Comparative pharmacokinetics of rVIII-SingleChain and octocog alfa (Advate(®) ) in patients with severe haemophilia A.

BACKGROUND: rVIII-SingleChain, a novel recombinant factor VIII (rFVIII), has been designed as a B-domain truncated construct with covalently bonded heavy and light chains, aiming to increase binding affinity to von Willebrand factor (VWF). Preclinical studies confirmed greater affinity for VWF, giving improved pharmacokinetic and pharmacodynamic properties compared with full-length rFVIII. AIM: To investigate the pharmacokinetics of rVIII-SingleChain and compare them against those of full-length rFVIII. METHODS: This study enrolled 27 patients with severe haemophilia A in the AFFINITY clinical trial programme. After a 4-day washout period, all patients received a single infusion of 50 IU kg(-1) octocog alfa (Advate(®) ); after a ≥4-day postinfusion washout period, they received a single infusion of 50 IU kg(-1) rVIII-SingleChain. Blood samples for pharmacokinetic assessments of each product were collected before infusion (predose) and at 0.5, 1, 4, 8, 10, 24, 32, 48 and 72 h postinfusion for both products. RESULTS: rVIII-SingleChain had a longer mean half-life (t1/2 ) (14.5 vs. 13.3 h), lower mean clearance (CL) (2.64 vs. 3.68 mL h(-1) kg(-1) ), higher mean residence time (20.4 vs. 17.1 h) and larger mean AUCinf (2090 vs. 1550 IU?h dL(-1) ) than octocog alfa, respectively. The mean AUCinf after rVIII-SingleChain infusion was ~35% larger than after octocog alfa. A similar pattern was observed for AUC0-last . No serious adverse events or inhibitors were reported. CONCLUSIONS: rVIII-SingleChain has a favourable pharmacokinetic profile compared with octocog alfa and was well tolerated. The prolonged t1/2 , larger AUC and reduced CL of rVIII-SingleChain may permit longer dosing intervals, thereby improving patient adherence to prophylactic treatment.

Fetal cardiac catheterization using a percutaneous transhepatic access technique: preliminary experience in a lamb model.

OBJECTIVES: Human fetal cardiac intervention has hitherto typically involved a percutaneous transventricular approach. In fetal lambs, a transhepatic approach to access the fetal intra-abdominal veins after exteriorization of the uterus by laparotomy has been described. We aimed to develop a percutaneous transhepatic technique for catheterization of the fetal heart at mid-gestation that avoids maternal laparotomy. METHODS: In 10 fetal lambs (90-97 days' gestation), access to the fetal venous system was attempted by percutaneous puncture with a 5-F sheath into the umbilical vein (n = 1) or a 16-gauge IV-catheter into the hepatic vein (n = 9). This was followed by cardiac catheterization using a 1.8-2.6-F tapered coronary catheter. Euthanasia and postmortem examination were performed immediately postprocedure in two cases, or after normal term delivery in the remaining cases that survived the procedure. RESULTS: In one case fetal position precluded procedural attempts, and in another, the fetus, accessed by a 5-F sheath, died from umbilical hemorrhage. In eight cases, access to the fetal hepatic vein was achieved. In seven of these cases, the access catheter was advanced into the inferior vena cava, followed by catheterization of the right atrium (all cases) and four cardiac chambers (three cases). One fetus died during cardiac catheterization owing to right ventricle perforation, and the other seven fetuses were alive at the end of the procedure (87.5% survival). Immediate postmortem after euthanasia in two of the fetuses that survived the procedure detected intraperitoneal bleeding (4 mL and 20 mL), while postnatal postmortem examination following uneventful delivery at term in the remaining five fetuses revealed no vascular or cardiac trauma. CONCLUSIONS: Ultrasound-guided percutaneous transhepatic cardiac catheterization is feasible in mid-gestational fetal sheep. This technique has the potential for translation into human fetal cardiac and circulatory interventions.

Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study.

