Penetrating skull stab.

Fatal skull stabs are rare. In the case reported here, a 28-year-old man sustained an isolated penetrating skull injury from a knife and died two days later. The bone shard with the stab puncture, which was neurosurgically removed before death, later allowed the reproducible exact assignment of the murder knife found at the scene to the stab as well as the estimation of the length of the intracranial stab channel.

A case of biliary adenofibroma of the liver with malignant transformation: a morphomolecular case report and review of the literature.

Background: Biliary adenofibroma is an exceptionally rare benign liver tumor with the potential for malignant transformation. In literature, only 21 cases have been described.

Clinical Presentation: In a healthy 63-year-old woman, a partly solid, partly cystic mass in the left lobe of the liver during a routine ultrasound examination was found.

Multiparametric Prostate Magnetic Resonance Imaging at 3 T: Failure of Magnetic Resonance Spectroscopy to Provide Added Value.

Purpose: To assess the effect of proton magnetic resonance spectroscopy imaging (MRSI) on the accuracy of multiparametric magnetic resonance imaging (mpMRI) at 3 T for prostate cancer detection.

Materials And Methods: Thirty-four patients with prostate cancer were included in this retrospective study. All patients underwent preoperative mpMRI on a 3-T scanner before radical prostatectomy.

Neuron-specific alterations in signal transduction pathways associated with Alzheimer's disease.

The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways.

Neuron-specific mitochondrial DNA deletion levels in sporadic Alzheimer's disease.

Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer´s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage and increase with age. To unravel the impact of mtDNA damage on AD development, we analyzed mtDNA deletion levels in diverse neuronal cell types of four brain regions (hippocampal CA1 and CA2 regions, nucleus tractus spinalis nervi trigemini, and the cerebellum) that exhibit differing levels of vulnerability to AD related changes at progressive Braak stages compared with age-matched controls.

Molecular pathology and age estimation.

Over the course of our lifetime a stochastic process leads to gradual alterations of biomolecules on the molecular level, a process that is called ageing. Important changes are observed on the DNA-level as well as on the protein level and are the cause and/or consequence of our 'molecular clock', influenced by genetic as well as environmental parameters. These alterations on the molecular level may aid in forensic medicine to estimate the age of a living person, a dead body or even skeletal remains for identification purposes.

Dermal schwannoma (neurilemmoma): a peculiar foreign body reaction?

Schwannoma is usually a subcutaneous benign neoplasm that derives from nerve sheath. Pain and neurologic symptoms are uncommon, and exclusively dermal tumors are very rare. Solitary schwannoma has a traumatic origin in some cases, and rarely occur as a part of neurofibromatosis or schwannomatosis.

Pathomorphological staging of subdural hemorrhages: statistical analysis of posttraumatic histomorphological alterations.

We examined 10 histomorphological alterations of 222 cases of subdural hemorrhages following mechanical closed brain injury (MBI) to determine the posttraumatic interval (PTI). These morphological features included red blood cells (RBCs), polymorphonuclear leukocytes (PMNs), macrophages (Ms), RBC-containing Ms, hemosiderin-containing macrophages, hematoidin, fibroblasts, endothelial cells, collagenous fibers and membrane formation. The interval between the time of brain injury and death ranged from a few minutes to 33 years.

Routine techniques in forensic neuropathology as demonstrated by gunshot injury to the head.

It will be vital to the practical activity of every forensic and/or clinical pathologist to be able to answer three questions regarding the reconstruction of a lethal event: the type and cause of death, as well as the survival time. The authors offer an overview of the application of selected morphological techniques in general forensic neuropathology, techniques that provide answers to some of the main questions in forensic neurotraumatology. The methods are illustrated by individual cases of lethal gunshot injury to the head from low velocity handguns.

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

Rationale: Noisy ventilation with variable Vt may improve respiratory function in acute lung injury.

Objectives: To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies.

Methods: In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group).

Hypoxic-ischemic changes in SIDS brains as demonstrated by a reduction in MAP2-reactive neurons.

Sudden infant death syndrome (SIDS) is characterized by a lack of any known morphological or functional organ changes that could explain the lethal process. In the present study we investigated the hypothesis of an association between hypoxic/ischemic injury and SIDS deaths. In a previous study, we could demonstrate by quantitative immunohistochemistry a distinct drop in microtubule-associated protein (MAP2) reactivity in neurons of adult, human brains secondary to acute hypoxic-ischemic injuries.

Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease.

Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate.

The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more?

It has been suggested that deletions of mitochondrial DNA (mtDNA) are important players with regard to the ageing process. Since the early 1990s, the 4977 bp deletion has been studied in various tissues, especially in postmitotic tissues with high energy demand. Unfortunately, some of these studies included less than 10 subjects, so the aim of our study was to quantify reliably the deletion amount in nine different regions of human brain, heart and skeletal muscle in a cohort of 92 individuals.

Shaken baby syndrome: re-examination of diffuse axonal injury as cause of death.

The discussion surrounding shaken baby syndrome (SBS) arose from the lack of evidence implicating diffuse axonal injury (DAI) as a cause of death. It was assumed instead that injury to the cervical cord, medulla, and nerve roots played a causal role. The present pathomorphological study examines 18 selected infants (<1-year-old) whose deaths were highly suspicious for SBS, exhibiting the classical SBS triad of acute subdural hemorrhage (SDH), retinal bleeding, and encephalopathy.

