Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches.

PubMed

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D'Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

Sundowning in Dementia: Clinical Relevance, Pathophysiological Determinants, and Therapeutic Approaches

PubMed Central

Canevelli, Marco; Valletta, Martina; Trebbastoni, Alessandro; Sarli, Giuseppe; D’Antonio, Fabrizia; Tariciotti, Leonardo; de Lena, Carlo; Bruno, Giuseppe

2016-01-01

Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice. PMID:28083535

Challenging clinical presentations of pernicious anemia.

PubMed

Oo, Thein Hlaing; Rojas-Hernandez, Cristhiam Mauricio

2017-09-01

Pernicious anemia (PA) is an autoimmune disease of multifactorial etiologies characterized by autoimmune chronic atrophic gastritis, cobalamin deficiency (CD) due to defective absorption of dietary cobalamin from the terminal ileum, and by the presence of intrinsic factor and parietal cell antibodies. PA is a very common cause of CD-related anemia worldwide. Despite advances in the understanding molecular biology and pathophysiology of PA, the diagnosis of PA remains challenging in many circumstances for many clinicians because of its diverse clinical manifestations and the limitations of currently available diagnostic tools. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anemia, non-anemic macrocytosis, autoimmune hemolytic anemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleu-kemia, bone marrow failure, bone marrow ring sideroblasts, and neurologic manifestations without anemia or macrocytosis. Herein, we provide an overview of the challenging clinical presentations of PA, diagnostic approach, and management.

Stress fractures: pathophysiology, clinical presentation, imaging features, and treatment options.

PubMed

Matcuk, George R; Mahanty, Scott R; Skalski, Matthew R; Patel, Dakshesh B; White, Eric A; Gottsegen, Christopher J

2016-08-01

Stress fracture, in its most inclusive description, includes both fatigue and insufficiency fracture. Fatigue fractures, sometimes equated with the term "stress fractures," are most common in runners and other athletes and typically occur in the lower extremities. These fractures are the result of abnormal, cyclical loading on normal bone leading to local cortical resorption and fracture. Insufficiency fractures are common in elderly populations, secondary to osteoporosis, and are typically located in and around the pelvis. They are a result of normal or traumatic loading on abnormal bone. Subchondral insufficiency fractures of the hip or knee may cause acute pain that may present in the emergency setting. Medial tibial stress syndrome is a type of stress injury of the tibia related to activity and is a clinical syndrome encompassing a range of injuries from stress edema to frank-displaced fracture. Atypical subtrochanteric femoral fracture associated with long-term bisphosphonate therapy is also a recently discovered entity that needs early recognition to prevent progression to a complete fracture. Imaging recommendations for evaluation of stress fractures include initial plain radiographs followed, if necessary, by magnetic resonance imaging (MRI), which is preferred over computed tomography (CT) and bone scintigraphy. Radiographs are the first-line modality and may reveal linear sclerosis and periosteal reaction prior to the development of a frank fracture. MRI is highly sensitive with findings ranging from periosteal edema to bone marrow and intracortical signal abnormality. Additionally, a brief description of relevant clinical management of stress fractures is included.

A Unified Pathophysiological Construct of Diabetes and its Complications.

PubMed

Schwartz, Stanley S; Epstein, Solomon; Corkey, Barbara E; Grant, Struan F A; Gavin Iii, James R; Aguilar, Richard B; Herman, Mary E

2017-09-01

Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects.

PubMed

Bianchin, Marino Muxfeldt; Londero, Renata Gomes; Lima, José Eduardo; Bigal, Marcelo Eduardo

2010-08-01

The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.

Female Pattern Hair Loss: a clinical and pathophysiological review*

PubMed Central

Ramos, Paulo Müller; Miot, Hélio Amante

2015-01-01

Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss. PMID:26375223

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

PubMed

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-02-08

To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy

PubMed Central

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-01-01

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: “portal” and “gastropathy”; or “portal” and “hypertensive”; or “congestive” and “gastropathy”; or “congestive” and “gastroenteropathy”. The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa

Virally associated arthritis 2008: clinical, epidemiologic, and pathophysiologic considerations

PubMed Central

Vassilopoulos, Dimitrios; Calabrese, Leonard H

2008-01-01

Several viruses have been associated with the development of inflammatory arthritis, including the hepatitis viruses (hepatitis B virus and hepatitis C virus), HIV, the parvovirus B19, the human T-cell lymphotropic virus-I, and the alphaviruses. Here, we review the epidemiology, the pathophysiological mechanisms, the pertinent clinical and laboratory findings as well as the principles of therapy of the most common virus-associated arthritides. We believe that the knowledge of these key diagnostic and therapeutic features of virus-associated arthritides is important for the rheumatologist of the 21st century. PMID:18828883

The non-motor syndrome of primary dystonia: clinical and pathophysiological implications

PubMed Central

Stamelou, Maria; Edwards, Mark J.; Hallett, Mark

2012-01-01

Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications. PMID:21933808

A Glimpse into Uveitis in the Aging Eye: Pathophysiology, Clinical Presentation and Treatment Considerations.

PubMed

Akinsoji, Elizabeth; Goldhardt, Raquel; Galor, Anat

2018-05-01

Uveitis describes a group of inflammatory conditions of the eye that have various underlying causes and clinical presentations. Susceptibilities to uveitis in the elderly may be attributed to age-related risk factors such as immunosenescence, increased immunological inflammatory mediators, and autoimmunity. Overall, anterior uveitis is more common than posterior and panuveitis in the general population and also in the elderly. Some causes of uveitis in the elderly are herpes simplex virus, ocular ischemic syndrome, sarcoidosis, and central nervous system lymphoma, and these will be discussed in detail herein. Eye care professionals need to consider the wide differential for uveitis, obtain the appropriate history, conduct a detailed clinical examination, and tailor management to the clinical presentation and underlying cause of disease. The challenges of polypharmacy and nonadherence in the elderly impact patient outcomes and must be taken into consideration when considering treatment.

Reclassification of clinical sleep disorders using traditional models of syndromic, neuroanatomic, pathophysiological and etiological diagnosis.

PubMed

Spitzer, A Robert

2014-09-01

Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Starobova, Hana; Vetter, Irina

2017-01-01

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280

The Pathophysiology of Insomnia

PubMed Central

Levenson, Jessica C.; Kay, Daniel B.

2015-01-01

Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented. PMID:25846534

Reform in teaching preclinical pathophysiology.

PubMed

Li, Yong-Yu; Li, Kun; Yao, Hong; Xu, Xiao-Juan; Cai, Qiao-Lin

2015-12-01

Pathophysiology is a scientific discipline that studies the onset and progression of pathological conditions and diseases, and pathophysiology is one of the core courses in most preclinical medical curricula. In China, most medical schools house a Department of Pathophysiology, in contrast to medical schools in many developed countries. The staff in Chinese Departments of Pathophysiology generally consists of full-time instructors or lecturers who teach medical students. These lecturers are sometimes lacking in clinic knowledge and experiences. To overcome this, in recent years, we have been trying to bring new trends in teaching pathophysiology into our curriculum. Our purpose in writing this article was to share our experiences with our colleagues and peers worldwide in the hope that the insights we have gained in pathophysiology teaching will be of some value to educators who advocate teaching reform in medical schools. Copyright © 2015 The American Physiological Society.

Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology.

PubMed

Stockler, Sylvia; Schutz, Peter W; Salomons, Gajja S

2007-01-01

Cerebral creatine deficiency syndromes (CCDSs) are a group of inborn errors of creatine metabolism comprising two autosomal recessive disorders that affect the biosynthesis of creatine--i.e. arginine:glycine amidinotransferase deficiency (AGAT; MIM 602360) and guanidinoacetate methyltransferase deficiency (GAMT; MIM 601240)--and an X-linked defect that affects the creatine transporter, SLC6A8 deficiency (SLC6A8; MIM 300036). The biochemical hallmarks of these disorders include cerebral creatine deficiency as detected in vivo by 1H magnetic resonance spectroscopy (MRS) of the brain, and specific disturbances in metabolites of creatine metabolism in body fluids. In urine and plasma, abnormal guanidinoacetic acid (GAA) levels are found in AGAT deficiency (reduced GAA) and in GAMT deficiency (increased GAA). In urine of males with SLC6A8 deficiency, an increased creatine/creatinine ratio is detected. The common clinical presentation in CCDS includes mental retardation, expressive speech and language delay, autistic like behaviour and epilepsy. Treatment of the creatine biosynthesis defects has yielded clinical improvement, while for creatine transporter deficiency, successful treatment strategies still need to be discovered. CCDSs may be responsible for a considerable fraction of children and adults affected with mental retardation of unknown etiology. Thus, screening for this group of disorders should be included in the differential diagnosis of this population. In this review, also the importance of CCDSs for the unravelling of the (patho)physiology of cerebral creatine metabolism is discussed.

Tics and Tourette: a clinical, pathophysiological and etiological review.

PubMed

Dale, Russell C

2017-12-01

Describe developments in the etiological understanding of Tourette syndrome. Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.

Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future.

PubMed

Holl, Dana C; Volovici, Victor; Dirven, Clemens M F; Peul, Wilco C; van Kooten, Fop; Jellema, Korné; van der Gaag, Niels A; Miah, Ishita P; Kho, Kuan H; den Hertog, Heleen M; Lingsma, Hester F; Dammers, Ruben

2018-05-14

Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient. We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH. After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH. Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The pathophysiology of migraine: implications for clinical management.

PubMed

Charles, Andrew

2018-02-01

The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Morel-Lavallee Lesions-Review of Pathophysiology, Clinical Findings, Imaging Findings and Management.

PubMed

Diviti, Sreelatha; Gupta, Nishant; Hooda, Kusum; Sharma, Komal; Lo, Lawrence

2017-04-01

Morel-Lavallee lesion is a post-traumatic soft tissue degloving injury. This is commonly associated with sports injury caused by a shearing force resulting in separation of the hypodermis from the deeper fascia. Most common at the greater trochanter, these injuries also occur at flank, buttock, lumbar spine, scapula and the knee. Separation of the tissue planes result in a complex serosanguinous fluid collection with areas of fat within it. The imaging appearance is variable and non specific, potentially mimicking simple soft tissue haematoma, superficial bursitis or necrotic soft tissue neoplasms. If not treated in the acute or early sub acute settings, these collections are at risk for superinfection, overlying tissue necrosis and continued expansion. In this review article, we discuss the clinical presentation, pathophysiology, imaging features and differential diagnostic considerations of Morel-Lavallee lesions. Role of imaging in guiding prompt and appropriate treatment has also been discussed.

Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management.

PubMed

Liakakos, T; Thomakos, N; Fine, P M; Dervenis, C; Young, R L

2001-01-01

To summarize the most common etiologic factors and describe the pathophysiology in the formation of peritoneal adhesions, to outline their clinical significance and consequences, and to evaluate the pharmacologic, mechanical, and surgical adjuvant strategies to minimize peritoneal adhesion formation. We performed an extensive MEDLINE search of the internationally published English literature of all medical and epidemiological journal articles, textbooks, scientific reports, and scientific journals from 1940 to 1997. We also reviewed reference lists in all the articles retrieved in the search as well as those of major texts regarding intraperitoneal postsurgical adhesion formation. All sources identified were reviewed with particular attention to risk factors, pathophysiology, clinical manifestations, various methods, and innovative techniques for effectively and safely reducing the formation of postsurgical adhesions. The formation of postoperative peritoneal adhesions is an important complication following gynecological and general abdominal surgery, leading to clinical and significant economical consequences. Adhesion occur in more than 90% of the patients following major abdominal surgery and in 55-100% of the women undergoing pelvic surgery. Small-bowel obstruction, infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery are the most common consequences of peritoneal adhesions. Despite elaborate efforts to develop effective strategies to reduce or prevent adhesions, their formation remains a frequent occurrence after abdominal surgery. Until additional information and findings from future clinical investigations exist, only a meticulous surgical technique can be advocated in order to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. Copyright 2001 S. Karger AG, Basel

Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment*

PubMed Central

Clarindo, Marcos Vinícius; Possebon, Adriana Tomazzoni; Soligo, Emylle Marlene; Uyeda, Hirofumi; Ruaro, Roseli Terezinha; Empinotti, Julio Cesar

2014-01-01

Researches on DH have shown that it is not just a bullous skin disease, but a cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to gluten is the starting point of an inflammatory cascade capable of forming autoantibodies that are brought to the skin, where they are deposited, culminating in the formation of skin lesions. These lesions are vesico-bullous, pruritic, and localized especially on elbows, knees and buttocks, although atypical presentations can occur. Immunofluorescence of perilesional area is considered the gold standard for diagnosis, but serological tests help in cases where it is negative. Patients who follow glutenfree diets have better control of symptoms on the skin and intestine, as well as lower risks of progression to lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring of possible side effects, some potentially lethal. PMID:25387490

[Autoantibody-associated autoimmune encephalitis and cerebellitis : Clinical presentation, diagnostic work-up and treatment].

PubMed

Lewerenz, J; Jarius, S; Wildemann, B; Wandinger, K-P; Leypoldt, F

2016-12-01

There is no other field of neurology where clinically relevant serological biomarkers have witnessed a surge in importance over the past decade resembling that in autoimmune encephalitis and cerebellitis. A multitude of newly discovered neuronal autoantibodies facilitate early diagnosis, estimation of prognosis, and therapeutic decision-making. However, this has led to growing uncertainty with regard to meaningful patient selection, the appropriate extent of testing, and management of seronegative cases. This review summarizes the essential aspects of the clinical presentation, diagnostic work-up, pathophysiology, and treatment of autoimmune encephalitis and cerebellitis.

Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments

PubMed Central

George, Paul M.; Steinberg, Gary K.

2016-01-01

Stroke remains a leading cause of death and disability in the world. Over the past few decades our understanding of the pathophysiology of stroke has increased, but greater insight is required to advance the field of stroke recovery. Clinical treatments have improved in the acute time window, but long-term therapeutics remain limited. Complex neural circuits damaged by ischemia make restoration of function after stroke difficult. New therapeutic approaches, including cell transplantation or stimulation, focus on reestablishing these circuits through multiple mechanisms to improve circuit plasticity and remodeling. Other research targets intact networks to compensate for damaged regions. This review highlights several important mechanisms of stroke injury and describes emerging therapies aimed at improving clinical outcomes. PMID:26182415

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

Hemorrhoids: from basic pathophysiology to clinical management.

PubMed

Lohsiriwat, Varut

2012-05-07

This review discusses the pathophysiology, epidemiology, risk factors, classification, clinical evaluation, and current non-operative and operative treatment of hemorrhoids. Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions. The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids. It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. In most instances, hemorrhoids are treated conservatively, using many methods such as lifestyle modification, fiber supplement, suppository-delivered anti-inflammatory drugs, and administration of venotonic drugs. Non-operative approaches include sclerotherapy and, preferably, rubber band ligation. An operation is indicated when non-operative approaches have failed or complications have occurred. Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy, but postoperative pain is invariable. Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence. The applications and outcomes of each treatment are thoroughly discussed.

95th Anniversary of Pathophysiology in Croatia.

PubMed

Kovač, Zdenko

2017-12-01

lasting legacy on generations to come. Professor Stjepan Gamulin made molecular medicine the working reality at Rebro. Both in clinical research, and in health system as diagnostic service and tool for all centers in Croatia, molecular measurement in tissue samples came into usage in daily physicians reasoning and therapy prescriptions. Macromolecular aspects of disease have come of age and became clinimetric signs of patients' condition. Professor Gamulin with his group and associated authors wrote the textbook of pathophysiology, which in upcoming 30 years had 7 editions, has become the bestseller in medicine. The textbook was translated and published in English and Albanian. In the most recent book professor Gamulin turned the focus of medical community to clinical epidemiology and a need for retrospective insights into medical efficiency. Medical performance can be improved with the improvement of understanding of underlying etiopathogenetic relations as the foundation of therapy-is the main message. Following the academic legacy and spirit of three charismatic authorities we established two methods of teaching/learning in medicine. The two methods opened up a new avenue, so important for the era of postgenomic plethora of information and demands of precision/personalized medicine. Methodology has been introduced timely. It is student-friendly and usable for advanced types of education. Problem based algorhytmic matrices stimulate analysis and resynthesis of etiopathogenetic pathways. Graphic presentation of the solution integrates horizontal, vertical and longitudinal aspects of the problem. The companion textbook in the form of problem solver has been published in 3 editions, and contains 128 study solved cases. It was published in English, as well. Out of algorhythmic analysis the etiopathogenetic clusters (EPCs) are composed of etiopathogenetic pathway analysis. EPCs are natural units of disease development, the crossing points of processes. They are integrative

The pathophysiology of Peyronie's disease.

PubMed

El-Sakka, Ahmed I; Salabas, Emre; Dinçer, Murat; Kadioglu, Ates

2013-09-01

To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease.

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

PubMed Central

Anandhakrishnan, Ananthi; Korbonits, Márta

2016-01-01

Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose (3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed anti-obesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and long-term weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need. PMID:28031776

Urinary proteomics in renal pathophysiology: Impact of proteinuria.

PubMed

Sancho-Martínez, Sandra M; Prieto-García, Laura; Blanco-Gozalo, Víctor; Fontecha-Barriuso, Miguel; López-Novoa, José M; López-Hernández, Francisco J

2015-06-01

Urinary differential proteomics is used to study renal pathophysiological mechanisms, find novel markers of biological processes and renal diseases, and stratify patients according to proteomic profiles. The proteomic procedure determines the pathophysiological meaning and clinical relevance of results. Urine samples for differential proteomic studies are usually normalized by protein content, regardless of its pathophysiological characteristics. In the field of nephrology, this approach translates into the comparison of a different fraction of the total daily urine output between proteinuric and nonproteinuric samples. Accordingly, alterations in the level of specific proteins found by this method reflect the relative presence of individual proteins in the urine; but they do not necessarily show alterations in their daily excretion, which is a key parameter for the understanding of the pathophysiological meaning of urinary components. For renal pathophysiology studies and clinical biomarker identification or determination, an alternative proteomic concept providing complementary information is based on sample normalization by daily urine output, which directly informs on changes in the daily excretion of individual proteins. This is clinically important because daily excretion (rather than absolute or relative concentration) is the only self-normalized way to evaluate the real meaning of urinary parameters, which is also independent of urine concentration. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concussion: the history of clinical and pathophysiological concepts and misconceptions.

PubMed

McCrory, P R; Berkovic, S F

2001-12-26

Concussion is a well-recognized clinical entity; however, its pathophysiologic basis remains a mystery. One unresolved issue is whether concussion is associated with lesser degrees of diffuse structural change seen in severe traumatic brain injury, or is the mechanism entirely caused by reversible functional changes. This issue is clouded not only by the lack of critical data, but also by confusion in terminology, even in contemporary literature. This confusion began in ancient times when no distinction was made between the transient effects of concussion and severe traumatic brain injury. The first clear separate recognition of concussion was made by the Persian physician, Rhazes, in the 10th century. Lanfrancus subsequently expanded this concept as brain "commotion" in the 13th century, although other Renaissance physicians continued to obscure this concept. By the 18th century, a variety of hypotheses for concussion had emerged. The 19th century discovery of petechial hemorrhagic lesions in severe traumatic brain injury led to these being posited as the basis of concussion, and a similar logic was used later to suggest diffuse axonal injury was responsible. The neuropathology and pathophysiology of concussion has important implications in neurology, sports medicine, medicolegal medicine, and in the understanding of consciousness. Fresh approaches to these questions are needed and modern research tools, including functional imaging and experimental studies of ion-channel function, could help elucidate this puzzle that has evolved over the past 3,000 years.

Hemorrhoids: From basic pathophysiology to clinical management

PubMed Central

Lohsiriwat, Varut

2012-01-01

This review discusses the pathophysiology, epidemiology, risk factors, classification, clinical evaluation, and current non-operative and operative treatment of hemorrhoids. Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions. The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids. It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. In most instances, hemorrhoids are treated conservatively, using many methods such as lifestyle modification, fiber supplement, suppository-delivered anti-inflammatory drugs, and administration of venotonic drugs. Non-operative approaches include sclerotherapy and, preferably, rubber band ligation. An operation is indicated when non-operative approaches have failed or complications have occurred. Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy, but postoperative pain is invariable. Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence. The applications and outcomes of each treatment are thoroughly discussed. PMID:22563187

Diabetic Retinopathy: Pathophysiology and Treatments.

PubMed

Wang, Wei; Lo, Amy C Y

2018-06-20

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM). It has long been recognized as a microvascular disease. The diagnosis of DR relies on the detection of microvascular lesions. The treatment of DR remains challenging. The advent of anti-vascular endothelial growth factor (VEGF) therapy demonstrated remarkable clinical benefits in DR patients; however, the majority of patients failed to achieve clinically-significant visual improvement. Therefore, there is an urgent need for the development of new treatments. Laboratory and clinical evidence showed that in addition to microvascular changes, inflammation and retinal neurodegeneration may contribute to diabetic retinal damage in the early stages of DR. Further investigation of the underlying molecular mechanisms may provide targets for the development of new early interventions. Here, we present a review of the current understanding and new insights into pathophysiology in DR, as well as clinical treatments for DR patients. Recent laboratory findings and related clinical trials are also reviewed.

