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At least 433 records · Page 24Linked to original sources
PubMed2006

The pathophysiology of cholesteatoma.

The pathogenesis of middle ear cholesteatoma continues to be highly debated. In recent years, there has been a substantial improvement in the understanding of the pathophysiology of this disease. This chapter provides a summary of the history and evolution of cholesteatoma and a review of the recent literature that pertains to the pathophysiology of congenital and acquired cholesteatoma. An emphasis is placed on the mechanism of osteolysis and the factors predictive of aggressiveness and recidivism.

Cholesteatoma, Middle Ear↗
PubMed2005

"Thermoregulation-dependent component" in pathophysiology of motor disorders in Parkinson's disease?

Parkinson's disease (PD) is a neurodegenerative disorder characterised by motor symptoms (resting tremor, brady- or akinesia and muscle rigidity), and also by postural problems gait disorder and fatigue as well as behavioural and autonomic symptoms, including thermoregulatory impairment. These symptoms are strikingly similar with some motor phenomena, evoked by the whole body cooling, though the primary cause of PD and cold-induced symptoms are apparently different. The review is focused on the hypothesis that thermoregulatory mechanisms are involved in pathophysiology of motor disorders in PD. The comparative analysis provides some examples of analogy between PD and the state of cooling in respect with tremor, muscle hypertonus, postural reactions and impairment of gross and fine muscle performance. This analogy cannot be considered as specific, because in some normal conditions the motor system utilises identical strategy to compensate for motor deterioration, e.g. at fatigue and ageing. However, such motor phenomena, as neuroleptic malignant syndrome and paired discharges of motor units indicate that the "thermoregulation-dependent component" exists in the pathophysiology of PD. Data on the influence of the whole body cooling and heating on muscle performance, rigidity and tremor in PD patients also provide evidence for the involvement of thermoregulatory mechanisms in PD.

Journal Article↗
PubMed2005

Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins.

Preeclampsia (PE) is a multisystem disorder that remains a major cause of maternal and foetal morbidity and death. To date, no treatment has been found that prevents the development of the disease. Endothelial dysfunction is considered to underlie its clinical manifestations, such as maternal hypertension, proteinuria, and edema; however, the precise biochemical pathways involved remain unclear. A current hypothesis invokes the occurrence of oxidative stress as pathogenically important, as suggested by the fact that in PE, the placental and circulating levels of lipid peroxidation products (F2-isoprostanes and malondialdehyde [MDA]) are increased and endothelial cells are activated. A potential mechanism for endothelial dysfunction may occur via nuclear transcription factor kappa B (NF-kappaB) activation by oxidative stress. Alternatively, the idea that the antiangiogenic placental soluble fms-like tyrosine kinase 1 factor (sFlt1) is involved in the pathogenesis of this disease is just emerging; however, other pathophysiological events seem to precede its increased production. This review is focused on evidence providing a pathophysiological basis for the beneficial effect of early antioxidant therapy in the prevention of PE, mainly supported by the biological effects of vitamins C and E.

Animals↗
PubMed2005

Interfering with the brain: use of RNA interference for understanding the pathophysiology of psychiatric and neurological disorders.

Psychiatric and neurological disorders are among the most complex, poorly understood, and debilitating diseases in medicine. The burgeoning advances in functional genomic technologies have led to the identification of a vast number of novel genes that are potentially implicated in the pathophysiology of such disorders. However, many of these candidate genes have not yet been functionalized and require validation in vivo. Traditionally, abrogating gene function is one of the primary means of examining the physiological significance of a given gene product. Several methods have been developed for gene ablation or knockdown, however, with limited levels of success. The recent discovery of RNA interference (RNAi), as a highly efficient method for gene knockdown, has been one of the major breakthroughs in molecular medicine. In vivo application of RNAi is further demonstrating the promise of this technology. Recent efforts have focused on applying RNAi-based knockdown to understand the genes implicated in neuropsychiatric disorders. However, the greatest challenge with this approach is translating the success of RNAi from mammalian cell cultures to the brain in animal models of disease and, subsequently, in patients. In this review, we describe the various methods that are being developed to deliver RNAi into the brain for down-regulating gene expression and subsequent phenotyping of genes in vivo. We illustrate the utility of various approaches with a few successful examples and also discuss the potential benefits and pitfalls associated with the use of each delivery approach. Appropriate tailoring of tools that deliver RNAi in the brain may not only aid our understanding of the complex pathophysiology of neuropsychiatric disorders, but may also serve as a valuable therapy for disorders, where there is an immense unmet medical need.

Animals↗
PubMed2006

From pathophysiology to targeted therapy for atherothrombosis: a role for the combination of statin and aspirin in secondary prevention.

