PubMed Health⌕ Search

Biomedical subjects

Kareem Abu-Elmagd

Publications and source records attributed to Kareem Abu-Elmagd.

At least 19 recordsLinked to original sources
PubMed2006

Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody.

BACKGROUND: Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. METHODS: All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. RESULTS: A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n=12), posttransplantation lymphoproliferative disease (n=5), human herpesvirus 6 infection (n=1), parvovirus infection (n=1), esophageal candidiasis (n=12), cryptococcosis (n=2), invasive mold infection (n=4), Nocardia infection (n=4), mycobacterial infection (n=3), Balamuthia mandrillaris infection (n=1), and toxoplasmosis (n=1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P<.001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P<.001), allograft failure (OR, 2.1; 95% CI, 1.1-4.4; P=.04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7-8.0; P=.001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5-19.5; P<.001). CONCLUSIONS: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.

Adolescent↗
PubMed2006

Bloodstream infections in organ transplant recipients receiving alemtuzumab: no evidence of occurrence of organisms typically associated with profound T cell depletion.

BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed against CD52, a cell surface antigen expressed on B and T lymphocytes, monocytes and NK cells. Its use results in a profound decrease in CD4 positive T lymphocytes. Alemtuzumab is used as induction immunosuppression and therapy for rejection in organ transplant recipients in some centers. We followed a cohort of 449 consecutive transplant recipients who received alemtuzumab to determine the occurrence of bloodstream infections, particularly those previously associated with decrease in CD4 positive T lymphocytes. PATIENTS AND METHODS: Fifteen percent (69/449) patients had at least one episode of bloodstream infection. However, no patient had bacteremia with Streptococcus pneumoniae, Listeria monocytogenes, non-typhoidal Salmonella or Mycobacterium avium complex. Fungaemia was rare, occurring in 1.5% of patients. The most common organisms isolated from the blood were Staphylococcus aureus (21 episodes), coagulase negative Staphylococcus (14 episodes), Klebsiella pneumoniae (12 episodes), Enterococcus faecium (11 episodes), Pseudomonas aeruginosa (10 episodes), Enterococcus faecalis (9 episodes) and Escherichia coli (7 episodes). DISCUSSION: We conclude that although alemtuzumab use is associated with profound CD4 positive T lymphocyte depletion, alemtuzumab does not seem to be associated with an increased risk of bloodstream infection with pathogens typically seen in other disorders of CD4 cell depletion, such as acquired immunodeficiency syndrome.

Adolescent↗
PubMed2006

Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial.

BACKGROUND & AIMS: Variceal bleeding refractory to medical treatment with beta-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. METHODS: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 +/- 26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. RESULTS: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81% and 62%; TIPS, 88% and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. CONCLUSIONS: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.

Adult↗
PubMed2006

Histopathologic characteristics of human intestine allograft acute rejection in patients pretreated with thymoglobulin or alemtuzumab.

BACKGROUND: We report herein the histopathologic characteristics of human intestine allograft acute rejection in a consecutive series of 48 patients receiving small bowel transplantations and treated with a preconditioning protocol between July 4, 2001 and January 31, 2004. METHODS: Recipient pretreatment was with an i.v. infusion of 5-10 mg/kg thymoglobulin or 30-60 mg of alemtuzumab (Campath 1H) over several hours prior to revascularization. Postoperative treatment was limited to tacrolimus (target 12-h trough level 10-15 ng/mL) unless additional drugs were needed to treat breakthrough rejection. RESULTS: A total of 3,497 biopsies of the allograft jejunum and/or ileum were obtained. A recently validated histological grading schema was prospectively utilized to grade acute rejection. A total of 116 acute rejection episodes were diagnosed (48 indeterminate, 36 mild, 11 moderate, and 21 severe). Several unique histopathologic features of allograft acute rejection were observed in the pretreated patients. First, scattered lamina propria neutrophilic inflammation often precedes the onset of acute rejection. Second, acute rejection is often associated with more prominent eosinophils in lamina propria or eosinophilic cryptitis. Third, certain acute rejection episodes are characterized by absence of crypts with intact surface villous epithelium. Finally, the mucosal damage associated with moderate or severe acute rejection can completely recover after additional immunosuppressive treatment. CONCLUSION: This study describes several characteristic histopathologic features of allograft small bowel acute rejection associated with thymoglobulin or alemtuzumab preconditioning. Recognition of these unique histopathologic features will enable accurate diagnosis and ensure successful weaning of immunosuppressive drugs.

