Human Synovia Contains Trefoil Factor Family (TFF) Peptides 1-3 Although Synovial Membrane Only Produces TFF3: Implications in Osteoarthritis and Rheumatoid Arthritis.

OBJECTIVE: Trefoil factor family peptide 3 (TFF3) has been shown to support catabolic functions in cases of osteoarthritis (OA). As in joint physiology and diseases such as OA, the synovial membrane (SM) of the joint capsule also plays a central role. We analyze the ability of SM to produce TFF compare healthy SM and its secretion product synovial fluid (SF) with SM and SF from patients suffering from OA or rheumatoid arthritis (RA). METHODS: Real-time PCR and ELISA were used to measure the expression of TFFs in healthy SM and SM from patients suffering from OA or RA. For tissue localization, we investigated TFF1-3 in differently aged human SM of healthy donors by means of immunohistochemistry, real-time PCR and Western blot. RESULTS: Only TFF3 but not TFF1 and -2 was expressed in SM from healthy donors as well as cases of OA or RA on protein and mRNA level. In contrast, all three TFFs were detected in all samples of SF on the protein level. No significant changes were observed for TFF1 at all. TFF2 was significantly upregulated in RA samples in comparison to OA samples. TFF3 protein was significantly downregulated in OA samples in comparison to healthy samples and cases of RA significantly upregulated compared to OA. In contrast, in SM TFF3 protein was not significantly regulated. CONCLUSION: The data demonstrate the production of TFF3 in SM. Unexpectedly, SF contains all three known TFF peptides. As neither articular cartilage nor SM produce TFF1 and TFF2, we speculate that these originate with high probability from blood serum.

Long-term outcome in a case of shaken baby syndrome.

Shaken baby syndrome is one of the most common causes of disability and death in infants younger than one year of age. The syndrome is the result of major mechanical forces affecting the head and central nervous system. The outcome for surviving children is often poor, with both physical and mental disabilities. Multicystic encephalomalacia has been reported as a finding after such shaking. The present case involves a one-month-old boy who was brought to hospital by his father because of somnolence and feeding aversion. Radiological imaging revealed subdural haematomas, and fundoscopy found retinal haemorrhages. During police interrogation, the father confessed to having shaken the infant. Cranial ultrasonography subsequently showed increasing damage of the brain; the boy's general condition worsened. Eight weeks after admission, he died due to renal insufficiency. Upon autopsy, the brain was atrophic, with massive pseudocystic changes of the parenchyma. The case presented impressively shows the possible serious outcome of an admitted incident of shaking and emphasises the importance of an accurate education of parents about its severe and possible lethal consequences.

[Reddish discoloration of the vascular intima in charred bodies]. / Zur rötlichen Verfärbung der Gefäßintima bei Brandleichen.

During the autopsy of fire victims, one often sees intensive reddening of the inner vascular layers resembling changes due to putrefaction. To determine the frequency of this phenomenon and the circumstances under which it occurs, in particular the presence of putrescence, signs of vitality and the extent of destruction by the fire, the fire fatalities autopsied at the Institutes of Legal Medicine in Freiburg, Halle and Würzburg were analyzed. In the concrete study, 259 fire deaths were investigated retrospectively and 21 prospectively. The study material included 191 males and 68 females aged 0 to 93 years. Vital exposure to the fire was found in 70%, perimortal exposure in 23 % and postmortem exposure in 7% of the cases. Red discoloration of the intima of the central vessels was seen in 106 victims (41%). This finding is most likely caused by postmortem heat-induced hemolysis, which occurs when the temperature in the body rises above 52 °C due to the effect of external heat. Therefore, a reddish discoloration of the intima cannot be regarded as sign of vitality.

The detection of surfactant proteins A, B, C and D in the human brain and their regulation in cerebral infarction, autoimmune conditions and infections of the CNS.

Surfactant proteins (SP) have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain, facilitation of cerebrospinal fluid secretion and maintenance of the latter's rheological properties.

[Efficiency of inspections of the corpse before cremation performed in the area of the Halle University Medical Centre]. / Effizienz der Krematoriumsleichenschau im Bereich des Universitätsklinikums Halle.

