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L E Rotstein

Publications and source records attributed to L E Rotstein.

52 records · Page 3Linked to original sources
PubMed1981

Studies into the mechanism of reversal of experimental acute hepatic failure by hepatocyte transplantation. 1.

The authors reported previously that single cell suspensions of syngeneic, allogeneic and xenogeneic hepatocytes can significantly improve survival in a rat model of acute hepatic failure induced by D-galactosamine. This report explores the mechanism by which hepatocyte transplantation reverses the toxin-induced hepatic necrosis. Radioautographic studies indicated that intraperitoneally administered hepatocytes labelled with tritiated thymidine did not repopulate the injured recipient liver. Hepatocytes irradiated with 10 000 rad (i.e., the cells were nonreplicating) also resulted in a significant (P less than 0.001) increase in animal survival when given to rats treated with D-galactosamine. Experiments with subcellular fractions of hepatocytes demonstrated that an intact cell was not required and that a heat stable "factor" (or factors) present in the cytosol fraction, which is not insulin or glucagon, is responsible for the increase in survival observed. This factor appears to increase the rate of endogenous regeneration of the injured recipient liver.

Animals↗
PubMed1981

Elimination of 51Cr-labelled target cells as a method of in vivo assessment of immune reactions.

This report describes the use of an in vivo 51Cr release assay which is able to monitor various immune reactions in the rat. This assay is able to quantitate the immune response to tumour and also to assess the relative efficacy of different immunostimulants in this tumour model. These data correlate well with survival studies in tumour-bearing rats. This assay can also measure the sensitizing effect of antigens from animals differing at both the major and minor histocompatibility locus using various routes of sensitization and various donor tissues. Allograft survival can also be correlated to in vivo 51Cr release. This method is both reproducible and specific. The in vivo 51Cr release assay is a useful and versatile means of monitoring the development of antitumour responses and the degree of sensitization to histocompatibility antigens in a variety of situations in the rat. It may therefore prove useful as a rapid method for screening new antitumour and immunosuppressive regimens to be used in various studies.

Adjuvants, Immunologic↗
PubMed1980

Cellular transplantation in the treatment of experimental hepatic failure.

The survival of Lewis rats with D-galactosamine-induced fulminant hepatic failure was prolonged if they were given intraperitoneal injections of single-cell suspensions of liver or bone marrow cells from normal rats. Suspensions of liver cells were also effective in prolonging the survival of rats with ischemia-induced hepatic necrosis. The liver cells did not act by repopulating the recipient liver.

Animals↗
PubMed1980

Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression.

Recent investigation of a biologically active synthetic polymer, NED 137, has demonstrated its ability to induce a B cell differentiation response to certain antigens, even in the presence of T cell depletion. In this report, the effect of T cell depletion combined with NED 137, on skin allografting, is explored in the Lewis strain rat. Animals were T cell-depleted by thymectomy, total body irradiation, and syngeneic marrow repopulation. They were then challenged with skin allografts +/- NED 137 treatment. Graft survival was significantly prolonged in the T-depleted rats regardless of treatment with NED 137. The drug did not increase the immune response to donor antigen as measured by in vivo lysis of 51Cr-labeled cells. Immunization with heterologous erythrocytes produced a low level of differentiation of IgM-producing cells in the T cell-depleted skin allografted group, but in contrast the T-depleted NED 137-treated rats had a normal response to immunization. These data suggest that selective stimulation of the humoral component of the immune response is feasible at a time when T cell-mediated function has been radically suppressed, without producing adverse effects on allograft survival.

Animals↗
PubMed1980

Allogeneic and xenogeneic hepatocyte transplantation in experimental hepatic failure.

