Orlistat-associated adverse effects and drug interactions: a critical review.

Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness.This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.     

Pharmacological management of hyponatremia

Introduction: Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. Furthermore, it is associated with increased morbidity and mortality.

Areas covered: This review discusses the efficacy and side effects of the currently available treatment options for hyponatremia and the differences in the pharmacological approach between the European and USA guidelines. Additionally, the authors provide their expert perspectives on current treatment strategies and what they expect from this field in the future.

Expert opinion: Several pharmacological options are available for the treatment of hyponatremia, but data from trials examining and comparing these treatments are missing. Regarding chronic hyponatremia, the role of vaptans should be further analyzed, focusing on comparisons with other active treatments on patient-relevant outcomes and not only on serum sodium concentration. Clinicians should be cautious to an overly rapid increase in serum sodium levels with all available treatment strategies. Finally, it is important to ascertain whether correction of serum sodium levels improves mortality in hyponatremic patients.     

Lipoprotein-associated phospholipase A2 activity is a marker of small, dense LDL particles in human plasma

BACKGROUND: Recent clinical studies showed that lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA(2) activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA(2) could be a marker of sdLDL in human plasma. METHODS: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA(2) activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA(2)). Non-HDL-Lp-PLA(2) activity and mass were calculated by subtracting the HDL-Lp-PLA(2) from total plasma Lp-PLA(2). RESULTS: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions < or =0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA(2) mass, total plasma Lp-PLA(2) activity and non-HDL-Lp-PLA(2) activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDL-Lp-PLA(2) activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA(2) activity and mass, but not Lp-PLA(2) mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL particle size. In multiple regression analysis, total plasma and non-HDL-Lp-PLA(2) activities were the second best predictors of the presence of sdLDL particles in human plasma after serum triglyceride concentrations. At serum triglyceride concentrations >1.356 mmol/L, total plasma and non-HDL-Lp-PLA(2) activity added significantly to the prediction of the presence of sdLDL in plasma. CONCLUSIONS: Lp-PLA(2) activity, but not the enzyme mass, is a marker of sdLDL in human plasma.     

Time-dependent changes in the expression of thyroid hormone receptor alpha 1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TR alpha 1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T(3) and T(4) levels in plasma were not changed at 2 weeks but T(3) was significantly lower and T(4) remained unchanged at 13 weeks. A twofold increase in TR alpha 1 expression was observed after 13 weeks in the non-infarcted area, P<0.05 versus sham operated, while TR alpha 1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TR beta 1 expression was found in the non-infarcted area at 13 weeks, P<0.05, while no change in TR beta 1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TR alpha 1 and 1.6-fold decrease in TR beta 1 expression versus untreated, P<0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TR alpha 1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TR alpha 1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TR beta 1 also contributes to fetal phenotypic changes. alpha1-adrenergic signalling is, at least in part, involved in this response.     

Foregut duplication cysts of the stomach with respiratory epithelium

Gastrointestinal duplication is a congenital rare disease entity. Gastric duplication cysts seem to appear even more rarely. Herein, two duplications cysts of the stomach in a 46 year-old female patient are presented. Abdominal computed tomography demonstrated a cystic lesion attached to the posterior aspect of the gastric fundus, while upper gastrointestinal endoscopy was negative. An exploratory laparotomy revealed a non-communicating cyst and a smaller similar cyst embedded in the gastrosplenic ligament. Excision of both cysts along with the spleen was performed and pathology reported two smooth muscle coated cysts with a pseudostratified ciliated epithelial lining (respiratory type).     

Intussusception of the bowel in adults： A review

Intussusception of the bowel is defined as the telescop- ing of a proximal segment of the gastrointestinal tract within the lumen of the adjacent segment. This condi- tion is frequent in children and presents with the classic triad of cramping abdominal pain, bloody diarrhea and a palpable tender mass. However, bowel intussusception in adults is considered a rare condition, accounting for 5% of all cases of intussusceptions and almost 1%-5% of bowel obstruction. Eight to twenty percent of cases are idiopathic, without a lead point lesion. Secondary intus- susception is caused by organic lesions, such as inflam- matory bowel disease, postoperative adhesions, Meckel＇s diverticulum, benign and malignant lesions, metastatic neoplasms or even iatrogenically, due to the presence of intestinal tubes, jejunostomy feeding tubes or after gas- tric surgery. Computed tomography is the most sensitive diagnostic modality and can distinguish between intus- susceptions with and without a lead point. Surgery is the definitive treatment of adult intussusceptions. Formal bowel resection with oncological principles is followed for every case where a malignancy is suspected. Reduction of the intussuscepted bowel is considered safe for benign lesions in order to limit the extent of resection or to avoid the short bowel syndrome in certain circumstances.     

Surgical outcome in patients with concomitant-infected abdominal aortic aneurysm and spondylitis

The coexistence of infected abdominal aortic aneurysms and spondylitis is rare but challenging. The etiology of the infection is frequently unknown. The aim of this study was to review the outcome of surgical repair of this complex disease. From 2004 to 2006, six patients were identified who underwent surgical repair of concomitant infected abdominal aortic aneurysm and spondylitis. Diagnosis, treatment and intermediate-term results are presented. The clinical manifestation included the signs of ongoing systemic infection, neurological deficit and abdominal or back pain. Computed tomography revealed abdominal aortic aneurysms associated with polysegmental spondylitis. Patients underwent radical debridement and aortic replacement with cryopreserved aortic allografts or silver-coated prostheses followed by antibiotic treatment. Only one patient received a simultaneous anterior vertebral stabilization. Greater omentum was placed in the abscess cavity. Intensive care unit and hospital stay averaged 3.0 and 28.0 days, respectively. Organisms were identified in all but one patient. Over a follow-up period of 4.4 years, four patients are alive and showing freedom from infection, and two patients had died unrelated at seven and eight months. In conclusion, surgical repair of infected aortic aneurysms with resection of infected tissues and implantation of a homograft or a silver-coated prosthesis achieved favorable results in this sick patient group. Simultaneous vertebral stabilization is rarely necessary.