Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?

BACKGROUND: Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. CASE PRESENTATION: We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. CONCLUSION: Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.

Germline mutations of STR-alleles include multi-step mutations as defined by sequencing of repeat and flanking regions.

Well defined estimates of mutation rates are a prerequisite for the use of short tandem repeat (STR-) loci in relationship testing. We investigated 65 isolated genetic inconsistencies, which were observed within 50,796 allelic transfers at 23 STR-loci (ACTBP2 (SE33), CD4, CSF1PO, F13A1, F13B, FES, FGA, vWA, TH01, TPOX, D2S1338, D3S1358, D5S818, D7S820, D8S1132, D8S1179, D12S391, D13S317, D16S539, D17S976, D18S51, D19S433, D21S11) in Caucasoid families residing in Austria and Switzerland. Sequencing data of repeat and flanking regions and the median of all theoretically possible mutational steps showed valuable information to characterise the mutational events with regard to parental origin, change of repeat number (mutational step size) and direction of mutation (losses and gains of repeats). Apart from predominant single-step mutations including one case with a double genetic inconsistency, two double-step and two apparent four-step mutations could be identified. More losses than gains of repeats and more mutations originating from the paternal than the maternal lineage were observed (31 losses, 22 gains, 12 losses or gains and 47 paternal, 11 maternal mutations and 7 unclear of parental origin). The mutation in the paternal germline was 3.3 times higher than in the maternal germline. The results of our study show, that apart from the vast majority of single-step mutations rare multi-step mutations can be observed. Therefore, the interpretation of mutational events should not rigidly be restricted to the shortest possible mutational step, because rare but true multi-step mutations can easily be overlooked, if haplotype analysis is not possible.

Severe bronchopulmonary dysplasia improved by noninvasive positive pressure ventilation: a case report.

INTRODUCTION: This is the first report to describe the feasibility and effectiveness of noninvasive positive pressure ventilation in the secondary treatment of bronchopulmonary dysplasia. CASE PRESENTATION: A former male preterm of Caucasian ethnicity delivered at 29 weeks gestation developed severe bronchopulmonary dysplasia. At the age of six months he was in permanent tachypnea and dyspnea and in need of 100% oxygen with a flow of 2.0 L/minute via a nasal cannula. Intermittent nocturnal noninvasive positive pressure ventilation was then administered for seven hours daily. The ventilator was set at a positive end-expiratory pressure of 6 cmH2O, with pressure support of 4 cmH2O, trigger at 1.4 mL/second, and a maximum inspiratory time of 0.7 seconds. Over the course of seven weeks, the patient's maximum daytime fraction of inspired oxygen via nasal cannula decreased from 1.0 to 0.75, his respiratory rate from 64 breaths/minute to 50 breaths/minute and carbon dioxide from 58 mmHg to 44 mmHg. CONCLUSION: Noninvasive positive pressure ventilation may be a novel therapeutic option for established severe bronchopulmonary dysplasia. In the case presented, noninvasive positive pressure ventilation achieved sustained improvement in ventilation and thus prepared our patient for safe home oxygen therapy.

Magnetic resonance imaging goes postmortem: noninvasive detection and assessment of myocardial infarction by postmortem MRI.

OBJECTIVE: To investigate the performance of postmortem magnetic resonance imaging (pmMRI) in identification and characterization of lethal myocardial infarction in a non-invasive manner on human corpses. MATERIALS AND METHODS: Before forensic autopsy, 20 human forensic corpses were examined on a 1.5-T system for the presence of myocardial infarction. Short axis, transversal and longitudinal long axis images (T1-weighted; T2-weighted; PD-weighted) were acquired in situ. In subsequent autopsy, the section technique was adapted to short axis images. Histological investigations were conducted to confirm autopsy and/or radiological diagnoses. RESULTS: Nineteen myocardial lesions were detected and age staged with pmMRI, of which 13 were histologically confirmed (chronic, subacute and acute). Six lesions interpreted as peracute by pmMRI showed no macroscopic or histological finding. Five of the six peracute lesions correlated well to coronary pathology, and one case displayed a severe hypertrophic alteration. CONCLUSION: pmMRI reliably demonstrates chronic, subacute and acute myocardial infarction in situ. In peracute cases pmMRI may display ischemic lesions undetectable at autopsy and routine histology. pmMRI has the potential to substantiate autopsy and to counteract the loss of reliable information on causes of death due to the recent disappearance of the clinical autopsy.

Fatal intoxication with naftidrofuryl.

