[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Changes in hoof health and animal hygiene in a dairy herd after covering concrete slatted floor with slatted rubber mats: a case study.

The objective was to investigate the effect of changing the flooring in the alleys of a barn from slatted concrete to slatted rubber mats on hoof disorders and animal hygiene in 44 loose-housed Brown Swiss dairy cows. Cows were examined for disorders of the hind hooves (hemorrhages, white line fissures, ulcers, heel horn erosion, and digital dermatitis) and for skin lesions. The dirtiness of the animals and of the floor was recorded. Climatic (temperature, humidity) and ammonia gas conditions were measured. Evaluations were carried out when the cows were housed on a concrete slatted floor and after 4 and 10 mo on soft flooring (slatted rubber mats, 29-mm thick). The anatomical portion of claw (medial, lateral), number of lactations (parity), and days in milk were included as covariates in the statistical model. Changing the flooring from slatted concrete to slatted rubber mats increased the score for white line fissures [1.0 ± 0.3 (concrete) vs. 2.5 ± 0.4 (10 mo rubber mats)] and influenced air humidity (i.e., the difference in the absolute humidity between the inside and outside of the barn increased from 1.5 ± 0.1 to 1.7 ± 0.2g/m(3)), whereas the other hoof disorders, skin lesions (score of 8.7 ± 0.3), the dirtiness of the animals (score of 5.9 ± 0.3), and the floor (score of 2.1 ± 0.1), and ammonia gas concentration (2.6 ± 0.3mg/kg) were not affected (overall scores or measures; mean ± SE). Lateral claws were more affected (except for heel horn erosion) than medial claws (estimated effects between 1.3 ± 0.2 and 3.0 ± 0.6). Parity influenced hoof disorders (except for hemorrhages) and skin lesions (estimated effects between -0.6 ± 0.3 and 0.5 ± 0.2). Days in milk influenced hoof disorders, but had no effect on skin lesions and on the dirtiness of the animal. Irrespective of floor type, the slots (2.6 ± 0.1) were dirtier than the slats (1.6 ± 0.1). In conclusion, covering slatted concrete flooring with slatted rubber mats partially impaired hoof health but did not influence skin lesions or the dirtiness of the cows or the floor. Similar results were found for climatic conditions, as ammonia gas concentration was not affected, but absolute humidity increased in the barn when rubber mats were present.

What happens with cow behavior when replacing concrete slatted floor by rubber coating: a case study.

An enhanced productive life cycle and improved animal welfare are aims pursued in dairy husbandry. This study assesses experimental observations on floor-associated behavior during the stepwise replacement of concrete slatted flooring by rubber mats. For this purpose, estrus (mounting) and hygiene behavior (licking while standing on 3 legs and caudal licking) within a herd of 50 loose-housed Brown Swiss dairy cows were analyzed by video observation before and after floor reconstruction. Still photographs and pedometers were used to asses step length and number of steps, representing walking behavior. Compared with the concrete floor surface, rubber coating led to an increase in step length (58 +/- 1 vs. 70 +/- 1 cm; n = 35) and in steps per day (4,226 +/- 450 vs. 5,611 +/- 495; mean +/- SEM; n = 9). Mounting was higher on the flooring covered with rubber mats (23 vs. 112). Collapsing or slipping during mounting only occurred on concrete slatted flooring (in 19 out of 23 mounting actions). Licking while standing on 3 legs and caudal licking increased up to 4-fold (105 vs. 511 observations). In conclusion, improvements were found in behavior when rubber-coated slatted floor surfaces were used in dairy cattle housing in transition from concrete flooring. Disorders in estrus and hygiene behavior were associated with the flooring of the barn and were relatively easy to investigate within the framework of farm welfare assessments.

Antisecretory effects of berberine with morphine, clonidine, L-phenylephrine, yohimbine or neostigmine in pig jejunum.

