Dysaccommodation of the stomach: therapeutic nirvana?

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder and has a complex pathophysiology. Impaired fundic relaxation in response to a meal is present in 40% of patients with FD. This review focuses on impaired gastric accommodation of the stomach as a pathophysiological mechanism and the possible therapeutic targets that can be derived from the current knowledge of the neuroregulation of the accommodation reflex. First the different means of gastric accommodation assessment are described and the relationship between symptoms and impaired gastric accommodation. The different therapeutic options are subsequently discussed in view of their molecular target, based on the different receptor subtypes involved in the accommodation reflex. Although impaired gastric accommodation is highly prevalent in dyspeptic patients and basic knowledge about the accommodation reflex enables to develop pathophysiologically targeted therapies, it is unlikely that therapies aimed at dysaccommodation of the stomach will lead to symptom relief in all dyspeptic patients. A major challenge is the development of methods that readily identify impaired accommodation in clinical practice.     

Sildenafil relieves symptoms and normalizes motility in patients with oesophageal spasm: a report of two cases

Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25-50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25-50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed.     

The influence of the helmet respirator on peak flow rate in aluminum potroom

The efficiency of the Racal Airstream helmet respirator in improving peak expiratory flow rates (PEFR) and symptoms (dyspnea, wheezing, and cough) in aluminum potroom workers with respiratory complaints was assessed in 19 workers. Peak expiratory flow readings and symptom recording from a 2-week working period with use of the respirator were compared with a period when the 3M 9906 disposable mask was used. The study was designed as a randomized, parallel, cross-over study with five or six daily measurements of PEFR and daily symptom recording. A significant number of workers (15) had a higher mean peak flow in the helmet period than in the nonhelmet period (p less than 0.01); symptoms did not improve significantly in the helmet period. Objective evidence of respiratory protection was observed for the group of workers as a whole, but the effect on symptoms as well as individual effect on peak flow was minor in the majority of the workers.     

Chronic intestinal pseudo-obstruction: manifestations, natural history and management

Chronic intestinal pseudo-obstruction (CIPO) is a rare pathological condition characterized by a marked derangement of gut propulsive motility mimicking mechanical obstruction, in the absence of any lesion occluding the gut lumen. This disease is often associated with a disabling and potentially life-threatening complications and is still too often unrecognized even in referral centres. As a result, patients receive neither appropriate care nor recognition of their severe health condition. Medical and surgical therapies are often unsatisfactory and long-term outcome turns out to be poor in the vast majority of cases. This article focuses on the main clinical features, the management and long-term outcome of patients affected by CIPO, with particular emphasis on those aspects which remain a matter of debate.     

Activation of human blood monocytes by oxidized polyunsaturated fatty acids: a possible mechanism for the generation of lipid peroxides in the circulation.

The ability of native and oxidized lipids and lipoproteins to stimulate production of reactive oxygen species (ROS; superoxide and hydrogen peroxide) by human blood monocytes has been studied in vitro. Neither native human low density lipoprotein (LDL), ''altered'' LDL (oxidized either by lipoxygenase, activated human monocytes or air) nor oxidized cholesterol had any significant effect on ROS production of monocytes. However, different oxidation products of a lipid emulsion (Lipofundin; largely consisting of linoleic acid oxidized either by lipoxygenase, Fe3+ or ultraviolet irradiation) greatly enhanced ROS production of monocytes. A hypothesis that activation of circulating leucocytes by oxidized fatty acids may generate oxidized plasma LDL, was tested in rabbits. Characteristics of LDL, separated from rabbit plasma 6 h after intravenous injection of an oxidized lipid emulsion, was compared to that of LDL isolated before the lipid treatment. Post-treatment LDL-fraction of plasma had increased lipid peroxide content and compared to the pretreatment LDL, caused a threefold increase in the incorporation of cholesterol into cultured (rat aortic) endothelial cells. The observed intense and lasting stimulation of monocytes by oxidized polyunsaturated fatty acids in vitro, and the generation of ''altered'' LDL by these oxidized lipids in vivo suggests a mechanism by which atherogenic oxidized LDL could form in the circulation.     

Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.     

Coccygectomy has a favorable effect on the intensity, manifestation, and characteristics of pain caused by coccygodynia: a retrospective evaluation of 34 patients followed for 3–18 years

Background  Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics, and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities. Materials and methods  Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were evaluated at an average of 7.6 (3–18) years of follow-up time. Results  Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate, 11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10⁻¹²). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications. Conclusion  Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The operation can be the choice of treatment if conservative measures fail.     

Beiträge zur Pathologie und Therapie der Toxischen Erkrankungen im Säuglings- und Kindesalter

Ohne Zusammenfassung     

Contribution of sensitivity, volume and tone to visceral perception in the upper gastrointestinal tract in man: emphasis on testing

Abstract  Upper gastrointestinal (GI) symptoms occur frequently in the general population, making them among the most common indications responsible for patients consulting the healthcare system. Consequently, understanding and characterization of the upper GI symptoms is important for the diagnosis and assessment of organ dysfunction. In practice, assessment of clinical symptoms is difficult and it is still to a large extent unclear how sensitivity, volume and tone contribute to visceral perception in the upper GI tract. The goal of advanced research in upper GI symptoms is to obtain a better understanding of the mechanisms involved in transduction, transmission, and perception under normal and pathophysiological conditions. An important step towards this goal is understanding the information provided by and the inherent limitations of the currently available measuring techniques. This article focuses on the sensory testing of the oesophagus, and methods and concepts used to assess the relation between gastric volumes or tone and upper GI symptoms. It also summarizes the contributions of these techniques towards identifying the components responsible for the generation of upper GI symptoms.