Inhibiteurs de la pompe à protons: la nouvelle génération

Acta Endoscopica - De nos jours, les patients en prise avec une pathologie d’intensité moyenne à forte en rapport avec l’hyperacidité sont traités de façon...     

Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides

Circulating angiotensin-1-converting enzyme (ACE) is a highly heritable trait, and a major component of the genetic variance maps to the region of the ACE gene. The strong effect of the locus, and the interest in ACE as a candidate gene for cardiovascular disorders, has led to extensive investigation of its relationship to the ACE phenotype, providing one of the most complete examples of quantitative trait locus (QTL) analysis in humans. Resequencing of ACE followed by haplotype analysis in families of British and French origin has shown that the genetic variants that are primarily associated with the ACE trait map to an 18 kb interval flanked by two intragenic, ancestral recombination breakpoints. This critical interval contains dozens of ACE-associated variants in Caucasians, but identification of which of these directly influence ACE concentration is ambiguous because of the almost complete linkage disequilibrium in European populations. In a complementary sequencing and genotyping study of individuals from West African families, we show that this population has much greater haplotype diversity across the gene. Through analysis of the contrasting relationships of the trait phenotype with haplotypes that carry different allelic combinations from those observed in Caucasians, we demonstrate that (at least) two major intragenic sites within the critical interval and (at least) one minor promoter site are associated with the ACE quantitative trait through additive effects. These results point to the importance of analysing diverse populations with different gene genealogies in gene-association studies.     

Elderly-onset rheumatoid arthritis

The treatment of elderly-onset rheumatoid arthritis pursues the same objectives as in younger patients: to control the clinical manifestations, to prevent structural damage, to preserve function, and to decrease excess mortality. In the elderly, the presence of co-morbidities and increased rate of drug-related adverse effects raise specific therapeutic challenges. Nonsteroidal anti-inflammatory drugs are associated with cardiovascular, gastrointestinal, and renal adverse events. The role for corticosteroid therapy remains controversial. Although glucocorticoids provide a short-term decrease in clinical activity and probably a medium-term decrease in structural damage, these benefits are offset by numerous adverse effects. Methotrexate was effective in clinical trials and observational studies and did not produce a higher adverse event rate compared to younger patients, provided renal function was normal. Data on the efficacy of TNFα antagonists in therapeutic trials are available only for etanercept. Disease activity decreased and function improved. The adverse event rate was higher in older patients, but this was also true of the conventional drugs used as comparators. Registry data confirm that TNFα antagonist therapy is effective in RA. An increased rate of infections was found only in some registries. To combat the 2-fold cardiovascular risk increase associated with RA, disease activity should be stringently controlled and all cardiovascular risk factors managed aggressively.     

Randomised clinical trial of Hydrofiber dressing with silver versus povidone-iodine gauze in the management of open surgical and traumatic wounds

This prospective, randomised clinical trial compared pain, comfort, exudate management, wound healing and safety with Hydrofiber dressing with ionic silver (Hydrofiber Ag dressing) and with povidone-iodine gauze for the treatment of open surgical and traumatic wounds. Patients were treated with Hydrofiber Ag dressing or povidone-iodine gauze for up to 2 weeks. Pain severity was measured with a 10-cm visual analogue scale (VAS). Other parameters were assessed clinically with various scales. Pain VAS scores decreased during dressing removal in both groups, and decreased while the dressing was in place in the Hydrofiber Ag dressing group (n = 35) but not in the povidone-iodine gauze group (n = 32). Pain VAS scores were similar between treatment groups. At final evaluation, Hydrofiber Ag dressing was significantly better than povidone-iodine gauze for overall ability to manage pain (P < 0.001), overall comfort (P < or = 0.001), wound trauma on dressing removal (P = 0.001), exudate handling (P < 0.001) and ease of use (P < or = 0.001). Rates of complete healing at study completion were 23% for Hydrofiber Ag dressing and 9% for povidone-iodine gauze (P = ns). No adverse events were reported with Hydrofiber Ag dressing; one subject discontinued povidone-iodine gauze due to adverse skin reaction. Hydrofiber Ag dressing supported wound healing and reduced overall pain compared with povidone-iodine gauze in the treatment of open surgical wounds requiring an antimicrobial dressing.     

