Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice.

Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177Lu-octreotate and 177Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177Lu-octreotate or 177Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177Lu-octreotide compared to 177Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177Lu-octreotate, respectively. 177Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8, TNSFS10, and TRADD were regulated after administration with 177Lu-octreotate. Treatment with 177Lu-octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD, and of the anti-apoptotic gene IL10 as well as the apoptosis-related gene TNF. Conclusion: 177Lu-octreotide gave somewhat better anti-tumor effects than 177Lu-octreotate. The similar effect observed in the treated groups with 177Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.

MR Imaging Features of Middle Cranial Fossa Encephaloceles and Their Associations with Epilepsy.

BACKGROUND AND PURPOSE: Middle cranial fossa encephaloceles are an increasingly recognized cause of epilepsy; however, they are also often encountered on neuroimaging in patients with no history of seizure. We characterized the MR imaging features of middle cranial fossa encephaloceles in seizure and nonseizure groups with the hope of uncovering features predictive of epileptogenicity. MATERIALS AND METHODS: Seventy-seven patients with middle cranial fossa encephaloceles were prospectively identified during routine clinical practice of neuroradiology at a tertiary care hospital during an 18-month period. Thirty-five of 77 (45%) had a history of seizure, 20/77 (26%) had temporal lobe epilepsy, and 42/77 (55%) had no history of seizures. Middle cranial fossa encephalocele features on MR imaging were characterized, including depth, area, number, location, presence of adjacent encephalomalacia, and degree of associated parenchymal morphologic distortion. MR imaging features were compared between the seizure and nonseizure groups. RESULTS: No significant difference in MR imaging features of middle cranial fossa encephaloceles was seen when comparing the seizure and nonseizure groups. Comparison of just those patients with temporal lobe epilepsy (n = 20) with those with no history of seizure (n = 42) also found no significant difference in MR imaging features. CONCLUSIONS: Anatomic MR imaging features of middle cranial fossa encephaloceles such as size, number, adjacent encephalomalacia, and the degree of adjacent parenchymal morphologic distortion may not be useful in predicting likelihood of epileptogenicity.

Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma.

BACKGROUND AND PURPOSE: Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point. MATERIALS AND METHODS: Twenty-three patients with suspected post-chemoradiotherapy glioblastoma progression underwent ferumoxytol-enhanced SWI. Segregation and extravascular localization of ferumoxytol imaging maps were generated as the voxelwise difference of the delayed (24 hours) from the early (immediately after administration) time point SWI maps. Continuous segregation and extravascular localization of ferumoxytol imaging map values were separated into positive and negative components. Image-guided biologic correlation was performed. RESULTS: Negative segregation and extravascular localization of ferumoxytol imaging values correlated with early and delayed time point SWI values, demonstrating that intravascular signal detected in the early time point persists into the delayed time point. Positive segregation and extravascular localization of ferumoxytol imaging values correlated only with delayed time point SWI values, suggesting successful detection of the newly developed extravascular signal. CONCLUSIONS: Segregation and extravascular localization of ferumoxytol MR imaging improves on current techniques by eliminating intrinsic tissue and intravascular ferumoxytol signal and may inform glioblastoma outcomes by serving as a more specific metric of macrophage content compared with uncorrected T1 and SWI techniques.

The overall and sex- and age-group specific incidence rates of cancer in people with schizophrenia: a population-based cohort study.

