RESUMEN
Petechial hemorrhages are of interest to forensic pathologists because of their association with pressure on the neck. This study shows the associations between ethanol, opioids in blood and the risk of petechiae in conjunctivae and eye lids of 865 medico-legally examined victims from intoxication, 112 (12.9 %) with petechiae. Livor mortis on the front, face down body position, higher body weight, and younger age of the victims were independently associated with higher risk of petechiae. These variables were used for adjustment in the logistic regression analyzes. We found associations between ethanol, opioids, and the risk of petechiae when analyzed simultaneously. The association between ethanol and the risk of petechiae differed in opioid negative and positive victims (interaction, p = 0.028). In the opioid negative group, the association was J-formed, victims with low to medium level ethanol having lower risk (OR = 0.77) than those without ethanol or opioids, whereas high ethanol level gave a 4-fold higher risk (OR = 3.97). In the opioid positive group, the J-formed pattern was reversed. Victims with low to medium level ethanol had more than 4 times higher risk (OR = 4.65), whereas high level ethanol gave a slightly elevated risk (OR = 1.34) only compared to no ethanol or opioids. The results suggest that ethanol and opioids have a complex association with the risk of petechiae independent of livor mortis, initial body position, body weight, and age in victims from intoxication. Of practical value for the post-mortem examination is that the pathologist must consider both the ethanol level and the presence of opioids when judging the significance of petechiae in the eye regions.
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Etanol , Púrpura , Analgésicos Opioides , Peso Corporal , Humanos , Cambios Post MortemAsunto(s)
Cicatriz/patología , Muerte Súbita Cardíaca/epidemiología , Infarto del Miocardio/patología , Miocardio/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Distribución por Sexo , Factores Sexuales , Adulto JovenRESUMEN
Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson's disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson's disease (n = 18) and gender and age matched healthy controls (n = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson's disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson's disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson's disease can occur independently of mitochondrial DNA damage and may not have a pathogenic role in the neurodegenerative process.
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Encéfalo/metabolismo , Complejo I de Transporte de Electrón/deficiencia , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Neuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Daño del ADN , ADN Mitocondrial/metabolismo , Complejo I de Transporte de Electrón/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/patología , Enfermedades Mitocondriales/patología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Neuronas/patología , Enfermedad de Parkinson/patología , Estudios Prospectivos , Agregación Patológica de Proteínas/metabolismo , Agregación Patológica de Proteínas/patología , alfa-Sinucleína/metabolismoRESUMEN
The extreme danger associated with entering enclosed spaces loaded with oxygen-depleting organic cargo in ships and tanks is obviously underestimated, both among crew and management. We present a case report to highlight this occupational hazard and to increase the knowledge about the imperative precautions, in order to prevent future accidents. An experienced customs officer was found lifeless at the bottom of the unattended cargo hold on a ship loaded with woodchips. The oxygen content in the cargo atmosphere was below 2%, which is incompatible with life. Forensic autopsy revealed injuries related to the fall, and there were no positive toxicological findings in blood, lung or urine. Management and workers must be taught about the extreme rapidity of developing unconsciousness and asphyxiant death when entering enclosed spaces loaded with oxygen-depleting cargo. Even a single inhalation can result in unconsciousness and death. Dozens of annual deaths and severe injuries can easily be prevented if simple precautions are followed.
