Biomedical subjects

B Brinkmann

Publications and source records attributed to B Brinkmann.

At least 19 recordsLinked to original sources

PubMed2001

The Y chromosome pool of Jews as part of the genetic landscape of the Middle East.

A sample of 526 Y chromosomes representing six Middle Eastern populations (Ashkenazi, Sephardic, and Kurdish Jews from Israel; Muslim Kurds; Muslim Arabs from Israel and the Palestinian Authority Area; and Bedouin from the Negev) was analyzed for 13 binary polymorphisms and six microsatellite loci. The investigation of the genetic relationship among three Jewish communities revealed that Kurdish and Sephardic Jews were indistinguishable from one another, whereas both differed slightly, yet significantly, from Ashkenazi Jews. The differences among Ashkenazim may be a result of low-level gene flow from European populations and/or genetic drift during isolation. Admixture between Kurdish Jews and their former Muslim host population in Kurdistan appeared to be negligible. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent (Kurds, Turks, and Armenians) than to their Arab neighbors. The two haplogroups Eu 9 and Eu 10 constitute a major part of the Y chromosome pool in the analyzed sample. Our data suggest that Eu 9 originated in the northern part, and Eu 10 in the southern part of the Fertile Crescent. Genetic dating yielded estimates of the expansion of both haplogroups that cover the Neolithic period in the region. Palestinian Arabs and Bedouin differed from the other Middle Eastern populations studied here, mainly in specific high-frequency Eu 10 haplotypes not found in the non-Arab groups. These chromosomes might have been introduced through migrations from the Arabian Peninsula during the last two millennia. The present study contributes to the elucidation of the complex demographic history that shaped the present-day genetic landscape in the region.

Alleles↗

PubMed2001

De novo mutation in the SCN5A gene associated with early onset of sudden infant death.

BACKGROUND: Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. METHODS AND RESULTS: In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms(1/2)) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A, which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. CONCLUSIONS: In this study, we report a de novo mutation in the sodium channel gene SCN5A, which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.

Age of Onset↗

PubMed2001

Was the pedestrian hit in an erect position before being run over?

If a pedestrian was run over by a car, the question can arise whether there was a preceding collision while the pedestrian was in an erect position. From a total of 53 selected autopsy reports, the findings associated with accidents known to involve running over in isolation (n=32) were compared to findings associated with a combined mechanism of a primary impact in an erect position and subsequent running over (n=21). Findings exclusively present in the combined group were wedge-shaped bone fractures ("Messerer"-wedges, 38%), glass fragment injuries (24%), traumatic amputations (10%), traces of car paint on the lower extremities (50%) and abrasions of the shoe soles (17%). These findings can be considered specific for a primary impact in an erect position. Fractures of the cervical and lumbar spine were present in the combined group in 33 and 17%, respectively. In contrast, in the run over group, there was only one case of fracture of the cervical and one of the lumbar spine and both cases involved direct contact with a car wheel. Fractures of the cervical and lumbar spine are, therefore, very indicative for a primary impact. "Bumper injuries", sacroiliac dislocations and fractures of the thoracic spine were approximately 2.5 times more common in the combined group than in the run over group. In the vast majority of cases, a clear differentiation between the two groups is, therefore, possible on the basis of the autopsy findings. This is especially relevant if an inspection of the car cannot be performed after a hit-and-run accident, which occurred in 26% of the cases in this study. In addition, the blood alcohol levels were higher in the run over group (mean=2.14g/l) as compared to the combined group (mean=1.53g/l).

Accidents, Traffic↗

PubMed2001

[The practice of medical postmortem examination].

BACKGROUND AND OBJECTIVE: The quality of the external examination of corpses has repeatedly been criticized. This study provides information on the performance of the external examination of bodies in practice which is necessary for improving the quality of the examination. METHODS: 1000 randomly selected medical practitioners from the "Arztekammer Westfalen-Lippe" were sent a questionnaire concerning personal data, the performance of the external examination of bodies and possible influencing of the decision on the manner of death (i.e. natural, unnatural or uncertain) by a third person. In addition reports of four typical cases were presented and a classification of the manner of death was requested. RESULTS: The return rate of the questionnaires was almost 30%, 289 questionnaires were evaluated. Although most doctors stated that the external examination took them 20 to 30 minutes, only 25% undressed the body completely. Almost 50% of the doctors had been influenced by a third person in the decision on the manner of death at least once, most often by the police. The four short cases were incomprehensibly often classified as "natural death", especially by internists. CONCLUSIONS: Signs of an unnatural cause of death will only be detected by chance if the body is only briefly examined and not undressed completely. If such signs are absent the manner of death should be classified as "uncertain" in unclarified or doubtful cases, even against attempted influencing by third persons. In order to avoid conflicts of interests it would be desirable if only specialized medical practitioners would perform the external examination of corpses.

