Myocardial infarction and abnormal origin of the circumflex coronary artery

Abnormal origin of the circumflex coronary artery without any stenosis is generally considered benign and without any particular ischemic risk. We report a case of a 21 year old man who suffered a posterior lateral myocardial infarction with objective criteria: electrocardiographic, echocardiographic and isotopic. The patient received thrombolytic therapy at H2. Angiography showed an abnormal origin of the circumflex coronary artery which was free of any stenosis. Certain cases of the circumflex artery anomaly can, therefore, be complicated by myocardial infarction, and the benign nature of the anomaly needs to be re-examined.     

Erosive cheilitis as an early manifestation in DRESS syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a distinct part of severe cutaneous adverse reactions (SCARs). It is characterized by fever, rash, hematologic abnormalities, lymphadenopathy, or/and different degrees of visceral organ involvement. Its diagnosis is particularly challenging due to the variability of its clinical presentations and its long latency period (2–6 weeks). Allopurinol, an uric acid‐lowering drug, has been incriminated in several cases of allopurinol‐induced DRESS syndrome. Through this paper, we present a case of allopurinol‐induced DRESS syndrome with initial oral mucosal involvement. A 69‐year‐old female patient presented with an erosive cheilitis that started 1 week prior to his presentation. The cheilitis was associated with maculopapular rash and fever. She started taking allopurinol, as treatment of Gout, 6 weeks before hospitalization. The histologic findings obtained from skin biopsy were consistent with a toxic drug reaction. A complete blood count (CBC) showed a moderate eosinophilia. Alteration of renal function was also noted, and the diagnosis of allopurinol‐induced DRESS syndrome was made. Systemic corticosteroid therapy was therefore started. The patient completely recovered and had been healthy for 3 years before developing a recurrence after re‐challenge with allopurinol.     

Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix

Aberrant DNA methylation is an early event in carcinogenesis and could serve as an additional molecular marker for the early diagnosis. The study was performed to investigate the promoter methylation of DAPK1, CDH13, and TWIST1 genes in uterine cervix lesions in an effort to examine whether this epigenetic event is involved in the process of cervical carcinogenesis, and whether it might be used as a molecular marker of cervical lesions.We conducted a retrospective study of 60 uterine cervix specimens, including 8 normal tissue samples, 10 benign lesions, 28 precancerous lesions (CIN1-3), and 14 squamous cell carcinomas (SCC). DNA hypermethylation was investigated using methylation-specific PCR. Immunohistochemistry was used to find p16^INK4A overexpression.No hypermethylated promoters were detected in normal tissues and benign lesions. However, promoter hypermethylation of CDH13, TWIST1, and DAPK1 increased progressively from CIN1 to cancer, reaching values higher than 50% for cancer. DAPK1 and CDH13 displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia (p < 0.05). A statistically significant association was observed between p16^INK4A expression and hypermethylation of DAPK1, TWIST1, and CDH13 (p < 0.0001).Hypermethylation of CDH13, DAPK1, and TWIST1 promoters is an early event in the initiation and progression of cervix neoplasia. CDH13, DAPK1, and TWIST1 genes are potential biomarkers of cervical cancer risk.     

Familial Mediterranean fever in a large Lebanese family: multiple MEFV mutations and evidence for a Founder effect of the p.[M694I] mutation

Familial Mediterranean fever (FMF) is an autoinflammatory autosomal recessive disease characterized by recurrent fever crises and serous inflammation. The MEFV gene responsible for the disease was identified on chromosome 16, and 5 of the mutations discovered so far in the gene are most frequently encountered in FMF patients: p.[M694V], p.[V726A], p.[M680I] and p.[M694I] in exon 10, and p.[E148Q] in exon 2. The present work describes multiple MEFV mutations and the corresponding haplotypes for 31 FMF patients as well as 32 "healthy" individuals of a large consanguineous Lebanese family. The DNAs were screened for MEFV mutations, and determination of the corresponding haplotypes was performed for all individuals by genotyping 4 microsatellites surrounding the gene. Five different mutations were detected in this one family, which is unexpected in such a genetic isolate. A phenotypic variability was also observed. The haplotype carrying the p.[M694I] allele, detected in all the family branches, was well conserved and therefore seems to be the ancestral one.     

Topical application of dimethylbenz[a]anthracene results in the generation of multiple melanocytic nevi in C3H/HeN mice

Melanocytic nevi are a common dermatological problem for which there are few in vivo models. It has been postulated that environmental factors contribute to their development. Experiments were therefore conducted to determine whether application of dimethylbenz[a]anthracene (DMBA) to the skin of mice would result in the development of melanocytic nevi. One hundred microliters of a 0.1%, 0.5%, or 1.0% solution of DMBA was applied to the dorsal skin of C3H/HeN mice. The mice were then observed for the appearance of pigmented lesions. Histological examination revealed perifollicular accumulations of nevus cells, which were S-100-protein and HMB-45-positive, confirming their melanocytic origin. Pigmented lesions did not occur in animals treated with vehicle alone. Dose response studies revealed both greater numbers of nevi and lesions with larger diameters as the dose of DMBA was increased from 0.1% to 0.5%. In no instance was an invasive melanoma observed even after 40 weeks. The fact that melanocytic nevi can be produced by topical application of DMBA suggests that xenobiotics may play a previously unrecognized role in the development of this common benign neoplasm. Because this is one of the only animal models for melanocytic nevi, further examination of this model may facilitate identification of the molecular and biochemical mechanisms that lead to the development of pigmented nevi and the factors that promote their evolution into invasive melanomas.     

von Hippel-Lindau syndrome: molecular diagnosis of two Lebanese families and analysis of the genotype-phenotype correlation

The von Hippel-Lindau syndrome (VHL) is a dominantly transmitted hereditary disorder associating multisystemic tumors affecting mainly the central nervous system, the kidneys, the pancreas, as well as pheochromocytomas. Mutations of the tumor suppressor gene VHL on chromosome 3 are responsible for the disease. This article reports for the first time the study of two Lebanese VHL affected families, presenting particularly hemangioblastomas of the central nervous system. Two different mutations of the VHL gene, S65W and F76S, respectively identified in the two families, confirmed the clinical diagnosis of the patients. Molecular diagnosis was then performed for at risk members of these families. This article reveals the importance of molecular diagnosis for suspected patients and of presymptomatic diagnosis for at risk members, especially that a close follow-up of carriers allows an early detection of tumors and prevents the metastasis stage, the most common cause of death of these patients.