears to have produced hepatic failure.

Hepatic Encephalopathy↗

Frozen section evaluation of donor livers before transplantation.

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.

Adenosine↗

Conflict of interest in the procurement of organs from cadavers following withdrawal of life support.

The University of Pittsburgh policy for procuring organs from non-heart-beating cadaver donors recognizes the potential for conflicts of interest between caring for a "hopelessly ill" patient who has forgone life-sustaining treatment and caring for a potential organ donor. The policy calls for a separation between those medical personnel who care for the gravely ill patient and those involved with the care of transplant recipients. While such a separation is possible in theory, it is difficult or impossible to attain in practice. However, such a separation of duties would be unnecessary if an arbitrator were appointed to monitor the proceedings as they take place on a case-by-case basis. In this way, the biases--real or potential--of the individuals involved could be identified, and the harmful effects of the unavoidable conflicts of interest could be minimized.

Attitude of Health Personnel↗

Extracorporeal support with a cadaver liver as a bridge to transplantation.

Extracorporeal liver perfusion (ECLP) has been used for detoxifying blood in patients in class IV hepatic encephalopathy. Palliation of the moribund patient utilizing extracorporeal devices with cross-circulation of a cadaver liver has been documented for over three decades. Common problems associated with this procedure which appear in the literature include cadaver liver distention, increased resistance to blood flow, and limited time of extracorporeal support due to cadaver liver failure. This report summarizes the experiences of the perfusion team in utilizing an extracorporeal circuit with an otherwise nontransplantable cadaveric liver, to support the decompensating hepatic patient as a bridge to transplantation. Between January and July 1992, three patients were supported for hepatic failure with ECLP. Two patients were placed on ECLP with a modified circuit containing two positive displacement pumps and one centrifugal pump. The third patient was placed on ECLP with a circuit that contained two centrifugal pumps and one positive displacement pump. Patient age ranged from 6 to 38 years and length of support ranged from 24 to 72 hours. In all three patients, a centrifugal pump was placed in the suprahepatic inferior vena cava line to facilitate cadaver liver drainage and decompression. Intensive monitoring of both patient and cadaver liver hemodynamics, hepatic function, and hematological status was performed. All three patients were successfully weaned from ECLP. Two patients received successful orthotopic liver transplantation. The third died of complications unrelated to ECLP after support was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Liver transplantation.

From more than 900 articles in the medical literature, published between August 1, 1991 and July 31, 1992, 46 were selected for review. During the year of review, major international symposiums were held on a new drug, FK506, and intestinal transplantation. In addition, at least one new attempt at a unifying hypothesis regarding graft adaptation was proposed. Other studies included living related donor transplantation, results with transplantation for alcoholics, and the controversy regarding the role of liver transplantation for the treatment of Budd-Chiari syndrome. Concerns regarding the recurrence of both hepatitis and primary hepatic malignancy following liver transplantation were also addressed. Two innovative approaches to the treatment of acute liver failure offer exciting promise for the future. Other subjects include histologic evaluation of renal dysfunction in patients with liver disease, quality of life after transplantation, and the proper distribution of precious donor livers.

Adult↗

Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group.

This report describes the clinical characteristics and demographics of patients enrolled into this rescue trial for patients experiencing refractory rejection after liver transplantation. Actuarial graft and patient survival at 12 months postconversion was 50% and 72%, respectively. Actual treatment success at 3 months postconversion was 70%. Karnofsky scores and liver function tests were significantly improved for patients continuing on therapy indicating clinical benefit in these patients. The safety profile of FK 506 is acceptable for such a high-risk group of patients. These preliminary clinical results support the conclusion that FK 506 can effectively control and reverse refractory rejection in a majority of liver transplantation patients.

Acute Disease↗

The analysis of benefit and risk of combined pancreatic and renal transplantation versus renal transplantation alone.

Currently, diabetes mellitus is the most common cause of renal failure in adults. However, combined pancreatic and renal transplantation (PRT) remains controversial when compared with renal transplantation alone (RTA) in diabetic recipients. We analyzed the results and morbidity in four age-matched groups--31 patients with Type I diabetes undergoing PRT before dialysis, 30 patients with diabetes who are dependent of dialysis undergoing PRT, 31 concurrent and historic patients with Type I diabetes undergoing RTA and 31 concurrent patients without diabetes undergoing RTA. All patients received cadaver donor organs and were managed with cyclosporine and prednisone immunosuppression with selective OKT3 induction. The four groups were comparable with respect to age, weight, gender, duration and severity of diabetes, dialysis type, number of retransplants, degree of sensitization, preservation time and matching. The groups differed with regard to duration of dialysis and period of follow-up evaluation, pretransplant blood transfusions, racial distribution and OKT3 induction therapy. PRT was associated with a greater morbidity rate as evidenced by a slightly higher incidence of rejection, infections and reoperations. The number of readmissions and hospitalization period during the first 12 months was also greater after PRT versus RTA. However, none of these differences were significant. No detrimental effect was noted on renal allograft function at one year; patient and graft survival was actually higher in the PRT groups. Quality of life was improved in nearly 90 percent of PRT recipients. Although the improved results after PRT may be attributed to selection bias, only lesser differences were noted among the four study groups. The aforementioned data suggest that appropriate patient selection can overcome the morbidity associated with PRT, resulting in excellent patient and graft survival with the potential for complete rehabilitation.

Actuarial Analysis↗