Biomedical subjects

Christopher J Sonnenday

Publications and source records attributed to Christopher J Sonnenday.

8 recordsLinked to original sources

PubMed2006

Does pancreatic duct stenting decrease the rate of pancreatic fistula following pancreaticoduodenectomy? Results of a prospective randomized trial.

Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.

Adult↗

PubMed2004

Isometric tubular epithelial vacuolization in renal allograft biopsy specimens of patients receiving low-dose intravenous immunoglobulin for a positive crossmatch.

BACKGROUND: Perioperative treatment with plasmapheresis and intravenous immunoglobulin (IVIG), combined with a tacrolimus-based immunosuppressive regimen, has been used successfully to allow renal transplantations in cross-match-positive recipients. A common finding in biopsy specimens of these allografts is isometric vacuolization of proximal tubular epithelium. This finding presents a diagnostic dilemma because it may occur secondary to IVIG treatment or tacrolimus nephrotoxicity. METHODS: We compared the frequency and severity of isometric tubular vacuolization in renal allograft biopsy specimens obtained during the first 10 days after transplantation in 24 patients who received one or more postoperative treatments with IVIG (100 mg/kg; as part of a desensitization protocol also involving plasmapheresis) with specimens obtained in 91 patients who did not receive IVIG. All patients received tacrolimus. Isometric vacuolization was graded on a 0 to 4 scale based on the fraction of proximal tubules involved: 0, none; 1, less than 10%; 2, 10% to 25%; 3, 26% to 50%; 4, more than 50%. RESULTS: There was a higher frequency of isometric tubular vacuolization (71 % vs. 31%) and more widespread involvement in patients who received IVIG and tacrolimus versus tacrolimus alone, although mean tacrolimus levels were not significantly different between these groups. In control, but not IVIG, biopsy specimens, there was a significant association between vacuolization score and blood tacrolimus level on the day of biopsy. CONCLUSIONS: Isometric tubular vacuolization is a common finding in renal transplant biopsy specimens of patients who receive low-dose IVIG and in many cases is likely to be related, at least in part, to IVIG. In these patients, this finding should not necessarily be interpreted as indicative of tacrolimus (or cyclosporine) nephrotoxicity.

Biopsy↗

PubMed2004

A novel chimeric ribozyme vector produces potent inhibition of ICAM-1 expression on ischemic vascular endothelium.

BACKGROUND: Inhibition of intercellular adhesion molecule-1 (ICAM-1) expression can ameliorate the inflammation induced by ischemia-reperfusion injury (IRI) in animal models. However, current strategies to reduce ICAM-1 expression have been limited by the lack of stability, poor specificity, and the transient nature of synthesized regulatory molecules (antisense/ribozyme). METHODS: A chimeric expression vector was generated by fusing a ribozyme targeting sequence against ICAM-1 to stabilizing stem-loop structures and nuclear localization signals that are components of endogenous U1 small nuclear RNA. Oligonucleotide scanning was used to predict accessible sites for targeting within the rat ICAM-1 transcript. Efficacy of the chimeric ribozyme vector was tested by transfection of rat aortic endothelial (RAE) cells (in vitro) and intraportal delivery in a rat hepatic IRI model (in vivo). RESULTS: Transfection of RAE cells with the chimeric ribozyme vector produced potent and specific inhibition of ICAM-1 mRNA and protein levels by >65%. This reduction in ICAM-1 expression was accompanied by a proportional decrease in neutrophil adhesion to RAE cells. In vivo intraportal delivery of the chimeric targeting vector to rats sustaining hepatic IRI produced a marked reduction in ICAM-1 expression on liver endothelium after reperfusion. CONCLUSIONS: A chimeric ribozyme vector effectively inhibited ICAM-1 expression in vascular endothelial cells and in rat liver following IRI, demonstrating a novel gene targeting technique that may be ideally suited to clinical applications aimed at ameliorating IRI.

Animals↗

PubMed2004

Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers.

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.

ABO Blood-Group System↗

PubMed2004

Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy.

The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A(1), A(2), and group B living donors. Mean (+/- SD) serum creatinine was 1.3 +/- 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.

