Increased tumor markers in patients with liver cirrhosis are often considered to be unspecific.The use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been explored.We aime...Increased tumor markers in patients with liver cirrhosis are often considered to be unspecific.The use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been explored.We aimed to answer the question,Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease,hepatitis B,or hepatitis C with available liver biopsy.Tumor markers CA 19-9,CA 15-3,and CA 125 were determined using routine laboratory methods and correlated with the extent of liver fibrosis.Fibrosis stages 1 and 2 were classified as minimal fibrosis;stages 3 and 4,as severe fibrosis.Tumor markers CA 19-9,CA 125,and CA 15-3 increased with stage of fibrosis.For separating patients with mild fibrosis(F1+F2)from patients with severe fibrosis(F3+F4),CA 19-9 had a sensitivity of 70.5%and a specificity of 88.6,CA 125 had 38.1%and 89.7%,and CA 15-3 had 19.0%and 93.0%,respectively.Logistic regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe fibrosis.The CA 19-9/CA 125 score achieved a similar specificity(97.1%vs.100%)but a higher sensitivity(42.9%vs.33.3%)than the widely used cirrhosis discriminant score of Bonacini.A specificity(98.5%)similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125,which had the best positive predictive value,92.9%.The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis(F3+F4)was confirmed in an independent group of patients with liver disease.The combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high specificity.Patients without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.展开更多
Piritramide is indicated for treatment of postoperative pain and analgosedatio n in the intensive care unit(ICU)setting.In an open prospective study the pha rmacokinetics of piritramide were investigated in four group...Piritramide is indicated for treatment of postoperative pain and analgosedatio n in the intensive care unit(ICU)setting.In an open prospective study the pha rmacokinetics of piritramide were investigated in four groups:newborns(NB,age :1-28 days)(n=8),infants 1(IF1,age:2-4 months)(n=7),infants 2(IF2,ag e:5-12 months)(n=14)and young children(YC,age:2-4 years)(n=10).The rec ommended paediatric dose range for therapy of postoperative pain is 50-200 μg/kg.Piritramide was administered intravenously as a single dose by bolus injecti on of 50 μg/kg.Blood samples were collected at 0,15,45,90 min and 3,6,9,12 h after application,and urine samples were collected before application and during the following intervals:1-2,2-6,6-12 h.Piritramide was measured in blood and urine by HPLC-ESI-MS.The following pharmacokinetic parameters:max imum plasma concentration(Cmax),distribution half-life(t1/2α),elimination half-life(t1/2β),total clearance(Clt)and median volume of distribution at equilibrium(Vdss)were calculated using a non-compartment and a two-compartment model for the disposition of piritramide(TOPFIT and NONMEM pharmacokinetic ana lysis).Newborns(NB)showed the highest maximumplasma concentrations(mean±SD)Cmax(79±240 μg/l)compared to the other three groups(IF1 36±367,IF2 12±8 1 and YC 16±9 μg/l)without statistical significance.The median elimination h alf-lives(t1/2β)were 702±720 min in NB,157±102 min in IF1,160±68 min in IF2 and 166±143 min in YC.For t1/2βthe difference between NB and the other t hree groups(IF1,IF2 and YC)was statistically significant(Mann-Whitney-U,P < 0.05).Clt was 15.9±16.7,46.6±76.9,235.5±454.1 and 338±168.1 ml/min in NB,IF1,IF2 and YC respectively.The total clearance increased exponentially wi th an elimination half-life of 702 min from 15.9 ml/min in NB to 46.6 ml/min in IF2.Differences between the NB/IF1 groups and IF2/YC groups were significantly significant(NB vs.IF2,NB vs.YC,IF1 vs.IF2 and IF1 vs.YC).Vdss was 2.0± 4.93,1.7±2.5,7.0±5.2 and 6.7±2.2 l/kg in NB,IF1,IF2 and YC respectively.In comparison to group IF1 the Vdss was significantly larger in groups IF2 and Y C(Mann-Whitney U,P < 0.05).Newborns showed a high initial concentration and a distinct prolongation of the elimination half-life of piritramide compared to infants,young children and adults.Therefore,dosage needed to treat postoperat ive pain should be reduced,and the repetitive doses should be geared to the ana lgesic effects.In infants and young children the elimination of piritramide is increased compared to adults;therefore the duration of the effects of piritra mide will be shortened,and dose intervals ought to be reduced.Subsequent clini cal trials for detailed dose adjustment of piritramide in paediatric patients co mparing pharmacokinetics and effectiveness are needed.展开更多
