RA-spezifische Autoantikörper gegen ein 68k-Antigen

Zusammenfassung Die Diagnostik vieler rheumatischer Systemerkrankungen wird heute durch den Nachweis von Autoantik?rpern unterstützt und erleichtert. Für die Serodiagnostik der Rheumatoiden Arthritis (RA) stehen nur die doch wenig spezifischen Rheumafaktoren zur Verfügung. Mit dem Ziel, neue krankheitsspezifische Autoantik?rper nachzuweisen, erfolgte eine besondere Proteinaufarbeitung aus Synovialisbiopsien und anderen Geweben. Western Blots der gewonnenen Proteine wurden eingesetzt, um Seren von RA-Patienten und solchen mit anderen rheumatischen Erkrankungen zu untersuchen. Die signifikanteste Immunreaktion von RA-Patienten richtete sich gegen ein 68k-Antigen, welches vermutlich ubiquit?r exprimiert wird, da es nicht nur in Synovialis, sondern in allen weiteren untersuchten Humangeweben und HeLa-Zellen nachgewiesen werden konnte. Der isoelektrische Punkt liegt bei 5,1, das Protein ist O-glykosyliert und im endoplasmatischen Retikulum und/oder Cytoplasma lokalisiert. Antik?rper gegen dieses 68k-Antigen waren bei 110 von 167 RA-Patienten nachzuweisen, was einer Sensitivit?t von 66% entspricht. Ihr Vorkommen war unabh?ngig vom Rheumafaktornachweis, da sie auch bei 7 von 12 seronegativen RA-Patienten zu finden waren, dagegen nur bei einem Patienten aus einer Kontrollgruppe von 98 Patienten mit anderen rheumatologischen Krankheitsbildern, bei einem von 22 HIV-Patienten und überhaupt nicht bei 55 Gesunden. Daraus resultiert eine RA-Spezifit?t für diesen Antik?rper von 99%. Wegen der auff?lligen Krankheitsspezifit?t der anti-68k-Antik?rper liegt es nahe, nach korrespondierenden autoreaktiven T-Zellen zu suchen, um die Rolle dieser neuen Autoreaktivit?t in dem Pathomechanismus der RA zu analysieren. Eingegangen: 20. Mai 1996 Akzeptiert: 13. Februar 1997     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

“Helper:” A critical events prompter for unexpected emergencies

Objective. The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment.Methods. The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group).Results. A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p=0.015); similarly MgSO₄ was appropriately ordered more often in the experimental group (p=0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p=0.004), and epinephrine infusion was ordered for refractory bradycardia (p=0.002) more often in the experimental than the control group.Conclusions. These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.This study was made possible by a grant from the Anesthesia Patient Safety Foundation. Results were presented, in part, at the meeting of the STA/SEA Orlando, Florida, January 1994.     

Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy

Background  

Hypophosphatasia (HP) is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP) gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism.     

Risperidone and falls in ambulatory nursing home residents with dementia and psychosis or agitation: secondary analysis of a double-blind, placebo-controlled trial.

OBJECTIVE: Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS: Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS: The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS: Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering.