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Biomedical subjects

R Pollak

Publications and source records attributed to R Pollak.

At least 91 records · Page 5Linked to original sources

Hepatocyte transplantation for the low-density lipoprotein receptor-deficient state. A study in the Watanabe rabbit.

The Watanabe heritable hyperlipidemic (WHHL) rabbit reproduces human familial hypercholesterolemia due to a congenital low-density lipoprotein receptor deficiency and is characterized by elevated serum LDL cholesterol levels and early atherosclerosis. We attempted to transplant normal allogeneic hepatocytes into WHHL rabbits without chronic immunosuppression to cure the LDL receptor-deficient state. Livers from normal New Zealand White (NZW) rabbits were digested by intraportal perfusion of collagenase solution. Pure hepatocytes (PH) were obtained by Percoll gradient separation and nonparenchymal (NP) liver cells by pronase digestion. PH and NP were incubated with fluorescein isothiocyanate-monoclonal anti-rabbit class I, anti-class II, and anti-T cell antibodies and subjected to flow cytometry analysis. PH and NP were also used as stimulators in one way mixed lymphocyte-hepatocyte cultures (MLHC), before and after ultraviolet B light (UVB) exposure. Intraportal and intrasplenic injection of allogeneic PH were also performed in homozygous WHHL rabbits. PH were attached to collagen-coated dextran microcarriers (mc-PH) for intraperitoneal injection. Recipient control and transplanted WHHL rabbits received a single dose of cyclosporine subcutaneously (10 mg/kg/s.c.) at the time of transplantation. PH were mainly class I-positive (77.6%) and class II-negative (5.9%), while 31.5% of NP cells were class II-positive. In MLHC, PH did not stimulate proliferation, (stimulation index: 0.97 +/- 0.21), unlike NP (SI: 23.7). This latter response was abrogated by prior exposure of NP to UVB light. Intraportal injection of PH (n = 4) reduced serum LDL cholesterol to 60% of baseline, an effect lasting 2-3 weeks, and dose-dependent. Intraperitoneal mc-PH, 4 x 10(8) (n = 4), reduced serum LDL cholesterol levels to 45% of baseline more than 4 weeks posttransplant (P = 0.04). We conclude that transplantation of normal allogeneic NZW rabbit mc-PH reduces serum LDL cholesterol levels in homozygous WHHL rabbits without chronic immunosuppression. Longitudinal studies will establish if less atherosclerosis develops in mc-PH WHHL recipients than sham controls.

Animals↗

The immunosuppressive properties of new oral prostaglandin E1 analogs.

Prostaglandins play an important role in cell-mediated immune responses. Their clinical use has been limited by poor oral bioavailability, short half-lives, and significant toxicity profiles. We studied the immunosuppressive properties of new, synthetic, prostaglandin E1 (PGE1) methyl ester analogs (misoprostol, enisoprost) with oral bioavailability using an allogeneic in vitro immunoassay. Our results show that the PGE1 analogs suppress alloproliferative responses and supplement the immunosuppressive activity of cyclosporine and methylprednisolone. Moreover, we demonstrate that addition of recombinant interleukin-2 to the PGE1 analogs restores alloimmune responsiveness and the expression of surface class II antigen and IL-2 receptors on responder lymphocytes. These studies, together with preliminary in vivo data in rodents and man, suggest that the new synthetic oral PGE1 analogs may provide therapeutic efficacy in clinical transplantation and a variety of immunologically mediated diseases.

Administration, Oral↗

Immunosuppressive effect of misoprostol: a new synthetic prostaglandin E1 analogue.

Prostaglandins are reported to play an important regulatory role in cell-mediated immunity. The immunosuppressive properties of a new synthetic oral prostaglandin E1 analogue, misoprostol, were studied in vivo in a rat heterotopic cardiac allograft model, and in vitro in mixed lymphocyte reaction. The results show that parenteral misoprostol, alone or in combination with low dose cyclosporin immunosuppressive therapy, significantly prolonged cardiac allograft survival compared with appropriate controls. Oral misoprostol alone in this model did not allow for measurable cardiac allograft prolongation. In vitro misoprostol demonstrated significant dose-response inhibition of the mixed lymphocyte culture assay. It is concluded that new prostaglandin E1 analogues with oral bioavailability may have important applications to clinical transplantation in man, and may be cyclosporin sparing.

Administration, Oral↗

Reconstructive surgery for immunosuppressed organ-transplant recipients.

Prolonged vascularized organ allograft survival and an improved quality of life are now possible for many transplant recipients. These advances are due largely to greater understanding of the immune response, the development of potent immunosuppressive agents (cyclosporin A), and improved surgical techniques. Thus more of these patients may require surgical procedures related or unrelated to their original operation, and the plastic surgeon, among other specialists, should be aware of the special problems of the immunocompromised transplant recipient who needs to undergo reconstructive surgery. We report our experience with 15 kidney, heart, and liver transplant recipients who required reconstructive surgery for a variety of conditions. The combined team approach by reconstructive and transplant surgeons is described, as well as the perioperative drug protocol and the special problems that immunosuppressed transplant recipients present. We conclude that these patients can successfully undergo major reconstructive procedures as long as the plastic surgeon not only performs technically flawless surgery, but also familiarizes himself or herself with the special problems of the immunosuppressed host, including the ever-present risk of sepsis and delayed and impaired wound healing, the potential for acute Addisonian crisis, and the possibility of multiple complicating comorbid conditions.