ABO Blood-Group System↗

PubMed2003

The hazards of basing acceptance of cadaveric renal allografts on pulsatile perfusion parameters alone.

BACKGROUND: Pulsatile perfusion (PP) is used by some centers to provide information that may aid in the selection of cadaveric renal allografts for transplantation. However, basing organ acceptance on PP parameters alone may lead to the discarding of kidneys from otherwise suitable donors. In this case series, we report the reevaluation and transplantation of kidneys refused by other centers after evaluation with PP. METHODS: Retrospective review of 14 cadaveric kidneys imported for repeat PP at our center after initially poor PP parameters from an outside organ procurement organization resulted in refusal by multiple centers. RESULTS: Median age of donors was 46 (range 21-64), and mean terminal serum creatinine was 1.3+/-0.6 mg/dL. Despite favorable donor characteristics, each kidney was refused by an average of 9.3 centers. Poor PP parameters and concerns about donor quality were the reasons for refusal in the majority of cases. Pulsatile-perfusion parameters at the outside center were poor: mean flow of 103 mL/min/100 g and mean resistance of 0.321 mm Hg/(mL/min/100 g). Repeat PP parameters at our center after importation were markedly improved (flow=167 mL/min/100 g and resistance=0.195 mm Hg/[mL/min/100 g]). Eleven of 14 kidneys were transplanted and currently have acceptable graft function (mean serum creatinine=1.6 mg/dL at a median follow-up of 12 months). CONCLUSIONS: This series describes the successful transplantation of 11 kidneys from acceptable donors that were initially discarded by multiple centers after poor PP parameters were obtained. The good allograft function in these organs emphasizes the importance of considering all donor factors when making allocation decisions.

Adult↗

PubMed2003

Concomitant surgery with laparoscopic live donor nephrectomy.

Routine live donor evaluations reveal unexpected silent pathologies. Herein, we describe our experience treating such pathologies at the time of laparoscopic donor nephrectomy. We have not encountered any previous reports of such an approach. We prospectively collected data on 321 donors. Concomitant surgeries at the time of procurement included two laparoscopic adrenalectomies, one colposuspension, one laparoscopic cholecystectomy, and one liver biopsy. Mean operative time was 321 min (range 230-380), with a mean blood loss of 280 mL (range 150-500). No blood transfusions were required. The left kidney was procured in four cases. The right kidney was obtained on one occasion. Mean hospital stay was 3 days (median 3, range 2-4). No short- or long-term complications have been identified. Mean follow-up time was 2.63 years (median 2.76, range 2.23-2.99). Four of the five kidney recipients were first-time transplants who had not yet started dialysis. Simultaneous surgical interventions at the time of laparoscopic live kidney donation are safe and can be undertaken in selected cases. This practice is beneficial to both the donor and the recipient, and is likely to become more commonplace with changing practice patterns involving donor evaluation and management.

Adenoma↗

PubMed2003

Renal transplantation at the Johns Hopkins Comprehensive Transplant Center.

A stagnant supply of transplantable organs in the face of a relentless burgeoning of transplant waiting lists has created a crisis. Necessity continues to be the mother of invention and as the crisis has deepened it has served as a crucible for the development of new ways to think about perennial problems. Our program has taken a 2-pronged approach to increasing the organ supply for our patients. First, through innovations like the laparoscopic donor nephrectomy, ABO-incompatible and positive-crossmatch transplantation protocols, unconventional paired kidney exchanges, and the use of altruistic donors we have more than doubled our utilization of live donor organs. At the same time, we have developed algorithms and interrogative techniques to enhance the intelligent use of kidneys from expanded criteria donors for patients who do not have an available live donor. The laparoscopic nephrectomy has proven to be a safe and effective way of removing a significant barrier to live donation. Our results from 100 ABOi, (+)XM, and PKE transplants are similar to national statistics for compatible live donor transplants, suggesting that existing paradigms of compatibility can be safely expanded. These encouraging early outcomes and the savings they transmit to the health care system have allowed us to obtain insurance coverage for the InKTP programs, setting the stage for further expansion of these opportunities to broaden the options for patients with end-stage renal disease.

ABO Blood-Group System↗