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V Mazzaferro

Publications and source records attributed to V Mazzaferro.

At least 55 records · Page 3Linked to original sources
PubMed1992

Relationship between the dose and whole blood level of cyclosporine after liver and kidney transplantation.

Descriptions of the immunosuppression protocols used after organ transplantation typically refer to the dose of cyclosporine (on a per weight basis) given to patients. In actual clinical practice, however, the amount of cyclosporine given to patients is determined principally by the concentration of the drug present in blood. In this study we determined the correlation between the dose of cyclosporine prescribed and the level of cyclosporine achieved in stable organ recipients three or more months following successful grafting. Seventy-five adult liver transplant recipients and 65 kidney transplant recipients who survived for more than three months after the transplant and who had stable graft function were included in the analysis. The cyclosporine dose and the cyclosporine level at the first out-patient visit were recorded for each patient. The median dose of cyclosporine used in liver recipients was 15 mg/kg/day. Seventeen percent of liver transplant recipients were on a maintenance dose of cyclosporine of less than 12 mg/kg/day. Fifteen percent were on a maintenance dose of greater than 22 mg/kg/day. The median dose utilized by kidney transplant recipients was 15 mg/kg/day. Twenty-eight percent of kidney recipients were on a maintenance dose of less than 12 mg/kg/day while 9% were taking more than 22 mg/kg/day. The median whole blood cyclosporine level in liver recipients was 1025 ng/ml (range 18-1925 ng/ml). The median level in kidney recipients was 542 ng/ml (range 79-1451 ng/ml). The majority of the liver and kidney recipients had cyclosporine levels within standard "therapeutic" ranges reported for each type of transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Morbidity and mortality after surgical resection of liver tumors. Analysis of 229 cases.

Two hundred and twenty-nine resections of hepatic tumors were performed over the past 10 years. The intraoperative death rate, 30-day operative mortality and major complication rate were 1.3%, 8.3% and 20%, respectively. Both morbidity and mortality were significantly related to the type of surgery and to the extent of the resection to contiguous organs and/or structures. Cirrhotic patients (40% in hepatocellular carcinoma) had a higher mortality rate (19%). Intraoperative blood loss was related to the extent of the resection and was significantly higher in patients with major complications and/or death. The main problem was postoperative liver failure in cirrhotic patients, which is difficult to predict and to treat.

Adolescent↗
PubMed1991

Further steps of hepatic stimulatory substance purification.

The hepatic stimulatory substance (HSS) extracted from weanling rat livers was purified 381,000-fold using chromatographic techniques including nondissociating polyacrylamide gel electrophoresis (nondenaturing PAGE). The activity of this highly purified HSS, named Acr-F4, was assessed in two in vivo models. In 40% hepatectomized rats, it produced a fivefold increase in the proliferative rate normally seen following this partial hepatectomy. In Eck fistula dogs, the level of base increase in hepatocyte renewal was amplified threefold by an infusion of Acr-F4 (50 ng/kg/day). Acr-F4 had no influence on the regenerative response of the kidney following a unilateral nephrectomy or of the bowel following a 40% resection of the small bowel. On the basis of these findings, it can be concluded that HSS (Acr-F4) has a high biological activity and is organ specific.

Animals↗
PubMed1991

Cyclosporine and liver regeneration studied by in vivo 31P nuclear magnetic resonance spectroscopy.

The changes in fructose-1-phosphate (F-1-P), intracellular pH, and ATP content of the liver after a fructose challenge were investigated noninvasively in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of dog liver four days after a portacaval shunt (PCS) with or without portal venous infusion of cyclosporin (CsA). The F-1-P metabolism was slower in PCS dogs (N = 2) as compared to either the normal (N = 2) or PCS + CsA-treated dogs (N = 3) (P less than 0.05). The intracellular pH temporarily decreased from 7.3 +/- 0.05 to 7.0 +/- 0.05 during the fructose challenge. The regenerative indexes were increased in the PCS + CsA group (P less than 0.01). These data obtained in vivo using 31P-NMR spectroscopy in the liver following a portacaval shunt, suggest that: (1) the energy status of the liver and the metabolic response to fructose are reduced in PCS compared to normal animals and (2) CsA treatment enhances the regenerative response of the liver and prevents the reduction in hepatic function associated with portacaval shunting.

