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Biomedical subjects

T Bajanowski

Publications and source records attributed to T Bajanowski.

At least 19 recordsLinked to original sources

Frequent but borderline methylation of p16 (INK4a) and TIMP3 in medulloblastoma and sPNET revealed by quantitative analyses.

Certain risk groups among tumors of the central nervous system (CNS) in children take an almost inevitably fatal course. The elucidation of molecular mechanisms offers hope for improved therapy. Aberrant methylation is common in malignant brain tumors of childhood and may have implications for stratification and therapy. Methylation of p16 (INK4A), p14 (ARF), TIMP3, CDH1, p15 (INK4B )and DAPK1 in medulloblastoma (MB) and ependymoma has been discussed controversially in the literature. DUTT1 and SOCS1 have not previously been analyzed. We examined methylation in MB, sPNET and ependymoma using methylation-specific PCR (MSP), quantitative Combined Bisulfite Restriction Analysis (COBRA) and direct and clone sequencing of bisulfite PCR products. We detected methylation of p16 (INK4A) (17/43), p14 (ARF) (11/42) and TIMP3 (9/44) in MB and others by MSP. CDH1 was not only methylated in MB (31/41), but also in normal controls. Evaluation of MSP results by quantitative COBRA and sequencing yielded methylation between the detection limits of COBRA (1%) and MSP (0.1%). Only p16 (INK4A )and TIMP3 were methylated consistently in medulloblastomas (p16 (INK4A ) 14%, TIMP3 11%) and p16 (INK4A) also in anaplastic ependymomas (1/4 tumors). Methylation ranged from 1-5%. Evaluation of methylation using MSP has thus to be supplemented by quantitative methods. Our analyses raise the issue of the functional significance of low level methylation, which may disturb the delicate growth factor equilibrium within the cell. Therapeutic and diagnostic implications urge into depth analyses of methylation as a mechanism, which might fill some of the gaps of our understanding of brain tumor origin.

Adolescent↗

Do risk factors differ between explained sudden unexpected death in infancy and sudden infant death syndrome?

BACKGROUND: In Germany, 2910 infants died in 2004; for many infants the reason was clear, especially prematurity or congenital abnormalities. However, 394 babies die every year suddenly and unexpectedly. The cause may be immediately clear, but is often not obvious. AIMS: (1) To describe the causes of explained sudden unexpected death in infancy (SUDI) and (2) to compare risk factors for sudden infant death syndrome (SIDS) and explained SUDI. METHODS: A 3-year population-based case-control study in Germany, 1998-2001. RESULTS: 455 deaths, of which 51 (11.2%) were explained. Most of these deaths were due to respiratory or generalised infections. The risk factors for SIDS and explained SUDI were remarkably similar except for sleep position and breast feeding. Prone sleeping position is a major risk factor for SIDS (adjusted odds ratio (OR) 7.16, 95% confidence interval (CI) 3.85 to 13.31) but not for explained SUDI (adjusted OR 1.71, 95% CI 0.25 to 11.57). Not being breast fed in the first 2 weeks of life is a risk factor for SIDS (adjusted OR 2.37, 95% CI 1.46 to 3.84) but not for explained SUDI (adjusted OR 0.39, 95% CI 0.08 to 1.83). CONCLUSIONS: Prone sleeping position is a unique risk factor for SIDS. Socioeconomic disadvantage and maternal smoking are risk factors for both SIDS and explained SUDI, and provide an opportunity for targeted intervention.

Age Distribution↗

Sudden infant death syndrome: no increased risk after immunisation.

BACKGROUND: Although previous studies have shown either no association between immunisation and SIDS or even a decreased risk of SIDS, adverse effects, including death, from immunisations continue to cause concern, especially when a new vaccine is introduced. METHODS: A large case control study with immunisation data on 307 SIDS cases and 971 controls. RESULTS: SIDS cases were immunised less frequently and later than controls. Furthermore there was no increased risk of SIDS in the 14 days following immunisation. There was no evidence to suggest the recently introduced hexavalent vaccines were associated with an increased risk of SIDS. CONCLUSIONS: This study provides further support that immunisations may reduce the risk of SIDS.

