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GaToroid is a novel configuration of a beam delivery system for charged particles therapy based on a steady-state, axis-symmetric field configuration. The basic idea is to use fixed toroidal magnets, producing an axis-symmetric (or periodical axis-symmetric) field configuration that can bend beams from several directions onto the patient location. In principle, neither magnets nor patient need to be moved. In addition, the field of the magnets of this toroidal gantry is static. Such system is perfectly adapted to FLASH therapy, a novel method of beam dose delivery that has shown benefits for electrons and potential for hadrons. In this paper we describe the magnetic design of a “compact GaToroid”, which could be built with iron-dominated magnets, suitable for 200 MeV electron beams, as well as protons at 70 MeV. The gantry profits from the use of toroidal quadrupoles, which greatly simplify the beam transmission. An additional novelty is the use of a resonant kicker as the vector magnet. Starting from the requirements for beam transmission, we derive first the magnet main characteristics (strength, aperture, size and mass) and report the detailed magnetic field calculations in support of the design.

Einleitung: Die kontinuierliche laterale Rotationstherapie (KLRT) wird häufig zur Optimierung der pulmonalen Funktionen bei Patienten mit einem schweren Thoraxtrauma eingesetzt. In dieser Studie wurde der Effekt der KLRT auf die Morbidität, die Mortalität und die Intensivstations- bzw. Krankenhausverweildauer untersucht. Methoden: Es erfolgte eine retrospektive Untersuchung von Patienten mit schwerem Thoraxtrauma aus dem TraumaRegister DGU®. Es wurden Patienten, die mit einer KLRT behandelt wurden, mit einer Kontrollgruppe verglichen, die bei vergleichbarer Verletzungsschwere eine konventionelle Therapie erhalten haben. Ergebnis: Es wurden 1476 Patienten (239 mit KLRT, 1237 ohne KLRT) in die Studie eingeschlossen. Beide Gruppen waren bezüglich demographischer Daten vergleichbar. Die mediane Dauer der KLRT betrug 6 (4–10) Tage. Patienten mit KLRT wurden 17 (10–26) Tage beatmet, Patienten ohne 14 (8–22) Tage (p= 0,001). Es zeigten sich signifikante Unterschiede im Hinblick auf die Intensivaufenthaltsdauer (KLRT: 23 [14–32] Tage; Kontrollgruppe: 19 [13–28] Tage; p= 0,002) und die Inzidenz einer Organdysfunktion (KLRT: 76,6 %, Kontrollgruppe: 67,6 %; p= 0,006). Es bestanden keine Unterschiede in der Häufigkeit einer Multiorgandysfunktion, der Mortalität und der Gesamtkrankenhausaufenthaltsdauer. Zusammenfassung: In dieser retrospektiven Untersuchung konnte kein Behandlungsvorteil für den Einsatz der KLRT bei traumatisierten Patienten nachgewiesen werden. Aufgrund der Limitationen einer retrospektiven Erhebung ist eine abschließende Bewertung des Nutzens der KLRT anhand der vorliegenden Ergebnisse nur bedingt möglich. Die Durchführung einer prospektiven kontrollierten Untersuchung ist für eine valide Prüfung dieses Therapiekonzepts unbedingt erforderlich.

Malignant hyperthermia (MH) is a life-threatening genetic sensitivity of skeletal muscles to volatile anesthetics and depolarizing neuromuscular blocking drugs occurring during or after anesthesia. Mortality of MH has been significantly reduced by using the skeletal muscle relaxant dantrolene. However, pharmacological disadvantages are known. By approval of a nanocrystalline dantrolene sodium suspension (DSS), a new product enters the market. DSS is a promising substance, but clinical data are lacking up to now. Especially with regard to newer knowledge on MH and its associated clinical presentations, there might be an increasing interest on DSS.

