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Biomedical subjects

D B Kaufman

Publications and source records attributed to D B Kaufman.

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

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Beneficial and detrimental effects of RBC-adsorbed antilymphocyte globulin and prednisone on purified canine islet autograft and allograft function.

We have examined the effects of prednisone, cyclosporine, azathioprine, and RBC-adsorbed goat antidog antilymphocyte globulin on islet graft function in totally pancreatectomized canines with purified, quantitatively defined, autologous, or allogeneic islets transplanted to the liver. The objectives were twofold: (1) to determine the potential detrimental effects to islet autograft function of the aforementioned agents, and (2) to determine the relative efficacy of the "nontoxic" agents in prolonging purified islet allograft function administered in doses that would be considered tolerable in human. The islet autograft studies demonstrated that prednisone given in doses of 1-2 mg/kg/day had a detrimental effect on islet autograft function, and that the combinations of immunosuppression involving CsA, azathioprine, and ALG were not detrimental to islet autograft function to the extent that hyperglycemia would ensue. In the subsequent allograft studies, three groups of canines received islet transplants: (1) controls (n = 5; 7860 +/- 750 islets/kg/weight), (2) canines given CsA and azathioprine (n = 6; 6810 +/- 890 islets/kg/body weight), and (3) canines given CsA, azathioprine, and RBC-adsorbed goat antidog ALG (n = 8; 6540 +/- 710 islets/kg/body weight). The mean (+/- SE) day of rejection (serum glucose greater than or equal to 200 mg/dl) in the group of canine islet allograft recipients receiving CsA, azathioprine, and ALG was 11.8 +/- 1.4 days--significantly prolonged versus islet allograft recipients receiving no immunosuppression (mean survival 4.8 +/- 1.1 days, P less than 0.03), and versus allograft recipients receiving CsA/azathioprine without ALG (mean survival 4.4 +/- 1.4 days, P less than 0.05). Prednisone appears to be detrimental to islet graft function, even at low doses. ALG was not toxic, and significantly extended the survival of canine islet allografts. The inclusion of steroids as part of maintenance immunosuppression, or as treatment for acute rejection of islets, in human islet transplants should be reconsidered, whereas ALG or other antilymphocyte agents should continue to be used.

Adsorption↗
PubMed1990

Differential roles of Mac-1+ cells, and CD4+ and CD8+ T lymphocytes in primary nonfunction and classic rejection of islet allografts.

The high rate of persistent hyperglycemia, termed primary nonfunction, after islet allotransplantation in C57BL/6 mice recipients of B10.BR strain islets, as compared with B10.BR recipients of C57BL/6 islets, led to a series of experiments to determine whether islet allograft primary nonfunction was attributable to technical aspects of the transplant procedure or whether it was a consequence of alloimmunity. Primary nonfunction was prevented by systemic pharmacologic immunosuppression of the host with cyclosporine. Selective immunodepletion of host CD4+ and CD8+ T lymphocytes significantly extended the time of classic rejection but did not significantly affect the rate of primary nonfunction. However, modulation of macrophages by administration to the host of silica completely abolished primary nonfunction. These observations, in conjunction with the immunohistological findings of intense macrophage infiltration in islet allografts from recipients exhibiting persistent post-transplant hyperglycemia, support the hypothesis that primary nonfunction results from a cell-mediated host-immune response of rapid onset that is dependent on macrophages or macrophage byproducts as the main effectors.

Animals↗
PubMed1990

IgG subclasses and IgM in rats: immunoregulatory effects of cimetidine on serum levels.

