Epidemiologie des Schwerverletzten Eine prospektive Erfassung der pr?klinischen und klinischen Versorgung Eine prospektive Erfassung der pr?klinischen und klinischen Versorgung

Trotz der gro?en medizinischen und sozio?konomischer Bedeutung der schweren Mehrfachverletzung existieren nur wenige aktuelle Daten zur Beschreibung dieses Kollektivs. Ziel der Untersuchung war es, die von 1993 – 1997 prospektiv und multizentrisch erfa?ten 2069 Patienten des DGU-Traumaregisters epidemiologisch zu untersuchen. Es erfolgte eine deskriptive Analyse der Inzidenz der Verletzungen und Komplikationen im Patientenkollektiv und des Umfanges therapeutischer Ma?nahmen. Der Verkehrsunfall war mit 56,7% die h?ufigste Unfallursache, das Durchschnittsalter betrug 38,5 ± 18,7 Jahre, das Verh?ltnis m?nnlich zu weiblich 2,6:1. Bei einem “Injury Severity Score” (ISS) von durchschnittlich 22,2 ± 13,1 Punkten war bei fast ausschlie?lich stumpfen Verletzungen das Thoraxtrauma die h?ufigste relevante Verletzung (AIS der Region Thorax ≥ 3 Punkte, 44,5%). Das Sch?del-Hirn-Trauma (SHT) mit einem AIS ≥ 3 (39,2%) beeinflu?te die Frühletalit?t (Tod ≤ 24 h nach Trauma, 51,7% der Verstorbenen) und die Gesamtklinikletalit?t (18,6%); 68,9% der Patienten zeigten Extremit?tenverletzungen; 71,7% der Patienten wurden im Bereitschaftsdienst aufgenommen (16–8 Uhr werktags, Wochenenden und Feiertage). Die Verletzten wurden Median 4 Tage beatmet, 6 Tage intensivstation?r behandelt und verweilten 19 Tage im Krankenhaus. An Komplikationen wurden Organversagen (Lunge 22%, Kreislauf 18,7%, Leber 9,6%, Niere 3,1%) und Sepsis (11,6%) erfa?t. Die durchgeführte epidemiologische Analyse stellt eine umfassende Beschreibung eines gro?en Kollektivs schwer Mehrfachverletzter dar. Die aktuellen Daten des DGU-Traumaregisters sind nutzbar zur Beantwortung wissenschaftlicher, klinischer und ?konomischer Fragen zum Qualit?tsmanagement.     

New mutations of the hydroxymethylbilane synthase gene in German patients with acute intermittent porphyria

Acute intermittent porphyria (AIP) is a low-penetrant, autosomal dominant disorder caused by decreased activity of hydroxymethylbilane synthase (HMBS; MIM 176 000), the third enzyme in the heme biosynthetic pathway. We report the first molecular analysis of HMBS gene mutations in classical AIP patients of German origin. The HMBS gene of 5 German AIP patients was analysed by DGGE-screening and direct sequencing of amplified genomic DNA. Five different mutations including four novel mutations were found. Three of them are single base substitutions that affected exon 3 (R16C), exon 10 (V202L), and intron 13 (T to A, IVS13+2) The two remaining mutations are frameshifts which produce a stop codon (del GA in exon 6 and insA in exon 14). These mutations are likely to be responsible for the decrease in HMBS activity found in both erythrocytes and non-erythroid cell lines (lymphocytes). Our results demonstrate the allelic heterogeneity of HMBS mutations in AIP patients of German origin.     

Bioactivation of diclofenac via benzoquinone imine intermediates-identification of urinary mercapturic acid derivatives in rats and humans.

The metabolism of diclofenac has been reported to produce reactive benzoquinone imine intermediates. We describe the identification of mercapturic acid derivatives of diclofenac in rats and humans. Three male Sprague-Dawley rats were administered diclofenac in aqueous solution (pH 7) at 50 mg/kg by intraperitoneal injection, and urine was collected for 24 h. Human urine specimens were obtained, and samples were pooled from 50 individuals. Urine samples were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Two metabolites with MH(+) ions at m/z 473 were detected in rat urine and identified tentatively as N-acetylcysteine conjugates of monohydroxydiclofenac. Based upon collision-induced fragmentation of the MH(+) ions, accurate mass measurements of product ions, and comparison of LC/MS/MS properties of the metabolites with those of synthetic reference compounds, one metabolite was assigned as 5-hydroxy-4-(N-acetylcystein-S-yl)diclofenac and the other as 4'-hydroxy-3'-(N-acetylcystein-S-yl)diclofenac. The former conjugate also was detected in the pooled human urine sample by multiple reaction-monitoring LC/MS/MS analysis. It is likely that these mercapturic acid derivatives represent degradation products of the corresponding glutathione adducts derived from diclofenac-2,5-quinone imine and 1',4'-quinone imine, respectively. Our data are consistent with previous findings, which suggest that oxidative bioactivation of diclofenac in humans proceeds via benzoquinone imine intermediates.     

Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients

BACKGROUND: There is increasing evidence for acute traumatic coagulopathy occurring prior to emergency room (ER) admission but detailed information is lacking. PATIENTS AND METHODS: A retrospective analysis using the German Trauma Registry database including 17,200 multiple injured patients was conducted to determine (a) to what extent clinically relevant coagulopathy has already been established upon ER admission, and whether its presence was associated (b) with the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand seven hundred and twenty-four patients with complete data sets were screened. RESULTS: Coagulopathy upon ER admission as defined by prothrombin time test (Quick's value) <70% and/or platelets <100,000 microl(-1), was present in 34.2% of all patients. There was an increasing incidence for coagulopathy with increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was observed in >40% of patients with >2000 ml, in >50% with >3000 ml, and in >70% with >4000 ml administered. Ten percentage of patients presented with clotting disorders although pre-clinical resuscitation was limited to 500 ml of i.v. fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15) versus 21 (S.D. 12) (p<0.001). Twenty-nine percentage of patients with coagulopathy developed multi organ failure (p<0.001). Early in-hospital mortality (<24h) was 13% in patients with coagulopathy (p<0.001) and overall in-hospital mortality totalled 28% (p<0.001). CONCLUSION: There is a high frequency of established coagulopathy in multiple injury upon ER admission. The presence of early traumatic coagulopathy was associated with the amount of intravenous fluids administered pre-clinically, magnitude of injury, and impaired outcome.     

Loss of balancing selection in the βS globin locus

Background  

Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations.     

Syndrome co-occurrence and treatment outcomes in youth mental health clinics

Despite widespread speculation that syndrome co-occurrence undermines treatment outcomes, this hypothesis has not been fully examined within clinical care settings. To address this gap, the authors investigated the relation between syndrome co-occurrence and outcome among 325 clinically referred youths. For every syndrome, higher initial severity was predictive of greater treatment gains and higher posttreatment symptom levels; contrary to speculation in the literature, co-occurrence effects were rare and modest in size, accounting for 0.6% of outcome variance on average. The results suggest that co-occurrence, though common in youth clinical care, is not an obstacle to treatment success in most cases. In addition to its substantive findings, the study illustrates how a dimensional approach can be used to shed new light on co-occurrence in clinical care.     

Vitamin D Receptor Expression in Vitiligo

Background:

Vitiligo is a progressive depigmenting disorder characterized by loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Vitamin D has stimulatory effects on melanocytes and acts through its nuclear Vitamin D receptor (VDR) on target cells.

Aims and Objectives:

The purpose of this study was to declare the role of Vitamin D in the pathogenesis of vitiligo.

Materials and Methods:

This case-control study included 30 vitiligo patients and 30 age, gender-matched healthy controls. Blood samples were withdrawn from the study subjects, and the serum 25(OH) D level was determined by an enzyme-linked immunosorbent assay technique. Serum 25(OH) D levels were divided into: Normal or sufficient (≥30 ng/ml), insufficient (< 30-> 20ng/ml), and deficient (≤20 ng/ml) levels. Skin biopsies were obtained from the depigmented lesions and clinically normal skin of vitiligo patients and from the controls, and VDR gene expression was determined using real-time polymerase chain reaction.

Results:

Only 10 patients with vitiligo (33.3%) had sufficient serum 25(OH) D levels (≥30 ng/ml), 12 patients (40%) had insufficient levels, and 8 patients (26.7%) had deficient levels. On the other hand, most of the controls (96.7%) had sufficient levels. The mean serum 25(OH) D level in patients was significantly decreased compared to controls (P < 0.001). The VDR-mRNA expression was also significantly decreased in lesional and nonlesional skin of patients compared to controls (P < 0.001, P < 0.001, respectively).

Conclusion:

Vitamin D deficiency influences the extent of vitiligo and could contribute to the pathogenesis of vitiligo through its immunomodulatory role and its role in melanogenesis.