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Biomedical subjects

B R Taylor

Publications and source records attributed to B R Taylor.

At least 19 recordsLinked to original sources
PubMed2000

Hepatic resection of noncolorectal nonneuroendocrine metastases.

Because hepatic resection is generally a safe procedure, the indications for resection of noncolorectal nonneuroendocrine (NCNNE) hepatic metastases have broadened. The prognostic features of NCNNE metastases treated surgically were reviewed to define better the value of resection. A retrospective review of patients undergoing liver resection for NCNNE metastases between 1978 and 1998 was undertaken. Thirty-seven patients were identified. Mean age was 56 years, with a median follow-up of 22 months. Primary tumor sites were grouped into gastrointestinal (GI) adenocarcinoma (small bowel, n = 4; pancreas, n = 2; esophagus, n = 1) and other (renal cell, n = 7; sarcoma, n = 7; melanoma, n = 5; adrenal, n = 3; unknown adenocarcinoma, n = 3; thyroid, n = 2; testicular, n = 1; ovarian, n = 1; breast, n = 1). All patients underwent surgery for cure. Metastases were synchronous in 14 patients. There was no surgical mortality. Overall 5-year survival rate was 45%. Five-year survival rates were better for patients with non-GI-origin metastases (60% v 0%; P =.01). Long-term survival was seen only in patients with non-GI-origin metastases. The extent of resection, presence of synchronous metastases, or disease-free interval from time of original disease to presentation with liver metastases were not predictive of outcome. We conclude that patients with NCNNE hepatic metastases can undergo liver resection with an expectation of prolonged survival. However, patients with liver metastases from GI primary tumors other than the colorectum are unlikely to show extended survival.

Adenocarcinoma↗
PubMed1999

In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells.

Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltransferase inhibitor (FTI) L-744,832 in an in vivo murine model of myeloid leukemia that is associated with inactivation of the Nf1 tumor suppressor gene. Nf1 encodes a GTPase activating protein for Ras, and Nf1-deficient (Nf1-/-) hematopoietic cells show hyperactive Ras signaling through the mitogen-activated protein (MAP) kinase pathway. L-744,832 inhibited H-Ras prenylation in cell lines and in primary hematopoietic cells and abrogated the in vitro growth of myeloid progenitor colonies in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). This FTI also partially blocked GM-CSF-induced MAP kinase activation, but did not reduce constitutively elevated levels of MAP kinase activity in primary Nf1-/- cells. Injection of a single dose of 40 or 80 mg/kg of L-744, 832 increased the amount of unprocessed H-Ras in bone marrow cells, but had no detectable effect on N-Ras. Adoptive transfer of Nf1-/- hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment. We speculate that the lack of efficacy in this model is due to the resistance of N-Ras and K-Ras processing to inhibition by this FTI.

Alkyl and Aryl Transferases↗
PubMed1999

Myeloid malignancies induced by alkylating agents in Nf1 mice.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML and MDS) are severe late complications of treatment with genotoxic chemotherapeutic agents. Children with neurofibromatosis type 1 (NF1) are predisposed to malignant myeloid disorders that are associated with inactivation of the NF1 tumor suppressor gene in the leukemic clone. Recent clinical data suggest that NF1 might be also associated with an increased risk of t-AML after treatment with alkyating agents. To test this hypothesis, we administered cyclophosphamide or etoposide to cohorts of wild-type and heterozygous Nf1 knockout mice. Cyclophosphamide exposure cooperated strongly with heterozygous inactivation of Nf1 in myeloid leukemogenesis, while etoposide did not. Somatic loss of the normal Nf1 allele correlated with clinical disease and was more common in 129/Sv mice than in 129/Sv x C57BL/6 animals. Leukemic cells showing loss of heterozygosity at Nf1 retained a structural allele on each chromosome 11 homolog. These studies establish a novel in vivo model of alkylator-induced myeloid malignancy that will facilitate mechanistic and translational studies.