Autopsy↗

PubMed2001

Results of a collaborative study of the EDNAP group regarding the reproducibility and robustness of the Y-chromosome STRs DYS19, DYS389 I and II, DYS390 and DYS393 in a PCR pentaplex format.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS390 and DYS393 and to determine whether uniformity of results could be achieved among different European laboratories. Laboratories were asked to analyze the five Y-STRs using singleplex and multiplex conditions in three bloodstains and one mixed stain (95% female and 5% male). All the laboratories reported the same results even for the mixed stain included in the exercise. This demonstrates the reproducibility and robustness of Y-chromosome STR typing even with multiplex formats and proves the usefulness of Y-STR systems for analyzing mixed stains with a male component.A total of 930 male samples from 10 different populations from Europe were also analysed for all the loci included in the pentaplex. Eight of these ten populations also included haplotype data. As for single gene analysis, haplotype diversity was higher in Germany and Italy and lower in Western European countries and Finland. Pairwise haplotype analysis shows the Finnish departure from the rest of the populations and a relatively homogeneity in the other European populations with F(ST) estimates lower than 0.05.UPGMA analysis shows an association of Western European population (Ireland, UK, Portugal and Galicia) on the one hand and central European populations on the other.

Blood Stains↗

PubMed2001

Mutation rates at two human Y-chromosomal microsatellite loci using small pool PCR techniques.

Polymorphic Y-chromosomal short tandem repeats (Y-STRs) are being employed for phylogenetic and evolutionary studies as well as for forensic applications. Precise knowledge of mutation types and rates is essential and has hitherto been obtained from computer simulation or small-sized father/son pairs, or derived from the more intensively studied autosomal STRs, respectively. To establish more accurate values we analysed about 18 000 DNA sequences isolated from sperm cells of three donors, representing highly validated offspring. Two loci were examined, i.e. DYS19 and DYS390. The methodology applied was small pool PCR with automated laser-induced fluorescence detection. The mutation rates for single repeat gains were determined as 0.18% [95% confidence interval (CI) 0.11--0.31%] for DYS390 and 0.21% (95% CI 0.13--0.33%) for DYS19, and two-repeat changes occurred in the order of 0.01%. Assuming a similar rate for the loss of repeats, which could not be detected with our approach, we predict an overall mutation rate of approximately 0.4% per gamete per generation for both Y tetranucleotide loci. Moreover, these results support the stepwise mutation mechanism based on replication slippage. We expect this approach to be useful for individual mutation risk determination, as well as for studies concerning male history.

DNA Mutational Analysis↗

PubMed2001

Prolonged QT interval and sudden infant death--report of two cases.

In the two cases where infants died suddenly and unexpectedly the electrocardiogram (ECG) of a younger sibling (case 1) and of a living twin (case 2) led to the suspicion that the two infants could have died from long QT syndrome (LQTS). In case 1, a His bundle (HB) dispersion and a pronounced hypoplasia of the right external nucleus arcuatus were detected. In case 2, a severe interstitial pneumonia and an accompanying mild myocarditis were found by histology. Molecular genetic investigations of the coding regions of the genes, HERG, KVLQT1 and SCN5A gave no indication for the mutations, thus, affecting related myocardial ion channels as possible sources of inhomogeneity of repolarisation. Since a molecular genetic deviation could not yet be elaborated the possible role of related disturbance remains unknown.

Arcuate Nucleus of Hypothalamus↗

PubMed2001

The results of an mtDNA study of 1,200 inhabitants of a German village in comparison to other Caucasian databases and its relevance for forensic casework.

Mitochondrial DNA control region sequences were determined in 1,200 male volunteers from one village area of Lower Saxony for the hypervariable region 1 (HV1). The 154 variable positions found resulted in 460 different haplotypes with a haplotype diversity value of 0.98165. The number of different haplotypes showed a nearly linear increase with the number of individuals typed. The haplotype diversity approached saturation level at a value of approximately 0.981 after typing 400 individuals. Furthermore, the number of different haplotypes and the haplotype diversity were calculated for four short amplicons of HV1 in order to establish the most variable section with a high efficiency for forensic casework.