Humans↗

Cooling experiments using dummies covered by leaves.

One main method to estimate the time of death is the measurement of the body temperature. The cooling of a corpse depends on a number of conditions including the surroundings. In cases where the cooling conditions differ from the defined standard, a corrective factor is used to characterise the influence of clothing, air movement, the properties of the supporting base and the humidity. Nothing is known about the significance of other circumstances, for example of a tegument by leaves or wet leaves. Therefore, the cooling of dummies which were placed on a 2-cm-thick layer of wet/dry leaves and covered by a 10-cm-thick layer of leaves was investigated. Corrective factors of 1.0 for wet leaves on the ground and of 1.3 and 1.5 for drier leaves were found. If the dummies were additionally covered, corrective factors ranged between 1.8 and 2.7.

Autopsy↗

Are autopsies of help to the parents of SIDS victims? A follow-up on SIDS families.

Little is known about what bereaved parents feel about the autopsy performed on their child. A multi-centre case control study of sudden infant death syndrome (SIDS) victims was carried out in Germany between 1998 and 2001, in which all infants had been autopsied. We performed a follow-up study 4-7 years after the parents had lost their child. A total of 141 parents filled in the questionnaire, which were sent to them by the study centre. Of these, 71% had had another child after the SIDS/sudden unexpected death in infancy. The majority (83%) of the participating parents found the autopsy helped them to cope better with the death. A large proportion (46%) did not want any professional help after the death, and 55% did not wish to have any contact with a self-help group. We conclude that the autopsy is helpful to the majority of bereaved parents. Professional help and self-help groups should be offered to the parents even if the majority in our study did not want to use either.

Adaptation, Psychological↗

Perforation of the pulmonary artery by a bronchial wall stent.

Implantation of stents into the bronchial walls is a newly developed method to treat lung emphysema, which is now being tested clinically. During this procedure, a bronchoscope carrying a Doppler ultrasonography head is placed into a segmental bronchus and the blood vessels running in parallel to the bronchus are localized. Once a safe location without blood vessels is found, the bronchial wall is perforated and a stent is placed within the wall to improve the expiratory volume of these "bypasses" to the adjacent lung parenchyma. We observed a fatal complication with this method in a 60-year-old man. The bronchial wall and the pulmonary artery were perforated by one of the stents inducing massive bleeding, which could not be stopped. The patient died due to aspiration of blood in combination with massive loss of blood. The general risk to perforate the pulmonary artery during this procedure cannot be estimated from this single observation but should be considered regarding the legal and clinical aspects.

Bronchi↗

Prevention of sudden infant death syndrome (SIDS) due to an active health monitoring system 20 years prior to the public "Back to Sleep" campaigns.

BACKGROUND: Before reunification, the post-neonatal mortality rate was lower in East Germany than in West Germany. Moreover, the incidence of SIDS (sudden infant death syndrome) was much lower in the East. METHODS: Mortality data on sudden infant death syndrome (SIDS) from West and East Germany since 1980 as well as post-neonatal mortality data for both states since 1970 were examined. 95% Confidence intervals were calculated for the rates. Witnesses from the former East Germany who were involved at the time were also interviewed and archives were searched. RESULTS: We found that as early as 1972 active monitoring of infant and child mortality rates in East Germany had shown that the prone sleeping position was dangerous for infants: the post-neonatal mortality rate was approximately 1 per 1000 live births lower in East than in West Germany during the 20 years before reunification. In contrast, in the West, prone sleeping was only discovered to be a risk factor for SIDS in the early 1990s. CONCLUSIONS: Active monitoring is an effective tool in the early detection of risk factors and serves to prevent unnecessary deaths.

Autopsy↗

Coincidence of different structures of mucosa-associated lymphoid tissue (MALT) in the respiratory tract of children: no indications for enhanced mucosal immunostimulation in sudden infant death syndrome (SIDS).

