Status of bacterial colonization, Toll-like receptor expression and nuclear factor-kappa B activation in normal and diseased human livers

Epidemiological data on bacterial translocation (BT), colonization and inflammation in normal human livers is lacking. In this study we investigated the status of bacterial colonization and inflammation in the normal, cirrhotic primary biliary cirrhosis (PBC), and nonalcoholic steatohepatitis (NASH) human liver tissues. Comparatively normal livers showed increased bacterial colonization than PBC and NASH. We analyzed mRNA levels of Toll-like receptors (TLR) 2 and TLR4, and protein levels of TLR4. Phosphorylated IKKα (pIKKα) protein estimation served as a marker for nuclear factor-kappa B (NF-κB) activation. In spite of the increased bacterial colonization in normal liver tissues, lower levels of TLR2/4 mRNA and TLR4 and pIKKα proteins were found compared to PBC and NASH indicating the maintenance of suppressed inflammation and immune tolerance in normal livers. To our knowledge, this is the first clinical evidence showing suppressed inflammation despite bacterial colonization in normal human livers thus maintaining liver immune homeostasis.     

Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe

Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related "clonal group A," a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans.     

Multiple Broad-Spectrum Beta-Lactamase Targets for Comprehensive Surveillance

Real-time PCR testing for bla_KPC, bla_NDM, bla_VIM, bla_IMP, and bla_CTX-M was performed on rectal swabs obtained from residents of two long-term acute-care facilities. While bla_KPC was detected in 69/102 swabs (67.6%), testing for four other targets increased the positivity rate for a broad-spectrum β-lactamase to 73.5% (McNemar''s P = 0.03).     

Image-guided cerebrospinal fluid shunting in children: catheter accuracy and shunt survival

Object Cerebrospinal fluid shunt placement has a high failure rate, especially in patients with small ventricles. Frameless stereotactic electromagnetic image guidance can assist ventricular catheter placement. The authors studied the effects of image guidance on catheter accuracy and shunt survival in children. Methods Pediatric patients who underwent placement or revision of a frontal ventricular CSF shunt were retrospectively evaluated. Catheters were placed using either anatomical landmarks or image guidance. Preoperative ventricular size and postoperative catheter accuracy were quantified. Outcomes of standard and image-guided groups were compared. Results Eighty-nine patients underwent 102 shunt surgeries (58 initial, 44 revision). Image guidance was used in the placement of 56 shunts and the standard technique in 46. Shunt failure rates were not significantly different between the standard (22%) and image-guided (25%) techniques (p = 0.21, log-rank test). Ventricular size was significantly smaller in patients in the image-guided group (p < 0.02, Student t-test) and in the surgery revision group (p < 0.01). Small ventricular size did not affect shunt failure rate, even when controlling for shunt insertion technique. Despite smaller average ventricular size, the accuracy of catheter placement was significantly improved with image guidance (p < 0.01). Shunt accuracy did not affect shunt survival. Conclusions The use of image guidance improved catheter tip accuracy compared with a standard technique, despite smaller ventricular size. Failure rates were not dependent on shunt insertion technique, but an observed selection bias toward using image guidance for more at-risk catheter placements showed failure rates similar to initial surgeries.     

A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C

Overall treatment results of chronic hepatitis C have improved markedly with the introduction of pegylated interferon-alpha (PEG–IFN-) and ribavirin combination therapy. However, cure rates in the most common genotype 1 infection are still unsatisfactory. IFN- dose–response studies on viral kinetics suggest that inadequate dosing might be a key factor but drug levels have hardly been tested, which is in part due to difficulties in measuring this cytokine in patient samples. We have shown recently that hepatitis C virus (HCV) replicons are highly sensitive to IFN-. In this report we tested whether the replicon system could be used as a sensitive bioassay to determine the amount of biologically active IFN- in serum or heparinized plasma of patients under therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA was developed that carries the gene encoding the firefly luciferase. Dose response studies with IFN- demonstrate that the amount of expressed luciferase directly correlates with the level of HCV replication. By using this cell-based assay, serum samples of HCV patients treated with different types and doses of IFN- were analyzed in parallel to IFN- standards made by serial dilutions of the same type of IFN- the patient was treated with. Based on nonlinear logistic models serum concentrations corresponding to 1.3–19 U/ml were determined in patients under standard or high dose IFN- therapy, and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-. In conclusion, the HCV-replicon based bioassay allows determining the levels of biologically active IFN- in serum and heparinized plasma of patients under treatment.     

