H. G. Kress

Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes From Hypercholesterolemic Patients

Objective—The intercellular adhesion molecule-1 (ICAM-1/CD54) and its ligand, CD11a/CD18, mediate endothelial adhesion of leukocytes and their consecutive transmigration. Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte–endothelial interactions. We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro. Methods and Results—A total number of 107 hypercholesterolemic patients were treated with 20 mg (n=52) or 40 mg (n=55) of simvastatin daily. After 6 weeks of treatment, peripheral blood mononuclear cells (PBMCs) expressed lower amounts of CD54-, CD18-, and CD11a-mRNA compared with pretreatment values. Surface expression of CD54 and CD18/CD11a on CD14+-monocytes also decreased significantly in both groups of patients. Moreover, simvastatin, atorvastatin, and cerivastatin were found to downregulate tumor necrosis factor (TNF)-&agr;–induced expression of CD54 and CD18/CD11a in isolated PBMCs obtained from normal donors as well as TNF-&agr;–dependent expression of these CAMs in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, all three statins were found to reduce the binding of PBMCs to TNF-&agr;–stimulated HUVECs in vitro. Conclusions—Statin-induced inhibition of expression of CD54 and CD18/CD11a in PBMCs and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities.

Continuous blockade of both brachial plexus with ropivacaine in phantom pain: a case report

A 39-year-old patient developed phantom pain after amputation of both upper arms following a burn injury. The pain did not respond to naproxen, morphine, carbamazepine, amitriptyline, calcitonin or transcutaneous electrical nerve stimulation (TENS). At the 39th post-operative day an axillary catheter was placed on the right side, as well as an interscalene catheter on the left. Ropivacaine 0.2% was infused, starting with a rate of 4 ml/h, that was increased to 6 ml/h during the subsequent 6 days. Within 20 min of catheter placement complete pain relief was achieved. The patient did not need any other analgesics and remained painfree for 7 months. Neither motor block, nor any other side effects occurred during the infusion of ropivacaine 0.2%. Thus, the patient not only received analgesia, but also got an effective treatment of established phantom pain. A similar approach with bupivacaine may not have been feasible, because of the possibility of toxic side effects. Ropivacaine is a long-acting local anaesthetic which is less toxic than bupivacaine and has the additional advantage of producing less motor-blockade in the concentration used, so the patient was able to move actively without experiencing any pain.

Gabapentin in der Therapie chronischer therapieresistenter Schmerzen

ZusammenfassungFragestellung. Untersuchung der Wirksamkeit und Verträglichkeit von Gabapentin bei der Behandlung von Patienten mit therapieresistenten Schmerzen. Methodik. Retrospektive Datenerhebung von Patienten mit chronischen therapieresistenten Schmerzen nach medikamentöser Vorbehandlung, die mit Gabapentin behandelt wurden. Ein Therapieerfolg wurde definiert als 50% Schmerzreduktion oder eine Schmerzintensität VAS ≤3. Ergebnisse. Annähernd die Hälfte der 99 Patienten (n = 49) wies einen Therapieerfolg auf. Patienten mit neuropathischen Schmerzen sprachen besser an (60% Responserate) als Patienten mit Schmerzen des Bewegungsapparates (35%). Allodynie trat vor der Therapie in der Gruppe der Therapieresponder doppelt so häufig auf (35 vs. 18%). Schwere Nebenwirkungen traten nicht auf. Schlussfolgerung. Gabapentin erwies sich als wirksames und verträgliches Medikament zur Behandlung neuropathischer Schmerzen.AbstractIntroduction. Gabapentin has been shown to reduce pain associated with diabetic neuropathia and postherpetic neuralgia. To date it is not known, whether gabapentin is generally effective in other types of pain. It was therefore the aim to study gabapentin in patients suffering from intractable pain with respect to efficacy, predictive factors and side effects. Methods. Retrospective analysis of the data sheet of pretreated patients suffering from intractable pain and treated with gabapentin as a third line drug at a university pain clinic. Pain intensity (visual analogue scale, VAS 0–10 cm), pain characteristics, diagnosis, pre- and co-treatment, and side effects were assessed. Response to treatment was defined as a 50% reduction in pain or a pain intensity of VAS ≤3. Results. 99 patients were included. Approximately half the patients (n = 49) responded to gabapentin. Patients suffering from neuropathic pain showed a higher response rate (60%) compared to patients with muscle-sceletal pain (35%). Allodynia was twice as high in the responders (35%) compared to the non-responders (18%) before treatment. No serious side effects were reported. Conclusion. Gabapentin was effective in approximately 50% of pretreated patients with intractable pain. Neuropathic pain responded better than pain of other origine. Allodynia may be a predictive factor for a positive treatment effect.

MTHFR and ACE Polymorphisms Do Not Increase Susceptibility to Migraine Neither Alone Nor in Combination.

The aim of this study was to confirm previous reports in order to substantiate the hypothesis that functional variants of two genes, namely methylenetetrahydrofolate reductase and angiotensin I converting enzyme, both involved in an important pathway of migraine, increase migraine susceptibility when present in combination.