Alkylating Agents↗
PubMed1997

A study of prognostic factors for hepatic resection for colorectal metastases.

BACKGROUND: Liver resection is accepted treatment for selected patients with colon cancer metastatic to the liver. There remains some controversy regarding the selection criteria, particularly which preoperative features are useful predictors of long survival postresection. METHODS: One hundred and twenty-three patients who had liver resection for colorectal metastases on the Hepato Pancreatic Biliary Service at The Toronto Hospital between August 1977 and June 1993 were studied. Seventy-seven had solitary lesions, 15 had single lesions with satellite nodules, and 31 had multiple lesions. Synchronous liver metastases were found in 40 patients and 83 patients had metachronous lesions. Fifty-one patients had formal lobectomies and 21 had extended lobectomies. RESULTS: Postoperative complications were seen in 28% of patients, but there were no operative or postoperative deaths. Overall actuarial 5-year survival was 34%. There was a significant difference in survival according to the number of metastases. Patients with single lesions had a 5-year survival of 47% compared with 16% for single lesions with satellite nodules, and 17% for multiple lesions. There were no significant differences in survival based on age, sex, synchronous versus metachronous lesions, status of lymph nodes at the time of original surgery, intraoperative blood replacement, or size of tumor. CONCLUSIONS: An aggressive approach to the surgical management of colorectal liver metastases is possible with low risk in centers specializing in liver surgery, and results in prolonged survival in one third of patients. The most reliable predictor of long-term survival is the number of metastases in the liver.

Adult↗
PubMed1997

Evaluation of liver transplantation for high-risk indications.

BACKGROUND: Appropriate use of orthotopic liver transplantation (OLT) requires continued assessment of the indications for transplantation as a number of diseases are associated with a poor prognosis. High-risk patients are those who have a poor survival or high incidence of recurrent disease (patients with tumours, hepatitis B- or hepatitis C-induced cirrhosis, fulminant hepatic failure or primary graft non-function). In addition, retransplantation may be associated with a poor outcome. METHODS: A retrospective review was made of the records of all adult patients undergoing OLT at this hospital between October 1985 and July 1994. RESULTS: A total of 396 liver transplants were performed in 364 patients. The 1- and 3-year actuarial survival rates were 81 and 69 per cent respectively. The overall survival rate of high-risk patients was significantly lower than that for all OLT recipients (P < 0.05). While no patients transplanted for hepatitis C have developed graft failure, recurrent hepatitis occurred in 15 of 35 patients. CONCLUSION: Strict selection criteria and appropriate perioperative investigations and interventions are required to improve the results of OLT in these high-risk patients.

Adolescent↗
PubMed1997

Presidential address 1996: "Dear Ministers of Health...." Canadian Association of General Surgeons.

The Canadian Association of General Surgeons, representing community and academic general surgeons throughout Canada, is concerned about the widespread effects of health care restructuring on clinical care, education and research. The general surgeon remains one of the critical members of the health care team and should have an adequate voice in ongoing discussions regarding health care reform.

Canada↗
PubMed1996

Treatment of Budd-Chiari syndrome with portosystemic shunt or liver transplantation.

BACKGROUND: Budd-Chiari syndrome is an uncommon disorder caused by obstruction to hepatic venous outflow, causing varying degrees of hepatic injury depending on the extent, severity, and acuity of the obstruction. PATIENTS AND METHODS: We reviewed the indications for operative intervention and the results of treating 32 patients with Budd-Chiari syndrome seen at Toronto Hospital between 1968 and 1995. RESULTS: Twenty-one patients underwent portosystemic shunt (PSS) and 7 patients underwent liver transplantation (LT) as their initial operative management. Three patients who initially had PSS subsequently required LT. Patients with cirrhosis found on biopsy and preservation of hepatocellular function were treated with PSS and showed no difference in outcome when compared with patients without cirrhosis (P = 0.35). Patients who were treated by PSS with retrohepatic vena caval compression, as shown by high caval gradients had outcomes similar to those for patients with low gradients (P = 0.31). Using the Kaplan-Meier method, 5-year survival of PSS patients was 57%. Liver transplantation was used to manage patients with hepatic decompensation, as well as patients with vena caval occlusion or failed PSS. The 5-year Kaplan-Meier survival for LT was 67%. CONCLUSIONS: Both PSS and LT are effective options in the management of Budd-Chiari syndrome. Portosystemic shunt is the preferred initial approach even with cirrhosis or retrohepatic caval compression as long as there is preservation of liver function and a patent vena cava. Liver transplantation should be used as primary therapy for patients with irreversible hepatic decompensation or vena caval occlusion, and it can be an effective salvage procedure following failed PSS.

