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Biomedical subjects

R Reding

Publications and source records attributed to R Reding.

At least 73 records · Page 4Linked to original sources
PubMed1994

Sequential treatment of biliary atresia with Kasai portoenterostomy and liver transplantation: a review.

Biliary atresia is the most frequent cause of chronic cholestasis in infants. When left untreated, this condition leads to death from liver insufficiency within the first 2 yr of life. The modern therapeutic approach consists of a sequential strategy with Kasai portoenterostomy as a first step and, in case of failure, liver transplantation. After portoenterostomy, no more than 20% to 30% of patients will live jaundice-free into adulthood. Illness in another third will be palliated, and these patients have extended survival, delaying liver transplantation to later childhood (2 to 15 yr). The remaining 30% to 40% will not benefit from the Kasai operation and will die of liver failure in infancy. The annual need of liver transplantation for biliary atresia is one case per million people. This indication represents 35% to 67% of the reported series of pediatric liver transplantation and between 5% and 10% of the indications for liver transplantation, all ages included. Approximately four of five children transplanted for biliary atresia will become long-term survivors with good physical and mental development; recurrence of the disease after transplantation has not been observed. Because most candidates are young children (< 3 yr) of small size (< 10 kg), there is a shortage of size-matched donors (which has been alleviated by the use of innovative techniques such as reduced and split livers). The resulting redistribution of the adult donor liver pool is ethically justified by the equal quality of the results after transplantation of a full-size or partial graft.

Adolescent↗
PubMed1994

Preformed antibody and complement rebound after plasma exchange: analysis of immunoglobulin isotypes and effect of splenectomy.

UNLABELLED: Splenectomy (Sx) has been proposed to attenuate post-PE (plasma exchange) rebound of isoagglutinins and xenogenic (XG) antibody (Ab) in both ABO-incompatible allografts and discordant xenografts. This study analyses the qualitative nature and kinetics of serum immunoglobulins as well as complement resynthesis after PE in sham-operated (PE) and splenectomized (PE+Sx) syngeneic LOU/C rats; non-PE sham-operated or splenectomized animals were used as controls. PE was performed in unanesthetized, unheparinized rats. Immunoglobulin isotypes and subclasses (IgM, IgG1, IgG2 alpha, IgG2b) of total circulating Ab were measured pre-PE and up to 21 days post-PE, using ELISA (enzyme-linked immunosorbent assay) and specific mouse antirat monoclonal Ab. Antiguinea-pig (GP) XG Ab (IgM, IgG2a) serum levels were measured using cellular ELISA with cultured GP endothelial cells as targets. Sx alone significantly reduced XG IgM serum levels (p < 0.0001). Maximal rebound of total and XG IgM was observed on day 3 post-PE, reaching 674% and 187% of the pre-PE levels, respectively; these overshoots were entirely suppressed by Sx (p < 0.005 for total IgM; p < 0.0001 for XG IgM). Total IgG2a, IgG2b and IgG1 as well as XG IgG2a serum levels did not show significant overshoot post-PE. The activity of the complement classical pathway (mean +/- SD), assessed by CH50, was decreased at 51 +/- 19% of basal value 15 minutes after PE, and had returned to baseline level by day 2 post-PE with or without Sx. IN CONCLUSION: (1) Six alone significantly reduced XG IgM serum levels; (2) early post-PE Ab rebound was mainly observed for IgM; (3) both total and XG IgM rebound was inhibited by Sx. This suggests that Sx probably removes a significant proportion of IgM producing cells undergoing post-PE stimulation. These data provide a rationale for combining PE with Sx in ABO-incompatible and discordant XG transplantation.

Animals↗
PubMed1994

Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts. Efficacy, toxicity, and dose regimen in 23 children.

Twenty-three pediatric liver transplant recipients (median age 3.9 years) were converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti-T lymphocyte antibodies either for AR prophylaxis or therapy before FK506 conversion. Full clinical and histologic responses to FK506 therapy were observed in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006). Acute FK506 toxicity included renal dysfunction in 12/23 children (52%), neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%), with a poor correlation with the corresponding FK506 trough plasma level. Moreover, a significant impairment of glomerular filtration rate was recorded in the 12 children who received FK506 treatment for more than 6 months (P = 0.002). FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n = 4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS was controlled, and the children were successfully retransplanted for chronic rejection under FK506. The occurrence of Epstein-Barr virus primary infection under FK506 therapy was found to constitute a significant risk factor for LPS (P = 0.027). In summary, full response to FK506 conversion was observed in 69% of uncontrollable AR cases; however, 74% and 22% of this probably over-immunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.

