Search PubMed⌕ Search

Biomedical subjects

J I Tchervenkov

Publications and source records attributed to J I Tchervenkov.

At least 19 recordsLinked to original sources
PubMed2003

Ureteral implantation technique and urologic complications in adult kidney transplantion.

AIM: To assess the incidence of urological complications and hematuria after adult kidney transplantation using the Lich-Gregoire (LG) versus the Taguchi (T) ureteral implantation technique. METHODS: We performed a retrospective analysis of 212 consecutive kidney transplants from our institution using an access database. RESULTS: Sixty four patients underwent ureteral implantation using the T technique, and the other 148, the LG implantation. Both groups were matched for donor/recipient characteristics and for cold/warm ischemia times. There were 23 urological complications in 17 patients. Twenty-seven patients developed complicated hematuria. The rates of urinary leak and ureteral stones were not different. There was a higher incidence of permanent ureteral strictures using the LG technique (P =.05). T technique was associated more frequently with hematuria, but there was no difference in the length of stay. CONCLUSIONS: We identified an increased incidence of permanent strictures with the LG technique. The rate of hematuria was higher in the T group. Both techniques can be used interchangeably with acceptable rates of urological complications. The simplicity of the T technique has made it the technique of choice in our institution.

Adult↗
PubMed2003

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Choledochostomy↗
PubMed2001

Pseudoaneurysm of the superior mesenteric artery after pancreas transplantation treated by endovascular stenting.

Pseudoaneurysm after pancreas transplantation can have serious consequences, including rupture, hemorrhage, and graft loss. We describe a 38-year-old patient who presented with a pseudoaneurysm of the donor superior mesenteric artery 1 month after pancreas transplantation. Selective arteriography was performed and the lesion was repaired with endovascular placement of a 28-mm covered stent. Laparotomy was avoided. The pancreatic graft was continuing to function well 9 months later. As far as we know, this minimally invasive approach was not previously reported. According to published series, pseudoaneurysms often occur secondary to infection and require operative intervention necessitating graft pancreatectomy. Patients can present with serious symptoms including hypotension and shock. Therefore, it is important to detect pseudoaneurysm in a timely manner. Computed tomography and Doppler ultrasound are important diagnostic tools in this regard. We demonstrated the utility of endovascular stenting in the treatment of pseudoaneurysm after pancreas transplantation. When used in a timely manner in well selected patients, endovascular stenting can abrogate the need for operative intervention and its attendant morbidity.

Adult↗
PubMed2001

Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation.

The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.

Animals↗
PubMed2001

Successful outcome after transplantation of a donor liver with focal nodular hyperplasia.

Because of the increasing gap in the number of patients awaiting organ transplantation and the supply of organ donors, reevaluation of donor criteria is an important issue in clinical transplantation. It has become necessary to make maximal use of the currently available donor pool. We describe a case of successful orthotopic liver transplantation in a 57-year-old man with Laënnec's cirrhosis using a liver containing an 8-cm focal nodular hyperplasia (FNH) lesion involving segments II and III and the caudate lobe. The donor liver was procured from a 46-year-old woman declared brain dead after a subarachnoid hemorrhage. Definitive pathological diagnosis was made at laparotomy by obtaining a Tru-cut (Allegiance Health Care Inc, Toronto, Ontario, Canada) core biopsy specimen. The recipient operation was performed uneventfully except for bleeding from the biopsy site. The patient did well postoperatively and was discharged on tacrolimus, mofetil mycophenolate, and prednisone therapy. He continues to thrive 2(1/2) years posttransplantation with no change in the size of the lesion. In well-selected donors, FNH should not be a contraindication for use in transplantation. However, FNH must be differentiated from hepatocellular adenoma. Although FNH has a benign course with little propensity for bleeding and almost no malignant potential, hepatic adenoma is reported to have a 15% to 33% chance of bleeding and rupture with a well-documented potential for neoplastic degeneration, making the liver unsuitable for donation.

Focal Nodular Hyperplasia↗
PubMed1998

Comparison of neoral dose monitoring with cyclosporine through levels versus 2-hr postdose levels in stable liver transplant patients.

