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In laser tissue soldering (LTS), a protein solution is thermally denatured and cross-linked to obtain a strong bond between tissues or tissue and a wound dressing. However, if the extension of the heat-affected zone is too large, wound healing is impaired by thermal tissue injuries. Therefore, heat input and coagulation depth have to be limited. We investigate the influence of wavelength and beam profile on coagulation depth using a soft tissue phantom in case of weakly (980 nm) and strong (1540 nm) absorbed laser radiation. The soft tissue phantom is doped with polystyrene (PS) beads to obtain similar scattering properties as natural tissue. The propagation of the laser radiation in the phantom is simulated by Monte-Carlo method and the optical penetration (OPD) depth calculated from isophotes. The simulation results are compared with the experimental determination of the coagulation volume. The results reveal that scattering effect of tissues on laser radiation increases the losses of a Gaussian beam profile laterally leading to a half-sphere coagulation volume. The depth profile of the coagulation follows approximately the intensity distribution of the laser beams as long as scattering effects are weak. As scattering effects become significant, as for 980-nm radiation, the intensity distribution of the laser beam in the tissue deviates from the original one, leading to different profile of the coagulation depth.

The root canal system morphology of the mandibular second molar was investigated by means of micro-computed tomography (μCT). The root canal configuration (RCC), foramina and accessory canals frequency of 93 mandibular second molars of an Egyptian sample were investigated by μCT scans. The RCC and main foramina number (MFN) are described by means of a four-digit system from coronal to apical. The most frequently observed RCCs in the mesial root were 2-2-1/1 (32.3%), 2-2-2/2 (28.0%), 1-1-1/1 (6.5%) and 2-1-1/1 (6.5%); an additional twelve different RCCs were also found here. In the distal root, the RCC 1-1-1/1 was observed in 81.7%; another ten different RCCs with a frequency of less than 5% were also observed in this root. Anastomoses be-tween the mesiobuccal and mesiolingual canals in the mesial root were witnessed in the coronal (20.5%), middle (19.4%) and apical (10.8%) thirds. Accessory canals were found in the coronal (mesiobuccal 15.0%, mesiolingual 12.9%, distobuccal 1.1%), middle (mesiobuccal 7.5%, mesiolingual 10.8%, distolingual 3.3%) and apical (mesiobuccal 19.3%, mesiolingual 16.2%, distolingual 10.8%, distobuccal 2.2%) thirds. The RCC of mandibular second molars showed a great variety. When compared with the first mandibular molar in a historical control from the same sample, the mandibular second molar presented less morphological diversifications. Yet, the mesial root canalsystem of the mandibular second molar showed more RCC variations, connecting and accessory canals than the distal root.

Although women attempt suicides equally or more often than men do, men are more likely to die of suicide than women (sex paradox of suicidal behavior). Furthermore, the male traits of aggression and impulsivity predict suicide completion. Here, we studied the second-to-fourth-finger length ratio (2D:4D), a proxy for prenatal androgen exposure, in 46 suicide corpses and 25 non-suicide corpses. We report significantly lower 2D:4D in male suicide corpses than non-suicide corpses (p = .030, partial η 2  = .147). There was no significant association between 2D:4D and the suicide method. Our findings indicate increased risk of suicide following higher prenatal androgen exposure in males. The results may improve future efforts to predict and prevent suicides., Competing Interests: Compliance with ethical standardsConflict of interestThe authors declare that they have no conflict of interest.FundingThis work was supported by intramural grants from the University Hospital of the Friedrich-Alexander University Erlangen-Nürnberg (FAU). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.Ethical approvalThis study was approved by the Ethics Committee of the Medical Faculty of the Friedrich-Alexander University Erlangen-Nürnberg (ID 4578).

Background: During neoplasia, glycosylation changes. In this setting, mucins, especially mucin 1 (MUC1), become carriers for oncofetal carbohydrates and relieve invasive growth. The recently described tumor-associated MUC1 epitope TA-MUC1 is primarily restricted to malignancies and is overexpressed in these tissues. The humanized monoclonal antibody PankoMab-GEX specifically recognizes TA-MUC1., Materials and Methods: Laryngeal cancer specimens (n=125) and normal tissue of head and neck (n=7) were used in this study. Paraffin-embedded sections were incubated with PankoMab-GEX. Staining reaction was carried out using peroxidase (POD) labeling and diaminobenzidine (DAB). Breast cancer tissue was used as positive control and negative control used non-specific mouse IgM. Semi-quantitative evaluation by two independent double-blinded investigators, including a pathologist, used the immunoreactive score (IRS) of Remmele and Stegner., Results: A total of 31 out of 125 laryngeal cancer specimens were classified as G1. Of these, 22 (71%) were completely negative for TA-MUC1, the remaining 9 showed very weak staining, with an IRS of 2. A total of 94 cases of cancer specimens were classified as G2 and G3; 34 of them were also negative, but 60 had an IRS of up to 9. All investigated normal tissue of the upper aerodigestive tract was completely negative for TA-MUC1., Conclusion: G1 tumors are completely negative or do not reach an IRS relevant range. The finding that G1 tumors are completely negative for TA-MUC1 or have IRS≤2 can be helpful for histopathological examination, especially concerning tumor grading. Therefore, this antibody holds great potential for use as a therapeutic antibody in laryngeal cancer., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

