[Community-associated MRSA and Panton-Valentine leukocidin (PVL): novel trends in epidemiology and forensic implications]. / "Community acquired" MRSA und das Panton-Valentine-Leukocidin (PVL): neue epidemiologische Entwicklungen und ihre forensische Bedeutung.

The propagation of multi-resistant bacteria, especially methicilline-resistant Staphylococcus aureus strains (MRSA), in hospitals and nursing homes is a well-known sanitary and therapeutic problem (Healthcare-associated MRSA, HA-MRSA). For some years, an increasing incidence of MRSA outside the hospital environment (Community-acquired or Community-Associated MRSA, CA-MRSA) has been observed all over the world, which, contrary to the hospital strains, produces the leukocytotoxic toxin PVL and causes purulent inflammations of the skin and necrotizing pneumonia. In previously healthy children and adolescents these pneumonias are fatal in most cases. The authors report a case of fatal necrotizing S. aureus pneumonia in a 16-year-old girl observed in 2001. The suspicion that the infection had been caused by a CA-MRSA strain following an influenza A infection was confirmed by the bacteriological investigation of a heart blood specimen stored for more than 2 years at 4 degrees C. In view of the bad prognosis and the fulminat course of these special pneumonias the attending physician could not be accused of having caused the death of the girl by omitting the indicated antibiotic treatment. This case of pneumonia caused by CA-MRSA was one of the first seen in Germany. The epidemiological situation suggests that a higher incidence has to be expected in the future.

[Has the transdermal patch gone up in smoke? A fatal fentanyl intoxication]. / Hatte sich das Pflaster in Rauch aufgelöst?-- Eine tödliche Fentanylintoxikation.

Recently, there has been an increase in fentanyl-related overdoses following administration of transdermal patches by the buccal, oral or intravenous route or via inhalation. A fatal intoxication is reported with clear evidence from toxicological analysis. However, the administration route and the fate of the patch remained elusive at the end of the investigations. Alcohol was present in the blood in small quantity (0.024%), whereas no other drug could be detected by basic strategies. Autopsy and microscopic examination failed to find sufficient evidence for a diagnosis. Fentanyl and norfentanyl were determined from body fluids and tissues by LC/MS/MS following liquid/liquid extraction. Both analytes were detectable in all specimens under investigation except muscle tissue where norfentanyl was absent. While the fentanyl concentration in the blood was considered potentially life-threatening on the basis of data obtained from living persons and fentanyl-related deaths, it was difficult to assess the other values because no comparative data were available. The history and circumstances of the case together with the toxicological findings suggest an intravenous or inhalative application of the patch. The latter assumption is supported by the fact that the body was found holding a cigarillo butt in his right hand. The case underlines the necessity to study fentanyl-related deaths more closely to allow a better interpretation of potential intoxications.

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. Gross autopsy and microscopic findings of these infants were compared with those of 19 victims of sudden infant death syndrome (SIDS; control group 1) and of 14 infants who died of disease or injuries/violence not involving the head, neck or eyes (control group 2). Symptoms of mechanical impact to the head were evident in seven of the SBS infants, but in none of the control infants. DAI was not detected in either the SBS or control cases. Localized axonal injury (AI) was regularly present in the brains of the SBS infants surviving longer than 1.5-3.0 h, but only occasionally in the craniocervical junction and within the nerve roots of the upper cervical cord; it was never present in the medulla. Epidural hemorrhage of the cervical cord was seen in four of the ten examined SBS cases, but in none of the control cases. Based on the absence of DAI in the brain and of signs of generalized cervical cord or nerve root injuries, we conclude that the cause of death in the SBS victims was a global cerebral ischemia secondary to SDH, focal vasospasm, trauma-induced transitory respiratory and/or circulatory failure.

Long-term administration of 3-deazaadenosine does not alter progression of advanced atherosclerotic lesions in apolipoprotein E-deficient mice.

