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Biomedical subjects

S S Kaufman

Publications and source records attributed to S S Kaufman.

At least 19 recordsLinked to original sources
PubMed2006

Safety and immunogenicity of varicella-zoster virus vaccine in pediatric liver and intestine transplant recipients.

Primary varicella-zoster virus (VZV) infections following organ transplantation may cause significant morbidity. We examined the safety and immunogenicity of Varivax after transplantation as a potential prophylactic tool. Pediatric liver and intestine transplant recipients without history of chickenpox received one dose of Varivax. VZV humoral and cellular immunity were assessed before and > or =12 weeks after vaccination. Adverse events (AE) and management of exposure to wild type VZV were monitored. Sixteen VZV-naïve subjects, 13-76 months of age, at 257-2045 days after transplantation were immunized. Five children developed mild local AE of short duration. Four subjects developed fever and four developed non-injection site rashes, three of whom received acyclovir. Liver enzymes did not increase during the month after vaccination. Eighty-seven percent and 86% of children developed humoral and cellular immunity, respectively. There were five reported exposures to varicella in four children, none of which resulted in chickenpox. One subject received VZV-immunoglobulin and another subject with liver enzyme elevations after exposure received acyclovir; all remained asymptomatic. Varivax was safe and immunogenic in pediatric liver and intestine transplant recipients. Larger studies are needed to establish the efficacy and role of varicella vaccination after transplantation.

Chickenpox↗
PubMed2001

Lack of utility of intestinal fatty acid binding protein levels in predicting intestinal allograft rejection.

INTRODUCTION: The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. MATERIALS AND METHODS: I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. RESULTS: Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. DISCUSSION: Serum I-FABP levels do not predict clinical intestinal allograft rejection.

Adult↗
PubMed2001

Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

Child↗
PubMed2001

Small bowel transplantation: selection criteria, operative techniques, advances in specific immunosuppression, prognosis.

Intestinal transplantation is now an accepted therapy for intestinal failure when parenteral nutrition therapy cannot be tolerated. During the past year, evidence has been provided indicating that neither stomach nor colon need to be included in the transplant, even if a primary motility disorder is the indication for surgery. The liver should be included in the composite allograft when there are clinical indications of portal hypertension resulting from parenteral nutrition associated cholestasis. When liver disease develops, operations intended to improve gut function should be avoided in preference of early listing for transplantation. During the past year, initial attempts at adult to child intestinal transplantation were carried out with some success; reduction in the diameter of the adult donor bowel may not be uniformly necessary. New immunosuppressive therapies have been employed recently, but few have been subjected to peer review. Experimental models have clarified the pathology, if not the immunobiology, of chronic intestinal allograft rejection and the ability of the liver to promote tolerance of a cotransplanted intestinal allograft. Treatment of posttransplant lymphoproliferative disease has been augmented by the use of anti-CD 20 antibody that targets Epstein-Barr virus infected B-cells for destruction with high specificity.

Child↗
PubMed2001

Omeprazole pharmacodynamics and gastric acid suppression in critically ill pediatric transplant patients.

OBJECTIVE: To characterize the pharmacodynamics and pharmacokinetics of omeprazole suspension in critically ill pediatric liver/intestinal transplant patients. DESIGN: Open-label pharmacodynamic and pharmacokinetic study. SETTING: Pediatric intensive care unit of an academic medical center. PATIENTS: Eleven pediatric liver and/or intestinal transplant patients. INTERVENTIONS: Extemporaneously prepared 0.5 mg/kg omeprazole suspension every 12 hrs via nasogastric tube before sequential measurements of omeprazole serum concentration and gastric pH monitoring. Gastric pH was monitored continuously for 48 hrs and plasma omeprazole concentrations were determined upon first and multiple dosing. MEASUREMENTS AND MAIN RESULTS: Mean onset of action of omeprazole in a sodium bicarbonate vehicle was 62 +/- 82 mins (range, 2-226 mins). Subjects <4 yrs of age exhibited a more variable onset of omeprazole action (range, 3-226 mins) when compared with older subjects (onset of action, 2-40 min). Omeprazole maximum concentration and area under the concentration-time curve for the dosage interval were significantly greater upon multiple dosing when compared with the first dose. Mean baseline gastric pH in this study population was 1.0 +/- 0.8. Gastric pH remained >4.0 for 78.8% +/- 18.9% of the first dosage interval and 97.8% +/- 5.4% of multiple dosage intervals regardless of age when administered twice daily as a suspension. CONCLUSION: These results support the use of omeprazole administered twice daily as a suspension to maintain gastric pH of >4.0 and to achieve maximal pharmacodynamic effect in pediatric liver and/or intestinal transplant patients.