OBJECTIVE: Investigation of the feasibility and preliminary effect of a short-term intensive preoperative exercise programme for elderly patients scheduled for elective abdominal oncological surgery. DESIGN: Single-blind randomized controlled pilot study. SETTING: Ordinary hospital in the Netherlands. SUBJECTS: Forty-two elderly patients (>60 years). INTERVENTIONS: Patients were randomly assigned to receive a short-term intensive therapeutic exercise programme to improve muscle strength, aerobic capacity, and functional activities, given in the outpatient department (intervention group; n =22), or home-based exercise advice (control group; n=20). MAIN MEASURES: Parameters of feasibility, preoperative functional capacity and postoperative course. RESULTS: The intensive training programme was feasible, with a high compliance and no adverse events. Respiratory muscle endurance increased in the preoperative period from 259 +/- 273 to 404 +/- 349 J in the intervention group and differed significantly from that in the control group (350 +/- 299 to 305 +/- 323 J; P<0.01). Timed-Up-and-Go, chair rise time, LASA Physical Activity Questionnaire, Physical Work Capacity and Quality of Life (EORTC-C30) did not reveal significant differences between the two groups. There was no significant difference in postoperative complications and length of hospital stay between the two groups. CONCLUSION: The intensive therapeutic exercise programme was feasible and improved the respiratory function of patients due to undergo elective abdominal surgery compared with home-based exercise advice.

International comparative field study evaluating the assay performance of AFSTYLA in plasma samples at clinical hemostasis laboratories.

Essentials AFSTYLA exhibits ≈50% underestimation in activity when the one-stage (OS) assay is utilized. A field study compared the performance of AFSTYLA with Advate in factor VIII activity assays. AFSTYLA activity can be monitored with both the chromogenic substrate and the OS assay. The consistent OS underestimation allows for a conversion factor to be applied to OS results. SUMMARY: Introduction AFSTYLA (antihemophilic factor [recombinant] single chain) is a novel B-domain truncated recombinant factor VIII (rFVIII). For AFSTYLA, an approximate 50% discrepancy was observed between results of the one-stage (OS) and chromogenic substrate (ChS) FVIII activity assays. An investigation was undertaken to test whether there is a linear relationship between ChS and OS assay results that would allow reliable clinical interpretation of results independent of the assay method used. Aims To provide confidence in future clinical monitoring, this field study investigated the performance of AFSTYLA and a full-length rFVIII (Advate® ) in FVIII activity assays routinely performed in clinical laboratories. Methods The comparison of AFSTYLA and Advate was performed in an international, multicenter and blinded field study of simulated post-infusion samples. The study documented the extent of variability between methods and laboratories and characterized the relationship between the ChS and OS assays. Results Results from 23 laboratories demonstrate that intra and interlaboratory variability in OS assays were similar for both products. When comparing within the OS assay format, there was a similar and reagent-correlated variability in response to different activators for both AFSTYLA and Advate. The OS underestimation was highly predictable and consistent across the complete range of FVIII plasma concentrations. Conclusion Post-infusion plasma AFSTYLA levels can be monitored in patients by the OS and ChS assays. The consistent and predictable difference between the two assay formats provides clinicians with adequate guidance on how to interpret the results of the OS assay using a single conversion factor.

The influence of vessel wall elasticity and peripheral resistance on the carotid artery flow wave form: a CFD model compared to in vivo ultrasound measurements.

The Doppler flow wave form and its derived measures such as the pulsatility index provide clinically important tools for the investigation of arterial disease. The typical shape of Doppler flow wave forms is physiologically known to be largely determined by both peripheral resistance and elastic properties of the arterial wall. In the present study we systematically investigate the influence of both vessel wall elasticity and peripheral resistance on the flow wave form obtained from a CFD-simulation of blood flow in the carotid bifurcation. Numerical results are compared to in vivo ultrasound measurements. The in vivo measurement provides a realistic geometry, local elasticities and an input flow wave form for the numerical experiment. Numerical and experimental results are compared at three different sites in the carotid branches. Peripheral resistance has a profoundly decreasing effect on velocities in the external carotid artery. If elasticity is taken into account, the computed peak systolic velocities are considerably lower and a more realistic smoothing of the flow wave form is found. Together, the results indicate that only if both vessel wall elasticity and positive peripheral resistance are taken into account, experimentally obtained Doppler flow wave forms can be reproduced numerically.

The effect of low-density diets on broiler breeder development and nutrient digestibility during the rearing period.