To provide healthcare professionals with a comprehensive assessment of donepezil 23 mg and its role in treating Alzheimer's disease (AD), the Donepezil 23 mg Expert Working Group (EWG) convened in June 2011 to critically evaluate the clinical trial database for this higher dose formulation and the members' clinical experience with its use. Discussions were based on a large, 6-month, phase 3 clinical trial in patients with moderate to severe AD that compared continuing donepezil 10 mg/day versus switching to 23 mg/day. In this trial, donepezil 23 mg/day demonstrated significantly greater cognitive benefits (mean change in Severe Impairment Battery score, 2.11 points; P < 0.001). Prespecified analyses showed that benefits were significant irrespective of concomitant memantine use. The EWG considered integrating these new data into clinical practice approaches. Dementia severity, tolerability of the 10 mg dose, and need for additional therapy were key selection criteria, as was monitoring of gastrointestinal side effects, as consideration of titration strategies is an important aspect of implementation. The EWG concluded that donepezil 23 mg is an efficacious therapy for moderate to severe AD, with or without concomitant memantine, extending the treatment opportunities available to manage moderate to severe AD dementia. EWG guidelines offer assistance to clinicians in choosing and implementing treatment options., (© 2013 Blackwell Publishing Ltd.)

The Bingel-Hirsch reaction consists in the reaction of a bromomalonate with electron-poor π bonds, for example, of carbon materials, yielding cyclopropane derivatives. The reactive nucleophile is generated in situ from the respective malonate using CBr(4) and a base. The resulting cyclopropane moiety links the carbon material's surface atoms covalently with the functional side groups of the malonate. So far, the reaction was limited to fullerenes and carbon nanotubes. Herein, we report on the first application of this reaction type for the surface modification of diamond nanoparticles. The surface of thermally annealed nanodiamond consists of fullerene-like sp(2) carbon atoms which exhibit a similar reactivity as those in the all-sp(2) carbon nanomaterials. It was found that the reaction proceeds smoothly and enables the grafting of a large variety of functional groups to the surface of nanodiamond. The generated nucleophiles are also able to react with carbonyl species on the diamond. This reaction pathway enables the grafting of malonates even on oxidized nanodiamond without prior thermal annealing., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The detection and removal of bacteria, such as E. coli in aqueous environments by using safe and readily available means is of high importance. Here we report on the synthesis of nanodiamonds (ND) covalently modified with specific carbohydrates (glyco-ND) for the precipitation of type 1 fimbriated uropathogenic E. coli in solution by mechanically stable agglutination. The surface of the diamond nanoparticles was modified by using a Diels-Alder reaction followed by the covalent grafting of the respective glycosides. The resulting glyco-ND samples are fully dispersible in aqueous media and show a surface loading of typically 0.1 mmol g(-1). To probe the adhesive properties of various ND samples we have developed a new sandwich assay employing layers of two bacterial strains in an array format. Agglutination experiments in solution were used to distinguish unspecific interactions of glyco-ND with bacteria from specific ones. Two types of precipitates in solution were observed and characterized in detail by light and electron microscopy. Only by specific interactions mechanically stable agglutinates were formed. Bacteria could be removed from water by filtration of these stable agglutinates through 10 μm pore-size filters and the ND conjugate could eventually be recovered by addition of the appropriate carbohydrate. The application of glycosylated ND allows versatile and facile detection of bacteria and their efficient removal by using an environmentally and biomedically benign material., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aim: Tumour markers hold a great relevance in the diagnosis and the follow-up treatment of different kinds of human carcinoma. Although head and neck cancer occurs frequently, there is still lack of appropriate tumour markers. Our investigation on the expression of sialyl Lewis A (CA19-9) in laryngeal carcinomas, consists of systematical analysis of oncofetal carbohydrates and of galectins 1 and 3 in different normal and malignant tissues of the aerodigestive tract., Materials and Methods: Paraffin-embedded sections of normal tongue, vocal cord, larynx, pharynx and epiglottis, representing normal control tissue and laryngeal cancer tissue were incubated with monoclonal antibodies against sialyl Lewis A and X (sLeA and X), Lewis Y (LeY), the Thomsen-Friedenreich (TF) antigen and galectin 1 and 3 (Gal-1 and -3). A staining reaction was carried out with ABC-peroxidase and diaminobenzidine (DAB). Tissue of breast cancer was used as a positive control. Mouse IgM, as isotype control antibody, was used as a negative control. Semi quantitative evaluation was carried out double-blinded, by two independent investigators, including a pathologist., Results: Squamous epithelia of all investigated normal tissues of the aerodigestive tract show nearly the same pattern. Most impressive findings are the very weak expression of Gal-1 and the total absence of the TF antigen. Laryngeal cancer reveals high amounts of sLeA, Gal-1 and the TF antigen., Conclusion: On the basis of our findings in normal tissue of the aeradigestive tract, these three markers qualified as potential tumour markers for carcinoma of the aerodigestive tract. In particular, the high expression of TF in cancer tissue and its absence from the normal tissue is promising for its establishment as a new tumour marker in this field.