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Accidentes de Trabajo , Asfixia/etiología , Espacios Confinados , Oxígeno/análisis , Asfixia/patología , Humanos , Masculino , Persona de Mediana Edad , Navíos , Madera/efectos adversosRESUMEN
Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Evolución Molecular , Mutación , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Cromosómicas no Histona/antagonistas & inhibidores , Proteínas Cromosómicas no Histona/genética , Femenino , Humanos , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genéticaRESUMEN
PURPOSE: PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of PTEN and PTEN pseudogene (PTENP1) gene expression in patients with locally advanced breast cancer given neoadjuvant chemotherapy. METHODS: The association between pretreatment PTEN and PTENP1 gene expression, response to neoadjuvant chemotherapy, and recurrence-free and disease-specific survival was assessed in 364 patients with locally advanced breast cancer given doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel in three phase II prospective studies. Further, protein expression of PTEN or phosphorylated Akt, S6 kinase, and 4EBP1 was assessed in a subgroup of 187 tumors. RESULTS: Neither PTEN nor PTENP1 gene expression level predicted response to any of the chemotherapy regimens tested (n = 317). Among patients without distant metastases (n = 282), a high pretreatment PTEN mRNA level was associated with inferior relapse-free (RFS; p = 0.001) and disease-specific survival (DSS; p = 0.003). Notably, this association was limited to patients harboring TP53 wild-type tumors (RFS; p = 0.003, DSS; p = 0.009). PTEN mRNA correlated significantly with PTENP1 mRNA levels (r s = 0.456, p < 0.0001) and PTEN protein staining (r s = 0.163, p = 0.036). However, no correlation between PTEN, phosphorylated Akt, S6 kinase or 4EBP1 protein staining, and survival was recorded. Similarly, no correlation between PTENP1 gene expression and survival outcome was observed. CONCLUSION: High intratumoral PTEN gene expression was associated with poor prognosis in patients with locally advanced breast cancers harboring wild-type TP53.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Fosfohidrolasa PTEN/genética , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
While estrogens have been shown to modulate EGFR/HER-1 and HER-2/neu expression in experimental systems, the effects of estrogen deprivation on expression levels of the HER-receptors and the neuregulin (NRG)1 ligand in breast cancers remain unknown. Here, we measured EGFR/HER-1-4 and NRG1 mRNA in ER positive tumors from 85 postmenopausal breast cancer patients before and after two weeks (n=64) and three months (n=85) of primary treatment with an aromatase inhibitor (AI). In tumors lacking HER-2/neu amplification, quantitative real-time PCR analyses revealed EGFR/HER-1 and NRG1 to vary significantly between the three time points (before therapy, after 2 weeks and after 3 months on treatment; P≤0.001 for both). Pair-wise comparison revealed a significant increase in EGFR/HER-1 already during the first two weeks of treatment (P=0.049) with a further increase for both EGFR/HER-1 and NRG1 after 3 months on treatment (P≤0.001 and P=0.001 for both comparing values at 3 months to values at baseline and 2 weeks respectively). No difference between tumors responding versus non-responders was recorded. Further, no significant change in any parameter was observed among HER-2/neu amplified tumors. Analyzing components of the HER-2/neu PI3K/Akt downstream pathway, the PIK3CA H1047R mutation was associated with treatment response (P=0.035); however no association between either AKT phosphorylation status or PIK3CA gene mutations and EGFR/HER-1 or NRG1 expression levels were observed. Our results indicate primary AI treatment to modulate expression of HER-family members and the growth factor NRG1 in HER-2/neu non-amplified breast cancers in vivo. Potential implications to long term sensitivity warrants further investigations.
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Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/metabolismo , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Neurregulina-1/metabolismo , Anastrozol , Neoplasias de la Mama/tratamiento farmacológico , Análisis Mutacional de ADN , Esquema de Medicación , Receptor alfa de Estrógeno/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Letrozol , Mutación , Nitrilos/uso terapéutico , ARN Mensajero/metabolismo , Receptor ErbB-2/metabolismo , Resultado del Tratamiento , Triazoles/uso terapéuticoRESUMEN
Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.
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ADN Mitocondrial/genética , Regulación de la Expresión Génica/fisiología , Homeostasis , Enfermedad de Parkinson/patología , Secuencia de Bases , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , Eliminación de Gen , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismoRESUMEN
Petechiae in conjunctivae and in the palpebrae/skin of the eyelids are of particular interest for the forensic pathologist, because of their association with pressure on the neck. They have been described in the eyelids of intoxicated persons both in case reports and in text books of forensic pathology. We studied 590 deaths caused by intoxication, and 75 had petechiae either in the conjunctivae, the eyelids, or in both locations. We examined the influence of drugs and ethanol on the location of the petechial hemorrhages in these deaths. Deaths with ethanol in blood and in urine/vitreous humor more often had petechiae in both locations than those without. This association was statistically significant, independent of body position and livor mortis. No association between the location of petechiae, medicinal drugs, or narcotics was found. These results suggest that ethanol may contribute to the development of petechial hemorrhages in deaths from intoxication.
