ABSTRACT
AIM OF THE STUDY: Open surgical removal of calcifications in chronic courses of calcifying tendinitis of the shoulder can be combined with acromioplasty. Independent of the surgical procedure not all patients achieve satisfactory surgical results. The aim of the study was to investigate whether preoperatively known epidemiologic, social, clinical and radiologic factors or intraoperative findings might influence the therapeutic outcome. METHODS: Following diagnostic arthroscopy, open removal of the calcifications was done as an isolated procedure (group A, n = 12) or combined with open acromioplasty (group/B, n = 24). Follow-up was 33 months for both groups. RESULTS: Clinical outcomes were comparable in both groups (Group A, 74.9 points; Group B 73.4 points, Constant-Murley score) and independent of gender, age, profession, duration of anamnesis, hospital-stay period, follow-up period, dominance of arm, preoperative Constant-Murley score, calcification morphology and size and acromial type. 20 patients in total achieved a clinical outcome of
Subject(s)
Calcinosis/surgery , Postoperative Complications/etiology , Rotator Cuff/surgery , Tendinopathy/surgery , Acromion/surgery , Adult , Aged , Arthroscopy , Calcinosis/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Tendinopathy/diagnosisABSTRACT
Recent work has established membrane phospholipids such as phosphatidylinositol-4,5-bisphosphate (PIP(2)) as potent regulators of K(ATP) channels controlling open probability and ATP sensitivity. We here investigated the effects of phospholipids on the pharmacological properties of cardiac type K(ATP) (Kir6.2/SUR2A) channels. In excised membrane patches K(ATP) channels showed considerable variability in sensitivity to glibenclamide and ATP. Application of the phosphatidylinositol phosphates (PIPs) phosphatidylinositiol-4-phosphate, PIP(2), and phosphatidylinositol-3,4,5-trisphosphate reduced sensitivity to ATP and glibenclamide closely resembling the native variability. Insertion of the patch back into the oocyte (patch-cramming) restored high ATP and glibenclamide sensitivity, indicating reversible modulation of K(ATP) channels via endogenous PIPs-degrading enzymes. Thus, the observed variability seemed to result from differences in the membrane phospholipid content. PIP(2) also diminished activation of K(ATP) channels by the K(+) channel openers (KCOs) cromakalim and P1075. The properties mediated by the sulphonylurea receptor (sensitivity to sulfonylureas and KCOs) seemed to be modulated by PIPs via a different mechanism than ATP inhibition mediated by the Kir6.2 subunits. First, polycations abolished the effect of PIP(2) on ATP inhibition consistent with an electrostatic mechanism but only weakly affected glibenclamide inhibition and activation by KCOs. Second, PIP(2) had clearly distinct effects on the concentration-response curves for ATP and glibenclamide. However, PIPs seemed to mediate the different effects via the Kir6.2 subunits because a mutation in Kir6.2 (R176A) attenuated simultaneously the effects of PIP(2) on ATP and glibenclamide inhibition. Finally, experiments with various lipids revealed structural features necessary to modulate K(ATP) channel properties and an artificial lipid (dioleoylglycerol-succinyl-nitriloacetic acid) that mimicked the effects of PIPs on K(ATP) channels.
Subject(s)
Adenosine Triphosphate/pharmacology , Glyburide/pharmacology , Membrane Proteins/metabolism , Animals , Cations/pharmacology , Cattle , Drug Interactions , Electrophysiology , Hypoglycemic Agents/pharmacology , Membrane Proteins/drug effects , Mice , Molecular Conformation , Oocytes , Phosphatidylinositol 4,5-Diphosphate/pharmacology , Phospholipids/chemistry , Phospholipids/pharmacology , Potassium Channels , Xenopus laevisABSTRACT
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of KATP channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4, 5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned KATP channels (Kir6.2 and SUR1). These phospholipids acted on the Kir6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of KATP-mediated currents. These results represent a mechanism for control of excitability through phospholipids.
Subject(s)
ATP-Binding Cassette Transporters , Adenosine Triphosphate/pharmacology , Phosphatidylinositol 4,5-Diphosphate/pharmacology , Phosphatidylinositol Phosphates/pharmacology , Potassium Channel Blockers , Potassium Channels, Inwardly Rectifying , Adenosine Triphosphate/metabolism , Animals , Cloning, Molecular , Diazoxide/pharmacology , Dose-Response Relationship, Drug , Mutation , Oocytes , Patch-Clamp Techniques , Phosphatidylinositol 4,5-Diphosphate/metabolism , Phosphatidylinositol Phosphates/metabolism , Phosphatidylinositols/pharmacology , Potassium Channels/genetics , Potassium Channels/metabolism , Receptors, Drug/metabolism , Receptors, Purinergic P2/metabolism , Receptors, Purinergic P2Y2 , Recombinant Fusion Proteins/metabolism , Sulfonylurea Receptors , Type C Phospholipases/metabolism , Xenopus laevisABSTRACT
Case report on a folie à deux (double insanity) in a relatively young, married couple who decompensated psychologically subsequent to the failure of different compensation mechanisms after premorbid strange behaviour and jointly developed delusions of ugliness and of injury. The history of the disease pattern of "folie à deux", or double insanity, is described, as well as the present-day definitions, and the case report is set against this background.
