A template for broad consent in biobank research. Results and explanation of an evidence and consensus-based development process.

BACKGROUND: Biobanks increasingly presume long-term storage of biomaterials and data that shall be used for future research projects which are today unspecified. Appropriate consent documents for sample donors must therefore explain the breadth of consent and other elements of the biobank governance framework. Recent reviews demonstrated high variability in what issues these documents mention or not and how the issues are explained. This might undermine the protection of sample donors, complicate networked biobank research, create research waste and impact on public trust. METHODS: A systematic analysis of international research guidelines and existing broad consent templates was performed. Based on this information an interdisciplinary expert group from the AKMEK (Permanent Working Party of German RECs) developed a draft template and organized a comprehensive stakeholder consultation. After revision the final template was consented by all 53 German RECs. RESULTS: This paper briefly explores the spectrum of potentially relevant issues for broad consent forms. It then elaborates the template and how it was designed to be applicable in different types of biobanks. DISCUSSION: To further improve the validity and applicability of broad consent forms in biobank and other big data research, practice evaluations are needed. We hope that in this regard the presented template supports the development of new consent forms as well as the evaluation and revision of existing ones.

[Doubtful nosological validity of the chronic whiplash syndrome]. / Fragliche nosologische Validität des chronischen Halswirbelschleudertraumasyndroms.

BACKGROUND: Since the 1980s, victims of traffic accidents in western countries increasingly report chronic symptoms which they attribute to a whiplash injury of the cervical spine. In an extensive review article published in 1996, it was, however, concluded that this so-called chronic whiplash syndrome has little nosological validity. It was now investigated whether this conclusion could be upheld by the results of later published studies. METHODS: Extensive evaluation was carried out of all the whiplash literature listed in Pubmed since 1996 with the question whether research over the last 15 years has achieved a better validation of this syndrome. RESULTS: Of the over 1,600 publications about whiplash since 1996, no study could be identified which confirmed the nosological validity of the chronic whiplash syndrome. CONCLUSION: As a positive consequence of the results of this study, accident victims suffering whiplash can be informed about the very good prognosis after whiplash in a more trustworthy way. Many iatrogenic injuries can thus be avoided. The expert opinion after whiplash without radiologically documented and/or neurologically confirmed significant acute traumatic injury which can cause chronic symptoms, should generally not be in favor of insurance benefits. The authors propose that all of a set of minimal criteria should be fulfilled if in exceptional cases a probable relationship between the trauma and chronic symptoms can be assumed.

Postmortem proteomic analysis in human amygdala of drug addicts: possible impact of tubulin on drug-abusing behavior.

Besides the ventral tegmental area and the nucleus accumbens as the most investigated brain reward structures, several reports about the relation between volume and activity of the amygdala and drug-seeking behavior have emphasized the central role of the amygdala in the etiology of addiction. Considering its proposed important role and the limited number of human protein expression studies with amygdala in drug addiction, we performed a human postmortem proteomic analysis of amygdala tissue obtained from 8 opiate addicts and 7 control individuals. Results were validated by Western blot in an independent postmortem replication sample from 12 opiate addicts compared to 12 controls and 12 suicide victims, as a second "control sample". Applying 2D-electrophoresis and MALDI-TOF-MS analysis, we detected alterations of beta-tubulin expression and decreased levels of the heat-shock protein HSP60 in drug addicts. Western blot analysis in the additional sample demonstrated significantly increased alpha- and beta-tubulin concentrations in the amygdala of drug abusers versus controls (P = 0.021, 0.029) and to suicide victims (P = 0.006, 0.002). Our results suggest that cytoskeletal alterations in the amygdala determined by tubulin seem to be involved in the pathophysiology of drug addiction, probably via a relation to neurotransmission and cellular signaling. Moreover, the loss of neuroprotection against stressors by chaperons as HSP60 might also contribute to structural alteration in the brain of drug addicts. Although further studies have to confirm our results, this might be a possible pathway that may increase our understanding of drug addiction.

[Death in seclusion - a worldwide phenomenon illustrated on fringe groups in Munich]. / Der Einsame Tod - Sterben in Randgruppen in München.

100 randomised cases where a person lived and died in isolation in Munich were analysed. Factors such as social background, living situation, education, physiological and psychological state of health were evaluated. Personal isolation (=seclusion) seems to depend on various social, financial, psychological or physical reasons. Lack of contact with other people not only leads to psychological problems, but isolation also contributes to increased illness and early death. In order to improve the present social situation in Munich preventive social measures are necessary to achieve increase in health status for the elder and a decrease in mortality rate.

Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain.

Although the predominant role of tryptophan hydroxylase 2 (TPH2) in the CNS and its influence on the vulnerability to psychiatric disorders have clearly been demonstrated in several studies, the role of TPH1 on neuronal mechanisms, respectively on behavioral traits is still poorly understood. In a previous study of tryptophan hydroxylase 1 (TPH1) and TPH2 mRNA expression in different human brain regions we observed significantly higher TPH1 than TPH2 mRNA concentrations in the pituitary (unpublished observations). Considering the importance of the pituitary in the functional circuits between brain and body, we investigated the TPH1 and TPH2 mRNA expression in more detail, using human postmortem samples of the posterior and anterior pituitary compared to cortex, hippocampus and raphe nuclei. Specimens were available from different psychiatric patients (drug abusers, n=12; suicide victims, n=11; schizophrenics, n=9) and controls (n=15). Additionally we performed immunohistochemical analysis applying monospecific antibodies for both TPH isoforms to verify that the mRNA is of cellular and not just vascular or other origin. Highest TPH2 mRNA levels were observed in the raphe nuclei in patients and controls. By contrast, in the anterior and posterior pituitary TPH1 was found to be the predominantly expressed isoform in all subgroups. TPH1 and TPH2 mRNA expression in the further brain regions was only marginal and nearly identical except in the hypothalamus where higher TPH1 than TPH2 mRNA levels could be measured. Interindividual differences between the subgroups were not detectable. The results of the present study extended our previous findings by the additional immunohistochemical determination of the neuronal TPH1 and TPH2 protein expression in the anterior pituitary and provide evidence against a strictly separated duality of the serotonergic system. It seems that TPH1 might also have an impact on neuronal mechanisms via hypothalamic-pituitary-adrenal axis regulation by its predominant localization in the pituitary. These observations may open up new research strategies not only for several psychiatric disorders, but also for the relationship between psychiatric and somatic diseases.

Is post-mortem CT of the dentition adequate for correct forensic identification?: comparison of dental computed tomograpy and visual dental record.

The gold standard for identification of the dead is the visual dental record. In this context, several authors emphasize computed tomography (CT) as valuable supportive tool for forensic medicine. However, studies focusing on diagnostic accuracy of post-mortem computed tomography (PMCT) are still missing. Therefore, the aim of this study was to compare diagnostic accuracy of the visual dental record and post-mortem computed tomography (PMCT) of the dentition for identification of the dead. Ten whole skulls were included into the study. The entire dentition of each skull was first examined with the visual dental record as a gold standard and second using dental PMCT scans, performed on a 64-multi-detector CT (MDCT). 3D reformations, multi-planar reformations (MPR), and CT-orthopantomography (OPG) were performed in the post-processing. All examinations were analyzed by three independent investigators regarding the criteria for identification of the dead, e.g., in case of disaster. PMCT for the dental identification of the dead was difficult to perform and time consuming. Due to dental overlays and corresponding artifacts, the definite periphery of the dental fillings/inlays was not accurately defined resulting in 2.9% incorrect and 64.1% false negative findings, especially synthetic inlays were hardly or not recognizable at all. For the identification of the dead especially in case of disasters with large numbers of victims, the visual dental record is still to be considered the gold standard. In the identification process itself, there is no room for error at all, although some non-concordant information may occur. Thus, PMCT should only be performed for identification in individual cases due to the relatively high error rate.

Expression of oxygen-regulated protein 150 (ORP150) in skin wound healing and its application for wound age determination.

Immunohistochemical study combined with morphometry was carried out to examine the expression of oxygen-regulated protein 150 (ORP150) using 58 human skin wounds of different ages (group I, 0-12 h; II, 1-5 days; III, 7-14 days; and IV, 17-21 days). In human wound specimens aged 4-12 h, neutrophils recruited at the wound showed no positive signals for ORP150. With the increase in wound age of > or =7 days, granulation tissue and angiogenesis were observed, with the migration of macrophages and fibroblasts with ORP150-positive reactions. In semi-quantitative analysis, the average of ORP150-positive ratios in group III was highest. In group III, all samples had an ORP150-positive ratio of >40%, and 17 samples showed >50%. In group IV, three out of ten samples showed a positive ratio of 40-45% and the remaining seven cases less than 40%. Collectively, with regard to the practical applicability with forensic safety, these observations suggest that an ORP150-positive ratio of >50% strongly indicates a wound age of 7-14 days.