Low-density diets might help to reduce hunger feeling in restricted-fed broiler breeders. Effects of low-density diets on nutrient digestibility and bird development were studied in Cobb 500 broiler breeder hens from 4 wk of age until the onset of the lay (wk 26). The experiment included 4 treatments. The control treatment was a normal density diet (ND; 2,600 kcal/kg). Treatments 2 and 3 had a 12 and 23% lower nutrient density than ND (LD12 and LD23, respectively) through inclusion of palm kernel meal, wheat bran, wheat gluten feed, and sunflower seed meal. Treatment 4 also had a 12% lower nutrient density than ND but included oats and sugar beet pulp (LD12(OP)). Total daily intake of energy, digestible lysine, calcium, retainable phosphorus, sodium, and linoleic acid was kept constant in the low-density dietary treatments. Animal performance and development of the intestinal tract and reproductive tract were determined in addition to digestibility and feed passage rate. The LD12(OP) provided a lower AME and nutrient digestibility than calculated and was related to lower live weights. Birds given LD23 and LD12(OP) showed a faster ovarian and oviduct development between wk 24 and 26 compared with ND. At 22 wk of age, LD23 and LD12(OP) diets resulted in higher empty jejunum and ileum weights. Low-density diets did not affect intestinal tract contents and decreased mean retention time of the contents. It was concluded that low-density diets can affect live weight and development of digestive and reproductive tracts.

Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. SUMMARY: Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for < 12 years) who had participated in a single-dose PK investigation with rVIII-SingleChain 50 IU kg-1 . PK sampling was performed for up to 96 h. Results A two-compartment population PK model with first-order elimination adequately described FVIII activity. Body weight and predose level of von Willebrand factor were significant covariates on clearance, and body weight was a significant covariate on the central distribution volume. Simulations using the model with various dosing scenarios estimated that > 85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL-1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg-1 ) and highest (50 IU kg-1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg-1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL-1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. SUMMARY: Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A.

Influence of a downstream narrowing on the flow profile in a tube.

The distance over which the upstream flow conditions in a tube are disturbed by a stenosis downstream, i.e. the outlet length, was investigated for Reynolds numbers in the range 210-2900. Two methods were used, the Navier-Stokes equations were solved with a computer and a physical model was constructed and maximal velocities were measured with an ultrasound Doppler system. The computer model showed that Re number does not influence the outlet length, varying the stenosis area from 25% to 90% has an effect. However, the outlet length remained small, below 70% of the diameter of the tube. The physical model confirmed for a 75% stenosis that the outlet length is small, this method set the limit at not more than 1.2 times the tube diameter.

Mortality and growth performance of broilers given drinking water supplemented with chicken-specific probiotics.

For application in broiler production, we developed a multispecies (MSPB) and a chicken-specific (CSPB) probiotic preparation in fluid form. The MSPB contained different probiotic species of human origin, whereas the CSPB consisted of 7 Lactobacillus species isolated from the digestive tract of chickens. In a field trial with broilers, MSPB treatment resulted in a slight increase (by 1.84%) in broiler productivity based on an index taking into account daily weight gain, feed efficiency, and mortality. The CSPB treatment reduced mortality in 2 subsequent field trials and raised productivity by 2.94 and 8.70%. In a controlled trial with broilers showing a high index of productivity, probiotic treatment further raised productivity by 3.72%. Based on the present 4 studies in combination with 9 studies published earlier, it is suggested that with higher productivity rates of the broilers the effect of probiotics becomes smaller.

Cerebral morbidity in preterm twins.

BACKGROUND: Whether twins are more prone to increased neonatal morbidity than singletons remains controversial. It was the aim of this study to define the special risks of preterm twins with an emphasis on cerebral morbidity. METHODS: A retrospective chart review was carried out of all consecutively born twins (n = 230) and the corresponding sets of singletons of a single level-III neonatal intensive care unit. The subjects had a gestational age between 24 and 37 weeks, and were born in 1990-98. RESULTS: Twin pregnancies were more often complicated by preterm contractions (odds ratio (OR) 4.03 (95% confidence interval (CI) 2.39, 6.78)) whereas gestosis was significantly less (OR 0.14 (95% CI 0.05, 0.41)). Grades III and IV intracranial bleeding occurred significantly more often in twins compared to singletons (OR 3.75 (95% CI 1.65, 8.97)), with infants of less than 32 weeks' gestational age being predominantly affected (OR 3.31 (95% CI 1.33, 8.29)). Infants of less than 32 weeks' gestational age developed respiratory distress syndrome more often than the corresponding singletons (OR 1.93 (95% CI 1.15, 3.25)). There were no differences in all observed items between the first- and second-born twins. CONCLUSION: Twins of less than 37 weeks' gestational age were significantly more often affected by high-grade intraventricular hemorrhage irrespective of birth order. Periventricular leukomalacia occurred twice as often as in singletons. There were no differences with respect to mortality and further morbidity except for respiratory distress syndrome in preterm twins of less than 32 weeks' gestational age.

The inhibitory effect of carboxymethylcellulose with high viscosity on lipid absorption in broiler chickens coincides with reduced bile salt concentration and raised microbial numbers in the small intestine.