Patients with fibromyalgia syndrome (FMS) generally present with chronic widespread pain, accompanied by a range of additional and non-specific symptoms, such as fatigue, disturbed sleep, and cognitive dysfunction, which tend to increase with overall severity. Previous studies have shown moderate cognitive impairment in patients with FMS, but there are few valid data explicitly assessing the relevance of these findings to everyday functions, such as driving ability. Therefore, we studied patients with FMS to assess the impact of FMS on tests that predict driving ability. Female patients with FMS were prospectively compared to a historical control group of healthy volunteers. The test battery comprised assessments of visual orientation, concentration, attention, vigilance, motor coordination, performance under stress, and reaction time. A total of 43 patients were matched to 129 controls. The results indicated that the patients’ psychomotor and cognitive performances were significantly non-inferior when compared to healthy controls (with 0.05% alcohol), with the exception of motor coordination. Patients and healthy controls showed an age-related decline in test performance. Correlations were smaller in patients and reversed for vigilance which was linked to a greater FMS symptom load in younger patients. The results of the present study demonstrate that, in general, the driving ability of patients with FMS was not inferior to that of healthy volunteers based on a standardized computer-based test battery. However, variables, such as younger age, depression, anxiety, fatigue, pain, and poor motor coordination, likely contribute to the subjective perception of cognitive dysfunction in FMS.

Introduction:IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence.Areas covered:The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes.Expert opinion:The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

Chronic posttraumatic pelvic pain (PPP) after pelvic ring fractures impacts negatively on quality of life issues. This study aimed to more clearly identify and quantify the problem.

This study investigated the effects of thiopental on endothelium-dependent relaxation (EDR), and especially the effects on nitric oxide-and prostacyclin-independent EDR. Fresh porcine coronary artery rings (4 mm long), were consecutively tested with and without 20 μg/ml thiopental in Krebs–Henseleit solution. Indomethacin (10 μmol/1) was used in all experiments to eliminate prostacyclin effects. Prostaglandin F2α(10 μmol/l) was used to induce contractions and bradykinin (10−10−10−5M) was used to induce EDR. Experiments were also carried out using 300 μmol/1 N-nitro-l-arginine to block nitric oxide production and to assess the influence of thiopental on nitric oxide-and prostacyclin-independent EDR. Thiopental induced statistically significant increases in EDR at concentrations of 10−6−10−5M bradykinin. Following nitric oxide production block, thiopental significantly reduced the relaxation response at concentrations of 10−8−10−5M bradykinin. At a clinically relevant concentration of 20 μg/ml thiopental, a significant increase in EDR and a significant reduction in nitric oxide-and prostacyclin-independent relaxation was observed in porcine epicardial coronary arteries.

Patients with traumatic brain injury (TBI) and skeletal injuries have increased rates of excessive bone healing (EH = hypertrophic callus formation and/or heterotopic ossification). Polytrauma patients are often attributed higher rates of delayed fracture union. This study compares 182 total fractures in 29 isolated polytrauma patients (POLY) and 48 patients after TBI and polytrauma (TBI+POLY), examining the clinical parameters of EH versus delay. A subset of 28 patients (13 TBI+POLY, 15 POLY) underwent serological testing for the following bone turnover parameters: carboxy-terminal extension peptide of type 1 procollagen (P1CP), pyridinolene cross-linked carboxy- terminal telopeptide (1CTP), insulin-like growth factor–1 (IGF-1), insulin-like growth factor binding protein–3 (IGFBP-3), and basic fibroblast growth factor (bFGF). There were higher rates of delayed union in the POLY patients (45% vs. 23%) and EH in the TBI+POLY patients (33% vs. 17%) (not significant = NS). More delayed unions were observed in diaphyseal fractures suffered by POLY (28%) than in TBI+POLY (15%) patients (NS). EH after pelvic fracture was apparent in 52% TBI+POLY and in 21% POLY fractures (NS). P1CP levels did not differ between the groups, but the collagen breakdown parameter 1CTP was significantly higher in the POLY group (p = 0.01–0.04). IGF-1 levels were below normal in both groups, and did not differ. IGFBP- 3, an IGF-1-inhibiting and collagenase-3-activating protein, was significantly higher in POLY patients (p = 0.017–0.037). bFGF levels did not vary between groups. Increased serum levels of 1CTP and IGFBP-3 in POLY patients suggest that EH in TBI patients is secondary to decreased collagen breakdown rather than increased synthesis.