AIMS: Decades of research show that people with schizophrenia have an increased risk of death from cancer; however, the relationship between schizophrenia and cancer incidence remains less clear. This population-based study investigates the incidence of seven common types of cancer among people with a hospital diagnosis of schizophrenia and accounting for the effects of age, sex and calendar time. METHODS: This population-based study used 1990-2013 data from three nationwide Swedish registries to calculate the incidence (in total, by age group and by sex) of any cancer and of lung, oesophageal, pancreatic, stomach, colon, (in men) prostate and (in women) breast cancer in 111 306 people with a hospital diagnosis of schizophrenia. The incidence in people with diagnosed schizophrenia was compared with the incidence in the general population. Risk estimates accounted for the effects of calendar time. RESULTS: In 1 424 829 person-years of follow-up, schizophrenia did not confer an overall higher cancer risk (IRR 1.02, 95% CI 0.91-1.13) but was associated with a higher risk for female breast (IRR 1.19, 95% CI 1.12-1.26), lung (IRR 1.42, 95% CI 1.28-1.58), oesophageal (IRR 1.25, 95% CI 1.07-1.46) and pancreatic (IRR 1.10, 95% CI 1.01-1.21) and a lower risk of prostate (IRR 0.66, 95% CI 0.55-0.79) cancer. Some age- and sex-specific differences in risk were observed. CONCLUSIONS: People with schizophrenia do not have a higher overall incidence of cancer than people in the general population. However, there are significant differences in the risk of specific cancer types overall and by sex calling for efforts to develop disease-specific prevention programmes. In people with schizophrenia, higher risk generally occurs in those <75 years.

Increased Notching of the Corpus Callosum in Fetal Alcohol Spectrum Disorder: A Callosal Misunderstanding?

BACKGROUND AND PURPOSE: In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population. MATERIALS AND METHODS: We performed a multicenter search for cases of fetal alcohol spectrum disorders and included all patients who had a sagittal T1-weighted brain MR imaging. Patients with concomitant intracranial pathology were excluded. The corpus callosum was examined for notches using previously published methods. A χ2 test was used to compare the fetal alcohol spectrum disorders and healthy groups. RESULTS: Thirty-three of 59 patients with fetal alcohol spectrum disorders (0-44 years of age) identified across all centers had corpus callosum notching. Of these, 8 had an anterior corpus callosum notch (prevalence, 13.6%), 23 had a posterior corpus callosum notch (prevalence, 39%), and 2 patients demonstrated undulated morphology (prevalence, 3.4%). In the healthy population, the anterior notch prevalence was 139/875 (15.8%), posterior notch prevalence was 378/875 (43.2%), and undulating prevalence was 37/875 (4.2%). There was no significant difference among the anterior (P = .635), posterior (P = .526), and undulating (P = .755) notch prevalence in the fetal alcohol spectrum disorders and healthy groups. CONCLUSIONS: There was no significant difference in notching of the corpus callosum between patients with fetal alcohol spectrum disorders and the healthy population. Although reported to be a marker of fetal alcohol spectrum disorders, notching of the corpus callosum should not be viewed as a specific finding associated with fetal alcohol spectrum disorders.

Anoxic Brain Injury Detection with the Normalized Diffusion to ASL Perfusion Ratio: Implications for Blood-Brain Barrier Injury and Permeability.

BACKGROUND AND PURPOSE: Anoxic brain injury is a result of prolonged hypoxia. We sought to describe the nonquantitative arterial spin-labeling perfusion imaging patterns of anoxic brain injury, characterize the relationship of arterial spin-labeling and DWI, and evaluate the normalized diffusion-to-perfusion ratio to differentiate patients with anoxic brain injury from healthy controls. MATERIALS AND METHODS: We identified all patients diagnosed with anoxic brain injuries from 2002 to 2019. Twelve ROIs were drawn on arterial spin-labeling with coordinate-matched ROIs identified on DWI. Linear regression analysis was performed to examine the relationship between arterial spin-labeling perfusion and diffusion signal. Normalized diffusion-to-perfusion maps were generated using a custom-built algorithm. RESULTS: Thirty-five patients with anoxic brain injuries and 34 healthy controls were identified. Linear regression analysis demonstrated a significant positive correlation between arterial spin-labeling and DWI signal. By means of a combinatory cutoff of slope of >0 and R2 of > 0.78, linear regression using arterial spin-labeling and DWI showed a sensitivity of 0.86 (95% CI, 0.71-0.94) and specificity of 0.82 (95% CI, 0.66-0.92) for anoxic brain injuries. A normalized diffusion-to-perfusion color map demonstrated heterogeneous ratios throughout the brain in healthy controls and homogeneous ratios in patients with anoxic brain injuries. CONCLUSIONS: In anoxic brain injuries, a homogeneously positive correlation between qualitative perfusion and DWI signal was identified so that areas of increased diffusion signal showed increased ASL signal. By exploiting this relationship, the normalized diffusion-to-perfusion ratio color map may be a valuable imaging biomarker for diagnosing anoxic brain injury and potentially assessing BBB integrity.

Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy.

BACKGROUND: The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8 weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT. METHODS: Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5 × 5 Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7 weeks (group C) and 8-13 weeks (group D). Patients receiving long-course RT (25 × 2 Gy) were grouped into those with an OTT of 9-11 weeks (group E) or 12-14 weeks (group F). Outcomes assessed were postoperative complications and early mortality. RESULTS: A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0·72 (95 per cent c.i. 0·40 to 1·32; P = 0·289), 0·50 (0·30 to 0·84; P = 0·009) and 0·39 (0·23 to 0·65; P < 0·001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups. CONCLUSION: These results suggest that surgery should optimally be delayed for 4-12 weeks (OTT 5-13 weeks) after SRT.

Defining the Normal Dorsal Contour of the Corpus Callosum with Time.

BACKGROUND AND PURPOSE: Morphological changes of the corpus callosum have been associated with a large number of congenital neurocognitive and psychiatric disorders. Focal defects or notches of the dorsal surface of the corpus callosum have not been well characterized. Our purpose was the following; 1) to characterize the dorsal contour of the corpus callosum during the life span, 2) to characterize the relationship of contour deviations to neighboring vessels, and 3) to determine whether contour deviations are congenital or acquired. MATERIALS AND METHODS: We retrospectively reviewed normal sagittal T1-weighted brain MR images. A "notch" was defined as a concavity in the dorsal surface at least 1 mm in depth. The corpus callosum was considered to be "undulating" if there were >2 notches, including an anterior and posterior notch. The presence of a pericallosal artery and its relationship to a notch were assessed. RESULTS: We reviewed 1639 MR imaging studies, spanning 0-89 years of age. A total of 1102 notches were identified in 823 studies; 344 (31%) were anterior, 660 (60%) were posterior, and 98 (9%), undulating. There was a positive correlation between the prevalence (P < .001) and depth (P = .028) of an anterior notch and age and a negative correlation between the prevalence of a posterior notch and age (P < .001). There was no difference between patient sex and corpus callosum notching (P = .884). Of the 823 studies with notches, 490 (60%) were associated with a pericallosal artery (P < .001). CONCLUSIONS: The prevalence and depth of notches in the anterior corpus callosum increase significantly with age; this finding suggests that most notches are acquired. There is a significant positive association between the presence of a corpus callosum notch and adjacent pericallosal arteries, suggesting that this may play a role in notch formation.

High prevalence of diabetes mellitus, hypertension and obesity among persons with a recorded diagnosis of intellectual disability or autism spectrum disorder.

BACKGROUND: Obesity and lack of physical activity are frequently reported in persons with intellectual disability (ID) or autism spectrum disorder (ASD). We hypothesised a higher prevalence of diabetes and hypertension in this population. METHOD: We used administrative data for all primary and specialist outpatient and inpatient healthcare consultations for people with at least one recorded diagnosis of diabetes mellitus, hypertension or obesity from 1998 to 2015. Data were drawn from the central administrative database for Stockholm County, Sweden. It was not possible to separate data for type 1 and type 2 diabetes. We stratified 26 988 individuals with IDs or ASD into three groups, with Down syndrome treated separately, and compared these groups with 1 996 140 people from the general population. RESULTS: Compared with the general population, men and women with ID/ASD had 1.6-3.4-fold higher age-adjusted odds of having a registered diagnosis of obesity or diabetes mellitus, with the exception of diabetes among men with Down syndrome. A registered diagnosis of hypertension was only more common among men with ID/ASD than in the general population. CONCLUSIONS: Diabetes and blood pressure health screening, along with efforts to prevent development of obesity already in childhood, are necessary for individuals with IDs and ASD. We believe that there is a need for adapted community-based health promotion programmes to ensure more equitable health for these populations.

Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer.

BACKGROUND: The Stockholm III Trial randomized patients with primary operable rectal cancers to either short-course radiotherapy (RT) with immediate surgery (SRT), short-course RT with surgery delayed 4-8 weeks (SRT-delay) or long-course RT with surgery delayed 4-8 weeks. This preplanned interim analysis examined the pathological outcome of delaying surgery. METHODS: Patients randomized to the SRT and SRT-delay arms in the Stockholm III Trial between October 1998 and November 2010 were included, and data were collected in a prospective register. Additional data regarding tumour regression grade, according to Dworak, and circumferential margin were obtained by reassessment of histopathological slides. RESULTS: A total of 462 of 545 randomized patients had specimens available for reassessment. Patients randomized to SRT-delay had earlier ypT categories, and a higher rate of pathological complete responses (11·8 versus 1·7 per cent; P = 0·001) and Dworak grade 4 tumour regression (10·1 versus 1·7 per cent; P < 0·001) than patients randomized to SRT without delay. Positive circumferential resection margins were uncommon (6·3 per cent) and rates did not differ between the two treatment arms. CONCLUSION: Short-course RT induces tumour downstaging if surgery is performed after an interval of 4-8 weeks.

Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial.

BACKGROUND: Radiotherapy (RT) in rectal cancer increases postoperative morbidity. A suggested reason is RT-induced bone marrow depression resulting in impaired leucocyte counts. The ongoing Stockholm III Trial randomizes patients with operable rectal cancers to short-course RT with immediate surgery (SRT), short-course RT with surgery delayed for 4-8 weeks (SRT-delay) and long-course RT with surgery delayed for 4-8 weeks (LRT-delay). This study examined differences between the randomization arms regarding leucocyte response and postoperative complications. METHODS: Patients randomized in the Stockholm III Trial between October 1998 and November 2010 were included. Data were collected in a prospective register. Additional data were obtained by retrospective review of clinical records. RESULTS: Of 657 randomized patients, 585 had data on leucocytes. The SRT arm had the highest proportion of postoperative complications (SRT, 52·5 per cent; SRT-delay, 39·4 per cent; LRT-delay, 41 per cent; P = 0·010). There was no association between low preoperative leucocyte count and postoperative complications (P = 0·238). Irrespective of randomization arm, patients with an impaired postoperative to preoperative leucocyte ratio had the highest rate of complications (low ratio, 56·6 per cent; intermediate ratio, 46·9 per cent; high ratio, 36·3 per cent; P = 0·010). The SRT arm had the highest proportion of low ratios (SRT, 48·9 per cent; SRT-delay, 22·8 per cent; LRT-delay, 22 per cent; P < 0·001). CONCLUSION: An impaired postoperative leucocyte response is associated with postoperative complications. The highest risk is with immediate surgery following short-course radiotherapy. REGISTRATION NUMBER: NCT 00904813 (http://www.clinicaltrials.gov).

Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer.