The effects of berberine alone or in combination with morphine, clonidine, L-phenylephrine or yohimbine were compared in Escherichia coli heat-stable enterotoxin (ST)-exposed ligated jejunal loops in 2 week old pigs. In addition, net water and electrolyte fluxes in normal jejunal loops were measured in the presence of neostigmine, morphine, clonidine, L-phenylephrine or yohimbine alone or in combination with berberine. Berberine, morphine, clonidine and L-phenylephrine each reduced the net secretion of water and electrolytes induced by ST (P less than 0.05). A significant enhancement of antisecretory effect was observed only with the combination of berberine and L-phenylephrine. Yohimbine or neostigmine augmented the net loss of water and electrolytes produced by ST. Yohimbine did not block the antisecretory action of berberine. In normal jejunum, there was no significant difference in water and ion absorption between adrenergic or opiate agonists alone and their combination with berberine. Neostigmine reversed absorption to net secretion in normal jejunum and this effect was significantly reduced by berberine. The anti-secretory action of berberine appears similar to that of alpha 2-adrenergic agonists, opiates, and anticholinergic agents.

Congenital cystic adenomatoid malformation type 4.

A 9-day-old boy presented in respiratory distress and with failure to thrive. The chest X-ray showed a hyperlucent area of the left lung. A resection of the markedly emphysematous segment 2 of the left upper lobe was performed assuming the emphysematous tissue was due to congenital lobar emphysema (CLE). Histological examination of the lung tissue, however, revealed a pattern consistent with congenital cystic adenomatoid malformation (CCAM) type 4. The therapy for CLE as well as for CCAM is similar, i.e., resection of the emphysematous tissue. As far as the prognosis is concerned, it is important to diagnose the exact type of malformation in order to exclude associated anomalies, as well as the risk of development of malignancies in later life. The frequency of associated malformations of CCAM type 4 is unknown. Although the risk for development of malignancies from CCAM type 4 is not clear at the moment, the possible development of malignancies justifies prompt resection shortly after diagnosis, even in asymptomatic patients. A life-long follow-up in those patients who had a resection of CCAM in early childhood is recommended.

Effect of potentially probiotic lactobacilli on faecal enzyme activity in minipigs on a high-fat, high-cholesterol diet-a preliminary in vivo trial.

Minipigs were fed a "Western-style", high-cholesterol diet for a baseline period, followed by the diet containing a mixture of three Lactobacillus strains with potential probiotic features, after which a normal pig diet was followed. The faecal enzyme activity for beta-glucuronidase and azoreductase, which are commonly considered as markers for procarcinogenic activity, was significantly reduced during the 5 weeks of "probiotic" supplementation. During the period of Lactobacillus administration, the cell counts for total anaerobes increased, whereas the total number of aerobes showed no change.

Characterisation and selection of probiotic lactobacilli for a preliminary minipig feeding trial and their effect on serum cholesterol levels, faeces pH and faeces moisture content.

Three out of 297 Lactobacillus strains isolated from pig faeces were selected for a feeding trial on account of their high bile-salt hydrolase (BSH) activity, bile-salt resistance, low pH tolerance and the production of antimicrobial substances. Two strains were identified as Lactobacillus johnsonii and one as Lactobacillus reuteri by DNA-DNA hybridisation. L. johnsoniii BFE 1061 produced a bacteriocin active against a range of lactic acid bacteria (LAB) and nonrelated bacteria including Clostridium perfringens. Six minipigs were maintained on a high-fat, high-cholesterol ('Western Style') diet for 17 weeks after which the diet was supplemented with the 'probiotic mixture' containing the above mentioned three Lactobacillus strains at 2 x 10(12) CFU per pig per day for five weeks. The mixture was given as a resuspended lyophilisate. During a two week follow-up period the minipigs received only the 'Western-style' diet without probiotic supplementation. A lowering effect on serum cholesterol levels was indicated after three weeks probiotic feeding, concomitant with an increase in the moisture content of the faeces and Lactobacillus cell numbers. Triglycerides, pH and number of lactic acid bacteria in faeces were not significantly influenced by probiotic supplementation.