Asunto(s)
Depresores del Sistema Nervioso Central/envenenamiento , Conjuntiva/irrigación sanguínea , Etanol/envenenamiento , Patologia Forense , Hemorragia/etiología , Conjuntiva/patología , Párpados/irrigación sanguínea , Párpados/patología , Humanos , PúrpuraRESUMEN
INTRODUCTION: When ischemic events ascribable to microembolization occur during open repair of proximal abdominal aortic aneurysms, a likely origin of atheroembolism is not always found. PRESENTATION OF CASE: A 78-year old man with enlargement of the entire aorta underwent open repair for a pararenal abdominal aortic aneurysm using supraceliac aortic clamping for 20min. Then the graft was clamped, the supraceliac clamp was removed, and the distal and right renal anastomoses were also completed. The patient was stable throughout the operation with only transient drop in blood pressure on reperfusion. Postoperatively the patient developed ischemia, attributable to microembolization, in legs, small intestine, gall bladder and kidneys. He underwent fasciotomy, small bowel and gall bladder resections. Intestinal absorptive function did not recover adequately and he died after 4 months. Microscopic examination of hundreds of intestinal, juxtaintestinal mesenteric, and gall bladder arteries showed a few ones containing cholesterol emboli. DISCUSSION: It is unsure whether a few occluded small arteries out of several hundred could have caused the ischemic injury alone. There had been only moderate backbleeding from aortic branches above the proximal anastomosis while it was sutured. Inadvertently, remaining air in the graft, aorta, and aortic branches may have been whipped into the pulsating blood, resulting in air microbubbles, when the aortic clamp was removed. CONCLUSION: Although both atheromatous particles and air microbubbles are well-known causes of iatrogenic microembolization, the importance of air microembolization in open repair of pararenal aortic aneurysms is not known and need to be studied.
RESUMEN
The risk of dying from sharp force injury is difficult to ascertain. To the best of our knowledge, no study has been performed in Norway regarding mortality due to sharp force injury or factors that impact survival. Thus, the objective of the present study was to investigate and assess mortality in subjects with sharp force injury. This retrospective study comprises data on 136 subjects (34 female, 102 male) with suspected severe sharp force injury (self-inflicted or inflicted by others) admitted to Haukeland University Hospital between 2001 and 2010. The majority of subjects were intoxicated, and the injury was most often inflicted by a knife. The incidence of sharp force injury in Western Norway is similar to the incidence in other European countries. Almost half of the subjects with self-inflicted injury died. In cases with injury inflicted by another individual, one in five died. Mortality rates were higher in those with penetrating chest injuries than those with penetrating abdominal injuries and higher in cases with cardiac injury compared to pleural or lung injury. Sharp force injury can be fatal, but the overall mortality rate in this study was 29%. Factors influencing mortality rate were the number of injuries, the topographic regions of the body injured, the anatomical organs/structures inflicted, and emergency measures performed.