The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control. HIF appears to play a particular role for the kidney, where renal EPO production, organ preservation from ischemia-reperfusion injury and renal tumorigenesis are prominent examples. Whereas HIF-1α is inducible in physiological renal mouse, rat and human tubular epithelia, HIF-2α is never detected in these cells, in any species. In contrast, distinct early lesions of biallelic VHL inactivation in kidneys of the hereditary VHL syndrome show strong HIF-2α expression. Furthermore, knockout of VHL in the mouse tubular apparatus enables HIF-2α expression. Continuous transgenic expression of HIF-2α by the Ksp-Cadherin promotor leads to renal fibrosis and insufficiency, next to multiple renal cysts. In conclusion, VHL appears to specifically repress HIF-2α in renal epithelia. Unphysiological expression of HIF-2α in tubular epithelia has deleterious effects. Our data are compatible with dedifferentiation of renal epithelial cells by sustained HIF-2α expression. However, HIF-2α overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms.

We report a case of infectious orbital cellulitis complicating a frontal sinusitis in a seventy-three-year-old patient. The onset of this orbital complication was sudden. A clinical examination and an orbital CT-scan allowed an early diagnosis. Despite an appropriate surgical and medical treatment, the patient retains an altered visual function. We consider the clinical causes and consequences of orbital cellulitis as well as their surgical indications.

We report a rare case of periorbital necrotizing fasciitis following a dacryocystorhinostomy procedure. We describe the common features of this rare infection of the skin and subcutaneous tissues and discuss the different management strategies as well as the controversial role of anti-inflammatory medication in treating this condition., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Stable covalent C-C bonding of aromatic moieties has been achieved using Diels-Alder reactions on surface-annealed nanodiamond. Subsequent functionalisation leads to tunable surface properties and molecule-like behaviour.

We describe an African patient with sarcoidosis involving the lacrimal glands. Gallium scintigraphy showed the so-called "panda sign".

Ocular side effects associated with biphosphonates have been described. Conjunctivitis, uveitis and scleritis are the most common adverse events. We report a case of bilateral toxic optic neuropathy with optic dies edema occurring soon after a pamidronate intravenous infusion in a patient who previously presented both a conjunctivitis and an uveitis of moderate intensity associated with alendronate therapy.

Background: The clinical relevance of the carbohydrate antigen Sialyl Lewis a (SLea) as a serum tumor marker in diagnosis and follow-up treatment is unquestioned in a broad spectra of human carcinomas. Overexpression of this antigen is combined with poor prognosis and malignant relapse. The aim of our study was the systematic investigation of SLea expression in squamous cell carcinoma of the larynx versus normal and phlogistic tissue., Materials and Methods: Paraffin-embedded sections of normal, phlogistic and squamous cell carcinoma tissue were incubated with a monoclonal antibody against SLea. The staining reaction was performed using ABC-Peroxidase and DAB. As a positive control tissue of breast cancer was used and the negative control was performed with unspecific mouse IgM. Semiquantitative evaluations were carried out double-blinded by two independent investigators, including a pathologist., Results: A very faint expression of SLea (Ca19-9) in normal laryngeal tissue, a moderate upregulation in phlogistic tissue and a dramatic upregulation in some types of squamous cell carcinoma of the larynx were observed. Laryngeal cancer is the most common cancer of the upper aerodigestive tract. Most cases of laryngeal cancer are squamous cell carcinoma and can be classified into: well differentiated (more than 75% keratinization), moderately differentiated (25-75% keratinization), and poorly differentiated (<25% keratinisation) carcinomas., Conclusion: The results of this study indicate that SLea is a potential tumor marker in carcinoma of the larynx.