BACKGROUND: Short-course radiotherapy (SRT) with immediate surgery and long-course chemoradiotherapy (CRT) are currently the standard preoperative treatment options for rectal cancer. SRT with surgery delayed for 4-8 weeks (SRT-delay) is an option described for patients with locally advanced tumours who are not fit for CRT. This study examined early toxicity, response to radiotherapy (RT) and short-term outcomes of SRT-delay. METHODS: Patients in the Stockholm region diagnosed with rectal cancer between January 2002 and December 2008, who received SRT (25 Gy over 5-7 days) and had surgery with resection of the primary tumour more than 4 weeks after the start of RT, were identified from a prospective register. Additional data were obtained by retrospective review of clinical records. RESULTS: A total of 112 patients had SRT and delayed surgery. The reasons given for SRT included primary unresectable disease and co-morbidities. Severe RT-induced toxicity was noted in six patients (5·4 per cent). Signs of tumour regression were seen on magnetic resonance imaging in 74 per cent of patients reassessed after RT. Pathological stage (44·9 versus 60·7 per cent stage 0-II; P < 0·001), tumour category (11·9 versus 29·4 per cent T0-T2; P < 0·001) and node category (45·8 versus 63·6 per cent N0; P = 0·014) were significantly lower than those at initial assessment. Nine patients (8·0 per cent) had a complete pathological response. CONCLUSION: The SRT-delay schedule was a feasible alternative with low toxicity. The study indicated a downstaging effect of SRT if surgery was delayed.

The degradation of arabinoxylan-rich cell walls in digesta obtained from piglets fed wheat-based diets varies depending on digesta collection site, type of cereal, and source of exogenous xylanase.

The objective of the present study was to compare the ability of experimental and commercial xylanases to degrade, in vitro, the arabinoxylan (AX) fraction in digesta from 28-d-old piglets fed a wheat (Triticum aestivum)-based diet (49% wheat). Pigs were euthanized at 1, 2, 3, or 4 h after feeding; stomach and ileum contents were isolated and frozen and later used for the in vitro studies. Xylan solubilization provided information regarding the ability of the enzymes to degrade AX during the harsh in vivo conditions prevailing in the gastrointestinal tract. The hydrolytic capacity of a commercial xylanase was compared with that of an experimental xylanase using stomach digesta (pH 1.8) obtained at 4 h after feeding. Relative to the control, both enzymes increased (P < 0.001) xylan solubilization 3-fold. In the ileal digesta (1 h), xylan solubilization was increased by 36% (P < 0.001). Inclusion of arabinofuranosidases (Ara f) with xylanases increased xylan solubilization in stomach samples (P = 0. 007 and P = 0. 030) but not in ileal samples (P = 0.873 and P = 0.997). Our results illustrate clearly the importance of using different conditions and substrates when enzyme performance is studied in vitro as a prescreening tool for setting up in vivo trials.

Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer.

BACKGROUND: To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. METHODS: Some 303 patients were randomized to either short-course RT (5 x 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). RESULTS: Demographic data were similar between groups and there were few protocol violations (5.0-6 per cent). Eight patients (2.6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). CONCLUSION: Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. REGISTRATION NUMBER: NCT00904813 (http://www.clinicaltrials.gov).

A comparison of three xylanases on the nutritive value of two wheats for broiler chickens.

Three xylanase products, xylanase A derived from Thermomyces lanuginosus, xylanase B from Humicola insolens and xylanase C from Aspergillus aculeatus, were examined for their effects on the nutritive value of wheat. The study investigated the effects of enzyme addition to broiler diets based on a low-metabolisable-energy (ME) wheat and a normal-ME wheat, with the emphasis on changes in composition of the NSP along the digestive tract in broiler chickens. There were significant (P<0.01) enzyme and wheat effects on the apparent ME, but there was no wheat x enzyme interaction on apparent ME. Weight gain and feed conversion efficiency (except xylanase C for normal wheat) were also significantly (P<0.01) increased by the xylanases. The enzymes differed in their effect on a number of important nutritional parameters. Xylanase A reduced (P<0.05) the excreta moisture level from 77.1 % in birds fed the normal-ME wheat control to 73.4 % and from 77.4 % in those fed the low-ME wheat to 73.0 %. The other two enzymes did not affect excreta moisture levels. The digesta viscosity in the duodenum, jejunum and ileum of birds fed both types of wheat was reduced (P<0.01) by xylanases A and C, but was increased (P<0.01) in the jejunum and ileum by xylanase B. The digestibility of the soluble NSP was mostly negative in the small intestine. The digestibility of the insoluble NSP differed (P<0.01) between the two wheats, with those in the low-ME wheat being more digestible (14 v. 28 %). When supplemented with xylanase A, the ileal digestibility of the insoluble NSP in the normal- and low-ME wheats was increased by 28 and 42 %, respectively. Xylanases B and C did not affect the digestibility of the insoluble NSP regardless of wheat type. It may be concluded that wheats with low or normal ME values vary in their responses to xylanase supplementation. Apart from having an elevated level of soluble NSP, low-ME wheat may also contain insoluble NSP, which in the present study appeared to be more easily degradable in the gut of the chicken.

Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin.

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30 g/kg of 89% deacetylated chitin (chitosan) or low-methoxyl (34% degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containing diets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin diet in vitro together with the absence of a hypocholesterolaemic effect of this diet when fed in vivo precludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.

Hypolipidaemic, gastrointestinal and related responses of broiler chickens to chitosans of different viscosity.

Broiler chickens (1-d-old) were fed ad libitum on a control diet based on maize and maize starch or diets containing low-, medium- or high-viscosity chitosans at an inclusion level of 15 g/kg. Body weights and feed intakes of chickens given chitosan-containing diets were generally depressed in comparison with those of control-fed animals on days 11 and 18 of the experiment. On days 12 and 19, feeding the low-viscosity-chitosan diet reduced plasma triacylglycerol and total plasma cholesterol concentrations in relation to chickens receiving the control diet, while the medium- and high-viscosity-chitosan-containing diets reduced total plasma cholesterol and elevated, although not significantly, plasma HDL-cholesterol concentrations compared with those of control-fed animals. Chitosan feeding generally improved plasma HDL-cholesterol:total cholesterol ratio in comparison with control feeding, which was attributed to the general reductions in plasma cholesterol concentrations rather than increases in plasma HDL-cholesterol concentrations. Feeding the high-viscosity-chitosan-containing diet significantly reduced the ileal digestibility of crude protein (N x 6.25) and crude fat compared with chickens given the control diet. The reduction in ileal crude fat digestibility was greatest among chickens receiving the high-viscosity-chitosan-containing diet and chitosan-containing diets reduced ileal fat digestibility by 8% on average compared with that of control-fed birds. However, increasing the viscosity of the chitosan fraction could not be correlated with increases in terminal ileal digesta viscosity and, therefore, it could not be established that increased ileal lumen viscosity alone contributed to reductions in body weight, feed intake and plasma cholesterol concentrations. However, the fact that ileal digestibility of fat was reduced by feeding chitosan to chickens suggests the action of other hypolipidaemic mechanisms.

Intake of rye bread ileostomists increases ileal excretion of fiber polysaccharide components and organic acids but does not increase plasma or urine lignans and isoflavonoids.

The excretion of starch, enzyme-resistant starch, dietary fiber components and organic acids (short-chain fatty acids plus lactic acid) as well as plasma and urine lignans and isoflavonoids was studied in eight ileostomists consuming mixed diets with wheat bread (low fiber diet) or rye bread (high fiber diet) in a crossover design. Average ileal excretions of enzyme-available starch were 3.5 g/d during the low fiber period and 4.1 g/d during the high fiber period. The excretion of enzyme-resistant starch was approximately the same (2.3 g/d) in both periods. In comparison with intake, similar amounts of total fiber residues were excreted both by subjects receiving the low fiber diet (3.4 g/d) and by those receiving the high fiber diet (2.7 g/d). However, subjects excreted significantly more of certain polysaccharide residues (fucose, galactose, and uronic acids) than they ingested. On average, the excretion of organic acids was 18.6 mmol/d during the low fiber period and 30.2 mmol/d during the high fiber period. No significant differences in plasma lignans were observed between the high fiber and the low fiber dietary periods. The present findings indicate that enzyme-available starch is highly digested and that a microbial breakdown of dietary fibers and probably other carbohydrates occurs in the small intestine. However, the bacterial activity in the ileostomists was not sufficient to cause an increased level in plasma lignans even when subjects consumed the high fiber rye diet.

