Hepatitis C infection and viremia in Dutch Hemophilia patients

Serum samples from 316 patients visiting the Dutch National Hemophilia Center were collected from 1979 to 1993 and stored at ?30°C. Patients were placed into three different groups: (1) patients ever treated with large pool non-hepatitis C virus (HCV)-safe concentrate (n=179); (2) patients treated with cryoprecipitate (n = 125); and (3) patients treated exclusively with HCV-save concentrate (n=12). In order to examine the prevalence of HCV infection in the different treatment groups serum samples were tested retrospectively for anti-HCV antibody using second generation enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA-2). Significant differences in the prevalence of HCV infection were found between these 3 groups (group 1: 99%, group 2: 66%, group 3: 0%). The safety of currently administered clotting products is demonstrated in 57 patients who remained without HCV markers between 1989 and 1993. To examine the natural course of HCV infection fresh-frozen plasma samples were obtained recently from a subgroup of 277 hemophilia patients for HCV-RNA detection by a well-validated cDNA-PCR assay. In contrast to other reports, no evidence was found for seronegative HCV carriers. None of 52 patients without anti-HCV had detectable HCV-RNA. Of 225 patients with anti-HCV, 182 (81%) were HCV-RNA positive. None of 39 anti-HCV positive patients with a negative HCV-RNA reaction had serum alanine aminotransferase (ALT) levels above 50 U/l, whereas 44% of HCV-RNA positive patients had persistently elevated ALT levels above 50 U/l. These results indicate that 20% of hemophilia patients who have been infected with HCV in the past eliminated the virus or have viral replication below the detection limit of polymerase chain reaction (PCR) without biochemical evidence of liver damage. © 1995 Wiley-Liss, inc.     

Influence of dose frequency on the therapeutic efficacies of ciprofloxacin and ceftazidime in experimental Klebsiella pneumoniae pneumonia and septicemia in relation to their bactericidal activities in vitro

The antibacterial activities of ciprofloxacin versus ceftazidime againstKlebsiella pneumoniae in vitro andin vivo were compared. Although there was only a minor difference in MBC values between both drugs ciprofloxacin demonstrated a high and dose-dependent bacterial killing ratein vitro and in lungs of leukopenic rats in contrast to the more time-dependent bactericidal activity of ceftazidime. After treatment of aK.pneumoniae pneumonia and septicemia the efficacy of ciprofloxacin was only slightly influenced by the mode of administration, either at 6-h intervals or continuously, whereas ceftazidime was far more effective after continuous administration. This resulted in a superior efficacy of ciprofloxacin after intermittent treatment as compared to ceftazidime, whereas ceftazidime was more effective after continuous administration as compared to ciprofloxacin. Also ciprofloxacin proved to be bactericidal against bacteria that were not actively growing, bothin vitro andin vivo, whereas ceftazidime was not.     

Helicobacter species are not detectable by 16S rDNA PCR in bile from Dutch patients with common bile duct stones

BACKGROUND: Some Helicobacter species colonize the intestinal tract. To explore the possible relation between Helicobacter spp. and gallbladder disorders, we have investigated their presence in bile of patients with biliary obstruction and dilatation of the bile ducts. METHODS: Bile was sampled from 31 Dutch patients with biliary obstruction identified by jaundice and dilatation of the bile ducts on ultrasound. Samples (n = 31) were obtained immediately following cannulation of the common bile duct (CBD) by endoscopic retrograde cholangiopancreatography (ERCP) (n = 29) or by peri-operative puncture of the gallbladder (n = 2). DNA was isolated from bile by binding to diatoms. Helicobacter spp. were detected by a sensitive (detection limit 1 CFU per reaction tube) 16S rDNA PCR with genus-specific primers. Duplicate samples were spiked with Helicobacter pylori DNA and subjected to PCR in order to check for inhibition. RESULTS: 28 patients had CBD stones (bile collected by ERCP (n = 26) or operatively (n = 2)), 2 had a pancreatic head tumor, and in 1 no abnormalities were found. In 1 of 21 amplifiable bile samples (10/31 inhibited) from Dutch patients with CBD stones, H. pylori 16S rDNA was found. CONCLUSION: Our data indicate that CBD stones in Dutch patients are not associated with the presence of Helicobacter spp. in bile.     

The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia

To prevent hemophilic arthropathy, prophylactic treatment of children with severe hemophilia should be started before joint damage has occurred. However, treatment is expensive, and the burden of regular venipunctures in young children is high. With the aim of providing information on starting prophylaxis on the basis of individual patient characteristics, the effect of postponing prophylaxis on long-term arthropathy was studied in a cohort of 76 patients with severe hemophilia born between 1965 and 1985. The median age at first joint bleed was 2.2 years (range, 0.2-5.8). Prophylaxis was started at a median age of 6 years (interquartile range [IQR], 4-9), and the median annual clotting factor use on prophylaxis was 1750 IU/kg/y (31 IU/kg/wk). Hemophilic arthropathy was measured by the Pettersson score (maximum, 78 points). At a median age of 19 years, the median Pettersson score was 7 points (IQR, 0-17). After 2 decades of follow-up, the Pettersson score was 8% higher (95% confidence interval, 1%-16%) for every year prophylaxis was postponed after the first joint bleed. This effect was independent of age at Pettersson score, age at first joint bleed, and prophylactic dose used. In conclusion, most patients have their first joint bleed after the age of 2 years. Patients who start prophylaxis soon after the first joint bleed show little arthropathy in adulthood. The longer the start of prophylaxis is postponed after the first joint bleed, the higher the risk of developing arthropathy.     