The performance of two detection techniques for body fluids, the Spectra-Physics(R) Revealtrade mark portable forensic laser system and the mercury-arc lamp Lumatec Superlite 400, was evaluated with various biological stains on different substrates. Serial dilutions of neat, 1/10, 1/100 and 1/1,000 using fluid semen, saliva, urine and blood were applied on glazed tiles, glass, PVC, wood, metal, stone, formica, carpet and cotton. Apart from the fact that blood traces were not detectable with the laser, both light sources showed comparable results regarding their detection capability. Clear advantages of the Lumatec Superlite 400, however, are its lower size, weight, purchase costs and the possibility to operate this light source by battery.

Two uncommon allelic variants have been observed at the locus ACTBP2 (SE33) and both were located far outside the ladder range of commercially available typing kits. The short variant showed a 60-bp deletion upstream of the 5'-flanking region with a typical type I repeat structure, which actually would have to be assigned as allele 16. The long allele revealed a typical type III sequence structure that has to be designated as allele 41.

The severity and duration of cognitive performance capacity deficits after intravenous administration of propofol were determined using the validated psychological test procedure syndrome short test (SKT), a simple reaction test and original driving licence exam questions. The test battery was performed before, immediately after, as well as 1 and 2 h after propofol administration in 23 persons. Immediately after propofol anaesthesia, six individuals had a slight performance loss, and four subjects showed mild deficits, consistent with medium organic neuropsychologic disorder or dementia. The status of the subjects rapidly changed for the better, and 2 h after propofol anaesthesia, only one person (4%) showed slight deficits of memory and attention. Therefore, it is suggested that patients refrain from any participation in road traffic for at least 2 h after propofol anaesthesia. Driving a car should not be admitted until an interval of 6 h has elapsed.

Background: Sialyl Lewis x (SLeX), sialyl Lewis a (SLeA), Lewis Y (LeY) and the Thomsen-Friedenreich (TF) antigen are carbohydrate motifs that mediate the adhesion between tumour cells and the endothelium. These antigens are usually not expressed in non-malignant tissue. Overexpression of SLeX and SLeA is combined with poor prognosis and malignant relapse. In this study, we analysed the combined expression of SLeX, SLeA, LeY and TF in normal squamous epithelium tissue of the penis shaft, glans and foreskin and in addition of the vagina and vulva., Materials and Methods: Paraffin-embedded slides of vaginal tissue (8), vulva tissue (8) and penis shaft (8) and glans tissue (8) were fixed and incubated with monoclonal antibodies against SLeX (IgM), SLeA (IgM), LeY (IgM) and TF (IgM). Staining reaction was performed with ABC reagent. The intensity of immunohistochemical reaction on images of the slides was analyzed using a semiquantitative score., Results: Strong focal expression of both sialyl Lewis antigens was found in the uretra of the penis shaft and on epithelial tissue of the glans, and permanent moderate expression of SLeX and SLeA in squamous epithelial tissue of the vagina. Moderate expression of TF was observed in male squamous epithelial tissues of the glans and foreskin and faint expression of TF was found in vulval epithelial tissue. Faint expression of Le Y was observed in female vulval epithelial tissue., Conclusion: Expression of SLeX, SLeA, LeY and especially of the TF antigen in normal non malignant epithelial tissue is surprising and can be explained by the function of this tissue in human reproduction. In addition, moderate TF expression seems to be restricted to epithelial tissue of the penis glans and foreskin.

The significance of both Purkinje cell numbers and various neuronal changes for the diagnosis and timing of hypoxic-induced brain lesions was investigated in tissue samples from the cerebellar cortex of 52 individuals with a history of acute or prolonged cerebral hypoxia/ischemia before death. Furthermore, the area of the Purkinje cell somata (PC size) was measured using an automatic image processing and analysis system (LEICA QWin). Significantly reduced numbers of Purkinje cells (<6 cells/unit length of 1 mm) and a decreased portion (<50%) of intact Purkinje cells could be detected in individuals with a period of resuscitation of at least 2 h after acute circulatory arrest. Average cell numbers of less than 4 cells/unit were found in individuals who suffered from diffuse brain swelling and were ventilated for at least 3 days, as well as in individuals who died of brain death. Moreover, the Purkinje cells in these cases exhibited shrunken somata compared to the controls. Specimens that were stored at room temperature up to 30 h after removal at autopsy showed no significant autolytic changes of the Purkinje cells. After 46 h, however, reduced Purkinje cell numbers and shrunken cell bodies were found.