Outcome of common iliac arteries after aortoaortic graft placement during elective repair of infrarenal abdominal aortic aneurysms

HYPOTHESIS: Supplemental oxygen can reduce intimal hyperplasia (IH) after stent deployment in a rabbit model. BACKGROUND: Endovascular stent placement is technically feasible, but long-term durability in vessels outside the aortoiliac system is compromised with postinterventional IH, which causes restenosis and failure of the arterial conduit. METHODS: Groups (n = 4 to 6) of female New Zealand white rabbits underwent placement of a 3-mm intraaortic stent with laparotomy and were placed in either normoxic (21% inspired oxygen concentration) or supplemental-oxygen (40% inspired oxygen concentration) environments for 0, 7, 14, and 28 days. The transarterial wall oxygen gradient was measured at 0, 7, and 28 days with an oxygen microelectrode. 5-Bromo-2'deoxyuridine (BrdU) was injected into the peritoneum before death to assess cellular proliferation. Aortic specimens were harvested en bloc and sectioned for analysis of cellular proliferation and intimal thickness. RESULTS: Intraaortic stent placement significantly decreased the transarterial wall oxygen gradient in the outer 70% of the vessel wall and was easily reversed at 7, 14, and 28 days with application of supplemental oxygen. Cellular proliferation was significantly decreased at 14 days (0.5% +/- 0.001% versus 2.3% +/- 0.002%; P <.001) and 28 days (0.4% +/- 0.001% versus 1.0% +/- 0.001%; P <.025) as measured with count of nuclei staining for 5-Bromo-2'deoxyuridine in the intima and media. Intimal thickness was significantly decreased at 28 days in oxygen-supplemented rabbits (intimal area/medial area = 0.50 +/- 0.07) as compared with controls (intimal area/medial area = 0.89 +/- 0.11; P <.025). CONCLUSION: This study shows the ability of supplemental oxygen to reverse arterial wall hypoxia, decrease cellular proliferation, and control IH at the deployment site of an intraarterial stent in a rabbit model. Forty-percent supplemental oxygen suppresses IH by 44% at 28 days as compared with normoxic control values. Cellular proliferation is reduced four-fold at 14 days and two-fold at 28 days in oxygen-supplemented rabbits as compared with control media after deployment. The clinical implications of these findings are significant, especially as the role of endovascular interventions continues to expand.     

Tocilizumab controls bone turnover in early polymyalgia rheumatica

ObjectivesThis study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR).MethodsTwenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients.ResultsPMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P < 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P = 0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r = 0.255 at W0 versus r = 0.641 in healthy controls) and its correction after treatment (r = 0.760 at W12 and r = 0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy.ConclusionsControl of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.     

Reproducibility and diagnostic value of a new method using ratios to diagnose anterior atlanto-axial subluxation on plain radiographs

ObjectivesMeasures on conventional radiography are used to detect, especially in rheumatoid arthritis, upper cervical spine instabilities (CSIs) with the anterior and posterior atlanto-dental intervals (AADI and PADI) measurements. Our objective was to evaluate the diagnostic performance and reliability of AADIs and PADIs extrapolated based on ratios in assessing anterior atlanto-axial subluxation (aAAS) when plain radiographs do not allow the measures.MethodsRadiographies of 119 patients were randomly selected. Two blinded observers performed two measurements of the odontoid sagittal diameter (O), axis body base sagittal diameter (C2), AADI, PADI, Clark station and Ranawat index, and the AADI/O, AADI/C2, PADI/O and PADI/C2 ratios were calculated. The diagnostic value of AADI and PADI extrapolated from the AADI/O, AADI/C2, PADI/O and PADI/C2 ratios was evaluated using ROC curves, with AADI > 2.9 mm used as the gold standard.ResultsAmong the 119 patients, 12 patients had aAAS (AADI > 2.9 mm), 6 of them had severe aAAS (AADI > 8.9 mm and/or a PADI < 14 mm), and 6 patients had vertical AAS (Clarks station = 2 or 3 and/or Ranawat index < 13 mm). The AADI extrapolated from the AADI/O and AADI/C2 ratios has excellent intra- and inter-observer reproducibility. The diagnostic value of the extrapolated AADI was high for aAAS (sensitivity 92%; specificity of 100%) and severe aAAS (sensitivity75%; specificity 100%). The diagnostic value of the extrapolated PADI was good but lower than the diagnostic value of the extrapolated AADI.ConclusionExtrapolated AADI can be used instead AADI to detect aAAS and severe aAAS.