Adolescent↗
PubMed2005

EBV-specific memory CD8+ T cell phenotype and function in stable solid organ transplant patients.

Immune responses to EBV in immunosuppressed (IS) solid organ transplant (SOTx) recipients have not been well characterized. Here we evaluate the phenotype and function of EBV-specific CD8+ T cells in peripheral blood isolated from "stable" IS SOTx recipients. The EBV-specific CD8+ T cell memory subset distribution in the peripheral blood of patients was examined by flow cytometric analysis using HLA-A2 tetramers incorporating BMLF1 (lytic), and LMP2 and EBNA3A (latent)-derived peptides, in conjunction with mAbs against the CD45RO, CD45RA, and CD62L markers. The ability of CD8+ T cells to produce IFN-gamma in response to the same EBV-derived peptides was measured by ELISPOT assay. Patients and healthy normal donors exhibited similar anti-EBV CD8+ T cell frequencies and specificities against the EBV epitopes evaluated. When compared to healthy normal donors, an overall significant expansion of the CD8+ T cell "effector memory" (CD45RO+/CD62L-) pool, including that of EBV "latent" (LMP2 and EBNA3A)-specific CD8+ T cells was detected in IS SOTx patients. However, the patients' EBV-specific CD8+ T cells showed decreased IFN-gamma production to the EBV-peptide stimulation. These results indicate that the impairment of EBV-specific CD8+ T cell activity is not due to clonal depletion, but is mainly due to impaired functional activation.

Antigens, Viral↗
PubMed2005

Augmentation of type-1 polarizing ability of monocyte-derived dendritic cells from chronically immunosuppressed organ-transplant recipients.

BACKGROUND: Chronic immunosuppressive (IS) therapy impairs normal T-cell immune surveillance and may predispose to opportunistic infections and malignancies that represent life-threatening complication of solid-organ transplantation (SOTx). Our study was designed to ascertain the impact of chronic in vivo administration of IS on the ability of monocyte-derived dendritic cells (MoDC) to differentiate, mature, and function ex vivo. The potential of these cells to be implemented for DC-based adoptive immunotherapy was also considered. METHODS: MoDCs were propagated by conventional procedures, their phenotype was analyzed by flow cytometry, and their function was assessed by mixed leukocyte reaction, enzyme-linked immunoadsorbent assay, and ELISPOT assays. Nuclear translocation of nuclear factor (NF)-kB was analyzed by electrophoretic mobility shift assay. RESULTS: Circulating DC1s in peripheral blood were reduced in SOTx patients. MoDCs generated from patients displayed higher endocytic activity versus normal DCs, indicating their comparative immaturity. Patients' DCs exposed to pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, and IL-6) were less able to mature, to stimulate recall antigen (Ag)- or allo-Ag-induced proliferation responses, or to secrete IL-12p70. These deficiencies were associated with a decrease in NF-kB translocation. In contrast, combination of pro-inflammatory cytokines and interferon (IFN)-gamma (a Th1-polarizing factor) augmented patients' DC1-type function and IL-12p70 production by way of an NF-kB-independent mechanism. CONCLUSIONS: Chronic IS restrains DC differentiation, maturation, and function at a transcriptional level; however, type-1 polarizing potential of patients' DC1 can be augmented ex vivo by a two-signal stimulation provided by pro-inflammatory cytokines and IFN-gamma. These results may have implications for DC-based immunotherapy of malignancies in the transplantation setting.

Active Transport, Cell Nucleus↗
PubMed2005

Central venous recanalization in patients with short gut syndrome: restoration of candidacy for intestinal and multivisceral transplantation.