BACKGROUND: We reported that cyclosporine 2-hr postdose levels (C2) correlate better with the AUC0-4 hr than trough levels (C0) in heart transplant patients receiving Neoral. METHODS: We compared Neoral dose adjustment with C0 (group 1: 100-200 ng/ml) vs. C2 (group 2: 700-1000 ng/ml; group 3: 300-600 ng/ml) in 35 stable adult patients >1 year after liver transplantation. The AUC0-4hr was calculated, and simultaneous blood samples were obtained to measure calcineurin inhibition. Clinical benefit was defined as the absence of rejection and no increase in serum creatinine at the 7-month follow-up. RESULTS: C2 correlated better with the AUC0-4 hr than C0 (r=0.92 vs. r=0.40). Neoral dose increased by 17% and 39% in groups 1 and 2, and decreased by 18% in group 3 (P=0.002 vs. group 1 and P=0.0004 vs. group 2). Serum creatinine increased by 2.1% and 16% in groups 1 and 2, and decreased by 5.1% in group 3 (P=0.006 vs. group 2). A clinical benefit was observed in 37.5%, 23%, and 82% of patients in groups 1, 2, and 3 (P=0.03 vs. group 1 and P=0.01 vs. group 2). Calcineurin inhibition was similar in all groups at 2-hr (44+/-17%, 39+/-30%, and 44+/-35%), in spite of different Neoral doses (2.9+/-0.9, 4.0+/-1.8, and 2.6+/-1.3 mg/kg/day) and C2 (857+/-226, 922+/-274, and 588+/-274 ng/ml). CONCLUSIONS: C2 correlated better with the AUC0-4 hr than C0. Neoral dose monitoring with a C2 range of 300-600 ng/ml resulted in a lower dose and greater clinical benefit compared to C0 or a higher C2 in stable liver transplant patients. The correlation between calcineurin inhibition and clinical events deserves further research.

Adult↗
PubMed1998

Pulmonary injury in recipients of discordant hepatic and renal xenografts in the dog-to-pig model.

Work in our lab demonstrated that the early post-operative course of discordant hepatic and renal xenotransplantation is complicated by a pulmonary injury. The aim of this study was to characterize the nature of this injury, as well as to determine whether endothelin-1 (ET-1) and inducible-nitric oxide synthase (iNOS) are present in this form of pulmonary injury. Dog-to-pig orthotopic liver and kidney xenografts were performed. Pulmonary artery pressures were monitored throughout all procedures. The lungs were stained with monoclonal antibodies for ET-1, endothelin converting enzyme-1, and iNOS. The lungs from pig recipients of hepatic or renal xenografts were compared to lungs from untreated pigs. Pulmonary artery pressures were elevated in recipients of liver xenografts when the suprahepatic caval cross clamp was placed and continued to rise to systolic levels following unclamping. The mean pulmonary artery pressures in recipients of renal and hepatic xenografts rose significantly following revascularization. Pathology in lungs from kidney and liver recipients was similar, showing congestion with peribronchial and septal edema, with diffuse adhesion of PMN to alveolar endothelium. ET-1, endothelin converting enzyme-1 (ECE-1), and iNOS staining was widespread and intense in alveolar and pulmonary arterial endothelium. Discordant xenotransplantation of livers and kidneys is associated with a significant early pulmonary injury that is associated with early PMN infiltration and expression of ET-1 and iNOS.

Animals↗
PubMed1998

Complement activation in discordant hepatic xenotransplantation.

Little is known about hyperacute rejection in hepatic xenotransplantation. Information from clinical xenoperfusions suggests that the liver may be rejected by a mechanism less vigorous than either kidney or heart xenografts. We used the in vitro model of porcine hepatic sinusoidal endothelial cells (PHEC) incubated with either complement replete or deficient human serum to determine the relative roles of the classical and alternate pathways of complement in the immediate response to hepatic xenotransplantation. Our results suggest that either the classical or alternate pathways are capable of independently activating the complement cascade upon exposure to the porcine hepatic sinusoidal endothelium. Our results also imply that either pathway alone is capable of initiating similar degrees of injury as the entire cascade.

Acute Disease↗
PubMed1998

Successful treatment of post-transplant lymphoproliferative disorder with interferon-alpha and intravenous immunoglobulin.

We report on the use of interferon-alpha (INF-a) and high-dose non-specific intravenous immunoglobulin (IVIg) in 2 patients (a 60-yr-old female and a 65-yr-old male) who developed post-transplant lymphoproliferative disorder (PTLD) 2 and 8 months after heart and liver transplantation, respectively. Both patients had received immunosuppression with ATG, CsA, azathioprine, and prednisone. The first patient did not receive additional immunosuppression with biological agents. The second patient developed 3 steroid-resistant acute rejection episodes requiring OKT3 (cumulative dose 100 mg) and ATG (cumulative dose 3450 mg). The first patient presented with nodules involving the liver, spleen, lungs and nasophar, ynx. The second patient presented with subcutaneous and liver nodules, as well as pert-portal and para-aortic lymphadenopathies. The histological diagnosis was diffuse B-cell PTLD in both patients. Despite reduction of immunosuppression, a progression of lesions was observed in both patients over 5 months and 2 months, respectively. The first patient received INF-alpha (2 x 10(6) IU, s.c. 3 times/wk) and IVIg (0.5 g/kg i.v. every 15 d) for.4 months, while the second patient received the same therapy for 12 and 7 months, respectively. Complete disappearance of all lesions was observed after 3 months of therapy in the first patient and after 7 months of therapy in the second patient, as assessed by CT scan. PTLD remains in remission 47 and 33 months after therapy, respectively. Our preliminary results suggest that the combination of INF-alpha and IVIg can be an effective therapy for PTLD which does not respond to reduction of immunosuppression.