Erectile dysfunction and coronary atherothrombosis in diabetic patients: pathophysiology, clinical features and treatment.

PubMed

Gazzaruso, Carmine

2006-03-01

The current review reports recent data available in the literature on the prevalence of erectile dysfunction and the association of erectile dysfunction with overt and silent coronary artery disease in patients with diabetes mellitus. The mechanisms by which erectile dysfunction is associated with coronary artery disease and potential clinical implications of this association have been extensively analysed. In particular, the role of endothelial dysfunction in the pathophysiology of erectile dysfunction and the potential clinical usefulness of erectile dysfunction to identify diabetic patients with silent coronary artery disease have been outlined. Finally, recent guidelines on the treatment of erectile dysfunction with phosphodiesterase-5 inhibitors in diabetic patients with and without coronary artery disease have been reported and discussed.

From morphology to clinical pathophysiology: multiphoton fluorescence lifetime imaging at patients' bedside

NASA Astrophysics Data System (ADS)

Mess, Christian; Zens, Katharina; Gorzelanny, Christian; Metze, Dieter; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.; Huck, Volker

2017-02-01

Application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of skin diseases. By means of multiphoton excitation, endogenous biomolecules like NADH, collagen or elastin show autofluorescence or second harmonic generation. Thus, these molecules provide information about the subcellular morphology, epidermal architecture and physiological condition of the skin. To gain a deeper understanding of the linkage between cellular structure and physiological processes, non-invasive multiphotonbased intravital tomography (MPT) and fluorescence lifetime imaging (FLIM) were combined within the scopes of inflammatory skin, chronic wounds and drug delivery in clinical application. The optical biopsies generated via MPT were morphologically analyzed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Independent morphometric algorithms reliably showed a perinuclear accumulation in lesional skin in contrast to an even distribution in healthy skin. Confirmatively, MPT-FLIM showed an obvious metabolic shift in lesions. Moreover, detection of the onset and progression of inflammatory processes could be achieved. The feasibility of primary in vivo tracking of applied therapeutic agents further broadened our scope: We examined the permeation and subsequent distribution of agents directly visualized in patientś skin in short-term repetitive measurements. Furthermore, we performed MPT-FLIM follow-up investigations in the long-term course of therapy. Therefore, clinical MPT-FLIM application offers new insights into the pathophysiology and the individual therapeutic course of skin diseases, facilitating a better understanding of the processes of inflammation and wound healing.

Assessing pathophysiology of cancer anorexia.

PubMed

Laviano, Alessandro; Koverech, Angela; Seelaender, Marilia

2017-09-01

Cancer anorexia is a negative prognostic factor and is broadly defined as the loss of the interest in food. However, multiple clinical domains contribute to the phenotype of cancer anorexia. The characterization of the clinical and molecular pathophysiology of cancer anorexia may enhance the efficacy of preventive and therapeutic strategies. Clinical trials showed that cancer anorexia should be considered as an umbrella encompassing different signs and symptoms contributing to appetite disruption in cancer patients. Loss of appetite, early satiety, changes in taste and smell are determinants of cancer anorexia, whose presence should be assessed in cancer patients. Interestingly, neuronal correlates of cancer anorexia-related symptoms have been revealed by brain imaging techniques. The pathophysiology of cancer anorexia is complex and involves different domains influencing eating behavior. Limiting the assessment of cancer anorexia to questions investigating changes in appetite may impede correct identification of the targets to address.

Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

PubMed

Azaña, J M; Torrelo, A; Matito, A

2016-01-01

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Pathophysiology and animal modeling of underactive bladder.

PubMed

Tyagi, Pradeep; Smith, Phillip P; Kuchel, George A; de Groat, William C; Birder, Lori A; Chermansky, Christopher J; Adam, Rosalyn M; Tse, Vincent; Chancellor, Michael B; Yoshimura, Naoki

2014-09-01

While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.

Pathophysiology and animal modeling of underactive bladder

PubMed Central

Tyagi, Pradeep; Smith, Phillip P.; Kuchel, George A.; de Groat, William C.; Birder, Lori A.; Chermansky, Christopher J.; Adam, Rosalyn M.; Tse, Vincent; Chancellor, Michael B.; Yoshimura, Naoki

2015-01-01

While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB. PMID:25238890

Genetics of liver disease: From pathophysiology to clinical practice.

PubMed

Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

2015-04-01

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[Pathophysiology of hypertension: what's new?].

PubMed

Büchner, Nikolaus; Vonend, Oliver; Rump, Lars Christian

2006-06-01

The pathophysiology of primary hypertension is still unresolved and appears more complex than ever. It is beyond the scope of this article to review all new scientific developments in this field. On clinical grounds, hypertension is divided into primary and secondary forms. Here, the authors discuss the pathophysiology of hypertension associated with three common disease entities showing a large overlap with primary hypertension: chronic kidney disease (CKD), obstructive sleep apnea (OSA), and hyperaldosteronism. Especially in CKD and OSA, the activation of the sympathetic nervous system plays a crucial role. It is the authors' belief that hypertension due to these three diseases is more common than previously appreciated and may account for about 20% of the hypertensive population. The knowledge of the underlying pathophysiology allows early diagnosis and guides optimal treatment of these hypertensive patients.

[Pathophysiology of hypertension : What are our current concepts?].

PubMed

Jordan, J

2015-03-01

In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecular"omics" techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care.

Recent advances in the pathophysiology of arterial hypertension: potential implications for clinical practice.

PubMed

Hering, Dagmara; Trzebski, Andrzej; Narkiewicz, Krzysztof

2017-03-01

Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudoresistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug‑induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug‑resistant hypertension. The well‑established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very recently, research on the role of vasopressinergic neurons, masked tachycardia, and impaired brain neural activity has provided novel insights into hypertension. This review briefly summarizes the role of the centrally mediated sympathetic nervous system in hypertension, the therapeutic strategies that distinctively target impaired neural reflex mechanisms, and potential implications for future clinical research and therapies.

Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study.

PubMed

Truini, A; Galeotti, F; Haanpaa, M; Zucchi, R; Albanesi, A; Biasiotta, A; Gatti, A; Cruccu, G

2008-12-01

Postherpetic neuralgia is an exceptionally drug-resistant neuropathic pain. To investigate the pathophysiological mechanisms underlying postherpetic neuralgia we clinically investigated sensory disturbances, pains and itching, with an 11-point numerical rating scale in 41 patients with ophthalmic postherpetic neuralgia. In all the patients we recorded the blink reflex, mediated by non-nociceptive myelinated Abeta-fibers, and trigeminal laser evoked potentials (LEPs) related to nociceptive myelinated Adelta- and unmyelinated C-fiber activation. We also sought possible correlations between clinical sensory disturbances and neurophysiological data. Neurophysiological testing yielded significantly abnormal responses on the affected side compared with the normal side (P<0.001). The blink reflex delay correlated with the intensity of paroxysmal pain, whereas the Adelta- and C-LEP amplitude reduction correlated with the intensity of constant pain (P<0.01). Allodynia correlated with none of the neurophysiological data. Our study shows that postherpetic neuralgia impairs all sensory fiber groups. The neurophysiological-clinical correlations suggest that constant pain arises from a marked loss of nociceptive afferents, whereas paroxysmal pain is related to Abeta-fiber demyelination. These findings might be useful for a better understanding of pain mechanisms in postherpetic neuralgia.

Modern iron replacement therapy: clinical and pathophysiological insights.

PubMed

Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

2018-01-01

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

Pancreatitis in dogs and cats: definitions and pathophysiology.

PubMed

Watson, P

2015-01-01

Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

Requirements for the formal representation of pathophysiology mechanisms by clinicians

PubMed Central

Helvensteijn, M.; Kokash, N.; Martorelli, I.; Sarwar, D.; Islam, S.; Grenon, P.; Hunter, P.

2016-01-01

Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for pathophysiology mechanisms. A number of obstacles stand in the way of this sharing—not least the technical and operational challenges that must be overcome to ensure that (i) the explicit biological meanings of the Physiome's quantitative methods to represent mechanisms are open to articulation, verification and study by clinicians, and that (ii) clinicians are given the tools and training to explicitly express disease manifestations in direct contribution to modelling. To this end, the Physiome and Clinical communities must co-develop a common computational toolkit, based on this blueprint, to bridge the representation of knowledge of pathophysiology mechanisms (a) that is implicitly depicted in electronic health records and the literature, with (b) that found in mathematical models explicitly describing mechanisms. In particular, this paper makes use of a step-wise description of a specific disease mechanism as a means to elicit the requirements of representing pathophysiological meaning explicitly. The computational blueprint developed from these requirements addresses the Clinical community goals to (i) organize and manage healthcare resources in terms of relevant disease-related knowledge of mechanisms and (ii) train the next generation of physicians in the application of quantitative methods relevant to their research and practice. PMID:27051514

Detrusor underactivity: Pathophysiological considerations, models and proposals for future research. ICI-RS 2013.

PubMed

van Koeveringe, Gommert A; Rademakers, Kevin L J; Birder, Lori A; Korstanje, Cees; Daneshgari, Firouz; Ruggieri, Michael R; Igawa, Yasuhiko; Fry, Christopher; Wagg, Adrian

2014-06-01

Detrusor underactivity, resulting in either prolonged or inefficient voiding, is a common clinical problem for which treatment options are currently limited. The aim of this report is to summarize current understanding of the clinical observation and its underlying pathophysiological entities. This report results from presentations and subsequent discussion at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2013. The recommendations made by the ICI-RS panel include: Development of study tools based on a system's pathophysiological approach, correlation of in vitro and in vivo data in experimental animals and humans, and development of more comprehensive translational animal models. In addition, there is a need for longitudinal patient data to define risk groups and for the development of screening tools. In the near-future these recommendations should lead to a better understanding of detrusor underactivity and its pathophysiological background. Neurourol. Urodynam. 33:591-596, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

PubMed Central

Chiu, Jeng-Jiann; Chien, Shu

2013-01-01

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate

Bipolar Pathophysiology and Development of Improved Treatments

PubMed Central

Bowden, Charles L.

2013-01-01

The purpose of this review is to provide strategies and their rationale which can facilitate scientifically productive investigations into genetic, neuronal, brain functional and clinical aspects of bipolar disorder. The presentation addresses both factors that have impeded and those that have facilitated landmark advances on the pathophysiology and treatment of bipolar disorders. Application of the strategies can provide a scientific platform that may be useful to basic and clinical scientists for the purposes of achieving seminal advances in understanding pathophysiology, including inherited and experience based contributors to disease expression. Current diagnostic criteria omit certain key symptoms, do not include illness course or family history and lack specification of the importance of fundamental symptomatology. Consideration of such factors in inclusion and exclusion criteria, and in assessment instruments in basic and clinical studies, serves to strengthen the capability of a research plan to test key hypotheses regarding moderating and mediating factors of this complex illness. For example, most studies of brain structure and function and of new interventions have selected subjects on the basis of traditional full syndromal criteria. Evidence indicates that additional consideration of principal behavioral domains of bipolar symptomatology, e.g., anxiety, psychosis, impulsivity, elevated psychomotor and cognitive processing speed, rather than strictly depressive or manic syndromes can provide more homogeneous samples for study, and increase the focus of experimental hypotheses. PMID:18582440

Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

PubMed Central

Corcoran, David

2018-01-01

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

Inflammation in the pathophysiology of essential hypertension.

PubMed

Montecucco, Fabrizio; Pende, Aldo; Quercioli, Alessandra; Mach, François

2011-01-01

In spite of the huge amount of research recently performed in this area, the pathogenesis of human hypertension remains elusive. Thus, hypertension has to be defined as "essential" for the majority of patients with high blood pressure. Given the lack of animal models useful to investigate essential hypertension, we analyze and discuss both clinical and basic research studies indicating that essential hypertension should be considered as a potential multifactorial inflammatory disease. The pathophysiology of essential hypertension might result from interactions between genetic and environmental factors. Morphological abnormalities in the renal parenchyma and arteries have also been shown to determine hypertension. Inflammatory processes might induce renal vasoconstriction, ischemia and injury that can sustain systemic hypertension. Arterial and tubulointerstitial infiltration of inflammatory cells in response to renal damage might further increase renal and vascular alterations through the production of oxidants and other soluble inflammatory mediators. The present review gives an update regarding the latest research on the possible direct role of inflammation in the pathophysiology of essential hypertension.

Somnambulism: clinical aspects and pathophysiological hypotheses.

PubMed

Zadra, Antonio; Desautels, Alex; Petit, Dominique; Montplaisir, Jacques

2013-03-01

Somnambulism, or sleepwalking, can give rise to a wide range of adverse consequences and is one of the leading causes of sleep-related injury. Accurate diagnosis is crucial for proper management and imperative in an ever-increasing number of medicolegal cases implicating sleep-related violence. Unfortunately, several widely held views of sleepwalking are characterised by key misconceptions, and some established diagnostic criteria are inconsistent with research findings. The traditional idea of somnambulism as a disorder of arousal might be too restrictive and a comprehensive view should include the idea of simultaneous interplay between states of sleep and wakefulness. Abnormal sleep physiology, state dissociation, and genetic factors might explain the pathophysiology of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

PubMed

Vinik, Aaron I; Chaya, Celine

2016-02-01

Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.

PubMed

Derksen, V F A M; Ajeganova, S; Trouw, L A; van der Helm-van Mil, A H M; Hafström, I; Huizinga, T W J; Toes, R E M; Svensson, B; van der Woude, D

2017-04-01

In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA. Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression. In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies. The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hypertension in pregnancy: Taking cues from pathophysiology for clinical practice.

PubMed

Sava, Ruxandra I; March, Keith L; Pepine, Carl J

2018-02-01

Pregnancy-related hypertension (PHTN) syndromes are a frequent and potentially deadly complication of pregnancy, while also negatively impacting the lifelong health of the mother and child. PHTN appears in women likely to develop hypertension later in life, with the stress of pregnancy unmasking a subclinical hypertensive phenotype. However, distinguishing between PHTN and chronic hypertension is essential for optimal management. Preeclampsia (PE) is linked to potentially severe outcomes and lacks effective treatments due to poorly understood mechanisms. Inadequate remodeling of spiral uterine arteries (SUAs), the cornerstone of PE pathophysiology, leads to hypoperfusion of the developing placenta. In normal pregnancies, extravillous trophoblast (EVT) cells assume an invasive phenotype and invade SUAs, transforming them into large conduits. Decidual natural killer cells play an essential role, mediating materno-fetal immune tolerance, inducing early SUA remodeling and regulating EVT invasiveness. Notch signaling is important in EVT phenotypic switch and is dysregulated in PE. The hypoxic placenta releases antiangiogenic and proinflammatory factors that converge upon maternal endothelium, inducing endothelial dysfunction, hypertension, and organ damage. Hypoxia-inducible factor 1-α is upstream of such molecules, whereas endothelin-1 is a major effector. We also describe important genetic links and evidence of incomplete materno-fetal immune tolerance, with PE patients presenting with autoantibodies, lower T reg , and higher T h 17 cells. Thus, PE manifestations arise as a consequence of mal-placentation or/and because of a predisposition of the maternal vascular bed to excessively react to pathogenic molecules. From this pathophysiological basis, we provide current and propose future therapeutic directions for PE. © 2018 Wiley Periodicals, Inc.

Dandy-Walker syndrome presenting as opisthotonus: proposed pathophysiology.

PubMed

Ondo, W G; Delong, G R

1996-02-01

A patient with radiographically confirmed Dandy-Walker syndrome who presented with opisthotonus, a rarely reported clinical manifestation, is reported. From four separate pharmacologic trials (baclofen, diazepam, levodopa/carbidopa, and trihexyphenidyl), combination baclofen and diazepam therapy was determined to be most efficacious. Opisthotonus and extensor posturing remain only rudimentarily understood. We review the subject and propose a specific mechanism relating our patient's anatomic and physiologic conditions.

Congenital portosystemic shunts: imaging findings and clinical presentations in 11 patients.

PubMed

Konstas, Angelos A; Digumarthy, Subba R; Avery, Laura L; Wallace, Karen L; Lisovsky, Mikhail; Misdraji, Joseph; Hahn, Peter F

2011-11-01

To evaluate the clinical anatomy and presentations of congenital portosystemic shunts, and determine features that promote recognition on imaging. Institutional review board approval was obtained for this HIPAA-compliant study. The requirement for written informed consent was waived. Radiology reports were retrospectively reviewed from non-cirrhotic patients who underwent imaging studies from January 1999 through February 2009. Clinical sources reviewed included electronic medical records, archived images and histopathological material. Eleven patients with congenital portosystemic shunts were identified (six male and five female; age range 20 days to 84 years). Seven patients had extrahepatic and four patients had intrahepatic shunts. All 11 patients had absent or hypoplastic intrahepatic portal veins, a feature detected by CT and MRI, but not by US. Seven patients presented with shunt complications and four with presentations unrelated to shunt pathophysiology. Three adult patients had four splenic artery aneurysms. Prospective radiological evaluation of five adult patients with cross-sectional imaging had failed prospectively to recognize the presence of congenital portosystemic shunts on one or more imaging examinations. Congenital portosystemic shunts are associated with splenic artery aneurysms, a previously unrecognized association. Portosystemic shunts were undetected during prospective radiologic evaluation in the majority of adult patients, highlighting the need to alert radiologists to this congenital anomaly. Copyright © 2010. Published by Elsevier Ireland Ltd.

Student perceptions of the use of presentations as a method of learning endocrine and gastrointestinal pathophysiology.

PubMed

Higgins-Opitz, Susan B; Tufts, Mark

2010-06-01

Second-year medical students at the Nelson R. Mandela School of Medicine (Durban, South Africa) were given a brief to prepare oral presentations on topics related to disorders of the gastrointestinal tract and endocrine system in the form of "patient-doctor" role play and to submit written documents about their topics. This initiative was introduced to assist medical students in their application and understanding of physiology to clinical situations. The aims of the student presentations were to improve the understanding of the physiological basis of diseases; promote independent research, active, and group-based learning; encourage social interactions; and develop presentation and peer review skills. Students rose to the challenge, producing a variety of presentations reflecting a wealth of creativity, humour, sensitivity to local cultural issues, and analytic thinking skills. The quality of the supporting posters and computer-generated slides was outstanding. Numerous "fun" prizes for specific individual and group performances were given based on peer and staff evaluations. This exercise ran over a 5-yr period before the introduction of a problem-based learning medical curriculum. Student feedback obtained over these years is reported here. Students were asked to complete semistructured questionnaires, which elicited feedback on various aspects of the learning exercise, including whether it should be continued and how it could be improved upon, especially if they were in groups that did not function well. The feedback obtained revealed that most students perceived the presentations to be fun, informative, creative/innovative, and, most importantly, beneficial to their learning. The majority of students felt that this exercise improved their understanding of pathophysiology, taught them to research independently, and encouraged better class interactions and group learning. The inclusion of such initiatives is beneficial not only to students' understanding and

Teaching Differential Diagnosis by Computer: A Pathophysiological Approach

ERIC Educational Resources Information Center

Goroll, Allan H.; And Others

1977-01-01

An interactive, computer-based teaching exercise in diagnosis that emphasizes pathophysiology in the analysis of clinical data is described. Called the Jaundice Program, its objective is to simplify the pattern recognition problem by relating clinical findings to diagnosis via reference to disease mechanisms. (LBH)

Pathophysiology of priapism: dysregulatory erection physiology thesis.

PubMed

Burnett, Arthur L

2003-07-01

While a modest amount of medical literature has been written on the topic of priapism, reports heretofore have focused predominantly on diagnostic and management related aspects of the disorder, providing meager information in regard to its pathophysiology. Accordingly the intent of this review was to explore the etiological and pathogenic factors involved in priapism. The review entailed an overview of traditional and modern concepts that have been applied to the pathophysiology of priapism and an evaluation of assorted observational and experimental data relating to this field of study. The basic exercise consisted of a literature search using the National Library of Medicine PubMed Services, index referencing provided through the Historical Collection of the Institute of Medicine of The Johns Hopkins University and a survey of abstract proceedings from national meetings relevant to priapism. Insight into the pathophysiology of priapism was derived from a synthesis of evolutionary clinical experiences, mythical beliefs, clinical variants and scientific advances associated with the field of priapism. The results can be summarized. 1) Clinicopathological manifestations of priapism support its basic classification into low flow (ischemic) and high flow (nonischemic) hemodynamic categories, commonly attributed to venous outflow occlusion and unregulated arterial overflow of the penis, respectively. 2) Factual information is insufficient to substantiate etiological roles for urethral infection, bladder distention, failed ejaculation, satyriasis and sleep apnea in priapism. 3) Features of the variant forms of priapism invoke changes in nervous system control of erection and penile vascular homeostasis as having pathogenic roles in the disorder. 4) Clinical therapeutic and basic science investigative studies have revealed various effector mechanisms of the erectile tissue response that may act in dysregulated fashion to subserve priapism. This exercise suggested that

"Amyand's Hernia" – Pathophysiology, Role of Investigations and Treatment

PubMed Central

SINGAL, Rikki; GUPTA, Samita

2011-01-01

ABSTRACT Background: In the present era, appendicitis and hernia are common problems but their presentations in different positions are rare to be seen. It is difficult to make diagnose pre-operatively of contents as appendicitis in obstructed hernia. The term "Amyand's hernia" was lost in the literature and we are describing its pathophysiology and management. The aggravating factors are: complex injuries related to hernia (size, degree of sliding, multiplicity, etc.), patient characteristics (age, activity, respiratory disease, dysuria, obesity, constipation). If not treated in the earliest stages then it can lead to significant morbidity and mortality. Existing literature describes almost exclusively its pathophysiology, investigations and treatment. Material and Methods: We have focused on clinical presentation, radiological investigations and management of "Amyand's hernia". In literature, there is still confusion regarding investigations and treatment. We are presenting such rare entity managed in time without encountering any post-operative complications. Results: Ultrasonography and Computed Tomography are useful tests but clinical correlation is necessary in incarcerated appendix. Regarding treatment, it is clear that if appendix is inflamed then it should be removed, but we concluded that if appendix is found to be normal in obstructed hernia then it should also be removed due to possible later inflammation. Conclusion: If the appendix found in the hernial sac is inflamed then chances of mortality increase. Although emergency surgery is indicated in all obstructed hernias, morbidity and mortality can be decreased if operated on time. Early recognition and its awareness, along with good surgical technique in such cases are keys to success when dealing with this problem. PMID:22879848

A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome.