PURPOSE: To assess feasibility and success of venous recanalization in patients with short gut syndrome who have lost their traditional central venous access and required intestinal or multivisceral transplantation. MATERIALS AND METHODS: Twelve patients between the ages of 7 and 55 years with short gut syndrome and long-standing total parenteral nutrition (TPN) dependency and/or hypercoagulability were treated. All had extensive chronic central venous occlusions and survival was dependent on restoration of access and planned transplantation. Central venous recanalizations were obtained via sharp needle recanalization techniques, venous reconstructions with stents, and/or extraanatomic access to the central venous system for placement of central venous tunneled catheters. RESULTS: Central venous access was restored in all patients without operative-related mortality. Three major hemodynamic perioperative technical complications were recorded and successfully treated. There were three self-limited early infectious complications. With a mean follow-up of 22 months, eight of the 12 patients were alive with successful small bowel or multivisceral transplantation; six of those became independent of TPN. The remaining four patients died of complications related to TPN (n = 3) or transplantation (n = 1). With a mean follow-up of 20 months, all but two of the recanalized venous accesses were maintained, for a success rate of 83%. CONCLUSIONS: Recanalizations of extensive chronic vein occlusions are feasible but associated with high risk. The technique is life-saving for TPN-dependent patients and can restore candidacy for intestinal and multivisceral transplantation. This approach is likely to be increasingly requested because of the current clinical availability of the transplant procedure.

Adolescent↗
PubMed2005

2003 report of the intestine transplant registry: a new era has dawned.

SUMMARY BACKGROUND DATA: The intestine has been more difficult to transplant than other solid organs. We analyzed registry data to determine the scope and success of intestine transplantation in the current era. METHODS: All known intestinal-transplant programs participated. Patient- and graft-survival estimates were obtained using the Kaplan-Meier product limit method and were analyzed with the Wilcoxon statistic. RESULTS: Sixty-one programs provided data on 989 grafts in 923 patients. Four patients were lost to follow-up. The short-gut syndrome was the most common primary indication for transplantation. Sixty-one percent of the recipients were < or =18 years. Proportionally more combined intestinal and liver transplants were performed in this group. More than 80% of all current survivors had stopped parenteral nutrition and resumed normal daily activities. A multivariate analysis of cases within the last 5 years revealed that transplantation of patients waiting at home, recipient age, antibody induction immune suppression, and center experience with at least 10 cases were associated with improved patient survival. One-year graft survival rates of 81% were achieved in patients who were induced with antithymocyte globulin and maintained on tacrolimus. CONCLUSIONS: Transplantation is an effective therapy for the treatment of patients with end-stage intestine failure who cannot tolerate parenteral nutrition. With newer immune suppressive protocols, 1-year graft and patient survival rates approach the results of liver transplantation. Further improvement in survival are expected with early referral since suitable donor organs are scarce and survival rates are better when patients are well enough to wait at home for their transplant.

Adult↗
PubMed2005

Carcinoma of donor origin after liver-intestine transplantation in a child.

Tumor-related complications after intestinal transplantation in children have been principally EBV driven post-transplant disorders. We describe the clinical course of a child, with a diagnosis of microvillus inclusion disease who received a liver and intestine allograft at the age of 9 months. His postoperative course was significant for multiple episodes of acute intestinal allograft rejection and eventually the development of post-transplant lymphoproliferative disorder (PTLD), which resolved. At 8 yr post-transplant he presented with masses in the intestine allograft mesentery and in the right lobe of the allograft liver, biopsy of which revealed a relatively undifferentiated tumor, suggestive of a carcinoma. In situ hybridization for X and Y chromosomes, revealed his tumor to be of donor origin. Treatment included debulking of the mesenteric mass with segmental enterectomy of the intestinal allograft, and stopping his immunosuppression for a period of 4 months; this resulted in complete resolution of his malignancy. Immunosuppression with tacrolimus and steroids was restarted because of intestinal allograft rejection; he died suddenly of unknown causes at 17 months post-diagnosis of carcinoma. The severely immunosuppressed state produced in this patient allowed for the development of an unusual donor derived carcinoma, which resolved spontaneously with withdrawal of immunosuppression. The mechanism of such regression of tumor may be related to restitution of immunologic competence, but is yet to be determined.

Child↗
PubMed2005

Sclerosing peritonitis after intestinal transplantation in children.

