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Biomedical subjects

P Foster

Publications and source records attributed to P Foster.

At least 73 records · Page 4Linked to original sources
PubMed1995

Improved viability of hepatic allografts from fasted donors is associated with decreased peripheral TNF activity.

Despite improvements in preservation solutions, hepatic allografts continue to be lost from primary nonfunction. Previous work by this group and others has established that donor fasting improves the viability of hepatic allografts. We have also established an association between viability of stored organs and serum TNF levels. The purpose of this study was to determine whether improved viability of hepatic allografts from fasted donors is associated with lower peripheral serum TNF levels. TNF was measured using a bioassay employing a WEHI cell line. Transplanted livers from fasted donors displayed gross deglycogenation had less bile flow postrevascularization and increased postoperative AST, but had significant improvement in viability and were associated with significantly less TNF recovered from the peripheral circulation. The association of improved viability and diminished serum TNF and previous work that links changes in postrevascularization TNF levels with changes in Kupffer cell activity suggest a possible cause for improved survival of recipients of fasted allografts.

Animals↗
PubMed1995

Inactivation of Kupffer cells after prolonged donor fasting improves viability of transplanted hepatic allografts.

Data from recent studies suggest that donor fasting imparts a beneficial effect on the viability of transplanted hepatic allografts. Because starvation may temporarily inactivate Kupffer cells, and because these cells are the likely mediators of liver injury after prolonged preservation-reperfusion, the purpose of this study is to establish a link between improved organ viability and Kupffer cell inactivation caused by donor allograft fasting. In an in vivo rat liver transplant model, 48 hours of donor fasting (1) improved allograft viability, (2) significantly decreased Kupffer cell phagocytosis, and (3) significantly decreased cytokine (tumor necrosis factor [TNF]) production postrevascularization. These data validate work from previous studies demonstrating that donor fasting improves allograft viability and furthermore support our previous research implicating activation of Kupffer cells as a causative agent of cold ischemia-preservation injury.

Animals↗
PubMed1995

Duane's retraction syndrome associated with chromosome 4q27-31 segment deletion.

PURPOSE/METHOD: A 15-year-old boy with bilateral blepharoptosis, bilateral type 1 Duane's retraction syndrome, and mild learning difficulties underwent chromosomal analysis. RESULTS/CONCLUSIONS: A de novo deletion of a segment of the long arm of chromosome 4 (4q27-31) was found. To our knowledge, no other individuals with this chromosome deletion have Duane's retraction syndrome. The chromosome defect lies close to the epidermal growth factor gene, 4q25, which was recently linked to Rieger's syndrome. We suggest that families with Duane's retraction syndrome should be assessed for linkage to the area of 4q27-31.

Adolescent↗
PubMed1995

An outbreak of cryptosporidiosis in south London: what value the p value?

An outbreak of cryptosporidiosis which affected 44 people in January and February 1991 was identified through local surveillance at a South London Public Health Laboratory. Preliminary enquiries revealed that more than half the patients were adult and that there were no common factors other than geographical association. A case-control study showed a significant association between illness and consumption of tap water supplied by a particular water company, as well as a dose response effect. There were no apparent breaches or irregularities in the water distribution system and no indication of a problem through routine monitoring indices. This incident demonstrates the problems of establishing the source of cryptosporidiosis outbreaks in the absence of evidence of environmental abnormality, as well as possibly indicating that water conforming to current treatment standards may occasionally contain sufficient numbers of Cryptosporidium oocysts to cause sporadic cases or clusters.

Adolescent↗
PubMed1995

Standardized comparison of performance indicators in trauma: a new approach to case-mix variation.

An institution's trauma survival rate can be compared with that predicted by TRISS using definitive outcome-based evaluation. This examines W, the difference between actual and predicted survival rates; Z, the statistical significance of this difference; and M, a measure of the similarity of injury severity mix to the prediction data base. However, it is possible for two institutions with the same survival rate within each band of injury severity to have very different W and Z scores whilst retaining a similar M score. Clearly this is unsatisfactory. A new statistic, Ws, is therefore proposed, which is standardized with respect to injury severity mix, producing more accurate comparisons between different institutions. Confidence intervals are used to graphically illustrate the magnitude of Ws, its direction, accuracy, and statistical significance. Data from the U.K. Major Trauma Outcome Study are used to demonstrate the calculations and presentation of Ws and its advantages.

Diagnosis-Related Groups↗
PubMed1995

A simple modification in operative technique can reduce the incidence of nonanastomotic biliary strictures after orthotopic liver transplantation.