Adolescent↗

PubMed2001

Fatal neglect of the elderly.

Maltreatment of the elderly is a common problem that affects more than 3% of the elderly. We report on two cases of fatal neglect. Risk factors of victims and caregivers were analysed in the context of the social history. In both cases, the victims had a dominant personality and the abusers (the sons) had been strictly controlled and formed by the parent. The victims showed typical risk factors such as living together with the abuser, isolation, dependence on care, income and money administration. Initially, the victims declined help from outside and self-neglect occurred. The unemployed perpetrators lived in social isolation and depended financially and mentally on the victims. In both cases no mental illness was present but there was a decrease of social competence. Legal medicine is predominantly involved in fatal cases in connection with external post-mortem examinations and autopsies. Also in the living, the medico-legal expert can assist in the identification of findings in elderly persons in cases of suspected abuse.

Aged↗

PubMed2001

The evidential value of STRs. An analysis of exclusion cases.

In this study, a total of 191 cases with STR exclusions out of 591 paternity cases were analysed using 2 STR sets, i.e. (set a) 5 STRs in 462 cases with 150 exclusions and (set b) 9 STRs in 129 cases with 41 exclusions. Set (a) was associated with four exclusions on average while set (b) showed five exclusionary loci on average. Double exclusions were observed in 18 cases and further elaborated. Of these, 2 ended up with probabilities of paternity of 0.1% and 0.4%, respectively and with a random occurrence of the hypothesis "mutation" of 1:20,000 and 1:50,000, respectively, while all other cases were associated with much lower frequencies. The conclusion is that the evidential value of a set of highly polymorphic STRs applied in paternity cases is usually extremely high.

Genetic Markers↗

PubMed2001

Scratched pustule or gunshot wound? A medical odyssey.

The diagnosis of a gunshot wound can be difficult especially if the morphology is not typical. In the case presented a neck injury was not recognised as a gunshot wound by several clinicians and radiologists although the bullet could be seen at the base of the patient's tongue and on all X-rays taken. This misinterpretation may have been caused by a "professional blinkers phenomenon".

Cervical Vertebrae↗

PubMed2001

The cloven hoof in legal medicine.

The injury of a horse's leg needed to be investigated to answer the question whether the fracture had been caused by an accident or by intentional manipulation. By toxicology and using scanning electron microscopy with an energy dispersive X-ray spectrometer (SEM-EDX) the suspicion obtained by morphology could be confirmed. Toxicologically a short term anaesthetic was found, and by EDX ferric oxide particles could be detected in the wound indicating that the injury was caused by a sharp pointed metallic instrument and not as stated by the owner by a wooden bar. As the result of the interdisciplinary investigation using modern techniques, there is no doubt that the owner attempted to fraudulently claim on an insurance policy.

Animals↗

PubMed2001

Paternity testing using Y-STR haplotypes: assigning a probability for paternity in cases of mutations.

In parentage testing with male children, Y-chromosomal STR evidence is gaining more and more importance. In some cases, multilocus haplotypes of related persons can differ at a single locus due to a mutation. In this work, a likelihood approach is presented for the calculation of a probability for paternity under consideration of a single mutation event on the Y-chromosome. The new methodology is applied to two case examples.

Child↗

PubMed2001

Trajectory reconstruction from trace evidence on spent bullets. II. Are tissue deposits eliminated by subsequent impacts?

STR-based individualisation of biological deposits on bullets after perforation of tissue, can identify the person injured or killed by a particular bullet and comparison with the firearms used can identify the weapon and thus possibly the person who did the shooting. In this study, the effect of subsequent impacts on intermediate targets such as loss of cells was investigated by amplification of mitochondrial (mt) DNA. Bovine tissue was perforated and the 9 mm Luger FMJ bullets were recovered from the bullet collector. The mt cytochrome-b (cyt-b) gene could be amplified by the polymerase chain reaction (PCR) from 14 out of 15 bullets. Examination with a scanning electron microscope (SEM) and an energy-dispersive X-ray spectrometer (EDS) demonstrated the presence of minute dried tissue deposits on all bullets (n = 10) but was not able to establish preferential locations. In a series of 25 gunshots, various intermediate targets (glass, wood, car metal, gypsum board, asphalt) were perforated/impacted following perforation of tissue and the cyt-b gene could be typed from all bullets. It is concluded that subsequent impacts on intermediate targets do not eliminate enough biological deposits to render DNA analysis impossible and that the amplification of mtDNA is a useful additional method.

Animals↗

PubMed2001

Immunohistochemical alterations after intravital and post-mortem traumatic myocardial damage.

Two series of experiments have been carried out on heart tissue for the occurrence of post-mortem and intravital myocardial damage. The first series was carried out on 18 porcine hearts collected immediately after the pigs were killed in a slaughterhouse. The hearts were subjected to stab wounds post-mortem, varying between 5 min and 140 min after death. The second series investigated were human hearts with intravital damage, i.e. 4 stab wounds, 1 gunshot, 13 contusions and ruptures. The time the trauma occurred before death varied between 0 and 30 min. The investigation comprised the four myocyte structural proteins myoglobin, FABP, troponin C, desmin and the three plasma proteins fibrinogen, fibronectin and C5b-9. Both series exhibited a variety of direct traumatic changes with a much broader zone in vital damage compared to post-mortem damage. In vital damage the zone of direct damage is in continuity with a further zone of indirect damage which is a three dimensional network. The signs of damage are contraction bands, depletion of structure antigens, contraction-associated accumulation of structure proteins, accumulation of plasma proteins on the cell surfaces and in the interstitium. In vital damages there is in addition an intrasarcolemmal accumulation of plasma proteins. The pattern of all damage is much broader and much more variegated in vital damage, thus vital damage can be clearly differentiated from post-mortem damage. bin, heart-type fatty acid binding protein (FABP), troponin, desmin, fibrinogen and fibronectin (Amberg 1995; Brinkmann et al. 1993; Glatz et al. 1994; Kleine et al. 1993; Leadbetter et al. 1989; Ortmann et al. 2000a, 2000b; Osuna et al. 1998; Thomsen and Held 1994, 1995). The aim of the present study was to elaborate reaction patterns of these marker proteins in mechanical heart trauma induced ante- and post-mortem and to explore their value for wound age determination in forensic casework.

Adolescent↗

PubMed2001

An annotated mtDNA database.

We have compiled a database of mitochondrial DNA (mtDNA) control region, hypervariable regions 1 (HVR1) and 2 (HVR2) sequences of a total of 14,138 individuals compiled from 103 mtDNA publications before 1 January 2000, 13 data sets published in 2000 and 2001 and 2 unpublished data sets of Iraqi Kurds and Indians from Kerala. By contacting the authors and by other means, we have confirmed and corrected sequence errors, eliminated duplications and harmonised the sequence format. These changes affected all but 26 of the 116 publications. Furthermore, we have implemented a geographic information system ("mtradius") which searches for closest matches to a given mtDNA control region sequence and displays them on a geographic map. A potential application is to estimate a chance matching probability when a forensic stain and a suspect have an identical mtDNA sequence: we suggest that the geographic area with the highest frequency of closely related mtDNA sequence types may be used to define a reference population to give the suspect the maximum benefit of doubt in accordance with the ceiling principle.

DNA Fingerprinting↗

PubMed2001

DNA commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome STRs.

During the past few years the DNA commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area, namely Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.

Alleles↗

PubMed2001

[CT-computer-template-assisted planning of implant and magnet position in epi-prosthetic management of facial defects].

BACKGROUND: The aesthetic result of a prosthetic reconstruction in the facial area depends on precise, long-term stable positioning of the facial prosthesis. For fixation of the facial prosthesis and contouring of the soft tissue, good long-term success can be achieved by implant-magnet systems. The precise positioning of the implants and magnets when only little bone is available is difficult and without any planning is often not possible. COMPUTER EVALUATION: Computer-supported evaluation of CT data with the aid of CT and drill templates can optimise the planning and carrying out of surgery. This procedure is illustrated with reference to the treatment of a patient following obital exenteration due to an embryonic rhabdomyosarcoma. The programs SIM/Plant and coDiagnostiX were compared with one another when carrying out the CT evaluation and planning the orbital prosthesis. In so doing, the great advantage of the definition of the CT window (grey levels), the freely definable panorama sections and cross-sections, as well as the three-dimensional, spatial representation using the programme coDiagnostiX on a conventional PC are made clear. The results of planning can be applied and implemented during surgery, with the aid of the CT and drill templates. DISCUSSION: The CT computer template-supported procedure is suitable for routine clinical use and can be recommended for planning of implant-fixed facial prosthesis in the orbital area when little bone is available or in the case of difficult anatomical relationships.

Adolescent↗