From 1993 to 2007, the Institute of Forensic Medicine in Halle conducted 882 post-mortems before cremation. These records were now used for a systematic analysis of these cases to assess the efficiency of so-called second inspections of the corpse carried out in the area covered by the Halle University Hospital. In the period under review, considerable fluctuations were found from year to year, but these are mainly attributable to changes in the Saxony-Anhalt burial law introduced in 2002. Our 882 post-mortems were based on 84,677 corpse inspections before cremation; thus, an autopsy was performed in about 1% of all cases. Males were significantly overrepresented, younger age groups were dominant and there was a relatively high percentage where the first inspection of the corpse could not determine the manner of death or had to declare death by an unnatural cause. With regard to the manner and cause of death, the results of the first inspection and the post-mortem differed significantly. In 17.6% of our 882 cases, only the post-mortem revealed that death had been due to an unnatural cause. Despite the presence of sometimes strong clues to an unnatural cause, 156 of these cases were classified as natural deaths (56.4%) or the manner of death was stated as undetermined (43.6%). For more than two thirds of these 156 cases we were able to inspect the records kept by the Departments of Public Prosecution. 105 of these at first overlooked cases of unnatural deaths turned out to be deaths by accident. The other cases included 11 suicides, and 36 deaths related to medical treatment. In the remaining four cases, the autopsy results strongly suggested homicide, but only in one of these four cases subsequent police investigations were able to identify the perpetrator. This outcome demonstrates that the rule of inspecting the corpse a second time before cremation is clearly indispensable, even in its currently rather limited form.

Collision victim travels for "seven kilometres" on top of the car that hit him.

CASE REPORT: A 26-year-old man, after a drinking binge, drove into a tram building site and collided with a track-grinding machine which left a fist-size hole in his windscreen. He then hit a construction worker who was catapulted onto the car roof. The worker held on to the antenna and the windscreen hole, while the car drove on for 7 km, reaching speeds of 90 km h(-1). The victim suffered several fractures and survived with relatively little consequential damage. The investigation showed the driver to have been under the influence of alcohol and cannabis. In trial, he claimed loss of memory and stated that he had noticed neither the accident nor the man on his car roof.

Medical examination of fitness for police custody in two large German towns.

Worldwide, there is a high risk of medical complications or death in police custody. This risk is often increased by unclear legislation, a lack of clearly defined responsibility and medical examination standards. Any solution to these problems requires as a very basis the systematic analysis of the medical examinations that determine whether a person is fit to be detained in custody. We analysed a total of 3,674 medical records on fitness for custody, taken from two large German towns (Halle/S and Bremen). The examined individuals were predominantly males or of a younger age. The indication in the majority of cases was acute alcoholic intoxication or drug withdrawal syndromes. Traumata and internal or mental diseases were also quite frequent. For approximately 50% of all cases, fitness for custody was declared on certain conditions. Only 39.8% were found to be unconditionally fit for detention in custody. In just under 10% of the cases, the person was found unfit for custody. These cases concerned mainly persons with psychological symptoms and advanced alcohol or drug withdrawal syndromes. We were able to show that the recent introduction of new police custody regulations in Halle/S had a significant influence on the medical decision on fitness for custody. Our detailed assessment has provided us with the basis to develop solutions for the improvement of medical care in police custody. The focus lies here on the organisation and legal regulation of the medical aspects of custody but also on policing and medical work.

Transfer of biological stains from different surfaces.

Highly sensitive short tandem repeat-based stain analysis of weak biological stains has been improved during the last years. The risk of transfer of cellular material from handled items contaminated with biological stains such as blood and saliva is of forensic relevance. Although the policemen working with crime scene items are very careful, there exists a potential risk of transfer contamination. To obtain estimates for the risk of stain transfer by handling, we have carried out an experimental study on 288 dried blood and saliva stains in two laboratories. DNA quantification showed only small amounts of DNA that could be transferred, especially from stains on paper and cotton. The saliva and especially the blood stains from plastic surface resulted in higher amounts of transferred DNA, depending on the relation of blood volume to included area: Of 192 direct transfers, 17% gave extracts above 10 pg DNA/µl, and only 3% of 96 secondary transfers resulted in amounts above 10 pg DNA/µl.

Basilar artery occlusion after multifactor coagulopathy including Rhizopus oryzae infection in burns.

The authors report a case of a 29-year-old male patient with severe burn injuries (54% TBSA) and inhalation injury. He developed a candidemia and a cutaneous zygomycotic superinfection with Rhizopus oryzae while he received burn intensive care. Despite aggressive surgery, sepsis persisted, and therapy was limited by uncontrollable coagulopathy and catecholamine refractory shock after 15 days. Autopsy revealed a thromboembolic occlusion of the basilar artery that resulted in liquefactive necrosis of the basal brain tissue and the brain stem. Because cerebral vessel occlusions after burn injuries are reported rarely, the current literature was reviewed, and possible pathophysiological aspects are discussed.