Adolescent↗
PubMed1994

Piggyback transplantation with side-to-side cavocavostomy is an ideal technique for right split liver allograft implantation.

BACKGROUND: Split liver grafting has not gained wide acceptance mainly because of different vascular and biliary technical problems. STUDY DESIGN: A new technique of right split liver transplantation is described. The piggyback implantation technique, using wide side-to-side cavocavostomy overcomes problems encountered when sharing the superhepatic vena cava cuff between two livers and obtains optimal drainage of venous allograft outflow, thus avoiding extensive bleeding at the transection margin. RESULTS: This technique was successfully used in two adult recipients. CONCLUSIONS: Piggyback transplantation using wide side-to-side cavocavostomy allows easy and safe implantation of the right split liver allograft.

Adult↗
PubMed1993

Monoclonal antibodies in prophylactic immunosuppression after liver transplantation. A randomized controlled trial comparing OKT3 and anti-IL-2 receptor monoclonal antibody LO-Tact-1.

A prospective trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were randomly divided into three groups according to immunosuppression during the first 10 days post-OLT: triple drug therapy only (TDIS: cyclosporine, steroids, azathioprine) (group I: n = 42); TDIS with a 10-day course of OKT3 (group II: n = 44); and LO-Tact-1 (anti-IL-2 receptor mAb) (group III: n = 43). Biopsy-proved acute rejection (AR) was treated using the same biopsy-guided protocol in the 3 groups. One-year patient survival rates were 67%, 84%, and 93% in groups I, II, and III, respectively (I vs. II, NS; I vs. III, P = 0.001; II vs. III, P = 0.044). Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection, with an overall rate of 89% during the first 3 months post-OLT, similar in the 3 groups. However, incidences of steroid-resistant rejection diagnosed during the 10 first days post-OLT were 54%, 24%, and 34% in groups I, II, and III and 46%, 26%, and 11%, respectively, during the 10-90 days interval. Sixteen patients with CMV had received OKT3, whereas the 5 remaining CMV cases had not (P = 0.019). In summary: (1) mAbs did not modify crude incidence of AR; (2) in the early period (< 10 days), TDIS immunoprophylaxis combined with OKT3 was more efficient than TDIS alone; (3) when compared with groups I and II, LO-Tact-1 apparently better prevented steroid-resistant rejection during the 10-90 days post-OLT; (4) OKT3 significantly increased incidence of CMV infection. In conclusion, TDIS with LO-Tact-1 seemed to achieve the better risk-benefit ratio in induction immunosuppression after OLT.

Acute Disease↗
PubMed1993

The unreliability of the lidocaine/monoethylglycinexylidide test for assessment of liver donors.

The serum monoethylglycinexylidide (MEGX) level 15 min (t15) after i.v. administration of lidocaine (1 mg/kg) in liver donors was retrospectively correlated with graft outcome and early hepatic function. Among the 35 orthotopic liver transplants studied, 4 recipients had to be retransplanted within 10 days post-OLT because of early graft nonfunction or dysfunction, and 3 recipients died, with a median (range) donor MEGX t15 (ng/ml) of 100 (86-119) and 169 (146-182), respectively. The remaining 28 OLT patients living with functioning grafts had a donor MEGX of 87 (18-245). No significant correlations could be found between donor MEGX t15 and recipient mean and peak glutamic-oxaloacetic and -pyruvic transaminases, total serum bilirubin, or mean and minimum prothrombin time values studied from day 1 to day 5 post-OLT. Moreover, categorization of donors using the MEGX t15 cut-off point of 80 ng/ml could not predict liver graft quality, as previously suggested. In summary, MEGX t15 in liver donors correlated neither with graft outcome nor with early functional parameters. Accordingly, the MEGX test should not be used as an isolated discriminatory evaluation for organ utilization.

Adult↗
PubMed1993

Impact of innovative techniques on the waiting list and results in pediatric liver transplantation.

