A study of beta 2-microglobulin skin deposits in dialyzed patients and healthy controls

This study reports on beta 2-microglobulin (beta 2M) deposits in the skin of 12 uremic patients and three kidney transplant recipients compared with eight healthy controls. Uremic patients were treated by hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or continuous ambulatory peritoneal dialysis (CAPD) for a period lasting from 1 to 19 years. Congo red staining of the skin was negative in patients and controls. However, immunofluorescent staining with an anti-beta 2-microglobulin monoclonal antibody was positive in the skin of all patients and of six of the eight controls. Beta 2M skin deposition is more intense in patients than in controls and increases with patient age and the duration of dialysis. A stron correlation is observed between the extent of skin beta 2M deposits and clinical manifestations due to beta 2M deposits in internal organs. However, no correlation is found between beta 2M skin deposits and sex or beta 2M serum levels.     

Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.

BACKGROUND: Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia. METHODS: In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1). RESULTS: We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly. CONCLUSIONS: This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.     

Double-blind, placebo-controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis

Pruritus is a common symptom among patients undergoing long-term hemodialysis. The effect of nicergoline, an ergoline, on pruritus was studied in products released during dialysis. In a first experiment series, 20 age-matched normal individuals, 25 patients receiving hemodialysis without pruritus, and 15 patients receiving hemodialysis with pruritus had intradermal tests with 500 micrograms of papaverine. All patients with pruritus had a small papaverine skin test response, and mean values were significantly (p less than 0.0001, Mann-Whitney U test) smaller in patients with pruritus. All patients with pruritus entered in a crossover, double-blind trial with nicergoline. In a first period of six dialyses, they received either nicergoline (daily oral dose, 30 mg, and intravenous dose during dialyses, 5 mg) or placebo. In the second period of six dialyses, patients received the crossover treatment. Nicergoline was effective in 13/15 patients, eight of these patients having a complete remission of pruritus. When nicergoline was stopped, patients relapsed within 24 to 48 hours. All patients who improved during the trial were then treated with a daily dose of 30 mg of nicergoline for 6 months. Seven patients had a complete remission, five had moderate symptoms, and one patient relapsed. This study demonstrated that some hemodialyzed patients with pruritus of unknown etiology had improvement with nicergoline.     

Serum {alpha}2-macroglobulin in haemodialysis patients: baseline and kinetic studies

The pathogenesis of dialysis related amyloidosis remains unresolveddespite the identification of ß₂-microglobulin (ß₂M)as the major protein constituent, as well as other proteinsbeing present in the deposits. Among the latter we have assessedthe serum concentrations of ₂-macroglobulin (₂M) both in thebaseline stage and during the haemodialysis (HD) procedure.We have also assessed the influence of the membrane on ₂M kinetics. Fifteen HD patients with histologically proven dialysis-relatedamyloidosis (DRA group) and 15 HD patients clinically and radiologicallyconsidered dialysis-related amyloidosis free (control group)were included in the baseline study. Blood was sampled the daybefore the second dialysis of the week and ₂M, ß₂Mand ₁, antitrypsin were determined along with the routine biologicalanalysis of these patients. Serum ₂M was greater in dialysis-relatedamyloidosis than in control patients (t = 2.35; P<0.026).Serum ß₂M was similar in both groups. The serum ₂Mand ß₂M correlated in patients with dialysis-relatedamyloidosis (r = 0.64; P<0.01), while no correlation wasfound in controls (r = 0.17; NS). Stepwise analysis taking thepresence of dialysis-related amyloidosis as the dependent variableretained the serum ₂M concentration as the first variable inthe model (F = 4.4; partial r = 0.38; P<0.046). The sameproteins were determined in another group of seven patients,before and hourly during HD as well as 2 and 8 h after the endof HD during nine consecutive dialyses (3 cycles of 3 HD eachusing AN69 and cuprophane membranes in a crossover design).Serum ₂M significantly increased from hour 3 and continued toincrease 2 hours post-HD (+11% and +9% with AN69 and cuprophanerespectively; P<0.001). Total proteins peaked at hour 4 (+4% and +3% P<0.01) and decreased after HD. Serum ß₂Msignificantly decreased with AN69 HD ( – 29% P<0.001)and remained unchanged during cuprophane HD. In conclusion, significant increases in serum ₂M are observedimmediately after and during the early post-dialysis periods,regardless of the membrane used. Further, serum ₂M correlateswith ß₂M only in patients with dialysis-related amyloidosis,and this variable was retained in the multivariate regressionanalysis to predict dialysis-related amyloidosis. Although thebaseline results require confirmation with larger studies, wepostulate that the present results are of relevance for dialysis-relatedamyloidosis pathogenesis since ₂M, previously identified indialysis related amyloid deposits, is closely related to acute-phasereactant proteins, and interacts with the main infiltratingcells of the deposits (macrophages). ₂M modifications couldrepresent a new manifestation of the inflammatory response tothe haemodialysis procedure.     