Fulminant, undetected Candida sepsis after an apparently survivable burn injury.

We report a 20-year-old male who suffered smoke inhalation injury and burns covering 26% of his TBSA, including his face, dorsal chest, and both the arms. The Abbreviated Burn Severity Index was 5 (likelihood of survival 95%). He underwent burn surgery, requiring massive transfusion. Postoperatively, he appeared increasingly hyperthermic, showed respiratory exhaustion, and was neutropenic (lowest white blood cell count was 0.8 Gpt with a normal granulocyte count). He developed acute respiratory distress syndrome, renal failure, and severe inflammatory response syndrome. Aggressive ventilation patterns, intermittent prone positioning, and high-dose catecholamine therapy were performed. Hydrocortisone therapy and antibiotic prophylaxis did not improve his clinical status. He died after 12 days of septic multiple organ failure. Legal medicine autopsy identified aggressive Candida famata mycosis. The organism mainly affected the alimentary canal, and there were multiple pyemic abscesses in tissues of the heart, liver, spleen, kidneys, lungs, and meninges. Histology confirmed gastric ulcers as the source of the Candida infection. Despite the autopsy findings, all intravital specimens collected (blood, urine, and tracheal mucus) and all clinical Candida antigen tests were unsuspicious. Postoperative neutropenia may be a warning sign of severe infection even in survivable burns. Suppression of immune response and possible previous gastric Candida colonization may contribute to hazardous outcomes. However, delayed and unreliable methods to detect fungal infections remain a major problem in burn care. Occult aggressive fungal sepsis resulting in early multiple organ failure should be kept in mind.

Deaths in German police custody.

BACKGROUND: According to the ministries of the interior of all German federal states, a total of 128 persons died in police custody between 1993 and 2003. METHODS: An inquiry to the forensic university institutes and regional court doctors showed that, within this period, post mortems were conducted in 75 of these cases. We were able to include 60 of these 75 cases in our evaluation and deficiency analysis, which were carried out under assessment of the post mortem records and partly by making use of the subsequent medical expert reports and the results of criminal investigation. RESULTS: The most frequent cause of death was acute alcoholic intoxication, followed by cerebrocranial traumata, internal diseases and fatal poisonings with medical or illegal drugs. In 23 cases, the person taken into custody had been seen by a physician in order to determine the person's fitness for detention in custody. Of these 23 cases, 15 (65.2%) revealed deficiencies in various areas of medical activity. Police officers had made mistakes in 33 of the 60 cases (55.0%), mainly because they failed to seek medical assistance or did not monitor the person with sufficient frequency. Our retrospective study however showed that in 16 cases (26.6%) death was very probably not preventable even if the person had received all necessary care. CONCLUSIONS: Our study gives recommendations on how to improve various measures to increase the quality of medical attention given to persons taken into police custody.

TH01, a tetrameric short tandem repeat locus in the tyrosine hydroxylase gene: association with myocardial hypertrophy and death from myocardial infarction?

TH01 is a tetrameric short tandem repeat locus located in intron 01 of the tyrosine hydroxylase gene. The tyrosine hydroxylase catalyzes the hydroxylation of L-tyrosine to L-DOPA and is the rate limiting enzyme in the synthesis of catecholamines like noradrenaline or adrenaline, which are pivotal in the regulation of blood pressure. In a clinical study a strong correlation between alleles *9.3 and *10 and essential hypertension was observed ([2] Hypertension 32: 676-682). To further investigate this association, we typed TH01 in 296 autopsy cases and correlated the genotypes to the heart weight as parameter for myocardial hypertrophy. No significant correlation was observed. Moreover, dividing the studied cases into 2 groups, one including 172 casualties from hypertension-associated diseases (myocardial infarction, left heart failure, aortic aneurysm, spontaneous intracerebral bleeding and cerebral infarction) and one consisting of 124 cases of death unrelated to hypertension, revealed similar allelic frequencies for both groups. Our data thus suggest that TH01 long alleles appear not to lead to a significant increase in the incidence of myocardial hypertrophy or other hypertension associated diseases. This could be explained by a relatively small impact of the TH01 genotype on the blood pressure or by counteraction of another mechanism related to catecholamines and their effect on the human body.