[Autopsy]. / Die wichtigsten Regeln für die Leichenschau.

The basic tasks of a physician when performing an autopsy are the establishment of death, the time of death, the manner of death and the cause of death as well as detecting communicable diseases. The person performing the autopsy must decide if a postmortem investigation is to be undertaken or whether the deceased can be buried without further examination. Thus, the physician has a crucial function that requires a high measure of diligence.

A new technique for the transcrestal sinus floor elevation and alveolar ridge augmentation with press-fit bone cylinders: a technical note.

BACKGROUND: The minimally invasive sinus floor elevation as first described by Summers is limited in the volume of augmentation that is possible. In contrast, the more invasive approach is the sinuslift of Tatum which is indicated for greater bone deficiencies. Therefore, a new technique was developed for transcrestal elevation of the sinus floor and alveolar ridge augmentation with bone dowels in press-fit technique. MATERIALS & METHODS: The crestal cortical bone is cut with a hollow grinder followed by an indirect sinus floor elevation with a plunger. The cylindrical defect is then filled with a cylindrical bone transplant with the press-fit technique. RESULTS: The method was tested in ten fresh porcine skulls and was successful when applied subsequently in two fresh human cadavers (both female, age 60 and 92 years). This was followed by the insertion of another cylinder in overlapping mosaic manner with the dowel-lift technique in the left maxilla in one cadaver. A sinoscopy of the second cadaver experiment showed no perforation of the maxillary sinus membrane. The result was convincing. CONCLUSION: A new method for transcrestal elevation of the maxillary sinus floor and alveolar ridge augmentation with bone cylinders in press-fit technique was developed. The operation combines the minimally invasive approach of Summers with a large augmentation volume otherwise requiring the direct technique of Tatum. These results should encourage further preclinical experiments.

Sex-specific fluorescent labelling of cells for laser microdissection and DNA profiling.

Sex-specific isolation of cells from mixtures would greatly facilitate forensic casework. Thus, male and female cell mixtures were marked with a fluorescent X/Y-probe CEP X SpectrumOrange/Y SpectrumGreen DNA probe kit for fluorescence in situ hybridization, and single cells were isolated via laser microdissection (LMD). DNA profiling of LMD isolated, hybridized cells showed usable short tandem repeat profiles for at least 20 cells, which are comparable with results from other studies. To simulate casework samples, the method was also optimized for air-dried samples.

[A new technique for transcrestal sinus floor elevation with press-fit bone cylinders (dowel lift): short communication of the first in vitro results]. / Eine neue Technik zur indirekten Sinusbodenelevation mit Knochendübeln in Press-fit-Technik (Dowel-Lift): Kurze Vorstellung der ersten In-vitro-Ergebnisse.

The minimally invasive sinus floor elevation as first described by Summers is limited in augmentation volume, whereas a more invasive approach is required for the technique of Tatum for larger bone defects. We developed a new technique for the transcrestal elevation of the sinus floor with bone dowels using a press-fit technique (dowel lift). We present the technique with first in vitro results in a fresh, unpreserved, human cadaver.

[Typical findings of maltreated children]. / So differenzieren Sie zwischen Unfall und Cewalttat. Indizien der Kindesmisshandlung.

Childhood maltreatment manifests in a variety of forms and the underlying causes are manifold. In contrast to other offences involving physical injury, reporting behavior has, statistically speaking, remained unchanged. Patterns of injury must first be established and documented, and this involves a complete examination of the child's body. Depending on the constellation of findings, a radiological diagnosis is usually necessary. When all the findings have been collected, the further steps to be taken--where indicated a report to the police--must be discussed. All the evidence must be recorded, and photos obtained of all externally visible injuries before they fade. It is not the task of the physician to develop criminalistic ambitions, for example, by grilling (a parent) on the cause of the injuries. However, he/she has a duty to do everything necessary to protect the well-being of the child.

[Paternity tests--current methods and legal background]. / Vaterschaftstests: Wie sie funktionieren und worauf es vor Gericht ankommt: Meins oder seins?