PubMed

Choi, Jun Yong; Kwon, Jiwon; Bae, Eun-Kee

2014-09-01

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome is a unique disease entity characterized by typical clinical and electroencephalographic (EEG) features in the setting of chronic alcoholism. We present two patients with distinctive serial MRI and EEG findings which suggest a clue to the underlying pathophysiologic mechanisms of SESA syndrome. Two patients with chronic alcoholism and alcoholic liver cirrhosis presented with generalized seizures and confused mental status. Brain MRI demonstrated restricted diffusion, increased T2-weighted signal intensity, and hyperperfusion in the presumed seizure focus and nearby posterior regions of the cerebral hemispheres. EEG showed periodic lateralized epileptiform discharges which were prominent in the posterior regions of the cerebral hemispheres ipsilateral to the side of brain MRI abnormalities. Even after patients clinically improved, these brain abnormalities persisted with progressive atrophic changes on follow-up brain MRI. These patients had not only the distinguishing clinical and EEG features of SESA syndrome, but also showed novel brain MRI abnormalities. These changes on MRI displayed characteristics of seizure-related changes. The posterior dominance of abnormalities on MRI and EEG suggests that the pathophysiologic mechanisms of SESA syndrome may share those of posterior reversible encephalopathy syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach.

PubMed

Ellis, Michael J; Leddy, John; Willer, Barry

2016-01-01

Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach.

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach

PubMed Central

Ellis, Michael J.; Leddy, John; Willer, Barry

2016-01-01

Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach. PMID:27605923

The pathophysiology of post-stroke aphasia: A network approach.

PubMed

Thiel, Alexander; Zumbansen, Anna

2016-06-13

Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS).

Pathophysiology of Portal Hypertension and Its Clinical Links

PubMed Central

Seo, Yeon Seok; Shah, Vijay H

2011-01-01

Portal hypertension is a major cause of morbidity and mortality in patients with liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic vasodilatation, and development of collateral circulation have been considered as major factors for the development of portal hypertension. Recently, sinusoidal remodeling and angiogenesis have been focused as potential etiologic factors and various researchers have tried to improve portal hypertension by modulating these new targets. This article reviews potential new treatments in the context of portal hypertension pathophysiology concepts. PMID:25755320

Delayed Ejaculation: Pathophysiology, Diagnosis, and Treatment

PubMed Central

2018-01-01

Delayed ejaculation (DE) is a poorly defined and uncommon form of male sexual dysfunction, characterized by a marked delay in ejaculation or an inability to achieve ejaculation. It is often quite concerning to patients and their partners, and sometimes frustrates couples' attempts to conceive. This article aims to review the pathophysiology of DE and anejaculation (AE), to explore our current understanding of the diagnosis, and to present the treatment options for this condition. Electronic databases were searched from 1966 to October 2017, including PubMed (MEDLINE) and Embase. We combined “delayed ejaculation,” “retarded ejaculation,” “inhibited ejaculation,” or “anejaculation” as Medical Subject Headings (MeSH) terms or keywords with “epidemiology,” “etiology,” “pathophysiology,” “clinical assessment,” “diagnosis,” or “treatment.” Relevant sexual medicine textbooks were searched as well. The literature suggests that the pathophysiology of DE/AE is multifactorial, including both organic and psychosocial factors. Despite the many publications on this condition, the exact pathogenesis is not yet known. There is currently no single gold standard for diagnosing DE/AE, as operationalized criteria do not exist. The history is the key to the diagnosis. Treatment should be cause-specific. There are many approaches to treatment planning, including various psychological interventions, pharmacotherapy, and specific treatments for infertile men. An approved form of drug therapy does not exist. A number of approaches can be employed for infertile men, including the collection of nocturnal emissions, prostatic massage, prostatic urethra catheterization, penile vibratory stimulation, probe electroejaculation, sperm retrieval by aspiration from either the vas deferens or the epididymis, and testicular sperm extraction. PMID:29299903

Pathophysiology 220.

ERIC Educational Resources Information Center

Smith, Lori

A description is provided of a course, "Pathophysiology 220," designed to provide junior nursing students at the University of Michigan's School of Nursing with theoretical knowledge of a broad range of pathophysiological conditions. Section I discusses the place of the course in the curriculum, the allotment of class time, course requirements,…

Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology

PubMed Central

Balint, Bettina; Vincent, Angela; Meinck, Hans-Michael; Irani, Sarosh R; Bhatia, Kailash P

2018-01-01

Abstract Movement disorders are a prominent and common feature in many autoantibody-associated neurological diseases, a group of potentially treatable conditions that can mimic infectious, metabolic or neurodegenerative disease. Certain movement disorders are likely to associate with certain autoantibodies; for example, the characteristic dyskinesias, chorea and dystonia associated with NMDAR antibodies, stiff person spectrum disorders with GAD, glycine receptor, amphiphysin or DPPX antibodies, specific paroxysmal dystonias with LGI1 antibodies, and cerebellar ataxia with various anti-neuronal antibodies. There are also less-recognized movement disorder presentations of antibody-related disease, and a considerable overlap between the clinical phenotypes and the associated antibody spectra. In this review, we first describe the antibodies associated with each syndrome, highlight distinctive clinical or radiological ‘red flags’, and suggest a syndromic approach based on the predominant movement disorder presentation, age, and associated features. We then examine the underlying immunopathophysiology, which may guide treatment decisions in these neuroimmunological disorders, and highlight the exceptional interface between neuronal antibodies and neurodegeneration, such as the tauopathy associated with IgLON5 antibodies. Moreover, we elaborate the emerging pathophysiological parallels between genetic movement disorders and immunological conditions, with proteins being either affected by mutations or targeted by autoantibodies. Hereditary hyperekplexia, for example, is caused by mutations of the alpha subunit of the glycine receptor leading to an infantile-onset disorder with exaggerated startle and stiffness, whereas antibodies targeting glycine receptors can induce acquired hyperekplexia. The spectrum of such immunological and genetic analogies also includes cerebellar ataxias and some encephalopathies. Lastly, we discuss how these pathophysiological considerations

Imaging Alzheimer's disease pathophysiology with PET

PubMed Central

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

2016-01-01

ABSTRACT Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD. PMID:29213438

The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of "The little match girl" case.

PubMed

Jeican, Ionuţ Isaia

2014-01-01

Hypothermia and death caused by hypothermia may be found in a number of fiction works, mainly in novels. In the well-known story "The Little Match Girl" by Hans Christian Andersen, one can notice that the descriptions of the phenomena occurring before the girl's death are in fact a literary presentation of the pathophysiological mechanisms of the onset of death through accidental hypothermia. This essay presents the medical aspects of the story written by Andersen.

Pathophysiology and management of multivalvular disease

PubMed Central

Unger, Philippe; Clavel, Marie-Annick; Lindman, Brian R.; Mathieu, Patrick; Pibarot, Philippe

2016-01-01

Multivalvular disease (MVD) is a common condition with a complex pathophysiology, dependent on the specific combination of valve lesions. Diagnosis is challenging as several echocardiographic methods commonly used for the assessment of stenosis or regurgitation have been validated only in patients with single valve disease. Decisions about the timing and type of treatment should be made by a multidisciplinary heart valve team, on a case-by-case basis. Several factors should be considered, including the severity and consequences of the MVD, the patient’s life expectancy and comorbidities, the surgical risk associated with combined valve procedures, the long-term risk of morbidity and mortality associated with multiple valve prostheses, and the likelihood and risk of reoperation. The introduction of transcatheter valve therapies into clinical practice has provided new treatment options for patients with MVD, and decision-making algorithms on how to combine surgical and percutaneous treatment options are evolving rapidly. In this Review, we discuss the pathophysiology, diagnosis, and treatment of MVD, focussing on the combination of valve pathologies that are most often encountered in clinical practice. PMID:27121305

Esophageal Achalasia: Pathophysiology, Clinical Presentation, and Diagnostic Evaluation.

PubMed

Schlottmann, Francisco; Neto, Rafael M L; Herbella, Fernando A M; Patti, Marco G

2018-04-01

Esophageal achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and failure of the lower esophageal sphincter to relax in response to swallowing. These abnormalities lead to impaired emptying of food from the esophagus into the stomach with resulting food stasis. Most patients experience severe dysphagia, and regurgitation can lead to aspiration and respiratory problems. Consequently, the quality of life of patients affected by achalasia is severely impacted. A thorough evaluation with upper endoscopy, barium swallow, and esophageal manometry is mandatory to establish the diagnosis and plan the optimal treatment. In selected patients, an ambulatory pH monitoring is recommended to distinguish between gastroesophageal reflux disease and achalasia.

Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon.

PubMed

Tfayli, Hala; Arslanian, Silva

2009-03-01

Type 2 diabetes mellitus (T2DM) in children and adolescents is an important Public Health problem against the backdrop of the epidemic of childhood obesity. The clinical presentation of T2DM in youth is heterogeneous from minimal symptomatology to diabetic ketoacidosis. The increasing rates of youth T2DM have paralleled the escalating rates of obesity, which is the major risk factor impacting insulin sensitivity. Additional risk factors include minority race, family history of diabetes mellitus, maternal diabetes during pregnancy, pubertal age group and conditions associated with insulin resistance (IR) - such as polycystic ovary syndrome (PCOS). The pathophysiology of T2DM has been studied extensively in adults, and it is widely accepted that IR together with beta-cell failure are necessary for the development of clinical diabetes mellitus in adulthood. However, pathophysiologic studies in youth are limited and in some cases conflicting. Similar to adults, IR is a prerequisite, but beta-cell failure is necessary for progression from normal glucose tolerance to prediabetes and frank diabetes in youth. Even though rates of T2DM in youth are increasing, the overall prevalence remains low if compared with type 1 diabetes mellitus (T1DM). However, as youth with T1DM are becoming obese, the clinical distinction between T2DM and obese T1DM has become difficult, because of the overlapping clinical picture with evidence of islet cell autoimmunity in a significant proportion of clinically diagnosed youth with T2DM. The latter are most likely obese children with autoimmune T1DM who carry a misdiagnosis of T2DM. Further research is needed to probe the pathophysiological, immunological, and metabolic differences between these two groups in the hopes of assigning appropriate therapeutic regimens. These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood

Pathophysiology and immunological profile of myasthenia gravis and its subgroups.

PubMed

Romi, Fredrik; Hong, Yu; Gilhus, Nils Erik

2017-12-01

Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present. Copyright © 2017. Published by Elsevier Ltd.

Alice in Wonderland Syndrome: A Clinical and Pathophysiological Review

PubMed Central

2016-01-01

Alice in Wonderland Syndrome (AIWS) is a perceptual disorder, principally involving visual and somesthetic integration, firstly reported by Todd, on the literary suggestion of the strange experiences described by Lewis Carroll in Alice in Wonderland books. Symptoms may comprise among others aschematia and dysmetropsia. This syndrome has many different etiologies; however EBV infection is the most common cause in children, while migraine affects more commonly adults. Many data support a strict relationship between migraine and AIWS, which could be considered in many patients as an aura or a migraine equivalent, particularly in children. Nevertheless, AIWS seems to have anatomical correlates. According to neuroimaging, temporoparietal-occipital carrefour (TPO-C) is a key region for developing many of AIWS symptoms. The final part of this review aims to find the relationship between AIWS symptoms, presenting a pathophysiological model. In brief, AIWS symptoms depend on an alteration of TPO-C where visual-spatial and somatosensory information are integrated. Alterations in these brain regions may cause the cooccurrence of dysmetropsia and disorders of body schema. In our opinion, the association of other symptoms reported in literature could vary depending on different etiologies and the lack of clear diagnostic criteria. PMID:28116304

Pisa syndrome in Parkinson's disease: An integrated approach from pathophysiology to management.

PubMed

Tinazzi, Michele; Geroin, Christian; Gandolfi, Marialuisa; Smania, Nicola; Tamburin, Stefano; Morgante, Francesca; Fasano, Alfonso

2016-12-01

Pisa syndrome was first described in 1972 in patients treated with neuroleptics. Since 2003, when it was first reported in patients with Parkinson's disease (PD), Pisa syndrome has progressively drawn the attention of clinicians and researchers. Although emerging evidence has partially clarified its prevalence and pathophysiology, the current debate revolves around diagnostic criteria and assessment and the effectiveness of pharmacological, surgical, and rehabilitative approaches. Contrary to initial thought, Pisa syndrome is common among PD patients, with an estimated prevalence of 8.8% according to a large survey. Furthermore, it is associated with the following specific patient features: more severe motor phenotype, ongoing combined pharmacological treatment with levodopa and dopamine agonists, gait disorders, and such comorbidities as osteoporosis and arthrosis. The present literature on treatment outcomes is scant, and the uneven effectiveness of specific treatments has produced conflicting results. This might be because of the limited knowledge of Pisa syndrome pathophysiology and its variable clinical presentation, which further complicates designing randomized clinical trials on this condition. However, because some forms of Pisa syndrome are potentially reversible, there is growing consensus on the importance of its early recognition and the importance of pharmacological adjustment and rehabilitation. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of “The little match girl” case

PubMed Central

JEICAN, IONUŢ ISAIA

2014-01-01

Hypothermia and death caused by hypothermia may be found in a number of fiction works, mainly in novels. In the well-known story “The Little Match Girl” by Hans Christian Andersen, one can notice that the descriptions of the phenomena occurring before the girl’s death are in fact a literary presentation of the pathophysiological mechanisms of the onset of death through accidental hypothermia. This essay presents the medical aspects of the story written by Andersen. PMID:26527999

Wolfram Syndrome: A Case Report and Review of Clinical Manifestations, Genetics Pathophysiology, and Potential Therapies

PubMed Central

McMillan, J. M.; Au, P. Y. B.; Suchowersky, O.

2018-01-01

Background Classical Wolfram syndrome (WS) is a rare autosomal recessive disorder caused by mutations in WFS1, a gene implicated in endoplasmic reticulum (ER) and mitochondrial function. WS is characterized by insulin-requiring diabetes mellitus and optic atrophy. A constellation of other features contributes to the acronym DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). This review seeks to raise awareness of this rare form of diabetes so that individuals with WS are identified and provided with appropriate care. Case We describe a woman without risk factors for gestational or type 2 diabetes who presented with gestational diabetes (GDM) at the age of 39 years during her first and only pregnancy. Although she had optic atrophy since the age of 10 years, WS was not considered as her diagnosis until she presented with GDM. Biallelic mutations in WFS1 were identified, supporting a diagnosis of classical WS. Conclusions The distinct natural history, complications, and differences in management reinforce the importance of distinguishing WS from other forms of diabetes. Recent advances in the genetics and pathophysiology of WS have led to promising new therapeutic considerations that may preserve β-cell function and slow progressive neurological decline. Insight into the pathophysiology of WS may also inform strategies for β-cell preservation for individuals with type 1 and 2 diabetes. PMID:29850290

Primary headache pathophysiology in children: the contribution of clinical neurophysiology.

PubMed

Pro, S; Tarantino, S; Capuano, A; Vigevano, F; Valeriani, M

2014-01-01

Although primary headaches are very prevalent also in pediatric age, most neurophysiologic studies in these diseases concerned only the adulthood. The neurophysiologic investigation of the pathophysiological mechanisms subtending migraine and tension-type headache in children and adolescents could be particularly interesting, since during the developmental age the migrainous phenotype is scarcely influenced by many environmental factors that can typically act on adult headache patients. The neurophysiologic abnormality most frequently found in adult migraineurs, that is the reduced habituation of evoked potentials, was confirmed also in migraine children, although it was shown to involve also children with tension-type headache. Some studies showed abnormalities in the maturation of brain functions in migraine children and adolescents. While the visual system maturation seems slowed in young migraineurs, the psychophysiological mechanisms subtending somatosensory spatial attention in migraine children are more similar to those of healthy adults than to those of age-matched controls. There are some still unexplored fields that will have to be subjects of future studies. The nociceptive modality, which has been investigated in adult patients with primary headaches, should be studied also in pediatric migraine. Moreover, the technique of transcranial magnetic stimulation, not yet used in young migraineurs, will possibly provide further elements about brain excitability in migraine children. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Noradrenergic dysregulation in the pathophysiology of PTSD.

PubMed

Hendrickson, Rebecca C; Raskind, Murray A

2016-10-01

A central role for noradrenergic dysregulation in the pathophysiology of post-traumatic stress disorder (PTSD) is increasingly suggested by both clinical and basic neuroscience research. Here, we integrate recent findings from clinical and animal research with the earlier literature. We first review the evidence for net upregulation of the noradrenergic system and its responsivity to stress in individuals with PTSD. Next, we trace the evidence that the α 1 noradrenergic receptor antagonist prazosin decreases many of the symptoms of PTSD from initial clinical observations, to case series, to randomized controlled trials. Finally, we review the basic science work that has begun to explain the mechanism for this efficacy, as well as to explore its possible limitations and areas for further advancement. We suggest a view of the noradrenergic system as a central, modifiable link in a network of interconnected stress-response systems, which also includes the amygdala and its modulation by medial prefrontal cortex. Particular attention is paid to the evidence for bidirectional signaling between noradrenaline and corticotropin-releasing factor (CRF) in coordinating these interconnected systems. The multiple different ways in which the sensitivity and reactivity of the noradrenergic system may be altered in PTSD are highlighted, as is the evidence for possible heterogeneity in the pathophysiology of PTSD between different individuals who appear clinically similar. We conclude by noting the importance moving forward of improved measures of noradrenergic functioning in clinical populations, which will allow better recognition of clinical heterogeneity and further assessment of the functional implications of different aspects of noradrenergic dysregulation. Published by Elsevier Inc.

Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

PubMed Central

Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.

2016-01-01

Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

Pathophysiology of chronic heart failure.

PubMed

Francis, G S

2001-05-07

Heart failure is a changing paradigm. The hemodynamic model, which served our needs well from the 1950s through the early 1980s, has now been largely abandoned, except for the management of decompensated patients in the hospital. The pathophysiology is exceedingly complex and involves structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca(2+) homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. A more contemporary working hypothesis is that heart failure is a progressive disorder of left ventricular remodeling, usually resulting from an index event, that culminates in a clinical syndrome characterized by impaired cardiac function and circulatory congestion. This change in the framework of our understanding of the pathophysiology of heart failure is predicated on the results of numerous clinical trials conducted during the past 20 years. New therapies are now evolving that are designed to inhibit neuroendocrine and cytokine activation, whereas drugs specifically designed to heighten cardiac contractility and "unload" the left ventricle have proven to be unhelpful in long-term management of patients with chronic heart failure. However, the hemodynamic model is still relevant for patients in the hospital with decompensated heart failure, where positive inotropic drugs and vasodilators are still widely used. The modern treatment of chronic heart failure is now largely based on the neurohormonal hypothesis, which states that neuroendocrine activation is important in the progression of heart failure and that inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Thus, the evolution of treatment for chronic heart failure as a result of clinical trials has provided much enlightenment for our understanding of the fundamental biology of the disorder, a reversal of the usual flow of information from basic science to

Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

PubMed

Sebastiani, Giada; Pantopoulos, Kostas

2011-10-01

In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references). This journal is © The Royal Society of Chemistry 2011

Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment.

PubMed

Kaufman, Bridget P; Guttman-Yassky, Emma; Alexis, Andrew F

2018-04-01

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and Black individuals than Whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation and treatment of AD in non-White ethnic groups, which are largely underappreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non-White patients, as well as greater inclusion of minority groups in clinical trials, to develop targeted treatments for a multi-ethnic population. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

PubMed

Andrade, Jason; Khairy, Paul; Dobrev, Dobromir; Nattel, Stanley

2014-04-25

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of

The pathophysiology of chronic noncommunicating hydrocephalus: lessons from continuous intracranial pressure monitoring and ventricular infusion testing.