Mucosa-associated lymphoid tissue (MALT) is the principal inductive site for mucosal immune responses that are capable of T and B cell responses and antigen-specific responses. In previous independent studies different structures of MALT, e.g. bronchus-, larynx- and nose-associated lymphoid tissue (BALT, LALT, NALT) have been described separately in various frequencies in the human respiratory tract over life spans. Because upper respiratory tract infections are common in infants, dysregulations of mucosal immune responses might be seriously involved in the aetiology of sudden infant death syndrome (SIDS). In the present study the coincidental occurrence of the three different MALT structures in the respiratory tract within the same patients were studied, and cases of SIDS and children who had died from different traumatic and natural causes of death (non-SIDS) were compared. First, the frequency of BALT and LALT in 46 children (35 SIDS, 11 non-SIDS) with or without NALT were examined. A tendency was found of a coincidence of respiratory MALT structures. In 50 additional cases of infant death (30 SIDS, 20 non-SIDS) from the multi-centric German Study on Sudden Infant Death Syndrome (GeSID) where death had occurred in the first year of life, the coincidence was evaluated. A coincidental occurrence of BALT, LALT and NALT or BALT and LALT (each about 30%) was found in both groups, whereby the coincidence in SIDS and the control patients did not differ. Interestingly, the children with coincidental MALT were strikingly older, supporting the hypothesis of respiratory MALT formation via environmental stimulation over time.

Bronchi↗

The San Diego definition of SIDS: practical application and comparison with the GeSID classification.

The new definition of the term sudden infant death syndrome (SIDS) and the criteria introduced in San Diego for the subclassification of cases have been used to re-classify the first 100 consecutive cases of sudden and unexpected infant deaths that were registered with the German SIDS study (GeSID). Although there are 30 different variables that have to be considered in the general and stratified sections of the San Diego definition, it is practical, in particular, as an international standard to perform scientific studies. The comparison of the San Diego definition and the classification used for GeSID shows similarities in the methods but differences in the criteria used. Nevertheless, the numbers of cases classified as SIDS and borderline SIDS are similar (San Diego n=69, GeSID n=74). The SIDS IA criteria of the San Diego definition were not fulfilled by any case because metabolic screening and vitreous chemistry were not included in the GeSID investigation scheme. An important advantage of the San Diego definition is the introduction of the category of unclassified sudden infant death, which includes cases for which no autopsy was performed. This demonstrates that such cases cannot be classified as SIDS. In conclusion, we recommend the universal acceptance and use of the San Diego SIDS definition.

Age Distribution↗

Unnatural causes of sudden unexpected deaths initially thought to be sudden infant death syndrome.

The aim of this clinicopathological study was to determine the frequency of infant deaths due to unnatural causes among cases of sudden and unexpected infant death. Nine institutes of legal medicine in Germany that took part in the German study on Sudden Infant Death Syndrome (GeSID), representing 35% of the German territory, investigated in a 3-year period (from 1998 to 2001) 339 cases of infant death that were not expected to be due to unnatural causes from the first external examination. All cases were investigated by complete, standardised, post-mortem examination including death scene investigation, autopsy, histology, toxicology and neuropathology. The frequency of unnatural deaths was 5.0% (n=17). The causes of death were head injury (n=7), suffocation (n=5), poisoning (n=2), neglect (n=2) and septicaemia due to aspiration of a foreign body (n=1). Two deaths were unsuspected accidents and 12 were due to infanticide. In 3 cases, it was not possible to differentiate between accidental death and infanticide. A complete postmortem examination including an analysis of the clinical history, death scene investigation, autopsy, histology, toxicology, and neuropathology is mandatory to differentiate sudden and unexpected deaths due to natural causes (e.g. SIDS) and cases of unnatural death.

Autopsy↗

Modifiable risk factors for SIDS in Germany: results of GeSID.

BACKGROUND: The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well-known risk factors in Germany since a local prevention campaign in 1992. DESIGN: A 3-y, population-based, case-control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. RESULTS: The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co-sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39). CONCLUSIONS: Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.

Adult↗

Infection, health problems, and health care utilisation, and the risk of sudden infant death syndrome.

