Biomedical subjects

F Gordon

Publications and source records attributed to F Gordon.

At least 19 recordsLinked to original sources

PubMed2000

Orthotopic liver transplantation for familial amyloidotic polyneuropathy: a pathological study.

Familial amyloidotic polyneuropathy (FAP), a hereditary form of systemic amyloidosis with clinically significant neuropathy and cardiomyopathy, is caused by a genetic defect of the transthyretin gene, which is mostly synthesized in the liver. Orthotopic liver transplantation (OLT) is thought to eliminate the amyloidogenic protein and currently is the only definitive treatment for this disorder. The aim of this study was to define the distribution and extent of amyloid deposition in tissues from these patients and evaluate the suitability of the resected FAP livers for transplantation into non-FAP patients. Surgical specimens from 14 patients removed at the time of OLT and autopsy tissues from 3 of the 14 were examined histologically using hematoxylin and eosin and Congo red-stained sections. The extent of amyloid deposits was evaluated, semiquantitatively graded from negative to marked, and correlated with clinical course and patient outcome. Amyloid deposits were consistently seen in hilar and vagus nerves. Liver lobular involvement was minimal in 1 and absent in the other 13 cases, with portal arterial amyloid deposits seen in 7 cases. At autopsy, extensive amyloid deposition in the heart was seen in all 3 cases with involvement of the conduction system. The extent of amyloid deposition at OLT did not correlate with the duration of symptoms before OLT or patient outcome after OLT. In conclusion, liver parenchymal involvement in FAP is minimal, and these explants are suitable for grafting in non-FAP patients. The recipients of such grafts must be carefully observed for the development of any amyloid-related disease, particularly cardiomyopathy. Of the tissues removed at OLT, the histopathologic confirmation of FAP is most consistently made by the examination of hilar and vagus nerves.

Adult↗

PubMed2000

Steatosis in donor and transplant liver biopsies.

The purpose of this study was to identify the significance and clinical correlation of steatosis in donor and posttransplantation liver biopsies. One hundred twenty-six liver biopsies with fatty change from 86 liver transplant patients were reviewed. Micro- and macro-steatosis were graded semiquantitatively and correlated with clinical and other pathologic parameters. Fifty-one donor biopsy specimens, from 50 patients, had combinations of micro- (predominantly) and macro-steatosis. One of 2 patients with high-grade micro- and macro-steatosis required a retransplantation on the third day. Three early deaths were not related to graft dysfunction. In 36 patients, steatosis developed after transplantation. In 13 of 36, steatosis was seen in the early postoperative period with a background of severe ischemic injury, 6 of whom died within 45 days posttransplantation. Other causes of steatosis developing after liver transplantation included hepatitis C (n = 12), alcoholic steatohepatitis (n = 3), diabetes mellitus or obesity (n = 7) and poor nutrition (n = 2). The presence of steatosis in 1 patient's donor and all posttransplantation biopsy specimens remained unexplained. In conclusion, (1) microsteatosis in donor liver biopsy specimens has no effect on graft function; (2) ischemic injury with development of steatosis in the early posttransplantation period may be associated with poor clinical outcome; and (3) steatosis in the posttransplantation period is uncommon and usually related to recurrent or acquired hepatitis C.

Biopsy↗

PubMed1999

Distal splenorenal shunt: role, indications, and utility in the era of liver transplantation.

HYPOTHESIS: The distal splenorenal shunt (DSRS) continues to play an important role in the management of recurrent variceal bleeding with minimal negative impact on subsequent orthotopic liver transplantation (OLT). DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary referral medical center. PATIENTS: From August 1, 1985, through October 31, 1997, a single team of surgeons performed 81 DSRS procedures for recurrent variceal hemorrhage. Eleven patients undergoing OLT subsequent to DSRS were compared with a group of 274 patients undergoing OLT without any previous shunt during the same period. MAIN OUTCOME MEASURES: Operative time, use of blood products, length of hospital stay, perioperative complications, and survival rates. RESULTS: Operative (30-day) mortality for DSRS was 6% (n = 5). From follow-up information available for 74 patients, the 1- and 5-year survival rates were 86.4% (n = 64) and 74.3% (n = 55), respectively. Recurrent variceal bleeding and hepatic encephalopathy occurred in 5 (6.8%) and 11 patients (14.9%), respectively, after DSRS. In 9 patients, DSRS was used as salvage for failed transjugular intrahepatic portosystemic shunt. CONCLUSIONS: Distal splenorenal shunt is a safe, durable, and effective treatment for controlling recurrent variceal hemorrhage in patients with acceptable operative risk and good liver function. It does not compromise future liver transplantation and can considerably delay the time until transplantation is required. Given the early occlusion rate and need for constant surveillance, transjugular intrahepatic portosystemic shunting should be reserved for patients with Child C classification cirrhosis with chronic hemorrhage or intractable ascites or as an emergency procedure for patients with uncontrollable bleeding using endoscopic therapy.

Adult↗

PubMed1999

Fibrosis/cirrhosis after orthotopic liver transplantation.