The wide application of liver transplantation in children is hampered by the shortage of size-matched pediatric donors; this results in high mortality rate on the waiting list, a long waiting time, worsening of the clinical condition of the waiting patient, deterioration of the overall results, and an increase in the cost. Reduced-size liver transplants have been shown to be a safe way to alleviate the shortage of size-matched organs. We have retrospectively analyzed the impact of the reduced-size liver transplants on the waiting list and the results in a consecutive series of 314 transplants performed in 261 children over an 8-year period (1984-1991). Among these 314 grafts, 160 (51%) were innovative techniques including 86 reduced livers (stricto senso), 66 partial livers (with preservation of the recipient vena cava), and 8 split livers. Such an extensive use of these technical variants allowed a sharp decrease in the waiting list mortality: from 14.9% between 1984 and 1989 to 6.6% in 1990 and 5% in 1991; the corresponding figures for infants registered under the age of 1 year were 25%, 13.3%, and 8.3%, respectively. Results obtained with a full-size graft or a technical variant were similar regarding surgical complications (with a significantly lower incidence of arterial thrombosis for the reduced transplants), graft loss, and patient survival. The 5-year survival of the whole group was 78.1% without any significant difference regarding type of transplant, indications (with the best results: 89.4% 5-year survival obtained in 41 children grafted for metabolic diseases), or age (the 5-year survival was 82.2% for the 41 infants transplanted under the age of 1 year, 78.9% for the 124 children transplanted between 1 and 3 years, and 81.3% for the 96 children transplanted between 6 and 15 years). This series of reduced-size liver transplants, which is the largest worldwide single institutional experience, confirms that the extensive use of reduced transplants in children is safe; this study also shows that innovative techniques, including the split liver, allow a drastic decrease of the waiting list mortality of candidates in the pediatric age range without alterations of the results.

Adolescent↗
PubMed1993

Epstein-Barr virus serology and Epstein-Barr virus-associated lymphoproliferative disorders in pediatric liver transplant recipients.

Epstein-Barr virus serology was performed before and after transplantation in 116 patients of a total series of 261 pediatric OLT recipients. Thirty-nine percent had no immunity before OLT, but this percentage decreased to 11.2% at 6 months and 10.5% at 2 years after transplantation. In this series, 10 children developed a B cell lymphoproliferative disease. Four had adenotonsillar involvement, 2 of them with associated digestive tract invasion. Three of these are alive, 2 after retransplantation for chronic rejection subsequent to arrest of immunosuppression. The fourth died from bone marrow aplasia. Three patients with multiorgan involvement died from multisystemic failure. The remaining 3 patients had a pseudotumoral mass. Two of these are alive, 1 after retransplantation for hepatic localization and secondary vascular and biliary complication. The last died from cachexia. Four patients developed the syndrome after viral reactivation, and 6 after primo infection. Four patients were under FK506 rescue therapy. We conclude that a high rate of EBV primo infection is observed in the first months after transplantation. A significant percentage will develop EBV-associated lymphoproliferative disease, which causes death in half of the patients, including all these with multiorgan involvement. Half of the patients may survive, but because immunosuppression must be stopped, retransplantation for chronic rejection is often necessary in survivors.

Adolescent↗
PubMed1993

FK506 (tacrolimus), a novel immunosuppressant in organ transplantation: clinical, biomedical, and analytical aspects.

The macrolide immunosuppressant FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent that was discovered in 1984. This agent, isolated from the fungus Streptomyces tsukubaensis, has a mechanism of action similar to that of cyclosporine. Experimental data were first published in 1987, and clinical trials were started 2 years later in Pittsburgh. The drug has a potent hepatotrophic effect, which could explain its success in liver transplantation. Particularly encouraging results were obtained in liver allograft recipients, suggesting a lower risk/benefit ratio than with other immunosuppressants. However, recent data show that the drug is not devoid of toxicity (mainly nephrotoxicity), which should the percent the need for careful blood monitoring. Several methods of analysis have been described, some satisfactory, others inadequate for routine monitoring. There is still a lack of specific methods to determine routinely the parent drug concentrations in biological fluids for clinical pharmacokinetics purposes. Despite greater experience in therapeutic drug monitoring, the correlation between FK506 concentrations and efficacy or toxicity is still unclear. More investigations are required to better understand and determine the appropriate use of FK506 in organ transplantation and treating autoimmune diseases.

Drug Monitoring↗
PubMed1992

Acute adenovirus hepatitis in liver transplant recipients.