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Homicidio/estadística & datos numéricos , Conducta Autodestructiva/epidemiología , Suicidio/estadística & datos numéricos , Heridas Punzantes/epidemiología , Adulto , Distribución por Edad , Nivel de Alcohol en Sangre , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Estudios Retrospectivos , Distribución por Sexo , Trastornos Relacionados con Sustancias/epidemiología , Heridas Punzantes/cirugíaRESUMEN
The sequencing of cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular , Células Clonales , Estudios de Cohortes , Variaciones en el Número de Copia de ADN/genética , Femenino , Genómica , Humanos , Persona de Mediana Edad , Mutación/genéticaRESUMEN
Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance to DNA damaging drugs in breast cancer better than TP53 mutations alone. Further, we hypothesized that redundant pathway(s) may compensate for loss of p53-pathway signaling and that these are inactivated as well in resistant tumour cells. Here, we assessed genetic alterations of the retinoblastoma gene (RB1) and its key regulators: Cyclin D and E as well as their inhibitors p16 and p27. In an exploratory cohort of 69 patients selected from two prospective studies treated with either doxorubicin monotherapy or 5-FU and mitomycin for locally advanced breast cancers, we found defects in the pRB-pathway to be associated with therapy resistance (p-values ranging from 0.001 to 0.094, depending on the cut-off value applied to p27 expression levels). Although statistically weaker, we observed confirmatory associations in a validation cohort from another prospective study (n = 107 patients treated with neoadjuvant epirubicin monotherapy; p-values ranging from 7.0 × 10(-4) to 0.001 in the combined data sets). Importantly, inactivation of the p53-and the pRB-pathways in concert predicted resistance to therapy more strongly than each of the two pathways assessed individually (exploratory cohort: p-values ranging from 3.9 × 10(-6) to 7.5 × 10(-3) depending on cut-off values applied to ATM and p27 mRNA expression levels). Again, similar findings were confirmed in the validation cohort, with p-values ranging from 6.0 × 10(-7) to 6.5 × 10(-5) in the combined data sets. Our findings strongly indicate that concomitant inactivation of the p53- and pRB- pathways predict resistance towards anthracyclines and mitomycin in breast cancer in vivo.
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Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Daño del ADN , Resistencia a Antineoplásicos/genética , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Estudios de Cohortes , Daño del ADN/genética , Análisis Mutacional de ADN , Doxorrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Mitomicina/uso terapéutico , Pronóstico , Proteína de Retinoblastoma/metabolismo , Transducción de Señal/genética , Insuficiencia del TratamientoRESUMEN
Wear debris-induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR-patients revealed numerous wear debris-loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis.
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Aleaciones , Cementos para Huesos , Prótesis de Cadera , Titanio , Adulto , Anciano , Anciano de 80 o más Años , Remoción de Dispositivos , Femenino , Reacción a Cuerpo Extraño/etiología , Reacción a Cuerpo Extraño/patología , Fricción , Articulación de la Cadera/patología , Prótesis de Cadera/efectos adversos , Histiocitos/patología , Humanos , Inflamación , Cápsula Articular/patología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Necrosis , Neutrófilos/patología , Osteólisis/sangre , Osteólisis/etiología , Osteólisis/patología , Polietileno/análisis , Falla de Prótesis , Titanio/sangre , Circonio/análisis , Circonio/sangreRESUMEN
OBJECTIVE: Polymerase gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neurodegeneration and aging. We studied the molecular mechanisms underlying POLG-related neurodegeneration using postmortem tissue from a large number of patients. METHODS: Clinical information was available from all subjects. Formalin-fixed and frozen brain tissue from 15 patients and 23 controls was studied employing a combination of histopathology, immunohistochemistry, and molecular studies of microdissected neurons. RESULTS: The primary consequence of POLG mutation in neurons is mitochondrial DNA depletion. This was already present in infants with little evidence of neuronal loss or mitochondrial dysfunction. With longer disease duration, we found an additional, progressive accumulation of mitochondrial DNA deletions and point mutations accompanied by increasing numbers of complex I-deficient neurons. Progressive neurodegeneration primarily affected the cerebellar systems and dopaminergic cells of the substantia nigra. Superimposed on this chronic process were acute, focal cortical lesions that correlated with epileptogenic foci and that showed massive neuronal loss. INTERPRETATION: POLG mutations appear to compromise neuronal respiration via a combination of early and stable depletion and a progressive somatic mutagenesis of the mitochondrial genome. This leads to 2 distinct but overlapping biological processes: a chronic neurodegeneration reflected clinically by progressive ataxia and cognitive impairment, and an acute focal neuronal necrosis that appears to be related to the presence of epileptic seizures. Our findings offer an explanation of the acute-on-chronic clinical course of this common mitochondrial encephalopathy.