A 52-year-old man was found dead in his bed. He had financial and psychosocial problems like separation from his wife and children or unemployment due to alcoholism. Under treatment of disulfiram he was presently abstinent from alcohol. As he had suffered from epileptic seizures and dizziness, he received valproic acid and the vasodilator naftidrofuryl, respectively. Autopsy showed no morphologic cause of death. Chemical analysis of blood revealed concentrations for valproic acid and disulfiram in the therapeutic and above the therapeutic range but far below the lethal level, respectively. No ethanol was found. However, the very high concentration of 7500 microg/L naftidrofuryl in whole blood was considered as cause of death, and the most probable manner of death seemed to be suicide. To our knowledge, this is the first reported case of a fatal poisoning with naftidrofuryl.

No association of serotonin transporter gene variation with sudden infant death syndrome (SIDS) in Caucasians.

Genetic studies on SIDS have been motivated by clinical, epidemiological, and/or neuropathological observations made of SIDS victims. One of the candidate genes is the serotonin transporter (5-HTT) gene, based on decreased serotonergic receptor binding observed in the brain-stems of SIDS victims. Two polymorphisms in the regulatory region of the 5-HTT gene differentially modulate gene expression (promoter, intron 2). The promoter allelic variants long (L) and extra long (XL) and the intron 2 12-repeat allele seem to be associated with SIDS; however, the 5-HTT promoter allele distribution varies widely by ethnicity. We investigated the DNA of 145 Caucasian SIDS cases and 58 controls and could find no significant association between our Caucasian SIDS cases and controls either for the promoter L allele and the intron 2 12-repeat allele, or for the combined L-12 haplotype as well as the L- or 12-containing genotypes.

Assessment of requests for assisted suicide by a Swiss right-to-die society.

Non-physician volunteers of Exit, the largest right-to-die organization in Switzerland, play an important role in assisted suicide. They conduct assessments and deliver lethal medications for a member to self-administer. This study analyses the content of 114 intake sheets (checklists) of Exit members whose requests for assisted suicide were granted in an effort to examine the frequency of depression and whether their relatives agreed with the member's decision to commit suicide (2 questions that can help increase the likelihood that the member's decision was both informed and voluntary). Exit's paperwork indicated that depression was found to exist in 27% of the cases, was more common among those under 65, and relatives explicitly disagreed with the member's decision in 5% of the cases.

Evaluation of 3D surface scanners for skin documentation in forensic medicine: comparison of benchmark surfaces.

BACKGROUND: Two 3D surface scanners using collimated light patterns were evaluated in a new application domain: to document details of surfaces similar to the ones encountered in forensic skin pathology. Since these scanners have not been specifically designed for forensic skin pathology, we tested their performance under practical constraints in an application domain that is to be considered new. METHODS: Two solid benchmark objects containing relevant features were used to compare two 3D surface scanners: the ATOS-II (GOM, Germany) and the QTSculptor (Polygon Technology, Germany). Both scanners were used to capture and process data within a limited amount of time, whereas point-and-click editing was not allowed. We conducted (a) a qualitative appreciation of setup, handling and resulting 3D data, (b) an experimental subjective evaluation of matching 3D data versus photos of benchmark object regions by a number of 12 judges who were forced to state their preference for either of the two scanners, and (c) a quantitative characterization of both 3D data sets comparing 220 single surface areas with the real benchmark objects in order to determine the recognition rate's possible dependency on feature size and geometry. RESULTS: The QTSculptor generated significantly better 3D data in both qualitative tests (a, b) that we had conducted, possibly because of a higher lateral point resolution; statistical evaluation (c) showed that the QTSculptor-generated data allowed the discrimination of features as little as 0.3 mm, whereas ATOS-II-generated data allowed for discrimination of features sized not smaller than 1.2 mm. CONCLUSION: It is particularly important to conduct specific benchmark tests if devices are brought into new application domains they were not specifically designed for; using a realistic test featuring forensic skin pathology features, QT Sculptor-generated data quantitatively exceeded manufacturer's specifications, whereas ATOS-II-generated data was within the limits of the manufacturer's specifications. When designing practically constrained specific tests, benchmark objects should be designed to contain features relevant for the application domain. As costs for 3D scanner hardware, software and data analysis can be hundred times as high compared to high-resolution digital photography equipment, independent user driven evaluation of such systems is paramount. INDEX TERMS: Forensic pathology, Rough surfaces, Surface Scanning, Technology Assessment.

Swiss doctors' attitudes towards end-of-life decisions and their determinants: a comparison of three language regions.