During a dispute, a boy was injured by a curtain rail which penetrated the skull in the left frontal region and led to severe brain injury. Despite intensive medical care, death occurred 10 days later due to malignant cerebral edema. With regard to the question whether the trauma resulted from throwing or pushing, some biomechanical aspects are discussed including individual morphologic findings as well as the kinetic energy required for penetrating the skull. According to the calculated data, we conclude that the velocity necessary for penetrating could be reached by throwing the curtain rail.

This study investigated the value of both gross features and histological findings for grading of brain swelling. For this purpose, the grooving of the temporal gyri (unci) as well as the extension of the cones at the basal part of the cerebellum were measured in 42 brains obtained at autopsy. Furthermore, the distension of perivascular spaces in tissue samples from seven different regions of the brains was evaluated histologically, assisted by an automatic image processing and analysis system. In each individual, the normal range of brain weight was calculated on the basis of the body height, using the formulae by Röthig and Schaarschmidt. The difference between this calculated (normal) value and the brain weight evaluated at autopsy was considered as a reliable criterion for the grade of brain swelling. There was no statistical evidence of a positive correlation between the various parameters. Hence, it can be concluded that both gross section and histological findings are of minimal significance for grading of brain swelling.

With the PALM MicroBeam system, precise laser microdissection of single cells from cell smears or tissue preparations is possible. Furthermore, this system uses a contact-free and therefore contamination-free laser pressure catapulting technique in which high energy generated by a focused laser pulse catapults single dissected cells into a collecting vessel. In this study, this technique was tested for forensic purposes with smear preparations from postcoital vaginal swabs, sperm swabs, and buccal cell swabs on different types of microscopic slides. Apart from super-frosted slides, cutting and catapulting of selected cells was possible in all cases. Subsequent polymerase chain reaction was performed using the genRES MPX-2 Amplification Kit. In the case of sperm cells stained with hematoxylin and eosin, fragments larger than approximately 200 bp could not be detected. Partial genetic profiles were obtained for DNA amounts originating from only two cell equivalents. Complete profiles, however, were observed with all preparations of a minimum of 10 epithelial cells, demonstrating a potential benefit of this technique for the contamination-free forensic analysis of extremely small specimens or mixed stains.

Since 1998, driving under the influence of drugs such as amphetamine, MDMA, MDE, cannabis, cocaine, heroine and morphine is sanctioned due to Section 24a of the Road Traffic Regulations of Germany. Therefore, from December 2000 to June 2002 altogether 751 roadside tests with the immunochemical test device Toxiquick were conducted on 302 drivers (273 male and 29 female) on oral fluid samples obtained during control actions in Franconia. The results of the tests are compared to the results obtained through quantification of corresponding blood samples by GC/MS. In general, in 75% the roadside test produced correct results and therefore gave helpful assistance to the police officers into the right direction regarding drug abuse. Except for cannabinoids, the number of false negative results was relatively small, whereas false positive results ranged between 32.2% for opiates and 10.7% for benzoylecgonine.

Objectives: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI)., Background: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers., Methods: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography., Results: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014)., Conclusions: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

Clostridial myonecrosis or gas gangrene occurs most frequently in contaminated wounds following trauma or surgery. It is caused by a wide variety of Clostridium species, the most common being Clostridium perfringens. Spontaneous, non-traumatic clostridial myonecrosis is uncommon and is usually associated with gastrointestinal and haematological malignancy, diabetes mellitus and peripheral vascular disease. The case of a previously healthy 16-year-old boy with acute onset of gastrointestinal symptoms, who died of bacterial sepsis without apparent preceding trauma, is presented here. Clostridium fallax was identified as the most probable causative agent. As far as is known, this is the first report of fatal sepsis in humans due to C. fallax, which has been described only rarely as a cause of gas oedema in animals.

A previous healthy 35-year-old man was found dead in his truck. Shortly before death he merely complained of influenza-like symptoms. The histological examination revealed evidence of a massive accumulation of sickle cells in smaller blood vessels. After molecular genetic analysis, the preliminary diagnosis of "sickle cell disease" was finally changed to the diagnosis of a sickle cell trait. It is presumed that an epileptic attack which also has to be considered as a concurring cause of death, precipitated sickling of the erythrocytes and led to a fatal sickle cell crisis.