Long-term graft dysfunction and/or graft loss after intestinal transplantation (ITx) is a significant concern. Sclerosing peritonitis (SP) is a manifestation of chronic allograft failure and its presence may also include classic arterial obliterative arteriopathy (OA) as in chronic rejection. We describe the clinical presentation and management of SP occurring after ITx in children. Case records of 121 children undergoing ITx from 1990 to 2003 were reviewed. Three children (2.4%) presented with SP of the intestine allograft at a mean time of 6.6 yr following ITx as follows: age at Tx (yr) 8.2, and 3.7, with indication for ITx being gastroschisis in two and midgut volvulus in one patient. Type of ITx was isolated intestine in one and liver/intestine in two patients. Gross findings of SP included fibrosis/strictures; microscopically SP showed fibrosis/serositis, and fibrous adhesions; one patient had evidence of chronic allograft vasculopathy. All patients presented with clinical signs and symptoms of bowel obstruction and gastrointestinal contrast studies confirmed distal ileal obstruction (DIO). Operative findings confirmed SP and DIO in all patients; all patients were initially treated with distal segmental intestine allograft resection and lysis of the fibrous peel. All three patients recovered, although two required repeat laparotomy, there is only one long-term survival. SP after ITx may be a different manifestation of long-term intestine allograft degeneration. Surgical resection appears to offer palliation.

Child↗
PubMed2005

Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (thymoglobulin).

Modifications in the timing and dosage of immunosuppression can ameliorate the morbidity and mortality that has prevented widespread use of intestinal transplantation (ITx) in children. Thirty-six patients receiving ITx, aged 5 months to 20 years were given 2-3 mg(kg of rabbit anti-thymocyte globulin (rATG, thymoglobulin) just before ITx, and 2-3 mg(kg postoperatively (total 5 mg(kg). Twice daily doses of tacrolimus (TAC) were begun enterally within 24 h after graft reperfusion with reduction of dose quantity or frequency after 3 months. Prednisone or other agents were given to treat breakthrough rejection. After 8-28 months follow-up (mean 15.8 +/- 5.3), 1- and 2-year patient and graft survival is 100% and 94%, respectively. Despite a 44% incidence of acute rejection in the first month, 16 of the 34 (47%) survivors are on TAC (n = 14) or sirolimus (n = 2) monotherapy; 15 receive TAC plus low dose prednisone; one each receive TAC plus sirolimus, TAC plus azathioprine and TAC plus sirolimus and prednisone. There was a low incidence of immunosuppression-related complications. This strategy of immunosuppression minimized maintenance TAC exposure, facilitated the long-term control of rejection, decreased the incidence of opportunistic infections, and resulted in a high rate of patient and graft survival.

Adolescent↗
PubMed2005

Short bowel syndrome: clinical guidelines for nutrition management.

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.

Combined Modality Therapy↗
PubMed2005

Immunosuppressant strategies for intestinal transplantation: a review of a tolerogenic regimen.

Intestinal, combined liver-intestinal, and multivisceral transplantation are now considered the standard of care for children and adults with permanent intestinal failure. Early attempts at intestinal transplantation were discouraging because of the high incidence of technical complications, rejection, and infection. Advances in the field of transplantation, including the introduction of tacrolimus, improved surgical techniques, and improvements in postoperative care, have led to a renewed interest in intestinal transplantation since 1990. The most significant achievement, however, has been the effective control of rejection and life-threatening infections. This article focuses on the experience to date of innovative strategies that induce lymphocyte depletion and reduction in the incidence of rejection. In this setting, low-maintenance immunosuppression is clinically achievable with an acceptable rate of allograft rejection. Subsequently, the long-term complications of immunosuppression are significantly reduced with achievement of better long-term survival, and an overall improvement in the quality of life.

Graft Rejection↗
PubMed2005

Somatropin for the treatment of short bowel syndrome in adults.

Somatropin (rDNA origin) injection (Zorbtive) is a highly purified preparation of human growth hormone (GH) produced from a mammalian cell line by recombinant DNA technology. It is the only human GH approved for the treatment of short bowel syndrome in patients receiving specialised nutritional support. The process of intestinal adaptation begins immediately after surgery and continues for 2-3 years. During this period, the bowel begins to increase fluid and nutrient absorption. Under the influence of tropic factors, such as GH, intestinal adaptation is enhanced. Supplying a therapeutic regimen of GH, optimised diet and glutamine supplementation for 4 weeks to patients with short bowel syndrome who are dependent on parenteral nutrition, has been shown to reduce their long-term requirements for parenteral nutrition.