OBJECTIVES: To investigate attitudes to end-of-life decisions, and the influence of cultural factors and of doctors' personal characteristics on these attitudes. METHOD: As part of a European research project (EURELD), a study on attitudes towards medical end-of-life decisions was conducted among doctors in the German-, French- and Italian-speaking areas of Switzerland. A written questionnaire was sent to a random sample of nine different types of specialist; it presented 14 statements on end-of-life decisions and doctors were asked whether they agreed or disagreed with them. RESULTS: The response rate was 64%. 1360 questionnaires were studied. The results show general agreement with statements on the alleviation of pain and other symptoms with possible life-shortening effect, as well as on non-treatment decisions. The language region was a strong determinant of agreement on some attitudes towards end-of-life decisions. Agreement on the use of lethal drugs and alleviation of pain and other symptoms with possible life-shortening effect was higher among French-speaking than among German- and Italian-speaking doctors. For nontreatment decisions, agreement was higher in the German-speaking region than in the French- and Italian-speaking regions of the country. Italian-speaking doctors were strongly opposed to any kind of end-of-life decision. Religious believers and those who attended a larger number of terminal patients tended to disagree more often with end-of-life decisions than the other doctors. CONCLUSIONS: In end-of-life decision-making, Switzerland represents "Europe in miniature". The impact on end-of-life decisions of cultural factors and the number of terminal patients attended needs further consideration.

STR analysis of artificially degraded DNA-results of a collaborative European exercise.

Degradation of human DNA extracted from forensic stains is, in most cases, the result of a natural process due to the exposure of the stain samples to the environment. Experiences with degraded DNA from casework samples show that every sample may exhibit different properties in this respect, and that it is difficult to systematically assess the performance of routinely used typing systems for the analysis of degraded DNA samples. Using a batch of artificially degraded DNA with an average fragment size of approx. 200 bp a collaborative exercise was carried out among 38 forensic laboratories from 17 European countries. The results were assessed according to correct allele detection, peak height and balance as well as the occurrence of artefacts. A number of common problems were identified based on these results such as strong peak imbalance in heterozygous genotypes for the larger short tandem repeat (STR) fragments after increased PCR cycle numbers, artefact signals and allelic drop-out. Based on the observations, strategies are discussed to overcome these problems. The strategies include careful balancing of the amount of template DNA and the PCR cycle numbers, the reaction volume and the amount of Taq polymerase. Furthermore, a careful evaluation of the results of the fragment analysis and of automated allele calling is necessary to identify the correct alleles and avoid artefacts.

DNA profiling: evaluation of the evidentiary value.

The evaluation of the evidentiary value of scientific evidence is the assessment of the strength of the link between a finding and a person. It is usually a statistical assessment but its presentation is full of pitfalls. The evaluation of scientific evidence must be based on a established methodology to both evaluate, expose and interpret the evidence. It is best based on a logical framework, e.g. the Bayesian theorem, and on likelihood ratios. The information of the scientist is usually a numerical one, e.g. the probability of observing two matching profiles. Assessments of simple stains as well as of stain mixtures with contributors of different ethnic origin and/or with related contributors or reference persons and even artifacts can be quantified and expressed by likelihood ratio(s). Thereby, scientific evidence can be integrated by juries into the continuous process of evaluating prior odds and changing them into posterior odds by new information in the case.

748 cases of suicide assisted by a Swiss right-to-die organisation.

BACKGROUND AND METHODS: In Switzerland, nonmedical right-to-die organisations offer instruction and personal guidance in committing suicide to members suffering from incurable diseases. Suicide is usually committed with a lethal dose of barbiturates prescribed by a physician. This study is a retrospective analysis of all case files of assisted suicide kept during the period 1990-2000 by "Exit Deutsche Schweiz", the largest Swiss right-to-die organisation. RESULTS: Between 1990 and 2000 Exit assisted in 748 suicides among Swiss residents (0.1% of total deaths, 4.8% of total suicides). 54.4% of the deceased were women. Mean age at death was 73 years in males and 72 years in females (range 18-101 years). Assisted suicide was over-proportionately represented in the German-speaking (p <0.0001), more urbanised (p <0.0001), predominantly Protestant (p <0.0001) cantons. Over the study period the annual number of Exit deaths more than tripled (p <0.0001). Of the 331 who died in Canton Zurich, 47.4% had cancer, 11.8% cardiovascular/respiratory disease, 12.4% neurological disease and 7.3% HIV/AIDS. The remaining 21.1% suffered from other, usually non-fatal conditions; 76% of these were women. There were no significant changes in sex, age and distribution of diagnoses during the study period. At first all the lethal substances were taken orally, but by the end of the study period 14% were administered via infusion or PEG catheter. All assisted suicides in the City of Zurich were duly notified to the authorities. CONCLUSIONS: The number of suicides assisted by "Exit Deutsche Schweiz" and the practices followed markedly expanded over this time. There was no apparent relaxation of the indications for assisted suicide. Notification of the authorities appeared to be total.