Acid-Base Equilibrium↗
PubMed1991

Role of estrogens and epidermal growth factor in hepatocellular carcinoma (HCC).

Estrogen (E) and epidermal growth factors (EGF) receptors were assayed in the liver of nine patients with hepatocellular carcinoma (HCC). Total E and nuclear E receptors were decreased significantly in neoplastic tissue as compared to the levels found in surrounding nonneoplastic tissue. The EGF receptor was decreased also in neoplastic tissue. On the basis of binding data, a decrease in the number but not in affinity of both the E and EGF receptors was found.

Carcinoma, Hepatocellular↗
PubMed1991

Quantitation of estrogen and androgen receptors in hepatocellular carcinoma and adjacent normal human liver.

Sex hormones have been shown to influence the development and course of several liver diseases. The worldwide predominance of hepatocellular carcinoma (HCC) in males has led to the suggestion that this disease might be hormone-responsive. Therefore, the hepatic estrogen (ER) and androgen receptor (AR) status of liver specimens from such patients was investigated. Samples were obtained from three female and six males patients undergoing liver resection; in each case, a small sample of both the tumor and adjacent normal tissue was collected. All patients had primary hepatocellular carcinoma without cirrhosis. In most cases, the tumor and the normal specimen had an equivalent content of cytosolic ER; however, three of the tumor samples (one female and two male) displayed considerably elevated cytosolic ER levels as compared to that of the normal tissue. In every sample, the tumor contained less nuclear ER than did the normal liver. When AR was measured, tumors of three patients (one female and two male) demonstrated a twofold elevation in cytosolic AR as compared to adjacent normal tissue. In the two male patients, an approximately twofold greater nuclear AR was found. Two other samples from male patients showed a modest elevation of cytosolic AR in the tumors. The patients whose tumors showed elevations in ER were not the same patients as those in whom the AR was elevated. Thus, these studies indicate that certain, but not all, specimens of HCC demonstrate either elevated ER or AR and suggest that a determination of receptor content might be useful prior to initiation of certain antihormone therapies.

Adult↗
PubMed1991

Hepatotrophic effects of FK506 in dogs.

Portacaval shunt (Eck fistula) in dogs causes hepatocyte atrophy and organelle disruption, as well as tripling of hepatocyte mitoses. After submitting dogs to this procedure, FK506 was infused into the tied-off left portal vein. The size, anatomic quality, and replication of hepatocytes were enhanced in the portion of liver infused with FK506, with a significant spillover effect in the noninfused portion. These hepatotrophic qualities of FK506 may explain part of FK506's efficacy for the treatment of chronic liver rejection. Also, the observations support a trial with this drug for the treatment of autoimmune liver diseases because, in addition to turning off the immunologic genesis of such disorders, repair and regeneration of the damaged liver may be augmented. Finally, these hepatrophic qualities are part of an emerging spectrum of biologic effects caused by drugs that may modulate the enzyme cis-trans peptidyl-prolyl isomerase (PPIase), the principal constituent of the cytosolic binding sites of FK506, repatomycin, cyclosporine, and presumably other immunosuppressive drugs as yet undiscovered.

Amino Acid Isomerases↗
PubMed1991

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo.

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Inflammatory pseudotumor of the liver: report of two cases.

Inflammatory pseudotumor of the liver is a very rare lesion. Herein we describe two cases of this entity which occurred in two women aged 22 and 49 years, respectively. Both cases were considered to be clinically malignant and only the histopathologic examination revealed the non-neoplastic nature of the disease. Ultrastructural and immunohistochemical studies further supported the evidence of a reactive disease.