Aged↗
PubMed1998

[A comparative randomized prospective multicenter study of Sandimmune vs Neoral in liver transplantation].

Despite two decades of use, there are limited data on the best way to administer and monitor cyclosporine for orthotopic liver transplantation (OLT). The present study was undertaken: 1) to establish the safety of a new formulation of cyclosporine, Neoral, 2) to determine if treatment with Neoral will improve the results of liver transplantation and 3) to study the relationship between pharmacokinetic parameters and clinical outcomes after OLT. A double-blind, randomized, comparison of Sandimmune and Neoral was conducted at 5 Canadian centers in 188 consecutive adults undergoing OLT. Patients were induced with intravenous cyclosporine (CsA) then switched to Neoral or Sandimmune. Dose adjustments were made daily, or as needed, to reach a target trough CsA level (C0) of 350 ng/mL in both groups. Pharmacokinetic studies were performed on days 5, 10, 15 and 30 after transplantation. The Neoral group stopped intravenous CsA earlier (p < 0.0001), and these patients required a lower median daily oral dose (p < 0.01) to maintain comparable trough CsA levels. Five Sandimmune patients, but no Neoral patients discontinued the study because of the inability to reach target trough levels of CsA within the prescribed time (p < 0.05). At 4 months, there were no differences between the two groups with respect to patient survival, graft survival or rejection-free survival. The incidence of serious adverse events was also similar and did not correlate with CsA profiles. The Neoral group had a higher area under the drug concentration curve (AUC) and peak CsA levels (Cmax). There was a correlation between freedom from graft rejection and both AUC and Cmax at days 5 and 10 post-transplant. In contrast, there was a poor correlation between C0 and graft rejection. In summary, Neoral appears to be safe and well tolerated by patients. Cmax and/or AUC maybe better markers for monitoring cyclosporine based immunosuppression after liver transplantation.

Administration, Oral↗
PubMed1997

Tacrine does not alter the potency of succinylcholine in the rat.

PURPOSE: Tacrine is a cholinesterase inhibitor used to manage Alzheimer's dementia. Given iv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known. METHODS: Groups of adult rats were given 2.5 mg.kg-1 tacrine (chronic groups) or l ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg.kg-1 tacrine iv. Twelve to 18 hr after the last gavage of tacrine or saline, and -20 min after iv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation. RESULTS: The ED50 and ED95 of succinylcholine in control rats were (mean +/- SD) 204 +/- 41 and 382 +/- 96 micrograms.kg-1, respectively in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 micrograms.kg-1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED50 and ED95 ranged from 166-197 and 277-396 micrograms.kg-1., respectively, in the tibialis muscle, and 248-333 and 546-667 micrograms.kg-1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group. CONCLUSION: Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.

Administration, Oral↗
PubMed1997

The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat.

Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants. We determined the magnitude and time course of the effects of chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min before (acute), and the cumulative dose-response curves of dTC at the tibialis and soleus muscles were determined during indirect train-of-four stimulation in the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and 95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and 61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05) but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC 1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration of THA therapy. We conclude that chronic THA therapy in rats causes resistance to dTC, with a tendency for the resistance to decrease with time, probably because of down-regulation of postsynaptic acetylcholine receptors. The same may apply to Alzheimer's patients taking THA chronically.

Administration, Oral↗
PubMed1997

Recurrence-free long-term survival after liver transplantation for hepatitis B using interferon-alpha pretransplant and hepatitis B immune globulin posttransplant.