Animals↗
PubMed2004

Lessons of organ-induced tolerance learned from historical clinical experience.

Although the reductionist approach has served science well for 400 years, the accumulation of details can obscure the truth if the original premise is incorrect. One such premise has been that successful organ transplantation and bone marrow engraftment are fundamentally different outcomes involving separate and distinct mechanisms. Some historical clinical observations pointed to a different conclusion almost from the beginning and included clues about how to induce tolerance with the aid of immunosuppression.

Bone Marrow Transplantation↗
PubMed2004

A clinicopathologic study of isolated intestinal allografts with preformed IgG lymphocytotoxic antibodies.

Humoral rejection of human small bowel allografts has not been well documented. The aim of this study was to determine the significance of preformed IgG lymphocytotoxic antibodies, as determined by the modified Amos crossmatch technique, in 6 of 28 (21.4%) adult isolated intestinal allograft recipients treated with tacrolimus basal immunosuppression. The crossmatch with dithiothreitol (DTT) was strongly positive in 5 grafts and weakly positive in the remaining one. The strongly positive crossmatch grafts (n=5) developed severe mucosal injuries immediately after reperfusion. Within the first 10 days after transplantation, 3 of the 5 strongly positive crossmatch grafts developed clinically and endoscopically documented severe mucosal congestion, cyanotic discoloration, and focal hemorrhage within the allograft. Simultaneous mucosal biopsy specimens demonstrated severe congestion, neutrophilic margination, and fibrin-platelet thrombi within the lamina propria microvasculature, along with focal hemorrhage, but with no histological neutrophilic or necrotizing arteritis, and the immunofluorescent findings were unremarkable. The other 2 strongly positive crossmatch allograft recipients developed macroscopic congestion of mucosa with microscopic foci of congestion and hemorrhage. In contrast, the recipient with a weakly positive crossmatch, as well as the 22 crossmatch negative recipients, exhibited none of these characteristic clinical, endoscopic, or microscopic findings (P <.05). With prompt augmentation of the immunosuppression therapy, the 3 grafts with the characteristic clinicopathologic syndrome were successfully reversed with the monoclonal antilymphocyte preparation OKT3. Thus there was no statistical difference (P >.05) in early graft survival and the frequency of acute rejection episodes between the crossmatch-positive and the crossmatch-negative groups within the first 6 months after transplantation. We conclude that preformed IgG lymphocytotoxic antibodies in isolated intestinal recipients can be associated with a characteristic clinicopathologic syndrome during the early postoperative course, similar to that observed in experimental animal models and in other solid organ transplantation. If recognized and treated aggressively, early graft failure can be avoided. The long-term significance of these preformed antibodies has yet to be determined.

Adult↗
PubMed2004

Graft versus host disease in intestinal transplantation.

Our aim was to analyze the clinical course and outcome of patients with graft vs. host disease (GVHD) after intestinal transplantation (ITx). All patients receiving ITx between May, 1990 and December, 2003 were retrospectively reviewed for evidence of GVHD. Two hundred and fifty patients underwent ITx during the study period. Graft vs. host disease was suspected clinically in 23 patients on the clinical basis of presentation such as skin rash, ulceration of oral mucosa, diarrhea, lymphadenopathy, or native liver dysfunction. Fourteen (eight children and six adults) patients (5.6% of total patient population) had GVHD confirmed by histopathological criteria including keratinocyte necrosis (n = 9), epithelial apoptosis of the native gastrointestinal tract (n = 4), and epithelial cell necrosis of oral mucosa (n = 1). Donor-cell tissue infiltration or extensive peripheral blood donor-cell chimerism was documented on seven occasions. The majority of cases of GVHD resolved with steroid administration and optimization of tacrolimus immunosuppression. The incidence of histologically proven GVHD after clinical intestinal transplantation is 6.5% (8/122) in children and 4.7% (6/128) in adults. Successful clinical management requires a high index of suspicion to minimize morbidity and mortality. Diagnostic and treatment strategies based on this experience are proposed.

Adolescent↗