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Zusammenfassung: Die Umsetzung der evidenzbasierten Medizin (EBM) in ihrem eigentlichen Sinn – als innovativer Weg der Verbesserung individueller Krankenversorgung durch die Synthese der besten verfügbaren externen Evidenz (d. h. der Ergebnisse klinischer Forschung) und der ärztlichen Erfahrung – ist in der Unfallchirurgie bislang nur unzureichend gelungen. Neben fachfremden Gründen wie zu theoretische und zu formale Ausgestaltung wurden die Besonderheiten chirurgischer Fächer von den Begründern der EBM nur unzureichend berücksichtigt. Die Bedeutung klinischer Studien wird zunehmend anhand hierarchisch aufgebauter Evidenzstufen bewertet; die Metaanalyse randomisierter Studien und nachfolgend diese selbst stellen den Referenzstandard für therapeutische Interventionsstudien dar. Der Nachweis einer ursächlichen Beziehung zwischen Intervention und Ergebnis hängt nicht nur vom Studiendesign, sondern auch von anerkannten Kausalitätskriterien, der A-priori-Wahrscheinlichkeit und der Größe des beobachteten Therapieeffekts ab. Die Unfallchirurgie weist gegenüber nichtoperativen Fächern spezifische Unterschiede auf, die für die Wahl des Studiendesigns und bei der Evidenzgraduierung berücksichtigt werden müssen. Die Ergebnisqualität ist untrennbar mit der operativen Expertise verbunden.

Over a five-year period, adult patients with marginal impaction of acetabular fractures were identified from a registry of patients who underwent acetabular reconstruction in two tertiary referral centres. Fractures were classified according to the system of Judet and Letournel. A topographic classification to describe the extent of articular impaction was used, dividing the joint surface into superior, middle and inferior thirds. Demographic information, hospitalisation and surgery-related complications, functional (EuroQol 5-D) and radiological outcome according to Matta’s criteria were recorded and analysed. In all, 60 patients (57 men, three women) with a mean age of 41 years (18 to 72) were available at a mean follow-up of 48 months (24 to 206). The quality of the reduction was ‘anatomical’ in 44 hips (73.3%) and ‘imperfect’ in 16 (26.7%). The originally achieved anatomical reduction was lost in12 patients (25.8%). Radiologically, 33 hips (55%) were graded as ‘excellent’, 11 (18.3%) as ‘good’, one (1.7%) as ‘fair’ and 15 (25%) as ‘poor’. A total of 11 further operations were required in 11 cases, of which six were total hip replacements.Univariate linear regression analysis of the functional outcome showed that factors associated with worse pain were increasing age and an inferior location of the impaction. Elevation of the articular impaction leads to joint preservation with satisfactory overall medium-term functional results, but secondary collapse is likely to occur in some patients.Cite this article: Bone Joint J2013;95-B:230–8.

We investigated whether patients who underwent internal fixation for an isolated acetabular fracture were able to return to their previous sporting activities.We studied 52 consecutive patients with an isolated acetabular fracture who were operated on between January 2001 and December 2002. Their demographic details, fracture type, rehabilitation regime, outcome and complications were documented prospectively as was their level and frequency of participation in sport both before and after surgery. Quality of life was measured using the EuroQol-5D health outcome tool (EQ-5D).There was a significant reduction in level of activity, frequency of participation in sport (both p < 0.001) and EQ-5D scores in patients of all age groups compared to a normal English population (p = 0.001). A total of 22 (42%) were able to return to their previous level of activities: 35 (67%) were able to take part in sport at some level. Of all the parameters analysed, the Matta radiological follow-up criteria were the single best predictor for resumption of sporting activity and frequency of participation.