Previous studies have demonstrated the efficacy of syngeneic hepatocyte transplantation in the treatment of D-galactosamine-induced acute hepatic failure in Lewis strain rats. This report describes the efficacy and immunological consequences of allogeneic and xenogeneic hepatocyte transplantation in the same model. The i.p. administration of allogeneic (minor and major histoincompatibility) hepatocytes or xenogeneic (rabbit or porcine) hepatocytes at a dose of 4 x 10(7) cells/rat given at 48 hr after toxin all resulted in significant improvement in survival compared to that of controls, and also comparable to the results obtained with syngeneic hepatocyte transplantation. Sensitization to i.p. allogeneic (WF) hepatocyte administration was demonstrated by in vivo 51Cr release, indirect immunofluorescent technique, and accelerated skin allograft rejection. Similarly, the in vivo 51Cr release assay was able to detect sensitization to porcine hepatocytes. Despite evidence of immunogenicity, redosing with either WF or porcine hepatocytes resulted in no overt toxicity. Furthermore, presensitization by either WF hepatocytes or skin allografts did not adversely affect survival after WF hepatocyte treatment in D-galactosamine-induced hepatic failure in Lewis strain rats. These data demonstrate that histocompatibility is not a constraint to successful hepatocyte transplantation and that repeated treatments are potentially safe and efficacious despite sensitization.

Animals↗
PubMed1980

A prospective randomized trial of the selective distal splenorenal shunt.

Distal splenorenal shunt has been compared in a prospective randomized way with end-to-side portacaval shunt in patients who have survived a major hemorrhage from esophageal varices. The operative mortality was higher after the elective shunt than after the portacaval shunt. However, most of these deaths occurred in the early phases of the study. Postoperative encephalopathy was significantly lower after the selective shunt than after the portacaval shunt. Follow-up studies to date show no significant difference in late survival.

Adult↗
PubMed1980

Comparison of the antitumor effects of a synthetic biopolymer and standard adjuvants.

The synthetic biopolymer NED 137 is capable of stimulating an immune response to tumor antigen. This article compares the efficacy of NED 137 to bacille Calmette-Guerin, Corynebacterium parvum, pyran, levamisole, and Freund's complete adjuvant in a rat tumor model where adjuvant treatment is administered after excision of subcutaneous tumor implants. A single intraperitoneal injection of NED 137 at 30 mg/kg body weight prolonged survival beyond 60 days with no evidence of recurrent or metastatic disease, whereas with the other adjuvants, animals survived a mean of 30 to 40 days with 100% local recurrence and a 60% to 90% incidence of pulmonary metastases. Use of NED 137 resulted in a greater lysis of tumor cells compared to other adjuvants when assessed in an in vivo 51Cr release assay. A phase I clinical study of high-risk gastrointestinal cancer patients treated with NED 137 is reported at a median survival time of 23 weeks (103 patients). This group is compared to a historical control group from the same institution. No NED 137-related toxicity has been noted to date.

Adenocarcinoma↗
PubMed1980

Reversal of toxic and anoxic induced hepatic failure by syngeneic, allogeneic, and xenogeneic hepatocyte transplantation.

This report describes the efficacy of syngeneic hepatocyte transplantation in an anoxic model and of xenogeneic (rabbit and porcine) hepatocyte transplantation in a toxic model of fulminant hepatic failure in the rat. Lewis strain rats that received 4 X 10(7) hepatocytes intraperitoneally at 48 hours after hepatic artery ligation had a significantly improved survival rate (79%, n = 14) when compared with control animals (38%, n = 21, P less than 0.05). Xenogeneic hepatocytes (4 X 10(7) cells/rat) given intraperitoneally to D-galactosamine-poisoned Lewis rats at 48 hours after toxin administration were able to significantly improve survival rate as compared with controls (71% versus 14%, n = 14, P less than 0.01 for rabbit; and 75%, n = 14 versus 12.5%, n = 16, P less than 0.001 for porcine). Although an increase in in vivo cytotoxicity could be demonstrated after procine hepatocyte transplantation, no adverse clinical effects were observed. The methodology for the harvest and storage of large numbers of hepatocytes from a large animal liver has been developed, and it is now feasible to proceed to the clinical application of hepatocyte transplantation for human fulminant hepatic failure.

