Outcome and management of isolated severe renal pelvis dilatation detected at postnatal screening

The aim of this study was to evaluate the incidence and outcome of isolated severe renal pelvis dilatation (RPD; APD > 15 ≤ 20 mm) in an unselected population of 2-month-old infants prospectively followed up for 12–14 months of life. Isolated severe renal pelvis dilatation was detected in 46 of the 11,801 (0.39%) infants screened. Nephro-urological investigations were initiated if RPD persisted, or if urinary tract infection (UTI) occurred during follow-up, and antibiotic therapy was administered only when UTI occurred. At follow-up, RPD persisted in 24 infants. Of these, 8 infants presented with vesico-ureteral reflux (VUR) of grade ≥ 3 and 16 with ureteropelvic junction obstruction (UPJO). Incidence of UTI was significantly higher (p < 0.001) in infants of the study group than in infants of the control group (13.9 vs 2.5%). Our data suggest that isolated severe RPD may be a self-limiting condition and that antibiotic prophylaxis (AP) for the prevention of UTI should not be performed. Considering RDP resolution and the incidence of UTI during follow-up, investigations for uropathy in infants with isolated, severe RPD are justified in persistent cases, or when UTI occurs during follow-up. Careful clinical monitoring for signs of UTI and treatment of each episode of UTI may be sufficient and safe.     

Outcome and management of isolated moderate renal pelvis dilatation detected at postnatal screening

The aim of this study was to evaluate the incidence and outcome of isolated moderate renal pelvis dilatation (RPD) [anterior–posterior diameter (APD) 10–15 mm] in an unselected population of 2-month-old infants prospectively followed for up to 12–14 months of life. Isolated moderate renal pelvis dilatation was detected in 282 of the 11,801 (2.4%), infants screened; 240 infants with normal renal ultrasound were enrolled as the control group. Resolution of RPD was considered when an APD ≤ 5 mm was found on two consecutive sonograms. Urological investigations were initiated if the RPD persisted or if urinary tract infection (UTI) occurred during follow-up, and antibiotic therapy was administered only when UTI occurred. The events of interest were resolution of the RPD, presence of uropathy and UTI. At follow-up, RPD persisted only in 18 infants; of these, four infants were diagnosed with vesicoureteral reflux (grade 1–3) and 14 with ureteropelvic junction obstruction. Of the 223 infants with RPD and 230 control infants who completed follow-up, UTI occurred in 3.6 and 2.5%, respectively. The incidence rate of UTI per 1000 person-months was 5.98 episodes in the patient group and 5.22 episodes in the control group. The rate ratio was 1.146 (95% confidence interval 0.389–3.54, p = 0.8). Our data suggest that isolated moderate RPD is essentially a self-limiting condition and that antibiotic prophylaxis for the prevention of UTI should not be performed. A non-invasive ultrasound scan performed during the follow-up is sufficient to diagnose a potentially dangerous and persistent RPD.     

Flamingo cadherin: a putative host receptor for Streptococcus pneumoniae

Streptococcus pneumoniae fructose bisphosphate aldolase (FBA) is a cell wall-localized lectin. We demonstrate that recombinant (r) FBA and anti-rFBA antibodies inhibit encapsulated and unencapsulated S. pneumoniae serotype 3 adherence to A549 type II lung carcinoma epithelial cells. A random combinatorial peptide library expressed by filamentous phage was screened with rFBA. Eleven of 30 rFBA-binding phages inhibited 90% of S. pneumoniae adhesion to A549 cells. The insert peptide sequence of 9 of these phages matched the Flamingo cadherin receptor (FCR) when aligned against the human genome. A peptide comprising a putative FBA-binding region of FCR (FCRP) inhibited 2 genetically and capsularly unrelated pairs of encapsulated and unencapsulated S. pneumoniae strains from binding to A549 cells. Moreover, FCRP inhibited S. pneumoniae nasopharyngeal and lung colonization and, possibly, pneumonia development in the mouse intranasal inoculation model system. These data indicate that FBA is an S. pneumoniae adhesin and that FCR is its host receptor.     

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing? technology

Background  

Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1–2 are derived from CYP2A7, and exons 3–9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology.     

Hypoxia,tumour-associated macrophages,microvessel density,VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival

Introduction  

Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer.     