Nonanastomotic strictures after liver transplantations are a source of significant morbidity, often necessitating retransplantation. The purpose of this study was twofold: first to identify features associated with the development of this lesion; second, to make technical modifications that will decrease the incidence of this problem. In the first part of this study, 15 of 131 patients were diagnosed with nonanastomotic biliary stricture. A stepwise logistic-regression analysis associated donor cold ischemic time and dopamine dose with the development of nonanastomotic biliary strictures. All these patients had arterial reconstruction after partial revascularization of the liver with portal venous blood. Because the bile duct receives its blood supply from only the hepatic artery, we hypothesized that the prolonged period of warm ischemia from staged reconstruction of the vascular supply would promote the development of this lesion. In a second part of this study, the stricture rate in 45 patients with simultaneous revascularization using both the hepatic artery and portal vein was compared with that in 83 patients from the first part of this study initially revascularized with portal venous blood. All patients in the second study had grafts preserved using UW solution. Only 1 patient with simultaneous revascularization developed a nonanastomotic biliary stricture. Because we were unable to identify any significant complications related to this method of revascularization, we propose that the hepatic artery and portal vein should be released simultaneously, especially in patients receiving a graft with prolonged storage time.

Adenosine↗
PubMed1995

An efficient delivery of historical information for the Mendelian Inheritance in Man database.

The ability to manage information with regard to changes in a database is critical for quality control. This information can also provide audit trails about the time of the change and the person who made the change. In addition, historical information can provide the proper context in which to interpret the relationships between the current and past data. In most genomic databases, only the most recent copy of the information is presented to the user, thereby losing the audit trail and the historical context. Therefore, we have constructed a delivery mechanism for the historical information in the Mendelian Inheritance in Man database. Furthermore, this feature was designed to optionally display only the changes so that the user can bypass the unchanged portions of the text. It was anticipated that technical problems would influence the acceptance of this information delivery. However, the involvement of the editorial staff became the critical factor.

Database Management Systems↗
PubMed1995

Comparison of six commercial plasma references for factor VIII, factor IX and von Willebrand factor. On behalf of the Subcommittee for Factor VIII and IX of the Scientific and Standardization Committee of the ISTH.

Six brands of normal reference plasma produced in the United States, with assigned assay values for factor VII and IX and, in four instances, ristocetin cofactor and van Willebrand antigen, were assayed in nine coagulation laboratories in academic institutions in the same country. Differences in mean assays of reference plasmas, as a percent of labelled potency, were significant and were greater than differences among laboratories. Standard methods of assigning potency to commercial reference plasmas are recommended.

Antigens↗
PubMed1994

Leflunomide controls rejection in hamster to rat cardiac xenografts.

Leflunomide is an isoxazole derivative that has the ability to prevent acute rejection of cardiac, renal, and skin transplants in strongly rejecting rat models. Furthermore, leflunomide is able to interact synergistically with CsA to inhibit allograft rejection and also reverse ongoing allograft rejection. In vitro studies suggest that the mechanism of action of leflunomide is via an interruption of cytokine signaling in T cells. This study defines the ability of leflunomide to prevent and reverse rejection of concordant xenografts. One hundred nine adult Lewis rats in 13 groups received abdominal heterotopic cardiac transplants from Golden Syrian hamsters. The xenograft survived 3.9 +/-0.3 days without treatment. When leflunomide was given at 2.5, 5, 10, 15, or 20 mg/kg by gavage daily, the cardiac xenograft survivals were 5.0 +/- 0.6, 8.0 +/- 3.0, 52.0 +/- 20.2, 76.5 +/- 21.14, and 58.9 +/- 28.1 days, respectively. The survival rates were 4.0 +/- 0 and 27.7 +/- 28.7 days when CsA was given at 10 and 20 mg/kg i.m., respectively. The combination of CsA at 10 mg/kg with leflunomide at 10 mg/kg or 5 mg/kg prolonged cardiac xenograft survival to 106.0 +/- 50.2 days and > 90 days, respectively. There were no observable side effects in the latter combination. Histologic studies of untreated graft hearts 4 days after transplantation revealed infarction of myocardium and severe RBC extravasation. In contrast, the rejected hamster hearts from long-term survivors showed massive mononuclear cell infiltration and myocardium fibrosis in contrast to the early rejected picture. Therapy with leflunomide begun on day 2 reversed these rejection responses by day 6. In addition, the increase in allospecific IgM titers observed on day 2 was reversed, and the allospecific IgM to IgG isotype switch that occurred in untreated animals was prevented by leflunomide. These observations demonstrate that leflunomide, at nontoxic doses, effectively controlled acute rejection of concordant xenografts and synergistic immunosuppressive effect was achieved with leflunomide and CsA.

