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Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers.

In a randomized, double-blind, placebo-controlled study in 12 healthy volunteers pharmacokinetics, safety and impact on the faecal microflora of cefepime were determined. For eight days eight volunteers received cefepime 1000 mg bd by constant infusion over 30 min, four volunteers received placebo. Concentrations of cefepime in serum and urine were measured by bioassay and HPLC. The correlation between the two methods was good and the bioassay results were used for pharmacokinetic calculations. The faecal flora was analysed twice before the study, twice during the study and four times after cefepime administration. There were no significant differences in the pharmacokinetic parameters between days 1 and 8. The following values (mean +/- S.D.) represent day 1. The maximum concentration of 72.69 +/- 12.2 mg/L immediately after infusion decreased to 0.56 +/- 0.17 mg/L after 12 h. The mean 12 h recovery in urine was 93.69 +/- 2.14%. Pharmacokinetic parameters based on an open two-compartment model were as follows (mean +/- S.D.): area under the curve, 142.65 +/- 18.35 mg.h/L; elimination half-life 110.3 +/- 8.3 min; steady state volume of distribution 16.0 +/- 1.9 L/70 kg; total clearance, 107.0 +/- 16.0 mL/min; renal clearance 103.0 +/- 15.2 mL/min. No accumulation was observed during the eight day study period with cefepime at this dosage; trough levels on days 2-7 ranged from 0.52 +/- 0.26 mg/L to 0.90 +/- 0.33 mg/L. In the cefepime treated group the following side-effects were noted: headache (5), fatigue (4), nausea/stomach ache (2), soft stool (2), transient scotoma (1). Side-effects in the placebo group were: headache (2) fatigue (3), nausea/stomach-ache (1), soft stool (2) and photophobia (1). During cefepime administration a decrease in the number of Escherichia coli and bifidobacteria in faeces was observed, whereas Bacteroides spp. and clostridia showed a slight increase. The numbers of faecal bacteria returned to normal 20 to 48 days after the study was completed.

Bacteroides↗

The impact of natural helminth infections and supplementary protein on growth performance of free-range chickens on smallholder farms in El Sauce, Nicaragua.

Three on-farm studies were conducted in Nicaragua during three consecutive years (1999-2001) to assess the impact of natural helminth infections on growth performance of free-range chickens aged 3-4 months. On all participating farms, half of the chickens were treated regularly with anthelmintics (Trifen avicola - a combined formulation of piperazine, phenothiazine and dichlorophen - or albendazole) to express the growth potential of non-infected birds, whereas the other half served as non-treated controls. In 1999, treated chickens had a 39% higher weight gain compared to the control group 6 weeks after the first treatment on 15 farms. In 2000 and 2001, treated chickens had similar weight gain as the control group 10 weeks after the first treatment on 7 farms and 12 farms, respectively. The main reason for the very-different weight gain figures seems to be the weather conditions. In 1999, the study site experienced a rainy season with precipitation far above average, whereas in 2000 and 2001 the rainy seasons had precipitations far below average. Based on these findings, routine use of anthelmintics in the study area would only be recommended in wet years when production losses due to helminth infections seem to be pronounced. In 2001, the study set-up included an assessment of the effect of protein supplementation (soybean) on growth on six farms. Supplemented chickens (treated and non-treated with anthelmintics) had 17% higher weight gain than non-supplemented. Protein supplementation affected neither worm burdens nor faecal egg counts for any of the studied helminths. The post-mortem examinations showed that Trifen reduced burdens of Ascaridia galli, Heterakis gallinarum, and cestodes (efficacies of 100, 100 and 67%, respectively). Albendazole reduced burdens of H. gallinarum (efficacy of 100%). Efficacies against other helminths were difficult to assess due to low worm burdens. Chickens treated with albendazole had lower Ascaridia and Heterakis faecal egg counts than non-treated chickens.

Animals↗

Modeling plasma lipoprotein-bile lipid relationships: differential impact of psyllium and cholestyramine in hamsters fed a lithogenic diet.