Inflammatory mechanisms are involved in initiation and progression of atherosclerotic lesions. Previous studies demonstrated antiinflammatory and consecutive antiatherosclerotic effects of the adenosine analogue 3-Deazaadenosine (c(3) Ado) on early lesion development. The present study evaluated the effect of long-term administration of c(3) Ado in a mouse model of advanced atherosclerosis. Apolipoprotein E-deficient mice (age, 35 weeks; n = 31) with already established advanced atherosclerotic lesions were fed either a diet supplemented with c Ado or a regular chow diet for 21 weeks. Treatment resulted in a significant reduction of serum homocysteine levels. Lesion size and lesion morphology, such as frequency of intraplaque hemorrhage, size of necrotic cores, thickness of fibrous caps, and macrophage content within the plaque, were not different between the groups. Lesion calcification, expression of alpha-actin, and intercellular adhesion molecule-1, but not vascular cell adhesion molecule-1, were inhibited by treatment with c(3) Ado. We could not detect any effect on serum concentrations of interleukin-10 (IL-10) and interleukin-1beta (IL-1beta) or on soluble adhesion molecules intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Electromobility shift assays of protein extracts isolated from aortas did not demonstrate different binding activities of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) after treatment with c Ado. Long-term treatment with the adenosine analogue 3-Deazaadenosine did not show significant effects on progression and stability of advanced atherosclerotic lesions in older apolipoprotein E-deficient mice. A potential antiatherosclerotic effect of c(3)Ado (eg, mediated through inhibition of adhesion molecules) might therefore be limited to prevention of early lesion formation and does not seem to play a relevant role in modifying advanced atherosclerotic disease.

[Fulminant liver failure in a patient on carbamazepine and levetiracetam treatment associated with status epilepticus]. / Fulminantes Leberversagen unter Therapie mit Carbamazepin und Levetiracetam nach einer Anfallserie.

A 22-year-old female with a history of developmental delay and seizures successfully treated with carbamazepine and levetiracetam developed fulminant hepatic failure and subsequently died. She had been admitted to the hospital following secondary generalized seizures of 35 min duration. A circulatory shock as well as intoxication was taken into consideration during the clinical course. Autopsy failed to reveal a macroscopically discernible cause of death. Significant findings on microscopic examination included acute tubular necrosis in the kidneys, pre-existing marked accumulation of neutral lipid within the hepatocytes as well as hyperacute liver damage with evidence of almost complete hepatocyte necrosis. Carbamazepine and levetiracetam were simultaneously determined from blood and tissues such as liver, lungs, muscle and kidneys by LC-MS/MS following addition of lamotrigine as an internal standard and liquid-liquid extraction. Validation data are given for levetiracetam. Both carbamazepine and levetiracetam were present in blood at concentrations within or below the therapeutic range, respectively. Moreover, tissue concentrations suggested long-term administration of anticonvulsant drugs, which is in accordance with the medical history. After excessive drug concentrations could be ruled out, the metabolic consequences of a prolonged carbamazepine therapy to cause severe hepatic injury in the present case are discussed. A mechanism of injury to the hepatocytes may be membrane damage by either an increased production of free radicals and/or a decreased free radical scavenging capacity. Following ischemia with reperfusion and during hyperthermia, large amounts of free radicals are formed. Induction of the mixed oxidase activity during longterm administration of carbamazepine may also increase production of free radicals, leaving the hepatic cell more vulnerable to oxidative injury.

Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning.

An ingestion of an unknown quantity of mirtazapine in a suicide attempt leading to death is described. Sertraline and amitriptyline have been co-ingested. Because mirtazapine is reported to be relatively safe in overdose, body fluids and tissues were investigated for both mirtazapine and desmethylmirtazapine by high-pressure liquid chromatography/tandem mass spectrometry following liquid-liquid extraction. The limit of detection was sufficiently low to also apply the assay in pharmacokinetic studies. The levels of amitriptyline and nortriptyline were very low (38 and 19 ng/mL femoral venous blood) and the amount of sertraline in blood taken from the femoral vein (880 ng/mL) was considerably lower than those seen in overdosage. Accumulation of mirtazapine and N-desmethylmirtazapine was evident in fluids and tissues involved in enterohepatic circulation and excretion. The concentration determined in a brain sample suggests a contribution of the metabolite to the drug's pharmacodynamic activity. Based on literature data, significant adverse or synergistic effects among the drugs detected as well as adverse reactions such as a serotonin reaction appeared less probable. Mirtazapine exhibits alpha(1)-antagonistic properties on the cardiac-vascular system and may cause hyponatraemia. In the face of the cardiac findings at autopsy and the lack of an apparent cause of death, these effects of mirtazapine may have initiated a process leading to death.

