"Death may come on like a stroke of lightening ..." : Phenomenological and morphological aspects of fatalities caused by manure gas

Due to the decomposition of biological material, hydrogen sulphide (H(2)S) is produced. In low concentrations, the well-known smell of "rotten eggs" is associated with H(2)S. In higher concentrations, H(2)S is an odourless and colourless gas that may cause rapid loss of consciousness, neurological and respiratory depression and imminent death-"... like a stroke of lightening". Hydrogen sulphide poisoning is an un-common incident that is often associated with colleague fatalities. In this study, 4 fatal accidents with 10 deceased victims are reported and the morphological and phenomenological aspects are presented. In these cases, the morphological findings, namely, discolouration of the livores, pulmonary pathologies and sub-mucosal or sub-serosal congestion bleeding were found in nearly all cases. Also the impending threat for colleagues, first aid helpers and professional rescue teams is demonstrated. The suspicion of a fatal H(2)S intoxication should be based on a precise scene analysis with respect to the possibility of life-threatening H(2)S intoxication for the helpers, the typical scent of rotten eggs, which may be noted on the corpses and the abovementioned morphological findings. The diagnosis should be confirmed by a qualitative and, if possible, quantitative analysis of H(2)S.

Functional and anatomical outcome of eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab following an exit strategy regimen.

AIMS To assess the functional and morphological outcome of eyes with neovascular AMD treated with intravitreal ranbizumab following an exit strategy treatment regime. METHODS The Bern treatment regime for neovascular AMD has a fixed injection schedule, even in the non-active stage of the disease. The regimen has been adapted from the PIER study treatment protocol. Eyes with non-active AMD will receive 4 injections in the first year, and 2 injections in the second year of follow-up before treatment stops. Patients that received ranibizumab for treatment and reached the exit criteria were identified, and charts were reviewed to assess functional and morphological outcome. RESULTS Only 2.6% of all patients (15 out of 575 patients) reached the exit criteria. Mean change in best corrected ETDRS visual acuity (VA) was 4.5±16.9 letters when comparing baseline VA to 4 weeks after the last injection (p=0.32). OCT mean foveal thickness was significantly thinner after last treatment (247.9±43.0 µm) compared to baseline (332.5±83.1 µm, p=0.002). The mean total number of ranibizumab injections was 15.6±8.0, and the mean total treatment period was 40.9±18.3 months. Twenty percent of eyes had geographic atrophy present at baseline versus 46.6% at the end of treatment. CONCLUSIONS Even with a fixed treatment regime and a defined treatment exit strategy, only a small percentage of patients reach exit criteria. Retinal thickness has been significantly reduced by repeated intravitreal ranibizumab injections, and geographic atrophy became more frequent.

Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

Molecular and pathogenetic aspects of tumor budding in colorectal cancer.

In recent years, tumor budding in colorectal cancer has gained much attention as an indicator of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival, and as an independent prognostic factor. Tumor buds, defined as the presence of single tumor cells or small clusters of up to five tumor cells at the peritumoral invasive front (peritumoral buds) or within the main tumor body (intratumoral buds), are thought to represent the morphological correlate of cancer cells having undergone epithelial-mesenchymal transition (EMT), an important mechanism for the progression of epithelial cancers. In contrast to their undisputed prognostic power and potential to influence clinical management, our current understanding of the biological background of tumor buds is less established. Most studies examining tumor buds have attempted to recapitulate findings of mechanistic EMT studies using immunohistochemical markers. The aim of this review is to provide a comprehensive summary of studies examining protein expression profiles of tumor buds and to illustrate the molecular pathways and crosstalk involved in their formation and maintenance.

Toward cell therapy using placenta-derived cells: disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table

Among the many cell types that may prove useful to regenerative medicine, mounting evidence suggests that human term placenta-derived cells will join the list of significant contributors. In making new cell therapy-based strategies a clinical reality, it is fundamental that no a priori claims are made regarding which cell source is preferable for a particular therapeutic application. Rather, ongoing comparisons of the potentiality and characteristics of cells from different sources should be made to promote constant improvement in cell therapies, and such comparisons will likely show that individually tailored cells can address disease-specific clinical needs. The principle underlying such an approach is resistance to the notion that comprehensive characterization of any cell type has been achieved, neither in terms of phenotype nor risks-to-benefits ratio. Tailoring cell therapy approaches to specific conditions also requires an understanding of basic disease mechanisms and close collaboration between translational researchers and clinicians, to identify current needs and shortcomings in existing treatments. To this end, the international workshop entitled "Placenta-derived stem cells for treatment of inflammatory diseases: moving toward clinical application" was held in Brescia, Italy, in March 2009, and aimed to harness an understanding of basic inflammatory mechanisms inherent in human diseases with updated findings regarding biological and therapeutic properties of human placenta-derived cells, with particular emphasis on their potential for treating inflammatory diseases. Finally, steps required to allow their future clinical application according to regulatory aspects including good manufacturing practice (GMP) were also considered. In September 2009, the International Placenta Stem Cell Society (IPLASS) was founded to help strengthen the research network in this field.