Two diets, with or without a nonfermentable carboxymethylcellulose (CMC) with high viscosity, were fed to broiler chickens beginning at 2 wk of age to study whether the anti-nutritive effect of gelling fibers on lipid digestibility may be associated with reduced intestinal bile salt concentration. Moreover, the microflora were examined to study whether possible changes in bile salt concentration coincide with alterations in microbial numbers. Carboxymethylcellulose depressed apparent lipid digestibility (P = 0.021). Feed intake and weight gain were not significantly affected. Water intake was increased in birds fed the CMC diet (P = 0.039). Bile acid concentration in small intestinal digesta was decreased (P = 0.047) in birds fed the CMC diet, which may have been caused by the increased water content of digesta (P < 0.001). The concentration of bile acids per gram dry matter or per milligram chromium was not reduced in small intestinal contents. Broiler chickens fed the CMC diet excreted more bile acids in the excreta (P < 0.001). Total aerobic and anaerobic microbial counts in the intestinal digesta were significantly increased in the duodenum plus jejunum (P = 0.038) but not in the ileum. Significant increases were found in the numbers of Clostridia (P = 0.017), Lactobacillus (P = 0.009), Bacteroides (P = 0.022), and yeasts and molds (P = 0.012). The present study supports the hypothesis that a nonfermentable gelling fiber (CMC) decreases apparent lipid digestibility by reducing the concentration of bile acids in the chyme in broiler chickens. Moreover, the ingestion of gelling fibers may increase the bacterial activity in the small intestine, which may further contribute to malabsorption of lipids.

A survey of the incidence of Salmonella species and Enterobacteriaceae in poultry feeds and feed components.

Between July 1990 and April 1991 the rate of contamination with Salmonella species of poultry feeds and feed components used by the Dutch feed industry was surveyed. Ten per cent of 360, 10 g samples of poultry feeds were found to be contaminated. Mash feeds, mostly used for layer-breeders, were far more frequently (21 per cent) contaminated than pelleted feeds (1.4 per cent). The rate of contamination of 130 samples of fish meal was 31 per cent, of 83 samples of meat and bone meal 4 per cent, 58 samples of tapioca 2 per cent and of 15 samples of maize grits 27 per cent. Twenty-eight serotypes of salmonellae were isolated, but no Salmonella enteritidis was found, despite the occurrence of an epidemic in poultry caused by this serotype since 1987. The serotypes isolated most frequently were not the same as those encountered in poultry flocks. The Enterobacteriaceae isolated from the feedstuffs were predominantly thermotrophic. They were shown to be useful markers of the rate of contamination with salmonellae and of the efficiency of decontamination of the feedstuffs by pelletisation.

[Probiotics]. / Probiotica.

Probiotics, living cultures of micro-organisms, are currently of great interest as counterparts to antibiotics. The idea behind the use of probiotics is that the development and stability of intestinal microflora can be enhanced. The protection against infections is increased, resulting in fewer health problems and increased productivity. The mechanism of action of probiotics is not yet known, although there are several hypotheses. There is increasing evidence to suggest that probiotics act by stimulating the host's immune systems. The only accepted example of effective protection against infections provided by living micro-organism is the 'Nurmi concept', whereby one-day-old chicks acquire an enhanced protection against Salmonella infections when they are administered the complex intestinal flora of older chicks. The effects of probiotics on the growth, feed conversion or production of farm animals are, even in specific situations, not consistent enough to consider their use out of economic considerations. Probiotics are used to (re)establish the intestinal flora of patients or persons with lactose intolerance. The claims that probiotics have cholesterol-lowering and anti-tumour actions are based on animal experiments and require further investigations.

Safety and pharmacokinetics of a recombinant fusion protein linking coagulation factor VIIa with albumin in healthy volunteers.