OBJECTIVE: The authors determined whether pretransplant reduction of hepatitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttransplantation can prevent HBV recurrence in patients undergoing liver transplantation (LT) for HBV cirrhosis. SUMMARY BACKGROUND DATA: Liver transplantation in patients with HBV cirrhosis is associated with a high rate of recurrence and reduced survival. In patients with evidence of replicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive serum or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttransplant, especially in patients with evidence of active viral replication pretransplant. Higher doses of HBIg posttransplant has reduced recurrence rates to 30% to 50%. Lamivudine, a nucleoside analogue that has shown early promise, also is associated with significant HBV recurrence. The authors report a reliable method of preventing viral recurrence in patients even with evidence for active HBV replication pretransplant. METHODS: Pretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneously. This dose was increased to 2 and then 3 million IU 3 times per week when patient's side effects permitted and was maintained until the patient underwent a LT. All patients were tested every 4 weeks for hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA. When patients became negative for HBeAg and HBV-DNA, they were listed for LT. Patients that were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HBIg 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the first 2 years. After 2 years, all patients received 2000 IU (10 mL) monthly. Additional HBIg immunoprophylaxis was given during intense immunosuppression for rejection. Posttransplant serum was tested for HBsAg, HBeAg, and HBV-DNA in all patients 1 week, 1 month, and every 3 months thereafter. Liver biopsies were done at least yearly and when liver enzymes were abnormal and were always tested for HBsAg and HBcAg by immunoperoxidase. RESULTS: Thirteen patients with decompensated HBV cirrhosis were transplanted. Pretransplant, eight patients had evidence of active viral replication at the initial assessment (HBeAg or HBV-DNA-positive serum or both). All eight were successfully treated with IFN (median duration, 24 weeks; range, 8-53) and converted to a negative status before transplantation. Side effects from IFN were minimal and well tolerated, except in one patient who required 6 million IU to convert to a nonreplicating status. The five patients that were only HBsAg positive were not treated with IFN pretransplant. After surgery, HBIg given as described achieved consistently serum levels greater than 1000 IU/L. Twelve of the 13 patients are alive with normal liver function and without serologic evidence of HBV recurrence at a median follow-up of 32 months (range, 9-56 months). None have evidence of HBV recurrence as measured by serum HBsAg/HBeAg/HBV-DNA at recent follow-up. The sera of the seven longest survivors has tested negative for HBV-DNA using the polymerase chain reaction method. In addition, a liver biopsy was obtained in six of these patients, the results of which also tested negative for HBV-DNA using polymerase chain reaction. Liver biopsy specimens have been negative for the presence of HBsAg and HBcAg by immunoperoxidase staining in all 12 patients. CONCLUSION: A reduction of viral load pretransplant with IFN and posttransplant HBIg prevents recurrence of hepatitis B and permits LT for HBV cirrhosis, even in patients with evidence of replicating virus. The IFN pretransplant was well tolerated, and the small frequent dosing of HBIg posttransplant did not cause side effects while achieving serum levels > 1000 IU/L.

Adult↗
PubMed1995

Indefinite allograft survival induced by the combination of multiple donor-specific transfusions, cyclosporine, and an anti-T cell monoclonal antibody in a protocol relevant to cadaveric organ transplantation. The importance of prolonged posttransplant cyclosporine coverage.

A single donor specific transfusion (DST) 24 hr pretransplant and Cyclosporine (CsA) are synergistic in inducing prolongation of allograft survival. This synergy was further potentiated by giving 3 additional DSTs at weekly intervals posttransplant, or by the additional administration of a small dose of the anti-T cell monoclonal antibody OX-52 24 hr pretransplant to the above protocol. This study determined whether indefinite survival can be achieved in the ACI-to-Lewis heart allograft model by combining an anti-T cell monoclonal antibody, 4 DSTs given once 24 hr pretransplant and weekly 3 times posttransplant, and CsA. CsA was given daily for 28 days or 60 days posttransplant. The dose consisted of CsA 5 mg/kg/day starting 24 hr pretransplant and continuing until day 7 posttransplant and followed by 2.5 mg/kg/day for either 21 more days (total CsA days = 28 days) or 53 days (total CsA days = 60 days). The anti-T cell monoclonal antibody OX52 (200 micrograms i.v.) was given once 24 hr pretransplant. DST (1 ml) was given 24 hr pretransplant and on days 7, 14, and 21 posttransplant. Low-dose CsA for 28 days never induced indefinite allograft survival. CsA for 60 days, however, resulted in the occasional indefinite allograft survival (> 1 year) even in this difficult model. The addition of DST 24 hr pre- and posttransplant on days 7, 14, and 21 to both 28 days and 60 days of CsA further prolonged allograft survival. The best survival was seen in the group given DST 24 hr pre- and on days 7, 14, and 21 posttransplant and 60 days of CsA, with all the allografts surviving beyond 100 days of CsA, with all the allografts surviving beyond 100 days and more than 50% surviving indefinitely (> 1 year). The addition of a single dose of OX52 24 hr pretransplant to the multiple DSTs and 28 days of CsA protocol significantly improved indefinite allograft survival but its influence was less dramatic when given to the multiple DSTs and 60 days of CsA protocol. This beneficial interaction between CsA, DST, and an anti-T cell MoAb offers a clinically applicable protocol for both living donor and cadaveric organ transplantation in inducing donor-specific hyporesponsiveness, and further investigations are warranted.

Animals↗