文摘Increased tumor markers in patients with liver cirrhosis are often considered to be unspecific.The use of this unspecific elevation to discriminate minimal fibrosis from severe fibrosis has never been explored.We aimed to answer the question,Do tumor markers predict severe liver fibrosis? The study group consisted of 125 patients with alcoholic liver disease,hepatitis B,or hepatitis C with available liver biopsy.Tumor markers CA 19-9,CA 15-3,and CA 125 were determined using routine laboratory methods and correlated with the extent of liver fibrosis.Fibrosis stages 1 and 2 were classified as minimal fibrosis;stages 3 and 4,as severe fibrosis.Tumor markers CA 19-9,CA 125,and CA 15-3 increased with stage of fibrosis.For separating patients with mild fibrosis(F1+F2)from patients with severe fibrosis(F3+F4),CA 19-9 had a sensitivity of 70.5%and a specificity of 88.6,CA 125 had 38.1%and 89.7%,and CA 15-3 had 19.0%and 93.0%,respectively.Logistic regression of a combined score of CA19-9 and CA 125 values revealed that an increase of 1 point of the CA 19-9/CA125 score resulted in a 1.6 times increase in likelihood of the presence of severe fibrosis.The CA 19-9/CA 125 score achieved a similar specificity(97.1%vs.100%)but a higher sensitivity(42.9%vs.33.3%)than the widely used cirrhosis discriminant score of Bonacini.A specificity(98.5%)similar to that of the CA 19-9/CA 125 score was reached by the easier determination of the combined elevation of CA 19-9 and CA 125,which had the best positive predictive value,92.9%.The excellent predictive ability of the combined elevation of CA 19-9 and CA 125 for severe liver fibrosis(F3+F4)was confirmed in an independent group of patients with liver disease.The combined elevation of CA 19-9 and CA 125 is useful for identifying patients with advanced fibrosis or cirrhosis with high specificity.Patients without a combined elevation of CA 19-9 and CA 125 still require histological examination to identify severe fibrosis or cirrhosis.
文摘Piritramide is indicated for treatment of postoperative pain and analgosedatio n in the intensive care unit(ICU)setting.In an open prospective study the pha rmacokinetics of piritramide were investigated in four groups:newborns(NB,age :1-28 days)(n=8),infants 1(IF1,age:2-4 months)(n=7),infants 2(IF2,ag e:5-12 months)(n=14)and young children(YC,age:2-4 years)(n=10).The rec ommended paediatric dose range for therapy of postoperative pain is 50-200 μg/kg.Piritramide was administered intravenously as a single dose by bolus injecti on of 50 μg/kg.Blood samples were collected at 0,15,45,90 min and 3,6,9,12 h after application,and urine samples were collected before application and during the following intervals:1-2,2-6,6-12 h.Piritramide was measured in blood and urine by HPLC-ESI-MS.The following pharmacokinetic parameters:max imum plasma concentration(Cmax),distribution half-life(t1/2α),elimination half-life(t1/2β),total clearance(Clt)and median volume of distribution at equilibrium(Vdss)were calculated using a non-compartment and a two-compartment model for the disposition of piritramide(TOPFIT and NONMEM pharmacokinetic ana lysis).Newborns(NB)showed the highest maximumplasma concentrations(mean±SD)Cmax(79±240 μg/l)compared to the other three groups(IF1 36±367,IF2 12±8 1 and YC 16±9 μg/l)without statistical significance.The median elimination h alf-lives(t1/2β)were 702±720 min in NB,157±102 min in IF1,160±68 min in IF2 and 166±143 min in YC.For t1/2βthe difference between NB and the other t hree groups(IF1,IF2 and YC)was statistically significant(Mann-Whitney-U,P < 0.05).Clt was 15.9±16.7,46.6±76.9,235.5±454.1 and 338±168.1 ml/min in NB,IF1,IF2 and YC respectively.The total clearance increased exponentially wi th an elimination half-life of 702 min from 15.9 ml/min in NB to 46.6 ml/min in IF2.Differences between the NB/IF1 groups and IF2/YC groups were significantly significant(NB vs.IF2,NB vs.YC,IF1 vs.IF2 and IF1 vs.YC).Vdss was 2.0± 4.93,1.7±2.5,7.0±5.2 and 6.7±2.2 l/kg in NB,IF1,IF2 and YC respectively.In comparison to group IF1 the Vdss was significantly larger in groups IF2 and Y C(Mann-Whitney U,P < 0.05).Newborns showed a high initial concentration and a distinct prolongation of the elimination half-life of piritramide compared to infants,young children and adults.Therefore,dosage needed to treat postoperat ive pain should be reduced,and the repetitive doses should be geared to the ana lgesic effects.In infants and young children the elimination of piritramide is increased compared to adults;therefore the duration of the effects of piritra mide will be shortened,and dose intervals ought to be reduced.Subsequent clini cal trials for detailed dose adjustment of piritramide in paediatric patients co mparing pharmacokinetics and effectiveness are needed.