PubMed

Eide, Per Kristian

2017-08-11

OBJECTIVE The pathophysiology of chronic noncommunicating hydrocephalus (ncHC) is poorly understood. This present study explored whether lessons about the pathophysiology of this clinical entity might be retrieved from results of overnight monitoring of pulsatile and static intracranial pressure (ICP) and ventricular infusion testing. METHODS The study cohort included adult patients (> 20 years of age) with chronic ncHC due to aqueductal stenosis in whom symptoms had lasted a minimum of 6 months. A reference cohort consisted of age- and sex-matched patients managed for communicating HC (cHC). Information about symptoms and clinical improvement following surgery was retrieved from a quality register, and results of overnight ICP recordings and ventricular infusion testing were retrieved from the hospital ICP database. RESULTS The cohort with ncHC consisted of 61 patients of whom 6 (10%) were managed conservatively, 34 (56%) by endoscopic third ventriculostomy (ETV), and 21 (34%) using ETV and subsequent shunt surgery. In patients responding to surgery, pulsatile ICP (mean ICP wave amplitude) was significantly increased to a similar magnitude in patients with ncHC and the reference cohort (cHC). Furthermore, intracranial compliance (ICC) was reduced in clinical responders. The results of ventricular infusion testing provided evidence that patients responding to ETV have impaired ventricular CSF absorption, while those requiring shunt placement after ETV present with impaired CSF absorption both in the intraventricular and extraventricular compartments. CONCLUSIONS The study may provide some lessons about the pathophysiology of chronic ncHC. First, increased pulsatile ICP and impaired ICC characterize patients with chronic ncHC who respond clinically to CSF diversion surgery, even though static ICP is not increased. Second, in patients responding clinically to ETV, impaired ventricular CSF absorption may be a key factor. Patients requiring shunt placement for clinical

A systems approach to bone pathophysiology.

PubMed

Weiss, Aaron J; Lipshtat, Azi; Mechanick, Jeffrey I

2010-11-01

With evolving interest in multiscalar biological systems one could assume that reductionist approaches may not fully describe biological complexity. Instead, tools such as mathematical modeling, network analysis, and other multiplexed clinical- and research-oriented tests enable rapid analyses of high-throughput data parsed at the genomic, proteomic, metabolomic, and physiomic levels. A physiomic-level approach allows for recursive horizontal and vertical integration of subsystem coupling across and within spatiotemporal scales. Additionally, this methodology recognizes previously ignored subsystems and the strong, nonintuitively obvious and indirect connections among physiological events that potentially account for the uncertainties in medicine. In this review, we flip the reductionist research paradigm and review the concept of systems biology and its applications to bone pathophysiology. Specifically, a bone-centric physiome model is presented that incorporates systemic-level processes with their respective therapeutic implications. © 2010 New York Academy of Sciences.

Current challenges and problems in teaching pathophysiology in Ukraine - another reaction to Churilov's paper.

PubMed

Ataman, Oleksandr V

2017-12-01

Pathophysiology in Ukraine has rich traditions and achievements in the scientific areas, as well as in teaching academic discipline. Its history, the main Ukrainian scientific schools and their famous representatives are briefly described. The content of existing study program, the main approaches to teaching, and some methodological and organizational problems needed to be solved are characterized. The necessity and usefulness of developing and implementing the three separate courses of discipline (Essential, Clinical and Advanced Pathophysiology) are substantiated. The place of Pathophysiology in the training of physicians with different kinds of their future activity is discussed. Relation of teaching Pathophysiology to Translational and Personalized Medicine is tried to be shown.

Rabies: changing prophylaxis and new insights in pathophysiology.

PubMed

Ugolini, Gabriella; Hemachudha, Thiravat

2018-02-01

Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert. Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible. Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.

Obesity: Pathophysiology and Intervention

PubMed Central

Zhang, Yi; Liu, Ju; Yao, Jianliang; Ji, Gang; Qian, Long; Wang, Jing; Zhang, Guansheng; Tian, Jie; Nie, Yongzhan; Zhang, Yi Edi.; Gold, Mark S.; Liu, Yijun

2014-01-01

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity. PMID:25412152

Reform in Teaching Preclinical Pathophysiology

ERIC Educational Resources Information Center

Li, Yong-Yu; Li, Kun; Yao, Hong; Xu, Xiao-Juan; Cai, Qiao-Lin

2015-01-01

Pathophysiology is a scientific discipline that studies the onset and progression of pathological conditions and diseases, and pathophysiology is one of the core courses in most preclinical medical curricula. In China, most medical schools house a Department of Pathophysiology, in contrast to medical schools in many developed countries. The staff…

Multicenter pathophysiologic investigation of erectile dysfunction in clinic outpatients in China.

PubMed

Li, Dongjie; Jiang, Xianzhen; Zhang, Xiaobo; Yi, Lu; Zhu, Xiangsheng; Zeng, Xiangyang; Guo, Xiaoliang; Tang, Yuxin

2012-03-01

To assess the pathophysiologic composition and age structure of erectile dysfunction (ED) in men visiting outpatient clinics in China. We studied 3327 consecutive ED outpatients (median age 39 years) from 2006 to 2010 in the 5 training hospitals in China. Every patient was independently evaluated by an experienced urologist/andrologist using comprehensive diagnostic procedures. The simplified International Index of Erectile Function was used to assess the severity of ED. Most patients (95.0%) were <60 years old, and none were >70 years old. The psychogenic patients were younger and had greater percentage than any other patients. Vasculogenic factors were a major etiology of organic ED. A significant difference was found in the age distribution between the patients with psychogenic ED and those with organic ED (P = .000). Diabetes, hypertension, coronary artery disease, and hyperlipidemia played significant roles in affecting the severity of ED in a statistical model, including age. The International Index of Erectile Function scores decreased with age (rs = -0.199, P = .000). Moreover, the percentage of severe and moderate cases increased with age (P = .003 and P = .002, respectively). However, the constituent ratio of patients sharply declined from 30.3% to 4.5% with age. The number of men visiting outpatient clinics with psychological ED is greater than the number with organic causes in China. The age of the Chinese patients with ED who seek medical help is young and this is mainly because of inadequate sex education to young men and because most older patients are reluctant to visit the hospital just for the loss of erectile function. Copyright © 2012 Elsevier Inc. All rights reserved.

Etiology of ejaculation and pathophysiology of premature ejaculation.

PubMed

Donatucci, Craig F

2006-09-01

Ejaculation is comprised of three stages of the male sexual response cycle, namely emission, ejection, and orgasm; however, in comparison with erection, which is a well-understood component of male sexual response, the pathophysiology of ejaculation has yet to be fully delineated. Premature ejaculation (PE), the most common sexual disorder in men, while believed to have a multifactorial etiology, is even less well understood. This article reviews the physiology of ejaculation, and the multifactorial pathophysiology of PE. The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24-26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. There were 16 invited presenters and discussants; the group focused on several educational objectives. Data were obtained by extensive examination of published peer-reviewed literature. Evidence supports that biologic mechanisms associated with neurotransmitters such as norepinephrine, serotonin, oxytocin, Gamma-amino-butyric acid, and nitric oxide (NO) as well as the hormone estrogen play central roles in ejaculation, and subsequently may mediate PE. There is also emerging evidence to show that hyperthyroidism may be a causal factor in PE. Recent data also suggest that psychogenic factors include high level of any experience by some men with PE. The pathophysiology of both lifelong and acquired PE appears to be both neurobiogenic and psychogenic. While psychogenic factors appear to be contributory to PE, pharmacologic intervention of PE can modify intravaginal ejaculatory latency time (IELT), which suggests that IELT is a biological variable, and is likely biologically dependent upon neurotransmitters and hormones.

Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus

PubMed Central

Abell, Sally K.; De Courten, Barbora; Boyle, Jacqueline A.; Teede, Helena J.

2015-01-01

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. PMID:26110385

PULMONARY PATHOPHYSIOLOGY AND LUNG MECHANICS IN ANESTHESIOLOGY: A CASE-BASED OVERVIEW

PubMed Central

Vidal Melo, Marcos F.; Musch, Guido; Kaczka, David W.

2012-01-01

The induction and maintenance of anesthesia, surgical requirements, and patients’ unique pathophysiology all combine to create a setting in which our accumulated knowledge of respiratory physiology and lung mechanics take on immediate and central importance in patient management. In this review we will take a case-based approach to illustrate how the complex interactions between anesthesia, surgery, and patient disease impact patient care with respect to pulmonary pathophysiology and clinical decision-making. We will examine two disparate scenarios: a patient with chronic obstructive pulmonary disease undergoing a lung resection, and a patient with coronary artery disease undergoing cardiopulmonary bypass. In each example we will illustrate how important concepts in pulmonary physiology and respiratory mechanics impact clinical management decisions. PMID:23089508

Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses

PubMed Central

Beule, Achim G.

2011-01-01

In this review, anatomy and physiology of the respiratory mucosa of nose and paranasal sinuses are summarized under the aspect of its clinical significance. Basics of endonasal cleaning including mucociliary clearance and nasal reflexes, as well as defence mechanisms are explained. Physiological wound healing, aspects of endonasal topical medical therapy and typical diagnostic procedures to evaluate the respiratory functions are presented. Finally, the pathophysiologies of different subtypes of non-allergic rhinitis are outlined together with treatment recommendations. PMID:22073111

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

PubMed Central

Unal, Hamiyet; Kemp, Jacqueline R.; Tirupula, Kalyan C.; Eguchi, Satoru; Vanderheyden, Patrick M. L.; Thomas, Walter G.

2015-01-01

The renin angiotensin system (RAS) produced hormone peptides regulate many vital body functions. Dysfunctional signaling by receptors for RAS peptides leads to pathologic states. Nearly half of humanity today would likely benefit from modern drugs targeting these receptors. The receptors for RAS peptides consist of three G-protein–coupled receptors—the angiotensin II type 1 receptor (AT1 receptor), the angiotensin II type 2 receptor (AT2 receptor), the MAS receptor—and a type II trans-membrane zinc protein—the candidate angiotensin IV receptor (AngIV binding site). The prorenin receptor is a relatively new contender for consideration, but is not included here because the role of prorenin receptor as an independent endocrine mediator is presently unclear. The full spectrum of biologic characteristics of these receptors is still evolving, but there is evidence establishing unique roles of each receptor in cardiovascular, hemodynamic, neurologic, renal, and endothelial functions, as well as in cell proliferation, survival, matrix-cell interaction, and inflammation. Therapeutic agents targeted to these receptors are either in active use in clinical intervention of major common diseases or under evaluation for repurposing in many other disorders. Broad-spectrum influence these receptors produce in complex pathophysiological context in our body highlights their role as precise interpreters of distinctive angiotensinergic peptide cues. This review article summarizes findings published in the last 15 years on the structure, pharmacology, signaling, physiology, and disease states related to angiotensin receptors. We also discuss the challenges the pharmacologist presently faces in formally accepting newer members as established angiotensin receptors and emphasize necessary future developments. PMID:26315714

Sickle cell dehydration: Pathophysiology and therapeutic applications.

PubMed

Brugnara, Carlo

2018-01-01

Cell dehydration is a distinguishing characteristic of sickle cell disease and an important contributor to disease pathophysiology. Due to the unique dependence of Hb S polymerization on cellular Hb S concentration, cell dehydration promotes polymerization and sickling. In double heterozygosis for Hb S and C (SC disease) dehydration is the determining factor in disease pathophysiology. Three major ion transport pathways are involved in sickle cell dehydration: the K-Cl cotransport (KCC), the Gardos channel (KCNN4) and Psickle, the polymerization induced membrane permeability, most likely mediated by the mechano-sensitive ion channel PIEZO1. Each of these pathways exhibit unique characteristics in regulation by oxygen tension, intracellular and extracellular environment, and functional expression in reticulocytes and mature red cells. The unique dependence of K-Cl cotransport on intracellular Mg and the abnormal reduction of erythrocyte Mg content in SS and SC cells had led to clinical studies assessing the effect of oral Mg supplementation. Inhibition of Gardos channel by clotrimazole and senicapoc has led to Phase 1,2,3 trials in patients with sickle cell disease. While none of these studies has resulted in the approval of a novel therapy for SS disease, they have highlighted the key role played by these pathways in disease pathophysiology.

Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension.

PubMed

Di Giosia, Paolo; Giorgini, Paolo; Stamerra, Cosimo Andrea; Petrarca, Marco; Ferri, Claudio; Sahebkar, Amirhossein

2018-02-14

This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events. Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause. Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.

Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy.

PubMed

Klimczak, Dominika; Jazdzewski, Krystian; Kuch, Marek

2017-02-01

Multiple factors underlie the pathophysiology of hypertension, involving endothelial dysregulation, vascular smooth muscle dysfunction, increased oxidative stress, sympathetic nervous system activation and altered renin -angiotensin -aldosterone regulatory activity. A class of non-coding RNA called microRNA, consisting of 17-25 nucleotides, exert regulatory function over these processes. This paper summarizes the currently available data from preclinical and clinical studies on miRNA in the development of hypertension as well as the impact of anti-hypertensive treatment on their plasma expression. We present microRNAs' characteristics, their biogenesis and role in the regulation of blood pressure together with their potential diagnostic and therapeutic application in clinical practice.

Evaluation of an online, case-based interactive approach to teaching pathophysiology.

PubMed

Van Dijken, Pieter Canham; Thévoz, Sara; Jucker-Kupper, Patrick; Feihl, François; Bonvin, Raphaël; Waeber, Bernard

2008-06-01

The aim of this study was to evaluate a new pedagogical approach in teaching fluid, electrolyte and acid-base pathophysiology in undergraduate students. This approach comprises traditional lectures, the study of clinical cases on the web and a final interactive discussion of these cases in the classroom. When on the web, the students are asked to select laboratory tests that seem most appropriate to understand the pathophysiological condition underlying the clinical case. The percentage of students having chosen a given test is made available to the teacher who uses it in an interactive session to stimulate discussion with the whole class of students. The same teacher used the same case studies during 2 consecutive years during the third year of the curriculum. The majority of students answered the questions on the web as requested and evaluated positively their experience with this form of teaching and learning. Complementing traditional lectures with online case-based studies and interactive group discussions represents, therefore, a simple means to promote the learning and the understanding of complex pathophysiological mechanisms. This simple problem-based approach to teaching and learning may be implemented to cover all fields of medicine.

Hypothyroid myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature.

PubMed

Sindoni, Alessandro; Rodolico, Carmelo; Pappalardo, Maria Angela; Portaro, Simona; Benvenga, Salvatore

2016-12-01

Abnormalities in thyroid function are common endocrine disorders that affect 5-10 % of the general population, with hypothyroidism occurring more frequently than hyperthyroidism. Clinical symptoms and signs are often nonspecific, particularly in hypothyroidism. Muscular symptoms (stiffness, myalgias, cramps, easy fatigability) are mentioned by the majority of patients with frank hypothyroidism. Often underestimated is the fact that muscle symptoms may represent the predominant or the only clinical manifestation of hypothyroidism, raising the issue of a differential diagnosis with other causes of myopathy, which sometimes can be difficult. Elevated serum creatine kinase, which not necessarily correlates with the severity of the myopathic symptoms, is certainly suggestive of muscle impairment, though it does not explain the cause. Rare muscular manifestations, associated with hypothyroidism, are rhabdomyolysis, acute compartment syndrome, Hoffman's syndrome and Kocher-Debré-Sémélaigne syndrome. Though the pathogenesis of hypothyroid myopathy is not entirely known, proposed mechanisms include altered glycogenolytic and oxidative metabolism, altered expression of contractile proteins, and neuro-mediated damage. Correlation studies of haplotype, muscle gene expression and protein characterization, could help understanding the pathophysiological mechanisms of this myopathic presentation of hypothyroidism.

The pathophysiology of delayed ejaculation

PubMed Central

2016-01-01

Delayed ejaculation (DE) is probably least studied, and least understood of male sexual dysfunctions, with an estimated prevalence of 1–4% of the male population. Pathophysiology of DE is multifactorial and including psychosexual-behavioral and cultural factors, disruption of ejaculatory apparatus, central and peripheral neurotransmitters, hormonal or neurochemical ejaculatory control and psychosocial factors. Although knowledge of the physiology of the DE has increased in the last two decade, our understanding of the different pathophysiological process of the causes of DE remains limited. To provide a systematic update on the pathophysiology of DE. A systematic review of Medline and PubMed for relevant publications on ejaculatory dysfunction (EjD), DE, retarded ejaculation, inhibited ejaculation, and climax was performed. The search was limited to the articles published between the January 1960 and December 2015 in English. Of 178 articles, 105 were selected for this review. Only those publications relevant to the pathophysiology, epidemiology and prevalence of DE were included. The pathophysiology of DE involves cerebral sensory areas, motor centers, and several spinal nuclei that are tightly interconnected. The biogenic, psychogenic and other factors strongly affect the pathophysiology of DE. Despite the many publications on this disorder, there still is a paucity of publications dedicated to the subject. PMID:27652227

Thyroid stimulating hormone suppression post-therapy in patients with Graves' disease: a systematic review of pathophysiology and clinical data.

PubMed

Yu, Huan; Farahani, Pendar

2015-04-08

Post-treatment hypothyroidism is common in Graves' disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves' disease. A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves' disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII positivity is associated with lower likelihood of TSH

Translational systems biology: introduction of an engineering approach to the pathophysiology of the burn patient.

PubMed

An, Gary; Faeder, James; Vodovotz, Yoram

2008-01-01

The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.

Pathophysiology and management of pediatric ascites.

PubMed

Sabri, Mahmoud; Saps, Miguel; Peters, John M

2003-06-01

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

Chemical sensitivity: pathophysiology or pathopsychology?

PubMed

Genuis, Stephen J

2013-05-01

Escalating numbers of people throughout the world are presenting to primary care physicians, allergists, and immunologists with myriad clinical symptoms after low-level exposure to assorted everyday chemicals such as smoke, perfumes, air fresheners, paints, glues, and other products. This clinical state is referred to by various diagnostic labels, including multiple chemical sensitivity disorder, environmental intolerance, chemical sensitivity (CS), and sensitivity-related illness, and has been the subject of much controversy within the health care community. The goal of this study was to provide a brief overview of the etiology, pathogenesis, clinical presentation, and management of CS. An evaluation of the medical community's response to this emerging diagnosis was also explored. This review was prepared by assessing available medical and scientific literature from MEDLINE, as well as by reviewing numerous books, toxicology journals, conference proceedings, government publications, and environmental health periodicals. A primary observation, however, is that there is limited scientific literature available on the issue of CS. The format of a traditional integrated review was chosen because such reviews play a pivotal role in scientific research and professional practice in medical issues with limited primary study and uncharted clinical territory. The sensitization state of CS seems to be initiated by a significant toxic exposure, occurring as a 1-time event, or on surpassing a threshold of toxicity after toxicant accrual from repeated lower-level exposures. Once sensitized through a toxicant-induced loss of tolerance, individuals exposed to inciting triggers such as minute amounts of diverse everyday chemicals may experience various clinical and immune sequelae, sometimes involving lymphocyte, antibody, or cytokine responses. Precautionary avoidance of inciting triggers will prevent symptoms, and desensitization immunotherapy or immune suppression may improve

The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

PubMed

Derksen, V F A M; Huizinga, T W J; van der Woude, D

2017-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

[Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations].

PubMed

von Arx, Thomas; Lozanoff, Scott; Zinkernagel, Martin

2014-01-01

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

PubMed Central

Leclerc, Jenna L.; Garcia, Joshua M.; Diller, Matthew A.; Carpenter, Anne-Marie; Kamat, Pradip K.; Hoh, Brian L.; Doré, Sylvain

2018-01-01

Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the different approaches to simulating SAH in rodents, in particular elucidating the key pathophysiology of the various methods and models. Ultimately, we suggest the development of standardized model of rodent SAH that better replicates human pathophysiology for moving forward with translational research. PMID:29623028

[Pathophysiology of sickle cell disease].

PubMed

Elion, J; Laurance, S; Lapouméroulie, C

2010-12-01

It has been 100 years since Herrick published the first medical case report of sickle cell disease. In 1949, Pauling discovered hemoglobin S (HbS). As early as the 1960-70s, emerged a coherent detailed molecular-level description of pathophysiology of sickle disease. It involved polymerization of deoxyhemoglobin S with formation of long fibers inside red blood cells (RBC) causing a distorted sickle shape and shortened lifespan. These changes constitute the basic disease process and account for hemolytic anemia and for obstructive events underlying vasoocclusive crises (VOC). However, they do not explain the mechanisms that trigger VOC. The purpose of this review is to present recent data on dehydration of sickle cell RBC, abnormalities in RBC adhesion to the vascular endothelium, the role of inflammatory events and of activation of all cells in the vessel, and abnormalities of vascular tone and carbon monoxide metabolism. These data provide new insight into the pathophysiology of the first molecular disease.

Gender aspects in heart failure. Pathophysiology and medical therapy.