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ADN Polimerasa Dirigida por ADN/efectos adversos , ADN Polimerasa Dirigida por ADN/genética , Degeneración Nerviosa/enzimología , Degeneración Nerviosa/patología , Adolescente , Adulto , Cerebelo/enzimología , Cerebelo/patología , Corteza Cerebral/enzimología , Corteza Cerebral/patología , Niño , ADN Polimerasa gamma , ADN Mitocondrial/genética , Progresión de la Enfermedad , Humanos , Lactante , Persona de Mediana Edad , Encefalomiopatías Mitocondriales/enzimología , Encefalomiopatías Mitocondriales/genética , Encefalomiopatías Mitocondriales/patología , Mutación/genética , Sustancia Negra/enzimología , Sustancia Negra/patología , Adulto JovenRESUMEN
BACKGROUND: Studies of the epidemiology of deaths from violent causes can provide valuable information for the treatment of traumas. We wished to ascertain whether the victims had survivable injuries and were accessible for treatment at the time of discovery of the injury. The purpose was to identify areas of intervention that may help save lives. MATERIAL AND METHOD: An overview of deaths from violent causes in Hordaland County in 2003 and 2004 was retrieved from the Cause of Death Registry, and information from autopsy records, hospital records and police reports was reviewed. In each case, an assessment was made of whether the injuries were survivable. If the patient was alive and could be reached and treated at the time when the incident was reported, he/she was defined as accessible for treatment. RESULTS: Altogether 191 deaths were included. We assessed the injuries as survivable in 26 cases. A total of 18 of these 26 patients were also assessed as accessible for treatment. All of these 18 patients died from falls or traffic accidents. 11 of the 18 patients were in the age group 75 years or older; this age group accounted for 41 cases (21.5%) of the total material. The records showed that in 12 of these 18 cases, it had been decided following an overall assessment not to initiate, or to discontinue, further life-saving treatment. INTERPRETATION: A small number of patients were deemed to have sustained survivable injuries while also being accessible for treatment. The results indicate that primarily efforts to prevent injuries will help reduce the number of deaths from violent causes.
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Accidentes/mortalidad , Violencia/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Adulto , Anciano , Asfixia/epidemiología , Causas de Muerte , Ahogamiento/epidemiología , Servicios Médicos de Urgencia/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/epidemiología , Análisis de Supervivencia , Heridas por Arma de Fuego/epidemiología , Heridas no Penetrantes/epidemiologíaRESUMEN
The role of mitochondria in the pathogenesis of neurodegeneration is an area of intense study. It is known that defects in proteins involved in mitochondrial quality control can cause Parkinson's disease, and there is increasing evidence linking mitochondrial dysfunction, and particularly mitochondrial DNA abnormalities, to neuronal loss in the substantia nigra. Mutations in the catalytic subunit of polymerase gamma are among the most common causes of mitochondrial disease and owing to its role in mitochondrial DNA homeostasis, polymerase gamma defects are often considered a paradigm for mitochondrial diseases generally. Yet, despite this, parkinsonism is uncommon with polymerase gamma defects. In this study, we investigated structural and functional changes in the substantia nigra of 11 patients with polymerase gamma encephalopathy. We characterized the mitochondrial DNA abnormalities and examined the respiratory chain in neurons of the substantia nigra. We also investigated nigrostriatal integrity and function using a combination of post-mortem and in vivo functional studies with dopamine transporter imaging and positron emission tomography. At the cellular level, dopaminergic nigral neurons of patients with polymerase gamma encephalopathy contained a significantly lower copy number of mitochondrial DNA (depletion) and higher levels of deletions than normal control subjects. A selective and progressive complex I deficiency was seen and this was associated with a severe and progressive loss of the dopaminergic neurons of the pars compacta. Dopamine transporter imaging and positron emission tomography showed that the degree of nigral neuronal loss and nigrostriatal depletion were severe and appeared greater even than that seen in idiopathic Parkinson's disease. Despite this, however, none of our patients showed any signs of parkinsonism. The additional presence of both thalamic and cerebellar dysfunction in our patients suggested that these may play a role in counteracting the effects of basal ganglia dysfunction and prevent the development of clinical parkinsonism.