Gender, age and ethnic aspects of analgesia in acute abdominal pain: is analgesia even across the groups?

Numerous studies have shown differences in pain perception between men and women, which may affect pain management strategies.

The plasmin-antiplasmin system: structural and functional aspects

The plasmin-antiplasmin system plays a key role in blood coagulation and fibrinolysis. Plasmin and (2)-antiplasmin are primarily responsible for a controlled and regulated dissolution of the fibrin polymers into soluble fragments. However, besides plasmin(ogen) and (2)-antiplasmin the system contains a series of specific activators and inhibitors. The main physiological activators of plasminogen are tissue-type plasminogen activator, which is mainly involved in the dissolution of the fibrin polymers by plasmin, and urokinase-type plasminogen activator, which is primarily responsible for the generation of plasmin activity in the intercellular space. Both activators are multidomain serine proteases. Besides the main physiological inhibitor (2)-antiplasmin, the plasmin-antiplasmin system is also regulated by the general protease inhibitor (2)-macroglobulin, a member of the protease inhibitor I39 family. The activity of the plasminogen activators is primarily regulated by the plasminogen activator inhibitors 1 and 2, members of the serine protease inhibitor superfamily.

Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina

Retinal degeneration is followed by significant changes in the structure and function of photoreceptors in humans and several genetic animal models. However, it is not clear whether similar changes occur when the degeneration is induced pharmacologically. Therefore, our aim was to investigate the influence of retinotoxic N-methyl-N-nitrosourea (MNU) on the function, morphology and underlying molecular pathways of programmed cell death.

Cultural and migration aspects in functional abdominal pain

Compared to Europe's mean immigrant contingent of 7.3 to 8.6 % Switzerland holds the highest contingent of foreign population with 23.5 %. Therefore it is of utmost importance that physicians have a knowledge of the specific characteristics of immigrant patients. The influence of personality factors (experience, behavior) is not independent from the influence of culturally-related environmental factors (regional differences in diet, pollutants, meanings, etc.). In addition, different cultural groups rate their quality of life differently. Psychological reasons for recurrent abdominal pain are stress (life events), effects of self-medication (laxatives, cocaine) and sexual abuse but also rare infectious diseases are more common among immigrants (e.g. tuberculosis, histoplasmosis, etc.). Migration-specific characteristics are mainly to find in the semiotics of the symptoms: not every abdominal pain is real pain in the abdomen. Finally, it is crucial to make the distinction between organic, functional and psychological-related pain. This can, however, usually only be accomplished in the context of the entire situation of a patient and, depending on the situation, with the support of a colleague from the appropriate cultural group or an experienced interpreter. In this review we limit ourselves to the presentation of the working population of the migrants, because these represent the largest group of all migrants. The specific situation of asylum seekers will also be refrained to where appropriate.

Dental erosion--an overview with emphasis on chemical and histopathological aspects

The quality of dental care and modern achievements in dental science depend strongly on understanding the properties of teeth and the basic principles and mechanisms involved in their interaction with surrounding media. Erosion is a disorder to which such properties as structural features of tooth, physiological properties of saliva, and extrinsic and intrinsic acidic sources and habits contribute, and all must be carefully considered. The degree of saturation in the surrounding solution, which is determined by pH and calcium and phosphate concentrations, is the driving force for dissolution of dental hard tissue. In relation to caries, with the calcium and phosphate concentrations in plaque fluid, the 'critical pH' below which enamel dissolves is about 5.5. For erosion, the critical pH is lower in products (e.g. yoghurt) containing more calcium and phosphate than plaque fluid and higher when the concentrations are lower. Dental erosion starts by initial softening of the enamel surface followed by loss of volume with a softened layer persisting at the surface of the remaining tissue. Dentine erosion is not clearly understood, so further in vivo studies, including histopathological aspects, are needed. Clinical reports show that exposure to acids combined with an insufficient salivary flow rate results in enhanced dissolution. The effects of these and other interactions result in a permanent ion/substance exchange and reorganisation within the tooth material or at its interface, thus altering its strength and structure. The rate and severity of erosion are determined by the susceptibility of the dental tissues towards dissolution. Because enamel contains less soluble mineral than dentine, it tends to erode more slowly. The chemical mechanisms of erosion are also summarised in this review. Special attention is given to the microscopic and macroscopic histopathology of erosion.

