[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.

Release and permeation of histamine in isolated caecum epithelia of pigs.

OBJECTIVE: The objective was to investigate the role of histamine in the porcine caecum with special regard to its release and permeation. MATERIAL AND METHODS: Caecal epithelia were mounted in Ussing chambers. Mast cells were stimulated by A23187 (1 micromol/l). Permeation and changes in short-circuit current (Isc) were assessed after unilateral application of 3H-labelled histamine (100 micromol/l). Mucosal-to-serosal (ms) and serosal- to-mucosal (sm) flux rates were calculated based on the contralateral appearance of radioactive histamine label (hist-rad; representing histamine plus catabolites) as well as histamine. 14C-mannitol fluxes were measured to assess paracellular permeability. RESULTS: Both A23187 and serosal addition of histamine increased Isc of caecal epithelia. The Isc increase due to A23187 was associated with an elevated histamine release from epithelia. A discrepancy between hist-rad and histamine fluxes (P<0.05) indicated efficient histamine catabolism (ca. 85%), which was decreased by blockage of diamine oxidase through aminoguanidine. Fluxes of histamine were correlated to 14C-mannitol fluxes. Fluxes of hist-rad and histamine were higher in the sm direction. CONCLUSIONS: Histamine can be released from endogenous stores and acts on the epithelium. The absorption of luminal histamine is predominantly restricted by paracellular permeability and catabolism. The latter is only partially catalysed by diamine oxidase.

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.

Luminal salmonella endotoxin affects epithelial and mast cell function in the proximal colon of pigs.

BACKGROUND: Salmonellosis and systemic endotoxaemia affect intestinal function. However, little is known about the functional importance of luminal Salmonella (S.) endotoxin during intestinal infection. METHODS: Pigs were either given or not given lipopolysaccharide (LPS, 30 mg day(-1)) of S. Typhimurium DT-104 orally for 14 days. Blood samples were taken weekly. After slaughter (day 14), epithelia of the proximal colon were investigated in Ussing chambers. Bacterial translocations to lung, liver, spleen and several lymph nodes were determined by culture. RESULTS: Endotoxin feeding increased plasma C-reactive protein (CRP) and histamine levels without evoking clinical signs. Postmortem, proximal colonic epithelia of LPS-treated animals showed both a decreased histamine release after mast cell stimulation with A23187 and a smaller increase in short-circuit current after A23187 application. Addition of the nitric oxide donor, sodium nitroprusside (SNP), also elicited lower increases in short-circuit current in the proximal colon of endotoxin-treated pigs. Endotoxin pre-feeding decreased colonic ion conductance, although mannitol and histamine fluxes were high in some epithelia of this group. Luminal Salmonella endotoxin increased bacterial translocation to proximal jejunal lymph nodes. LPS applied to colonic epithelia in vitro had no electrophysiological effects. CONCLUSIONS: Luminal endotoxin elicits an acute phase response and affects intestinal electrolyte transport and mast cell function. Furthermore, LPS induces epithelial spots of increased mannitol permeability that could be identical to spots of enhanced bacterial translocation.

Effect of nitric oxide on electrolyte transport across the porcine proximal colon.

The effect of nitric oxide (NO) on ion transport in the porcine proximal colon was investigated in slide-stripped epithelia mounted in Ussing chambers. The serosal addition of the NO-donors sodium nitroprusside (SNP, 0.5 mM) or S-nitroso-N-acetylpenicillamine (SNAP, 0.5 mM) induced a steep increase of short-circuit current ( I(sc)). The stimulatory effect of SNP on I(sc) could not be blocked by piroxicam or tetrodotoxin. Potassium channel inhibitors (quinidine, tetraethylammonium or barium) added serosally reduced the SNP- or SNAP-induced increases of I(sc). In chloride-free solutions, the SNP-induced increase of I(sc) was smaller than in chloride-containing solutions. Cl(- )and Na(+) flux measurements demonstrated that SNP diminished Cl(-) and Na(+) net absorption. Pre-treatment with barium was able to block the inhibitory effect of SNP on NaCl net absorption totally. NO effects on paracellular pathways were assessed by measuring flux rates of [(14)C]-D-mannitol. SNP did not change unidirectional D-mannitol flux rates. In conclusion, NO inhibits NaCl net absorption in the proximal colon of pigs by acting directly on the enterocyte. The antiabsorptive (and/or prosecretory) effect of NO depends on a functional basolateral potassium conductance.

Histamine-induced chloride secretion is mediated via H2-receptors in the pig proximal colon.

OBJECTIVE: The aim of this study was to investigate the action of histamine on function of epithelia in the pig proximal colon. MATERIAL AND METHODS: Isolated epithelia of the pig proximal colon were prepared by slide-stripping and mounted in Ussing chambers. Short-circuit current (Isc) was measured after serosal addition of histamine (20 micromol/l) with or without pretreatment with histamine receptor antagonists (H1: chlorpyramine, 10 micromol/l; H2: famotidine, 100 micromol/l; H3: thioperamide, 10 micromol/l), a cyclooxygenase inhibitor (indomethacin, 10 micromol/l), or a neuronal conduction blocker (tetrodotoxin, 1 micromol/l). Alternatively, histamine receptor agonists (H1: 2-pyridylethylamine; H2: dimaprit; H3: R-alpha-methylhistamine, each 100 micromol/l) were added to the serosal side. Flux studies using 14C-mannitol, 22Na+ and 36Cl- were performed in the presence of 100 micromol/l histamine on the serosal side. RESULTS: Serosal application of histamine induced a rapid rise in Isc with a maximum 3 min after addition, followed by a slow decrease. Only pretreatment with famotidine decreased the epithelial response to histamine. Pretreatments with chlorpyramine, thioperamide, indomethacin or tetrodotoxin did not change histamine-induced increases in Isc. Action of histamine could be simulated by dimaprit, but not by 2-pyridylethylamine or R-alpha-methylhistamine. Histamine induced an increase in serosal-to-mucosal chloride flux leading to a decrease of chloride net absorption. Fluxes of sodium and mannitol were not affected by histamine. CONCLUSIONS: In contrast to the importance of H1-receptors in other gut epithelia, histamine acts directly via H2-receptors in the porcine proximal colon. Changes in Isc after histamine addition are primarily due to chloride secretion. The paracellular permeability is not influenced by histamine.

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.

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.

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.

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.

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.

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.

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.