Adult↗
PubMed1990

Hepatic arterial embolization with microencapsulated mitomycin C for unresectable hepatocellular carcinoma in cirrhosis.

From 1986 to 1988, 35 patients with a hepatoma judged either inoperable or unresectable because of coexistent cirrhosis were treated with hepatic arterial embolization of mitomycin C microcapsules. Five of these 35 patients (14.5%) could not be treated because of inability to selectively cannulate the hepatic artery and were therefore excluded from the evaluation (feasibility rate, 86%). There were 24 men and six women with a median age of 57 years (range, 47 to 79) who could be classified as Okuda I (14 pts) or Okuda II (16 pts) and Child Class A:18 and Child Class B:12 in the remaining patients. A median dose of 0.5 mg mitomycin C/kg was administered to each subject and the treatment was repeated at 5 to 6 week intervals. Seventy courses were administered to these 30 patients (median, two courses/patient; range, 1 to 4). Minor complications were frequent (63%) but always either resolved spontaneously or after appropriate medical treatment. Neither severe renal nor hepatic toxicity was observed. No specific treatment related mortality was observed. When alpha-fetoprotein levels and tumor volume were assessed to evaluate the response to treatment using established criteria for identifying a response, an objective response was found in 43% of the cases treated. The actuarial median survival was 7 months and the 1-year actuarial survival was 36% (51% for those rated as Child Class A and 0% for those identified as Child Class B, P = 0.04 and 78% rated as Okuda Types I and 0% Okuda type II, P = 0.0001). The excellent quality of life and the increased survival rate experienced after mitomycin C microcapsule embolization suggest that this treatment modality can be used successfully in patients seen in the West who have unresectable hepatoma.

Aged↗
PubMed1990

A clinicopathologic study of primary hepatic carcinoid tumors.

Six cases of primary hepatic carcinoid tumors were studied with combined immunocytochemical and electron microscopic techniques. Positive tumor immunostaining with PHE5, LK2H10, neuron-specific enolase (NSE), serotonin, gastrin, and insulin antibodies was observed. At the ultrastructural level, cytoplasmic dense granules were seen in all the cases tested. This finding supports a putative origin of these carcinoids found in the liver from a pluripotential stem cell. The clinical course and follow-up of these cases suggests that this unusual hepatic neoplasm has a more favorable prognosis than other forms of hepatic cancer.

Adult↗
PubMed1990

Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections.

Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk.

Adult↗
PubMed1990

Liver transplantation in patients with previous portasystemic shunt.

Over a 9-year period, 58 patients who had previous portasystemic shunt procedures underwent orthotopic liver transplantation (OLTx) under a cyclosporine-steroid immunosuppressive regimen. The types of shunt used were distal splenorenal (18 patients), mesocaval (17 patients), end-to-side portacaval (11 patients), side-to-side portacaval (5 patients) and proximal splenorenal (7 patients). The mean interval between shunt and transplantation was 6 years. There was no statistical difference in survival between patients with previous shunts and the entire population of patients with primary liver transplantation performed during the same period of time. Age, sex, shunt patency, status of portal vein, and use of vein or artery graft did not affect survival. Child's classification had a significant influence on graft survival, even though no difference was subsequently observed in patient survival. A progressively improved intraoperative strategy and the use of veno-venous bypass and University of Wisconsin preservation solution had a significant impact on blood loss, length of operation, length of stay in intensive care unit, and ultimately, on survival. Distal splenorenal and mesocaval shunts with no or minimal hilum dissection are safer shunts if subsequent transplantation is planned; in fact, their 9-year survival was 87%, whereas all other shunts were associated with a survival no better than 52% (p less than 0.006).

Adolescent↗
PubMed1990

Childbearing after liver transplantation.

Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient had a set of twins); 13 were by cesarean section, 7 by vaginal delivery. Eleven of the 13 cesarean births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for cesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year all have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2-18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2 1/2 years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature cesarean births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable.

Adult↗