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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 181 records · Page 10Linked to original sources
PubMed1988

Topological localization of a segment of the eel voltage-dependent sodium channel primary sequence (AA 927-938) that discriminates between models of tertiary structure.

Antibodies were raised against a synthetic peptide corresponding to residues 927-938 of the eel electroplax sodium channel primary sequence. This segment, lying between putative internal repeat domains II and III, is postulated to be exposed on the cytoplasmic surface of the membrane in several recent models of channel tertiary structure and on the external surface in another. The antiserum and affinity-purified IgG derived from it specifically recognize the peptide and the eel sodium channel in a solid-phase radioimmunoassay and bind to a single diffuse band of 260-280 kDa on Western blots of eel electroplax membrane proteins. All reactions are blocked by co-incubation of the antibodies with the synthetic peptide (1 microM). The antibody immunoprecipitates the solubilized channel in a form that retains its characteristic high-affinity binding of saxitoxin. In eel electroplax, the antibodies label only the innervated membrane known to contain sodium channels; at the ultrastructural level, this labeling is exclusively associated with the cytoplasmic surface of the membrane. Sodium channels containing the epitope are not seen in the postsynaptic membrane or in the membrane of the presynaptic nerve terminal. Segment 927-938 of the eel sodium channel is accessible on the surface of the protein in its solubilized form and is exposed in the cytoplasmic face of the innervated membrane of the electroplax in situ. This location is consistent with 3 models of channel structure but not with a fourth.

Amino Acid Sequence↗
PubMed1988

Histocompatibility and liver transplant outcome. Does HLA exert a dualistic effect?

An analysis of more than 500 liver transplants has demonstrated that HLA compatibility is associated with diminished allograft survival. Liver transplants with zero mismatches for class I and/or class II HLA antigens have shown significantly lower actuarial survival rates than transplants with one or more mismatches for these loci. In a group of 119 failed liver allografts from patients undergoing retransplantation, a higher incidence of failure due to rejection correlated with a lower degree of HLA compatibility especially for HLA-DR. In contrast, the incidence of liver transplant failures due to primary nonfunction was relatively higher with HLA-DR compatible transplants. Considering the role of HLA as a restriction element in cellular interactions during the immune response, these findings suggest that HLA compatibility may have a dualistic effect on liver transplant outcome. On one hand, HLA compatibility reduced transplant rejection--and on the other hand, it may enhance other immunological mechanisms leading to allograft dysfunction, particularly in patients at risk of developing recurrent autoimmune diseases or infection.

Graft Rejection↗
PubMed1988

Liver transplantation in the treatment of bleeding esophageal varices.

From March 1980 to July 1987, 1000 patients with various end-stage liver diseases received orthotopic liver transplants. Of the 1000 patients, three hundred two had definite histories of bleeding from esophageal varices before transplantation. There were 287 patients with nonalcoholic liver diseases and 15 patients with alcoholic cirrhosis. All patients had very poor liver function, which was the main indication for liver transplantation. One- through 5-year actuarial survival rates of the 302 patients were 79%, 74%, 71%, 71%, and 71%, respectively. These survival rates are far better than those obtained with other available modes of treatment for bleeding varices when liver disease is advanced. Long-term sclerotherapy is the treatment of primary choice for bleeding varices. Patients in whom sclerotherapy fails should be considered for liver transplantation unless clear contraindications exist.

Esophageal and Gastric Varices↗
PubMed1988

Intrahepatic bile duct strictures after human orthotopic liver transplantation. Recurrence of primary sclerosing cholangitis or unusual presentation of allograft rejection?

One of 55 patients transplanted for sclerosing cholangitis during the cyclosporin-steroid era (March 1980-June 1986) developed intrahepatic biliary strictures in the absence of allograft rejection within the 1st year posttransplantation. Although many causes underlie biliary pathology in the postoperative period (i.e., arterial injury, ischemia, chronic rejection, cholangitis), recurrent disease remains a possibility.

Adult↗
PubMed1988

Cadaveric renal transplantation at the University of Pittsburgh: a two and one-half-year experience with the point system.

From January 1, 1986 to July 30, 1988, 530 consecutive cadaver kidney transplantations were performed with patient selection by a point system that took into account time awaiting an organ, donor-recipient matching, degree of presensitization, and some less important factors. The effect of the system was to diminish judgmental factors in case selection which in the past, had probably operated to the disadvantage of "undesirable" potential recipients, including older ones. Primary 1-year graft survival (74%) and graft survival after retransplantation (71%) were lower than in the earlier time. However, the results with triple-drug therapy using CsA, AZA and P demonstrated 88% 1-year graft survival for primary graft recipients and 74% in highly sensitized patients, with comparable patient mortality. These latter observations provide some assurance that the concepts of equitable access and efficient utilization of a scarce resource are not mutually exclusive.

Actuarial Analysis↗
PubMed1988

Changing perspectives on liver transplantation in 1988.

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.

Actuarial Analysis↗
PubMed1988

Equitable allocation of extrarenal organs: with special reference to the liver.

A national plan is proposed for the equitable allocation of extrarenal organs, with particular reference to the liver. The principles of the plan include preferential use of the organs in the local and regional area of procurement, with national listing of the organs left over after the original cut. At each of the local, regional, and national levels, the allocation is based on total points awarded for medical urgency, time waiting, blood group conformity, and physical location of both donor and recipient. The plan, which should be applicable as well for allocation of hearts, is compatible with international sharing with nearby countries such as Canada.