AIM: To examine whether symptoms suggestive of infection, health problems, and health care utilisation are risk factors for SIDS. METHODS: Matched case-control study with 333 SIDS infants and 998 control infants matched for region, age, gender, and reference sleep. Information was obtained by parental interview, paediatrician completed questionnaire, and hospital admission data. RESULTS: No symptoms were associated with SIDS after adjustment for potential confounders. Illness in the last four weeks as reported by the paediatrician did not differ between cases and controls. Developmental problems and special investigations at any stage of life significantly increased the risk of SIDS (adjusted OR = 2.14 and 2.07). Admission to hospital after the first week of life was associated with an increased risk of SIDS (adjusted OR = 1.88). CONCLUSION: Symptoms of infection and illness are no longer risk factors for SIDS in communities such as Germany where few infants sleep prone. The increased risk of SIDS with developmental problems may indicate that infants which subsequently die of SIDS are abnormal or in some way vulnerable.

Analysis of Variance↗

Suffocation and poisoning--the hard-hitting side of Munchausen syndrome by proxy.

Munchausen syndrome by proxy (MSBP) is a severe and difficult to diagnose form of child abuse characterised by the simulation, aggravation or production of symptoms of illness in a child by an adult. MSBP often leads to multiple hospitalisations and has a high mortality and long-term morbidity. This study describes the cases of 5 families with 8 children affected who presented with unexplained neurological or gastrointestinal symptoms or even loss of consciousness. All were victims of poisoning or suffocation by their mothers. Two of those children died and were initially diagnosed as SIDS or natural death, respectively. They were only recognised as MSBP victims after another sibling had fallen ill with similar symptoms. The cases are discussed in consideration of the relevant literature. In addition warning signs of this forensically relevant syndrome and a strategy for the management of suspected MSBP cases are described.

Asphyxia↗

German study on sudden infant death (GeSID): design, epidemiological and pathological profile.

The German study on sudden infant death (GeSID) is a multi-centre case-control study aiming at the assessment of etiological factors and risk factors of SIDS. This report describes the study design and the methods applied and presents some general findings. Between 1998 and 2001, 455 cases of sudden and unexpected death of infants aged between 8 and 365 days were recruited into the study. The study comprised at least 11 out of the 16 German states with 18 centres involved. In 1999 and 2000, 75% of all SIDS cases registered with the Federal Office of Statistics (ICD 10/R95, n=384) in the study area were recruited into the study (n=286). A standardised autopsy including extended histology, microbiology, virology, toxicology and neuropathology investigations was carried out. Of the parents 82% (n=373) agreed to fill in an extensive questionnaire containing 120 questions reflecting all important aspects of the infant's development. For each SIDS case, the parents of three living control infants were interviewed. These controls were matched for age, gender and region (n=1,118). The response rate of the controls was 58.7%. Data were linked with medical records obtained from obstetrics departments, the children's hospitals, and general practitioners. Death scene investigation was performed in 4 study areas (cases: n=64, controls: n=191). All cases were classified into one of 4 categories using defined criteria: 7.3% of the children were assigned to category 1 (no pathological findings: SIDS), 61.1% to category 2 (minor findings: SIDS+), 20.4% to category 3 (severe findings: SIDS+) and 11.2% to category 4 (findings which explained the death: non-SIDS). In case conferences the previous history and circumstantial factors were included and an extended category (E-cat.) was defined. The consideration of these factors for the final classification is of great importance in the causal explanation of some cases. An analysis of 18 main variables in cases of categories 1-3 (SIDS) compared to the cases of category 4 (non-SIDS) showed significant differences for the sleeping position, coughing the day before death and breast-feeding indicating that the cases of both groups should be separated for further analyses.

Autopsy↗

Analysis of 155 consecutive forensic exhumations with emphasis on undetected homicides.