Atherothrombosis results from direct interaction between the atherosclerotic plaque and arterial thrombosis, and underlies most forms of cardiovascular disease (CVD). The pathophysiology of atherosclerosis is now recognised to involve endothelial dysfunction and dyslipidemia with cholesterol accumulation, as well as critical immuno-inflammatory and apoptotic dimensions. Erosion or rupture of a vulnerable, lipid-rich, inflammatory atherosclerotic plaque triggers the formation of a platelet-rich thrombus that may partially or completely occlude the artery, with resultant clinical scenarios including stable and unstable angina, acute myocardial infarction (MI) and ischaemic stroke. Insight into the pathophysiology of atherothrombosis indicates that an integrated risk factor approach, focusing particularly on management of dyslipidaemia (with a statin) and thrombosis (with aspirin), may constitute an optimal therapeutic approach. Both agents have established roles in secondary prevention. Statin action on atherogenic lipoproteins mediates plaque stabilisation, modification of plaque morphology and attenuation of inflammation, and may lead to plaque regression, while aspirin reduces platelet activation and aggregation, decreases release of inflammatory cytokines at sites of vascular injury and attenuates vasoconstriction. Given these complementary modes of action, this combination would be a logical choice for reducing atherothrombotic risk in patients with CVD. Meta-analysis of 5 major clinical studies has demonstrated that the combination of pravastatin plus aspirin was significantly more effective than either agent alone in reducing the relative risk of key cardiovascular endpoints including MI and ischaemic stroke. This combination may therefore represent an important, cost-efficient therapeutic approach to reduction of cardiovascular risk and prevention of recurrent events in stable CVD.

Animals↗
PubMedDate not supplied

Pathophysiology of histological changes in early pregnancy loss.

An early pregnancy loss (EPL) or first-trimester miscarriage is the most common complication of human reproduction, with an incidence ranging between 50 and 70% of all conceptions. Two-thirds of EPL cases present with a thinner and fragmented trophoblastic shell, and reduced cytotrophoblast invasion of the tips of the spiral arteries. This leads to incomplete plugging during early pregnancy, and premature onset of the maternal circulation throughout the placenta. The excessive entry of maternal blood into the intervillous space has a direct mechanical effect on the villous tissue, and an indirect oxidative stress effect that contributes to cellular dysfunction and/or damage. Correlation of in vivo and in vitro data suggests that overwhelming oxidative stress of the placental tissues represents a common pathophysiological mechanism for the different etiologies of EPL. Autosomal trisomies are the most frequent karyotypic abnormalities found in EPL, but the comparison of data from different cytogenetic studies is difficult because of the lack of clinical information in many cases on maternal age, gestational age, time of fetal demise and the cytogenetic methodology employed. The majority of authors did find a weak association between villous morphologic features and chromosomal abnormalities, with the exception of partial mole triploidy. The comparison of ultrasound findings and placental histological data indicates that villous changes following fetal demise in utero could explain the overall low predictive value of placental histology alone in identifying an aneuploidy or another non-chromosomal etiology. By contrast, the histological features of complete and partial hydatidiform molar EPL are so distinctive that most cases of molar EPL are correctly diagnosed by histological examination alone. Overall, histopathology when correlated with in vivo ultrasound/Doppler has provided novel clues to the pathophysiology of EPL. Prospective studies are needed to evaluate the impact of these findings on routine histopathologic examination in first-trimester miscarriages.

Adult↗
PubMed2006

Modulation of phosphoinositide-protein kinase C signal transduction by omega-3 fatty acids: implications for the pathophysiology and treatment of recurrent neuropsychiatric illness.

The phosphoinositide (PI)-protein kinase C (PKC) signal transduction pathway is initiated by pre- and postsynaptic Galphaq-coupled receptors, and regulates several clinically relevant neurochemical events, including neurotransmitter release efficacy, monoamine receptor function and trafficking, monoamine transporter function and trafficking, axonal myelination, and gene expression. Mounting evidence for PI-PKC signaling hyperactivity in the peripheral (platelets) and central (premortem and postmortem brain) tissues of patients with schizophrenia, bipolar disorder, and major depressive disorder, coupled with evidence that PI-PKC signal transduction is down-regulated in rat brain following chronic, but not acute, treatment with antipsychotic, mood-stabilizer, and antidepressant medications, suggest that PI-PKC hyperactivity is central to an underlying pathophysiology. Evidence that membrane omega-3 fatty acids act as endogenous antagonists of the PI-PKC signal transduction pathway, coupled with evidence that omega-3 fatty acid deficiency is observed in peripheral and central tissues of patients with schizophrenia, bipolar disorder, and major depressive disorder, support the hypothesis that omega-3 fatty acid deficiency may contribute to elevated PI-PKC activity in these illnesses. The data reviewed in this paper outline a potential molecular mechanism by which omega-3 fatty acids could contribute to the pathophysiology and treatment of recurrent neuropsychiatric illness.