Hamsters fed a lithogenic diet become hyperlipemic with elevated very-low-density lipoprotein (VLDL) and high-density lipoprotein 2 (HDL2) cholesterol pools and develop lithogenic bile in which chenodeoxycholate (cheno) typically predominates. The relationship between these distorted lipoprotein and bile lipid profiles and gallstone induction was investigated in male Syrian hamsters fed for 5 weeks a gallstone-inducing purified diet (5% butter, 0.4% cholesterol) or the same diet supplemented with 5% psyllium or 1% cholestyramine, agents known to alter bile acid metabolism. The gallstone diet essentially doubled plasma cholesterol level, whereas psyllium decreased it to near normal, and cholestyramine to a subnormal level, while correcting the distorted distribution of cholesterol among lipoproteins. Both the gallstone diet and psyllium produced cholesterol-laden livers, in contrast to subnormal values produced by cholestyramine. Fecal bile acid excretion was increased eightfold with cholestyramine and fourfold with psyllium relative to the value produced by the gallstone diet and a literature control value. Supersaturated bile developed with the gallstone diet (lithogenic index [LI], 2.3 +/- 0.6), whereas the LI was decreased by psyllium (1.2 +/- 0.4) and cholestyramine (0.7 +/- 0.3). The gallstone diet decreased the concentration of bile acids in gallbladder bile, but greatly increased the percentage of taurochenodeoxycholic acid, whereas psyllium preferentially decreased all taurine-conjugated bile acid levels and expanded glycocholate output. Cholestyramine greatly decreased the secretion of biliary cholesterol and cheno independent of its conjugation. Accordingly, psyllium increased the glycine to taurine ratio of gallbladder bile fivefold, whereas cholestyramine did not affect this ratio, but increased the cholate to cheno ratio dramatically (25-fold) as compared with a threefold increase with psyllium. This combination of biliary lipid and bile acid alterations induced coordinated responses in the LI and the hydrophobicity index (HI) such that cholesterol gallstones developed in 11 of 12 hamsters fed the gallstone diet, whereas only one of 11 of the psyllium-fed and none of 12 cholestyramine-fed hamsters had cholesterol stones. Thus, psyllium and cholestyramine differentially increased bile acid excretion, which improved the lipoprotein profile and inhibited cholesterol gallstone formation. Both agents operated by different means to decrease biliary cholesterol secretion and the percentage of cheno, which decreased the LI and HI, respectively.

Analysis of Variance↗

Selecting soybean meal characteristics preferred for swine nutrition.

As environmental constraints become more important issues for the animal industry, selecting feed ingredients that yield good animal performance but also minimize environmental impact of animal production becomes critical. The objective of this research was to identify which compositional features would be desirable for soybean meal to maximize nutritional value and minimize animal waste. Eight soybean samples were selected from a database of 72, such that maximal variability for CP, NDF, and ADF content was obtained. Samples were subsequently processed into meal using standardized procedures. In Experiment 1, 8 cannulated pigs were used to determine ileal digestibility following a Latin square design. In Experiment 2, 5 of the samples were used in complete feeds and 10 pigs were used in a crossover Latin square design to determine the total tract digestibility, odorants in fresh and 5-d-old manure, and ammonia emission from manure. Differences up to 6% in ileal DM digestibility and 8% in ileal CP digestibility were observed. This difference was reduced to 1.1% for total tract DM digestibility and 4% for total tract CP digestibility. Differences in odorant concentration were 3-fold and for in vitro ammonia emission were 42%. The only compositional variable with a significant effect on digestibility was stachyose, which negatively affected ileal digestibility of DM (r = -0.80, P = 0.02) and energy (r = -0.73, P = 0.04). None of the compositional variables measured affected ileal CP digestibility. Ileal CP digestibility, however, was correlated with estimated CP fermentation in the large intestine (r = -0.86, P = 0.06) and with in vitro ammonia emission after 48 h (r = -0.81, P = 0.09). In conclusion, nutritionally relevant variability exists in soy varieties. Low stachyose content is important for maximizing ileal energy digestibility of soybean meal. Although no compositional variable was identified that explained differences in ileal CP digestibility, maximizing ileal CP digestibility is of interest for maximizing the nutritional value of soybean meal and possibly for reducing ammonia and odor emissions.

Ammonia↗

Flaking corn: processing mechanics, quality standards, and impacts on energy availability and performance of feedlot cattle.

Based on performance of feedlot cattle, steam flaking increases the value of corn by 18%, considerably more than is suggested by tabular values. Tabular values underestimate the energy availability of flaked corn by failing to account for digestibility of the nonstarch OM that is increased by flaking by the same magnitude (10%) as starch. Correcting for improvement in digestibility of nonstarch OM increases the NEg value of steam-flaked corn to 1.70 Mcal/kg, a value very close to values calculated from cattle performance trials. Digestibility of starch from corn grain is limited by the protein matrix that encapsulates starch granules, and by the compact nature of the starch itself. Disruption of the protein matrix (by shear forces on hot grain during flaking) is the first limiting step toward optimizing starch digestion. Five critical production factors influence the quality of steam-flaked corn: steam chest temperature, steaming time, roll corrugation, roll gap, and roll tension. For optimal shear, it is important that rolls be hot and that kernels be hot when flaked. Steam chests should be designed to allow a steaming time of at least 30 min at maximum roller mill capacity producing a flake of 0.31 kg/L (24 lb/bushel). As little as 5% moisture uptake during steaming appears adequate. The rate of flaking and distribution of kernels across the rolls also are critical. Quality standards for steam-flaked corn include measurements of flake thickness, flake density, starch solubility, and enzyme reactivity. Flake density, the most common quality standard, closely associated with starch solubility (r2 = 0.87) and enzyme reactivity (r2 = 0.79), still explains only 63% of the variability in percentage fecal starch and 52% of the variability in starch digestibility. Direct determination of fecal starch can explain 91% of the variability in starch digestion. The NEg value of corn can be predicted from fecal starch: NEg= 1.78 - 0.0184FS. Starch digestion is a Kappa Curve function of hot flake density, reaching a maximum at a flake density of approximately 0.31 kg/L. Flaking to a density of less than 0.31 kg/L, though increasing starch solubility, may reduce DMI, increase variability of weight gain among animals within a pen, and predispose cattle to acidosis and bloat without increasing starch digestion. We recommend that the steam-flaking process be optimized on the basis of fecal starch analysis.