The pathophysiology of the serotoninergic system in malignant hyperthermia (MH) is not completely understood. The serotonin-2 (5HT(2A)) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) induces typical MH symptoms, including skeletal muscle rigidity, an increase in body temperature, hyperventilation and acidosis in conscious MH-susceptible (MHS) pigs. Whether these symptoms are directly generated in skeletal muscle, result from central serotonergic overstimulation or from a porcine stress syndrome remains unresolved. In this study the in vivo effects of DOI on anaesthetized (and thus stress-protected) MHS and MH-normal (MHN) pigs were investigated.

Zusammenfassung: Die maligne Hyperthermie (MH) ist eine genetisch bedingte, potentiell letale Disposition der Skelettmuskulatur gegenüber volatilen Anästhetika und depolarisierenden Muskelrelaxanzien, die sich während oder nach einer Narkose ausprägt.Dantrolen ist zum jetzigen Zeitpunkt das einzige Medikament, dass eine effektive und spezifische Therapie beim Menschen darstellt und die Mortalität der MH signifikant senken kann. Dantrolen ist ein Muskelrelaxans, dass die elektromechanische Koppelung inhibitiert. Obwohl der genaue Wirkmechanismus nicht abschließend geklärt ist, sprechen aktuelle Studien dafür, dass Dantrolen den Ryanodinrezeptor, der als Kalziumfreisetzungskanal des sarkoplasmatischen Retikulums fungiert, direkt hemmt.Dantrolen wird gegenwärtig nicht nur zur Therapie der MH, sondern auch bei anderen Erkrankungen, wie z.B.dem malignen neuroleptischen Syndrom (MNS) eingesetzt.Dantrolen ist schlecht wasserlöslich und daher aufwendig in der klinischen Handhabung.Neue Präparationen mit verbesserten pharmakokinetischen Eigenschaften wurden synthetisiert.Deren Zulassung zur klinischen Therapie wird jedoch aus ökonomischen Gesichtspunkten bis auf weiteres nicht realisiert.

In monocrotaline (MCT)-treated rats the -adrenoceptor-G-protein-adenylyl cyclase system—determined in crude membrane preparations from whole ventricular tissue—was desensitized not only in right (RV) but also in left ventricles (LV). This study aimed to assess the specific contribution of cardiomyocytes to these -adrenoceptor changes. Six-week-old male Wistar rats were treated with 60 mg/kg body weight MCT intraperitoneally; within 4–6 weeks, rats developed marked RV hypertrophy. Cardiomyocytes were isolated from RVs and LVs. In RV cardiomyocytes of MCT-treated rats, -adrenoceptor density was significantly reduced whereas it was unaltered in LV cardiomyocytes. Reduction of RV cardiomyocyte -adrenoceptors was due to a selective 1-adrenoceptor reduction. Isoprenaline (100 M)–induced cAMP increase was significantly reduced in RV but not in LV cardiomyocytes of MCT-treated rats. G protein–coupled receptor kinase activity was increased in RV but not in LV cardiomyocytes. 1-Adrenoceptor density and noradrenaline-induced increase in inositol phosphate formation were significantly reduced only in RV but not in LV cardiomyocytes from MCT-treated rats. It is concluded that in cardiomyocytes of MCT-treated rats, cardiac -adrenoceptors and 1-adrenoceptors are chamber-specifically desensitized only in the RV. Thus, changes in cardiac -adrenoceptors determined in membrane preparations from whole tissue homogenates do not correctly reflect changes occurring in cardiomyocytes.