Previous studies have demonstrated an immunomodulatory role for cimetidine on antibody production. In these experiments we measured IgG subclasses and IgM in rats and also examined the effects of cimetidine on serum levels. Four week-old Sprague-Dawley rats were given cimetidine in three different treatment regimens. IgG subclasses and IgM determinations were carried out by radial immunodiffusion method on sera when animals were 6 and 8 weeks old. IgG1 levels in 6 week-old animals who received intraperitoneal cimetidine on days 1, 2, 3, 4, 5, 6, 8, 9, 15 and 16 were significantly higher (305 +/- 12 mg/l vs 236 +/- 53 in control animals). By 8 weeks of age in control animals, IgG1 levels had fallen to 78 mg/l and were statistically lower than the levels in all cimetidine treatment groups. Eight week-old control animals also demonstrated a four-fold fall in IgG2b levels (613 +/- 310 mg/l) when compared to in 6 week-old control (2295 +/- 1057 mg/l) animals, or 8 week-old animals who had received cimetidine. Animals receiving intravenous cimetidine on days 4, 11 and 18 had significantly lower (133 +/- 3 mg/l) serum levels of IgG2c, at 6 weeks of age, as compared to control animals (177 +/- 16); however, no statistically significant differences in IgG2c levels were observed in 8 week-old animals. No statistically significant differences in the levels of IgG2a or IgM were observed in either 6 or 8 week-old control and experimental animals. It appears that cimetidine does influence certain IgG subclasses, however, route and timing of cimetidine administration are critical in modulating these effects.

Animals↗
PubMed1990

Canine pancreatic islet transplantation: a comparison of two isolation techniques.

A new method (type B) for isolation of canine islets was developed, utilizing intraductal collagenase perfusion, stationary digestion, filtration and tissue separation by means of a dextran density gradient. The results of this technique were compared with those of a previously established method (type A). Islets were autotransplanted either via the splenic or the portal vein. Lasting normoglycemia was obtained in 5/8 intrasplenic type B transplants (63%), 6/8 intrahepatic type B transplants (75%), 5/6 intrasplenic type A transplants (83%) and 0/3 intrahepatic type A transplants. No difference was found in metabolic parameters 2 weeks after successful transplantation following type A or B islet isolation. Islet yield was higher with type A and purification better with type B isolation. Both techniques are relatively simple and inexpensive. Because of its higher purification rate and the success of intrahepatic islet transplantation method B has replaced method A as the routine procedure in our laboratory.

Animals↗
PubMed1990

Immunoglobulins in hemophilia: correlation between IgG subclasses, IgE and HIV antibody.

Twenty-two patients with hemophilia who had received factor VIII concentrate were evaluated. Only 12 of 22 were seropositive for HIV. Elevation of IgG, IgG1, IgM and IgE was not related to HIV seropositivity. Means of IgG1, IgG2, and IgG3 were significantly higher in patients with elevated IgG. Means of IgG2 and IgG3 were significantly lower in patients with elevated (greater than or equal to 251) serum IgM. Seven of the 22 patients demonstrated elevated (greater than or equal to 100) serum IgE; mean serum IgA was significantly lower, though in normal range, in these seven patients. Alterations in serum immunoglobulins in patients with Hemophilia are frequently seen, however, like other immune-dysfunction in these patients, these abnormalities can not be attributed to their HIV status.

Adolescent↗
PubMed1990

Purified canine islet autografts. Functional outcome as influenced by islet number and implantation site.