Purpose. To analyse the functional and radiological outcomes of the Bristow-Latarjet procedure in patients with recurrent anterior glenohumeral instability.Methods. Records of 29 patients were reviewed retrospectively. Date of first dislocation, injury mechanism, and number of recurring dislocations before and after surgery were recorded. The overall function and stability of the shoulder was evaluated.Results. 24 (83%) of the glenohumeral instabilities were caused by trauma. The mean number of recurring dislocations was 8 (95% confidence interval [CI], 0–18); one patient had had 40 recurrences. No dislocation ensued postoperatively. The overall functional outcome was good, with a mean Rowe score of 90 points (95% CI, 78–100). Scores of 17 (59%) of the patients were excellent, 7 (24%) were good, 3 (10%) were fair, and 2 (7%) were poor.Conclusion. The Bristow-Latarjet procedure is a good surgical treatment for recurrent anterior-inferior instability of the glenohumeral joint.

Zusammenfassung: Pulsierende elektromagnetische Felder (PEMF) werden seit langem für die symptomatische Behandlung von Erkrankungen und Verletzungsfolgen des Bewegungsapparats propagiert, aufgrund ihrer zweifelhaften wissenschaftlichen Reputation von verschiedenen Kostenträgern jedoch nicht finanziert. Die Pulsierende SignalTherapie (PST) gilt als Spielart der PEMF. Hersteller sprechen von mehr als 100.000 erfolgreichen und nebenwirkungsfreien Behandlungen unter den Bedingungen randomisierter Studien (RCT). Für das Indikationsgebiet der symptomatischen Gonarthrose kann diese Behauptung nicht aufrechterhalten werden. Tatsächlich zeigten die 2 verfügbaren, methodisch mangelhaften RCT mit Einschluss von nur 126 Patienten keinen konsistenten Vorteil der PST gegenüber einer Scheinbehandlung. Auch 2 korrespondierende Studien zur PEMF wiesen keinen Vorteil der aktiven gegenüber einer Plazebotherapie nach. 5 Jahre nach dem vom Bundesausschuss der Ärzte und Krankenkassen erstellten kritischen Gesundheitstechnologiereport existieren keine Daten, die eine Empfehlung oder gar Kostenübernahme der PST für die Behandlung der Gonarthrose rechtfertigen würden.

Zusammenfassung: Die Zusammenhangsbegutachtung gehört zu den verantwortungsvollsten Aufgaben der am berufsgenossenschaftlichen Heilverfahren beteiligten Ärzte. Praktisch jede Problemstellung lässt sich klar und einfach lösen, wenn man die Fragenldquor1. War der angeschuldigte Unfall geeignet, den Körperschaden hervorzurufen?ldquoundldquor2. War der Unfall rechtlich wesentlich?ldquochronologisch bearbeitet. Die kritische Würdigung der wissenschaftlichen Literatur ist Voraussetzung für eine fundierte Abwägung konkurrierender Kausalitäten. Am Beispiel des so genannten posttraumatischen Zervikalsyndroms nachldquorHWS-Distorsionldquolässt sich gut belegen, dass der aktuelle klinisch-epidemiologische Kenntnisstand nur im Einzelfall die Einschätzung einer Eignung erlaubt, da die Effektstärke demografischer und sonstiger Variablen als überwiegend einzuschätzen ist und die geforderte rechtliche Wesentlichkeit des Ereignisses im Regelfall für die Betrachtung der langanhaltenden und häufig erst später auftretenden Symptome, nicht erfüllt wird.

The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m2reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD.

Zusammenfassung: Das Konzept der Versorgung schwerster abdomineller Verletzungen nach Prinzipien desldquordamage controlldquofindet auch im deutschen Sprachraum zunehmend Verbreitung. Die Indikation zurldquordamage controlldquo-Versorgung stellt sich bei Vorliegen der Trias Azidose, Hypothermie und Koagulopathie (AHK-Syndrom). Als Zugang wird eine Medianlaparotomie gewählt. Bei Hohlorganverletzungen wird keine primäre Anastomose erzwungen, im Vordergrund steht die Kontaminationskontrolle. Methoden der Wahl sind die Anlage eines Anus praeter oder der temporäre Blindverschluss. Bei Milzrupturen steht die Splenektomie im Vordergrund. Massiv blutende Leberverletzungen werden durch Packing ggf. mit temporärer Gefäßokklusion kontrolliert. Abschließend erfolgt ein temporärer Bauchdeckenverschluss. Nach intensivmedizinischer Stabilisierung wird eine definitive Versorgung im Intervall vorgenommen.