The causes and pathologic changes leading to fibrosis and cirrhosis after orthotopic liver transplantation (OLT) are not fully defined. The computerized pathology files were searched for cases of fibrosis/cirrhosis after OLT. Of 493 grafts from 435 patients, 35 grafts from 32 patients of posttransplantation liver fibrosis/cirrhosis were identified and retrieved (7%). Detailed histopathologic examinations of all post-OLT liver biopsy specimens were performed in conjunction with clinical, virologic, serologic, and molecular diagnostics information. Two cases with subcapsular septa and fibrous tissue close to hilum were excluded as false positives. Fibrosis/cirrhosis was confirmed in the remaining 33 grafts. In 20, the underlying cause was recurrent viral hepatitis, including eight with hepatitis C, 10 with hepatitis B, and two with combined hepatitis C and B. Another two with pretransplantation chronic hepatitis B developed cirrhosis without detectable virologic markers after OLT; these were biliary type secondary to obstruction in one, and chronic changes due to severe graft ischemia in one. Three patients acquired hepatitis C after OLT, with molecular confirmation available in two. In five patients, the underlying causes were Budd-Chiari syndrome and autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary biliary cirrhosis, alcohol-induced liver disease, and recurrent bile duct carcinoma. Three cases had centrilobular fibrosis but without bridging septa or cirrhosis as a result of chronic rejection. It was concluded that (1) Cirrhosis after OLT is uncommon (7%). (2) Chronic rejection does not lead to cirrhosis, but it may result in centrilobular fibrosis. (3) In most (70%) cases, cirrhosis after OLT is attributed to recurrent or acquired viral hepatitis.

Biopsy↗

PubMed1998

Combined liver-kidney transplantation in patients with cirrhosis and renal failure: effect of a positive cross-match and benefits of combined transplantation.

Patients with renal failure after liver transplantation have a particularly poor prognosis. Therefore, in the setting of end-stage renal disease requiring dialysis or severe renal insufficiency that will not improve after liver replacement, combined liver-kidney transplantation (LKT) is the preferred approach. We have adopted a policy of LKT in patients with end-stage liver disease and renal insufficiency undergoing dialysis or with a creatinine clearance less than 35 mL/min and evidence of chronic renal dysfunction. Since 1991, we have performed 208 orthotopic liver transplantations. Fourteen patients (8%) have undergone combined LKT, including 6 patients undergoing hemodialysis. Cytotoxic cross-matches (modified Amos technique and antihuman globulin method) were performed on 13 of 14 patients and were positive in 3 patients. Two patients died less than 4 months after LKT and 12 patients are alive and well. Graft survival censored for patient death was 100% for liver allografts and 93% for renal allografts, with a mean follow-up of 39 +/- 24 months. The most recent serum creatinine level in the patients with the 11 functioning grafts was 1.1 +/- 0.6 mg/dL. Biopsy-proven acute rejection occurred in 50% of simultaneous liver allografts. By contrast, only a single episode (6%) of renal allograft dysfunction was attributable to acute rejection. All rejection episodes occurred in the first 90 days after transplantation and were steroid sensitive. Three of 14 combined procedures were performed in the setting of a positive cytotoxic cross-match. In 2 recent patients, the results were confirmed by positive cross-matches to the donor's T and B cells by flow cytometry. Flow cytometric cross-matches reverted to negative 1 hour after liver transplantation and several hours before the administration of antithymocyte globulin. The cross-matches remained negative on postoperative days 1 and 7. Presently, all 3 patients with a positive cross-match enjoy normal hepatic and renal function at 631, 706, and 2275 days follow-up. Renal scans were performed in 4 LKT recipients not previously undergoing hemodialysis and indicated varying and unpredictable degrees of function in the native and transplanted kidneys. In conclusion, combined LKT can be performed safely and is associated with a low rate of acute rejection, even in the setting of a positive cross-match. Predicting which patients with renal insufficiency will benefit from LKT remains challenging; however, these results suggest that LKT should be encouraged in patients with evidence of irreversible renal insufficiency who require liver transplantation.

Adult↗

PubMed1998

Inhibition of mitogen-activated protein kinase activity and proliferation of an early osteoblast cell line (MBA 15.4) by dexamethasone: role of protein phosphatases.

