Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy

BACKGROUND: It is controversial whether proton pump inhibitor use leads to fundic gland polyp development. AIM: To determine whether fundic gland polyp development is due to proton pump inhibitor use and to investigate mechanisms involved. METHODS: Proton pump inhibitor use and the presence of fundic gland polyps were assessed in consecutive patients undergoing oesophagogastroduodenoscopy. Biopsies from fundic gland polyps and gastric mucosa were taken. Dysplasia was graded as negative, low or high grade. Prevalence of parietal cell hyperplasia and parietal cell protrusions and the proportional cystic area were assessed. RESULTS: 599 patients participated, 322 used proton pump inhibitors, 107 had fundic gland polyps. Long-term proton pump inhibitor use was associated with an increased risk of fundic gland polyps (1-4.9 years use: OR 2.2, 95% CI: 1.3-3.8; > or =5 years: OR 3.8, 95% CI: 2.2-6.7) while short-term therapy (<1 year) was not (OR 1.0, 95% CI: 0.5-1.8). Low-grade dysplasia was found in one fundic gland polyp. Fundic gland polyps associated with long-term proton pump inhibitor use had a larger proportional cystic area and higher frequency of parietal cell hyperplasia and parietal cell protrusion. CONCLUSIONS: Long-term proton pump inhibitor use is associated with an up to fourfold increase in the risk of fundic gland polyps. Risk of dysplasia is negligible. Aetiologically, these polyps seem to arise because of parietal cell hyperplasia and parietal cell protrusions resulting from acid suppression.     

In utero exposure to phthalates and fetal development

The diesters of benzene-1,2-dicarboxylic (phthalic) acid, commonly known as phthalates, are a family of industrial compounds, primarily used as plasticizers in enormous quantities for a variety of industrial uses in the formulation of plastics. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer. These plasticizers are not covalently bound to the polymer and leach out into the environment, thus becoming ubiquitous environmental contaminants. Cumulating evidence points out on the adverse effects of phthalate exposure during intrauterine life. Recently, it has been documented that in utero phthalate exposure is associated with a shorter duration of pregnancy. Phthalates induce and activate a subset of peroxisome proliferator-activated receptors (PPARs) and have an intrinsic pro-inflammatory activity, while some natural PPAR agonists induce cyclooxygenase (COX)-2 expression. To this regard, COX-2 is thought to be overexpressed in chorioamnionitis (CA), a fetal systemic inflammatory response syndrome and a leading cause of preterm birth. An adequate maternal dietary intake of essential fatty acids, well known anti-inflammatory agents, is indispensable to fetal development. Recently, it has been shown that phthalates alter the placental essential fatty acids (EFAs) homeostasis so potentially leading to abnormal fetal development. Likewise, a possible down-regulation of COX-2 by omega-3 fatty acids has been suggested. As a consequence, maternal supplementation with omega 3 during pregnancy could counteract the adverse effects of phthalates exposure in the human fetus. Here, we analyze the existing evidence on the link between antenatal phthalate exposure and abnormal fetal development, as well as on possible therapeutic tools to fight the adverse effect of this exposure.     

Acute influence of cigarette smoke in platelets, catecholamines and neurophysins in the normal conditions of daily life

Cigarette smoking is firmly linked to the occurrence of acutecoronary events. In twenty-two healthy volunteers in normalconditions of daily life we studied the acute influence of smokingon the following parameters: beta-thromboglobulin, thromboxaneB₂, epinephrine, norepinephrine, estrogen-stimulated neurophysin,and nicotine-stimulated-neurophysin. Our results show that inour population and following our protocol, smoking did not induceplatelet activation, thromboxane formation, catecholamine releaseor estrogen-stimulated-neurophysin secretion. However, smokingdid provoke a significant increase of nicotine-stimulated-neurophysin(p<0.05) which reflects vasopressin increase and which mightexplain the high incidence of ischaemic accidents in cigarettesmoking via the vasoactive properties of vasopressin.     

Acute Interstitial Pneumonitis and Carbamazepine Therapy

ABSTRACT. A 14-year-old girl with skin rash and acute interstitial pneumonitis is presented. She had been taking carbamazepine for two months. Withdrawal of carbamazepine resulted in a prompt improvement of the clinical picture and a normalization of lung function tests. A hypersensitivity reaction to carbamazepine is suggested and the importance of a skin rash as first sign of a generalized reaction is stressed. Lymphocyte-stimulation-tests with carbamazepine were strongly positive in the patient and not in healthy persons nor in patients taking carbamazepine without adverse effects.