Near-drowning and clinical laboratory changes.

Opposite to clinical laboratory findings in experimental drowning of animals (erythrocytic lysis, hyperkalemia, and final cardial fibrillation) are the observations in drowned humans (increase of pCO2, hypoxic encephalopathy), which leads to a different pathophysiological interpretation of the drowning process. This process, however, is recently discussed again, therefore an additional study seemed to be recommended. In a retrospective study, 31 cases of near-drowning (23 cases: fresh water; 8 cases: brackish water) clinical laboratory data were analysed.

A phase II study of irinotecan (CPT-11) and carboplatin in patients with limited disease small cell lung cancer (SCLC).

Purpose: The aim of this phase II trial was to evaluate the efficacy and safety of a combination chemotherapy containing irinotecan (CPT-11) and carboplatin as first-line treatment of patients with small cell lung cancer (SCLC).

Patients And Methods: From December 2002 to May 2004 61 patients with limited disease (IASLC classification) were enrolled who were not suitable for concurrent chemo-radiotherapy. Eighteen of the 61 patients (29.

Cerebral hypoxia and ischemia: the forensic point of view: a review.

In cases with suspected brain anoxia/ischemia and hypoxia/hypoxemia a neuropathological investigation should give additional information to elucidate the cause of death and its pathophysiological mechanisms. Primary ischemic brain damage is associated with morphological and biochemical alterations. While acute ischemic neuronal injury reveals axon sparing and selective neuronal lesions due to the release of large quantities of glutamate, late neuronal death is associated with antiapoptotic growth factors, and decreased expression of microtubule-associated proteins and tubulin.

Tissue-specific deletion patterns of the mitochondrial genome with advancing age.

Aging is a multifactorial process and a lot of theories have been put forward to explain the deterioration of organ function with advancing age. The free radical hypothesis developed by Harman is amongst the most prominent today and has been focused on mitochondrial aging in the last decades. Applying a long PCR approach we screened human skeletal muscle, heart, caudate nucleus and cerebellum of 50 individuals for large-scale deletions of mitochondrial DNA (mtDNA).

Microtubule-associated protein 2 (MAP2)--a promising approach to diagnosis of forensic types of hypoxia-ischemia.

The loss of neuronal immunoreactivity of the cytoskeletal microtubule-associated protein 2 (MAP2) is known to be a marker of--at least--transient functional failure of neurons following ischemia. Because there are no specific neuropathological findings in forensic types of acute hypoxia-ischemia, detection of this relevant cause of death is often complicated and a reliable ischemic biomarker would be of great importance. We therefore investigated the neuronal immunoreactivity of MAP2 in human cases of forensic significance.

Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart.

During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism.

Methodical approach to brain hypoxia/ischemia as a fundamental problem in forensic neuropathology.

A review is given summarizing different methods that have been applied to the specific forensic neuropathological question of brain hypoxia/ischemia. On the microscopic level the authors applied routine stains and immunohistochemistry (MAP2, ALZ 50, GFAP, CD68, beta-APP) for characterization of the functional activity of neurons as well as of different cell types in various brain areas. Moreover, using molecular techniques for evaluation of the mitochondrial 4977-bp deletion in correlation to hypoxia and to age brain tissue and single cell analyses are described.

Mitochondrial mutagenesis in the brain in forensic and pathological research.

Accumulation of alterations to the mitochondrial DNA (mtDNA) would be expected to significantly impair the bioenergetic function of mitochondria in the affected host cells. Many of these changes have been associated with several specific diseases and the process of aging. These mutations may be the result of mitochondrial oxidative stress, which is increased with age of individuals and specific degenerative diseases.

Time course of cortical hemorrhages after closed traumatic brain injury: statistical analysis of posttraumatic histomorphological alterations.

We examined 305 autopsied brains for histomorphological alterations to determine the time course of reactions in cortical hemorrhages following traumatic closed brain injury. Eighteen morphological criteria were considered: red blood cells (RBCs), polymorphonuclear leukocytes (PMNs), macrophages (Ms), RBC-containing Ms, hemosiderin, hematoidin, lipid-containing Ms, fibroblasts, endothelial cells, collagenous fibres, gemistocytic astrocytes, fibrillary gliosis, hemosiderin-containing astrocytes, neuronal damage, neuronophagy, axonal swelling (beta-amyloid precursor protein: beta-APP), axonal bulbs (van Gieson stain), and mineralisation of neurons. The interval between the time of brain injury and death ranged from 1 min to 58 years.

Fatal versus non-fatal heroin "overdose": blood morphine concentrations with fatal outcome in comparison to those of intoxicated drivers.

The study was performed to distinguish fatal from non-fatal blood concentrations of morphine. For this purpose, blood levels of free morphine and total morphine (free morphine plus morphine conjugates) in 207 cases of heroin-related deaths were compared to those in 27 drivers surviving opiate intoxication. The majority of both survivors and non-survivors were found to show a concomitant use of depressants including alcohol or stimulants.