[Causality of an accident in subsequent fatal pulmonary embolism a few hours after trauma]. / Zur Frage der Unfallkausalität einer wenige Stunden nach dem Trauma aufgetretenen letalen Lungenthrombembolie.

An 87-year-old woman, who was largely immobilized in a wheelchair, suffered rib fractures and an unstable fracture of the pelvic ring in a fall. Approximately 2 1/2 hours later she developed marked clinical symptoms of pulmonary thromboembolism and died 5 hours after the accident. The question to be discussed with regard to the causality was the unusually short interval of only 2 1/2 to 5 hours between the accident and the clinical signs of embolism leading to her death. Current literature gives only rough outlines stating that thromboembolism can occur as early as the first day after the trauma. An alternative theory explaining the pulmonary thromboembolism may be the breaking off of a pre-existing thrombus due to manipulation during transport or diagnostic measures in connection with the unstable fracture of the pelvic ring.

[Traumatic heart rupture or infarct?]. / Traumatische Herzruptur oder Infarkt?

A 70-year-old motorist driving on the wrong side of the road caused a car-to-car head-on collision and died some minutes later. The autopsy revealed a lethal rupture of the right heart ventricle. The insurance company argued that driving on the wrong side was an act of gross negligence so that the damage was not covered by the full comprehensive insurance. Surprisingly, the microscopic examination of the myocardium performed by a clinical pathologist brought to light a severe myofibrillar degeneration (MFD) which was interpreted as diagnostic of acute myocardial infarction. It was supposed that this could have caused an incapacity of the driver to control his car, which in turn would commit the insurance to payment. A critical re-evaluation of the heart tissue material, however, revealed the pattern of trauma-induced hypercontraction banding of the myocardium along the cleft edges but no findings suggestive of myocardial infarction. Thus, the accident was not the result of a cardiac attack. But there was a severe preexisting pathology including cardiac hypertrophy, scarring of the myocardium, siderophages of the lungs, and an infarction of the pons, so that a cerebral dysfunction was the most plausible explanation for the accident. Thus, gross negligence had to be denied, and the insurance company was obliged to pay. This observation points to the existence of two different variants of MFD: Clinical pathologists are familiar with "tyical" MFD occurring in reperfusion after ischemia, in catecholamine toxicity, and around infarct necroses. But hypercontraction banding, regularly found along penetrating heart lesions and well known to forensic pathologists, is uncommon in clinical pathology.

CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury.

The immune response in the central nervous system (CNS) is under tight control of regulatory mechanisms, resulting in the establishment of immune privilege. CNS injury induces an acute inflammatory reaction, composed mainly of invading leukocytes and activated microglial cells/macrophages. The generation of this robust immune response requires binding of receptors such as CD14, a pattern recognition receptor of the immune system. CD14, a surface molecule of monocytic cells, is up-regulated after monocyte stimulation and is involved in cellular activation. To examine CD14 expression in human brain lesions we investigated sections of brains obtained at autopsy from 25 cases following closed traumatic brain injury (TBI) and 5 control brains by immunohistochemistry. Detection of CD14 in controls demonstrated constitutive expression by perivascular cells, but not in parenchymal microglial cells, equivalent to known expression pattern of ED2 in rats. Following TBI, numbers of CD14(+) cells in perivascular spaces and in the brain parenchyma increased in parallel within 1-2 days, both at the lesion and in adjacent perilesional areas. The number of CD14(+) cells in perivascular spaces and in the brain parenchyma reached maximum levels within 4-8 days and remained elevated until weeks after trauma. In contrast to activated parenchymal microglia/macrophages, resting parenchymal microglial cells lacked CD14. Thus, early CD14 expression constitutes an essential part of the acute inflammatory CNS response following trauma.