Journal Article↗
PubMed2000

Disaccharidase activities and fat assimilation in pediatric patients after intestinal transplantation.

BACKGROUND: Intestinal transplantation has become an accepted therapy for short bowel syndrome and other types of intestinal failure. In order to assess digestive capabilities and feeding practices in a group of 22 pediatric patients after intestinal transplantation, we assessed mucosal disaccharidase activities and assimilation of total dietary lipid and vitamin E. Twelve of the patients had undergone contemporaneous liver transplantation. METHODS: Mucosal biopsies were assayed for disaccharidase activities between 15 and 412 days after transplantation in 7 of the 22 when all were receiving some enteral nutrition and were free of rejection. Coefficients of lipid absorption were determined in those patients receiving total enteral feeding (two-thirds polymeric/one-third elemental) between 43 and 1032 days after transplantation; oral vitamin E tolerance tests were done at about the same time. RESULTS: Activities of lactase, sucrase, maltase, and palatinase consistently exceeded reference ranges (P<0.05). Mean coefficient of lipid absorption equaled 86+/-12% and was not influenced by duration of time after transplantation. No patient required dietary lipid restriction. No significant absorption of vitamin E was demonstrated until 160 days after transplantation. Vitamin E absorption did correlate with length of time elapsed after surgery (r=0.64, P<0.0011). CONCLUSIONS: The results of this investigation show that, in the absence of histologic or clinical indications of allograft rejection, pediatric intestinal transplant recipients do not have primary disaccharidase deficiencies. Similarly, absorption of usual dietary lipid content is adequate once weaning from parenteral nutrition is complete. In contrast, early assimilation of vitamin E is poor. Vitamin E absorption subsequently improves, but the mechanism is obscure.

Child↗
PubMed2000

Isolated intestinal transplantation for intestinal failure.

OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal failure. However, some experience life-threatening complications from parenteral nutrition, and in these individuals intestinal transplantation may be lifesaving. METHODS: This is a retrospective review of 28 consecutive isolated small bowel transplants performed in eight adults and 20 children between December 1993 and June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient and graft survivals were 93% and 71%, respectively. The causes of graft loss were hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n = 1), and patient death (n = 1). The median length of time required until full enteral nutrition was 27 days. All 28 patients have experienced acute rejection of their small bowel grafts and rejection led to graft failure in five. Jaundice and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and hyperbilirubinemia was completely reversed in all patients with functional grafts within 4 months of transplantation. Three patients developed post-transplant lymphoproliferative disease (11%). Three recipients developed cytomegalovirus enteritis and all were successfully treated. CONCLUSIONS: Patient survival after intestinal transplantation is comparable to parenteral nutrition for patients with intestinal failure. Better immunosuppressive regimens are needed to decrease the risk of graft loss from acute rejection. The incidence of posttransplant lymphoproliferative disorder is higher after intestinal transplantation than after other solid organ transplants and the risk of cytomegalovirus enteritis is low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the absence of established cirrhosis can be reversed.

Adolescent↗
PubMed1998

Small bowel bacterial overgrowth as a cause of chronic diarrhea after liver transplantation in children.

Children who have undergone liver transplantation may develop chronic diarrhea for a number of reasons. Three children who underwent liver transplantation for liver failure, all of whom had had previous biliary and intestinal surgeries and whose postoperative course was marked by signs and symptoms of intestinal malabsorption including chronic diarrhea, are described. Duodenal aspirates showed a panoply of bacterial species, and duodenal histology featured villus atrophy in two: one associated with luminal gram-positive cocci and another with acute and chronic duodenitis. Oral antibiotics cleared the symptoms. Small bowel bacterial overgrowth may need to be considered in children with chronic diarrhea after liver transplantation, especially when previous intestinal surgery has taken place. Long-term antibiotic therapy may be required to effectively eradicate the offending organisms to suppress symptoms.