Adolescent↗
PubMed1996

Nutritional status and function in patients following Whipple procedure compared with controls.

OBJECTIVE: Despite the potential for nutritional deficits in patients undergoing pancreaticoduodenectomy or Whipple procedure, long-term assessment of nutritional status has largely been ignored. This study assessed nutritional status of 24 Whipple patients compared with matched post-cholecystectomy controls. METHODS: Clinical assessment was by subjective global assessment, body composition was assessed by bioelectric impedance analysis and functional assessment was by respiratory muscle strength and skeletal muscle function performed by electrical stimulation of the ulnar nerve of the wrist and hand-grip dynamometry. RESULTS: Whipple patients studied 4.6+/-0.7 years since surgery and controls (4.8+/-0.7 years since surgery) were all judged clinically to be in a good nutritional state. Compared with controls, Whipple patients had significantly lower body weight (Whipple: 72.5+/-2.8 kg, control: 83.9+/-3.3 kg, p<0.05) however, the mean body weight of both Whipple and controls was above ideal weight (Whipple: 113.3+/-4.3%, control: 122.3+/-3.7% p = NS). No significant differences in functional performance were observed between groups. Energy intake of Whipple and controls was also comparable. In the Whipple group, neither the extent of gastric resection or the pathological diagnosis had an effect on the nutritional parameters studied. CONCLUSIONS: Long-term follow-up of patients having undergone Whipple procedure failed to reveal the presence of any nutritional or functional deficits suggesting that a full nutritional recovery is possible after this surgery.

Aged↗
PubMed1996

ZBP-89, a Krüppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter.

We have shown previously that a GC-rich element (GGGGCGGGGTGGGGGG) conferring epidermal growth factor (EGF) responsiveness to the human gastrin promoter binds Sp1 and additional undefined complexes. A rat GH4 cell line expression library was screened by using a multimer of the gastrin EGF response element, and three overlapping cDNA clones were identified. The full-length rat cDNA encoded an 89-kDa zinc finger protein (ZBP-89) that was 89% identical to a 49-kDa human factor, ht(beta), that binds a GTGGG/CACCC element in T-cell receptor promoters. The conservation of amino acids between the zinc fingers indicates that ZBP-89 is a member of the C2H2 zinc finger family subclass typified by the Drosophila Krüppel protein. ZBP-89 is ubiquitously expressed in normal adult tissues. It binds specifically to the gastrin EGF response element and inhibits EGF induction of the gastrin promoter. Collectively, these results demonstrate that ZBP-89 functions as a repressor of basal and inducible expression of the gastrin gene.

Amino Acid Sequence↗
PubMed1996

The use of household surveys in community-oriented primary care health needs assessments.

OBJECTIVE: This study demonstrates the use of a community household survey and how it can provide information beyond that obtained with secondary epidemiologic data alone. METHODS: Adults in 215 randomly selected households in an inner-city neighborhood in Bronx, NY, were assessed by in-person interviews in homes of neighborhood residents. The survey collected data on self-reported health status, source and quality of medical care, possible barriers to obtaining medical care, and perceptions of the community. Demographic information was also obtained. Mortality rates, birth outcomes, and census data were obtained from secondary data sources. RESULTS: The overall health of the community members surveyed was poor, and rates of self-reported health status, mortality rates, and poor birth outcomes were all generally higher than city-wide rates. More than half the respondents were using hospital-based outpatient clinics or emergency room care as their primary source of medical care. Nearly half the respondents had no personal health provider, and most respondents could not obtain medical advice over the phone or be seen within a week. A number of barriers to obtaining medical care were found to be associated with either gender or ethnic group. These findings are being used as the basis for a number of community-oriented primary care (COPC) outreach efforts. CONCLUSIONS: Although household surveys are expensive to conduct, the information garnered from this survey could not be obtained from secondary data sources and was important in determining the direction of outreach and intervention programs being carried out in the community by the COPC clinic.