Animals↗
PubMed2004

Possible role of D-serine in the pathophysiology of Alzheimer's disease.

Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site on the N-methyl-D-aspartate (NMDA) receptor that has been implicated in the pathophysiology of Alzheimer's disease (AD). The purpose of the study was to determine whether serum levels of D- and L-serine in patients with AD are altered as compared with normal controls. Serum levels of D- and L-serine in patients of AD and age- and gender-matched normal controls were determined using a high-performance liquid chromatography (HPLC). Serum levels of D-serine in the patients with AD were slightly (z=-1.77, p=0.078) lower than those of normal controls. In contrast, serum levels of L-serine in the patients were slightly (z=-1.73, p=0.083) higher than those of controls. In addition, the percentage (%) of D-serine in the total (L+D) serine in the patients was significantly (z=-2.36, p=0.018) lower than that of controls. The present study suggests that the reduced activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine may play a role in the pathophysiology of AD.

Aged↗
PubMed2004

The pathophysiology of primary headache.

Headache research has been a productive area, and understanding of primary headache pathophysiology has increased greatly. There are many more questions that need to be answered to gain a better understanding of the primary headache process. For the clinician,there is value in understanding the pathophysiology of primary headache, because this understanding can help improve diagnostic acumen and shape treatment plans to provide patients with more effective treatment.

Analgesics↗
PubMed2005

The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage.

We propose here a conceptual framework for understanding the optic nerve head (ONH) as a biomechanical structure. Basic principles of biomechanical engineering are used to propose a central role for intraocular pressure (IOP)-related stress and strain in the physiology of ONH aging and the pathophysiology of glaucomatous damage. Our paradigm suggests that IOP-related stress and strain (1) are substantial within the load-bearing connective tissues of the ONH even at low levels of IOP and (2) underlie both ONH aging and the two central pathophysiologies of glaucomatous damage--mechanical failure of the connective tissues of the lamina cribrosa, scleral canal wall, and peripapillary sclera, and axonal compromise within the lamina cribrosa by a variety of mechanisms. Modeling the ONH as a biomechanical structure generates a group of testable hypotheses regarding the central mechanisms of glaucomatous damage and provides a logic for classifying the principal components of the susceptibility of an individual ONH to a given level of IOP.

Animals↗
PubMed2005

Does episodic hypoxia affect upper airway dilator muscle function? Implications for the pathophysiology of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is characterised by repetitive collapse of the upper airway during sleep owing to a sleep-related decrement in upper airway muscle activity with consequent failure of the pharyngeal dilator muscles to oppose the collapsing pressure that is generated by the diaphragm and accessory muscles during inspiration. The causes of upper airway obstruction during sleep are multi-factorial but there is evidence implicating intrinsic upper airway muscle function and impaired central regulation of the upper airway muscles in the pathophysiology of OSA. The condition is associated with episodic hypoxia due to recurrent apnoea. However, despite its obvious importance very little is known about the effects of episodic hypoxia on upper airway muscle function. In this review, we examine the evidence that chronic intermittent hypoxia can affect upper airway muscle structure and function and impair CNS control of the pharyngeal dilator muscles. We review the literature and discuss results from our laboratory showing that episodic hypoxia/asphyxia reduces upper airway muscle endurance and selectively impairs pharyngeal dilator EMG responses to physiological stimulation. Our observations lead us to speculate that episodic hypoxia--a consequence of periodic airway occlusion--is responsible for progression of OSA through impairment of the neural control systems that regulate upper airway patency and through altered respiratory muscle contractile function, leading to the establishment of a vicious cycle of further airway obstruction and hypoxic insult that chronically exacerbates and perpetuates the condition. We conclude that chronic intermittent hypoxia/asphyxia contributes to the pathophysiology of sleep-disordered breathing.

Animals↗
PubMed2004

Drowning: a review of epidemiology, pathophysiology, treatment and prevention.

Although often preventable, drowning remains a leading cause of accidental death, especially in children. New definitions classify drowning as the process of experiencing respiratory impairment from submersion or immersion in a liquid. The key pathophysiological feature in drowning is hypoxia. Accurate neurological prognosis cannot be predicted from the initial clinical presentation, laboratory, radiological, or electrophysiological examinations. Prompt and aggressive resuscitation attempts are crucial for optimal survival. This article reviews the epidemiology, pathophysiology, treatment, and prevention of drowning.

Drowning↗
PubMed2006

[Pathophysiology of Behcet's disease].