PubMed

Regitz-Zagrosek, V; Lehmkuhl, E; Lehmkuhl, H B; Hetzer, R

2004-09-01

Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology and lead to differences in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and post-menopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic HF is different in both genders. Medical therapy in heart failure has usually not been specified according to gender and gender specific analysis has been neglected in most large survival trials. Only a post-hoc analysis of gender differences led to the recognition of increased mortality with digitalis therapy in women. Single studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor blockers did not reach significant end points in women whereas meta-analyses showed overall positive effects. Side effects of ACEI are more common and pharmacokinetics of beta-blockers are different in women. Angiotensin receptor blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be particularly advantageous in postmenopausal women in whom the natural modulation of the RAS by estrogens is lost.

Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis.

PubMed

Skyler, Jay S; Bakris, George L; Bonifacio, Ezio; Darsow, Tamara; Eckel, Robert H; Groop, Leif; Groop, Per-Henrik; Handelsman, Yehuda; Insel, Richard A; Mathieu, Chantal; McElvaine, Allison T; Palmer, Jerry P; Pugliese, Alberto; Schatz, Desmond A; Sosenko, Jay M; Wilding, John P H; Ratner, Robert E

2017-02-01

The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment. © 2017 by the American Diabetes Association.

Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis

PubMed Central

Bakris, George L.; Groop, Per-Henrik; Handelsman, Yehuda; Insel, Richard A.; Mathieu, Chantal; Palmer, Jerry P.; Pugliese, Alberto; Sosenko, Jay M.; Ratner, Robert E.

2017-01-01

The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, “The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis” on 10–12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment. PMID:27980006

Mitochondrial diabetes: molecular mechanisms and clinical presentation.

PubMed

Maassen, J Antonie; 'T Hart, Leen M; Van Essen, Einar; Heine, Rob J; Nijpels, Giel; Jahangir Tafrechi, Roshan S; Raap, Anton K; Janssen, George M C; Lemkes, Herman H P J

2004-02-01

Mutations in mitochondrial DNA (mtDNA) associate with various disease states. A few mtDNA mutations strongly associate with diabetes, with the most common mutation being the A3243G mutation in the mitochondrial DNA-encoded tRNA(Leu,UUR) gene. This article describes clinical characteristics of mitochondrial diabetes and its molecular diagnosis. Furthermore, it outlines recent developments in the pathophysiological and molecular mechanisms leading to a diabetic state. A gradual development of pancreatic beta-cell dysfunction upon aging, rather than insulin resistance, is the main mechanism in developing glucose intolerance. Carriers of the A3243G mutation show during a hyperglycemic clamp at 10 mmol/l glucose a marked reduction in first- and second-phase insulin secretion compared with noncarriers. The molecular mechanism by which the A3243G mutation affects insulin secretion may involve an attenuation of cytosolic ADP/ATP levels leading to a resetting of the glucose sensor in the pancreatic beta-cell, such as in maturity-onset diabetes of the young (MODY)-2 patients with mutations in glucokinase. Unlike in MODY2, which is a nonprogressive form of diabetes, mitochondrial diabetes does show a pronounced age-dependent deterioration of pancreatic function indicating involvement of additional processes. Furthermore, one would expect that all mtDNA mutations that affect ATP synthesis lead to diabetes. This is in contrast to clinical observations. The origin of the age-dependent deterioration of pancreatic function in carriers of the A3243G mutation and the contribution of ATP and other mitochondrion-derived factors such as reactive oxygen species to the development of diabetes is discussed.

Massive ovarian oedema: a misleading clinical entity.

PubMed

Machairiotis, Nikolaos; Stylianaki, Aikaterini; Kouroutou, Paraskevi; Sarli, Polixeni; Alexiou, Nikolaos Konstantinos; Efthymiou, Elias; Maras, Athanasios; Alexiou, Nikolaos Georgios; Nikolaou, Spyridon Evaggelos; Courcoutsakis, Nikolaos; Papakonstantinou, Eleni; Zarogoulidis, Paul; Barbetakis, Nikolaos; Paliouras, Dimitrios; Gogakos, Apostolos; Machairiotis, Christodoulos

2016-02-03

Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels

PubMed Central

Judd, Eric K.; Calhoun, David A.; Warnock, David G.

2015-01-01

Summary Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. The pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Existing dogma attributes the increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects in the distal nephron. However, emerging research, which has identified and has begun to define the function of amiloride-sensitive sodium channels and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. This review integrates these findings to better define the role of the vasculature and aldosterone in the pathophysiology of resistant hypertension. In addition, a brief guide to the treatment of resistant hypertension is presented. PMID:25416662

Pathophysiology and treatment of resistant hypertension: the role of aldosterone and amiloride-sensitive sodium channels.

PubMed

Judd, Eric K; Calhoun, David A; Warnock, David G

2014-01-01

Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. The pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Existing dogma attributes the increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects in the distal nephron. However, emerging research, which has identified and has begun to define the function of amiloride-sensitive sodium channels and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. This review integrates these findings to better define the role of the vasculature and aldosterone in the pathophysiology of resistant hypertension. In addition, a brief guide to the treatment of resistant hypertension is presented.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected].

PubMed

Karnik, Sadashiva S; Unal, Hamiyet; Kemp, Jacqueline R; Tirupula, Kalyan C; Eguchi, Satoru; Vanderheyden, Patrick M L; Thomas, Walter G

2015-10-01

The renin angiotensin system (RAS) produced hormone peptides regulate many vital body functions. Dysfunctional signaling by receptors for RAS peptides leads to pathologic states. Nearly half of humanity today would likely benefit from modern drugs targeting these receptors. The receptors for RAS peptides consist of three G-protein-coupled receptors—the angiotensin II type 1 receptor (AT1 receptor), the angiotensin II type 2 receptor (AT2 receptor), the MAS receptor—and a type II trans-membrane zinc protein—the candidate angiotensin IV receptor (AngIV binding site). The prorenin receptor is a relatively new contender for consideration, but is not included here because the role of prorenin receptor as an independent endocrine mediator is presently unclear. The full spectrum of biologic characteristics of these receptors is still evolving, but there is evidence establishing unique roles of each receptor in cardiovascular, hemodynamic, neurologic, renal, and endothelial functions, as well as in cell proliferation, survival, matrix-cell interaction, and inflammation. Therapeutic agents targeted to these receptors are either in active use in clinical intervention of major common diseases or under evaluation for repurposing in many other disorders. Broad-spectrum influence these receptors produce in complex pathophysiological context in our body highlights their role as precise interpreters of distinctive angiotensinergic peptide cues. This review article summarizes findings published in the last 15 years on the structure, pharmacology, signaling, physiology, and disease states related to angiotensin receptors. We also discuss the challenges the pharmacologist presently faces in formally accepting newer members as established angiotensin receptors and emphasize necessary future developments. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Growth and Development Symposium: Inflammation: Role in the etiology and pathophysiology of clinical mastitis in dairy cows.

PubMed

Ballou, M A

2012-05-01

Genetic selection for increased milk production in dairy cattle was not associated with an attenuated inflammatory response. The systemic and local inflammatory responses contribute to altered metabolism, reduced production performance, and increased cull rate of lactating dairy cows with clinical mastitis. More aggressive inflammatory responses were observed during the peripartum period when compared with cows in late lactation after an intramammary challenge with purified lipopolysaccharide. The epidemiology of clinical mastitis indicates that the greatest incidence is observed during the peripartum period; therefore, an enhanced inflammatory response with concomitant suppression in other immune responses may be involved in the etiology and severity of the clinical mastitis observed in peripartum cows. Milk production losses and compositional changes are observed among all mammary quarters from a cow with clinical mastitis, but the responses are more severe and sustained among infected quarters. The infected mammary quarters reflect both the systemic and local reactions, whereas uninfected quarters represent only the systemic response. The systemic effects of the inflammatory response include reduced DMI, hyperthermia, and changes in whole-body nutrient partitioning affecting mammary epithelial substrate availability, whereas local inflammatory effects include energetic requirements of the increased inflammatory leukocyte pool, decreased synthetic capacity of mammary epithelium independent of substrate availability, and paracellular leakage of milk components from the alveolar lumen into the extracellular fluid. Research has focused on improving host immunological defenses, attenuating the inflammatory response, or improving the resolution of the disease state to limit the deleterious effects during clinical mastitis. This paper highlights the role inflammation plays in the etiology and pathophysiology of clinical mastitis as well as potential management

Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review.

PubMed

Lee, Mi Suk; Sohn, Kyungwoo; Kim, Yun Hee; Hwang, Min-Woo; Kwon, Young Kyu; Bae, Na Young; Chae, Han

2013-06-01

The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI)] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE) type had the highest digestive functions and the So-Eum (SE) type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.

Ocular toxoplasmosis: recent aspects of pathophysiology and clinical implications.

PubMed

Pleyer, Uwe; Schlüter, Dirk; Mänz, Martin

2014-01-01

Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome. © 2014 S. Karger AG, Basel.

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

PubMed Central

Stirnemann, Jérôme; Belmatoug, Nadia; Camou, Fabrice; Serratrice, Christine; Froissart, Roseline; Caillaud, Catherine; Levade, Thierry; Astudillo, Leonardo; Serratrice, Jacques; Brassier, Anaïs; Rose, Christian; Billette de Villemeur, Thierry; Berger, Marc G.

2017-01-01

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD—but also carriers of GBA1 mutation—have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat). PMID:28218669

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

PubMed

Slater, James; Rill, Velisar

2003-04-01

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United States and 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 sub-clinical disease. Electron-beam and spiral 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 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 disease.

Apogeotropic variant of lateral semicircular canal benign paroxysmal positional vertigo: is there a correlation between clinical findings, underlying pathophysiologic mechanisms and the effectiveness of repositioning maneuvers?

PubMed

Riga, Maria; Korres, Stavros; Korres, George; Danielides, Vasilios

2013-08-01

The apogeotropic variant of horizontal semicircular canal (h-SCC) benign paroxysmal positional vertigo (BPPV) is attributed to canalithiasis of the anterior arm or cupulolithiasis. This study is an attempt to distinguish the most effective maneuvers for each case, by investigating any correlation, between the clinical findings or the treatment options and the possible location of the displaced debris. A review of the literature (1990-2012) was conducted via the PubMed database with the search terms "apogeotropic nystagmus and benign paroxysmal positional vertigo." Articles on central nervous system lesions were excluded. The studies included in the analysis provided detailed diagnostic and therapeutic protocols, supported by the resolution of the signs and symptoms through repositioning maneuvers. Descriptive statistics were used to summarize the findings. Intergroup and intragroup comparisons were performed through Pearson's χ or Fischer's exact test. Protocols vary considerably among studies. Nystagmus from seated to supine position is the best studied secondary clinical sign and possibly a clinical indication of cupulolithiasis. In patients with symmetrical responses in the head yaw test, no significant differences can be detected in the occurrence of secondary signs of lateralization compared to patients with asymmetrical responses. The Gufoni maneuver seems to be effective in all pathophysiologic types of apogeotropic h-SCC BPPV. The Barbeque and Vannucchi-Asprella maneuvers mainly target at lithiasis of the anterior ampullary arm. The results of this analysis may imply that different clinical subgroups of h-SCC BPPV may regard to different pathophysiologic and therapeutical mechanisms.

Pathophysiological insights in sickle cell disease.

PubMed

Odièvre, Marie-Hélène; Verger, Emmanuelle; Silva-Pinto, Ana Cristina; Elion, Jacques

2011-10-01

The first coherent pathophysiological scheme for sickle cell disease (SCD) emerged in the sixties-seventies based on an extremely detailed description of the molecular mechanism by which HbS in its deoxy-form polymerises and forms long fibres within the red blood cell that deform it and make it fragile. This scheme explains the haemolytic anaemia, and the mechanistic aspects of the vaso-occlusive crises (VOCs), but, even though it constitutes the basic mechanism of the disease, it does not account for the processes that actually trigger VOCs. This paper reviews recent data which imply: red blood cell dehydration, its abnormal adhesion properties to the endothelium, the participation of inflammatory phenomenon and of a global activation of all the cells present in the vessel, and finally, abnormalities of the vascular tone and of nitric oxide metabolism. These data altogether have shed a new light on the pathophysiology of the first molecular disease i.e. sickle cell disease.

CFTR, bicarbonate, and the pathophysiology of cystic fibrosis.

PubMed

Borowitz, Drucy

2015-10-01

The gene that encodes for the cystic fibrosis transmembrane regulator protein (CFTR) was identified in 1989, yet major pathophysiologic questions remain unanswered. There is emerging evidence that CFTR is a bicarbonate channel, a driver of chloride-bicarbonate exchange and through its action on local pH, a regulator of other ion channels and of proteins that function optimally in a neutral environment. In both the respiratory and gastrointestinal (GI) tracts, bicarbonate drives ionic content and fluid on epithelial surfaces, allows mucins to unfold and become slippery, and contributes to innate immunity. In the GI tract bicarbonate neutralizes gastric acid to support digestion and absorption. When CFTR is dysfunctional, lack of bicarbonate secretion disrupts these normal processes and thus leads directly to the clinical symptoms and signs of CF. This article synthesizes evidence from cell, animal, and human investigations that support these concepts. Bicarbonate secretion does not seem to be the same in all tissues and varies with physiologic demand. Thus, tissue type and whether conditions are baseline or stimulated needs to be taken into account when evaluating the evidence concerning the role of bicarbonate in the pathophysiology of CF as a regulator of local pH. Basic and applied research that focuses on the role of CFTR-mediated bicarbonate secretion helps explain many of the diverse clinical manifestations that are CF. © 2015 Wiley Periodicals, Inc.

The pathophysiology of transfusional iron overload.

PubMed

Porter, John B; Garbowski, Maciej

2014-08-01

The pathophysiologic consequences of transfusional iron overload (TIO) as well as the benefits of iron chelation therapy are best described in thalassemia major, although TIO is increasingly seen in other clinical settings. These consequences broadly reflect the levels and distribution of excess storage iron in the heart, endocrine tissues, and liver. TIO also increases the risk of infection, due to increased availability of labile iron to microorganisms. The authors suggest that extrahepatic iron distribution, and hence toxicity, is influenced by balance between generation of nontransferrin-bound iron from red cell catabolism and the utilization of transferrin iron by the erythron. Copyright © 2014 Elsevier Inc. All rights reserved.

Pathophysiology of osteoporosis: new mechanistic insights.

PubMed

Armas, Laura A G; Recker, Robert R

2012-09-01

Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Barrett’s esophagus in 2016: From pathophysiology to treatment

PubMed Central

Martinucci, Irene; de Bortoli, Nicola; Russo, Salvatore; Bertani, Lorenzo; Furnari, Manuele; Mokrowiecka, Anna; Malecka-Panas, Ewa; Savarino, Vincenzo; Savarino, Edoardo; Marchi, Santino

2016-01-01

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE. PMID:27158534

The rise of pathophysiologic research in the United States: the role of two Harvard hospitals.

PubMed

Tishler, Peter V

2013-01-01

Pathophysiologic research, the major approach to understanding and treating disease, was created in the 20th century, and two Harvard-affiliated hospitals, the Peter Bent Brigham Hospital and Boston City Hospital, played a key role in its development. After the Flexner Report of 1910, medical students were assigned clinical clerkships in teaching hospitals. Rockefeller-trained Francis Weld Peabody, who was committed to investigative, pathophysiologic research, was a critical leader in these efforts. At the Brigham, Harvard medical students observed patients closely and asked provocative questions about their diseases. Additionally, physicians returned from World War I with questions concerning the pathophysiology of wartime injuries. At the Boston City Hospital's new Thorndike Memorial Laboratory, Peabody fostered investigative question-based research by physicians. These physicians expanded pathophysiologic investigation from the 1920s. Post-war, Watson and Crick's formulation of the structure of DNA led shortly to modern molecular biology and new research approaches that are being furthered at the Boston Hospitals.

Pathophysiology of renal denervation procedures: from renal nerve anatomy to procedural parameters.

PubMed

Ammar, Sonia; Ladich, Elena; Steigerwald, Kristin; Deisenhofer, Isabel; Joner, Michael

2013-05-01

Endovascular renal denervation techniques have been clinically adopted for the treatment of resistant arterial hypertension with great success. Despite the favourable early results achieved with this technology, a clear understanding of the pathophysiology underlying this novel treatment is lacking. In addition, non-responsiveness to renal denervation remains a nidus for treatment failure in distinct patients. In search of meaningful surrogate parameters relating to treatment responsiveness, the current article reviews the existing knowledge on renal nerve anatomy, changes occurring after denervation and procedural parameters collected during denervation. From preclinical experience, the most reliable morphological parameter reflecting successful renal denervation is the presence of axonal degeneration. Most procedural and clinical parameters need extended investigation before adopting them as potential surrogate parameters for successful renal denervation. As a consequence, there is an imperative need for dedicated research revealing the pathophysiology of renal denervation procedures. In this regard, close co-operation of engineers, researchers and clinicians is warranted to turn renal denervation into a milestone treatment of arterial hypertension.

Prevalence, pathophysiological mechanisms and factors affecting urolithiasis.

PubMed

Khan, Aslam

2018-05-01

The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi. In this review, composition of kidney stones, its prevalence/incidence, explanation of pathophysiological mechanisms and role of various factors; urinary pH, uric acid, parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin, matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm-Horsfall protein, inter-α-inhibitors, have been discussed in detail.

The role of beta-endorphin in the pathophysiology of major depression.

PubMed

Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N

2009-10-01

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta

Constipation: Pathophysiology and Current Therapeutic Approaches.

PubMed

Sharma, Amol; Rao, Satish

2017-01-01

Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

Central Sensitivity Syndromes: Mounting Pathophysiologic Evidence to Link Fibromyalgia with other Common Chronic Pain Disorders

PubMed Central

Kindler, Lindsay L.; Bennett, Robert M.; Jones, Kim D.

2009-01-01

Objective To review emerging data from the fields of nursing, rheumatology, dentistry, gastroenterology, gynecology, neurology, and orthopedics that supports or disputes pathophysiologic similarities in pain syndromes studied by each specialty. Methods A literature search was performed through PubMed and Ovid using the terms fibromyalgia, temporomandibular joint disorder, irritable bowel syndrome, irritable bladder/interstitial cystitis, headache, chronic low back pain, chronic neck pain, functional syndromes and somatization. Each term was linked with pathophysiology and/or central sensitization. This paper presents a review of relevant articles with a specific goal of identifying pathophysiological findings related to nociceptive processing. Results The extant literature presents considerable overlap in the pathophysiology of these diagnoses. Given the psychosomatic lens through which many of these disorders are viewed, demonstration of evidence based links supporting shared pathophysiology between these disorders could provide direction to clinicians and researchers working to treat these diagnoses. Conclusions Central sensitivity syndromes denotes an emerging nomenclature that could be embraced by researchers investigating each of these disorders. Moreover, a shared paradigm would be useful in promoting cross-fertilization between researchers. Scientists and clinicians could most effectively forward the understanding and treatment of fibromyalgia and other common chronic pain disorders through an appreciation of their shared pathophysiology. PMID:21349445

Translational Systems Biology and Voice Pathophysiology

PubMed Central

Li, Nicole Y. K.; Abbott, Katherine Verdolini; Rosen, Clark; An, Gary; Hebda, Patricia A.; Vodovotz, Yoram

2011-01-01

Objectives/Hypothesis Personalized medicine has been called upon to tailor healthcare to an individual's needs. Evidence-based medicine (EBM) has advocated using randomized clinical trials with large populations to evaluate treatment effects. However, due to large variations across patients, the results are likely not to apply to an individual patient. We suggest that a complementary, systems biology approach using computational modeling may help tackle biological complexity in order to improve ultimate patient care. The purpose of the article is: 1) to review the pros and cons of EBM, and 2) to discuss the alternative systems biology method and present its utility in clinical voice research. Study Design Tutorial Methods Literature review and discussion. Results We propose that translational systems biology can address many of the limitations of EBM pertinent to voice and other health care domains, and thus complement current health research models. In particular, recent work using mathematical modeling suggests that systems biology has the ability to quantify the highly complex biologic processes underlying voice pathophysiology. Recent data support the premise that this approach can be applied specifically in the case of phonotrauma and surgically induced vocal fold trauma, and may have particular power to address personalized medicine. Conclusions We propose that evidence around vocal health and disease be expanded beyond a population-based method to consider more fully issues of complexity and systems interactions, especially in implementing personalized medicine in voice care and beyond. PMID:20025041

Pathophysiology and implications of intradialytic hypertension.

PubMed

Van Buren, Peter Noel

2017-07-01

Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess. Intradialytic hypertension patients have lower albumin and predialysis urea nitrogen levels, which may contribute to small reductions in osmolarity that prevents blood pressure decreases. Intradialytic vascular resistance surges remain implicated as the driving force for blood pressure increases, but mediators other than endothelin-1 may be responsible. Beyond dry weight reduction, the only controlled intervention shown to interrupt the blood pressure increase is lowering dialysate sodium. Patients with recurrent intradialytic hypertension should be identified as high-risk patients. Dry weight should be re-evaluated, even if patients do not clinically appear volume overloaded. Antihypertensive drugs should be prescribed because of the persistently elevated ambulatory blood pressure. Dialysate sodium reduction should be considered, although the long term effects of this intervention are uncertain.

Rotator Cuff Tear Arthropathy: Pathophysiology, Imaging Characteristics, and Treatment Options.

