Treatment of sequelae of burns in children

Burn sequelae in children are conveyed in the form of retraction, deformity and growth problems together with dyschromia and trophic disorders. All the plastic surgical procedures can be used to correct them: full thickness or split thickness skin grafts, Z plasty and its derivatives (trident plasty, IC flaps), expansion, flaps, artificial skin, and dermabrasion. In most cases, these procedures will be combined. The aim of surgical treatment coordinated with rehabilitation is to restore the function, correct the deformities induced, improve the morphological aspect and permit normal growth. Good knowledge of the paediatric environment is, however, required to cope with the specificities of the child: treat the severe local inflammation, get the family to participate in the projects of rehabilitation, sometimes with the help of social services, maintain normal schooling, accompany the disorders in body schema, and, finally, prolong follow-up until growth is complete, a challenge in these patients who are often very young at the time of the accident.     

Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism

Muscular dystrophy is a general term encompassing muscle disorders that cause weakness and wasting, typically leading to premature death. Membrane instability, as a result of a genetic disruption within the dystrophin-glycoprotein complex (DGC), is thought to induce myofiber degeneration, although the downstream mechanism whereby membrane fragility leads to disease remains controversial. One potential mechanism that has yet to be definitively proven in vivo is that unregulated calcium influx initiates disease in dystrophic myofibers. Here we demonstrate that calcium itself is sufficient to cause a dystrophic phenotype in skeletal muscle independent of membrane fragility. For example, overexpression of transient receptor potential canonical 3 (TRPC3) and the associated increase in calcium influx resulted in a phenotype of muscular dystrophy nearly identical to that observed in DGC-lacking dystrophic disease models, including a highly similar molecular signature of gene expression changes. Furthermore, transgene-mediated inhibition of TRPC channels in mice dramatically reduced calcium influx and dystrophic disease manifestations associated with the mdx mutation (dystrophin gene) and deletion of the δ-sarcoglycan (Scgd) gene. These results demonstrate that calcium itself is sufficient to induce muscular dystrophy in vivo, and that TRPC channels are key disease initiators downstream of the unstable membrane that characterizes many types of muscular dystrophy.     

Effect of plant neutrophil elastase inhibitor on leucocyte migration, adhesion and cytokine release in inflammatory conditions

BACKGROUND AND PURPOSE

The serine and cysteine peptidase inhibitor, BbCI, isolated from Bauhinia bauhinioides seeds, is similar to the classical plant Kunitz inhibitor, STI, but lacks disulphide bridges and methionine residues. BbCI blocks activity of the serine peptidases, elastase (K_iapp 5.3 nM) and cathepsin G (K_iapp 160.0 nM), and the cysteine peptidase cathepsin L (K_iapp 0.2 nM). These three peptidases play important roles in the inflammatory process.

EXPERIMENTAL APPROACH

We measured the effects of BbCI on paw oedema and on leucocyte accumulation in pleurisy, both induced by carrageenan. Leucocyte–endothelial cell interactions in scrotal microvasculature in Wistar rats were investigated using intravital microscopy. Cytokine levels in pleural exudate and serum were measured by elisa.

KEY RESULTS

Pretreatment of the animals with BbCI (2.5 mg·kg⁻¹), 30 min before carrageenan-induced inflammation, effectively reduced paw oedema and bradykinin release, neutrophil migration into the pleural cavity. The number of rolling, adhered and migrated leucocytes at the spermatic fascia microcirculation following carrageenan injection into the scrotum were reduced by BbCI pretreatment. Furthermore, levels of the rat chemokine cytokine-induced neutrophil chemo-attractant-1 were significantly reduced in both pleural exudates and serum from animals pretreated with BbCI. Levels of interleukin-1β or tumour necrosis factor-α, however, did not change.

CONCLUSIONS AND IMPLICATIONS

Taken together, our data suggest that the anti-inflammatory properties of BbCI may be useful in investigations of other pathological processes in which human neutrophil elastase, cathepsin G and cathepsin L play important roles.     

Twenty-three novel BRCA1 and BRCA2 sequence variations identified in a cohort of Swiss breast and ovarian cancer families

BRCA1 and BRCA2 are the major genes predisposing to breast-ovarian cancer (i.e., breast or ovarian cancer or both). Since 1994, hundreds of distinct germline alterations have been reported in these two genes. Besides pathogenic mutations resulting in loss of function of the protein, an increased number of variants of unknown clinical significance have been described. In a cohort of 350 Swiss breast-ovarian cancer families, the systematic search for BRCA1/BRCA2 germline mutations was carried out using denaturating high-performance liquid chromatography as the first screening procedure. The screening strategy resulted in the identification of 23 alterations not previously reported: 9 in BRCA1 and 14 in BRCA2. By using the available tools to assign a functional role to newly identified sequence variations, 5 (22%) of these were classified as new disease-causing mutations, 5 (22%) were classified as benign polymorphisms, and the remaining 13 (56%) alterations were considered as unclassified variants. These data illustrate the major challenge for clinical oncologists currently facing the interpretation of alterations identified in BRCA1 or BRCA2. The key points are to classify these genetic variations as pathogenic mutations, benign polymorphisms, or variants of unknown clinical significance and to adequately use this information for the management of high-risk individuals and their families.     