History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia

Protein C (PC) deficiency is an autosomal dominant inherited disorder associated with spontaneous and recurrent thrombotic events. Factor V Leiden (FVL) increases the risk of thrombosis in PC-deficient type I families. We have investigated the relationship between PC deficiency genotype and clinical phenotype in a large four-degree Italian family followed since 1988. Methods: PC activity and antigen levels were quantified; sequencing of PC DNA was performed to identify polymorphism. FVL and factor II (G20210A) polymorphism were screened. Results: PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type. Of 15, eight were heterozygous for FVL. The two subjects with PC < 6%, homozygous for Arg32Cys and heterozygous for FVL, suffered from thrombosis during childhood. Of 11, six subjects with PC deficiency and heterozygous for FVL showed the first thrombosis at an age between 21 and 54. None of the five PC-deficient subjects, who were wild type for FVL, showed thrombosis. Two subjects with PC > 70%, both heterozygous for FVL developed thrombosis in the presence of another risk factor. This study suggests that FVL and PROC mutations increase the risk of thrombosis in subjects with PC deficiency, which could be considered as a 'variable' risk factor. The thrombosis-prone PC-deficient families carry additional risk factors for thrombosis.     

Joint distraction results in clinical and structural improvement of haemophilic ankle arthropathy: a series of three cases

Summary. The incidence of haemophilic arthropathy in multiple joints decreased due to treatment with clotting factor. Nowadays patients are enabled to live a rather normal life, resulting in more (sports) trauma-induced arthropathy in isolated joints like the ankle. As surgical treatment options, fusion of the tibiotalar joint and total ankle replacement are available. Both standard treatments have complications and therefore an alternative treatment is desired. In this study, treatment of haemophilic ankle arthropathy with joint distraction was explored. Three patients with haemophilic ankle arthropathy were treated with joint distraction using an Ilizarov external fixator. Clinical outcomes like function, participation and pain were evaluated in retrospect with three different questionnaires: haemophilia activities list, impact on participation and autonomy and the Van Valburg questionnaire. Structural changes were assessed blinded on X-ray by the Pettersson score and ankle images digital analysis (AIDA) and by an MRI score. All three patients were very satisfied with the clinical outcome of the procedure. They reported a clear improvement for self-perceived functional health, participation in society and autonomy and pain. Partial ankle joint mobility was preserved in the three patients. The Pettersson score remained the same in one patient and slightly improved in the two other patients, while joint space width measured by AIDA and the MRI score demonstrated improvement for all three patients after ankle distraction. This study suggests that joint distraction is a promising treatment for individual cases of haemophilic ankle arthropathy, without additional risk of bleedings during treatment.     

Immature articular cartilage is more susceptible to blood-induced damage than mature articular cartilage: an in vivo animal study

OBJECTIVE: Cartilage of young but skeletally mature dogs is more susceptible to blood-induced damage than that of old dogs. The aim of the present study was to investigate whether cartilage of skeletally immature individuals is even more adversely affected by exposure to blood than that of mature individuals, as suggested by clinical practice experience with humans. METHODS: Right knees of 3 groups of 6 beagle dogs (skeletally immature, young mature, and old animals) were injected with autologous blood on days 0 and 2. On day 4, cartilage matrix proteoglycan turnover (content, synthesis, and release), synovial inflammation, and cartilage-destructive properties of the synovial tissue were determined and compared with those of the left uninjected control knees. RESULTS: Subsequent to intraarticular bleeding, cartilage proteoglycan content decreased in an age-dependent manner, with the largest decrease occurring in cartilage of immature animals. Proteoglycan synthesis per cell also decreased in an age-dependent manner, with the largest decrease occurring in the immature animals. Cartilage proteoglycan release increased in all 3 groups, but the decrease was not age dependent. Interestingly, immature animals showed a large increase in cartilage DNA content upon exposure to blood, whereas mature animals did not. Histologic analysis showed a mild synovitis in animals of all ages, but catabolic inflammatory activity was found only in immature animals. CONCLUSION: Joints of skeletally immature dogs appeared to be more susceptible than joints of mature dogs to the adverse effects of a joint hemorrhage. These data suggest that for humans, specifically young children are at risk for joint damage after a joint hemorrhage.     

多对比、各向同性、单层块3D-MRI在多发性硬化中的应用

本研究描述了各向同性、单层块三维数据集组[双反转恢复序列(double inversion-recovery,DIR)、液体衰减反转恢复序列(fluid-attenuated inversion