Zusammenfassung Mecklenburg-Vorpommern liegt seit 1998 an der Spitze der Verkehrsunfallzahlen mit tödlichem Ausgang (Statistisches Bundesamt Wiesbaden). Eine der Haupttodesursachen für Erwachsene in Mecklenburg-Vorpommern sind Unfälle im Straßenverkehr. Wissenschaftliche Auseinandersetzungen, die sich interdisziplinär mit den spezifischen Problemen des Bundeslandes Mecklenburg-Vorpommern zum Thema Verkehrsunfälle beschäftigen, existieren bisher nicht. Nach 18-monatiger Vorbereitung und Planung werden seit dem 08. Januar 2001 im Rahmen einer prospektiven, nichtinterventionellen Studie innerhalb des Forschungsverbundes Community Medicine an der Ernst-Moritz-Arndt-Universität reale Unfälle erstmalig unter Berücksichtigung sowohl von lokalen, umwelt- und landesspezifischen sowie fahrzeugtechnischen als auch individuell psychologischen Aspekten untersucht und analysiert. Anhand der gewonnenen Einsichten über Fahrverhalten, Unfallursachen und Unfallverursacher konnten bereits jetzt konkrete primäre Präventionsmaßnahmen zur Reduktion der Unfälle erarbeitet werden.

Human plasma PAF-AH (platelet-activating factor-acetylhydrolase) is a Ca(2)+-independent phospholipase A2 of hematopoietic origin associated with LDL and HDL; it degrades PAF and oxidizes phospholipids. We show that human macrophages synthesize PAF-AH as a premedial Golgi precursor containing high mannose N-linked glycans. Secreted PAF-AH possesses a molecular mass of approximately 55 kDa and contains mature N-linked glycans. Secreted PAF-AH activity (90 +/- 4% of the total) bound to a wheat germ lectin column and could be eluted with N-acetylglucosamine, whereas digestion with N-acetylneuraminidase II completely abolished enzyme absorption. Tunicamycin significantly reduced cell-associated PAF-AH activity and inhibited enzyme secretion; but it did not alter the ratio of secreted to cell-associated enzyme (1.8 at 6 h and 3.1 at 24 h), suggesting that glycosylation is not essential for PAF-AH secretion. Digestion of cell-associated PAF-AH or secreted PAF-AH with peptide N-glycosidase F affected neither catalytic activity nor its resistance to proteolysis with trypsin or proteinase K; in addition, it did not affect PAF-AH association with LDL, but significantly increased its association with HDL. We suggest that macrophage-derived PAF-AH contains heterogeneous asparagine-conjugated sugar chain(s) involving sialic acid, which hinders its association with HDL but does not influence the secretion, catalytic activity, or resistance of PAF-AH to proteases.

Evidence-based medicine (EBM) is an efficient, modern tool to validate decisions in patient care. Its principles and aims are discussed by health-care providers of all disciplines; however, major controversies still exist on the widespread view of EBM as a simple academic instrument. This paper elucidates the background for the necessary implementation of EBM in Germany and the meaning of `evidence'. We introduce the features of a workshop as the best way to learn basic techniques of EBM, and we provide aspects of its application to clinical practice.

Adenylyl cyclase activity plays a central role in the regulation of most cellular processes. At least eight different adenylyl cyclases have been identified, which are endowed with various and sometimes opposing regulatory properties. Recently we have localized the human genes encoding two of these adenylyl cyclases: the gene for type 11 adenylyl cyclase is located on chromosome 2 (sub-band 2p15.3), the gene for type VIII is located on chromosome 8 (sub-band 8824.2). More recently the type I gene has been located on chromosome 7 (sub-band 7pl2–7p13). Using in situ hybridization, we have now localized the genes for three other adenylyl cyclases: the type III gene has been localized on chromosome 2 in the sub-band 2p22–2p24, the type V gene on chromosome 3 at position 3q13.2–3q21, and the type VI gene on chromosome 12 at position 12q12–12q13. It therefore appears that all adenylyl cyclase genes, known at present are located on different chromosomes and thus are likely to be independently regulated.