BACKGROUND: Development of neutralizing antibodies remains the most problematic complication in treating congenital hemophilia. Control and prevention of bleeding events in such patients with recombinant factor VIIa (rFVIIa) is limited by the short half-life of the available product. Here, we report on the pharmacokinetics and safety of a novel, recombinant fusion protein linking coagulation FVIIa with albumin (rVIIa-FP) in a first-in-human study in healthy male subjects. METHODS: Forty healthy male subjects between 18 and 35 years of age were included and dosed in five consecutive cohorts. In each cohort, six subjects were randomized to a single dose of rVIIa-FP (140, 300, 500, 750, or 1000 µg kg(-1) ) and two to placebo. All subjects received anticoagulation with an oral vitamin K antagonist to reach an international normalized ratio between 2 and 3 prior to dosing with rVIIa-FP/placebo. Dosing with oral vitamin K antagonist was continued at a fixed dose for 6 days after injection of rFVIIa. RESULTS AND CONCLUSIONS: Tolerance of rVIIa-FP was good at all dose levels. No serious adverse events were observed. None of the subjects developed anti-drug antibodies. The maximum baseline-corrected mean (SD) FVIIa plasma activity increased in a dose-proportional manner. Across the dose range, the median half-life was consistent, ranging from 6.1 to 9.7 h. At the highest dose of 1000 µg kg(-1) , the median FVIIa activity-based half-life was 8.5 h. Clearance ranged from 7.62 to 12.74 mL h(-1) kg(-1) . Compared with the commercially available rFVIIa product, rVIIa-FP had a reduced clearance resulting in an approximately 3- to 4-fold increase in half-life.

Favorable response of pediatric stem cell recipients to human protein C concentrate substitution for veno-occlusive disease.

Plasminogen activator inhibitor 1 is known to be elevated in patients with hepatic VOD after intensive chemotherapy. To re-establish endogenous fibrinolysis and to inhibit thrombin formation, we used non-APC (zymogen) to normalize PAI-1 levels. As a consequence of thrombin formation inhibition and the consecutive inhibition of the coagulation cascade, this treatment is expected to reduce the elevated D-dimer level. Six pediatric stem cell recipients with moderate or severe VOD after busulfan or total body irradiation conditioning regimen are reported here who were therapy-refractory to defibrotide or rt-PA therapy. All patients had low levels of PC activity (16-39%). The administration of PC (60-240 IU/kg) led to a rapid and sustained rise in PC activity (target level >80%) with near normalization of prothrombin and partial thromboplastin time in all patients. Elevated PAI-1 levels declined. Five of the six patients showed a good clinical response with prompt resolution of clinical, sonographic, and laboratory signs of hepatic blood flow obstruction, while one patient with severe VOD, as well as concomitant liver GVHD and CMV disease, had a slow but detectable response to PC therapy. All patients survived.

[International interhospital transfer by scheduled airline]. / Internationaler Interhospitaltransfer mit dem Linienflugzeug.

BACKGROUND AND OBJECTIVE: International long-distance travel increasingly takes elderly and sometimes already ill persons to foreign countries. In case of illness it is usually best, for both medical and social reasons, that the person return home. This study was undertaken to assess possibilities and limits of bringing such patients home by scheduled airline. PATIENT AND METHODS: The transportation reports and case notes of 95 patients who had been repatriated to Germany in 1995 and 1996 for medical reasons were analysed retrospectively. The mean age was 56 (16-94) years. 50% of the patients had medical, 23% surgical, 19% neurological and 8% psychiatric illnesses. RESULTS: None of the patients died during transport. The NACA score (National Advisory Committee for Aeronautics, USA) for determining the degree of severity of an illness (point scale 1-7) in this group of patients was between 1 and 4, median of 3. Five patients with a score of 5 or higher were judged not to be fit for transport. Two were repatriated by ambulance plane, in three transport was postponed by a few days. No invasive procedures, other than providing intravenous access, were necessary. CONCLUSIONS: Patients who fall ill abroad can be safely and carefully brought home by scheduled airliner over great distances without additional risk caused by the transport. Ambulance planes are needed only in illnesses with an NACA score of 4 or higher.

Xylanase in broiler diets with differences in characteristics and content of wheat.

1. Experiments were conducted to measure the effect of xylanase supplementation on the performance of broilers fed on wheat-based diets containing high and low extract viscosity wheat (experiment 1), baking and feeding quality wheat (experiment 2) and with variation in wheat content (experiment 3). 2. Xylanase supplementation improved food conversion ratios by 2.2-2.9% and body weight gain by 0.2-2.5%. This was independent of wheat characteristics but slightly dependent on the wheat content of the diet. These effects were related to a lowering of digesta viscosity. 3. Differences in extract viscosity of wheat were not reflected in broiler digesta viscosity. 4. Reduction of digesta viscosity resulted in only a slight improvement of litter score. Reduced intestinal viscosity decreased relative pancreas weight and to a lesser extent relative small intestinal weight. 5. Baking quality wheat Baldus gave better performance than the feed quality wheats Apollo and Slejpner. 6. It was concluded that xylanase supplementation of wheat-based diets invariably had a positive effect on broiler performance.