Animal Feed↗

Safety evaluation of phytosterol esters. Part 4. Faecal concentrations of bile acids and neutral sterols in healthy normolipidaemic volunteers consuming a controlled diet either with or without a phytosterol ester-enriched margarine.

A study was conducted in 12 healthy males and 12 females (mean age 36 years) to assess the impact of a margarine enriched with phytosterol esters on faecal concentrations of bile acids and sterols. During the run-in period, volunteers consumed 40 g of a control margarine for 21 consecutive days if male, and for 28 days if female. Half of the volunteers were then randomly allocated to consume the control margarine for another 21 or 28 days, respectively. The remaining subjects consumed 40 g of a margarine containing 8.6 g vegetable oil phytosterol (46% (w/w) beta-sitosterol, 26% campesterol, 20% stigmasterol). Throughout the total study subjects consumed the same diet adjusted for individual energy requirements. The phytosterol ester-enriched spread significantly enhanced faecal neutral sterol concentrations from about 40 mg/g to 190 mg/g dry weight faeces. Faecal neutral sterol metabolites increased from about 30 mg/g to about 50 mg/g. The major parent sterols excreted were cholesterol, sitosterol, campesterol and stigmasterol. Sitosterol, campesterol and stigmasterol comprised 28%, 15% and 12% of the total faecal neutral sterols, reflecting the composition of the sterol enriched margarine. The major sterol metabolites excreted were metabolites formed by, predominantly, oxidation at the 3-position and metabolites saturated at the 5,6 position in a beta-configuration. Faecal secondary bile acid concentration was reduced by vegetable oil sterols from 7.6 mg/g dry faeces to 6.0 mg/g. Consumption of vegetable oil phytosterols slightly but significantly increased the faecal concentration of 4-cholesten-3-one. However, 4-cholesten-3-one concentration remained very low (< 2 mg/g) and in line with values reported in the literature for subjects fed high or low fat diets. No sterol oxides could be detected in the faeces. We conclude that in healthy adult males and females a high intake of vegetable oil phytosterol esters does increase the amount of neutral sterols in the faeces, as expected, but does not result in the increased formation of bile acids or sterol metabolites.

Adult↗

Sub-clinical parasitism in spring-born, beef suckler calves: epidemiology and impact on growth performance during the first grazing season.

Sub-clinical parasitism in spring-born single suckled beef calves was investigated from the middle of their first grazing season until weaning or housing later the same year. The study was conducted on four beef suckler herds in southern England over a 3-year period and involved a total of 334 spring-born beef suckler calves and their dams. The animals were grazed extensively on pastures naturally infected with nematode larvae. At the start of each period of observation, faecal samples were taken from calves and cows and subjected to routine worm egg counts; calves were re-sampled at the end of the grazing season. In July in each year and at each location the calves were ranked by initial weight within sex, paired according to rank and randomly allocated to either an untreated control group or a group in which the calves were each treated with an ivermectin sustained-release (SR) bolus. The calves in both trial groups, and their dams, were grazed together until weaning or housing. The calves were weighed at the initial allocation and at the end of the study. The adult cows were not treated with any anthelmintic during the study. The faecal nematode egg counts (FECs) conducted in July showed that the suckler cows were excreting worm eggs at low concentrations: range 0-100 eggs per gram (epg), with one individual count of 500epg, 88% of the cows sampled had counts of <50epg. Similarly, the counts from the calf samples were fairly low in July: range 0-250epg, 73% of the calves sampled had counts of <50epg. By the end of the grazing season, the faecal samples from the untreated control calves showed higher values: range 0-650epg, with only 58% having an epg of <50. The average rate of daily liveweight gain in the untreated heifer calves was 0.79kg per day, the corresponding figure for the heifer calves treated with the ivermectin SR bolus in mid-summer was 0.88kg per day; the difference of 90g per day was significantly different (P=0.0118). The average rate of daily liveweight gain in the untreated bull calves was 0.91kg per day, the corresponding figure for the bull calves treated with the ivermectin SR bolus in mid-summer was 1.01kg per day; the difference was significantly different (P=0.0169).

