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Biomedical subjects

M D Pescovitz

Publications and source records attributed to M D Pescovitz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Zinc deficiency and its repletion following liver transplantation in humans.

Zinc deficiency is common in patients with end-stage liver disease but its prevalence and resolution in liver transplant recipients has not been reported. We hypothesized that with normalization of liver function after transplant, zinc levels should rapidly return to normal, obviating the need for oral supplementation. Serum zinc levels were obtained as part of routine laboratory studies just prior to liver transplantation in 34 patients. Of these, 22 had at least one additional zinc level obtained post-transplant. The charts of these 34 patients were retrospectively reviewed for pre- and post-transplant zinc, albumin, protein, and cholesterol levels, prothrombin times, use of oral zinc supplementation, and patient demographics including age, gender, cause of liver failure, UNOS status at the time of transplant, and the use of a pre-transplant trans-jugular intrahepatic portosystemic shunt (TIPS). Post-transplant, the patients received standard enteral formula for nutrition. The overall zinc level for the group was 37.4 +/- 9.0 micrograms/dl (mean +/- s.d., normal = 60-150 micrograms/dl). Thirty-two of the 34 patients (94%) had a zinc level in the subnormal range. There were no differences in zinc levels between patients with alcoholic and non-alcoholic liver failure, males versus females, UNOS status (low = status 1 and 2, high = 3 and 4), pre-transplant use of TIPS nor correlation between age and zinc level. All 22 patients who had a post-transplant zinc level demonstrated an increase from 40.1 +/- 9.7 micrograms/dl to 68.5 +/- 14.1 micrograms/dl (p < and = 0.0001, paired t-test). Our findings indicate that zinc deficiency, generally profound, should be assumed to be present in every patient with end-stage liver disease awaiting transplant. During the waiting period oral supplementation with zinc should be provided. The degree of deficiency is not effected by cause of liver failure, UNOS status, or the presence of TIPS. Following transplantation, zinc levels rapidly recover, obviating the need for checking levels and oral supplementation.

Administration, Oral↗
PubMed1995

Reduced human IgG anti-ATGAM antibody formation in renal transplant recipients receiving mycophenolate mofetil.

Exposure to the equine-derived polyclonal antithymocyte preparation, ATGAM, frequently elicits human anti-ATGAM antibody formation. The influence of concomitant immunosuppressants on this antiantibody response has not been established. We therefore evaluated IgG antibody formation to ATGAM in 47 patients receiving ATGAM as part of a prospective, randomized, double-blinded study of mycophenolate mofetil versus azathioprine for maintenance immunosuppression after primary cadaveric renal transplantation. All patients received ATGAM for induction of immunosuppression plus methylprednisolone, prednisone, and cyclosporine. In addition, patients were randomized to receive maintenance immunosuppression consisting of either azathioprine (AZA) 1-2 mg/kg/day, mycophenolate mofetil 2 gm/day (MMF2), or mycophenolate mofetil 3 gm/day (MMF3). Patient sequential sera were independently tested for IgG anti-ATGAM antibody by 2 laboratories, which were blinded to treatment arm assignments, using enzyme-linked immunosorbent assays. Both laboratories found significantly greater anti-ATGAM antibody formation in group AZA compared with groups MMF2 and MMF3: laboratory 1 reported sensitization rates in the 3 groups of 94% (AZA), 50% (MMF2) (P < 0.02 vs. AZA), and 60% (MMF3) (P < 0.05 vs. AZA); and laboratory 2 reported rates of 67% (AZA), 17% (MMF2) (P < 0.02 vs. AZA), and 10% (MMF3) (P < 0.02 vs. AZA). In addition, fewer patients formed high titer antibody in the MMF arms compared to the AZA arm: 56% (AZA), 0% (MMF2) (P < 0.02 vs. AZA), and 20% (MMF3) (P < 0.02 vs. AZA) of patients for laboratory 1; and 20% (AZA), 0% (MMF2) (P < 0.05 vs. AZA), and 0% (MMF3) (P < 0.05 vs. AZA) of patients for laboratory 2. Differences in test results between the 2 laboratories were explained by differences in the sensitivity of their respective immunoassays and in the criteria used for assigning a positive result to test specimens. In this protocol, MMF at 2-3 gm/day was associated with a reduced incidence and titer of IgG anti-ATGAM antibody formation compared with standard azathioprine dosing. Although MMF previously has been reported to inhibit T cell responses that mediate acute cellular rejection, this is the first demonstration that MMF significantly inhibits human B cell responses to antigen in vivo.