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Cuerpo Estriado/patología , ADN Polimerasa Dirigida por ADN/genética , Enfermedades Mitocondriales/genética , Degeneración Nerviosa/genética , Trastornos Parkinsonianos/genética , Sustancia Negra/patología , Adolescente , Adulto , Cuerpo Estriado/metabolismo , ADN Polimerasa gamma , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Mutación , Degeneración Nerviosa/patología , Neuronas/metabolismo , Neuronas/patología , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Sustancia Negra/metabolismoRESUMEN
BACKGROUND: Many studies indicate rural location as a separate risk for dying from injuries. For decades, Finnmark, the northernmost and most rural county in Norway, has topped the injury mortality statistics in Norway. The present study is an exploration of the impact of rurality, using a point-by-point comparison to another Norwegian county. METHODS: We identified all fatalities following injury occurring in Finnmark between 2000 and 2004, and in Hordaland, a mixed rural/urban county in western Norway between 2003 and 2004 using data from the Norwegian Cause of Death Registry. Intoxications and low-energy trauma in patients aged over 64 years were excluded. To assess the effect of a rural locale, Hordaland was divided into a rural and an urban group for comparison. In addition, data from Statistics Norway were analysed. RESULTS: Finnmark reported 207 deaths and Hordaland 217 deaths. Finnmark had an injury death rate of 33.1 per 100,000 inhabitants. Urban Hordaland had 18.8 deaths per 100,000 and rural Hordaland 23.7 deaths per 100,000. In Finnmark, more victims were male and were younger than in the other areas. Finnmark and rural Hordaland both had more fatal traffic accidents than urban Hordaland, but fewer non-fatal traffic accidents. CONCLUSIONS: This study illustrates the disadvantages of the most rural trauma victims and suggests an urban-rural continuum. Rural victims seem to be younger, die mainly at the site of injury, and from road traffic accident injuries. In addition to injury prevention, the extent and possible impact of lay people's first aid response should be explored.
Asunto(s)
Población Rural , Heridas y Lesiones/mortalidad , Adulto , Anciano , Causas de Muerte/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Sistema de Registros , Factores de Tiempo , Heridas y Lesiones/etiologíaRESUMEN
Three classic cases and one exceptional case are reported. The unique case of decapitation took place in a traffic accident, while the others were seen after homicide, vehicle-assisted suicide, and after long-jump hanging. Thorough scene examinations were performed, and photographs from the scene were available in all cases. Through the autopsy of each case, the mechanism for the decapitation in each case was revealed. The severance lines were through the neck and the cervical vertebral column, except for in the motor vehicle accident case, where the base of skull was fractured. This case was also unusual as the mechanism was blunt force. In the homicide case, the mechanism was the use of a knife combined with a saw, while in the two last cases, a ligature made the cut through the neck. The different mechanisms in these decapitations are suggested.
Asunto(s)
Decapitación/etiología , Decapitación/patología , Accidentes de Tránsito , Adulto , Desmembramiento de Cadáver , Femenino , Patologia Forense , Homicidio , Humanos , Masculino , Persona de Mediana Edad , SuicidioRESUMEN
During a 6 month period (July 2010-January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as "Death", is occasionally found in street drugs offered as "ecstasy" or "amphetamine". The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15-50) with 67% males; in non-fatal cases 27 years (20-47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17-3.30), which is in the reported lethal range of 0.6-3.1 mg/L in peripheral blood and 1.2-15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01-0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58-3.30), 2.56 (1.52-3.23) and 0.52 mg/L (0.17-1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal "ecstasy" or "speed" drugs.