Animals↗

Impact of ciprofloxacin in the human-flora-associated (HFA) rat model: comparison with the HFA mouse model.

The ecological impact of different doses of ciprofloxacin was investigated in an experimental germ-free rat model into which human fecal flora was inoculated. Animals received oral doses (gavage) of 0, 0.25, 2.5, and 25 mg/kg body weight (bw) of ciprofloxacin once daily for 5 weeks. All doses of ciprofloxacin significantly reduced aerobic populations. Elimination of Enterobacteriaceae and reduction of bifodibacteria were noticed in the group treated with 25 mg/kg of the antibiotic. The rest of the intestinal flora was not affected. These effects were reversible after the treatment ended. The percentage of resistant enterococci increased in rats treated with 2.5 and 25 mg/kg; however, this increase was not statistically significant. There was a significant (P < 0.05) emergence of ciprofloxacin-resistant Bacteroides fragilis group with 25 mg/kg bw, which is equivalent to a human therapeutic dosage of the antibiotic. The MIC values and the percentage of resistance remained elevated 2 weeks after the end of treatment in this anaerobic population. Although sub-populations of enterococci and Enterobacteriaceae showed decreased susceptibility after ciprofloxacin administration, resistance was not evident. The ability of an exogenous strain of Salmonella to colonize the intestine of animals treated with 25 mg/kg of ciprofloxacin confirmed that the drug disrupted the colonization barrier effect of the indigenous flora at the high dose level tested. No changes in the metabolic parameters occurred during the antibiotic treatment. The results obtained in the HFA rat model were similar to those obtained in our previous study using the HFA mice model where ciprofloxacin at 0.125, 1.25, and 12.5 mg/kg bw induced a decrease of enterococci and Enterobacteriaceae populations. The high dose of ciprofloxacin also induced a decrease in bifidobacteria counts, an increase in levels of resistant B. fragilis group and a significant (P < 0.05) disruption of the colonization resistance of the barrier flora in HFA mice.

Animals↗

Exocrine function following the whipple operation as assessed by stool elastase.

What impact does pancreaticoduodenectomy (PD) have on exocrine function? Does the pancreatic anastomosis remain patent? When stool elastase became available for testing in November 2001, we began preoperative assessment and then increasingly employed postoperative measurements. From December 2001 until March 2006, 182 patients underwent PD by the same surgeon. Preoperative stool elastase was measured in 138 (76%) patients and was repeated postoperatively at 3 +/- 1 month, 12 +/- 2 months, and 24 +/- 3 months. At the same time periods, an abdominal CT scan was used to assess patency of the pancreatic anastomosis as implied by pancreatic duct dilation in the remnant (dilation = duct >3 mm or, if duct dilated preoperatively, then duct that failed to decrease in size). All cases were reconstructed with duct-to-mucosa pancreaticojejunostomy. Stool elastase was expressed as normal (>200 microg/gram stool), moderately reduced (100-200 microg/gram), or severely reduced (<100 microg/gram). Preoperative stool elastase values were "normal" in 78% (pancreatic cancer 32% normal vs. all other groups >78%; P < or = 0.001). As compared with preoperative values, the percent of cases with reduced elastase levels at 3 months, 1 year, and 2 years postoperatively was 48%, 73%, and 50%, respectively. The CT scans at the time of the 69 stool elastase measurements after PD showed pancreatic duct dilation in the pancreatic remnant in 9 of 69 (9%) stools but was not more frequent in the group with decreased elastase. Based on cases elastase, one third of patients about to have PD will have exocrine insufficiency, an observation most common among the patients with pancreatic cancer (68%). Stool elastase levels are further depressed in the majority of cases after PD from parenchymal loss because we could not implicate an occluded pancreatic anastomosis. These results suggest that, after PD, exocrine supplementation should be given to all patients with pancreatic cancer, especially those with impending adjuvant therapy. To further improve the long-term results after PD, each surgeon should assess the effect of their own type of pancreaticoenteric technique on exocrine function.

Exocrine Pancreatic Insufficiency↗

Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers.

BACKGROUND: In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. METHODS: Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. RESULTS: ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. CONCLUSION: The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by improvement of some measurable laboratory indices of well-established physiological functions of host, e.g. markers of antioxidative defence system.

Adult↗

Evaluation of two current generation enzyme immunoassays and an improved isolation-based assay for the rapid detection and isolation of rotavirus from stool.

