Acquired resistance against a secondary infection with Listeria monocytogenes in mice is not dependent on reactive nitrogen intermediates.

During an infection, inflammatory mediators can induce the production of nitric oxide, a reactive nitrogen intermediate (RNI) which plays a role in antimicrobial activity against a wide variety of pathogens. In vitro experiments have shown that release of RNI by macrophages is mediated by tumor necrosis factor alpha (TNF). Since TNF is essential for acquired resistance during a secondary Listeria monocytogenes infection in mice, the aim of the present study was to determine whether RNI are also involved in the course of such an infection. Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose of (LD50) L. monocytogenes were infected intravenously with 10LD50 of L. monocytogenes. During a primary infection, the number of bacteria in the liver and spleen, as well as the concentration of RNI in plasma, increased. During a secondary infection, the number of bacteria in the liver and spleen decreased whereas no significant increase in the concentration of RNI in plasma was observed. Neutralization of endogenously produced TNF and gamma interferon by subcutaneous injection of alginate-encapsulated monoclonal antibody-forming cells during a secondary infection resulted in an increase in the number of bacteria in the liver and spleen an increase in the concentration of RNI in plasma. When the production of RNI was inhibited by treatment of mice with competitive NO-synthase inhibitor N omega-nitro-L-arginine methyl ester hydrochloride (L-Name) and an iota-arginine-deficient diet during a secondary infection, the proliferation of L. monocytogenes in the liver and spleen was not affected whereas the concentration of RNI in plasma of these mice was significantly reduced. Our findings that inhibition of RNI formation during a secondary infection does not affect the proliferation of L. monocytogenes in the liver and spleen and that enhanced elimination of bacteria from these organs is not accompanied by an increase in the concentration of RNI in plasma led to the conclusion that resistance against a secondary infection with L. monocytogenes is not dependent on RNI.     

Preferential expression of IgG2b in nose draining cervical lymph nodes and its putative role in mucosal tolerance induction

Induction of intranasal tolerance prevents the body from eliciting unwanted immune responses against harmless antigens that enter the body through the nasal mucosa. To study the intrinsic capacities of the cervical, nose draining lymph nodes (CLN), which are essential for tolerance induction, genes that are differentially expressed in CLN and not in peripheral lymph nodes (PLN) were characterized. The gene that is predominantly overexpressed in CLN codes for IgG2b. This is confirmed by a higher percentage of IgG2b+ B220+ cells in CLN compared with any PLN. However, this predominance of IgG2b-positive B cells in the CLN is not specific for the lymph node itself but rather determined by the region drained by lymph nodes at the cervical site, as transplanted PLN at these locations show a comparable predominance. It was demonstrated that IgG2b, when compared with IgG1, led to differential activation of dendritic cells (DC) through Fc receptor signalling. The results point to a unique local combination of cells and factors in the nose draining CLN leading to highly specialized immune reactivity. The results point out that predominance of a distinct IgG isotype in a lymphoid environment may lead to highly specialized immune reactivity.     

Pitfalls in the analysis of electrogastrographic recordings.

Electrogastrography (EGG) is a noninvasive method to study gastric myoelectrical activity in humans. Because frequency characteristics are the most reliable parameters and visual analysis of the EGG recordings is notoriously difficult, automated frequency analysis, especially running spectrum analysis, is often used. However, EGG frequency spectra can be misinterpreted easily. Movement artifacts and noise from various sources can result in abnormal frequency spectra with significant power in the low-frequency and high-frequency range, or even make the EGG completely uninterpretable. Signals that differ from a sinusoid waveform have harmonics in the high-frequency range of the spectrum and may be interpreted as abnormal. Visual inspection of raw signals and frequency spectra remains essential in the analysis of EGG signals. The value of computerized analysis should not be overrated. EGG is an important research tool, but a clinical role still needs to be established.     

Congenital laryngeal stenosis; a rare cause of dyspnea in the newborn infant

Congenital laryngeal obstruction is a rare but serious cause of severe, often fatal, post partum asphyxia. The condition should be recognized and in most cases an artificial airway has to be established immediately because hypoxia allows little time for extensive evaluation. Thereafter a further diagnostic procedure by means of laryngobronchoscopy and contrast laryngography should be performed. The clinical picture of two cases with a congenital laryngeal stenosis is described and the initial therapeutic approach is discussed.     