Administration, Oral↗
PubMed1998

Methotrexate in patients with Crohn's disease after 6-mercaptopurine.

OBJECTIVE: The objective of this study was to describe the clinical outcome of children with Crohn's disease treated with subcutaneous methotrexate. SUBJECTS/METHODS: Fourteen patients (10 boys) with extensive Crohn's disease diagnosed at a mean age of 10.6 +/- 3.6 years had previously received various medical therapies for 4.3 +/- 4.0 years. Because of the severity of their disease, 6-mercaptopurine had been introduced but discontinued because of the patients' failure to respond (n = 11) or the development of pancreatitis (n = 3). Subsequently, low-dose, weekly, subcutaneous methotrexate was initiated. Pediatric Crohn's Disease Activity Index scores and prednisone requirement were followed as outcome measures. RESULTS: Overall, 9 (64%) of the 14 patients showed improvement, including 6 (55%) of 11 patients who had previously received an adequate trial of 6-mercaptopurine and all three patients who were intolerant of 6-mercaptopurine. Improvement in clinical and laboratory measures occurred by 4 weeks and were similar whether (n = 8) or not (n = 6) the dose of corticosteroids was increased before the start of subcutaneous methotrexate. Three patients were tapered from their initial methotrexate dose after the minimization of corticosteroids and remain well. One patient receiving daily corticosteroids died suddenly after acute onset of illness. Among patients responding, methotrexate was discontinued because of side effects (n = 2) or electively (n = 2). Of the latter two patients, one has resumed methotrexate after disease relapse, whereas the other patient has had a sustained remission. CONCLUSIONS: Low-dose, weekly, subcutaneous methotrexate can induce remission in some pediatric patients with Crohn's disease who fail to adequately respond to other immunomodulator medications.

Adolescent↗
PubMed1998

Pudendal nerve function in normal and encopretic children.

BACKGROUND: Abnormal pudendal nerve function contributes to fecal retention and incontinence in adults. To determine the role of pudendal neuropathy in childhood, we prospectively evaluated pudendal nerve function in normal and encopretic children. METHODS: We studied pudendal nerve terminal motor latency in 23 encopretic children and in an equal number of similarly aged, normal children. Anal manometry and electromyography were also obtained in all children. RESULTS: Pudendal nerve latency in the encopretic children equaled 1.58 +/- 0.33 msec, which was the same as that in control children. Of the 75 pudendal nerves tested, latency was prolonged in only one encopretic child. In contrast, anal electromyography demonstrated nonrelaxation of the external anal sphincter in 75% of the encopretic children but in only 13% of the normal children (p < 0.001). Anorectal manometry demonstrated, on average, lower and sphincter pressures at rest and with squeezing in the encopretic children (p < 0.01), but only 17% had sphincter pressures more than two standard deviations below normal. CONCLUSIONS: Other than poor relaxation response of the external anal sphincter during evacuation, these data reveal a paucity of functionally important abnormalities in encopretic children. In particular, we find no evidence that abnormal pudendal nerve function is important in the etiology or pathogenesis of encopresis in children.

Anal Canal↗
PubMed1998

Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome.

BACKGROUND: Small bowel bacterial overgrowth is a common complication of short bowel syndrome, and although it is often controlled with antimicrobial therapy, alternative strategies may occasionally be needed. METHODS: Six patients with bacterial overgrowth are described, who did not respond to antimicrobial therapy and required additional medical or surgical measures to control the overgrowth. RESULTS: Recalcitrant bacterial overgrowth was successfully treated with periodic small bowel irrigation with a balanced hypertonic electrolyte solution, colonic flushes, encouraging frequent stooling, intestinal lengthening procedure, or probiotic therapy with Lactobacillus plantarum 299V and Lactobacillus GG. CONCLUSIONS: Small bowel bacterial overgrowth should be aggressively evaluated in patients with short bowel syndrome who are not progressing in a normal manner. Inadequate or incomplete response to antibiotic therapy is common, and several additional treatment possibilities are available.

Anti-Bacterial Agents↗