Soft-Tissue Simulation for Cranio-Maxillofacial Surgery: Clinical Needs and Technical Aspects

Computerized soft-tissue simulation can provide unprecedented means for predicting facial outlook pre-operatively. Surgeons can virtually perform several surgical plans to have the best surgical results for their patients while considering corresponding soft-tissue outcome. It could be used as an interactive communication tool with their patients as well. There has been comprehensive amount of works for simulating soft-tissue for cranio-maxillofacial surgery. Although some of them have been realized as commercial products, none of them has been fully integrated into clinical practice due to the lack of accuracy and excessive amount of processing time. In this chapter, state-of-the-art and general workflow in facial soft-tissue simulation will be presented, along with an example of patient-specific facial soft-tissue simulation method.

Morphological and functional 3-Tesla magnetic resonance imaging of saphenous vein coronary artery bypass grafts

Evaluation of a novel non-invasive tool for postoperative follow-up of patients postelective saphenous vein coronary artery bypass graft (CABG) was performed. Ten patients were included. Their bypass grafts supplied the right coronary artery (7), marginal branches (1), diagonal branches (2), and the circumflex artery (n=1). Each bypass was examined intraoperatively using Doppler flow measurement. Patients were examined with a 3-Tesla magnetic resonance imaging (MRI) scanner (MAGNETOM Verio, Siemens, Erlangen, Germany) within one week postsurgery using MR-angiography with an intravasal contrast agent and velocity encoded phase-contrast flow measurements. Intraoperative Doppler flow measurements revealed regular flow patterns in all vascular territories supplied. The median intraoperative flow rate was 50 ml/min with an inter-quartile range (IQR) of 42-70 ml/min. The clinical postoperative course was uneventful. MRI showed all grafts to be patent. The median postoperative flow rate was 50 ml/min (IQR: 32-65 ml/min). MRI flow rates agreed well with intraoperative Doppler flow measurements (mean difference: -2.8±20.1 ml/min). This initial study demonstrates that 3-Tesla MRI flow measurements correlated well with Doppler thus reconfirming the graft patency postCABG. Further refinement and broader application of this technique may facilitate follow-up postCABG potentially replacing empiric clinical judgment by reliable non-invasive imaging.

[Analgesia for pediatric patients. Standards and special aspects]

In this paper we describe the assessment and medical treatment of pain in children according to the concept of the Centre of Pediatrics and Adolescent Medicine at the university of Freiburg, Germany. Opiate therapy in children as well as novel data about the association of paracetamol (acetaminophen) and wheezing/asthma bronchiale in children are discussed. Special aspects of analgesia for painful procedures and a nitrous oxide/oxygen mixture which has been recently introduced in Germany are described. The second part of the paper presents results of our prospective study about continuous infusion of fentanyl and midazolam in a fixed combination in 19 critically ill patients with a median age of 46 months, 40% of these patients had an ARDS. The mortality rate was 21%. A median dose of fentanyl of 3.9 microg/kg/h (midazolam 0.26 mg/kg/h) was infused. The fentanyl serum level (median 4.2 ng/ml, range 1.7-17.8 ng/ml) correlated significantly with the administered dose while the midazolam serum levels (median 911 ng/ml, range 234-4 651 ng/ml) correlated neither with the administered dose nor with any of the analysed parameters. Conclusion: A standard protocol for the assessment and treatment of pain should be established in every pediatric hospital. The data about the association of asthma bronchiale and paracetamol cannot be interpreted conclusively, but show that even for well known substances clinical trials may lead to new awareness. The study data about continuous infusion of fentanyl and midazolam show a good correlation of the fentanyl application to serum levels, while midazolam appears to be not the optimal substance for continuous sedation in this setting.

Morphological and biochemical T2 evaluation of cartilage repair tissue based on a hybrid double echo at steady state (DESS-T2d) approach

To use a new approach which provides, based on the widely used three-dimensional double-echo steady-state (DESS) sequence, in addition to the morphological information, the generation of biochemical T2 maps in one hybrid sequence.