Standardized classification unsuitable for spontaneous reporting: the example of osteonecrosis of the jaw

Objective: This study assessed the impact of using a standardized definition of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the analysis of a spontaneous reporting database.

Methods: All notifications of osteonecrosis of the jaw (ONJ) in the French National Pharmacovigilance Database as of 31 December 2013 were analyzed. First, we considered all reports of ONJ with bisphosphonates as BRONJ. Second, we applied the 2014 definition of BRONJ from the American Association of Oral and Maxillofacial Surgeons (AAOMS), retaining only bisphosphonates as antiresorptive medication. In the absence of any one of these criteria, or missing data, cases were not considered as BRONJ.

Results: The first analysis found 158 cases of ONJ, among which 153 were associated with bisphosphonate use. The second analysis identified only 43 cases of BRONJ (28.1%).

Conclusion: The definition of BRONJ as laid down by the AAOMS is not suitable for use in spontaneous reporting database. The use of the AAOMS definition alone should be avoided, as it leads to the exclusion of over 70% of cases. When cases of ONJ are identified, all results should be presented including confirmed and excluded cases.     

Vitamin D3 Supplementation Alleviates Left Ventricular Dysfunction in a Mouse Model of Diet-Induced Type 2 Diabetes: Potential Involvement of Cardiac Lipotoxicity Modulation

Cardiovascular Drugs and Therapy - To evaluate the effectiveness of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse...     

Absence of human papillomavirus DNA detected by polymerase chain reaction in French patients with esophageal carcinoma

Recent studies have suggested that esophageal human papillomavirus infection could be a risk factor for esophageal squamous cell carcinoma. The aim of this study was to evaluate the prevalence of human papillomavirus DNA sequences in the esophagus of French patients with esophageal squamous cell carcinoma. Multiplex polymerase chain reactions with consensus primers directed to the L1 gene or specific primers for human papillomavirus types 6, 11, 16, 18, 31, and 33 directed to E6 gene (40 cycles followed by restriction mapping of the amplified products) were used to determine the presence of human papillomavirus DNA sequences in esophageal squamous cell carcinoma (n = 75), normal adjacent mucosa (n = 49), and metastatic lymphadenopathies (n = 5). As an internal control, a target located in the embryonic myosin heavy-chain gene was used in each reaction. Human papillomavirus DNA sequences could not be detected in any of the tumoral samples, the normal adjacent mucosa, or the metastatic lymphadenopathies. Human papillomavirus seems not to be implicated in esophageal carcinogenesis, at least in French patients, because the viral genomes are not associated with esophageal squamous cell carcinomas.     

Antioxidant effects and anti-elastase activity of the calcium antagonist nicardipine on activated human and rabbit neutrophils--a potential antiatherosclerotic property of calcium antagonists?

Activated neutrophils which produce certain proteases, such as elastase and reactive oxygen species (ROS) are involved in oxidative stress and inflammation. In the present study, we have shown that nicardipine, a calcium channel blocker, affects the release of elastase and superoxide anion radicals (O₂ ^–) in vitro during human and rabbit neutrophil respiratory bursts. The drug inhibited the release of elastase and O₂ ^– by fMLP (N-formyl-methionylleucin-phenylalaninin), calcium ionophore (A23187) and PMA (phorbol-myristate-acetate)-stimulated human and rabbit neutrophils. Besides the release of elastase, strongly inhibited in the fMLP and A23187 stimulated systems, nicardipine affected elastase and O₂ ^– in a dose-dependent manner. The corresponding 50% inhibitory concentration (IC₅₀) of nicardipine for elastase, released in PMA-stimulated human and rabbit neutrophils, was 15.95 ± 0.17 M and 18.06 ± 0.08 M, respectively, whereas for O₂ ^–, the IC₅₀ of nicardipine in PMA, fMLP and A23187-stimulated human and rabbit neutrophils was 55.41 ± 0.09 M and 58.43 ± 0.03 M, 45.21 ± 0.13 M and 37.19 ± 0.53 M, 33.54 ± 0.09 M and 30.54 ± 0.29, respectively. The mechanisms underlying the inhibition of elastase and superoxide anion radicals by nicardipine appear related to an inhibiting effect on the mobilisation of cytosolic calcium and on activation of protein kinase C (PKC). These antioxidant and anti-elastasic activities contribute to the properties of nicardipine, as positive side effects of its antihypertensive activity and may be useful to prevent inflammatory disorders (tissue damage, oxidative injury) involved in the pathogenesis of hypertension.     

Rheumatoid flat foot and deformity of the first ray

OBJECTIVE: To study the relationship between flat foot and forefoot deformities in rheumatoid arthritis (RA) in order to improve understanding of the progression of deformity and thus provide more appropriate treatment. METHODS: Anteroposterior and lateral weight-bearing radiographs were obtained of 308 feet of patients with RA and 202 feet of patients with neck pain (control feet). RESULTS: In women with RA, we observed with disease duration an increased frequency of flat foot that was correlated with first ray deformity (chiefly metatarsus primus adductus) and severe stages of disability. Flat foot increased very markedly after 3-4 years of disease duration. In control women, flat feet were more frequent after the age of 50 years. CONCLUSION: In RA the inflammatory and mechanical factors leading to foot deformity must receive early medical treatment to avoid progressive hindfoot deformities that lead to disability.     

A prospective national study on colonoscopy and sigmoidoscopy in 2000 in France

AIM: The aim of this study was to evaluate the practice of colonoscopy and sigmoidoscopy in France in 2000. METHODS: A prospective study was conducted in November 2000 using questionnaires sent to all gastroenterologists practicing in France (N=2858) who were asked to reply to items concerning colonoscopies and sigmoidoscopies performed on two workdays chosen in advance. The response rate was 32.8%. Data were extrapolated to establish estimates for the entire year. RESULTS: An estimated 894000 colonoscopies and 115320 sigmoidoscopies were performed in 2000. Single-use material was used in 22.1% of the procedures. Indications for endoscopy were mainly hematochezia (21.6%), gastrointestinal symptoms (35%) and surveillance of patients with a history of previous polypectomy (15%). Colorectal cancer screening was the indication for 20% of colonoscopies. Abnormal findings were reported for 54.8% of the endoscopies (polyps for 287218 procedures and cancer for 32799). Failure was noted in 4.9% of colonoscopies. The complication rate was 0.48%. Most polyps were adenomas (64.4%) or hyperplasic polyps (28.1%). The overall estimated number of colonoscopies with polypectomy was 224133. CONCLUSION: In 2000 there was an increased rate of colonoscopy for colorectal cancer screening (20%) but an overall decrease (2.5%) in the total number of colonoscopies compared to 1999. Abnormal findings were disclosed by 54.8% of the procedures. Extrapolation from these data indicates that colonoscopic screening enabled the diagnosis of 32799 colorectal cancers.