Starch and dietary fiber components are excreted and degraded to variable extents in ileostomy subjects consuming mixed diets with wheat- or oat-bran bread.

The study was conducted to determine if the excretion of starch and dietary fiber components varies in ileostomy subjects consuming diets high or low in dietary fiber. Excretion of starch, enzyme-resistant starch and dietary fiber components was studied in nine human subjects with ileostomies, who consumed (in a crossover design) a wheat bread-based diet (daily intake 274 g starch, 2.4 g enzyme-resistant starch and 14.4 g total dietary fiber) and a high fiber diet based on oat-bran bread (daily intake 243 g starch, 2.7 g enzyme-resistant starch and 40.2 g total dietary fiber). Food and excreta were collected on d 3 and 17. No significant differences in excretion of starch, enzyme-resistant starch or dietary fiber components were found on these 2 d in each dietary period. When subjects consumed the wheat bread-based diet they excreted (mean +/- SD) 3.3 +/- 1.7 g starch and 2.4 +/- 0.4 g enzyme-resistant starch daily, whereas when consuming the oat bran-based diet they excreted 4.5 +/- 3.1 g starch and 2.5 +/- 0.4 g enzyme-resistant starch. During both dietary periods subjects excreted significantly greater amounts of certain dietary fiber polysaccharide residues (fucose, galactose and uronic acid) than they ingested. This indicates a contribution of endogenous and/or microbial material to the dietary fiber value in ileostomy effluents. However, significantly less excretion of some dietary fiber polysaccharide residues, especially glucose residues, during the oat-bran bread-based dietary period was also noted. This was presumably caused by a degradation of mixed-linked (1,3),(1,4)-beta-D-glucans.

Total dietary fiber determined as neutral sugar residues, uronic acid residues, and Klason lignin (the Uppsala method): collaborative study.

A joint AOAC/American Association of Cereal Chemists (AACC) collaborative study was conducted to determine by the Uppsala method the dietary fiber content and its composition in various foods. The method includes preparation of a residue by treatment with thermostable alpha-amylase and amyloglucosidase and then ethanol precipitation of solubilized dietary fiber components while leaving low-molecular weight carbohydrates in solution. After acid hydrolysis of residue, neutral polysaccharide residues are determined as alditol acetates by gas-liquid chromatography, uronic acid residues are determined by colorimetry, and ash-free acid-insoluble residue (Klason lignin) is determined gravimetrically. Total dietary fiber, including enzyme-resistant starch, is calculated as the sum of nonstarch polysaccharide residues and Klason lignin. Nine laboratories completed the study, analyzing in duplicate 8 unknown dried products that included 4 cereal products, green peas, potato fiber, carrots, and apples. Total dietary fiber contents of products tested ranged from 4.6 to 84.3%, with an average RSDR value of 8.4% (range, 4.8-11.1%). Total neutral polysaccharide residues ranged from 3.8 to 64.1%, with an average RSDR value of 7.5% (range, 5.4-10.5%). Individual neutral sugars (rhamnose, arabinose, xylose, mannose, galactose, and glucose) and uronic acid residues present at more than 1% generally had good RSDR values (3.3-22.8%), whereas, as expected for Klason lignin, only the wheat bran sample with a high content (16%) had an excellent RSDR value (5.0%). The gas chromatographic-colorimetric-gravimetric method (Uppsala method) for determination of total dietary fiber (as neutral sugar residues, uronic acid residues, and Klason lignin) has been adopted first action by AOAC INTERNATIONAL.