Adult↗
PubMed1988

Immunological factors influencing liver graft survival.

Donor-recipient ABO blood group mismatching is associated with a decreased graft survival rate in liver transplantation. We have been unable to demonstrate an effect of high levels of panel reactive antibody or a positive donor-specific cytotoxic antibody cross-match on graft survival. A limited analysis of HLA-matching for the A, B, and DR loci suggests a paradoxical effect, but much more experience is needed before the true effect of HLA matching on graft outcome can be reliably evaluated.

ABO Blood-Group System↗
PubMed1988

A liver transplant center information management system.

A comprehensive microcomputer-based data management system has been developed to facilitate candidate selection and to track clinical performance for the liver transplant program at the University of Pittsburgh. A relational database manager, dedicated statistical analysis software, and presentation graphics are all elements that have been integrated into the system.

Humans↗
PubMed1987

Indications for pediatric liver transplantation.

Two hundred fifty pediatric (less than 18 years of age) patients underwent orthotopic liver transplantation because of end-stage liver disease and were given combination therapy with cyclosporine and prednisone. The most common indications for transplantation in decreasing order of frequency were biliary atresia, inborn errors of metabolism, and postnecrotic cirrhosis. The 5-year actuarial survival for the entire group was 69.2%. Age and diagnosis did not influence survival. Infections were the most common cause of death, followed by liver failure and cerebrovascular accident. The impact of retransplantation on survival depends on the indication. The survival is better when retransplantation is carried out after rejection than because of technical complications, and the latter has a better survival than does primary graft nonfunction. The difference in survival among these groups is statistically significant. The quality of life for 164 of 173 survivors is good to excellent; only nine children are currently experiencing medical problems. A persistent problem in pediatric transplantation is the scarcity of small donors.

Adolescent↗
PubMed1987

Liver transplantation before 1 year of age.

Since 1981, 20 infants younger than 1 year of age received 26 orthotopic liver transplants. Immunosuppression was with cyclosporine and corticosteroids. Thirteen (65%) of the recipients were discharged from the hospital. To date, 12 (60%) of the 20 recipients are surviving, with follow-up of 1 to 56 months (average 14 months). The 5-year actuarial survival is 53.8%. The allograft liver function in the majority of surviving infants is excellent. The predominant causes of mortality were primary nonfunction of the allograft (three patients) and sepsis (three). Major morbidity was caused by hepatic artery thrombosis (five patients), gastrointestinal complications (six), biliary tract complications (five), and bacterial and viral infections (13). Six patients underwent retransplantation; three of these six survived. Results could be improved by prevention of hepatic artery thrombosis, by decreasing the incidence of sepsis, and by procurement of more and better suited pediatric donors.

Actuarial Analysis↗
PubMed1987

Topographical localization of the C-terminal region of the voltage-dependent sodium channel from Electrophorus electricus using antibodies raised against a synthetic peptide.

A peptide corresponding to amino acid residues 1783-1794 near the C terminus of the electric eel sodium channel primary sequence of the eel (Electrophorus electricus) sodium channel has been synthesized and used to raise an antiserum in rabbits. This antiserum specifically recognized the peptide in a solid-phase radioimmunoassay. Specificity of the antiserum for the native channel protein was shown by its specific binding to a 280-kDa protein in immunoblots of eel electroplax membrane proteins. The antiserum also specifically labeled the innervated membrane of the eel electroplax in immunofluorescent studies; noninnervated membrane was not labeled, consistent with the known distribution of sodium channels in this tissue. The membrane topology of the peptide recognized by this antiserum was probed in binding studies using oriented electroplax membrane vesicles. These vesicles were 98% "right-side-out" as determined by [3H]saxitoxin binding. Binding of the antipeptide antiserum to this fraction was measured before and after permeabilization with 0.01% saponin. Specific binding to intact vesicles was low, but this binding increased 10-fold after permeabilization, implying a cytoplasmic orientation for the peptide. Confirmation for this orientation was then sought by localizing the antibody bound to intact electroplax cells with immunogold electron microscopy. Gold particles identifying the antibody were found almost exclusively associated with the cytoplasmic surface of the innervated membrane. Our data imply that the region of the sodium channel primary sequence near the C terminus that is recognized by our antiserum is localized on the cytoplasmic side of the membrane; this localization provides some further constraints on models of sodium channel tertiary structure.

Animals↗
PubMed1987

Liver transplantation today.

In summary, liver transplantation has truly come of age. To put things in perspective, the recipient waiting list at the University of Pittsburgh never includes fewer than 200 suitable candidates, and it continues to grow in spite of the fact that we are now doing essentially one transplant per day. There are many excellent transplant centers throughout the United States and Europe, the only limiting factor being the supply of donors. Orthotopic liver transplantation is now covered by most major health insurance carriers, and some form of government coverage is anticipated for the indigent. As the supply of donors increases with aggressive education programs, the need for transplantation centers will also increase. However, this should not be uncontrolled growth. Mandatory training in transplantation surgery will surely be required as a prerequisite to the establishment of transplant centers in the future. The field of organ transplantation is the newest and most dynamic in medicine today. The results are encouraging and acceptable and offer the only hope to many persons dying of end-stage organ failure. With improvements in immune modulation at hand, organ transplantation will soon become a commonplace procedure offering a completely normal life expectancy.

Graft Rejection↗