Adult↗
PubMed1995

Preservation of postprandial intestinal hyperemic response after small bowel transplantation.

Postprandial intestinal hyperemia (PIH) is a normal physiological phenomenon and is thought to accommodate the increased intestinal metabolic demand during food digestion. Lack of such a response could lead to malabsorption. The purpose of this study was to determine whether transplanted intestine retains the ability to mediate PIH. Nineteen rats with syngeneic orthotopic small bowel transplantation (SBT) and 13 normal controls were further divided into two subgroups to receive gastric gavage of either 2 mL of Ensure Plus (EP) high-calorie liquid nutrition or 2 mL of normal saline. Intestinal blood flow was determined before, and 20 and 45 minutes after the gavage, employing a colored microsphere technique. The results showed that basal blood flow to the transplanted intestine (56.7 +/- 26.7 mL/min/100 g) was similar to that of normal intestine (64.2 +/- 35.8 mL/min/100 g; P > .1). EP feeding elicited a marked increase in intestinal blood flow (PIH phenomenon) in both normal and SBT animals. The magnitudes of flow increase were similar for the two groups (249 +/- 99% versus 241 +/- 76% of baseline 45 minutes after EP feeding in the normal and transplanted intestine, respectively; P > .1). The results indicate that hyperemic response to feeding is normal in syngeneic orthotopic SBT.

Animals↗
PubMed1995

Tube jejunostomy in liver transplant recipients.

BACKGROUND: Nutritional support after liver transplantation most often uses intravenous hyperalimentation followed by nasoduodenal tubes until adequate intake is achieved. Because of difficulties with nasoduodenal tubes, we place jejunostomy tubes (j-tube) at the time of the transplantation, allowing immediate postoperative enteral nutrition. This review analyzes the complications of this procedure in transplant recipients. METHODS: J-tubes were placed in 108 of 119 adults who underwent liver transplantation between October 1989 and June 6, 1994. These patients were retrospectively reviewed for the type and frequency of j-tube-related complications. J-tube feeds with a semielemental formula were started within 24 to 48 hours after transplantation. RESULTS: Eighteen complications occurred in 16 patients. Six were mechanical obstructions of the j-tube because of kinking by the fascia. Six exploratory laparotomies were required, two each for infection, small bowel obstruction, or catheter displacement. Four other infections were treated by local incision and drainage or percutaneous drainage. One tube required surgical removal in the operating room. CONCLUSIONS: Tube jejunostomies can be safely placed at the time of liver transplantation with a low risk of serious complications. We recommend the routine use of j-tubes in patients receiving a liver transplant for the immediate posttransplantation institution of enteral nutrition.

Abscess↗
PubMed1995

Nutrition support following liver transplantation: comparison of jejunal versus parenteral routes.

Liver failure patients are chronically malnourished at the time of transplant. We have used jejunostomy tubes (j-tube) placed at the time of liver transplantation for immediate postoperative enteral nutrition. We compared the effectiveness of this means of nutrition to total parenteral nutrition (TPN). Sixty-three adult patients fed enterally (ENT) with a semi-elemental diet were retrospectively compared to 21 adult controls alimented with TPN, both beginning after liver transplantation. Data collected included: day to initiation of nutrition, day of achieving goal nutrition, day of removal of nasogastric tube, day of initiation of oral nutrition, day of achieving oral nutritional goal, and serum albumin, cholesterol, SGOT, SGPT, GGT, and bilirubin. Intestinal complications of diarrhea, ileus, and perforation were analyzed. Statistical analyses used an unpaired t-test for continuous data, and Chi square for categorical data. Caloric requirements, percentage ideal body weight, age, and initial cholesterol and albumin were equal. Fifty-four of the ENT patients were fed only by j-tube; 9 ENT patients also required TPN. ENT patients started on nutrition sooner (3 +/- 1.7 vs. 1.7 +/- 0.9 days, p = 0.001), reached goal oral nutrition sooner (19.5 +/- 11 days vs. 38.6 +/- 24.6 days, p = 0.0061, Mann-Whitney U test), and had a lower frequency of prolonged postoperative ileus (8.3%, vs. 33%, p = 0.009) than TPN patients. ENT patients had a greater frequency of diarrhea than TPN controls (73% vs. 25%, p < 0.001). This diarrhea was self-limited, lasting 3 to 5 days, and responded to anti-motility drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Ultrasound-guided pediatric liver transplant biopsy using a spring-propelled cutting needle (biopsy gun).