Chlortetracycline modulates acute phase response of ex vivo perfused pig livers, and inhibits TNF-alpha secretion by isolated Kupffer cells.

Tetracyclines have been shown to have anti-inflammatory effects in addition to their antimicrobial action. We investigated the effects of in vivo administration of chlortetracycline (CTC) on ex vivo perfused pig livers. The retention and clearance of Salmonella choleraesuis, production of acute phase proteins C-reactive protein (CRP), and haptoglobin (HPG) by whole livers were studied. The in vitro modulation by CTC of TNF-alpha secretion by pig Kupffer cells (KC) was also studied. Pigs were dosed orally with CTC for three days, and given injections of Salmonella LPS 24 h before removal of the liver. Salmonella retention and clearance by livers of pigs given CTC was lower than by control livers (p < 0.01 and p < 0.05, respectively). We demonstrated an increase of CRP and HPG by livers from control pigs after a three-hour perfusion while pigs from CTC pretreated pigs varied in this response. Further, CTC decreased the secretion of TNF-alpha by cultured KC incubated in vitro with LPS. Modulation of TNF-alpha production by CTC suggests a potential for attenuating the inflammatory response. However, this possible beneficial action of CTC was accompanied by a significant decline in the antimicrobial effect of the liver.

Acute phase response to Salmonella in a pig liver perfusion model.

Livers from 7- to 14-day old pigs were maintained on a perfusion apparatus for 3 h. The perfused livers maintained physiologic and immunologic functions during perfusion. The perfused livers retained 78-94% of a non-recirculating inoculum of approximately 1-5 x 10(8) Salmonella choleraesuis (Scs), and cleared 94.9 +/- 1.7% of the retained (Scs) during the 3-h perfusion period. When the acute phase response (APR) was induced in liver donor pigs 24 h before liver perfusion, the perfused livers had diminished capability to retain, and greatly diminished capability to clear Scs. When sterile, filtered, and concentrated liver perfusate (LP) from previous, LPS-perfused livers was added to the perfusion fluid (PF) at 50 min of Scs perfusion (passive APR), Scs clearance was inhibited. When sterile, filtered LP from previously Scs perfused livers was added to the system, liver clearance was abolished, and Scs always grew in such livers during the 3 h perfusion period. The LP of livers perfused with Scs enhanced growth of Scs in an in vitro assay. These observations suggest that products of the acute phase response favor growth of Scs in vitro and in vivo.

The effect of source of fiber on ileal and fecal amino acid digestibility and bacterial nitrogen excretion in growing pigs.

Studies were carried out with six barrows (initial BW 50 kg) to determine the effect of two fiber sources on the apparent ileal and fecal N and amino acid digestibilities and bacterial N excretion in feces. The pigs, fitted with a simple T-cannula at the distal ileum, were fed three cornstarch-based diets formulated to contain 16% CP from soybean meal according to a repeated 3 x 3 Latin square design. Diet 1 did not contain additional fiber. Diets 2 and 3 contained 10% powdered cellulose and 10% barley straw (ground through a 2-mm mesh screen), included at the expense of cornstarch, respectively. The pigs were fed 900 g at each meal twice daily, 0800 and 2000. Feces were collected for 48 h after a 10-d adaptation period. Thereafter, ileal digesta were collected for 24 h. Chromic oxide was used as a digestibility marker. With the exception of leucine, the inclusion of fiber did not affect (P greater than .05) the ileal digestibilities of the indispensable amino acids. The values for the average of the ileal digestibilities of the indispensable amino acids were 85.3, 82.9, and 83.2% for diets 1, 2, and 3, respectively. On the other hand, the inclusion of fiber decreased (P less than .05) the fecal digestibilities of all the indispensable amino acids. The values for the average of the fecal digestibilities of the indispensable amino acids were 91.7, 87.4, and 89.1% for diets 1, 2, and 3, respectively. These decreases resulted from an increase (P less than .05) in the excretion of bacterial N, which was measured using 2,6-diaminopimelic acid as a marker. In conclusion, as measured with the ileal analysis method, the inclusion of fiber had little effect on the digestible amino acid supply.

