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  • 1
    ISSN: 1432-1041
    Keywords: Ciclosporin ; metabolism ; metabolites ; liver dysfunction ; kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n=19), II with elevated liver enzyme activity or bilirubin concentration in serum (n=20), and III with cholestasis (n=8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III〉I=II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.
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  • 2
    ISSN: 1432-1076
    Keywords: Liver transplantation ; Liver function tests ; Prognostic tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pre-operative risk of paediatric liver transplantation candidates (n=41) was assessed in a prospective study by means of clinical symptoms, conventional static and liver blood flow dependent dynamic liver function tests. Nine patients died during the 365-day waiting period. The data were subjected as covariates to a survival analysis in the Cox proportional hazards model. There was a significant relationsship between the results of mono-ethylglycinexylidide (MEGX) formation and ICG test and the 365-day survival rate. In the stepwise analysis, none of the remaining parameters improved the predictive ability when added to the dynamic liver function test results. The assessment of post-transplantation liver function was studied in 27 patients during the first 28 postoperative-day period. In addition, liver function was studied in a cross-sectional study 1–7 years after successful liver transplantation in children with complete or partial rehabilitation. In the early postoperative period severe organ damage was indicated by both static and dynamic liver function tests. In the later course after transplantation no deterioration of liver function measured with MEGX formation was to be observed. These findings demonstrate the usefulness of dynamic liver function tests in the pre- and post-transplant assessment of liver function.
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  • 3
    ISSN: 1432-1076
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Es wird eine Zwerchfellanomalie bei einem 7jährigen Jungen beschrieben, welche erstmals mit 6 Jahren auftritt und sich lediglich in einer Asymmetrie des Thorax bei tiefer Einatmung äußert. Röntgenologisch ergeben sich bei ruhiger Atmung völlig normale Verhältnisse. Der Junge vermag jedoch willkürlich durch eine bestimmte Bewegung sein linkes Zwerchfell ruckartig um etwa 4 Querfinger in die Höhe zu verlagern bei extremem Tiefstand des rechten. Abgrenzung dieser Zwerchfellanomalie gegen Zwerchfellhernie,-lähmung, Relaxatio diaphragmatica totalis oder partialis, rudimentäre Eventeratio und Diaphragma molle. Als Wesen dieser anscheinend noch nicht beschriebenen Zwerchfellanomalie wird eine Wandschwäche des linken Zwerchfells, vermutlich auf erworbener Grundlage, angenommen.
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  • 4
    ISSN: 1432-1076
    Keywords: Key words Kidney transplantation ; Graft survival ; Infant ; Children preschool
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Between 1975 and 1994, 46 children under 6 years of age received a total of 52 renal transplants. Obstructive uropathy and dysplasia accounted for most causes of terminal renal failure (17 and 12 cases respectively). Four patients required a second, 1 patient a third transplantation. Cadaveric organs were used on 33 occasions; 19 patients received a living-related donor kidney. Immunosuppression was performed with azathioprine in 5, with cyclosporine A in 21 and combined azathioprine/cyclosporine therapy in 20 cases. After 1 year, graft survival was 81%, and after 5 years 78%. Creatinine clearance declined slightly between 1 and 5 years from 69 to 56 ml/min per 1.73 m2. Main causes of graft failure were thrombotic complications in 6 cases and death with functioning graft in 5 cases. Graft thrombosis occurred only in grafts from young donors under the age of 7 years and after vascular anastomosis to the iliac vessels. Only two transplants were lost in rejection episodes. Patient survival was 94% after 1 and 90% after 5 years. Two patients died due to septiacemia, 1 died of a ruptured aortic aneurysm, 1 of cerebral ischaemia and 1 suddenly of unknown cause. Patient and graft survival was not different compared with 204 patients aged 6–16 years who received a renal transplantation during the same time period at our institution. After transplantation the patients receiving cyclosporine A showed a marked catch-up growth in the 1st year. The median standard deviation score (SDS) of body length improved from −2.63 to −1.39 standard deviations. Conclusion Renal transplantation is the treatment of choice in end-stage renal failure in children under 6 years.
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  • 5
    ISSN: 1432-1041
    Keywords: Ciclosporin liver transplantation ; metabolites ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their clinical course. There were no significant differences between both groups in blood Cs level, kidney function before transplantation, liver function or co-administration of other potentially nephrotoxic drugs. A correlation matrix involving both groups showed a significant correlation between the blood concentration of metabolite M1c9 and serum creatinine and urea, and an inverse correlation with creatinine clearance. During a nephrotoxic episode the blood concentrations of metabolites M1c9 and M1A were significantly elevated in patients in Group II. Analysis of the time course revealed significantly higher blood levels of M19 and M1c9 in Group II patients compared with those in Group I for the first 10 days after transplantation. Serum creatinine and urea concentrations remained significantly elevated, the creatinine clearance being significantly reduced throughout the period of observation. The elevated blood concentrations of ciclosporin metabolites M1c9 and M19 during nephrotoxic episodes suggest that these metabolites are associated with ciclosporin nephrotoxicity. It could not be decided if the elevated metabolite concentrations were the result of and/or the reason for impaired kidney function.
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  • 6
    ISSN: 1432-1041
    Keywords: Ciclosporin ; Liver transplantation ; metabolites ; cholestasis ; rejection ; M19 ; M1A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and γ-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.