BACKGROUND: Rapid and accurate rotavirus testing is important in decisions involving patient care and management. Quality assurance testing needs to be periodically performed, especially among widely used assays having a direct impact on patient care. OBJECTIVES: To evaluate the current generation Kallestad Pathfinder Direct antigen Detection system (PTH), and the widely used Rotaclone(R) Rotavirus EIA Diagnostic Kit (RTC), in comparison with an improved cell culture amplification-antigen detection (CCA-Ag) isolation-based assay. STUDY DESIGN: Two hundred stool specimens (specimen stored at > or =-75 degrees C), which had been previously tested by PTH, were tested by RTC and CCA-Ag. Discordant specimens were retested by PTH, blocking assay, polyacrylamide gel electrophoresis (PAGE), and/or electron microscopy (EM). RESULTS: Among 200 stool specimens, 197 were in accord by PTH, RTC and CCA-Ag. The sensitivity, specificity, positive and negative predictive values for RTC, PTH and CCA-Ag were, 100, 99, 99, 100, 100, 99, 99, 100; and 98, 100, 100, 98%, respectively. Among five initially discordant specimens, two required a period of 10 days to affect isolation. A non-cultivatable (CCA-Ag negative) but true positive specimen, was identified as rotavirus group A serotype G2 by RT-PCR. Four true positive but discordant specimens were blocking assay negative using one or both EIA kits. CONCLUSIONS: PTH and RTC are excellent rotavirus detection system. However, PTH is more expensive (ca. $3.50 vs. $2.00 per test), mandates a slightly longer turn-around time (ca. 1 vs. 1.5 h), and necessitates slightly more hands-on manipulative/preparative steps. Blocking assay was not a reliable confirmatory test for the resolution of specimen discordancy. A combination of CCA-Ag, PAGE, EM, and/or perhaps RT-PCR, is recommended as an appropriate test panel for the resolution of discordant results during assay evaluation. The newly modified and simplified 48-h rotavirus isolation-based assay may serve as a base line methodology in laboratory evalaution studies, as a laboratory support methodology during drug/vaccine efficacy trials, or for the testing of sources (e.g., biopsy/autopsy tissues) not approved for assay by commercial rotavirus kits.

Antigens, Viral↗

Health evaluation of free-ranging and semi-captive orangutans (Pongo pygmaeus pygmaeus) in Sabah, Malaysia.

Baseline data on health of free-ranging wildlife is essential to evaluate impacts of habitat transformation and wildlife translocation, rehabilitation, and reintroduction programs. Health information on many species, especially great apes, is extremely limited. Between 1996 and 1998, 84 free-ranging orangutans captured for translocation, underwent a complete health evaluation. Analogous data were gathered from 60 semi-captive orangutans in Malaysia. Baseline hematology and serology; vitamin, mineral and pesticide levels; and results of health evaluations, including physical examination, provide a baseline for future monitoring. Free-ranging and semi-captive orangutans shared exposure to 11 of 47 viruses. The semi-captive orangutans had significantly higher prevalence of antibodies to adenovirus (P < 0.0005) and rota (SA 11) virus (P < 0.008). More free-ranging than semi-captive animals had antibodies to Japanese encephalitis virus (P < 0.08) and foamy virus (P = 0.05). Exposure to parainfluenza and langat viruses was detected exclusively in semi-captive animals and exposure to sinbis virus was only found in free-ranging orangutans. There was evidence of exposure to respiratory syncytial virus, coxsackie virus, dengue virus, and zika virus in both groups. Ebstein-Barr virus was ubiquitous in both groups. Prevalence of antibodies against mumps virus changed from 0% in 1996 to 45% in 1998. No antibodies were detected to many important zoonotic viral pathogens, including herpesvirus and hepatitis virus. Prevalence of Balantidium coli and Plasmodium pitheci infections and exposure to mycobacterium was higher in the semi-captive animals. Differences in exposure to pathogens between the groups may be due to environmental factors including differences in exposures to other species, habitat quality, nutritional status, and other potential stressors. Differences in health parameters between captive and free-ranging orangutans need to be considered when planning conservation areas, translocation procedures, and rehabilitation protocols. Because survival of the orangutan is linked to animal and ecosystem health, results of this study will assist wildlife conservation programs by providing baseline health information.

Animals↗

Rectal bleeding in infancy: clinical, allergological, and microbiological examination.