We have previously shown that liver plasma membrane (Ca2+-Mg2+)-ATPase activity is inhibited by glucagon. To investigate the possible involvement of a GTP-binding (G) protein in this regulation, we have examined the effects of pertussis toxin and cholera toxin on inhibition of (Ca2+-Mg2+)-ATPase by glucagon. Treatment of liver plasma membranes with pertussis toxin did not affect the sensitivity of (Ca2+-Mg2+)-ATPase to the hormone. In contrast, treatment of plasma membranes or prior injection of animals with cholera toxin prevented inhibition of the (Ca2+-Mg2+)-ATPase by glucagon. Even though adenylate cyclase activity was increased by cholera toxin treatment, addition of cyclic AMP did not mimic the effect of cholera toxin in blocking glucagon-mediated inhibition of (Ca2+-Mg2+)-ATPase activity. These data suggest that a cholera toxin-sensitive protein, perhaps Gs or a Gs-like protein, is involved in the regulation of liver (Ca2+-Mg2+)-ATPase activity. The results emphasize the possible role of Gs-like proteins in regulation of enzymes other than adenylate cyclase and suggest that the study of (Ca2+-Mg2+)-ATPase may provide a useful enzymatic system to examine such regulation.

Recently, we characterized a cDNA clone that encodes a human brain adenylyl cyclase (HBAC1). In the present study, we identified a second population of mRNA suspected to encode a new brain adenylyl cyclase (HBAC2). The amino acid sequence of HBAC2 displays significant homology with HBAC1 in the highly conserved adenylyl cyclase domain (250 aminio acids), found in the 3' cytoplasmic domain of all mammalian adenylyl cyclases. However, outside this domain, the homology is extremely low, suggesting that the corresponding mRNA originates from a different gene. We report here the first chromosomal localization of the adenylyl cyclase genes determined by in situ hybridization of human metaphase chromosomal spreads using human brain cDNA probes specific for each mRNA. The probe corresponding to HBAC1 exhibited a strong specific signal on chromosome 8q24, with a major peak in the band q24.2. In contrast, the HBAC2 probe hybridized to chromosome 5p15, with a major peak in the band p15.3. The two cDNAs hybridized at the two loci without any cross reactivity. Thus, in human brain, a heterogeneous population of adenylyl cyclase mRNAs is expressed, and the corresponding genes might be under the control of independent regulatory mechanisms.

Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites.

Zusammenfassung: Die benigne symmetrische Lipomatose Madelung ist eine seltene Erkrankung, die durch das diffuse Wachstum nicht-gekapselter Lipome charakterisiert ist. ber eine enge tiopathogenetische Beziehung zu Alkohol- und Nikotinabusus, metabolischen Strungen und malignen Tumoren wurde berichtet. Rezidive nach chirurgischer Therapie sind hufig, wenn auch im Einzelfall zufriedenstellende funktionelle und kosmetische Resultate erzielt werden knnen. Wir berichten ber einen Fall mit ungewhnlicher Lipomverteilung.

The Bone & Joint Journal provides the latest evidence to guide the clinical practice of orthopaedic surgeons. The benefits of one intervention compared with another are presented using outcome measures; some may be specific to a limb or joint and some are more general health-related quality of life measures. Readers will be familiar with many of these outcome measures and will be able to judge the relative benefits of different interventions when measured using the same outcome tool; for example, different treatments for pain in the knee measured using a particular knee score. But, how should readers compare outcomes between different clinical areas using different outcome measures? This article explores the use of standardised effect sizes.Cite this article: Bone Joint J2014;96-B:853–4.

The importance for observing the intention-to-treat approach in clinical studies is explained.Cite this article: Bone Joint J2013;95-B:1443–4.