Lungs removed at necropsy normally collapse due to the loss of negative pleural pressure leading to a quite unnatural appearance of both gross and histological specimens. In order to demonstrate the influence of post-mortem lung retraction on the degree of alveolar expansion, a histomorphometrical analysis was performed in lungs from a 9-month-old healthy infant. Tissue specimens from the right lung were obtained at autopsy and routinely fixed after retraction ('routinely fixed lung'), whereas the left lung was fixed in situ before opening the thoracic cage ('in situ fixed lung'). The size of the alveoli as well as the thickness of the alveolar walls were measured using an automatic image processing and analysis system (Leica QWIN) in both lungs. The mean alveolar size was 8.7 x 10(3) microm(2) in the routinely fixed lung (alveoli, n=1.1576) and 10.9 x 10(3) microm(2) in the in situ fixed lung (alveoli, n = 841). In contrast, the diameter of the alveolar walls showed no significant difference in both lungs. The average thickness of the alveolar walls was 7.9 microm (measuring sites, n = 1.190) in the routinely fixed lung and 8.1 microm in the in situ fixed lung (measuring sites, n = 1.027), respectively. The results provide evidence of significantly reduced aeration in the retracted and routinely fixed lung which could be of special forensic interest in cases of suspicious infanticide, stillbirth or infant death by drowning or suffocation.

Neuronal apoptosis has been investigated in paraffin-embedded brain tissue from 103 individuals who had sustained blunt head injury by use of the in situ nick translation (ISNT) technique. In order to provide reliable data for a forensic wound age estimation, a quantitative morphometric analysis was performed. Apoptotic neuronal cells could be detected in a cortical contusion with a wound age of 45 min at the earliest and in the majority of the cases with postinfliction intervals up to 2 weeks, numerous ISNT-positive cells were found adjacent to the traumatically injured area. The presented data indicate that neuronal apoptosis peaks at about 1 day and persists for at least 22 weeks after blunt head injury. The time-dependent occurrence of apoptotic cells can contribute to a forensic timing of cortical contusions and complements other immunohistochemical parameters, especially in the early postinfliction interval.

In this study the development of a 13-locus multiplex-PCR system fitting the updated demands for paternity testing in Germany is described. For this purpose an existing multiplex PCR system that allows the simultaneous amplification of eight different STR loci together with the sex-specific locus amelogenin ( genRESMPX-2, Serac, Germany) was extended. Whereas some of the primers were taken from the underlying multiplex system, suitable primer sequences were chosen for the STR loci D19S433, TPOX, TH01, D16S539, D5S818, D2S1338 and FGA. Primers of loci resulting in potentially overlapping fragment sizes were labelled with the fluorescent dyes 6-FAM, JOE and NED. Reaction conditions, such as annealing temperature, concentrations of primers and polymerase or buffer conditions were optimised to obtain a robust amplification and reproducible genotype analysis for various sample sources. Full DNA profiles from single source samples were reliably typed from template DNA amounts of as low as 120 pg, suggesting a potential use of this system also in forensic casework analysis. With a mean exclusion chance (MEC) of 99.9989% and a power of discrimination (P(D)) of about 1x10(14) (Caucasians), the new multiplex PCR system provides a significant and sensitive system for forensic DNA analysis. On the basis of these studies, a commercial kit system is now provided by Serac (Bad Homburg, Germany, genRESMPX-3).

A 27-year-old worker in a metal processing factory was found dead in a basin, sitting in a solution containing potassium dicyano argentate, potassium cyanide, master batch and brightener 'Elfit 73'. The worker was wearing an acid-resisting overall, rubber boots and a simple dust respirator. While the cyanide concentration in the stomach contents was only 0.05 microg/ml, it was 7.7 microg/g in the lung tissue, 6.3 microg/ml in the heart blood and 31 microg/ml in the femoral vein blood. The different concentrations suggest an initial lethal inhalation of cyanide and an extensive post-mortem diffusion of cyanide through primarily non-injured skin of buttocks and legs. The possibility of a post-mortem cyanide diffusion bars from concluding a vital sign from a high cyanide concentration in a blood sample of one single body site.

This is the report of a 62-year-old man who committed suicide by drilling through his anterior chest wall with an electric power drill. Death was caused by pericardial tamponade combined with bleeding into the pleural cavity. The skin lesion at the left hemithorax was similar to a bullet entrance wound., (Copyright 2002 Elsevier Science Ireland Ltd.)

A man was found unconscious near a ladder in a house. After resuscitation he was brought to a hospital and X-rays of the skull showed that two 12-cm long nails had completely penetrated the cranial cavity. The nails were operatively removed and after treatment for 5 weeks, the patient was transferred to a rehabilitation centre with a decreasing hemiparesis on the left side and general deterioration and then, after an attempted suicide to a psychiatric hospital. The perforating cranio-cerebral injury from a pneumatic nail gun known to reach only low muzzle velocities is a very unusual finding.