Using a modification of the basic principles of pancreatic intraductal collagenase digestion and density gradient purification to isolate canine islets, in conjunction with simultaneous fluorogenic and dithizone islet staining, we quantified the yield, purity, and viability of the isolated islets. We then determined the combined influences of total and weight-corrected islet counts and implantation site on immediate and long-term functional outcome of purified canine islet autografts. Weight-corrected islet counts were 100% sensitive and specific in differentiating successful and unsuccessful islet autografts implanted to the liver (n = 10) and spleen (n = 10) of pancreatectomized dogs. The threshold number of islets required to achieve normoglycemia in the liver (4400 islets/kg) and spleen (4650 islets/kg) were nearly identical. Islet autografts failed to ameliorate hyperglycemia when implanted to the renal subcapsular space (n = 5) at counts of 4400 to 5500 islets/kg. The mean one- and three-month intravenous glucose tolerance test K-values of dogs with purified islet autografts to the liver (-1.43 +/- 0.27 and -1.69 +/- 0.27, respectively) and spleen (-1.78 +/- 0.36 and -1.64 +/- 0.3, respectively) were also similar. Time needed to achieve normoglycemia , however, was significantly (P less than 0.02) shorter for intrahepatic islets (1.0 +/- 0.0 days posttransplant) than intrasplenic islets (6.8 +/- 2.3 days posttransplant). The long-term durability of islet autograft function was not unlimited. Overall, thirteen canine islet autograft recipients have been followed for greater than or equal to 12 months posttransplant (range 12-18 months), seven canine islet autograft recipients (five intrahepatic and two intrasplenic) have had spontaneous recurrence of hyperglycemia at 2, 6, 11, 13, 14, 8, and 16 months, respectively. The phenomenon depended only on the number of islets implanted. The data underscore the significance of quantitatively defined islet preparations and the importance of islet number and implantation site on immediate and long-term functional outcome of canine islet autografts.

Animals↗
PubMed1989

Fatal fungal peritonitis in an adolescent on continuous ambulatory peritoneal dialysis: association with deferoxamine.

An unusual case of Rhizopus microsporus (mucormycosis) fungal infection in a teenage boy on continuous ambulatory peritoneal dialysis is presented. Premortem cultures were negative and the patient developed a rapidly disseminated fatal infection. The patient was being treated with deferoxamine (DFO) for iron and aluminum overload. An argument is made for a probable association between DFO and this fatal fungal infection in patients with end-stage renal disease.

Adolescent↗
PubMed1989

A simple method of canine pancreatic islet isolation and intrahepatic transplantation.

Clinical pancreatic islet transplantation has been impeded by the inability to isolate an adequate mass of functional tissue that will ameliorate diabetes. A simplified method of canine islet isolation was developed that allowed for either intrasplenic or intrahepatic transplantation. Following total pancreatectomy, parenchymal digestion was accomplished by intraductal collagenase perfusion and stationary incubation. The digested tissue was dispersed by filtration through a steel mesh (400 microns), washed, and separated on a discontinuous dextran density gradient. Enhanced islet tissue (2-4 ml) was recovered from the uppermost interface of the gradient and autotransplanted. The islet isolation procedure was tested in two series of dogs undergoing either intrasplenic or intrahepatic engraftment. Immediate and sustained normoglycemia (plasma glucose less than 200 mg%) was obtained in 5 of 8 dogs (63%) in the intrasplenic group and 6 of 8 dogs (75%) in the intrahepatic group. The mean fasting plasma glucose concentration 2 weeks after transplantation was 102.8 +/- 6.4 mg% in the intrasplenic group and 103.3 +/- 8.4 mg% in the intraportal group. The mean IVGTT K-values 2 weeks after transplantation were -1.41 +/- 0.35% and -1.21 +/- 0.13%, respectively. On the basis of insulin content, the islet yield was 33.0 +/- 3.7% of the total pancreas in the intrasplenic group and 33.0 +/- 3.1% in the intrahepatic group. Islet mass was enhanced 10.2 +/- 1.5 and 20.0 +/- 6.2 fold, respectively, on the basis of insulin/amylase ratios. The success rate in this canine model compared favorably with previously published results from other laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Immunodeficiency in patients with hemophilia: an underlying deficiency and lack of correlation with factor replacement therapy or exposure to human immunodeficiency virus.

Nineteen patients with hemophilia, five of whom were classified as untreated, were immunologically evaluated by the measurement of cell surface markers, natural killer cell activity, mitogenic responses, polyclonal immunoglobulin production, and serologic evidence of human immunodeficiency virus infection. No correlations were found between human immunodeficiency virus infection and immune abnormalities, or between patients who did or did not receive factor therapy, although the abnormalities were more profound in those who received treatment. An intrinsic B cell abnormality in patients with hemophilia is suggested.

Acquired Immunodeficiency Syndrome↗