Calcium balance and intact PTH variations during haemodiafiltration

BACKGROUND.: Recent approaches to prevent and treat secondary hyperparathyroidismin dialysis patients include decreasing dialysate Ca contentfrom 1.75 to 1.5 mM or lower. We have recently observed thatby decreasing dialysate Ca to 1.25 mM a rise in intact parathormoneserum levels occurs despite adequately controlled predialysisCa and phosphate serum levels. In that study complementary treatmentwith high-dose 1(OH) vitamin D3 was required to suppress theparathormone. In the present study we aimed to assess the totalCa balance as well as the modifications in parathormone inducedby the dialysis session in order to understand the reasons forwhich the rise in parathormone was induced. METHODS.: Fourteen HD patients treated with haemodi-afiltration threetimes/week gave their informed consent for the study. They weredistributed in two groups with identical treatment but for thedialysate Ca content which was 1.5 and 1.25 mM respectivelyand for the amount of oral CaCO₃ received. Total and ionizedCa, phosphate, pH, and albumin as well as parathormone weremeasured in serum before and after dialysis and in the spentdialysate during two dialysis sessions. RESULTS.: Serum ionized Ca (normalized to pH 7.4) did not change during1.25 mM dialysate Ca and significantly increased with 1.5mM(P<0.001). The end-dialysis values being 1.25±0.02and 1.38±0.02 mM respectively. Total Ca significantlydecreased with 1.25mM dialysate Ca (P<0.04) and increasedwith 1.5mM (P<0.003), the end-dialysis values being 2.51±0.03and 2.75±0.04mM respectively. In the dialysate the differencein ionized Ca concentrations, fresh minus spent dialysate was–1.78±1.12 mmol/l (NS) and 4.26±1.47 mmol/l(P<0.02) respectively for 1.25 and 1.5 mM dialysate Ca. Thedifference in total Ca concentrations, fresh minus spent dialysatewas –0.1±0.01 mmol/l (P<0.005 and –0.002±0.01 mmol/l (NS) respectively. Phosphate removal was higherin 1.25 mM dialysate-Ca-treated patients (40.4±1.75 mmol/sessionversus 34±1.3 mmol/session respectively, P<0.015).The use of 1.25 mM dialysate Ca did not result in a change inserum parathormone, while the use of 1.5 mM resulted in a decreaseof 43±15% (P<0.02) in patients with marked hyperparathyroidism. CONCLUSIONS.: Our data remind us of the difficulty in assessing Ca balancesand identifies the phosphate content as one of the factors influencingthe amount of ionized Ca in the dialysate. Although the long-termparathormone increase we observed using 1.25 mM dialysate Camay well not be explained only by the acute intradialytic modifications,the negative Ca balance identified here (which was missed withthe analysis of ionized Ca alone), and the lack of parathormoneinhibition may participate in the relapse of hyperparathyroidism.     