A case of attempted homicide is reported where a 31-year-old woman was shot in the left nostril with a pellet from an air rifle. The projectile channel reconstruction showed penetration of the nasal septum, the maxillary and sphenoid cavities and the dura mater, with the pellet finally lodging in the anterior cranial fossa between the sinus cavernosus and the internal carotid artery. The patient was finally discharged from hospital in a good physical condition without any neurological symptoms. Although the muzzle velocity of the air rifle was within the legal limits, the present case demonstrates the potential lethality of air weapons considering the site of entrance of the pellet.

A case of death due to car fire is described where the carbonised skull of the cremated corpse showed an ovoid defect of the cranial bone. The question arose whether this formed fracture was caused by a gunshot. But the reconstruction of the cranial remains with detached parts of the tabula externa provided evidence that the suspicious defect was to be classified as an uncommon heat-induced post-mortem artefact.

In this study, the effect of sample purification on total signal intensities of samples amplified with genRES MPX-2 (nine-locus multiplex) prior to capillary electrophoretic analysis has been investigated. Sample purification with the Qiaquick PCR purification kit led to an increase of the relative fluorescent signal intensity by a factor of 3.8 +/- 0.8. In contrast, the application of larger sample volumes led to a decrease of signal intensities from 20% to 80%, depending on whether the samples were purified or not. In addition, increase of injection time showed a linear increase of signal intensity between 3 s and 10 s. Increasing the number of PCR cycles from 30 to 33 also led to a significant increase of signal intensities. Nevertheless, this increase greatly depended on the fragment lengths and was sometimes accompanied by the appearance of non-specific signals. In combination, optimisation of sample preparation and increase of injection time may intensify signals up to 12-fold, thereby increasing the overall sensitivity of the assay. This may be of special interest for forensic analysis of microspecimens containing limited amounts of DNA.

The course of MIB-1 expression by brain macrophages adjacent to cortical contusions has been immunohistochemically investigated during the first 30 weeks after human brain injury, in order to provide data for a forensic wound age estimation. A positive nuclear staining for MIB-1 could be observed earliest after a postinfliction interval of 3 days and regularly in cases with a survival time between 7 and 14 days, whereas in uninjured brain tissue (control group) no cellular MIB-1 reactivity was visible.

A 55-year-old male nurse was accused of having introduced his fingers by force into the anus of a 20-year-old female patient. Debris from the fingernails of the suspect recovered 2 days after the incident was analysed with the VNTR locus D1S80, the triplex PCR system AmpFlSTR Blue kit, the AmpFlSTR Profiler kit and the pentaplex system genRES MPX. The D1S80 singleplex reaction revealed indications of DNA from the victim in the fingernail debris of the left hand. Using the AmpFlSTR Blue kit and AmpFlSTR Profiler, DNA alleles of the victim were found at four additional loci, while allelic drop-out was observed at five other loci. Only the pentaplex kit genRES MPX revealed alleles at all loci which could be assigned to the victim. Calculation of likelihood ratios resulted in a value of 1.4 x 10(5) using the combination of the multiplex systems AmpF1STR Blue kit and AmpFlSTR Profiler and 2.8 x 10(8) for the genRES MPX kit. This case demonstrates the high sensitivity of the new genRES MPX kit and that DNA profiling of fingernail debris is possible despite a time lapse of 2 days between the incident and recovery of the evidential material.

In a total of 104 individuals who had sustained traumatic brain injury (TBI), the course of glial immunoreactivity was investigated at the injured cortical area during the first 30 weeks after the trauma, in order to provide data for a forensic wound age estimation. Glial cells were stained with antibodies against the intermediate filament protein vimentin, the extracellular matrix protein tenascin and the serine protease inhibitor alpha1-antichymotrypsin (alpha1-ACT). Injury-induced glial staining reactions could be observed, at the earliest, after a post-infliction interval of 3.1 h for alpha1-ACT, 22 h for vimentin and 7 days for tenascin.

The case of a young man who committed suicide in a lions' den of a zoo is presented. Special attention is paid to the injury pattern which was characterised by numerous penetrating, stab-like wounds and lesions. The remarkable circumstances and history of this incident are most likely connected to a psychological or psychiatric disorder of the victim.

In a total of 104 individuals who had sustained traumatic brain injury (TBI), the time-dependent vascular response was investigated at the injured cortical area during the first 30 weeks after the trauma. The immunohistochemical staining of the cerebral blood vessels was performed with antibodies against laminin, type IV collagen, tenascin, thrombomodulin and factor VIII associated antigen. Compared to the immunoreactivity in unaltered control tissue, a significantly increased vascular expression could be detected in cortical contusions after a postinfliction interval of at least 3 h for factor VIII, after 1.6 days for tenascin or after 6.8 days for thrombomodulin, whereas the immunostaining for laminin and type IV collagen was regularly positive even in the vascular endothelium of uninjured brain tissue.