Effect of level of dietary neutral detergent fiber on ileal apparent digestibility and ileal nitrogen losses in pigs.

A study was conducted with 20 barrows (average BW 25 kg) to determine the effect of various levels of neutral detergent fiber (NDF) in the diet on the apparent ileal nutrient digestibility and ileal diaminopimelic acid (DAPA) content, and consequently on the amount of ileal endogenous nitrogen. The pigs were fitted with a post-valvular T-cecal cannula. They were fed .8 kg/d of a corn starch-based semisynthetic diet formulated to contain equal amounts of protein and starch and 0, 60, 120, or 180 g of purified NDF/kg of diet, included at the expense of glucose. The purified NDF (pNDF) was isolated from wheat bran using an incubation procedure with pancreatin. Ileal digestibility of NDF was approximately 17% and was independent of the pNDF level in the diet. By increasing the amount of pNDF in the diets, apparent ileal digestibilities of dry matter (DM), nitrogen (N), neutral detergent insoluble N (NDF-N), and ash decreased linearly (P < .05). The DAPA content of the ileal digesta (g/d) was not affected by the percentage of pNDF in the diets. Calculation of the ileal bacterial N excretion indicated that more than 50% of the ileal N was of bacterial origin. With increased percentage of dietary pNDF, both endogenous and exogenous N in ileal chyme were linearly increased (P < .05). Thus, an increase in the dietary fiber content leads to a decreased apparent ileal protein digestibility due to increased ileal losses of both endogenous and exogenous protein.

Tracer studies of urea kinetics in growing pigs: II. The effect of starch infusion at the distal ileum on urea recycling and bacterial nitrogen excretion.

Six gilts, with an average BW of 70 kg, were fitted with a simple T-cannula at the distal ileum to study the effect of continuous starch infusion on urea kinetics by means of a radioisotope dilution technique. The pigs were fed twice daily 600 g of a cornstarch-based diet formulated to contain 16% CP by supplementation with isolated soy protein. Infusion of starch, compared with water, decreased (P < .05) plasma urea concentration, urea pool size, and entry, excretion, and degradation rates; urea turnover rate and urea space were not affected (P > .05). Expressed as a percentage of total entry rate, approximately 40% of urea was recycled into the digestive tract in both infusion treatments. The stimulation of microbial fermentation in the large intestine resulted in an increase (P < .05) in fecal N excretion, which was mainly due to an increased excretion of bacterial N. This increase could not be attributed to a greater secretion of urea into the large intestine and its subsequent utilization by the intestinal microflora. The increased bacterial N assimilation after starch infusion led to a reduction in ammonia absorption from the large intestine, which in turn was reflected by a reduced urinary N excretion. As a result, the overall N balance was not affected. In a second experiment, two barrows, with an average BW of 80 kg, were fed twice daily 1.4 kg of a cereal-based diet. The body urea pool of both pigs was labeled with a single injection of 1 g and 2 g of [15N]urea, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lead on glucose metabolism, ion flux, and collagen synthesis in cerebral capillaries of calves.

Brain capillary function was assessed in 4- to 6-week-old calves given lead acetate (15 mg/kg of body weight) orally for 7 to 8 days. Neurologic signs of lead poisoning included CNS depression, blindness, and hyperesthesia. Brain capillaries were isolated from cerebral cortex of control and lead-treated calves and evaluated for metabolic indicators, ion transport, and prolyl hydroxylase activity. In lead-treated calves, the rate of glucose metabolism was less than half that in controls. Ion efflux of 45Ca or 36Cl from endothelial cell suspensions was not affected by lead treatment. Prolyl hydroxylase activity in endothelium and proline-to-hydroxyproline ratio in endothelial basement membranes were similar in control and lead-poisoned calves. Results indicate that lead may inhibit energy metabolism, but not ion transport or collagen biosynthesis in brain capillaries of calves and, compared with suckling rats, damage to the blood-brain barrier is less important. In calves, neuronal tissue may be the primary target for the CNS effects of lead.