OBJECTIVE: Rectal bleeding is an alarming symptom and requires additional investigation. In infants it has been explained mainly by hypersensitivity. In addition to dietary antigens, intraluminal microbial agents challenge the immature gut mucosa. Although controlled in the mature gut, these antigens may induce inflammation in the developing gastrointestinal tract. The objectives of this study were to evaluate prospectively the clinical course of rectal bleeding and evaluate the impact of cow's milk allergy and aberrant gut microbiota on the condition. Because withdrawal of cow's milk antigens from the infants' diet is used as a first treatment without evidence of its efficacy, we also aimed to asses the effect of a cow's milk-elimination diet on the duration of rectal bleeding. METHODS: The study involved 40 consecutive infants (mean age: 2.7 months) with visible rectal bleeding during a 2-year period at the Tampere University Hospital Department of Pediatrics. Most of the infants (68%) were fully breastfed. At enrollment the infants were randomly allocated to receive a cow's milk-elimination diet (n = 19) or continue their previous diet (n = 21) for 1 month. Findings of colonoscopy, fecal bacterial culture, fluorescence in situ hybridization of selected gut genera, specific detection of fecal enteroviruses, rotaviruses, and adenoviruses, fecal electron microscopy for viruses, and mucosal electron microscopy for viruses were assessed. During each visit the severity of atopic eczema, if any, was assessed according to the SCORAD method. In evaluating the extent of sensitization, serum total immunoglobulin E (IgE) and specific IgE and skin-prick tests for cow's milk, egg, and wheat were studied. Cow's milk allergy was diagnosed by elimination and provocation testing. Five patients were hospitalized; all others were treated on an outpatient basis. The follow-up visits were scheduled 1 month later and at the age of 1 year. Sixty-four healthy reference infants were selected as controls according to the following criteria: age and timing of fecal sampling being identical to within 1 month. RESULTS: Altogether, 32 (80%) infants manifested bloody stools during follow-up (mean [range]: 2.1 [1-15] per day). The mean number of days with rectal bleeding on follow-up was 6. Typically, bloody stools occurred irregularly, for which reason the mean time to the last occurrence of rectal bleeding was 24 (range: 1-85) days from admission. Atopic eczema at presentation or during follow-up was diagnosed in 38% of the infants. Increased specific IgE concentrations or a positive skin-prick test were uncommon. The growth of the infants was normal on admission and during follow-up. Colonoscopy revealed typically focal mucosal erythema and aphthous ulcerations. The mucosa appeared normal in less than half of the patients. No anorectal fissures or colonic polyps were found. Light microscopy revealed that the overall architecture of the mucosa was well maintained. Acute inflammation or postinflammatory state and focal infiltration of eosinophils in the lamina propria were the most common abnormalities. A cow's milk-elimination diet did not affect the duration of rectal bleeding. Cow's milk allergy was diagnosed in 7 (18%) patients. Virus-particle aggregates were found in the microvillus layer of the colon epithelium in 8 cases. The surface epithelium of the virus-positive colon biopsy specimens regularly showed degenerative changes in the microvillus layer and epithelial cells. Electron microscopy study of the colon biopsies disclosed virus particles (30 nm in diameter) on the surface of epithelial cells. Virus particles or RNA were present in feces in only a minority of the patients. All fecal cultures were negative for Salmonella, Shigella, and Yersinia. Campylobacter jejuni was found in the feces of 1 patient, and fecal cultures were positive for Clostridium difficile in 4 patients, Staphylococcus aureus in 8 patients, and yeast in 2 patients. Fluorescence in situ hybridization revealed that at the time of admission the total numbers of bacteria and the numbers of bifidobacteria and lactobacilli in feces were lower in the patients compared with controls. The fecal concentrations of microbes characterized in this study (Bacteroides, bifidobacteria, Clostridium, lactobacilli, and enterococci) did not differ significantly between the time of admission and the second visit in the patients or controls. At the age of 1 year, 7 patients still suffered from cow's milk allergy, 5 of whom also suffered from multiple food allergies. Atopic eczema and histopathologically confirmed inflammation of the colonic mucosa at presentation were associated with persistence of cow's milk allergy at the age of 1 year. No patients exhibited gastrointestinal complaints or visible blood in stools. CONCLUSIONS: Rectal bleeding in infants is generally a benign and self-limiting disorder. Bloody stools occurred irregularly for only a few days during the following months. As in a previous report, most infants were exclusively breastfed. In the majority of the patients the cause of the condition remains unknown. An association with viruses can be seen in some patients. The microbes that commonly lead to bloody diarrhea in older children and adults, Salmonella, Shigella, and Yersinia, were absent in the present material. The low bifidobacterial numbers in fecal samples may indicate a significant aberrance that may provide a target for probiotic intervention to normalize gut microbiota. The gut microbiota overall seemed stable, because the numbers of major groups of microbiota tested did not change significantly between the time of admission and after 1 month. Cow's milk allergy among these patients is more uncommon than previously believed. Cow's milk challenge is thus essential in infants who become symptom-free during a cow's milk-free diet to reduce the number of false-positive cow's milk-allergy diagnoses.