PubMed

Eajazi, Alireza; Kussman, Steve; LeBedis, Christina; Guermazi, Ali; Kompel, Andrew; Jawa, Andrew; Murakami, Akira M

2015-11-01

The purpose of this article is to review the biomechanical properties of the rotator cuff and glenohumeral joint and the pathophysiology, imaging characteristics, and treatment options of rotator cuff tear arthropathy (RCTA). Although multiple pathways have been proposed as causes of RCTA, the exact cause remains unclear. Increasing knowledge about the clinical diagnosis, imaging features, and indicators of severity improves recognition and treatment of this pathologic condition.

Posterior reversible encephalopathy syndrome in liver transplant patients: clinical presentation, risk factors and initial management.

PubMed

Cruz, R J; DiMartini, A; Akhavanheidari, M; Iacovoni, N; Boardman, J F; Donaldson, J; Humar, A; Bartynski, W S

2012-08-01

Posterior reversible encephalopathy syndrome (PRES) is an uncommon but well-known complication after transplantation diagnosed by characteristic radiological features. As limited data on this complex syndrome exist we sought to better define the incidence, clinical presentation and risk factors for PRES in liver transplant (LTx) patients. We conducted a retrospective analysis of 1923 adult LTx recipients transplanted between 2000 and 2010. PRES was diagnosed radiologically in 19 patients (1%), with 84% of cases occurring within 3 months post-LTX. We compared this cohort of PRES patients to 316 other LTx recipients also requiring radiographic imaging within 3 months after LTx for neurological symptoms. Seizure was the most common clinical manifestation in the PRES group (88% vs. 16%, p< 0.001) and 31% had an intracranial hemorrhage. Those with hemorrhage on imaging were more likely to be coagulopathic. PRES patients were significantly more likely to have had alcoholic liver disease and infection/sepsis. These factors may be related to a common pathway of vascular dysregulation/damage that appears to characterize this complex syndrome. Intracranial bleeding and seizures may be the end result of these phenomena. The relationship of these associated factors to the hypothesized pathophysiology of PRES is discussed. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hypertension: physiology and pathophysiology.

PubMed

Hall, John E; Granger, Joey P; do Carmo, Jussara M; da Silva, Alexandre A; Dubinion, John; George, Eric; Hamza, Shereen; Speed, Joshua; Hall, Michael E

2012-10-01

Despite major advances in understanding the pathophysiology of hypertension and availability of effective and safe antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic hypertension. Impaired renal-pressure natriuresis and chronic hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. © 2012 American Physiological Society

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

PubMed Central

McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira

2016-01-01

Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

PubMed Central

Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

2011-01-01

Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

[Pathophysiology and Prognostic Factors of Autoimmune Encephalitis].

PubMed

Prüß, H

2016-05-01

More and more forms of autoimmune encephalitis are being identified with the clinical spectrum ranging from epilepsy over movement disorders to psychosis. The increasing appreciation of clinical symptoms raises questions about the underlying pathophysiological mechanisms and prognostic factors. Numerous novel findings on the aetiology demonstrate that diverse tumours, but also infections of the central nervous system such as Herpes encephalitis can trigger autoimmune encephalitis. Antibodies against neuronal surface epitopes are directly pathogenic in the majority of cases. They act via binding and internalization of target proteins, receptor blockage, or activation of complement. Most relevant for the patients' prognosis are the type and titer of antibodies (e. g. against NMDA, GABA, AMPA receptors or voltage-gated potassium channel complexes), associated tumours, sufficiently aggressive immunotherapies, and imaging as well as cerebrospinal fluid biomarkers. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical presentation of familial exudative vitreoretinopathy.

PubMed

Ranchod, Tushar M; Ho, Lawrence Y; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

2011-10-01

To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. Case series, retrospective review. We included 273 eyes of 145 patients. Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. Demographics on presentation and clinical staging. Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, <1 month-49 years). A positive family history of FEVR was obtained in 18% of patients. A positive family history for ocular disease consistent with but not diagnosed as FEVR was obtained in an additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage 3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds were seen in 77 eyes, 64 of which were temporal or inferotemporal in location. The FEVR patient population is remarkable for the wide range of age at presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Copyright © 2011 American Academy of

The Effect of Self-Explanation of Pathophysiological Mechanisms of Diseases on Medical Students' Diagnostic Performance

ERIC Educational Resources Information Center

Peixoto, José Maria; Mamede, Sílvia; de Faria, Rosa Malena Delbone; Moura, Alexandre Sampaio; Santos, Silvana Maria Elói; Schmidt, Henk G.

2017-01-01

Self-explanation while diagnosing clinical cases fosters medical students' diagnostic performance. In previous studies on self-explanation, students were free to self-explain any aspect of the case, and mostly clinical knowledge was used. Elaboration on knowledge of pathophysiological mechanisms of diseases has been largely unexplored in studies…

The pathophysiology of lifelong premature ejaculation

PubMed Central

2016-01-01

For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

A Review of the Clinical Manifestations, Pathophysiology and Management of Opioid Bowel Dysfunction and Narcotic Bowel Syndrome

PubMed Central

Azizi, Zahra; Javid Anbardan, Sanam; Ebrahimi Daryani, Naser

2014-01-01

Opioids are widely used for the treatment of malignant and non-malignant pains. These medications are accompanied by adverse effects, in particular gastrointestinal symptoms known as opioid bowel dysfunction (OBD). The most common symptom of OBD is refractory constipation that is usually stable regardless of the use of laxatives. Narcotic bowel syndrome (NBS) is a subset of OBD described as ambiguous chronic pain aggravated by continual or increased opioid use for pain relief. Pathophysiology of these disorders are not definitely disentangled. Some challenging hypothesis have been posed leading to specific management in order to mitigate the adverse effects. This article is a review of the literature on the prevalence, pathophysiology and management of OBD and NBS. PMID:24829698

[SKIN PATHOLOGY IN DIABETES MELLITUS: CLINICAL AND PATHOPHYSIOLOGICAL CORRELATIONS (REVIEW)].

PubMed

Kochet, K; Lytus, I; Svistunov, I; Sulaieva, O

2017-12-01

Skin pathology is registered in vast majority of patients with diabetes mellitus (DM). Despite the abundance of publications on dermatological problems in DM, there is still a number of gaps to be discussed in terms of pathophysiological mechanisms. The goal of this review was to assess the mechanisms of development of different skin pathologies under DM. One of the key pathogenic mechanisms of skin lesions in diabetes is hyperglycemia and the effects of the advanced glycation end products, inducing oxidative stress, endothelial dysfunction and inflammation; that in its turn can accelerate the mechanisms of skin aging, the development of diabetic dermopathy and scleredema diabeticorum. Imbalance of growth factors, cytokines and hormones under insulin resistance, is associated with increased proliferation of keratinocytes, fibroblasts and sebocytes, mast cell dysfunction and melanogenesis disorders in acanthosis nigricans, acrochordons, acne and inflammatory dermatitis in diabetic patients. In addition, authors discuss the role of dendritic cells and macrophages dysfunction in impairment of peripheral tolerance and diabetic wounds pathogenesis in patients with DM.

Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

PubMed

Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David

2016-06-01

Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

Starry Sky Pattern in Hematopoietic Neoplasms: A Review of Pathophysiology and Differential Diagnosis.

PubMed

Dy-Ledesma, Janelyn L; Khoury, Joseph D; Agbay, Rose Lou Marie C; Garcia, Mar; Miranda, Roberto N; Medeiros, L Jeffrey

2016-11-01

The starry sky pattern is a distinctive histologic feature wherein a rapidly proliferating hematolymphoid neoplasm contains scattered histiocytes with abundant pale cytoplasm in a background of monomorphic neoplastic cells. The cytoplasm of these histiocytes typically contains cellular remnants, also known as tingible bodies, incorporated through active phagocytosis. Although common and widely recognized, relatively little is known about the pathophysiological underpinnings of the starry sky pattern. Its resemblance to a similar pattern seen in the germinal centers of secondary follicles suggests a possible starting point for understanding the molecular basis of the starry sky pattern and potential routes for its exploitation for therapeutic purposes. In this review, we discuss the historical, pathophysiological, and clinical implications of the starry sky pattern.

Pathophysiology of gadolinium-associated systemic fibrosis

PubMed Central

Drel, Viktor; Gorin, Yves

2016-01-01

Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis. PMID:27147669

[Pathophysiology and treatment of orofacial pain.

PubMed

Shinoda, Masamichi; Noma, Noboru

"Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms. Clinically, it is well known that the etiologic differential diagnosis which consists of careful history-taking and physical examination is essential for therapeutic decision in patients with orofacial pain. This report outlines the current knowledge on the pathophysiology, diagnosis, treatment of orofacial pain.

Deep brain stimulation for severe autism: from pathophysiology to procedure.

PubMed

Sinha, Saurabh; McGovern, Robert A; Sheth, Sameer A

2015-06-01

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

PubMed

Cho, Hyong Jin; Skowera, Anna; Cleare, Anthony; Wessely, Simon

2006-01-01

Chronic fatigue syndrome is a controversial condition especially concerning its clinical definition and aetiopathogenesis. Most recent research progress has been made in phenomenology and pathophysiology and we focused our review on these two areas. The phenomenology research supports the notion of a discrete fatigue syndrome which can be distinguished from depression and anxiety. The current case definition, however, may need an improvement based on empirical data. Recent advances in understanding the pathophysiology of chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis constitute other findings, but the question of whether these alterations are a cause or consequence of chronic fatigue syndrome still remains unanswered. Immune system involvement in the pathogenesis seems certain but the findings on the specific mechanisms are still inconsistent. Genetic studies provide some evidence of the syndrome being a partly genetic condition, but environmental effects seem to be still predominant and identification of specific genes is still at a very early stage. The recent findings suggest that further research is needed in improving the current case definition; investigating overlaps and boundaries among various functional somatic syndromes; answering the question of whether the pathophysiologic findings are a cause or consequence; and elucidating the involvement of the central nervous system, immune system and genetic factors.

Graph theory findings in the pathophysiology of temporal lobe epilepsy.

PubMed

Chiang, Sharon; Haneef, Zulfi

2014-07-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning.

PubMed

Rogge, M M

2001-01-01

Pathophysiology, heavily content driven, has typically been taught through the use of traditional behavioral pedagogy and a reliance on the formal lecture. The author describes the limitations of this approach to teaching pathophysiology and describes the use of narrative pedagogy and Socratic questioning as alternative methods of instruction to augment lecture methods. Specific strategies for transforming traditional classroom teaching by using Socratic questions in a pathophysiology course for nurse practitioners are described. Student and faculty reactions to the initial efforts to transform pathophysiology instruction are also described.

Post-Stroke Sleep-Disordered Breathing—Pathophysiology and Therapy Options

PubMed Central

Stevens, David; Martins, Rodrigo Tomazini; Mukherjee, Sutapa; Vakulin, Andrew

2018-01-01

Sleep-disordered breathing (SDB), encompassing both obstructive and central sleep apnea, is prevalent in at least 50% of stroke patients. Small studies have shown vast improvements in post-stroke functional recovery outcomes after the treatment of SDB by continuous positive airway pressure. However, compliance to this therapy is very poor in this complex patient group. There are alternative therapy options for SDB that may be more amenable for use in at least some post-stroke patients, including mandibular advancement, supine avoidance, and oxygen therapy. There are few studies, however, that demonstrate efficacy and compliance with these alternative therapies currently. Furthermore, novel SDB-phenotyping approaches may help to provide important clinical information to direct therapy selection in individual patients. Prior to realizing individualized therapy, we need a better understanding of the pathophysiology of SDB in post-stroke patients, including the role of inherent phenotypic traits, as well as the contribution of stroke size and location. This review summarizes the available literature on SDB pathophysiology and treatment in post-stroke patients, identifies gaps in the literature, and sets out areas for further research. PMID:29536012

Pediatric IBS: an overview on pathophysiology, diagnosis and treatment.

PubMed

Chogle, Ashish; Mintjens, Stijn; Saps, Miguel

2014-04-01

Irritable bowel syndrome (IBS) is a common disorder in children and adults. The pathogenesis and pathophysiology of IBS remains incompletely understood. The biopsychosocial model, which conceptualizes chronic pain as a dysregulation of the gut-brain-homeostasis with peripheral and central factors mutually influencing each other, is the most accepted framework to explain IBS. Twin and family aggregation studies suggest a genetic component that does not exclusively explain the higher prevalence of IBS in certain families. Social learning (environmental factors) and maladaptive coping predispose children to develop IBS with greater disability and more frequent medical consultations. Early-life events constitute an additional risk factor for the development of IBS and other functional gastrointestinal disorders (FGIDs). Children with a history of cow's milk protein hypersensitivity or abdominal surgeries have a higher prevalence of IBS and other FGIDs years later. IBS frequently follows an episode of acute gastrointestinal inflammation (infectious or non-infectious). This article discusses the importance, known pathophysiological mechanisms, clinical approach, and evidence-based therapeutic options for the management of IBS in children and adolescents. Copyright 2014, SLACK Incorporated.

Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways

PubMed Central

Balouch, Muhammad A.; Kolek, Matthew J.; Darbar, Dawood

2014-01-01

Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. Genetic approaches to understanding the pathophysiology of AF have led to the identification of several biological pathways important in the pathogenesis of the arrhythmia. These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. While common and rare genetic variants in these pathways are associated with increased susceptibility to AF, they differ substantially among patients with lone versus typical AF. Furthermore, how these pathways converge to a final common clinical phenotype of AF is unclear and might also vary among different patient populations. Here, we review the contemporary knowledge of AF pathogenesis and discuss how derangement in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis may contribute to this common and important clinical disorder. PMID:25054116

The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy.

PubMed

Bosi, Marcello; De Vito, Andrea; Gobbi, Riccardo; Poletti, Venerino; Vicini, Claudio

2017-03-01

The objective of this study is to highlight the importance of anatomical and not-anatomical factors' identification for customized therapy in OSAHS patients. The data sources are: MEDLINE, The Cochrane Library and EMBASE. A systematic review was performed to identify studies that analyze the role of multiple interacting factors involved in the OSAHS pathophysiology. 85 out of 1242 abstracts were selected for full-text review. A variable combinations pathophysiological factors contribute to realize differentiated OSAHS phenotypes: a small pharyngeal airway with a low resistance to collapse (increased critical closing pressure), an inadequate responses of pharyngeal dilator muscles (wakefulness drive to breathe), an unstable ventilator responsiveness to hypercapnia (high loop gain), and an increased propensity to wake related to upper airway obstruction (low arousal threshold). Identifying if the anatomical or not-anatomical factors are predominant in each OSAHS patient represents the current challenge in clinical practice, moreover for the treatment decision-making. In the future, if a reliable and accurate pathophysiological pattern for each OSAHS patient can be identified, a customized therapy will be feasible, with a significant improvement of surgical success in sleep surgery and a better understanding of surgical failure.

Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications

PubMed Central

Kim, Sangwon F.; Mollace, Vincenzo

2013-01-01

The nitric oxide (NO) and cyclooxygenase (COX) pathways share a number of similarities. Nitric oxide is the mediator generated from the NO synthase (NOS) pathway, and COX converts arachidonic acid to prostaglandins, prostacyclin, and thromboxane A2. Two major forms of NOS and COX have been identified to date. The constitutive isoforms critically regulate several physiological states. The inducible isoforms are overexpressed during inflammation in a variety of cells, producing large amounts of NO and prostaglandins, which may underlie pathological processes. The cross-talk between the COX and NOS pathways was initially reported by Salvemini and colleagues in 1993, when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous “receptor” targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. Since then, numerous studies have furthered our mechanistic understanding of these interactions in pathophysiological settings and delineated potential clinical outcomes. In addition, emerging evidence suggests that the canonical nitroxidative species (NO, superoxide, and/or peroxynitrite) modulate biosynthesis of prostaglandins through non-COX-related pathways. This article provides a comprehensive state-of-the art overview in this area. PMID:23389111

Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.

PubMed

Ellis, Demetrius

2015-01-01

Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.

Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice.

PubMed

Bondulich, Marie K; Jolinon, Nelly; Osborne, Georgina F; Smith, Edward J; Rattray, Ivan; Neueder, Andreas; Sathasivam, Kirupa; Ahmed, Mhoriam; Ali, Nadira; Benjamin, Agnesska C; Chang, Xiaoli; Dick, James R T; Ellis, Matthew; Franklin, Sophie A; Goodwin, Daniel; Inuabasi, Linda; Lazell, Hayley; Lehar, Adam; Richard-Londt, Angela; Rosinski, Jim; Smith, Donna L; Wood, Tobias; Tabrizi, Sarah J; Brandner, Sebastian; Greensmith, Linda; Howland, David; Munoz-Sanjuan, Ignacio; Lee, Se-Jin; Bates, Gillian P

2017-10-27

Huntington's disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Weekly administration from 5 to 11 weeks of age prevented body weight loss, skeletal muscle atrophy, muscle weakness, contractile abnormalities, the loss of functional motor units in EDL muscles and delayed end-stage disease. Inhibition of myostatin/activin A signaling activated transcriptional profiles to increase muscle mass in wild type and R6/2 mice but did little to modulate the extensive Huntington's disease-associated transcriptional dysregulation, consistent with treatment having little impact on HTT aggregation levels. Modalities that inhibit myostatin signaling are currently in clinical trials for a variety of indications, the outcomes of which will present the opportunity to assess the potential benefits of targeting this pathway in HD patients.

An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

PubMed

Hammer, Heinz F

2014-02-01

This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects

PubMed Central

Bilo, Grzegorz; Grillo, Andrea; Guida, Valentina; Parati, Gianfranco

2018-01-01

Morning hours are the period of the day characterized by the highest incidence of major cardiovascular events including myocardial infarction, sudden death or stroke. They are also characterized by important neurohormonal changes, in particular, the activation of sympathetic nervous system which usually leads to a rapid increase in blood pressure (BP), known as morning blood pressure surge (MBPS). It was hypothesized that excessive MBPS may be causally involved in the pathogenesis of cardiovascular events occurring in the morning by inducing hemodynamic stress. A number of studies support an independent relationship of MBPS with organ damage, cerebrovascular complications and mortality, although some heterogeneity exists in the available evidence. This may be due to ethnic differences, methodological issues and the confounding relationship of MBPS with other features of 24-hour BP profile, such as nocturnal dipping or BP variability. Several studies are also available dealing with treatment effects on MBPS and indicating the importance of long-acting antihypertensive drugs in this regard. This paper provides an overview of pathophysiologic, methodological, prognostic and therapeutic aspects related to MBPS. PMID:29872338

The pathophysiology of peptic ulcer disease.

PubMed

Brooks, F P

1985-11-01

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.

Extranasopharyngeal angiofibroma: clinical and radiological presentation.

PubMed

Szymańska, Anna; Szymański, Marcin; Morshed, Kamal; Czekajska-Chehab, Elżbieta; Szczerbo-Trojanowska, Małgorzata

2013-02-01

Nasopharyngeal angiofibroma (NA) is a rare, vascular tumor affecting adolescent males. Due to aggressive local growth, skull base location and risk of profound hemorrhage, NA is a challenge for surgeons. Angiofibromas have been sporadically described in extanasopharyngeal locations. We review ten cases of extranasopharyngeal angiofibroma (ENA) and discuss the incidence, clinical presentation and management of this pathology. The group consisted of 4 males and 5 females aged 8-49. There were 7 patients with nasal angiofibroma, 1 patient with laryngeal angiofibroma, 1 patient with oral angiofibroma and another patient with infratemporal fossa tumor. In patients with nasal angiofibroma most common presenting symptoms were nasal obstruction and epistaxis. Patients with laryngeal angiofibroma suffered from mild dysphagia and patients with the infratemporal fossa tumor had painless cheek swelling. In four patients with nasal tumor computed tomography (CT) demonstrated mass with strong to intermediate contrast enhancement. In one patient with nasal tumor carotid angiography demonstrated pathological vessels without intensive tumor blush. Infratemporal fossa tumor showed intensive contrast enhancement on CT and magnetic resonance imaging (MRI) scans, and abundant vascularity on angiography. Laryngeal and oral angiofibroma required no radiological imaging. Three nasal tumors were evaluated before introduction of CT to clinical practice. All patients underwent surgery. No recurrences developed. ENAs differ significantly from NAs regarding clinical and radiological presentations. They lack typical clinical and radiological features as they develop in all age groups and in females, may be less vascularised, arise from various sites and produce a variety of symptoms.

Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy.

PubMed

Mansilha, Armando; Sousa, Joel

2018-06-05

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies.

Pathophysiology of hypertension in obese children: a systematic review.

PubMed

Wirix, A J G; Kaspers, P J; Nauta, J; Chinapaw, M J M; Kist-van Holthe, J E

2015-10-01

Hypertension is increasingly common in overweight and obese children. The mechanisms behind the development of hypertension in obesity are complex, and evidence is limited. In order to effectively treat obese children for hypertension, it is important to have a deeper understanding of the pathophysiology of hypertension in obese children. The present review summarizes the main factors associated with hypertension in obese children and discusses their potential role in its pathophysiology. Systematic searches were conducted in PubMed and EMBASE for articles published up to October 2014. In total, 60 relevant studies were included. The methodological quality of the included studies ranged from weak to strong. Several factors important in the development of hypertension in obese children have been suggested, including endocrine determinants, such as corticosteroids and adipokines, sympathetic nervous system activity, disturbed sodium homeostasis, as well as oxidative stress, inflammation and endothelial dysfunction. Understanding the pathophysiology of hypertension in overweight and obese children is important and could have implications for its screening and treatment. Based on solely cross-sectional observational studies, it is impossible to infer causality. Longitudinal studies of high methodological quality are needed to gain more insight into the complex mechanisms behind the development of hypertension in obese children. © 2015 World Obesity.