Sequence Analysis of the Haemagglutinin and Fusion Protein Genes of Peste-des-petits Ruminants Vaccine Virus of Indian Origin

The amino acid composition of the two surface proteins of peste-des-petits ruminants vaccine virus belonging to lineage four from India were deduced from the nucleotide sequence. The fusion (F) protein gene of PPRV Sungri/96 is 2405 nucleotides long and in relation to the length, it is 80 nucleotides longer than that of PPRV Nigeria/75/1 which are found to be present at the 5′UTR of this virus. The complete F gene alignment with other morbillivirus reveals a homology of 89% with PPRV/Nigeria/75/1 and 48–51% with other morbilliviruses. The F protein of PPRV Sungri/96 exhibited characteristics similarity to those of other morbillivirus F proteins. The overall amino acid similarity with its counterpart PPRV Nigeria/75/1 was 96%; with other morbilliviruses it is 65–74%. The PPRV Sungri/96 haemagglutinin (H) protein gene is 1954 nucleotides long and showed a sequence homology of 90.7% with PPRV/Nigeria/75/1 and with other morbilliviruses it ranged from 33% to 45%. At amino acids level, PPRV Sungri/96 showed a homology of 92.3% with PPRV/Nigeria/75/1 and 34–49% with other morbilliviruses. The phylogenetic tree constructed for F and H gene reveals four separate groups which is very similar to that found in other genes. To the best of our knowledge this is the first report describing the F and H genes of an Indian isolate. *The sequence data reported in this paper have been submitted to the GenBank and have been assigned the Accession Number: AY560591. P. Dhar and D. Muthuchelvan equally contributed to the work.     

Clinical experience with low profile fixed wire balloon catheter system for percutaneous transluminal coronary angioplasty

Clinical records of the first 45 consecutive patients (66 lesions) in whom the Probe TM a balloon on the wire, was used for percutaneous transluminal coronary angioplasty have been reviewed. The aim of this analysis was to establish the efficacy and safety of this device. Majority of the lesions taken up were considered severe and difficult to cross. The probe was the 1st catheter used in 51 lesions (77%) and in 15 lesions (23%) it was used after other balloon catheters. In 88% (58/66) of lesions treated the Probe reduced the stenosis to less than 50% of the luminal diameter. Of the 45 patients treated 39 (87%) had a successful result. Of the 19 patients with multiple lesions 74% (14/19) had complete revascularisation and in 16% (3/29) had the most significant vessel dilated. Two patients (3%) required urgent coronary artery bypass surgery for acute occlusions. There was no hospital death. Of 50 probe devices used 5 (10%) malfunctioned: the balloon ruptured (at 5 Bars pressure) in 2 instances, balloon twisted causing "Volvulous" in 1 and balloon failed to deflate in 2 cases. The probe has significant advantages over other balloon systems for treating severe coronary lesions because of its low profile. It is however a delicate catheter system and prone to malfunction if not handled with care. Our results show that it is an excellent system for opening difficult and tight coronary lesions.     

Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease

There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate-pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease.     

Meditation acutely improves psychomotor vigilance,and may decrease sleep need

Background  

A number of benefits from meditation have been claimed by those who practice various traditions, but few have been well tested in scientifically controlled studies. Among these claims are improved performance and decreased sleep need. Therefore, in these studies we assess whether meditation leads to an immediate performance improvement on a well validated psychomotor vigilance task (PVT), and second, whether longer bouts of meditation may alter sleep need.