Identification of markers for Helicobacter pylori strains isolated from children with peptic ulcer disease by suppressive subtractive hybridization

Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex- and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.     

Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis

KRAS somatic mutations are the main predictive factor for non response to EGFR-targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination.     

Psychiatrie phénoménologique,médecine de la personne et big data

Next to psychoanalysis, neurosciences and cognitivism is a historical trend in psychiatry, which lies in the minority and is not taught much: phenomenological psychiatry. Inspired by Husserl and Merleau-Ponty, it echoed in Ricoeur's work; carried by Binswanger, Minkowski, Tatossian, Lanteri-Laura, it still has its promoters and its researchers. The pathology thought as a lost of “pouvoir-être” allows oneself to consider the patient as his or her own norm. The whole analysis of the diagnostical process (between intuition and inference) and the “constructions” of the various theoretical resorts leading to practice are thus put to work. We will state how the everyday life of clinical psychiatry borrows more, sometimes without knowing it, from phenomenological psychiatry than from neurosciences or from the tools of clinical standardisation. Then, we would like to look into the possibility that this psychiatry inspired by philosophy might contribute to the dialogue between this medicine known as personalized or precision medicine (use of big data to come) as renewal of the Evidence-Based Medicine and, on the other side, the medicine of the person (cf. francophone observatory of the medicine of the person), which links with the Values Based Medicine we will examine.     

Allergen extracts for immunotherapy: to mix or not to mix?

Allergen immunotherapy (AIT) is established as a curative treatment for allergic rhinitis, asthma, as well as insect venom allergy. AIT is based on the administration of natural allergen extracts via the subcutaneous or sublingual routes to reorient the immune system towards tolerogenic mechanisms. In this regard, since many patients are poly-allergic, mixtures of allergen extracts are often used with a potential risk to cause allergen degradation, thereby affecting treatment efficacy. Herein, we discuss the advantages and drawbacks of mixing homologous (i.e., related) or heterogeneous (i.e., unrelated) allergen extracts. We provide evidence for incompatibilities between mixes of grass pollen and house dust mite extracts containing bodies and feces, and summarize critical points to consider when mixing allergen extracts for AIT.     

Six-month prognosis of patients with lung cancer admitted to the intensive care unit

Background

Intensive care unit (ICU) admission of patients with lung cancer remains debated because of the poor short-term prognosis. However, ICU admission of such patients should also be assessed on the possibility to administer specific anticancer treatment and the long-term outcome thereafter.

Objectives

To identify predictive factors of hospital and 6-month mortality in critically ill lung-cancer patients.

Design and setting

Retrospective study conducted in the ICU of a university hospital.

Patients

One hundred five consecutive lung-cancer patients included between 1 January 1997 and 31 December 2006.

Interventions

None.

Results

Of the 105 patients (mean age 64.8 years), 87 (83%) had a non-small cell lung cancer (NSCLC). Extensive disease was diagnosed in 85 patients (83%) (NSCLC stages IIIB and IV or disseminated small cell lung cancer). The main reasons for ICU admission were acute respiratory failure (59%) and/or hemoptysis (45%). Forty-three patients (41%) needed mechanical ventilation (MV). The ICU, hospital and 6-month mortality rates were 43, 54 and 73%, respectively. A performance status (PS) ≥2 [odds ratio OR = 3.6 (95% confidence interval CI (1.5–8.7)] and acute respiratory failure [OR = 3.5 (95% CI (1.5–8.4)] predicted hospital mortality. In a multivariate Cox model, the cancer progression [hazard ratio HR = 6.1 (95% CI 2.2–17)] and the need for MV [HR = 3.6 (95% CI 1.35–9.4)] were independently associated with 6-month mortality. Two-thirds of the ICU survivors were able to receive anticancer treatment.

Conclusions

ICU admission should be considered in selected patients with lung cancer (PS <2, no cancer disease progression).     

Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

Background  

Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.     

Imatinib and solid tumours

Imatinib mesylate (Gleevec, Glivec, Novartis, Basel, Switzerland) is a small molecule inhibitor of the tyrosine kinase c-abl, c-kit and the platelet derived growth factor receptor (PDGFR). Imatinib was developed for the treatment of chronic myeloid leukaemia (CML) but was approved both in Europe and the US fro the treatment of CML and gastrointestinal stromal tumors (GIST). Given its activity against both c-kit and PDGFR kinases and its remarkable safety profile, imatinib has been 'tried' in several solid tumors; results however have often been deceiving. We review the current data regarding the activity of imatinib in solid tumors, including GIST.