What is precise pathophysiology in development of hypertension in pregnancy? Precision medicine requires precise physiology and pathophysiology.

PubMed

Gao, Qinqin; Tang, Jiaqi; Li, Na; Liu, Bailin; Zhang, Mengshu; Sun, Miao; Xu, Zhice

2018-02-01

It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. However, is the physiology of placental vessels the same as that of nonplacental vessels? What is the pathophysiology of placental vessels in development of pregnancy hypertension? This review aims to provide a comprehensive summary of special features of placental vascular regulations and the pathophysiological changes linked to preeclamptic conditions. Interestingly, some popular theories or accepted concepts could be based on our limited knowledge and evidence regarding placental vascular physiology, pharmacology and pathophysiology. New views raised could offer interesting ideas for future investigation of mechanisms as well as targets for pregnancy hypertension. Copyright © 2017 Elsevier Ltd. All rights reserved.

The clinical utility of posturography.

PubMed

Visser, Jasper E; Carpenter, Mark G; van der Kooij, Herman; Bloem, Bastiaan R

2008-11-01

Postural instability and falls are common and devastating features of ageing and many neurological, visual, vestibular or orthopedic disorders. Current management of these problems is hampered by the subjective and variable nature of the available clinical balance measures. In this narrative review, we discuss the clinical utility of posturography as a more objective and quantitative measure of balance and postural instability, focusing on several areas where clinicians presently experience the greatest difficulties in managing their patients: (a) to make an appropriate differential diagnosis in patients presenting with falls or balance impairment; (b) to reliably identify those subjects who are at risk of falling; (c) to objectively and quantitatively document the outcome of therapeutic interventions; and (d) to gain a better pathophysiological understanding of postural instability and falls, as a basis for the development of improved treatment strategies to prevent falling. In each of these fields, posturography offers several theoretical advantages and, when applied correctly, provides a useful tool to gain a better understanding of pathophysiological mechanisms in patients with balance disorders, at the group level. However, based on the available evidence, none of the existing techniques is currently able to significantly influence the clinical decision making in individual patients. We critically review the shortcomings of posturography as it is presently used, and conclude with several recommendations for future research.

Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed.

PubMed

Miller, Wayne L

2016-08-01

Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Volume overload and fluid congestion remain primary issues for patients with chronic heart failure. The pathophysiology is complex, and the simple concept of intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert clinicians of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in patients with chronic heart failure and help guide individualized, appropriate therapy-not all volume overload is the same. © 2016 American Heart Association, Inc.

Renal cell carcinoma: Review of etiology, pathophysiology and risk factors.

PubMed

Petejova, Nadezda; Martinek, Arnost

2016-06-01

The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm. A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015. Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.

The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

PubMed Central

Pasquali, Renato

2012-01-01

Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

Central voice production and pathophysiology of spasmodic dysphonia.

PubMed

Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

2018-01-01

Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Orthostatic intolerance: potential pathophysiology and therapy.

PubMed

Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se

2004-09-30

Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

Pathophysiology of migraine

PubMed Central

Goadsby, Peter J.

2012-01-01

Migraine is a common disabling brain disorder whose pathophysiology is now being better understood. The study of anatomy and physiology of pain producing structures in the cranium and the central nervous system modulation of the input have led to the conclusion that migraine involves alterations in the sub-cortical aminergic sensory modulatory systems that influence the brain widely. PMID:23024559

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

PubMed Central

Robinson, Shenandoah

2013-01-01

Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is

Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation.

PubMed

Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

2018-06-04

Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p < 0.001), and showed a longer duration from onset to DLB diagnosis (p < 0.001) than the other clusters. Patients in cluster II (neuropsychiatric-predominant, n = 22) were older at disease onset (78.1±5 versus 73.6±6.1 and 73.6±4.2 in clusters I and III, respectively, both p < 0.01), presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p < 0.001). Patients in cluster III (parkinsonism-predominant, n = 13) showed a shorter time from onset to presence of parkinsonism (p < 0.001) and dementia (0.008). Three subtypes of clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

Fibromyalgia: harmonizing science with clinical practice considerations.

PubMed

Perrot, Serge; Dickenson, Anthony H; Bennett, Robert M

2008-01-01

This review summarizes the present and emerging knowledge base on the pathophysiology, diagnosis, and management of fibromyalgia. Fibromyalgia is the most common chronic pain syndrome encountered in general medicine and rheumatology. Historically, contemporary concepts of fibromyalgia have evolved in terms of its clinical description and parallel advances in the understanding of its pathophysiology. A generally accepted paradigm postulates that fibromyalgia is the clinical expression of a rheumatologic disorder in which the associated pain is driven primarily by central sensitization and possibly through changes in several neuronal systems but not necessarily reliant on peripheral processes. Several agents, including serotonin-norepinephrine reuptake inhibitors (ie, duloxetine and milnacipran), opioids (ie, tramadol), and the alpha2-delta ligand pregabalin, which recently received U.S. regulatory approval for the treatment of fibromyalgia, have been evaluated in clinical trials, demonstrating benefit in terms of pain reduction and improvement in core symptoms (ie, fatigue and sleep disturbance). The European League Against Rheumatism has developed updated guidelines for the management of fibromyalgia.

Identification and Treatment of Pathophysiological Comorbidities of Autism Spectrum Disorder to Achieve Optimal Outcomes

PubMed Central

Frye, Richard E.; Rossignol, Daniel A.

2016-01-01

Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. In this paper we review some of the pathophysiological abnormalities associated with ASD and their potential associated treatments. Overall, there is evidence for some children with ASD being affected by seizure and epilepsy, neurotransmitter dysfunction, sleep disorders, metabolic abnormalities, including abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, redox and mitochondrial metabolism, and immune and gastrointestinal disorders. Although evidence for an association between these pathophysiological abnormalities and ASD exists, the exact relationship to the etiology of ASD and its associated symptoms remains to be further defined in many cases. Despite these limitations, treatments targeting some of these pathophysiological abnormalities have been studied in some cases with high-quality studies, whereas treatments for other pathophysiological abnormalities have not been well studied in many cases. There are some areas of more promising treatments specific for ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. Clearly, there are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future, but more research is needed to better define subgroups of children with ASD who are affected by specific pathophysiological abnormalities and

[Current concepts in pathophysiology of CRPS I].

PubMed

Nickel, F T; Maihöfner, C

2010-02-01

Knowledge about the pathophysiology underlying the complex regional pain syndrome (CRPS) has increased over the last years. Classically, CRPS has been considered to be mainly driven by sympathetic dysfunction with sympathetically maintained pain being its major pathogenetic mechanism. Currently, the disease is understood as result of a complex interplay between altered somatosensory, motor, autonomic and inflammatory systems. Peripheral and central sensitization is a common feature in CRPS as in other neuropathic pain syndromes. One important mechanism is the sensitization of spinal dorsal horn cells via activation of postsynaptic NMDA-receptors by chronic C-fiber input. Differential activity of endogenous pain modulating systems may play a pivotal role in the development of CRPS, too. Neuronal plasticity of the somatosensory cortex accounts for central sensory signs. Also the motor system is subject to central adaptive changes in patients with CRPS. Calcitonin-gene related peptide (CGRP) and substance P mediate neurogenic inflammation. Additionally other proinflammatory cytokines involved in the inflammatory response in CRPS have been identified. In terms of the sympathetic nervous system, recent evidence rather points to a sensitization of adrenergic receptors than to increased efferent sympathetic activity. Particularly the expression of alpha (1)-adrenoceptors on nociceptive C-fibers may play a major role. These pathophysiological ideas do not exclude each other. In fact they complement one another. The variety of the involved systems may explain the versatile clinical picture of CRPS. Georg Thieme Verlag KG Stuttgart, New York.

Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers

PubMed Central

Liu, Jian-ping; Wang, Ting-ting; Wang, Dang-ge; Dong, An-jie; Li, Ya-ping; Yu, Hai-jun

2017-01-01

The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment. PMID:27569390

Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers.

PubMed

Liu, Jian-Ping; Wang, Ting-Ting; Wang, Dang-Ge; Dong, An-Jie; Li, Ya-Ping; Yu, Hai-Jun

2017-01-01

The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment.

Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues.

PubMed

Classen, Joseph; Koschel, Jiri; Oehlwein, Christian; Seppi, Klaus; Urban, Peter; Winkler, Christian; Wüllner, Ullrich; Storch, Alexander

2017-08-01

Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and Management.

PubMed

Baxi, Ameya Jagdish; Restrepo, Carlos S; Vargas, Daniel; Marmol-Velez, Alejandro; Ocazionez, Daniel; Murillo, Horacio

2016-01-01

Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of diseases related to sarcomere gene mutations exhibiting heterogeneous phenotypes with an autosomal dominant mendelian pattern of inheritance. The disorder is characterized by diverse phenotypic expressions and variable natural progression, which may range from dyspnea and/or syncope to sudden cardiac death. It is found across all racial groups and is associated with left ventricular hypertrophy in the absence of another systemic or cardiac disease. The management of HCM is based on a thorough understanding of the underlying morphology, pathophysiology, and clinical course. Imaging findings of HCM mirror the variable expressivity and penetrance heterogeneity, with the added advantage of diagnosis even in cases where a specific mutation may not yet be found. The diagnostic information obtained from imaging varies depending on the specific stage of HCM-phenotype manifestation, including the prehypertrophic, hypertrophic, and later stages of adverse remodeling into the burned-out phase of overt heart failure. However, subtle or obvious, these imaging findings become critical components in diagnosis, management, and follow-up of HCM patients. Although diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography, recent studies have demonstrated increased utility of multidetector computed tomography (CT) and particularly cardiac magnetic resonance (MR) imaging in diagnosis, phenotype differentiation, therapeutic planning, and prognostication. In this article, we provide an overview of the genetics, pathophysiology, and clinical manifestations of HCM, with the spectrum of imaging findings at MR imaging and CT and their contribution in diagnosis, risk stratification, and therapy. (©)RSNA, 2016.

Imaging the pathophysiology of major depressive disorder - from localist models to circuit-based analysis

PubMed Central

2014-01-01

The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard’ of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research. PMID:24606595

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

PubMed

Slater, James; Rill, Velisar

2004-04-01

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.

Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome

PubMed Central

Ellis, Demetrius

2016-01-01

Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology.

PubMed

Hintze, Justin M; Ludlow, Christy L; Bansberg, Stephen F; Adler, Charles H; Lott, David G

2017-10-01

Objective The purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task-specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia) and ( etiology, aetiology, diagnosis, pathogenesis, or pathophysiology). Conclusion The diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high-speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia. Implications for Practice A 3-tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

Vulvodynia: Definition, Prevalence, Impact, and Pathophysiological Factors.

PubMed

Pukall, Caroline F; Goldstein, Andrew T; Bergeron, Sophie; Foster, David; Stein, Amy; Kellogg-Spadt, Susan; Bachmann, Gloria

2016-03-01

Vulvodynia constitutes a highly prevalent form of chronic genital pain in women, and current information regarding its definition, prevalence, impact, and pathophysiologic factors involved is needed. To update the scientific evidence published in 2010 from the Third International Consultation of Sexual Medicine pertaining to the definition, prevalence, impact, and pathophysiologic factors of women's sexual pain. An expert committee, as part of the Fourth International Consultation of Sexual Medicine, comprised of researchers and clinicians from biological and social science disciplines, reviewed the scientific evidence on the definition, prevalence, impact, and pathophysiologic factors related to chronic genital pain. A review of the definition, prevalence, impact, and pathophysiological factors involved in vulvodynia. Vulvodynia is a prevalent and highly impactful genital pain condition. Numerous factors have been implicated in its development and maintenance. What is becoming increasingly apparent is that it likely represents the end point of different factors that can differ from patient to patient. Longitudinal research is needed to shed light on risk factors involved in the expression of vulvodynia, as well as in potential subgroups of affected patients, in order to develop an empirically supported treatment algorithm. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report.

PubMed

Kondo, Tatsuya; Nakamura, Miwa; Kitano, Sayaka; Kawashima, Junji; Matsumura, Takeshi; Ohba, Takashi; Yamaguchi, Munekage; Katabuchi, Hidetaka; Araki, Eiichi

2018-01-30

Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known. A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient's syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner. Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case.

Pathophysiology of diverticular disease.

PubMed

Schieffer, Kathleen M; Kline, Bryan P; Yochum, Gregory S; Koltun, Walter A

2018-06-07

Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome. Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome. Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.

Postoperative ileus: Recent developments in pathophysiology and management.

PubMed

Bragg, Damian; El-Sharkawy, Ahmed M; Psaltis, Emmanouil; Maxwell-Armstrong, Charles A; Lobo, Dileep N

2015-06-01

Postoperative ileus (POI) is a frequent occurrence after abdominal and other types of surgery, and is associated with significant morbidity and costs to health care providers. The aims of this narrative review were to provide an update of classification systems, preventive techniques, pathophysiological mechanisms, and treatment options for established POI. The Web of Science, MEDLINE, PubMed and Google Scholar databases were searched using the key phrases 'ileus', 'postoperative ileus' and 'definition', for relevant studies published in English from January 1997 to August 2014. POI is still a problematic and frequent complication of surgery. Fluid overload, exogenous opioids, neurohormonal dysfunction, and gastrointestinal stretch and inflammation are key mechanisms in the pathophysiology of POI. Evidence is supportive of thoracic epidural analgesia, avoidance of salt and water overload, alvimopan and gum chewing as measures for the prevention of POI, and should be incorporated into perioperative care protocols. Minimal access surgery and avoidance of nasogastric tubes may also help. Novel strategies are emerging, but further studies are required for the treatment of prolonged POI, where evidence is still lacking. Although POI is often inevitable, methods to reduce its duration and facilitate recovery of postoperative gastrointestinal function are evolving rapidly. Utilisation of standardised diagnostic classification systems will help improve applicability of future studies. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Dysmotility in Esophageal Atresia: Pathophysiology, Characterization, and Treatment

PubMed Central

Faure, Christophe; Righini Grunder, Franziska

2017-01-01

Esophageal dysmotility is almost universal after esophageal atresia (EA) repair and is mainly related to the developmental anomaly of the esophagus. Esophageal dysmotility is involved in the pathophysiology of numerous symptoms and comorbidities associated with EA such as gastroesophageal reflux disease, aspiration and respiratory complications, and symptoms of dysphagia and feeding disorders. High-resolution esophageal manometry (HREM) has facilitated the characterization of the dysmotility, but there is an incomplete correlation between symptoms and manometrical patterns. Impedance coupled to HREM should help to predict the clinical outcome and therefore personalize patient management. Nowadays, the management of esophageal dysmotility in patients with EA is essentially based on treatment of associated inflammation related to peptic or eosinophilic esophagitis. PMID:28620599

Pathophysiology of pulmonary hypertension in acute lung injury

PubMed Central

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

Pathophysiology, Evaluation, and Treatment of Bloating

PubMed Central

Gabbard, Scott L.; Crowell, Michael D.

2011-01-01

Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention. PMID:22298969

Cutaneous approach towards clinical and pathophysiological aspects of hyperglycemia by ATR FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Eikje, Natalja Skrebova; Sota, Takayuki; Aizawa, Katsuo

2007-07-01

Attempts were made to non-invasively detect glucose-specific spectral signals in the skin by ATR-FTIR spectroscopy. In vivo spectra were collected from the inner wrists of healthy, prediabetes and diabetes subjects in the 750-4000 cm -1 region, with a closer assessment of the glucose-related region between 1000 and 1180 cm -1. Spectra in vivo showed glucose-specific peaks at 1030, 1080, 1118 and 1151 cm -1, as a variety of glucose solutions are found in vitro. Based on the differences of intensities at 1030 and 1118 cm -1 two spectral patterns were seen: I 1118 > I 1030 for a diabetes and I 1030> I 1118 for non-diabetes subjects. The peak at 1030 cm -1 was used to assess glucose concentrations in the skin due to its good correlation with glucose concentrations in vitro. Calculated mean values of the peak at 1030 cm -1 showed evidence of correlation with blood glucose levels when grouped as <= 140, 140-200 and >= 200 mg/dL, though there was no constant correlation between them when compared before/after OGTT or at the fasting/postprandial states. Absorbances at 1030 cm -1 were not only increased in a dose-dependent manner in a diabetes patient, but were also generally higher than in non-diabetes subjects at 30 min OGTT assessment. Also we could monitor absorbances at 1030 cm -1 and determine their changes in the skin tissue at different times of OGTT. We assume that our approach to in vivo measurement and monitoring of glucose concentrations at 1030 cm -1 may be one of the indicators to assess glucose activity level and its changes in the skin tissue, and has further implications in the study of clinical and pathophysiological aspects of hyperglycemia in diabetes and non-diabetes subjects by ATR-FTIR spectroscopy.

Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.

PubMed

Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F; Ebihara, Hideki; Scott, Dana P; Hjelle, Brian; Feldmann, Heinz

2014-05-13

The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.

Pathophysiology, prevention, and treatment of ebullism.

PubMed

Murray, Daniel H; Pilmanis, Andrew A; Blue, Rebecca S; Pattarini, James M; Law, Jennifer; Bayne, C Gresham; Turney, Matthew W; Clark, Jonathan B

2013-02-01

Ebullism is the spontaneous evolution of liquid water in tissues to water vapor at body temperature when the ambient pressure is 47 mmHg or less. While injuries secondary to ebullism are generally considered fatal, some reports have described recovery after exposure to near vacuum for several minutes. The objectives of this article are to review the current literature on ebullism and to present prevention and treatment recommendations that can be used to enhance the safety of high altitude activities and space operations. A systematic review was conducted on currently available information and published literature of human and animal studies involving rapid decompression to vacuum and ebullism, with subsequent development of an applicable treatment protocol. Available research on ebullism in human and animal subjects is extremely limited. Literature available identified key pathophysiologic processes and mitigation strategies that were used for treatment protocol design and outlining appropriate interventions using current best medical practices and technologies. Available literature suggests that the pathophysiology of ebullism leads to predictable and often treatable injuries, and that many exposures may be survivable. With the growing number of high altitude and space-related activities, more individuals will be at risk for ebullism. An integrated medical protocol can provide guidance for the prevention and treatment of ebullism and help to mitigate this risk in the future.

Pathophysiology of Glucocorticoid Signaling.

PubMed

Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

2018-06-01

Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pathophysiology of Trigger Points in Myofascial Pain Syndrome.

PubMed

Money, Sarah

2017-06-01

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. Trigger point pathophysiology in myofascial pain syndrome, which involves muscle stiffness, tenderness, and pain that radiates to other areas of the body, is considered. The causes of trigger points and several theories about how they develop are reviewed, and treatment approaches, including stretching, physical therapy, dry needling, and injections, are offered.

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

PubMed

Maseroli, Elisa; Scavello, Irene; Vignozzi, Linda

2018-05-02

Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International

Concepts of scientific integrative medicine applied to the physiology and pathophysiology of catecholamine systems.

PubMed

Goldstein, David S

2013-10-01

This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body's monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems-especially Parkinson disease-and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. Published 2013. Compr Physiol 3:1569-1610, 2013.

Concepts of Scientific Integrative Medicine Applied to the Physiology and Pathophysiology of Catecholamine Systems

PubMed Central

Goldstein, David S.

2016-01-01

This review presents concepts of scientific integrative medicine and relates them to the physiology of catecholamine systems and to the pathophysiology of catecholamine-related disorders. The applications to catecholamine systems exemplify how scientific integrative medicine links systems biology with integrative physiology. Concepts of scientific integrative medicine include (i) negative feedback regulation, maintaining stability of the body’s monitored variables; (ii) homeostats, which compare information about monitored variables with algorithms for responding; (iii) multiple effectors, enabling compensatory activation of alternative effectors and primitive specificity of stress response patterns; (iv) effector sharing, accounting for interactions among homeostats and phenomena such as hyperglycemia attending gastrointestinal bleeding and hyponatremia attending congestive heart failure; (v) stress, applying a definition as a state rather than as an environmental stimulus or stereotyped response; (vi) distress, using a noncircular definition that does not presume pathology; (vii) allostasis, corresponding to adaptive plasticity of feedback-regulated systems; and (viii) allostatic load, explaining chronic degenerative diseases in terms of effects of cumulative wear and tear. From computer models one can predict mathematically the effects of stress and allostatic load on the transition from wellness to symptomatic disease. The review describes acute and chronic clinical disorders involving catecholamine systems—especially Parkinson disease—and how these concepts relate to pathophysiology, early detection, and treatment and prevention strategies in the post-genome era. PMID:24265239

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

PubMed

Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

2016-04-01

Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

[Thinking about the present primary open angle glaucoma early diagnosis concepts and methods].