In search of objective manometric criteria for colonic high-amplitude propagated pressure waves

Abstract The aims of this study were to explore all characteristics of high-amplitude propagated contractions (HAPCs) that would allow them to be distinguished from nonHAPC colonic pressure waves, and to develop computer algorithms for automated HAPC detection. Colonic manometry recordings obtained from 24 healthy volunteers were used. Automated analysis was performed to detect propagated pressure waves and to determine their amplitude, duration and area under the curve (AUC). For each of these variables distribution plots were made. Automated HAPC counts were compared to visual counts by experienced investigators. Distribution plots of 141093 colonic pressure waves lacked a bimodal pattern, as was also the case for propagated contractions (n = 8758). With increasing high-amplitude thresholds for HAPC detection, a gradual decrease in the automatically detected HAPC number was observed. These findings precluded determination of a threshold. Taking visually detected HAPCs as reference, amplitude thresholds of 100 mmHg in two channels, and 80 mmHg in one channel yielded the highest sensitivity (92%). In conclusion, objective criteria to distinguish HAPCs from other propagated pressure waves on the basis of their amplitude, duration or AUC do not exist. Automated detection of HAPCs using empirically derived criteria leads to an acceptable degree of correlation with visually detected HAPCs.     

Potential of genetic translational research in gastroenterology

The concept that genetic variation underlies inter-individual differences in drug response and contributes to the risk of developing common, complex disorders is expanding rapidly. Consequently the interest in genetic translational research has increased. Polymorphic DNA markers, either microsatellites or single nucleotide polymorphisms (SNPs), are used to assess genetic identities and track genetic differences between individuals. Given their abundance and stability, SNPs hold great promise as markers for mapping disease susceptibility loci for common, complex disorders by association studies. For this purpose the development of inexpensive, accurate, high-throughput methods for scoring large numbers of SNPs from hundreds of patients and controls is critical. Furthermore, gene expression profiling using DNA microarrays is likely to become a useful diagnostic tool enabling classification of disease phenotype based on molecular basis of disease pathogenesis, revealing information that cannot be obtained by histological assessment. Moreover, identification of differentially expressed genes in affected versus control tissue or over time in affected tissue will lead to better understanding of the mechanisms underlying disease and ultimately to the development of more effective drug therapies. To illustrate the potential of genetic translational research, several examples in the field of gastroenterology are described.     

Prolonged manometric recordings of oesophagus and lower oesophageal sphincter in achalasia patients

BACKGROUND AND AIMS: Conventional short term manometry is a valuable tool in the diagnosis of achalasia but the technique may fail to detect intermittent motor events. The aim of this study was to investigate the pattern of lower oesophageal sphincter (LOS) and oesophageal pressures during prolonged recording in patients with achalasia. METHODS: Eleven patients with idiopathic achalasia were studied. Prolonged combined oesophageal pH and manometric recordings of the pharynx, LOS, and stomach were performed using a pH glass electrode and a multiple lumen assembly incorporating a Dent sleeve connected to a portable water perfused manometric system. RESULTS: LOS pressure varied during the day. Postprandial LOS pressures were lower than those recorded preprandially (1.2 v 1.8 kPa; p=0.005) and basal LOS pressures were significantly higher during phase III of the migrating motor complex than during the subsequent phase I (3.3 v 1.8 kPa; p=0.028). Complete LOS relaxations were occasionally observed in seven patients (0.48/h). Complete LOS relaxations were longer in duration than incomplete LOS relaxations (10.8 v 2.8 s; p=0.01) and 57% of complete relaxations fulfilled the criteria of a transient LOS relaxation (TLOSR). Complete LOS relaxations were associated with oesophageal pressure waves with higher amplitudes and longer durations. In addition, a higher proportion of these oesophageal pressure waves were spontaneous (55.6% v 0%; p<0.02) and multipeaked (72.7% v 0%). During prolonged manometry, high amplitude oesophageal pressure waves (>10 kPa) were recorded in six patients and retrograde oesophageal pressure waves in four, phenomena which were not observed during short term manometry. CONCLUSION: In contrast with short term stationary manometry, prolonged manometry in achalasia patients revealed the occurrence of complete LOS relaxations, TLOSRs, variations in LOS pressure associated with a meal or phase III, and high amplitude and retrograde oesophageal pressure waves.     

Zellweger syndrome in a preterm,small for gestational age infant

Summary A preterm (gestational age 34 weeks), small for gestational age infant (birth weight <P _2,3) is described. Because of unexplained slightly disturbed liver function tests at age 2 months, extensive metabolic examinations were performed. Elevated blood levels of very long-chain fatty acids, pipecolic acid and abnormal levels of bile acid intermediates were detected, suggesting a peroxisomal disorder. The plasmalogen content of erythrocytes was decreased. Morphologically distinct peroxisomes were absent in the liver. In fibroblasts an accumulation of very long-chain fatty acids, decreased activity of acyl-CoA: dihydroxyacetone phosphate acyltransferase and impairedde novo biosynthesis of plasmalogens was found.In summary, a mild variant of the classical cerebro-hepato-renal syndrome of Zellweger was found without the characteristic clinical facial signs.