Adult↗
PubMed1995

Rat phenol-preferring sulfotransferase genes (Stp and Stp2): localization to mouse chromosomes 7 and 17.

The phenol-preferring sulfotransferases aryl sulfotransferase IV and N-hydroxyarylamine sulfotransferase catalyze sulfate conjugation of N-hydroxy-2-acetylaminofluorene, a metabolite capable of causing hepatocarcinogenesis in rats. We utilized published cDNA sequences of these sulfotransferases to type the progeny of two multilocus crosses and determined that the genes, aryl sulfotransferase (Stp) and N-hydroxyarylamine sulfotransferase (Stp2), map to positions on mouse chromosomes 7 and 17.

Animals↗
PubMed1995

Quality of life, nutritional status, and gastrointestinal hormone profile following the Whipple procedure.

BACKGROUND: To compare the quality of life, nutritional status, and gastrointestinal profiles of post-Whipple patients and postcholecystectomy patients. METHODS: A cross-sectional survey of post-Whipple procedure patients and age- and sex-matched postcholecystectomy patients was performed. Quality of life was assessed using six instruments: Time Trade-off Technique, Direct Questioning of Objectives, Gastrointestinal Quality of Life Index, Sickness Impact Profile, Physician Global Assessment, and Visick Scale. A gastrointestinal symptomatology questionnaire was completed. Nutritional status was assessed by weight, the Subjective Global Assessment instrument, and skin anthropometry. Fasting and postprandial serum gastrin, somatostatin, insulin, pancreatic glucagon, enteroglucagon, and pancreatic polypeptide were measured. RESULTS: The quality of life and gastrointestinal function of the Whipple patients was excellent and was not significantly different from that of the control subjects. There were no significant differences in gastrointestinal symptomatology although 5 Whipple patients complained of greasy bowel movements, and 1 patient reported difficulty maintaining weight. Despite this, nutritional status was within normal limits in all subjects. Six patients in the Whipple group followed a diabetic diet, 1 required insulin, and 3 required an oral hypoglycemic agent, whereas none of the control subjects were diabetic. There were no significant differences in the mean basal, peak, or integrated postprandial responses of the gut hormones with the exception of pancreatic polypeptide and gastrin (in patients having a standard Whipple procedure only). CONCLUSION: Quality of life and nutritional status are excellent in patients following a Whipple procedure.

Adult↗
PubMed1994

Liver transplantation for hepatocellular carcinoma.

Twenty-nine patients with hepatocellular carcinoma (HCC) underwent orthotopic liver transplantation (OLTx) at the University of Toronto. Four patients did not have cirrhosis. Of the 25 patients with cirrhosis, 19 had known or suspected HCC before OLTx. Eleven patients tested positive for the hepatitis B surface antigen (HBsAg). No patients received adjuvant chemotherapy. None of the patients have developed recurrent HCC in a follow-up of 9 to 87 months (mean: 33 months). The actuarial post-transplant survival of all patients at 3 months, 1 year and 3 years was 75%, 61%, and 46%, respectively. The survival of HBsAg-negative patients was 69% at 3 years, whereas HBsAg-negative patients had a 3-year survival of 18% (p = 0.045). These results suggest that OLTx for carefully selected patients with otherwise unresectable HCC is associated with a low risk of recurrence. HBsAg-positive patients with HCC have a high mortality, suggesting that they make poor candidates for OLTx.

Adult↗