Paternity expertises are established on the basis of so-called STR (short-tandem repeat) polymorphisms. As a rule, they are requested by a judge for use as evidence in the clarification of the question of fathershaft in civil court cases. In addition to this, however, they are being requested more and more frequently by private persons, in the majority of cases with the aim of challenging presumptive fathershaft. In this latter case, however, it must be noted that when a minor is involved, the consent of the person who has the care and custody of the child must be available.

Digoxigenin labelling and laser capture microdissection of male cells.

Laser capture microdissection (LMD) is a relatively new technique for the isolation of single cells. The application in forensic investigations has become more and more widespread, especially to select spermatozoa out of mixtures with vaginal cells. In particular in cases with low numbers of sperm it could be profitable to isolate all male cells (e.g. sperm and male epithelial cells) instead of focussing on the sperm only. Therefore, the specific labelling and detection of the male cells in a male/female cell mixture is necessary. In order to label all cells carrying a Y-chromosome we used a digoxigenin labelled chromosome Y hybridisation probe (Q Biogen). The stained cells were isolated with the SL microCut LMD system from Molecular Machines & Industries AG (MMI). At least ten diploid male cells were required to obtain a partial STR profile, with 20 cells, a full profile could be obtained.

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e. stabilization or reestablishment of the circulatory and respiratory system) or of the early clinical care (e.g. prompt diagnosis and treatment of an intracranial space occupying mass, maintenance of a competent circulatory and respiratory system, and others) by and large constitute the current treatment based on considerable organizational and logistical efforts. These and other components of the head injury treatment are certainly worthwhile of a systematic analysis as to their efficacy or remaining deficiencies, respectively. Deficits could be associated with delays of providing preclinical rescue procedures (e.g. until intubation of the patient or administration of fluid). Delays could also be associated in the hospital with the diagnostic establishment of intracranial lesions requiring prompt neurosurgical intervention. By support of the Federal Ministry of Education and Research and under the auspices of the Forschungsverbund Neurotraumatology, University of Munich, a prospective system analysis was carried out on major aspects of the pre- and early clinical management at a population based level in patients with traumatic brain injury. Documentation of pertinent data was made from August 1998 to July 1999 covering a catchment area of Southern Bavaria (5.6 mio inhabitants). Altogether 528 cases identified to suffer from severe head injury (GCS < or = 8 or deteriorating to that level within 48 hrs) were enrolled following admission to the hospital and establishment of the diagnosis. Further, patients dying on the scene or during transport to the hospital were also documented, particularly as to the frequency of severe head injury as underlying cause of mortality. The analysis included also cases with additional peripheral trauma (polytrauma). The efficacy of the logistics and organization of the management was studied by documentation of prognosis-relevant time intervals, as for example until arrival of the rescue squad at the scene of an accident, until intubation and administration of fluid, or upon hospital admission until establishment of the CT-diagnosis and commencement of surgery or transfer to the intensive care unit, respectively. The severity of cases studied in the present analysis is evident from a mortality of far above 40% of cases admitted to the hospital, which was increased by about 20% when including prehospital mortality. The outcome data notwithstanding, the emerging results demonstrate a high efficacy of the pre- and early clinical management, as indicated by a prompt arrival of the rescue squad at the scene, a competent prehospital and early clinical management and care, indicative of a low rate of avoidable complications. It is tentatively concluded on the basis of these findings that the patient prognosis is increasingly determined by the manifestations of primary brain damage vs. the development of secondary complications.

Ninhydrin treatment as a screening method for the suitability of swabs taken from contact stains for DNA analysis.

More and more swabs containing unknown traces of biological material are submitted for forensic DNA analysis. Most of the samples are swabs taken from handled items such as tools, weapons and handles etc. Therefore, we tried to develop a screening method in order to focus the investigation on samples containing biomolecules, such as amino acids which might be associated with nucleic acids. A total of 285 swabs taken from various items collected during crime scene investigations were treated with ninhydrin which leads to a purple colour for samples containing amino acids. Of the swabs 158 were classified as ninhydrin positive and 76% of these samples yielded DNA profiles that fulfil the criteria for inclusion in the German national DNA database (profile frequency greater than 1 in 100,000) or in DNA mixtures which could at least be compared with suspects. In comparison only 9% of the 127 samples shown to be ninhydrin negative, revealed a usable DNA profile. Consequently, ninhydrin treatment was found to be an effective screening method which resulted in an increase in the rate of successfully typed samples and subsequently in a reduction of the costs due to the lower number of samples that needed to be typed.