Characteristics of pharmacotherapy of rheumatic diseases in advanced age]

Drug treatment in the polymorbid elderly should focus on the more important symptoms. Pharmacokinetic differences should be considered, e.g. a reduced volume of distribution and decreased liver and renal function. Special alterations in the pharmacodynamics with respect to the central nervous system and other organs are important. Drug therapy in the elderly has to be done very cautiously. The indication, dosage and duration of therapy has to be evaluated again and again. Antirheumatics in the elderly should improve the quality of life avoiding untowanted side effects, especially of the gastrointestinal tract, the renal function and bone marrow. Non-narcotic analgesics and opioids may be helpful, when antirheumatics were not tolerated.     

Ileus bei ausgedehnten intraabdominellen Verkalkungen nach Peritonitis

Zusammenfassung. Wir berichten über einen 48 j?hrigen Patienten. In Folge einer bakteriellen Peritonitis hatten sich ausgedehnte intraabdominelle Verkalkungen gebildet. Diese hatten einen Obstruktionsileus verursacht. Im Rahmen einer Revisionslaparotomie wurden die Kalkspangen entfernt. Zur Rezidivprophylaxe veranla?ten wir eine percutane Bestrahlung mit 15 Gy. Zus?tzlich erfolgte eine systemische Indometacin-Applikation. Eine Literaturrecherche ergab nur 2 vergleichbare F?lle.      

Laparoscopic mesh repair of incisional hernia: an alternative to the conventional open repair?

Background Tension-free incisional hernia repair using alloplastic material increasingly replaces conventional repair techniques. This change resulted in a decreased recurrence rate (50% vs. 10%, respectively). Recently, laparoscopic approaches for the intraperitoneal tension-free mesh application have been introduced. The decreased trauma at the incision site and the reduction in wound infections appear to be the main advantages. The aim of the present study was to evaluate the early and long-term complications as well as patients’ contentment. Methods Laparoscopic hernia repair with intraperitoneal polytetrafluroethylene (PTFE) mesh implantation was performed on 62 patients at the Klinikum Grosshadern between 2000 and 2005 (29 males, 33 females age 60.7). Intra- and postoperative complications were registered prospectively and retrospectively analyzed. In addition, 57 patients were evaluated for recurrence, postoperative pain and patient contentment (median follow-up 409 days). Results A low complication rate was observed in our patient collective. One trocar bleeding occurred. Three patients presented with wound hematoma. The recurrence rate was 8% (2/25). Sixty-two percent of the patients were free of complaints postoperatively. Eighty-five percent would once again choose the laparoscopic approach for incisional hernia repair. Conclusion The laparoscopic technique was associated with a low recurrence rate, a small rate of wound infections and high patient comfort. Thus, the laparoscopic approach for mesh implantation appears to be a safe and effective method for the treatment of incisional hernias. The efficiency for laparoscopic intraperitoneal mesh implantation, however, should be further evaluated within a prospectively randomized multicenter trial. M. Stickel and M. Rentsch contributed equally.     

Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge

The aim of this study was to investigate the potential of a composite matrix, containing esterified hyaluronic acid and gelatin, to facilitate the osteochondral differentiation of culture-expanded, bone marrow-derived mesenchymal progenitor cells. The cell loading characteristics and the effects of the matrix on cell differentiation were examined in vitro and in vivo. Empty and cell-loaded composites were cultivated for up to 28 days in a chemically defined medium with or without transforming growth factor-beta1 (TGF-beta1). A type II collagen-rich extracellular matrix was produced by cells loaded in the matrix and cultured in the presence of TGF-beta1. Empty and cell-loaded matrices were also implanted subcutaneously in immunodeficient mice. Three types of implant were used: empty (group I), cell-loaded matrices (Group II), and cell-loaded matrices cultured for 14 days in vitro in defined medium with TGF-beta1 (group III). No osteochondral differentiation was found in implanted empty matrices; however, the matrix supported osteochondrogenic cell differentiation in the cell-loaded implants. Preculture in vitro in a chondrogenic medium increased the percentage of osteochondral tissue found in the constructs after 3 weeks. These results indicate the potential use of this composite matrix for delivery of bone marrow-derived mesenchymal progenitor cells for the repair of chondral and osseous defects. The results also indicate that this composite matrix is useful for in vitro tissue engineering.     

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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Behandlung mit Mexiletin

Summary Pharmacokinetics of the antiarrhythmic agent mexiletine were found to be highly variable. Ineffective or toxic doses can be avoided by monitoring mexiletine concentrations in patients plasma. However, the success of antiarrhythmic therapy is mainly determined by the severety of the underlying disease. Therefore, the efficacy of treatment with mexiletine should be controlled by Holter monitoring.

Herrn Prof. Dr. G. Schütterle zum 60. Geburtstag gewidmet     

Pharmacokinetic study of methotrexate,folinic acid and their serum metabolites in children treated with high-dose methotrexate and leucovorin rescue

Summary The pharmacokinetics of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diaminomethylpteroic acid (APA), folinic acid, and 5-methyltetrahydrofolate (5-MTHF) have been studied during 21 high-dose MTX (HDMTX) infusions (5 g·m^–2 in 24 h) with leucovorin (LCV) rescue, a component of the therapy of 5 children with acute lymphoblastic leukemia (ALL).The median steady-state concentration of MTX was 66 mol·l^–1. Three elimination half-lifes were determined for MTX: 1.8 h, 6.4 h and a terminal 15 h. The median systemic MTX clearance was 110 mg·m^–2·min^–1.The 7-OHMTX level increased during each infusion and a C_max of 19 mol·l^–1 was achieved at the end. Its initial half-life was 5 h and the terminal half-life was 12 h. Thus, the peak serum concentration ratio of 7-OHMTX to MTX was reached 24 h after the end of the infusion at a median ratio of 8.The MTX metabolite APA was detected in concentrations less than 0.06 mol·l^–1. The median folinic acid level during rescue, 48 h after starting the infusion, was 7.0 mol·l^–1 and 18 h following the last dose of LCV it was 0.44 mol·l^–1, leading to ratios of folinic acid to MTX of 31 and 6, respectively. The median 5-MTHF level during rescue was 0.44 mol·l^–1 with a median ratio of 5-MTHF to MTX of 2.Twenty infusions with 48 h MTX levels of less than 0.5 mol·l^–1 were without marked toxicity. Only one patient with a 48 h MTX concentration of 5.5 mol·l^–1 and a ratio of 5-MTHF to MTX of 0.08 suffered from ulcerating mucositis and septicaemia despite increased and prolonged LCV rescue.     

Psychophysiologic Therapy for Chronic Headache in Primary Care

BACKGROUND: Headaches account for a high percentage of office visits to primary care physicians, with migraine and tension-type headaches the most common. This article provides a summary of psychophysiologic therapies for migraine and tension-type headache and considers psychosocial factors relevant to headache. Psychophysiologic therapy of headache consists primarily of relaxation and biofeedback. METHOD: Representative controlled studies, meta-analysis, and reviews are utilized to assess the efficacy of biofeedback and relaxation for migraine and tension-type headache. RESULTS: Psychophysiologic therapy comprising biofeedback and relaxation can be provided in standard or limited therapist contact formulas to patients as sole therapy or concurrently with medical therapy. Effectiveness has been demonstrated for thermal biofeedback-and electromyograph biofeedback-assisted relaxation with minimal or no side effects. A typical treatment protocol is offered to exemplify the integration of psychophysiologic therapy into primary care practice. CONCLUSION: Psychophysiologic therapy represents an important adjunctive treatment for chronic benign headache that can be incorporated into primary care.