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J Nery

Publications and source records attributed to J Nery.

At least 19 recordsLinked to original sources
PubMed2003

Characterization of adenovirus p21 gene transfer, biodistribution, and immune response after local ocular delivery in New Zealand white rabbits.

Previous studies suggest that local gene therapy with rAd-p21(WAF1/Cip-1) [. Arch. Ophthalmol. 120, (2002) 941-949] may provide an effective adjunctive anti-proliferative treatment to prevent glaucoma surgery failure. To further investigate rAd-p21 in this indication, we have characterized several parameters of local gene delivery to conjunctiva including, vector delivery and transgene expression in target tissue, inflammatory response, biodistribution to non-target tissues, and immune response. Quantitative PCR and RT-PCR assays were employed to evaluate rAd-p21 dissemination and gene transfer following a single subconjunctival injection. In target tissue, significant levels of rAd-p21 DNA were found in 6/6 animals 1 and 4 days after injection. rAd-p21 DNA and RNA could be detected in the un-injected contralateral eye but at levels that were 10000-100000 lower than in the injected eye. Expression of human p21 transgene in conjunctival fibroblasts was confirmed by immunohistochemistry. Biodistribution of rAd-p21 following subconjunctival injection was substantially limited to ocular tissue. In 1/6 rabbits, rAd-p21 DNA was found in whole blood, liver, and spleen at levels that were barely detectable. All non-target organs were negative on day 4. In contrast, in a rabbit injected intravenously as a positive control, all blood samples and tissues samples were positive. rAd-p21 delivery to conjunctiva followed by filtration surgery caused an early acute inflammatory response, which by day 14 was indistinguishable from placebo-treated eyes. Neutralizing anti-adenovirus antibodies were detected following administration of rAd-p21 to conjunctiva, however, vector delivery and transgene expression were unaffected in a subsequent administration to the contralateral eye in the same animal. These results show that local delivery to conjunctiva may be a suitable delivery mode for ocular gene therapy.

Adenoviridae↗
PubMed2000

Intestinal transplantation for short gut syndrome attributable to necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening condition of the neonatal age, which frequently requires surgical intervention. After extensive bowel resection, a small proportion of these patients may develop chronic short gut syndrome (SGS) and require chronic total parenteral nutrition (TPN) use. Intestinal transplantation has been performed in these patients as a life-saving option. This study reviews our experience with intestinal transplantation for SGS attributable to NEC emphasizing the mode of presentation, natural history, timing, and outcome. METHODS: A retrospective chart review was performed for all pediatric patients who underwent small bowel transplantation for NEC at the University of Miami between August 1994 and March 1999. RESULTS: Eleven transplants were performed for 10 patients with NEC (8 male and 2 female; median age: 1.75 years [range: 10 months to 10. 1 years]). Procedures performed were isolated intestinal transplants (n = 2), combined liver-intestinal transplants (n = 6), and multivisceral transplants (n = 3). All patients were born prematurely with median birth weight of 1.640 kg (range: 810 g to 2. 730 kg). They developed NEC in the first few days of life and subsequently underwent an average of 5 surgeries per patient before transplant. Transplant was indicated for liver failure in 8 patients and recurrent central line sepsis in 2 others. At present, 6 patients are alive with an overall 1-year and 3-year actuarial survival of 60% and a median follow-up of 29 months (range: 9-46 months). Six children have been weaned off TPN after a median time of 71 days (range: 19-131) from transplantation. All survivors are at home with functional grafts. CONCLUSION: Intestinal transplantation provided a reasonable outcome in patients with NEC-associated SGS who had already developed life-threatening complications related to TPN. Intestinal transplantation replaced the diseased intestine and liver, enfranchised patients from TPN, and conferred improved quality of life. These patients should be actively considered for intestinal transplantation and referred to a transplant center as soon as possible.

Child↗
PubMed1999

Transplantation of islets of Langerhans in patients with insulin-requiring diabetes mellitus undergoing orthotopic liver transplantation--the Miami experience.

Most patients with cirrhosis of the liver have detectable insulin resistance. In 60-80% of patients with cirrhosis, impaired glucose tolerance can be uncovered; approximately 20% of these patients eventually develop overt diabetes. Theoretically, insulin resistance and glucose intolerance could be improved or reversed by orthotopic liver transplantation alone or in association with a simultaneous transplant of pancreatic islet cells from the same donor. To investigate these possibilities we initiated a pilot study of simultaneous liver and pancreatic islet cell transplantation in seven patients with diabetes and liver cirrhosis. Donor bone marrow cells were also infused to enhance the acceptance of the grafts. Seven patients who received only orthotopic liver transplantation and donor bone marrow cells were used as historical controls. The preliminary results of this pilot trial suggest that islet cell transplantation in conjunction with orthotopic liver transplantation improves glucose metabolism in patients with liver cirrhosis in association with reduced insulin requirements and HbA1c levels. These results were evident in spite of pre- and post-transplant basal C-peptide levels that were unchanged. Further evaluation of the effects of orthotopic liver transplantation with or without islet cell transplantation will require a randomized prospective trial including accurate metabolic evaluation with the euglycemic insulin clamp technique.

Adolescent↗
PubMed1999

Cadaveric small bowel/split liver transplantation in a child.

Scarcity of size-matched grafts continues to be a major limiting factor for liver and combined liver/intestinal transplants in the pediatric population. It is reported that 29% of pediatric patients listed for hepatic transplantation die while waiting for a donor. The reported mortality of pediatric patients awaiting intestinal transplantation is about 40%. We report on a technique of segmental liver and intestinal transplantation in a child. To our knowledge, this is the first report of a combined split liver-intestinal transplantation. We used a cadaveric donor, but the technique can also be performed with a live donor. The adult recipient of one segment of the liver was discharged home without complications. The child who received the combined liver intestinal graft developed intestinal perforation and severe rejection and died. If this technique is applied successfully, the adverse effects and mortality of a long pretransplant waiting period in pediatric patients may be avoided.

Adult↗
PubMed1999

Mouse adenovirus (MAV-1) expression in primary human endothelial cells and generation of a full-length infectious plasmid.

Using RT-PCR, we show that mouse adenovirus type I (MAV-1) is capable of infecting and expressing in various cell types, specifically human endothelial cells. The capability of MAV-1 to infect and express in human endothelial cells makes it a potentially useful alternative to the use of human adenoviruses type 2/5 (Ad2/5) in virus-based gene therapy, although presently MAV-1 can only be produced at lower titers than Ad2/5. In this report, we present methods for the purification of MAV-1 DNA and use of this DNA along with a modified bacteria-based homologous recombination protocol to generate a full-length plasmid clone of MAV-1 DNA. Using various transfection procedures, we show that this plasmid MAV-1 DNA can generate plaques of MAV-1 virus, albeit at low efficiencies (about 0. 2 p.f.u./microg DNA). Furthermore, the construction of an MAV-1 plasmid along with its capability to express in human cells justifies the full development of MAV-1 into a system of gene therapy.

Adenoviridae↗
PubMed1998

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis.

BACKGROUND: Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS: Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS: Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION: Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.

Adult↗
PubMed1998

Intraoperative donor cholangiography.

Biliary drainage has long been called the Achilles' heel of liver transplantation, and biliary complications compromise the success of liver transplantation by increasing graft loss and the rates of a required second operation, morbidity, and mortality. One cause of complications is unrecognized anomalous biliary anatomy. We examined 73 intraoperative donor duct cholangiograms (IODDCs) to assess our ability to identify biliary anomalies intraoperatively. Normal anatomy was seen in 42% (31/73); some part of the right-sided biliary system drained into the left bile duct in 22% (16/73); trifurcated systems with a single branch point for the right posterior, right anterior, and left ducts appeared in 16% (12/73); low insertion of a right segmental duct to the hepatic duct was seen in 11% (8/73); and drainage of a right segmental duct into the cystic duct or into the hepatic duct at the cystic duct origin was noted in 8% (6/73). It was believed that the last group represented a condition that dictated extra caution in biliary reconstruction. The incidence of radiographic recognition of these anomalies was more than twice the clinical recognition in our patient population, implying that many such "problem" ducts usually go unrecognized. IODDCs facilitate training of transplant fellows. Costs are low, and morbidity is nil.

Cholangiography↗
PubMed1998

Adenovirus enterocolitis in human small bowel transplants.

This report describes two cases of pediatric small bowel transplant patients who developed diffuse adenovirus enterocolitis of their allografts. Based upon the presenting symptoms for this complication, in both patients a differential diagnosis of allograft rejection versus viral infection was clinically entertained. The clinical condition in both instances rapidly deteriorated and both patients died shortly after the development of the symptoms of fulminant septicemia. Autopsies were performed and histologic examination revealed extensive denudation of the gastrointestinal mucosa with edema and a marked acute and chronic inflammatory infiltrate involving the entire wall of the grafts. Numerous viral intranuclear and intracytoplasmic inclusions were evident and an immunohistochemical stain specific for adenovirus was strongly positive in the infected cells. In addition, while in the first case the adenovirus appeared confined to the GI tract, the second patient displayed numerous viral inclusions in the lung as well as within multiple liver abscesses. At this point, the incidence of adenovirus as a cause of gastroenteritis in small bowel transplant patients remains to be determined. We believe that the importance of recognizing this particular type of viral infection in this group of patients lies primarily in differentiating it from other viral organisms (e.g., CMV) that require a specific antiviral therapy. Moreover, an identification of this entity could help avoid a misdiagnosis of rejection which could lead to an unnecessary increase in immunosuppressive therapy and a possible exacerbation of the underlying condition.

Adenovirus Infections, Human↗
PubMed1998

Successful management of calyceal fistula following simultaneous pancreas-kidney transplantation.

Calyceal fistula is an unusual complication of renal transplantation. We report a case of calyceal fistula after simultaneous pancreas-kidney transplant that developed after thrombosis of a lower pole artery. Surgical correction was successfully achieved with a lower pole nephrectomy, closure of the involved calyces, and placement of a ureteral stent and a pedicle of greater omentum graft over the affected parenchyma.

Adult↗