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Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines in human solid tumours and inhibition of VEGF-induced angiogenesis suppresses tumour growth. Some groups of malignant lymphoma, including peripheral T-cell lymphomas and Hodgkin's disease, are characterized by a conspicuous proliferation of small vessels. To test the hypothesis that VEGF may also be involved in the angiogenesis in lymphomas and other lesions of the lymphoid system, VEGF expression was analysed in tissues, employing in situ hybridization with a 35S-labelled RNA probe specific for this cytokine. Significant expression of VEGF transcripts was observed in Hodgkin's disease and peripheral T-cell lymphomas, particularly of the angioimmunoblastic type. In contrast, expression of this cytokine was minimal or absent in follicle centre lymphoma and chronic lymphocytic leukemia of B-cell type. VEGF was mainly observed in reactive non-lymphoid CD68-negative cells, which probably represent fibroblasts or myofibroblasts. In normal and ulcerated tonsils, VEGF was expressed in the squamous epithelium but only rarely found in the lymphoid tissue. Although infectious mononucleosis tonsils contained high numbers of VEGF-positive cells in the interfollicular zone, expression of this cytokine was not found in Epstein-Barr virus (EBV)-infected cells, as determined by simultaneous in situ hybridization for VEGF and EBV-encoded small nuclear RNAs (EBER). In 5/8 cases of Castleman's disease, germinal centres containing small vessels also showed expression of VEGF, in contrast to normal tonsillar germinal centres which are devoid of both vessels and VEGF transcripts. It is concluded that VEGF may be involved in the induction of the angiogenesis of both peripheral T-cell lymphomas and Hodgkin's disease, but not in low-grade B-cell lymphomas. In contradistinction to solid tumours, in which this cytokine is commonly secreted by the tumour cells themselves, in malignant lymphoma VEGF is not a product of neoplastic cells. Vascularization of germinal centres in Castleman's disease may also be a consequence of abnormal local expression of VEGF.

By means of in situ proton magnetic resonance spectroscopy ((1)H-MRS) time-dependent metabolic changes in brain are measured for the estimation of post-mortem intervals (PMIs). An isolated whole head and a whole young sheep from an abattoir with known time of death were stored at approximately 21°C, and localized (1)H-MRS (TR/TE 2,500/25 ms) of the brain was performed at various PMIs with a clinical 1.5 T whole-body scanner using a quadratur head coil. In the isolated head, additional metabolites including free trimethylammonium (fTMA), propionate, and butyrate, and especially acetate, could be detected as described in previous studies. In the head of the whole animal, especially fTMAs and lactate were found in the late PMI but no further metabolites of relevance. These preliminary findings support the hypothesis that in a whole-body corpse, the distribution of bacteria from the gastrointestinal tract up to the brain in the late post-mortem interval can influence the metabolic decomposition of brain tissues. In further studies, it should be kept in mind that an isolated head does not represent authentic circumstances and is, therefore, not an ideal model for brain decomposition in intact corpses.

Two cases of regurgitation of gastric juice peri mortem are reported which resulted in lesions of the thoracic skin and led to the suspicion of being caused by another possibly dangerous chemical agent. In both cases, however, other causes of death could be established. Neither could any foreign chemical substances be detected by extensive toxicological investigations nor were any alterations of esophagus and gastric mucosa revealed in the course of the autopsy. Histological investigations demonstrated a circumscribed recent necrosis of the epidermis and dermis. Therefore, regurgitation of the acidic gastric content as the agent impairing the skin was most likely. The impressive histological appearance of the peri mortem regurgitation skin lesions lesions may be due to the circulatory arrest as well as stagnation of vital cellular reactions and repair mechanisms, dehydration of the altered tissue and postmortem permanence of the impairing agent.

Hiatus hernias of the diaphragma are rarely recorded under forensic aspects. Their relevance is demonstrated by the case of an elderly lady who was suffering from severe abdominal pain after dinner. She vomited several times and died 4 days later. After a forgery of the notarial last will and testament was revealed, a post-mortem was performed and a paraesophageal hiatus hernia was detected. The toxicological investigation revealed high levels of pethidin, and a married couple, both of them medical doctors, responsible for the forgery of the last will was charged with murder. The pathogenetic reconstruction led to the conclusion that a mechanism of 'self-tamponing' was initiated on the grounds of a pre-existing paraesophageal hernia filled up by the last meal ingested. The blockage of the gastrointestinal passage way induced severe abdominal pain and permanent vomiting, furthermore resulting in hemorrhagic infarction and perigastritis. Death from natural cause was finally appreciated by the court and the accused were acquitted. The post-mortem estimation of paraesophageal hiatus hernias is discussed, particularly, the necessity of an in situ preparation with separate incision of the translocated part and histological investigation. A synoptic expertise of clinicians, toxicologists and forensic pathologists is mandatory for estimating the relevance of high levels of analgesics.

The succession of insects is commonly used for estimation of the postmortem interval (PMI). In the warm season there are many insect species, which enable us to estimate the time of death, but in the cold season there are less species. For the estimation of a seasonal pattern, we examined 117 human corpses found in domestic environment during the year 2001. We found three typical ‘summer species’, active from May until October, three further species active from April until November. One blowfly species (Calliphora vicina) and the family of scuttle flies were active all over the year. These insects may be useful for PMI estimation in winter; however, further research concerning the developmental rate of scuttle flies is required. The distinct seasonal pattern of the early colonizing blowfly species allows to allocate the time of death to a particular time interval even in cases of long PMIs if empty puparia of these insects are found. q 2003 Elsevier Science Ireland Ltd. All rights reserved.

The authors report on three cases of myiasis which rarely occurs in the civilized world. Poor social conditions, old age, alcoholism, diabetes and vascular occlusive disease were predisposing co-factors. All three victims showed large necrotizing skin ulcerations, but in no case a generalized infection had developed. Therefore the probable benefit from the maggot infestation concerning these ulcerating skin lesions is discussed. For centuries clinicians have observed that maggots provide debridement of necrotic wounds particularly in Military Medicine. With the advent of antibiotics their therapeutic use declined. Recently "biosurgery" (syn. maggot or larval therapy) again became a promising tool for therapy of infected, necrotizing skin-ulcerations. Besides wound debridement marked anti-microbial activity and secretion of proteolytic enzymes could be detected. Maggot debridement is an valuable and cost-effective treatment option for patients with nonhealing wounds.

A case of fatal carbon monoxide poisoning is presented where three members of a family, aged between 23 and 66 years, died while having dinner. After analysing the scene and evaluating the personal circumstances there was no doubt that death was due to accidental carbon monoxide poisoning. The fact that three persons of different ages died almost simultaneously as well as the technical reconstruction appears noteworthy to the authors. Scrutiny of the technical circumstances revealed that the waste air containing carbon monoxide was re-routed because of the oppressively hot weather conditions. The fumes from the stove heating in the living room flowed into the chimney and from there via another pipe into the kitchen oven and finally reached the atmosphere of the kitchen where the three members of the family died.

Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils. Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1- positive cells from cytotoxicity directed at viral antigens.