Aktuelle Schmerztherapie onkologischer Patienten

ZusammenfassungGrundlagen: Wenngleich Schmerz eines der häufigsten Symptome bei Patienten mit fortgeschrittener Tumorekrankung ist, gibt es den „Krebsschmerz” als solchen nicht. Schmerzen bei Krebspatienten können verschiedene Ursachen und pathogenetische Mechanismen zugrunde liegen und sowohl akuter als auch chronischer Natur sein.Methodik: In einer Übersicht werden die aktuellen Schmerztherapiekonzepte bei onkologischen Patienten zusammengestellt.Ergebnisse: Vor dem Beginn jeder Schmerzbehandlung muß eine genaue Schmerzanalyse erfolgen und eine Schmerzdiagnose gestellt werden, bevor ein Behandlungskonzept entwikkelt werden kann. Wegen der besonderen Situation des Krebskranken sollte die Schmerztherapie nach Möglichkeit von psychosozialen Maßnahmen begleitet sein. Das multimodale und interdisziplinäre Therapiekonzept beinhaltet daher meist eine Kombination mehrerer Verfahren, sowohl palliative Maßnahmen am erkrankten Organ (Operation, Chemo-, Radio- und Hormontherapie) als auch die symptomatische Schmerzbekämpfung. Wichtig ist ein rechtzeitiger Behandlungsbeginn nach WHO-Stufenschema mit oraler Analgetikagabe. Gegebenenfalls können Opioide auch parenteral bzw. rückenmarksnah mittels Katheders (epidural, intrathekal oder intraventrikulär) appliziert werden. Wenn der Schmerz segmental begrenzt auftritt, sollten bereits frühzeitig entsprechende temporäre oder definitive (neurolytische) regionale Blockaden eingesetzt werden.Schlußfolgerungen: Nur noch in äußerst seltenen Fällen müssen dekomprimierende und destruierende neurochirurgische Eingriffe als letzter Ausweg zur Schmerztherapie durchgeführt werden. Nichtinvasive Verfahren wie TENS (transkutane elektrische Nervenstimulation), physikalische Therapie, Akupunktur und psychologische Verfahren können mit gutem Erfolg begleitend zur Symptomlinderung beitragen.SummaryBackground: Pain often occurs in cancer patients and its treatment has to be according to the general guidelines for pain relief. As so-called cancer pain maybe caused by various mechanisms and can have both acute and chronic components, a detailed pain assessment followed by an at least preliminary pain diagnosis is necessary prior to symptomatic treatment. Many options for the therapy of cancer pain exist, and in most cases a proper combination of invasive and non-invasive approaches has to be chosen.Methods: The current concepts of pain management in cancer patients are reviewed.Results: Pain relief in cancer patients is commonly achieved by a multimodal, multidisciplinary concept, which includes palliative therapy of the malign process (surgery, radiation, etc.) and palliative symptomatic pain management. If the pain is well localized and restricted to certain peripheral parts of the body, spinal, peripheral or symphatic nerve blocking (temporary using local anesthetics) or permanent (using neurodestructive methods) may results in very good therapeutic effects. Analgesic pharmacotherapy should be carried out orally according to WHO guidelines for the treatment of cancer pain (so-called WHO analgesic ladder). In case of side effects, opioids may be alternatively applied via epidural or spinal catheters.Conclusions: In any case additional options such as TENS, SCS, physiotherapy, acupuncture or psychological approaches may be beneficial. Only if all these options fail, also neurosurgical destructive procedures are to be considered a last resort.

Akupunktur bei sympathischer Reflexdystrophie

Der Begriff sympathische Reflexdystrophie (SRD) faßt zahlreiche Krankheitsbilder, wie posttraumatisches Ödem, Schulter-Arm-Syndrom, Algodystrophie, Morbus Sudeck und Kausalgie, zusammen. Nach einem schädigenden Ereignis, jedoch unabhängig von dessen Art und Lokalisation, entwickelt sich typischerweise im distalen Bereich (Hand/Fuß) einer betroffenen Extremität eine Trias von autonomen, motorischen und sensiblen Störungen.Ziel der Therapie einer SRD ist in 1. Linie die Beseitigung von Schmerz und Schwellung. Vor allem physikalische Therapie ist wesentlich bei der Behandlung. Außerdem sollte möglichst früh invasiv sympathikolytisch behandelt werden. Auch Akupunktur kann die sympathische Aktivität reduzieren und analgetisch wirken, somit also dem Behandlungskonzept der SRD zumindest prinzipiell entsprechen. Während sich Hinweise auf eine sympathikolytische Wirkung der Akupunktur an distalen Extremitäten finden lassen, ist ihr möglicher therapeutischer Nutzen bei der SRD bisher nicht eindeutig nachgewiesen, jedoch zumindest diskussionswürdig.The term ”reflex sympathetic dystrophy” (RSD) is used for various syndromes, e.g. posttraumatic edema, shoulder-hand syndrome, algodystrophy and causalgia. The clinical symptoms of RSD are characterized by a triad of autonomic, sensory and motor disturbances, which usually develop in the distal region of an affected extremity. The main symptoms are swelling, a side difference in skin temperature (autonomic symptoms), reduced active movements and muscular strength (motor symptoms) and spontaneous, deep, diffuse pain with an orthostatic component (sensory system). As soon as possible the treatment of RSD should include sympatholytic strategies and obligatory physical therapy. Acupuncture has also been reported to reduce sympathetic activity. The analgestic effect of acupuncture is well known, and therefore from an at least theoretical point of view, it should make sense to use acupuncture in the treatment of RSD. To date, however, no prospective, randomized, controlled, clinical long-term studies have been done. One short-term study showed promising results, but did not reach statistical significance. In that study acupuncture treatment seemed to alleviate the major symptoms of RSD. Since acupuncture rarely has side effects, its role as an additional option in the treatment of RSD should be further investigated.