The appropriateness of surveillance colonoscopy intervals after polypectomy

BACKGROUND:

Adherence to surveillance colonoscopy guidelines is important to prevent colorectal cancer (CRC) and unnecessary workload.

OBJECTIVE:

To evaluate how well Canadian gastroenterologists adhere to colonoscopy surveillance guidelines after adenoma removal or treatment for CRC.

METHODS:

Patients with a history of adenomas or CRC who had surveillance performed between October 2008 and October 2010 were retrospectively included. Time intervals between index colonoscopy and surveillance were compared with the 2008 guideline recommendations of the American Gastroenterological Association and regarded as appropriate when the surveillance interval was within six months of the recommended time interval.

RESULTS:

A total of 265 patients were included (52% men; mean age 58 years). Among patients with a normal index colonoscopy (n=110), 42% received surveillance on time, 38% too early (median difference = 1.2 years too early) and 20% too late (median difference = 1.0 year too late). Among patients with nonadvanced adenomas at index (n=96), 25% underwent surveillance on time, 61% too early (median difference = 1.85) and 14% too late (median difference = 1.1). Among patients with advanced neoplasia at index (n=59), 29% underwent surveillance on time, 34% too early (median difference = 1.86) and 37% later than recommended (median difference = 1.61). No significant difference in adenoma detection rates was observed when too early surveillance versus appropriate surveillance (34% versus 33%; P=0.92) and too late surveillance versus appropriate surveillance (21% versus 33%; P=0.11) were compared.

CONCLUSION:

Only a minority of surveillance colonoscopies were performed according to guideline recommendations. Deviation from the guidelines did not improve the adenoma detection rate. Interventions aimed at improving adherence to surveillance guidelines are needed.     

Factors associated with relapses among patients treated for acute urticaria

The benefit of corticosteroids in acute urticaria is controversial. Our objective was to determine the factors associated with relapses in patients presenting with acute urticaria. A retrospective observational study, including all patients with acute urticaria who visited the angioedema reference center of Academic Public Hospitals – Saint‐Antoine in Paris between January 2015 and June 2017, was conducted. The study inclusion criterion was a diagnosis of acute urticaria in an adult patient. The urticaria was spontaneous or inducible urticaria. The primary outcome was relapse at day 7 and the secondary outcome was relapse at week 6. A total of 184 patients with a first episode of acute urticaria were included. Most of the patients were female (66%) with a mean age of 42 ± 16 years. Corticosteroid administration for treatment of acute urticaria was used in 102 (55%) patients. Overall, 85 (46%) patients had relapses after less than 7 days whereas 168 (91%) patients had relapses after more than 6 weeks. In univariate analysis, the rate of corticosteroid administration was significantly higher in cases of relapse after less than 7 days. No difference in relapse rates after more than 6 weeks appeared. In the multivariate analysis, the independent factor associated with relapses after less than 7 days was the administration of corticosteroids as treatment of acute urticaria (odds ratio, 1.93; 95% confidence interval, 1.06–3.57; P = 0.03). The prevalence of corticosteroid administration for patients with acute urticaria was high. Corticosteroid administration was an independent risk factor associated with relapses after less than 7 days.     

RAW TROPICAL OYSTERS AS VEHICLES FOR MULTIDRUG-RESISTANT Vibrio parahaemolyticus

The following study aimed to determine the antimicrobial susceptibility profile of Vibrio parahaemolyticus strains from fresh and frozen oysters Crassostrea rhizophorae sold in Fortaleza-Brazil. An antibiogram was performed on 87 isolates using nine antibiotics: gentamicin (Gen 10 µg), ampicillin (Amp 10 µg), penicillin G (Pen 10U), ciprofloxacin (Cip 5 µg), chloramphenicol (Chl 30 µg), nalidixic acid (Nal 30 µg), tetracycline (Tet 30 µg), vancomycin (Van 30 µg) and erythromycin (Ery 15 µg). All strains were resistant to at least one antibiotic, and 85 (97.7%) were multi-resistant, with predominance of the Van+ Pen+Amp resistance profile (n = 46). Plasmid resistance to Pen, Amp and Ery was detected. Thus, the risk that raw oyster consumption poses to the health of consumers is highlighted, due to the fact that these bivalves may host antibacterial-resistant microorganisms.