The course of GFAP expression by astrocytes has been immunohistochemically investigated during the first 30 weeks after human brain injury. In order to provide reliable data for a forensic wound age estimation, a quantitative morphometric analysis was performed considering the different topographic regions of the cortex as well as of the white matter. Compared to the GFAP immunoreactivity in unaltered control tissue, significantly increased numbers of GFAP positive astroglial cells could be detected adjacent to the cortical contusion from 1 day up to 4 weeks after brain injury.

In 1998 the Federal Criminal Police Office of Germany (BKA) established a central genetic database of offenders and suspects to facilitate comparisons with biological samples from future criminal offences. The five obligatory short tandem repeat (STR) loci in this database (TH01, SE33, vWA, FGA and D21S11) were co-amplified in a new PCR pentaplex analysing system together with the sex-specific locus amelogenin. Due to overlapping fragment sizes, amplification products were fluorescent dye-labelled with different colours, separated by electrophoresis and detected directly using the ABI PRISM 310 Genetic Analyzer. Reproducible and reliable results were obtained from as low as 125 pg template DNA, indicating high specificity and sensitivity of the assay. Environmental studies and enzymatic digest with DNase I revealed an excellent stability of the pentaplex system with typeable results even in cases of partially degraded DNA. Complete and reproducible DNA typing was possible in blood-stain mixtures with the minor component as low as 10%. Mean stutter peak intensities were analysed for all loci and ranged from 2.7 +/- 0.8% (TH01) to 10.6 +/- 1.6% (vWA) of the main signal intensity. Allele frequencies were determined in a North Bavarian population sample (n = 121). The combination of five systems resulted in a mean exclusion chance of 99.86% and a power of discrimination of 99.999996%. No deviation from Hardy-Weinberg equilibrium could be found.

Unlabelled: Up to now reliable data were available on cases of lethal child neglect in the area of the Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period from 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany., Results: The study center received information on 19 cases of lethal child neglect. Extrapolated to all institutes of legal medicine, this corresponds to 20 cases and thus 3.5 cases a year in the whole of West Germany in the period studied. There is to be added a dark-field which cannot be limited more precisely. However, the cases of fatal child neglect might have occurred much more seldom than fatal child abuse caused by use of physical violence. Slightly more than half the victims were younger than 1 year, the oldest one was 7 10/12 years old. Most frequently the children died of starvation and thirst. Mostly the mothers/nursing mothers killed the child alone or together with the victim's father/stepfather. In the majority of the cases there was not a close affection between parents and child. Nearly 30% female/male perpetrators suffered from chronic alcohol abuse. Only 15 (= 56%) of 27 female/male perpetrators were sentenced to imprisonment (period between 7 months on probation and 10 years). Mitigation circumstances existed for nearly half the persons sentenced to imprisonment. It is true that child neglect is a rarer crime, but the experts of legal medicine always have to indicate errors made during the external inspection of the corpse (among others failures to see indications of neglect).

Unlabelled: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously., Results: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

Unlabelled: No reliable data are available on cases of lethal child abuse (by active force) in the area of Federal Republic of Germany prior to reunification (the former West Germany). In a multicenter study we therefore examined the police and court records for such cases occurring in the period 1 January 1985 to 2 October 1990 in nearly the entire area of Federal Republic of Germany., Results: The study center received information on 58 cases of lethal child abuse. Extrapolated to all institutes of legal medicine, this corresponds to 62 cases in all of West Germany in the period studied. An approximately equal number of unreported cases should be added to this figure. Including unreported cases, at least 20 cases of lethal child abuse occurred per year; thus only one in every two cases ever came to light. Almost two thirds of the victims were younger than one year old. At autopsy 59% exhibited signs of repeated abuse at autopsy. By far the most common cause of death was direct impact from a blunt object, usually to the head. Mostly, the male person to whom the victim relates most closely (father, stepfather, partner of the mother) has killed the child. Twenty-one of the 74 persons charged saw the charges against them dropped or were acquitted due to lack of evidence; 51 received sentences ranging from one year probation to life. In the remaining two cases the outcome of the trial was unknown. Signs of abuse were readily apparent at autopsy in almost all cases. The high number of unreported cases underscores the need to educate medical students and practicing physicians to be on the look-out for signs of abuse and argues for an increase in the rate of autopsy.