We constructed a short multidimensional screening instrument for chronic pain patients based on the items contained in the Symptom Check List-90-Revised (SCL-90-R). The proposed dimensional structure of the SCL-90-R was recently shown to be irreproducible in chronic pain patients. As a consequence, the use of the Global Severity Index (GSI) was recommended, although it did not capture all information contained in the many items of the SCL-90-R. Based on an exploratory factor analysis, a six-dimensional structure using 27 items from the SCL-90-R was explored utilizing the data of 2780 chronic pain patients. A short form was prospectively tested on 581 patients in the same setting. Criteria for item selection were high convergent and low discriminant correlations. The assessment of the dimensions was kept short, but a minimum of four items were retained. A questionnaire yielding the dimensions (I) depressive symptoms, (II) dysthymic symptoms, (III) vegetative symptoms, (IV) agoraphobic symptoms, (V) symptoms of social phobia, and (VI) symptoms of mistrust was obtained. Additionally, the GSI of the SCL-90-R could be estimated precisely (r=0.96). The SCL-27 can be used for screening psychopathology in chronic pain patients. The scoring algorithm of the SCL-27 can be used for the 90-item form as well.

Zusammenfassung: Das maligne neuroleptische Syndrom (MNS) stellt eine schwerwiegende Komplikation der Therapie mit antipsychotischen Pharmaka dar. Wir berichten ber einen 65-jhrigen Patienten, der zur Therapie einer schweren depressiven Episode mit psychotischen Symptomen mit Haloperidol, Diazepam und Mirtazapin eingestellt wurde. Er entwickelte viele der MNS definierenden bzw. assoziierten Zeichen und Symptome: Hyperthermie, Rigor, erhhte Kreatinphosphatkinase, Leukozytose, erhhte Leberenzyme, eingeschrnktes Bewusstsein und vegetative Strungen. Zwei Tage nach Beginn des MNS war eine sekundre Pneumonie festzustellen, die sich aufgrund einer Brustwandrigiditt entwickelt haben knnte. Die intensivmedizinische Behandlung beinhaltete das sofortige Absetzen des auslsenden Agens, die supportive Therapie mit Rehydratation und Katecholaminen sowie die Applikation von Dantrolen. Nach 23-tgiger Intensivtherapie waren alle pathologischen Werte normalisiert und der Patient wurde auf eine internistische Station berwiesen. Drei bedeutende Theorien der Pathogenese wurden aufgestellt: 1. Blockade zentraler Rezeptoren; 2. Skelettmuskelzellen als primres Zielsubstrat und 3. sympathoadrenerge Hyperaktivitt. Die Differentialdiagnose beinhaltet u. a. maligne Hyperthermie und Serotoninsyndrom.

In rats, injection of the alkaloid monocrotaline (MCT) causes right ventricular hypertrophy and cardiac failure. In order to study whether, in MCT-treated rats, changes in the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system might be comparable to those found in human primary pulmonary hypertension, we assessed in right and left ventricles from MCT-treated rats the components of the β-adrenoceptor system: the receptor number and subtype distribution (by (-)-[125I]iodocyanopindolol binding), the G-proteins (by quantitative Western blotting), and the activity of adenylyl cyclase. A single injection of 60 mg/kg i.p. MCT caused in rats right ventricular hypertrophy (RVH); part of the rats developed cardiac failure (RVF). In these rats the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system was markedly changed β-adrenoceptors were desensitized due to a decrease in receptor number, an uncoupling of the receptor from the Gs-adenylyl cyclase system, a decrease in Gsand a decrease in the activity of the catalytic unit of adenylyl cyclase. In general, these changes were more pronounced in right ventricles vleft ventricles, and in rats with RVF vrats with RVH. On the other hand, cardiac muscarinic receptors and Giappeared not to be altered. We conclude that in MCT-treated rats changes in the cardiac β-adrenoceptor-G-protein(s)-adenylyl cyclase system occur that resemble those observed in human primary pulmonary hypertension. Thus, MCT-treated rat appears to be a suitable animal model to study in more detail the pathophysiology of the development of right heart failure, and to identify new therapeutic possibilities.