A total of 155 consecutive forensic exhumations performed in Münster, Germany from 1967 to 2001 were evaluated retrospectively on the basis of the autopsy report, the police report and the death certificate. Histology and toxicology were performed in most cases. The postmortem intervals varied from 8 days to 8 years. Compared to other countries, the autopsy rate was low (1.2-1.4%) and the exhumation rate high (0.016%): principle of reciprocity. The cause of death could be clearly determined in 103 cases (66.5%) and histology or toxicology were decisive in 40%. Some findings were discernable using immunohistochemistry after considerable postmortem intervals, such as acute myocardial infarction after 1 year and pneumonia after 2 years and a diazepam intoxication was determined after 4.5 years. Major deviations between the cause of death as stated on the death certificate and as diagnosed after autopsy existed in 57 cases (37%). A more detailed analysis revealed five subgroups. 1. primary suspicion of intoxication (n=18) confirmed in 6 cases including 3 homicides (with parathion, clozapin, diazepam) which are described in more detail. 2. primary suspicion of homicide other than poisoning (n=51) confirmed in 19 cases. There was a serial killing of 15 patients by injection of air. In the remaining 4 cases, a shaken infant, craniocerebral injuries from blows with beer bottles, a craniocerebral gunshot and a multiplicity of blunt force injuries were diagnosed. The latter two cases are described in more detail. Superficial external examinations and the low autopsy rate were 2 common reasons for the occurrence of "buried homicides" (n=22)-not a single forensic autopsy had been performed directly after the death of the victims. 3. primary suspicion of medical malpractice (n=39). 4. accidents including traffic accidents (n=30). 5. clarification of the cause of death, circumstances or identity (n=17). Exhumations were frequently successful for recovering evidence which should better have been collected immediately after the death of an individual. Exhumations can also be regarded as an instrument to evaluate the quality of death certificates and death investigations.

Adolescent↗

Evaluation of the Reid index in infants and cases of SIDS.

The Reid index is an instrument for the evaluation of chronic bronchitis. The thickness of the mucosa and of its gland layer are measured and the relationship is expressed as a gland/wall ratio. Specimens were obtained from 124 autopsies from the German National Study on SIDS (GeSID). The cases were divided into three groups: group 1 typical SIDS ( n=47), group 2 SIDS with signs of mild inflammation of the respiratory tract ( n=50) and group 3 unnatural death controls ( n=23). The Reid index was measured in sections from the trachea, bifurcation/main bronchi and bronchioli (staining HE and PAS). The Reid index was remarkably constant throughout the different levels of the respiratory tract (standard deviation range 0.06-0.10). A comparison of the three groups did not show statistically significant differences. Group 1: mean Reid index trachea 0.37, bifurcation/main bronchi 0.38, bronchioli 0.39. Group 2: mean Reid index trachea 0.40, bifurcation/main bronchi 0.38, bronchioli 0.38. Group 3: mean Reid index trachea 0.39, bifurcation/main bronchi 0.38, bronchioli 0.41. It can be concluded that the dimensions of bronchial glands do not vary in cases of SIDS as compared to controls. This demonstrates that the Reid index has no significance in the vast majority of SIDS cases and that acute inflammation commonly does not produce an elevated Reid index. In addition, the Reid index was confirmed to be a valid instrument to study the respiratory tract including the trachea due to its stability and it was found that the Reid index is age-dependent: compared to adults, the ratios in infants were higher.

Bronchi↗

Fracture properties of the human mandible.

A total of seven human mandibles were struck to breaking point under standardised conditions using a pendulum. The cortical deformation for two impact directions was measured with strain gauge strips located at eight defined sites. Fronto-median impacts led to mostly bilateral and always multiple fractures in the posterior area of the bone, especially in the collum and the condyle. The fracture threshold was between 2.5 and 3.1 kN. Lateral impact caused fractures near the impact area as direct fractures of the ipsilateral corpus. Mainly single and double fractures were observed. For lateral impact the fracture threshold was between 0.6 and 0.8 kN.

Adult↗

Deformation characteristics of the human mandible in low impact experiments.

A total of 11 human mandibles were subjected to physical impacts under standardised conditions. Two impact sites and directions were tested and the impact load was varied in four steps. Two occlusional strengths were applied and the influence of simulated soft tissue covering was recorded. The deformation of the bones was measured using strain gauge strips located at eight defined sites. In a series of frontal to occipital impacts the frontal areas and the collum showed the largest length changes. Increasing impact intensities led to a proportional increase of the length changes. An increase of the occlusional strength was either protective (at the collum) or it increased the deformation (frontal area). The soft tissue covering was only partly protective. Lateral impact was characterised by a compression on the side of the impact and stretching on the other side only. The intensity and speed of deformation increased with increasing distance from the site of impact. A fixed occlusion caused an increase of compression at the site of impact and an increasing stretching in the frontal part of the bone and at the opposite collum.

Adult↗