Cognitive-behavioral therapy for panic disorder in patients being treated for alcohol dependence: Moderating effects of alcohol outcome expectancies

Anxiety disorders commonly co-occur with alcohol use disorders and reliably mark a poor response to substance abuse treatment. However, treating a co-occurring anxiety disorder does not reliably improve substance abuse treatment outcomes. Failure to account for individual differences in the functional dynamic between anxiety symptoms and drinking behavior might impede the progress and clarity of this research program. For example, while both theory and research point to the moderating role of tension-reduction alcohol outcome expectancies (TR-AOEs) in the association between anxiety symptoms and alcohol use, relevant treatment studies have not typically modeled TR-AOE effects. We examined the impact of a hybrid cognitive-behavioral therapy (H-CBT) treatment for panic disorder (independent variable) on response to a community-based alcohol dependence treatment program (dependent variable) in patients with higher vs. lower TR-AOEs (moderator). The H-CBT treatment was generally effective in relieving participants' panic symptoms relative to controls. However, TR-AOEs interacted with study cohort (H-CBT vs. control) in predicting response to substance abuse treatment. As expected, the H-CBT was most effective in improving alcohol use outcomes among those with the highest TR-AOEs. The study's primary methodological limitations are related to the quasi-experimental design employed.     

Tumor-targeting nanodelivery enhances the anticancer activity of a novel quinazolinone analogue

GMC-5-193 (GMC) is a novel anticancer small-molecule quinazolinone analogue with properties that include antimicrotubule activity and inherent fluorescence. The aim of this study was to produce and optimize a systemically administered liposomal formulation for tumor-targeting delivery of GMC to enhance the anticancer effect of this compound and evaluate its bioefficacy. GMC was encapsulated within a cationic liposome, which was decorated on the surface with an anti-transferrin receptor single-chain antibody fragment (TfRscFv) as the tumor-targeting moiety to form a nanoscale complex (scL/GMC). Confocal imaging of fluorescent GMC uptake in a human melanoma cell line, MDA-MB-435, showed higher cellular uptake of GMC when delivered via the liposome complex compared with free GMC. Delivery of GMC by the tumor-targeting liposome nanoimmunocomplex also resulted in a 3- to 4-fold decrease in IC(50) values in human cancer cells [DU145 (prostate) and MDA-MB-435] compared with the effects of GMC administered as free GMC. In addition, the GMC nanoimmunocomplex increased the sensitivity of cancer cells to doxorubicin, docetaxel, or mitoxantrone by approximately 3- to 30-fold. In the MDA435/LCC6 athymic nude mice xenograft lung metastases model, GMC was specifically delivered to tumors by the nanoimmunocomplex. These data show that incorporation of small-molecule therapeutic GMC within the tumor-targeting liposome nanocomplex enhances its anticancer effect.     

Psychological problems in gastroenterology outpatients: A South Australian experience. Psychological co-morbidity in IBD,IBS and hepatitis C

Background

In independent studies, IBD, IBS and HCV have each been associated with a substantially increased risk of psychological problems such as depression and anxiety and impairment of quality of life compared to the general healthy population. However, the relative psychological burden for each of these diagnoses is unknown as it has never been compared contemporaneously at one institution. Current local data are therefore needed to enable an evidence-based allocation of limited clinical psychological resources.

Methods

Overall, 139 outpatients (64 IBD, 41 HCV, and 34 IBS) were enrolled in this cross-sectional study. The HADS, SCL90, SF-12 and appropriate disease-specific activity measures were administered. Differences between groups were assesed with ANOVA, the Chi-Square test and the independent samples t-test (two-tailed).

Results

Each of the three groups had significantly lower quality of life than the general population (p < 0.05). Overall, a total of 58 (42%) participants met HADS screening criteria for anxiety and 26 (19%) participants for depression. The HCV group had a significantly higher prevalence of depression than either of the other groups (HCV = 34%, IBS = 15% and IBD = 11%, p = 0.009). In the SCL90, the three disease groups differed on 7 out of 12 subscales. On each of these subscales, the HCV group were most severely affected and differed most from the general population.

Conclusion

Patients with these common chronic gastrointestinal diseases have significant impairment of quality of life. Anxiety is a greater problem than depression, although patients with HCV in particular, should be regularly monitored and treated for co-morbid depression. Evaluation of specific psychological interventions targeting anxiety is warranted.