The SCL-90-R is a widely-used questionnaire for self-report of psychological distress and multiple aspects of psychopathology, as part of the evaluation of chronic pain patients and other non-psychiatric populations. The aim of this study is the presentation of clinical results of this multidimensional questionnaire in a convenience sample of 3540 chronic pain patients treated in a multidisciplinary pain centre. Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA), single scale factor analyses and Cronbach’s alphas are used to assess the internal structure and correlation to other instruments (CES-D, STAI, MPSS) to assess construct validity. It is shown that the 9 dimensions postulated by Derogatis et al.(1977 a) cannot at all be distinguished in chronic pain patients. The use of single subscores of the SCL-90-R, often employed as a screening instrument for specific diagnoses, such as depression, is at least questionable in chronic pain patients.

Performance analysis based on simulated results is a fundamental task of integrated circuit design. An approach to automated performance characterization of analog and mixed mode functional blocks is presented. The key points of this approach are an introduction of a procedural simulation method and a dedicated programming language for its implementation. Starting from a structural description of a building block and a set of specifications on its operational conditions the proposed method supports the generation of a comprehensive set of electrical properties, whereas no restrictions on underlying fabrication technologies or application domains of the circuit have to be taken into account. The flexibility of the proposed approach is demonstrated for two circuit examples, which differ both in their fabrication technology and in their application areas.

We report on eight cases in which ceramic implants were used to replace bone grafts. The results of this pilot study show definite usefulness of tricalcium phosphates, whereas hydroxyapatite did not prove suitable.

Sixteen patients suffering from pain due to a “battered” root syndrome (BRS) [1] were treated with spinal cord stimulation (SCS). All patients had undergone spinal surgery and complained of severe intractable radicular pain. The myelograms revealed an amputated root, the computerized tomograms showed periradicular scar tissues, electromyograms and/or sensory evoked potentials showed pathological changes. Electrical root stimulation via an indwelling, Teflon-coated needle reduced pain significantly within 30 min (80–100 Hz, 0.2–0.3 V). Root blocks with 1 ml bupivacaine (0.5%) abolished the patient's pain completely. No patient revealed major psychosomatic or psychosocial problems. Employing this patient selection schedule, 75% of the patients were pain-free after a mean follow-up period of 16 months range 6–30.

Nineteen patients with chronic pain due to a traumatic peripheral neuropathy were treated by means of implanted nerve stimulation. In 11 (58%) pain was completely relieved and in four (21%) it was reduced sufficiently to discontinue analgesics. The average follow-up was 11.5 months. The technique is described and the failures discussed. The necessity for implanting the stimulator proximally is emphasised.

We report our experience with sacroiliac joint arthrodesis in cases of overt osteoarthritis. Twenty-two operations were performed over a period of 3.5 years and reviewed between 12 and 55 months postoperatively. The clinical picture and diagnostic steps are discussed. We conclude that if the selection of patients is strict we can expect 70% satisfactory results.

The U.Q.S. is clinically described and a working hypothesis of its possible pathogenetic pathways is forwarded.

Background. Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH) susceptible (MHS) skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN) swine. Methods. MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5 mg⋅kg-1. The clinical occurrence of MH was defined by changes of central-venous pCO2, central-venous pH, and body core temperature. Results. Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation. Conclusions. The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.

The development of interdisciplinary pain clinics is discussed; the organization and staffing is described, and an outline plan is presented. It is emphasized that interdisciplinary pain clinics are the best means of medical care for patients suffering from chronic pain.