Erfassung muskuloskeletaler Beschwerden mittels Fragebogen

Zusammenfassung Der standardisierte Fragebogen zur Erfassung muskuloskeletaler Beschwerden des japanischen Komitees zum Studium arbeitsbedingter Gesundheitsstörungen im Hals-Arm-Gebiet wurde auf Deutsch übertragen und seine Reliabilität und Validität überprüft. Im Fragebogen wird anhand eines Körperschemas nach der Häufigkeit (nie/selten, gelegentlich, fast täglich) von Beschwerden (Schmerzen, Steifigkeit, Müdigkeit) in 12 Körperregionen gefragt. Der Fragebogen wurde gleichzeitig mit ärztlichen Palpationsuntersuchungen bei 644 Personen aus zwölf Berufsgruppen im Dienstleistungssektor eingesetzt. Auf Grund einer Faktoranalyse der Fragebogenresultate kann festgestellt werden, dass Beschwerden regional getrennt (nämlich im Nacken-Schultergebiet, dem Rücken und je der rechten und linken oberen Extremität) auftreten und für diese Regionen die Symptome zu Indizes zusammengefasst werden können. Diese Indizes sind reliabel (Cronbach 0.8). Mit zunehmenden Indexwerten nehmen schmerzhafte Palpationsbefunde stetig zu. Beschwerden korrelieren mit vermehrtem Medikamentenkonsum und Arztkonsultationen. Der Fragebogen stellt folglich ein valides Untersuchungsinstrument für muskuloskeletale Beschwerden am Arbeitsplatz dar.

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Summary The standardized illustrated questionnaire on musculoskeletal disorders of the Japanese Committee on Occupational Cervico-brachial Disorders was translated into German. This questionnaire, composed of 37 items about the occurrence (never/seldom, occasionally, almost daily) of symptoms (pain, stiffness, fatique) in twelve body regions, was used together with medical examinations (pressure points), and further information was gathered on the consumption of analgetics and medical visits prompted by musculoskeletal symptoms. The questionnaire's reliability and validity were tested in 644 persons from twelve occupational groups within the service sector. Factoranalyses showed that symptoms can be grouped into four distinct regions of occurrence: neck/shoulder/area, back/low back, and both left and right upper extremities. Indices based on these regions are consistent (Cronbach 0.8). Palpation findings steadily increase with increasing index values. The consumption of medicaments and medical visits positively correlate with the indices. Consequently the questionnaire is judged to be a valid instrument for studying musculoskeletal disorders at the workplace.

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Résumé Le questionnaire illustré et standardisé sur les symptômes musculaires et osseux du comité japonais sur la cervico-brachialgie professionelle a été traduit en allemand et sa reliabilité et validité ont été testées. Le questionnaire est composé de 37 variables sur la fréquence (jamais/rarement, par occasion, presque toujours) des symptômes (douleur, raideur, fatigue) dans douze régions du corps. Il était distribué simultanément aux examens médicaux parmi 644 personnes de douze groupes d'employés dans le secteur de service. D'autres informations concernent la fréquence de la consommation des analgésiques et des visites médicales pour des douleurs musculaires. Une analyse factorielle a montré que les symptômes peuvent être groupés en quatre régions du corps: nuque/épaules, dos et les extrémités supérieurs. Les indices sur ces régions sont consistant (Cronbach 0.8). Les douleurs provoquées par la palpation augmentent avec la valeur de l'index. La consommation des analgésiques et les consultations sont correlées avec les indices. Par conséquent, le questionnaire illustré est un instrument valable pour étudier les problèmes musculaires sur les lieux de travail.

     

Persistent dysphagia after removal of an adjustable gastric band for morbid obesity: a rare complication

Esophageal and gastric pouch dilatations are not uncommon after laparoscopic adjustable gastric banding for morbid obesity. Most of the cases are treated by gastric band deflation or removal. We report here the case of a 44‐year‐old woman with vomiting and severe dysphagia persisting despite gastric band removal, in relation with a scar stenosis and a gastric pouch trapped in the thorax, treated by laparoscopic surgery. This case underlines the usefulness of high‐resolution manometry in the diagnostic work‐up of these often difficult cases.