Anti-Bacterial Agents↗

Low-dose oral acyclovir for prevention of herpes simplex virus infection during OKT3 therapy.

This report evaluates the incidence of clinically significant HSV infection among 23 renal allograft recipients receiving OKT3 for treatment of steroid- or ALG-resistant acute rejection. No HSV infections occurred among the five HSV seronegative patients studied; three of 11 HSV seropositive patients (27%) treated with a ten-day course of low-dose acyclovir prophylaxis developed HSV infection. All three occurred after acyclovir was stopped. Five of six evaluable seropositive patients (83%) who did not receive acyclovir prophylaxis suffered HSV infection. We conclude that low-dose oral acyclovir may be effective in the prevention of HSV infection during OKT3 treatment of seropositive patients. Continuation of acyclovir prophylaxis for two to four weeks following the conclusion of OKT3 therapy may prevent occurrence of delayed infections.

Acyclovir↗

The natural history of and therapy for perirenal fluid collections following renal transplantation.

Fluid collections following renal transplantation are not rare and may be associated with serious complications. We studied the incidence, clinical features, pathology and treatment outcome of perirenal fluid collections after kidney transplantation. Between January 1977 and June 1985, 386 consecutive renal transplants were performed at our university. All allografts were studied with B-mode ultrasonography together with a renal scan in the immediate post-transplant period, at 6-month intervals or when clinically indicated. Symptomatic fluid collections, those associated with rejection episodes and those containing more than 50 to 100 ml. fluid were aspirated under sonographic control via aseptic techniques. There were 190 fluid collections (49 per cent) observed during followup (2 to 11 years). Of these collections 98 (51 per cent) were estimated to be less than 50 ml. in volume, were clinically insignificant and resulted in no morbidity. A total of 92 collections was aspirated with 1 aspiration being diagnostic and therapeutic in 57 instances (serous or serosanguinous fluid). The 35 collections remaining were revealed to be lymphoceles on biochemical grounds. Of 13 lymphoceles associated with rejection episodes 8 resolved on initial aspiration. Of the recurrent lymph collections 27 were treated with repeated aspiration, tetracycline sclerotherapy or an operation (10 were treated with marsupialization into the peritoneal cavity). No large collections of urine or blood were detected and 1 infected lymphocele required external drainage. No renal allograft was lost as a result of a fluid collection and over-all graft survival was not affected by the development of perirenal fluid collections. We conclude that perirenal fluid collections are detected commonly in the post-transplant period using B-mode ultrasonography. The majority of these collections are small and will require careful observation only or they will resolve with a single aspiration. Aggressive diagnostic and therapeutic measures are used only for those collections that are symptomatic or result in allograft dysfunction. A rational approach to the diagnosis and treatment of peritransplant fluid collections is described in the form of an algorithm.

Body Fluids↗

The preperitoneal approach and prosthetic buttress repair for recurrent hernia. The evolution of a technique.

Repair of recurrent groin hernias is associated with a high incidence of repeat recurrences (2-19%). Reported herein is a 10-year experience of the management of recurrent groin hernias through the use of the preperitoneal approach with the addition of a reinforcing prosthetic mesh buttress. Two hundred and three recurrent groin hernias in 195 patients (192 men, three women) were treated between July 1975 and October 1986. The preperitoneal approach to the inguinal region was performed under regional anesthesia to define the nature of the recurrent hernia. Initial experience in a randomized trial between the use of local endogenous tissue repair versus endogenous repair with a prosthetic polypropylene mesh buttress demonstrated superiority of the latter in reducing repeat recurrences of anatomically defined direct or combined recurrent hernias. Pure indirect and femoral recurrences did not mandate mesh reinforcement. Long-term follow-up was available for 115 hernias (56%) in 102 patients (52.3%) over a period of 6 months to 10 years. Eight patients had repeat recurrences a mean of 30 +/- 22 months after repair. Six recurrences (four direct, two indirect) occurred in an early experience, when no mesh was used. Two recurrences (one indirect and one lateral to the mesh) representing 1% of all hernias (1.7% of those followed-up) have occurred after routine use of the mesh buttress, with the last re-recurrence seen in December 1982. Three ventral hernias (1.5%) occurred at the wound of entry, but none have occurred since placement of the mesh was modified to cover this wound. There were five (2.5%) wound infections and one (0.5%) hydrocele with no re-recurrences. It is concluded that the preperitoneal approach to recurrent groin hernias, together with the appropriate use of a reinforcing mesh buttress, is safe, allows anatomic definition of the hernial defect, and is followed by few repeated recurrences. The evolution of this approach during the last 10 years has made it the procedure of choice for the management of all recurrent groin hernias at the University of Illinois College of Medicine.

Female↗

The relationship between flow cytometer crossmatch results and subsequent rejection episodes in cadaver renal allograft recipients.

Flow cytometry (FC) T and B cell crossmatches were done retrospectively for 38 cadaver renal transplant recipients (29 first and 9 retransplants--minimum follow-up 12 months) using both current pretransplant serum and peak-reactive sera. An increase in median fluorescence intensity (channel shift) and/or an increase in the number of donor T and/or B cells binding antibody in test sera occurred in 23 cases. These 23 patients experienced a greater number of reversible rejection episodes as compared with patients with negative FC crossmatches (65% vs. 33%), P = 0.031. Graft outcome, however, was not different in the two groups. Thus, a positive FC crossmatch allows for the detection of subliminal levels of donor presensitization and is associated with a greater number of rejection episodes. A positive FC crossmatch is not predictive of ultimate graft loss.

B-Lymphocytes↗