Animals↗

The nutritional value of degermed, dehulled corn for pigs and its impact on the gastrointestinal tract and nutrient excretion.

Three experiments were designed to assess the feeding value and potential environmental benefits of feeding degermed, dehulled corn, a low fiber by-product originating from the corn dry milling process, to pigs. Twelve 27-kg (SE = 0.8) barrows were used in Exp. 1 to measure the apparent fecal digestibility of DM, GE and N of degermed, dehulled corn compared with corn grain. Two diets were formulated to contain either 96.4% of degermed, dehulled corn or corn grain plus supplemental vitamins and minerals. Digestibilities of DM, GE, and N were greater in degermed, dehulled corn (96.2, 96.0, and 93.6%, respectively) compared with corn grain (89.0, 89.0, and 78.4%, respectively) (P < 0.01). Overall, a 67 and 29% reduction in DM and N excretion, respectively, was observed. In Exp. 2, eight 70-kg (SE =1.8) barrows were surgically fitted with ileal cannulae and fed the same diets as in Exp. 1, to measure the ileal digestibility of nutrients in degermed, dehulled corn. Ileal digestibility of DM, energy, and N was 13, 15, and 7% greater in degermed, dehulled corn (P < 0.05). Apparent ileal digestibility coefficients of leucine, methionine, and phenylalanine were greater in degermed, dehulled corn compared with corn grain (P < 0.05) while a trend for a lower tryptophan digestibility in degermed, dehulled corn was observed (P = 0.067). In Experiment 3, 96 nursery pigs with an initial average BW of 8.8 kg (SE = 0.08), fed a starter diet formulated with degermed, dehulled corn or corn grain as the major grain source, were used in a 28-d growth performance study. At the end of the study, 24 pigs (1 pig per pen) were sacrificed and gastrointestinal tract measurements were taken. Daily growth rates of pigs were the same between diets (0.64 kg/d). A trend for reduced feed intake (P = 0.073) in pigs fed degermed, dehulled corn led to a 4% improvement in gain to feed (P < 0.05). Feeding degermed, dehulled corn had no effect on gut fill, gastrointestinal tract weight, or liver weight (P > 0.05). Ileal villus lengths and crypt depths were not affected by feeding degermed, dehulled corn although ileal villus widths were greater in pigs fed corn grain. Results from these trials suggest that corn processed to remove poorly digestible fiber fractions provides more digestible nutrients than corn grain. As a result, degermed, dehulled corn reduces fecal and N excretion, thus providing a means to reduce nutrient excretion.

Animal Feed↗

Evaluating measures to control intestinal parasitic infections.

Intestinal parasitic infections are among the most common infections of humans in developing countries, but the resources available for their control are severely limited. Careful evaluation of control measures is essential to ensure that they are cost-effective. The evaluation of the effects of control on intestinal helminths and intestinal protozoa requires an understanding of the different epidemiological patterns of these two groups of parasites. The transmission dynamics and morbidity associated with the major helminth infections (Ascaris lumbricoides, Trichuris trichiura and the hookworms) are dependent on the size of the worm burdens. Thus the important parameter for evaluating the impact of control on morbidity and transmission is the intensity of infection, which can be assessed by determining the mean density of parasite eggs in faecal specimens. Estimation of intensity is subject to systematic errors, however, due to the complex pattern of worm burden distributions. The frequency distribution of burdens is highly overdispersed, and individuals exhibit predisposition to particular levels of infection. Furthermore, mean intensity is age-dependent, in a species-specific manner, and is clustered spatially and within families. These complex patterns imply that the estimation of intensity is exceptionally sensitive to the size and demographic structure of the population sample selected for assessment. They also have the effect that prevalence estimates, the most commonly used measures of infection in communities, can seriously mislead. Paradoxically, prevalence is least useful where infection is most common because the relationship between prevalence and intensity is most markedly non-linear when the prevalence is high. Thus in areas where control is most needed, evaluation using prevalence might suggest that control had failed while evaluation by intensity would, correctly, show the measure of success. With the major protozoan infections (Entamoeba histolytica, Giardia duodenalis and Cryptosporidium parvum) an estimate of intensity is of little value and the central parameter for evaluation is prevalence. Prevalence does exhibit age and spatial heterogeneity, which may be species-specific, so there remains a need to ensure a consistent sample structure, although this is less critical than for the helminths. The major constraint on evaluating the control of protozoan infections is the need to identify pathogenic species and, in some cases, pathogenic strains. Harmless commensal protozoans are ubiquitous and often morphologically very similar to pathogens, but their control is both unnecessary and impracticable. Species such a E. histolytica appear to exist as strains with differing pathogenicity, thus control will be cost-effective only if the focus is on pathogenic strains. Effective diagnosis is therefore central to the evaluation of the control of protozoan infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Impact of the nematophagous fungus Duddingtonia flagrans on Muellerius capillaris larvae in goat faeces.