Biopsy is the best way to diagnose allograft rejection, the most common complication following liver transplantation. The authors reviewed 99 consecutive ultrasound-guided cutting needle biopsies in 19 infants and children. Conscious sedation was used with 95 biopsies. General anesthesia was used with four biopsies, all in patients undergoing percutaneous biliary procedures at the same time. Ninety-eight biopsies were diagnostic. Only one major complication occurred: biloma. Ultrasound-guided cutting needle biopsy of pediatric liver transplant patients can be performed safely and efficaciously.

Biopsy, Needle↗
PubMed1994

Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction.

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.

Administration, Oral↗
PubMed1994

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Porcine peripheral blood CD4+/CD8+ dual expressing T-cells.

The porcine T-cell population is unique in that there is a large percentage of CD+CD8+ dual expressing peripheral T-cells. This paper reviews the data available on these porcine T-cells and compares them to the much rarer dual expressing T-cells in humans. The percent of dual expressing cells increases with activation in in vitro culture with various antigens including pseudorabies virus. The percent of resting dual expressing cells also increases with the age of the pig. Flow-cytometric-sorted dual expressing cells responded in culture to the super antigen staphylococcal enterotoxin B. Selected CD4+CD8- cells cultured in vitro developed expression of CD8 and maintained the dual expressing phenotype for the 12 weeks of culture. Dual expressing cells freshly prepared from porcine blood did not express the IL-2 receptor as demonstrated by their failure to bind FITC-IL-2 and an anti-porcine IL-2 receptor monoclonal antibody. In response to activation with phorbol myristic acetate, CD4, but not CD8, was down regulated on the dual expressing T-cells. In summary, porcine dual expressing T-cells constitute a substantial percentage of the porcine peripheral T-cell pool. These cells appear to contain the majority of the memory T-cell with their frequency increasing with blood donor age and in vitro culture. Although the receptor specificity is not known, they have a functional receptor. Finally, the function of the two accessory molecules CD4 and CD8 in these cells is not known, but their regulation is distinct, thereby suggesting no equivalent roles in immune function.

Animals↗
PubMed1994

Summary of workshop findings for porcine T-lymphocyte antigens.

Fifty-four mAb preselected in the first round of the first porcine CD workshop for their possible reactivity with T-lymphocyte specific antigens and/or activation antigens were further analysed in a second round. PBMC, thymocytes and nylon-wool purified T lymphocytes derived from peripheral blood, mesenteric lymph nodes and spleen served as target cells for flow cytometric analyses. For the classification of activation antigens several experiments were performed with activated, mitogen-stimulated T lymphocytes and long-term T-lymphocyte cultures. Out of the 54 mAb, 35 mAb could be distributed to six different CD clusters and two swine workshop clusters (SWC). Five mAb could be distributed to the porcine CD2, four mAb to the CD4. Six mAb seemed to recognize the porcine CD5 and two mAb the porcine CD6 analogue. Six mAb were directed against the porcine CD8, whereas two different epitopes could be defined. One mAb was directed against the porcine CD25 analogue. Nine mAb could be clustered to the SWC1, defining an antigen on T lymphocytes and cells of the myeloic linage. Two mAb with high T-cell specificity were clustered to the SWC2.

Animals↗
PubMed1994

Analysis of monoclonal antibodies reactive with the porcine CD2 antigen.

As result of the First International Swine CD Workshop, six monoclonal antibodies (mAbs) (numbers 014, 023, 024, 057, 128, and 130) clustered closely to the internal standard anti-porcine CD2 mAb, MSA4. Despite the close clustering, the cluster was split into two subgroups. To further characterize the relationship between these mAbs, they were used in flow cytometry to inhibit binding of MSA4 to porcine lymphocytes. mAbs 014 (1038-8-31), 023 (MAC83), 024 (MAC80), 057 (PG168), and 128 (MSA4) completely inhibited the binding of MSA4, mAb 130 (MSA2) failed to inhibit MSA4 binding. On dual parameter flow cytometry comparing MSA2 with MSA4, all MSA2+ cells were MSA4+, two thirds of the MSA4+ cells were MSA2-. We conclude that five of the mAbs bind to the same or a closely related epitope on porcine lymphocytes. mAb 130 appears to have aberrantly clustered with the CD2 group of mAb.

Animals↗