An acute or fulminant adenovirus hepatitis developed in 5 of 224 pediatric patients who were recipients of orthotopic liver transplants. All had received prednisolone, azathioprine, and cyclosporine as basal immunosuppression, and four received monoclonal (OKT3) or polyclonal (antithymocyte globulin) antibodies for steroid-resistant rejection episodes. These patients initially had high fever and a worsening condition for a mean of 73 days after transplantation (range 44 to 140 days). Results of biochemical tests showed very high serum levels of lactate dehydrogenase. Aspartate aminotransferase values were always markedly more elevated than those of alanine aminotransferase. Two patients had severe leukopenia. Results of histologic studies of the liver showed extensive areas of confluent necrosis and targetlike hepatocyte nuclei. Typical intranuclear viral inclusions were observed on electron microscopy. Adenovirus was cultured in all patients and in two relatives. Two patients died of liver failure; others recovered after cessation of immunosuppression. We conclude that adenovirus hepatitis can be fatal in liver transplant recipients. There is no specific treatment, and immunosuppression must be discontinued.

Adenovirus Infections, Human↗
PubMed1992

Complicated duodenal ulcer, vagotomy or distal resection--own experience.

An analysis of clinical material through 10-year-period (1980-1989) is presented. There were 708 gastric operations performed for gastroduodenal ulcer disease. Most frequently distal gastric resections (585) were used, 233 in B. I. and 352 in B II. modification. Selective proximal vagotomy (SPV) was less frequently used (only 116 cases). Authors think there is no reason for a general use of SPV for each form of duodenal ulcer because of very serious competition with the H2 blockers. A different individual proved choice of the method as well as an appropriate subtle operating technique is considered to be essential.

Duodenal Ulcer↗
PubMed1992

ABO-incompatible orthotopic liver allografting in urgent indications.

The influence of ABO-compatibility was reviewed in 70 emergency orthotopic hepatic transplantations (OHT) performed at our institution in 60 highly urgent recipients between February 1984 and March 1989. Thirty-eight were ABO-identical (Id); 16, compatible (Comp), and 16, incompatible (Inc) transplants, respectively. The three groups did not differ statistically with respect to the indications, the adult/child ratio and the proportions of first OHT and retransplantations. Graft survival rates of ABO-Id, ABO-Comp and ABO-Inc OHT at one year were 47, 38 and 19 per cent, respectively (p less than 0.02). Incidences of perioperative mortality, arterial thrombosis and irreversible rejection were slightly (although not significantly) higher in the ABO-Inc group. Retransplantation rates were 19, 7 and 36 per cent in the ABO-Id, Comp and Inc groups, respectively. Patient survival rates at one year were 59 per cent for the ABO-Id group versus 43 per cent for both ABO-Comp and Inc combinations (NS). The results of this series of highly urgent OHT confirm that graft survival is lower with ABO-Inc livers; their use should be strictly considered as a short term life-saving procedure. Improvement of patient survival after a first urgent ABO-Inc OHT may require an aggressive policy of retransplantation.

ABO Blood-Group System↗
PubMed1991

Surgical management of 552 carcinomas of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded). Results of the French Surgical Association Survey.

Five hundred fifty-two cases of primary carcinoma of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded) collected from 55 surgical centers were reviewed retrospectively. Three hundred seven patients (56%) had upper-third lesions (proximal carcinoma), whereas 71 (13%) and 101 (18%), respectively, had middle-third and lower-third bile duct carcinomas. The remaining patients had diffuse lesions. Resectability rates were 32% for upper-third localization compared to 47% and 51% for middle-third and lower-third localization, respectively. The operative mortality rate for proximal carcinomas was significantly lower with resection (16%) compared with palliative surgery (31%) (p less than 0.05). Overall 1-year survival (operative deaths excluded) was 68% after tumor resection compared to 31% after palliative surgery (p less than 0.001). Long-term results after surgical resection correlated with local and regional extension of the disease. The results of this study show that resection of extrahepatic bile duct carcinomas, particularly in an upper-third localization, often is associated with worthwhile long-term survival.

Adenoma, Bile Duct↗
PubMed1991

[Pancreatic penetration of antibiotics].

Antibiotic therapy is indicated in acute pancreatitis because the most common complication and the mean reason for mortality is a bacterial infection. Concentrations of nine antibiotics from various classes were studied in the pancreatic tissue and pancreatic juice of patients and dogs. The volume of distribution is the most valuable parameter for predicting the potential pancreatic penetration of a substance. As a result of our pharmacokinetic studies mezlocillin and cefotiam, especially ciprofloxacin, have the most antiinfectious potential in treatment of acute pancreatitis. Metronidazole is suitable for combination in cases of pancreatic infections covering anaerobic bacteria.

Animals↗