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  • 7
    ISSN: 1432-1076
    Keywords: Paediatric renal transplantation ; Pre-emptive transplantation ; Nephropathic cystinosis ; Growth development ; Long-term outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From 1970 to 1991 a total of 244 renal transplantations were performed in 203 children at the Medical School in Hannover. The mean patient age was 10.4 years with a range between 11 months and 16.9 years. Fifty-nine children received a living donor graft from one parent and 144 received cadaveric grafts. Forty-two children were transplanted without prior dialysis treatment. After 20 years the overall survival rates were 86% for the patients and 39% for the first grafts. Grafts from donors below 5 years of age had a less favourable survival (44% after 5 years). Pre-emptive transplantation yielded comparable results with the benefit of a shorter period of uraemia. Hypertension developed in 80% of transplanted patients. Only children with living related donor grafts had significantly less hypertensive problems independent of the immunosuppressive regimen. Post-transplantational growth improved under cyclosporin. Children with nephropathic cystinosis also showed catch up growth after transplantation under cyclosporin. The long-term outcome and rehabilitation of grown-up recipients were encouraging.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 10 (1986), S. 109-110 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Alors que la résection de métastases hépatiques métachrones des cancers colorectaux peut Être considérée comme une thérapeutique à visée curative dans certains cas, on sait peu de choses en ce qui concerne le pronostic après résection de lésions hépatiques synchrones. Auparavant, ces lésions n'étaient traitées qu'à visée palliative. Nous avons analysé les observations de 36 patients ayant eu une résection à visée curative de métastases hépatiques synchrones des cancers colorectaux traités entre 1977 et 1987 dans le service de chirurgie de l'Hôpital Universitaire de Hanovre. Dans 19 cas, la résection hépatique était effectuée en mÊme temps que la colectomie et dans 17 cas, après un intervalle médian de 2 mois. Il n'y avait aucune mortalité dans les deux séries. La survie médiane était de 28 mois pour tous les patients: le temps de récidive médian était de 13.5 mois. La probabilité de survie à 5 ans pour tous les patients était de 20%. Il n'y avait aucune différence observée selon que la lésion hépatique avait été réséquée simultanément ou pas (survie médiane 18 mois vs 31 mois). La survie n'était pas différente selon que les lésions hépatiques étaient simples ou multiples (26 vs 28 mois). Chez 21 des 36 patients, les métastases ont récidivé. Chez sept de ces patients, une résection à visée curative a pu Être proposée à nouveau. La survie chez ces sept patients était significativement améliorée par rapport aux 14 autres patients (p〈0.05). On conclut que la résection de métastases hépatiques synchrones des cancers colorectaux est valable. Le fait que la résection soit simultanée ou retardée n'a pas d'importance.
    Abstract: Resumen En tanto que la resección de metástasis hepáticas, metacrónicas del cancer colorrectal es considerada como un aproche potencialmente curativo, poco se conoce sobre el pronóstico después de la resección de metástasis hepáticas sincrónicas; en el pasado estos pacientes han sido generalmente sometidos a terapia paliativa solamente. Por consiguiente, nos propusimos analizar la información sobre 36 pacientes sometidos a resección curativa de metástasis sincrónicas de carcinomas colorrectales en el período 1977–1987 en el Departamento de Cirugía de la Escuela de Medicina de Hannover. En 19 pacientes se combinó la resección hepática con la resección del colon; en los otros 17 pacientes la resección hepática fue realizada después de un intervalo promedio de 2 meses de efectuada la resección primaria. No hubo mortalidad operatoria con ninguno de los 2 aproches. El tiempo promedio de sobrevida fue de 28 meses para la totalidad de los pacientes con un intervalo libre de recurrencia promedio de 13.5 meses. La probabilidad global de supervivencia a 5 a∼nos para la totalidad de los pacientes fue de 20%. No se hallaron diferencias significativas entre los pacientes sometidos a resección hepática inmediata o diferida (sobrevida promedio de 18 meses versus 31 meses). Las tasas de sobrevida no fueron diferentes para la resección de metástasis solitarias o de metástasis mÚltiples (26 versus 28 meses). Veinte y uno de los 36 pacientes presentaron recurrencia de sus metástasis hepáticas. En 7 de ellos se pudo realizar de nuevo una resección curativa; estos 7 pacientes exhibieron una sobrevida significativamente mejor (p〈0.05) en comparación con los 14 pacientes residuales. Es nuestra conclusión que pacientes con metástasis hepáticas sincrónicas de cancer colorrectal pueden beneficiarse de la resección del tumor primario y de las metástasis hepáticas. Es obvio que el momento de la resección hepática—inmediata versus diferida—no influye sobre las tasas de sobrevida.
    Notes: Abstract Whereas resection for metachronous liver metastases from colorectal cancer is considered to be a potentially curative approach, little is known about the prognosis after resection of synchronous liver metastases. In the past, these patients usually underwent only palliative therapy. Therefore, we have analyzed the data of 36 patients who underwent curative hepatic resection of synchronous liver metastases from colorectal carcinomas from 1977 to 1987 at the Department of Surgery, Hannover Medical School. In 19 patients, liver resection was combined with colonic resection; in the other 17 patients, hepatic resection was performed after a median interval of 2 months following resection of the primary tumor. No operative mortality was observed in either of the approaches. The median survival time was 28 months for all patients with a median recurrence-free interval of 13.5 months. Overall 5-year survival probability for all patients was 20%. There were no significant differences observed between immediate or delayed liver resection (median survival 18 months versus 31 months). Survival rates were not different after resection of solitary versus multiple liver metastases (26 versus 28 months). Twenty-one of the 36 patients had a recurrence of their liver metastases. In 7 of them, curative liver resection could be performed again. These 7 patients had a significantly improved survival (p〈0.05) compared to the residual 14 patients. It is concluded that patients with synchronous liver metastases from colorectal cancer may profit from resection of the primary tumor and liver metastases. Timing of liver resection—immediate versus delayed—obviously has no impact on survival rates.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 17 (1993), S. 261-262 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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