Colonic volvulus is the third leading cause of colonic obstruction worldwide, occurring at two principal locations: the sigmoid colon and cecum. In Western countries, sigmoid volvulus preferentially affects elderly men whereas cecal volvulus affects younger women. Some risk factors, such as chronic constipation, high-fiber diet, frequent use of laxatives, personal past history of laparotomy and anatomic predispositions, are common to both locations. Clinical symptomatology is non-specific, including a combination of abdominal pain, gaseous distention, and bowel obstruction. Abdominopelvic computerized tomography is currently the gold standard examination, allowing positive diagnosis as well as detection of complications. Specific management depends on the location, patient comorbidities and colonic wall viability, but treatment is an emergency in every case. If clinical or radiological signs of gravity are present, emergency surgery is mandatory, but is associated with high morbidity and mortality rates. For sigmoid volvulus without criteria of gravity, the ideal strategy is an endoscopic detorsion procedure followed, within 2 to 5 days, by surgery that includes a sigmoid colectomy with primary anastomosis. Exclusively endoscopic therapy must be reserved for patients who are at excessive risk for surgical intervention. In cecal volvulus, endoscopy has no role and surgery is the rule.

While type 1 hyperlipidemia is associated with lipoprotein lipase or apoCII deficiencies, the etiology of type 5 hyperlipidemia remains largely unknown. We explored a new candidate gene, APOA5, for possible causative mutations in a pedigree of late-onset, vertically transmitted hyperchylomicronemia. A heterozygous Q139X mutation in APOA5 was present in both the proband and his affected son but was absent in 200 controls. It was subsequently found in 2 of 140 cases of hyperchylomicronemia. Haplotype analysis suggested the new Q139X as a founder mutation. Family studies showed that 5 of 9 total Q139X carriers had hyperchylomicronemia, 1 patient being homozygote. Severe hypertriglyceridemia in 8 heterozygotes was strictly associated with the presence on the second allele of 1 of 2 previously described triglyceride-raising minor APOA5 haplotypes. Furthermore, ultracentrifugation fraction analysis indicated in carriers an altered association of Apoa5 truncated and WT proteins to lipoproteins, whereas in normal plasma, Apoa5 associated with VLDL and HDL/LDL fractions. APOB100 kinetic studies in 3 severely dyslipidemic patients with Q139X revealed a major impairment of VLDL catabolism. Lipoprotein lipase activity and mass were dramatically reduced in dyslipidemic carriers, leading to severe lipolysis defect. Our observations strongly support in humans a role for APOA5 in lipolysis regulation and in familial hyperchylomicronemia. IntroductionRaised plasma triglyceride (TG) levels are an independent risk factor for coronary artery disease (1) and are influenced by both genetic and environmental factors. Severe hypertriglyceridemia (HTG) is a general condition with a few well-documented genetic contributors, including lipoprotein lipase (LPL), APOC2, and APOE, as well as environmental factors such as diet and/or conditions such as pregnancy and diabetes (2-5). While genetic factors account for a large proportion of the rare type 1 hyperlipidemia, the complex interaction between genetics and environment is only partly understood in the more common type 5 hyperlipidemia.A strong candidate for severe HTG is the recently discovered human apolipoprotein A-V (APOA5) gene based on its profound modulation of plasma TG concentration. In mice, apoa5 overexpression lowered plasma TG concentration (6-8) whereas mice lacking Apoa5 had a 4-fold increase in plasma TG concentration (6). In humans, independent studies have demonstrated that variant haplotypes with either the S19W or the c.A-3G APOA5 polymorphisms are strong determinants of plasma TG

No abstract

No abstract