Animals↗
PubMed1979

Elective management of the patient who has bled from esophageal varices.

Variceal hemorrhage can be controlled by nonsurgical means in over 50% of patients. As a result, their general hepatic status can often be improved by preoperative preparation for the elective procedure. The major problem following elective end-to-side portacaval shunting is encephalopathy; it occurs in up to one half of patients who undergo this shunting procedure. Mesocaval shunting has been proposed as a better operation because of lower frequency of encephalopathy; however, the authors' experience has not confirmed this. Distal splenorenal shunting, as shown by the results of a prospective controlled trial, does have a lower frequency of encephalopathy, but the initial morbidity and mortality are higher and an improvement in the duration of survival is not yet evident.

Esophageal and Gastric Varices↗
PubMed1979

Thrombosis of the portal vein following distal splenorenal shunt.

Portal vein thrombosis with a patent shunt is a distinct clinical entity which can follow selective distal splenorenal shunt and should be looked for in patients in whom ascites and abdominal pain develop postoperatively. Possible mechanisms include an increase in blood viscosity and a decrease in portal flow which may be aggravated by inadequate devascularization.

Adult↗
PubMedDate not supplied

The effect of portal diversion on the early stages of liver carcinogenesis in the rat.

The effect of portal diversion by ameroid constriction was studied in the carcinogenic process in the rat after initiation of foci by diethylnitrosamine and after the establishment of putative preneoplastic nodules. Portal diversion or portal diversion plus partial hepatectomy did not act to promote or select for the development of nodules. Furthermore, portal diversion did not alter the natural history of established nodules. These results suggest that vascular factors are not important at these early stages of the carcinogenic process in the rat liver.

Animals↗
PubMedDate not supplied

Recurrence of hyperparathyroidism after total parathyroidectomy and autotransplantation in peritoneal dialysis patients.

OBJECTIVE: To evaluate the effectiveness of total parathyroidectomy (PTX) with autotransplantation in the treatment of secondary hyperparathyroidism (HPT), and to assess recurrence rate of HPT in this peritoneal dialysis (PD) population. DESIGN: A retrospective study in a single home PD unit. PATIENTS: Between 1994 and 1998, 19 of 574 patients on PD underwent PTX for treatment of secondary HPT. MAIN OUTCOME MEASURES: Clinical and biochemical improvement, recurrence of HPT, improvement in anemia post-PTX. RESULTS: Nineteen (3.3%) patients required PTX between 1994 and 1998. These 5 men and 14 women ranged in age from 22 to 66 years; they had been on maintenance PD pre-PTX for 47.5 +/- 38.1 months, and were followed for 26.1 +/- 15.5 months post-PTX. Sixteen patients had temporary hypocalcemia that was managed by oral (n = 10) or intravenous (n = 6) calcium supplements and calcitriol, while 3 patients had severe "hungry bone" syndrome postoperatively. One patient had recurrent laryngeal nerve palsy post-PTX. Bone pain disappeared in all 12 patients. Pruritus improved in 12/13 patients; fatigue improved in 15/16 patients. Comparison showed significant differences between hemoglobin and hematocrit values 1 month pre-PTX and 12 months post-PTX (p < 0.05). Parathyroid hormone (PTH) level in 15 (79%) patients returned to normal (< or = 7.6 pmol/L) during the first month post-PTX. In 5/12 (42%) patients, PTH level was < or = 7.6 pmol/L 2 years post-PTX, while in 2/12 (17%), PTH was > 22.8 pmol/L (three times normal) 2 years post-PTX, and 3/5 (60%) patients had a PTH > 22.8 pmol/L 3 years post-PTX. CONCLUSIONS: Total PTX with autotransplantation is associated with a tendency for recurrence of HPT. Our findings suggest that total PTX with autotransplantation may be an ineffective procedure in controlling HPT over the long term.

Adult↗