In vitro effects of a mixture of Escherichia coli heat-stable enterotoxins on chloride flux in everted jejunal sacs of male pigs.

In vitro effects of a mixture of Escherichia coli heat-stable enterotoxins (STa and STb) on isolated jejunum of 3-week-old male pigs were studied, using everted intestinal sac techniques. Heat-stable enterotoxins increased chloride secretion and chloride absorption in everted intestinal sacs. The increase of secretory flux was greater than that for absorptive flux. Vasoactive intestinal peptide (6 x 10(-9) M) increased chloride secretion, but had no effect on chloride absorption. Neither vasoactive intestinal peptide nor pilocarpine (10(-5) M) had additive effect to ST. Secretory effects of ST were not blocked by atropine (2 x 10(-5) M), clonidine (10(-6) M), or morphine (4.2 x 10(-6) M).

Effect of berberine on intestinal secretion mediated by Escherichia coli heat-stable enterotoxin in jejunum of pigs.

Intraluminal perfusion with Escherichia coli heat-stable enterotoxin (ST) reversed water and electrolyte movements from net absorption to net secretion in porcine jejunal segments. Addition of berberine hydrochloride (3.2 X 10(-5) M) to the perfusate reduced the jejunal secretory response of water, sodium, potassium, and chloride to ST and enhanced water and electrolyte absorption in control segments. At lower concentrations (1.1 X 10(-5) M), berberine reduced the secretory response in ST-exposed segments, but only the decrease of sodium flux was significant. In the presence of berberine, the mucosal enzyme activities of adenosine triphosphatase and disaccharidases were not significantly different between control and ST-exposed segments. Doses of 1, 2, 3, 4, 5, and 10 mg of berberine were injected into ligated loops of proximal part of the jejunum with 1 ml of ST filtrate. At doses of 2 or more mg/loop, berberine was effective in reducing water and electrolyte secretions induced by ST; the effect was dose-dependent. These findings indicate that berberine may be an effective antidiarrheal agent in E coli heat-stable enterotoxin mediated secretory diarrhea and provide a basis for the frequent empirical use of berberine alkaloid and berberine-containing plants in gastroenteritis and infectious diarrhea in Asian and other countries.

Effects of Escherichia coli heat-stable enterotoxin, atropine, clonidine, and morphine on chloride efflux from isolated enterocytes.

The effects of Escherichia coli heat-stable enterotoxin (ST) on chloride efflux rate were investigated in 3 fractions of enterocytes isolated in a villus-to-crypt gradient from porcine jejunum. There was no difference in chloride efflux rates between mature and immature cells from controls. Heat-stable enterotoxin significantly increased chloride efflux in all fractions. Morphine inhibited ST-augmented secretion in mature enterocytes. Atropine or clonidine had no effect. Calcium efflux rates and glucose or glutamic acid metabolism were not altered by ST. The results indicate that ST may stimulate chloride secretion in both villus and crypt cells and that opiates inhibit intestinal secretion by a direct action on villus epithelial cells.

Cytokine release by porcine livers perfused with lipopolysaccharide or live Salmonella choleraesuis.

OBJECTIVE: To develop a model to study the kinetics and relative amounts of cytokines produced by liver cells during enteric infection. DESIGN: Salmonella enteriditis lipopolysaccharide (LPS)- or live S choleraesuis-stimulated isolated livers from clinically normal pigs and pigs with active acute phase response. ANIMALS: 7- to 14-day-old salmonellosis-free pigs, 4 to 12/group. PROCEDURE: Livers were removed and perfused with oxygenated Krebs-Henseleit solution for 30 minutes and with S choleraesuis or LPS added for 7 minutes. Livers were then perfused with 500 ml of fresh solution in a closed loop procedure for 180 minutes. Perfusate samples were collected for tumor necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6) bioassays. RESULTS: Tumor necrosis factor-alpha values remained constant during perfusion of normal livers and increased in those exposed to LPS. Interleukin 6 values increased in perfusate from normal livers from 30 to 150 minutes, then decreased. In livers from pigs with an active acute phase response, TNF alpha values were reduced; IL-6 appeared by 2 minutes and decreased after 25 minutes. CONCLUSIONS: Isolated livers could be kept viable for 3 hours, and IL-6 and TNF alpha could be measured by the bioassays used. CLINICAL RELEVANCE: Model can be used for studying and modifying the response of liver cells to infective agents.