The small lungworm Muellerius capillaris is very prevalent in goats and causes production losses. Its control is particularly difficult. The nematophagous fungus Duddingtonia flagrans has been shown to be effective in trapping a large range of gastro-intestinal nematode larvae but its trapping activity against small lungworm remains to be assessed. The purpose of this work was firstly, to evaluate the ability of first-stage larvae of M. capillaris (L1) to induce trap formation in in vitro conditions and secondly, to determine the effect of D. flagrans on the L1 infectivity to snails. In experiments on agar, the presence of L1 failed to induce any D. flagrans traps whereas in the same conditions, gastro-intestinal third-stage larvae induced 44-135 traps/cm(2) depending on the species. Moreover, when the traps were pre-induced by Haemonchus contortus larvae, the L1 of M. capillaris were not trapped. For the in vivo trial, two goats naturally infected with M. capillaris received D. flagrans chlamydospores at the daily dose rate of 5x10(5) spores/kg BW for 8 days. Faeces were collected individually before, during and 11 days after spore administration. On each day of harvest, the initial larval output was determined. The remaining faeces were subjected to coproculture at 21 degrees C for 7 days. At the end of this period, L1 were collected and used to infect snails (30 snails per goat isolate each snail given 40 L1 by direct deposit of the larvae on the foot of the snail). These snails were artificially challenged in contrast to others that were exposed to natural infection by exposure to faeces carrying first-stage M. capillaris larvae. The natural infection used the same number of snails, i.e. 30 snails deposited on the faeces of each goat. After 3 weeks at room temperature, the infective larvae present in the snail foot were counted. There was no difference in the survival of the L1 in faeces after coproculture whether the faeces contained D. flagrans or not. The infectivity of the extracted larvae from the two goats before and after fungal administration was the same. The number of infective larvae per snail obtained after "natural" infection showed variations that were not related to the presence of D. flagrans mycelium in faeces. These trials clearly indicate that D. flagrans was unable to trap or to alter the infectivity of M. capillaris first-stage larvae and thus cannot be considered as a non-chemotherapeutic alternative approach to the control of the small lungworm in goats.

Animals↗

Selective and on-demand drenching of lambs: impact on parasite populations and performance of lambs.

AIM: To determine whether drenching regimes for lambs by which a proportion (10%) of the heaviest animals was selectively left untreated, or animals are only drenched 'on demand' when faecal nematode egg counts (FEC) exceeded a threshold level, would result in measurable increases in parasite larval challenge in the autumn and/or decreases in the performance of lambs. METHODS: A replicated study compared three drenching strategies in which mobs of lambs (n=360 in total) received either: a five-drench preventive programme, administered to all animals (Treatment 1); a five-drench preventive programme, but the 10% heaviest animals left untreated each time (Treatment 2); or drench treatments administered only when FEC exceeded 500 eggs per gram of faeces (epg) (Treatment 3). After the five-drench programme, animals in Treatments 1 and 2 were treated according to FEC as for Treatment 3. A triple-combination drench containing ivermectin, oxfendazole and levamisole, administered orally, was used for all treatments. There were nine farmlets, allowing three replicates of each treatment, in a completely randomised design. Parasite infestations on pasture were measured in autumn by pasture plucks, and worm burdens were monitored in tracer lambs, while the performance of lambs was assessed by liveweight gains, fleece weights, and body condition and dag scores. RESULTS: Increased numbers of Haemonchus contortus and Trichostrongylus colubriformis larvae on pasture were found in the autumn on farmlets treating selectively or on-demand (Treatments 2 and 3). No differences were detected in other parasite species. Mean liveweight gains did not differ between treatments but some differences were detected between drenched and undrenched lambs in Treatment 2. Mean body condition and mean dag scores of lambs in Treatment 3 tended to be lower and higher, respectively, than those of lambs in Treatment 1; Treatment 2 was generally intermediate. CONCLUSIONS: Drenching strategies for lambs designed to slow the development of anthelmintic resistance, by increasing the pool of susceptible worms available to dilute resistant survivors after treatment, resulted in increased numbers of H. contortus and T. colubriformis but not other species of parasite on pasture. The increased parasite challenge to lambs in the autumn was associated with small production losses, which may be acceptable to farmers wishing to implement such strategies. It is clear that further work is required on the interaction between management practices and the population dynamics of parasites, especially with regard to creating pools of susceptible genotypes to slow the development of drench resistance.

Albendazole↗

Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of beta-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.

Animals↗