SUBJECT: Pathophysiology of Behçet's disease (BD) is complex. Recent experimental data shed new light on the mechanisms leading to organ lesions. MAIN ISSUES: Neutrophils and cytotoxic lymphocytes are now recognized as key effector cells in BD. Genetic susceptibility, environmental factors (virus and/or bacterial infections), inflammatory response abnormalities (heat shock proteins, dysregulated NO production) and abnormal immune response play also a major role in BD pathogeny. PERSPECTIVES: Better understanding of the BD pathophysiology will allow the development of new therapies more specific of BD.

Behcet Syndrome↗
PubMed2005

Advances in the pathophysiology of developmental epilepsies.

Pediatric epilepsies display unique characteristics that differ significantly from epilepsy in adults. The immature brain exhibits a decreased seizure threshold and an age-specific response to seizure-induced brain injury. Many idiopathic epilepsy syndromes and symptomatic epilepsies commonly present during childhood. This review highlights recent advances in the pathophysiology of developmental epilepsies. Cortical development involves maturational regulation of multiple cellular and molecular processes, such as neurogenesis, neuronal migration, synaptogenesis, and expression of neurotransmitter receptors and ion channels. These normal developmental changes of the immature brain also contribute to the increased risk for seizures and unique responses to seizure-induced brain injury in pediatric epilepsies. Recent technological advances, especially in genetics and imaging, have yielded exciting discoveries about the pathophysiology of specific pediatric epilepsy syndromes, such as the emergence of channelopathies as the cause of many idiopathic epilepsies and identification of malformations of cortical development as a major source of symptomatic epilepsies in children.

Adolescent↗
PubMedDate not supplied

Central cord injury: pathophysiology, management, and outcomes.

BACKGROUND CONTEXT: Cervical spinal trauma can result in a heterogeneous collection of spinal cord injury syndromes. Acute traumatic central cord syndrome is a common category of which no uniform consensus on the etiology, pathophysiology, and treatment exists. PURPOSE: To evaluate and review potential pathophysiology, current treatment options, and management of central cord injuries. STUDY DESIGN: Comprehensive literature review and clinical experience. METHODS: A systematic review of Medline for articles related to central cord and spinal cord injury was conducted up to and including journal articles published in September 2005. CONCLUSIONS: Central cord injuries is a clinical definition which is composed of a heterogeneous population for which medical management and surgical decompression and stabilization provide improved neurologic recovery.

Central Cord Syndrome↗
PubMed2005

Nongenomic actions of aldosterone: physiological or pathophysiological role?

The actions of aldosterone are usually divided into persistent genomic mediated by the classical mineralocorticoid receptor versus acute nongenomic actions. Rapid, nongenomic effects of aldosterone have been shown in a variety of tissues, although the physiological relevance of these nongenomic actions remains to be established. There is now growing evidence that both the nongenomic and genomic actions of aldosterone, are mediated via the same classical mineralocorticoid receptor, and there is cross talk between the nongenomic and classical actions of steroid hormones. Activation of tissue-specific, second messenger pathways may contribute to integration of nongenomic and classical actions of aldosterone. Further studies are required to determine the physiological or pathophysiological role of these nongenomic actions of aldosterone and whether they might amplify pathophysiological effects of aldosterone.

Aldosterone↗
PubMed2004

Coronary artery disease: new insights into the pathophysiology, prevalence, and early detection of a monster menace.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States and other industrialized countries. In the undeveloped world a similar epidemic is brewing. A new pathophysiologic paradigm has emerged, which assigns the mediators of inflammation a much larger role in the disease process. This paradigm has helped explain the unpredictable nature of many adverse consequences of CAD. The long latent phase of the disease, and often sudden initial presentation, make efforts at early detection extremely important. Considerable work has been devoted to identify, as well as influence, predisposing risk factors for developing arteriosclerosis. Novel markers of inflammation, like C-reactive protein, have been identified and compared to traditional risk factors. In addition, new imaging modalities introduce the possibility of screening for subclinical disease. Electron beam and multidetector computed tomography (CT) scanners, as well as other techniques, are emerging as powerful tools to detect early disease presence and allow intervention to take place before major clinical events occur. Advances in our understanding of the pathophysiology of CAD, and our ability to image the stages of silent disease will go hand in hand to revolutionize our approach to prevention and treatment of this deadly malady.

Aged↗
PubMed2005

Uremic bleeding: pathophysiology and clinical risk factors.

Renal insufficiency appears clinically to be associated with a bleeding tendency. This has been documented in clinical settings including as a complication of medical interventions such as surgery and also in spontaneous bleeding events at gastrointestinal and intracranial sites. The pathophysiology that underlies this tendency appears to involve platelet dysfunction and an imbalance of mediators of normal endothelial function. It is also may be complicated by the co-morbidities in this population, such as vascular disease, hypertension and anemia, and the medical interventions required to treat such co-morbidities. This article reviews the evidence, the pathophysiology and the risk factors for increased bleeding in patients with chronic renal insufficiency.

Hemorrhage↗