Evaluation of phagocytosis, bactericidal activity, and production of superoxide anion, nitric oxide, and tumor necrosis factor-alpha in Kupffer cells of neonatal pigs.

OBJECTIVE: To evaluate the activity of Kupffer cells (KC) of control neonatal pigs and neonatal pigs treated with endotoxin and to compare activity of KC with that of pulmonary alveolar macrophages (PAM). SAMPLE POPULATION: Kupffer cells and PAM obtained from 24 neonatal pigs (7 to 10 days old). PROCEDURE: Pairs (n = 7) of littermates served as treated (lipopolysaccharide [LPS]) or untreated pigs. Pigs were euthanatized 24 hours after treatment, and cells were isolated. Cells were obtained from 10 other neonatal pigs for other assays. Functional activity of cells was evaluated by use of in vitro assays to evaluate bactericidal activity, phagocytosis, and production of superoxide anion (SOA), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-alpha). Each assay was repeated on cells obtained from 4 to 6 pigs. RESULTS: Phagocytic activity was similar in KC and PAM, but bactericidal activity and production of SDA and TNF-alpha was lower in KC. Neither KC nor PAM produced NO in response to LPS stimulation. Phagocytosis, bactericidal activity, and production of SOA were enhanced for KC obtained from neonatal pigs treated with LPS. The PAM from LPS-treated neonatal pigs had similar bactericidal activity to PAM obtained from untreated pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Functional capacity of KC is affected by endotoxin. This provides additional information of the role the liver plays in immune surveillance. In addition, the response of KC in neonatal pigs exposed to endotoxin is of value for understanding gram-negative bacterial sepsis, which is a major cause of mortality in neonatal pigs.

Colonic nitrite and immunoglobulin G concentrations in dogs with inflammatory bowel disease.

OBJECTIVE: To evaluate lavage analytes as markers of mucosal inflammation in healthy dogs and dogs with inflammatory bowel disease (IBD). DESIGN: Case control study. ANIMALS: 9 healthy dogs and 10 dogs with IBD. PROCEDURE: A polyethylene glycol electrolyte solution was administered into the dogs colons via a rectal balloon catheter prior to colonoscopy. Lavage solution was allowed to remain intraluminally for 30 minutes and then was withdrawn. Lavage supernatant samples were immediately analyzed for total protein, IgG, and nitrite concentrations and myeloperoxidase activity. Mucosal biopsy specimens were obtained from the descending colon and histologically reviewed. RESULTS: All dogs with IBD had mild to severe lymphocytic-plasmacytic colitis, whereas 8 of 9 healthy dogs did not have substantial mucosal inflammation. Myeloperoxidase activity was not detected in lavage samples from healthy dogs or dogs with IBD. Total protein concentration was not significantly different between groups. Mean nitrite and IgG concentrations were significantly higher in samples from dogs with IBD (1.83 nmol/ml and 46 mg/dl, respectively), compared with samples from healthy dogs (0.245 nmol/ml and undetectable concentrations, respectively). Severity of lesions was not correlated with nitrite or IgG concentration. CLINICAL IMPLICATIONS: Assay of nitrite and IgG concentrations in colonic lavage fluid is a simple, objective means of evaluating mucosal inflammation in dogs with IBD. Potential uses include monitoring response to treatment and evaluation of complex cases of chronic intestinal inflammation.