Animals↗
PubMed1994

Leflunomide in experimental transplantation. Control of rejection and alloantibody production, reversal of acute rejection, and interaction with cyclosporine.

Leflunomide is a compound recently shown to reduce T and B cell-mediated responses in a number of experimental rat, mouse, and human systems. To explore its potential as an immunosuppressant, we studied leflunomide in 128 Brown-Norway/Lewis cardiac transplants and in 48 unoperated Lewis rats. At doses ranging from 0.63 mg/kg to 10 mg/kg given for 7 days, leflunomide significantly prolonged graft survival compared with controls. When cyclosporine or leflunomide was given for 21 days at a dose of 5 mg/kg, indefinite graft survival occurred in 3/6 animals receiving leflunomide but in none of the 21-day cyclosporine-treated animals. When acute rejection was allowed to develop for four days in untreated rats, leflunomide but not cyclosporine reversed the rejection, returning histology to a normal appearance by seven days. Alloantibody responses measured in microcytoxicity assays as well as total allospecific IgG and IgM in the rejecting animals also were returned to baseline levels by leflunomide but not cyclosporine. When both drugs were used together, a synergistic effect was observed at low doses of both drugs. Pharmacokinetics studies showed that their combined use for up to 28 days did not affect the trough levels of cyclosporine or cyclosporine elimination, suggesting that the synergistic effect was not caused by reduced elimination. The toxicity of each drug was negligible in a group of 32 rats receiving the drugs alone or in combination as measured by serial observation of general appearance, testing of serum ALT, AST, bilirubin, creatinine, white blood cell counts, hemoglobin, and gross necropsy appearance. Weight gain was slightly reduced by both drugs but combined drug use did not alter the pattern. The results of these experiments show leflunomide to be a potent, well-tolerated immunosuppressant, synergistic in its activity with cyclosporine, and would seem to encourage a closer look at this drug for potential use in man.

Abdomen↗
PubMed1994

Radiotherapy for parotid cancer.

BACKGROUND: Parotid malignancies represent a heterogeneous group of tumors primarily managed by surgical extirpation. Moderately high recurrence rates are seen after surgery alone, and postoperative radiotherapy has been used for patients with higher risks for local failure. METHODS: To assess the role of radiotherapy in the management of patients with malignant tumors of the parotid gland, the records of 68 patients receiving megavoltage therapy at our institution from 1966 to 1989 were reviewed. Patients were placed into three groups for analyses. Group I was composed of 41 patients receiving radiotherapy following total gross removal of parotid cancer by surgical procedures, varying from excisional biopsy through total parotidectomy. Radiation dose for this group ranged from 4,995 to 6,500 cGy. Group II was composed of 10 patients treated with radiotherapy after incisional biopsy or excision with positive margins. These patients received radiation doses of 4,000-9,470 cGy. Group III was composed of 17 patients receiving radiotherapy for a postsurgical local recurrence. Their radiation dose ranged from 4,300 to 8,400 cGy. RESULTS: Two of the 41 patients from group I developed a local recurrence. Two of these patients also developed distant metastases, one concurrent. Two of 10 group II patients failed locally, whereas three developed distant metastases. Only nine of the 17 patients in group III were controlled locally, and four patients developed distant dissemination. CONCLUSION: Total gross excision of parotid cancer, sparing facial nerve if possible and followed by regional radiotherapy, provides excellent rates of local control and survival with modest toxicity. Patients presenting postoperatively with gross residual tumor or recurrence after surgery should be considered for trials of more aggressive treatment with combined chemotherapy or altered fractionation schemes of irradiation.

Actuarial Analysis↗
PubMed1994

The status of online Mendelian inheritance in man (OMIM) medio 1994.

During the last year many changes have been introduced into the system of maintaining OMIM. There are three major components of the reorganization. First, a distributed editorial system was introduced which provides a three-tiered editorial board with senior editors, science writers and subject editors. Second, MIM entries have been restructured to provide separate gene and phenotype information and to organize them into separate catalogs. The restructuring also establishes clearly defined sections for entering new information, converts old entries to the new structure, and establishes a file maintenance and editorial system in SGML format. Third, the entry numbering and naming system has been modified. In addition, the information has been made available through a variety of output media, including books, CD-ROM and online access based on the IRx, WAIS, Gopher and WWW formats.

Books↗