Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (I)

Occupational diseases Nos. 2108 and 2110 correspond to intervertebral disc-related diseases of the lumbar spine from many years of carrying or lifting heavy loads, occupations in extreme postures of full flexion or oscillation of the whole body when seated, and which compel the cessation of all activities which are or could be the cause for the origin, exacerbation or recurrence of the disease. These occupational diseases came into force at the start of 1993, but there have been considerable problems in their implementation. The present Part I of the contribution is the result of the work of an interdisciplinary study group and contains medical criteria for the assessment of possibly strain-related clinical characteristics and the evaluation of other possible causes. Part II is to be published in Volume 4/2005 and will deal with questions related to forced cessation and to the assessment of the loss of earning ability. Agreement was reached in many areas related to the assessment of occupational claims. This should allow for evidence-based decision making in the future for the occupational diseases Nos. 2108 and 2110.     

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.     

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

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.