Chronic glucocorticoid therapy causes rapid bone loss and clinical osteoporosis. We found that although the glucocorticoid, dexamethasone, stimulated osteoblast maturation, it also inhibited proliferation of a preosteoblastic cell line, MBA-15.4. The dexamethasone-induced decline in preosteoblast proliferation correlated with a 30-40% reduction in protein kinase C/TPA-stimulated mitogen-activated protein kinase (MAPK) activity. These steroid effects only became evident after 6-24 h treatment, implying that dexamethasone acts on de novo synthesis of proteins. Because MAPK is inactivated by dephosphorylation of tyrosine and threonine residues, cells were treated concomitantly for 24 h with dexamethasone and inhibitors of tyrosine (sodium orthovanadate) and/or serine/threonine phosphatases (sodium fluoride). MAPK activity and cell proliferation were restored when MBA-15.4 cells were treated with vanadate, suggesting that dexamethasone up-regulates tyrosine phosphatase activity. Inactivation of serine/threonine phosphatases with sodium fluoride had no effect. Inhibition of the PKA pathway (which is growth inhibitory in mature osteoblasts) with H-89 did not reverse the effects of dexamethasone. Pretreatment with dexamethasone inhibited both peak- and extended activation plateau-phases of MAPK activity. Both phases were fully restored by pretreatment with vanadate, implicating more than one tyrosine phosphatase. Cycloheximide, alone or in combination with dexamethasone, prevented drop-off from plateau to basal levels, suggesting that an inducible dual-specificity phosphatase regulates the plateau-phase. We conclude that dexamethasone may inhibit preosteoblast growth via a novel tyrosine phosphatase pathway.

Animals↗

PubMed1997

Effect of chemotherapy on thyroid hormone concentration in patients with malignant hematologic diseases.

Malignant hematologic diseases are severe illnesses for which complex forms of treatment are used and to which a great variety of metabolic changes are anticipated. Both lymphomas and leukemias, as well as chemotherapy, can induce abnormalities in thyroid hormone metabolism without overt disease, thus leading to what is known as euthyroid sick syndrome (ESS). In the present report, 25 patients with lymphomas and leukemias were studied to evaluate the effect of chemotherapy on thyroid hormone concentration. After chemotherapy, the most frequent and significant alteration was a decrease in serum triiodothyronine concentration.

Adolescent↗

PubMed1996

Insulin resistance in offspring of hypertensive subjects.

OBJECTIVE: To assess whether apparently healthy subjects with a family history of systemic hypertension have a higher risk of presenting the insulin resistance syndrome. SUBJECTS: Three hundred and eighty-six subjects aged 20-65 years. SETTING: A middle socio-economic class urban community from Mexico City. METHOD: All subjects and, when necessary, their first-degree relatives, answered a questionnaire and underwent a physical examination with measurement of height, weight and blood pressure. Serum insulin, glucose, cholesterol and triglycerides were measured during fasting and 2 h after an oral load of 75 g glucose. RESULTS: A family history of systemic hypertension was present for 167 (43%) of the subjects, of whom 123 (31%) were obese. Subjects with a family history of hypertension had higher systolic blood pressures than did those without such a history (120 +/- 15 versus 115 +/- 10 mmHg). In the logistic regression model, the body mass index and age showed statistically significant effects on the fasting glucose:insulin ratio and on serum insulin levels after an oral load of glucose. When men and women were analysed separately, only in men were higher systolic and mean blood pressures and lower glucose:insulin ratios observed. In the logistic regression analysis the body mass index was a significant predictor of the glucose:insulin ratio and serum insulin levels after an oral load of glucose, especially in men. CONCLUSION: Apparently healthy male offspring of hypertensive parents have higher blood pressure levels and lower insulin sensitivities than do offspring of normotensive parents. Insulin resistance was related to obesity, but not to a family history of hypertension, as had previously been reported by other research groups.

Adult↗

PubMed1990

Connections between the pontine central gray and the ventromedial hypothalamus are essential for lordosis in female rats.

Lesions and knife cuts were used to study central gray (CG) and ventromedial hypothalamic (VMH) mediation of sexual receptivity in female rats. Lesions of the midbrain-pontine CG eliminated lordosis in female rats. Bilateral sagittal knife cuts that bracketed the rostral pontine CG also eliminated lordosis, and an experiment with the retrograde tracer Fluoro-Gold confirmed the effectiveness of these cuts in severing the lateral connections linking the VMH and the CG. Finally, females with a unilateral hypothalamic cut combined with a contralateral CG transection almost never showed lordosis. Each cut, at a different level for each side of the brain, transected axons linking the VMH and the CG. The demonstration that this combination eliminated lordosis provides new evidence that the lateral connections between the VMH and the CG are essential for the display of sexual receptivity in female rats.

Afferent Pathways↗

PubMed1983

The extended role and the effects of stress on A&E nurses in US.

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Accidents↗

PubMed1983

Mechanisms of hydrocephalus in cerebral cysticercosis: implications for therapy.

Patients with hydrocephalus secondary to cerebral cysticercosis are a highly heterogeneous group. The mechanisms of hydrocephalus in these patients are multiple. Intraventricular cysts may be found in the 3rd and 4th ventricles, the sylvian aqueduct, and the foramen of Monro. Intraventricular cysts can be suspected when the 3rd and 4th ventricles or aqueduct remain enlarged despite shunting. Intraventricular contrast medium demonstrates the presence of the parasites. The intraventricular cysts should be removed surgically. Hydrocephalus due to cisternal cysticercosis can be diagnosed by isotope cisternography. These patients should receive shunts, but the long term prognosis is probably poor. Guidelines for the management of hydrocephalus due to cysticercosis are suggested.

Adult↗

PubMed1983