PubMed

Ren, Zeqin

2014-05-01

Early diagnosis of primary open-angle glaucoma has not been clear and consistent in concepts and methods. At present, according to the pathophysiology process of optic nerve damage and its detection technology, early diagnosis on the concept still belongs to the early clinical diagnosis instead of preclinical diagnosis, and on the method depends on the fundus as morphological index combined with the visual field as functional index. The direction of early clinical diagnosis mainly lies in exploring more effective diagnosis index, rather than blindly adopt new diagnostic technology.

Third-space fluid shift in elderly patients undergoing gastrointestinal surgery: Part 1: Pathophysiological mechanisms.

PubMed

Redden, Maurine; Wotton, Karen

2002-06-01

Third-space fluid shift, the movement of body fluid to a non-functional space, is a frequently occurring and potentially fatal clinical phenomenon. Little published research exists however in medical or nursing journals concerning its incidence, significance and ramifications in elderly patients undergoing major gastrointestinal surgery. This initial article, part I, explores fluid movement between fluid compartments and uses these principles to discuss the pathophysiology of the two distinct phases of third-space fluid shift. Part II will examine the criteria nurses could use in the clinical assessment of patients in both first and second phases third-space fluid shift and discuss the clinical reliability of these criteria.

An update on oxidative stress-mediated organ pathophysiology.

PubMed

Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Review of the Pathophysiology and Treatment of Psychosis in Parkinson’s Disease

PubMed Central

Zahodne, Laura B.; Fernandez, Hubert H.

2011-01-01

Psychotic symptoms in Parkinson’s disease (PD) are relatively common, and in addition to being a disturbance to patients’ daily lives, they have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past fifteen years, from an initial interpretation of symptoms as dopaminergic drug side effects to the current view of a complex interplay of extrinsic and disease-related factors. The present article reviews the unique clinical features of psychosis as expressed in PD, associated risk factors, and current theories behind its pathogenesis, including medications, visual processing deficits, sleep disturbances, genetics, and neurochemical and structural abnormalities. Finally, we review both traditional and emergent management strategies for PD psychosis, including antipsychotic agents, cholinesterase inhibitors, electroconvulsive therapy (ECT), and other pharmacological and psychological interventions. PMID:18665659

Dry eye disease: pathophysiology, classification, and diagnosis.

PubMed

Perry, Henry D

2008-04-01

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease.

PubMed

Bonini, Matteo; Usmani, Omar S

2015-12-01

Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable. © The Author(s), 2015.

Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.

PubMed

Beam, Teresa A; Loudermilk, Emily F; Kisor, David F

2017-02-01

A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variations cannot be used to positively predict MH since the condition is genetically heterogeneous with variable expression and incomplete penetrance. At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca 2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace. Copyright © 2017 the American Physiological Society.

Pathophysiology of luteal-phase deficiency in human reproduction.

PubMed

Nakajima, S T; Gibson, M

1991-03-01

There are numerous probable mechanisms for the clinical occurrence of a luteal-phase deficiency. Defects may occur in either the proliferative, luteal, or luteal-rescue stage of a menstrual cycle. In each of these three domains, alterations in the trophic stimulation or the response at either the ovarian or endometrial level further subdivide the etiologies for luteal-phase deficiency. Additional development of new concepts in the areas of intraovarian signaling, the possible role of growth factors, and the measurement of newly discovered luteal products will enable us to expand our thought process. With a better understanding of the pathophysiology of luteal-phase deficiency, it is anticipated that new treatments will be devised to address precisely a given specific etiologic factor.

Pre-eclampsia: pathophysiology, diagnosis, and management

PubMed Central

Uzan, Jennifer; Carbonnel, Marie; Piconne, Olivier; Asmar, Roland; Ayoubi, Jean-Marc

2011-01-01

The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure >140 mmHg or diastolic blood pressure ≥90 mmHg and 24-hour proteinuria ≥0.3 g). Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia. PMID:21822394

Spinal infections: clinical and imaging features.

PubMed

Arbelaez, Andres; Restrepo, Feliza; Castillo, Mauricio

2014-10-01

Spinal infections represent a group of rare conditions affecting vertebral bodies, intervertebral discs, paraspinal soft tissues, epidural space, meninges, and spinal cord. The causal factors, clinical presentations, and imaging features are a challenge because the difficulty to differentiate them from other conditions, such as degenerative and inflammatory disorders and spinal neoplasm. They require early recognition because delay diagnosis, imaging, and intervention may have devastating consequences especially in children and the elderly. This article reviews the most common spinal infections, their pathophysiologic, clinical manifestation, and their imaging findings.

Review article: the pathophysiology, differential diagnosis and management of rumination syndrome.

PubMed

Tack, J; Blondeau, K; Boecxstaens, V; Rommel, N

2011-04-01

Rumination syndrome, characterised by the effortless, often repetitive, regurgitation of recently ingested food into the mouth, was originally described in children and in the developmentally disabled. It is now well-recognised that rumination syndrome occurs in patients of all ages and cognitive abilities. To review a scholarly review on our current understanding of the rumination syndrome. The review was conducted on the basis of a medline search to identify relevant publications pertaining to the pathophysiology, clinical diagnosis and management of rumination syndrome. The Rome III consensus established diagnostic criteria for rumination syndrome in adults, children and infants. A typical history can be highly suggestive but oesophageal (high resolution) manometry/impedance with ingestion of a meal may help to distinguish rumination syndrome from other belching/regurgitation disorders. The pathophysiology is incompletely understood, but involves a rise in intra-gastric pressure, generated by a voluntary, but often unintentional, contraction of the abdominal wall musculature, at a time of low pressure in the lower oesophageal sphincter, causing retrograde movement of gastric contents into the oesophagus. To date, controlled trials in the treatment rumination syndrome are lacking. The mainstay of treatment for rumination syndrome is explanation and behavioural treatment which consists of habit reversal techniques that compete with the urge to regurgitate. Chewing gum, prokinetics, baclofen and even antireflux surgery have been proposed as adjunctive therapies, but high quality studies are generally lacking. Rumination is an under-recognised condition with incompletely understood pathophysiology. Behavioural therapy seems effective, but controlled treatment trials are lacking. © 2011 Blackwell Publishing Ltd.

Current status of functional gastrointestinal evaluation in clinical practice

PubMed Central

Ang, Daphne; Fock, Kwong Ming; Law, Ngai Moh; Ang, Tiing Leong

2015-01-01

Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient’s care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients’ persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools. PMID:25715853

Identifying coagulopathies in the pathophysiology of cold stress syndrome in the Florida manatee Trichechus manatus latirostris.

PubMed

Barratclough, Ashley; Conner, Bobbi J; Brooks, Marjory B; Pontes Stablein, Alyssa; Gerlach, Trevor J; Reep, Roger L; Ball, Ray L; Floyd, Ruth Francis

2017-08-09

Cold stress syndrome (CSS) in the Florida manatee Trichechus manatus latirostris has been defined as morbidity and mortality resulting from prolonged exposure to water temperatures <20°C. The pathophysiology is described as multifactorial, involving nutritional, immunological and metabolic disturbances; however, the exact mechanisms are unknown. We hypothesized that thromboembolic complications contribute to the pathophysiology of CSS in addition to the previously described factors. During the winter of 2014-2015, 10 Florida manatees with clinical signs of CSS were presented to Lowry Park Zoo, Tampa, FL, USA. Thromboelastography (TEG) and coagulation panels were performed at admission. In addition, coagulation panel data from 23 retrospective CSS cases were included in the analyses. There were numerous differences between mean values of TEG and coagulation parameters for healthy manatees and those for CSS cases. Among TEG parameters, reaction time (R), clot formation time (K) and percentage of clot lysed after 30 min (LY30) values were significantly different (p < 0.05) between the 2 groups. CSS cases also had significantly higher mean D-dimer concentration and coagulation factor XI activity, prolonged mean activated partial thromboplastin time (aPTT) and significantly decreased mean antithrombin activity. These combined abnormalities include clinicopathologic criteria of disseminated intravascular coagulation, indicating an increased risk of thromboembolic disease associated with manatee CSS.

[Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

PubMed

Watanabe, Ken

2009-01-01

The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models

PubMed Central

Manganozzi, Lucilla; Moretti, Raffaella; Vexler, Zinaida S.; Gressens, Pierre

2016-01-01

BACKGROUND Arterial ischemic stroke occurs most frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared to childhood. This concept was recently challenged by clinical studies showing marked motor disabilities after stroke in neonates, with the severity of motor and cortical sensory deficits similar in both perinatal and childhood ischemic stroke. The understanding of the triggers and the pathophysiological mechanisms of perinatal stroke has greatly improved in recent years, but many aspects remain still unclear. METHODS In this review, we will focus on the pathophysiology of perinatal stroke and on therapeutic strategies that can protect the immature brain from the consequences of stroke by targeting inflammation and brain microenvironment. RESULTS Studies in neonatal rodent models of cerebral ischemia have shown a potential role for soluble inflammatory molecules as important modulators of injury and recovery. A great effort has been made and is still in act to try neuroprotective molecules based on the new physiopatological acquisition. CONCLUSION In this review we aim to give a comprehensive view of new insights concerning pathophysiological mechanism of focal and global perinatal brain injury and its new therapeutic approaches. PMID:26002050

Resident's Morning Report: An Opportunity to Reinforce Principles of Biomedical Science in a Clinical Context

ERIC Educational Resources Information Center

Brass, Eric P.

2013-01-01

The principles of biochemistry are core to understanding cellular and tissue function, as well as the pathophysiology of disease. However, the clinical utility of biochemical principles is often obscure to clinical trainees. Resident's Morning Report is a common teaching conference in which residents present clinical cases of interest to a…

Pathophysiology of septic shock: From bench to bedside.

PubMed

McConnell, Kevin W; Coopersmith, Craig M

2016-04-01

Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not been successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pathophysiology of Septic Shock: From Bench to Bedside

PubMed Central

McConnell, Kevin W.; Coopersmith, Craig M.

2016-01-01

Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. PMID:27085986

Summary of papers presented at the 2012 seventh international cough symposium

PubMed Central

2013-01-01

Twenty six papers were presented as posters in the Seventh International Symposium on Cough; 12 papers were presented in the Basic Science of Cough session, and 14 papers presented in the Clinical Science of Cough session. These papers explored a wide spectrum of cough-related areas including pathophysiological mechanisms, treatment and detection of cough, and symptom assessment and perception, and were grouped into several general themes for facilitate the discussion. Studies presented in these posters have provided new information that should improve our knowledge on the basic physiology and pharmacology of cough, and the peripheral and central neural mechanisms involved in the generation of the cough motor pattern. In addition, in the clinical science section, studies reporting potential new anti-tussive agents and further characterisation of cough symptoms and perception have provided a base for the fruitful strategies for the development of novel anti-tussive therapies and cough management. PMID:23639195

A Supernumerary Nipple-Like Clinical Presentation of Lymphangioma Circumscriptum.

PubMed

Taylor, Dustin; Kash, Natalie; Silapunt, Sirunya

2018-01-01

Lymphangioma circumscriptum is a superficially localized variant of lymphangioma. The characteristic clinical presentation is a "frogspawn" grouping of vesicles or papulovesicles on the proximal limb or limb girdle areas. Though most lymphangiomas develop congenitally, the lymphangioma circumscriptum subtype is known to present in adults. We report a case of lymphangioma circumscriptum on the left inframammary area of an African American female with an unusual supernumerary nipple-like clinical presentation. Our patient presented with a firm, smooth, hypopigmented papule, and the clinical diagnosis of keloid was made initially. However, she returned reporting growth of the lesion and was noted to have a firm, exophytic, lobulated, pink to skin-colored nodule. Histopathological examination demonstrated dilated lymphatic vessels, consistent with the diagnosis of lymphangioma. The presentation as a firm, hypopigmented papule and later exophytic, lobulated, skin-colored nodule in our case represents a clinical presentation of lymphangioma circumscriptum not previously described in the literature. Correct diagnosis in lymphangioma circumscriptum is vital, as recurrence following surgical resection and secondary development of lymphangiosarcoma and squamous cell carcinoma following treatment with radiation have been reported. Thus, it is important to consider lymphangioma circumscriptum in the differential of similar lesions in the future to allow appropriate diagnosis, treatment, and monitoring.

[Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].

PubMed

Duboc, H; Dior, M; Coffin, B

2016-08-01

In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

GLUTAMATE ABNORMALITIES IN OBSESSIVE COMPULSIVE DISORDER: NEUROBIOLOGY, PATHOPHYSIOLOGY, AND TREATMENT

PubMed Central

Pittenger, Christopher; Bloch, Michael H.; Williams, Kyle

2011-01-01

Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics. PMID:21963369

Intraoperative Floppy Iris Syndrome: Pathophysiology, Prevention, and Treatment

PubMed Central

Flach, Allan J.

2009-01-01

Purpose: To extend upon previous reports, observations, and discussions of intraoperative floppy iris syndrome (IFIS) with the goal of providing new insight into the syndrome’s pathophysiology, prevention, and treatment. Methods: Following a review of IFIS and its relationship to autonomic pharmacology, evidence for anatomic changes following exposure of humans and other animals to autonomic drugs is described. The clinical implications for these findings are discussed as they relate to the treatment and prevention of this syndrome. Results: IFIS has been associated with the use of adrenergic antagonists even after they have been discontinued years prior to surgery. Some investigators believe that this persistence of IFIS reflects anatomic structural change. Evidence from laboratory experiments and human clinical studies using topically applied and systemic autonomic drugs supports the possibility of anatomic changes coexisting with IFIS observed during cataract surgery. Conclusions: IFIS is a relatively rare syndrome, often associated with the use of systemic α-blockers and conditions that influence dilator muscle tone. Laboratory and clinical evidence supports the possibility of anatomic changes following the use of autonomic drugs. The persistence of IFIS years after cessation of treatment with α-blockers suggests that the potential risks of discontinuing these drugs prior to cataract surgery outweigh potential benefits. PMID:20126500

Advanced imaging in COPD: insights into pulmonary pathophysiology

PubMed Central

Milne, Stephen

2014-01-01

Chronic obstructive pulmonary disease (COPD) involves a complex interaction of structural and functional abnormalities. The two have long been studied in isolation. However, advanced imaging techniques allow us to simultaneously assess pathological processes and their physiological consequences. This review gives a comprehensive account of the various advanced imaging modalities used to study COPD, including computed tomography (CT), magnetic resonance imaging (MRI), and the nuclear medicine techniques positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Some more recent developments in imaging technology, including micro-CT, synchrotron imaging, optical coherence tomography (OCT) and electrical impedance tomography (EIT), are also described. The authors identify the pathophysiological insights gained from these techniques, and speculate on the future role of advanced imaging in both clinical and research settings. PMID:25478198

[Malabsorption is a leading clinical sign of small bowel disease].

PubMed

Parfenov, A I; Krums, L M

The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.

Clinical presentation of nasopharyngeal carcinoma in Sarawak Malaysia.

PubMed

Tiong, T S; Selva, K S

2005-12-01

Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia. The clinical presentation in Sarawak has not been well documented. A retrospective review of 213 selected NPC cases was undertaken on the clinical records in Sarawak General Hospital, Sarawak, from June 1999 to June 2003. There were 116 patients in Kuching and 97 in Serian. There were twice as many males as females. The youngest patient was 16 and the oldest 88 years old with a mean age of 51 years. The four most common symptoms in order of frequencies were cervical lymphadenopathy, epistaxis, hearing loss and diplopia. 80.8% of the patients presented with cervical lymphadenopathy and about 85% of the patients presented in the advanced stages. Very small percentages of the patients were found to have single presenting symptoms of epistaxis (2.4%) and hearing loss (0.5%).

Work-Related Musculoskeletal Disorders of the Hand and Wrist: Epidemiology, Pathophysiology, and Sensorimotor Changes

PubMed Central

Barr, Ann E.; Barbe, Mary F.; Clark, Brian D.

2006-01-01

The purpose of this commentary is to present recent epidemiological findings regarding work-related musculoskeletal disorders (WMSDs) of the hand and wrist, and to summarize experimental evidence of underlying tissue pathophysiology and sensorimotor changes in WMSDs. Sixty-five percent of the 333 800 newly reported cases of occupational illness in 2001 were attributed to repeated trauma. WMSDs of the hand and wrist are associated with the longest absences from work and are, therefore, associated with greater lost productivity and wages than those of other anatomical regions. Selected epidemiological studies of hand/wrist WMSDs published since 1998 are reviewed and summarized. Results from selected animal studies concerning underlying tissue pathophysiology in response to repetitive movement or tissue loading are reviewed and summarized. To the extent possible, corroborating evidence in human studies for various tissue pathomechanisms suggested in animal models is presented. Repetitive, hand-intensive movements, alone or in combination with other physical, nonphysical, and nonoccupational risk factors, contribute to the development of hand/wrist WMSDs. Possible pathophysiological mechanisms of tissue injury include inflammation followed by repair and/or fibrotic scarring, peripheral nerve injury, and central nervous system reorganization. Clinicians should consider all of these pathomechanisms when examining and treating patients with hand/wrist WMSDs. PMID:15552707

Catatonia as presenting clinical feature of subacute sclerosing panencephalitis

PubMed Central

Dayal, Prabhoo; Balhara, Yatan Pal Singh

2014-01-01

Catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis (SSPE), especially in the initial stages of illness. However, there is only one reported case of SSPE presenting as catatonia among children. In this report, however, there were SSPE-specific changes on EEG and the catatonia failed to respond to lorazepam. We describe a case of SSPE in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical EEG findings when assessed at first contact. He responded to lorazepam and EEG changes emerged during the course of follow-up. PMID:24891908

Intestinal barrier dysfunction in cirrhosis: Current concepts in pathophysiology and clinical implications

PubMed Central

Tsiaoussis, Georgios I; Assimakopoulos, Stelios F; Tsamandas, Athanassios C; Triantos, Christos K; Thomopoulos, Konstantinos C

2015-01-01

The intestinal lumen is a host place for a wide range of microbiota and sets a unique interplay between local immune system, inflammatory cells and intestinal epithelium, forming a physical barrier against microbial invaders and toxins. Bacterial translocation is the migration of viable or nonviable microorganisms or their pathogen-associated molecular patterns, such as lipopolysaccharide, from the gut lumen to the mesenteric lymph nodes, systemic circulation and other normally sterile extraintestinal sites. A series of studies have shown that translocation of bacteria and their products across the intestinal barrier is a commonplace in patients with liver disease. The deterioration of intestinal barrier integrity and the consulting increased intestinal permeability in cirrhotic patients play a pivotal pathophysiological role in the development of severe complications as high rate of infections, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding, progression of liver injury and hepatocellular carcinoma. Nevertheless, the exact cellular and molecular mechanisms implicated in the phenomenon of microbial translocation in liver cirrhosis have not been fully elucidated yet. PMID:26301048

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.

PubMed

Maldonado, José R

2017-12-26

Delirium is the most common neuropsychiatric syndrome encountered by clinicians dealing with older adults and the medically ill and is best characterized by 5 core domains: cognitive deficits, attentional deficits, circadian rhythm dysregulation, emotional dysregulation, and alteration in psychomotor functioning. An extensive literature review and consolidation of published data into a novel interpretation of known pathophysiological causes of delirium. Available data suggest that numerous pathological factors may serve as precipitants for delirium, each having differential effects depending on patient-specific patient physiological characteristics (substrate). On the basis of an extensive literature search, a newly proposed theory, the systems integration failure hypothesis, was developed to bring together the most salient previously described theories, by describing the various contributions from each into a complex web of pathways-highlighting areas of intersection and commonalities and explaining how the variable contribution of these may lead to the development of various cognitive and behavioral dysfunctions characteristic of delirium. The specific cognitive and behavioral manifestations of the specific delirium picture result from a combination of neurotransmitter function and availability, variability in integration and processing of sensory information, motor responses to both external and internal cues, and the degree of breakdown in neuronal network connectivity, hence the term acute brain failure. The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches. Copyright © 2017 John Wiley & Sons, Ltd.

A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a more precise definition of scalp health.

PubMed

Schwartz, James R; Messenger, Andrew G; Tosti, Antonella; Todd, Gail; Hordinsky, Maria; Hay, Roderick J; Wang, Xuemin; Zachariae, Claus; Kerr, Kathy M; Henry, James P; Rust, Rene C; Robinson, Michael K

2013-03-27

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Pathophysiology and Management of Parkinsonian Tremor.

PubMed

Helmich, Rick C; Dirkx, Michiel F

2017-04-01

Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease. The pathophysiology of Parkinson's tremor is different from that of other motor symptoms such as bradykinesia and rigidity. In this review, the authors discuss evidence suggesting that tremor is a network disorder that arises from distinct pathophysiological changes in the basal ganglia and in the cerebellothalamocortical circuit. They also discuss how interventions in this circuitry, for example, deep brain surgery and noninvasive brain stimulation, can modulate or even treat tremor. Future research may focus on understanding sources for the large variability between patients in terms of treatment response, on understanding the contextual factors that modulate tremor (stress, voluntary movements), and on focused interventions in the tremor circuitry. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

PubMed

Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

2013-04-01

Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

The varied clinical presentations of major depressive disorder.

PubMed

Rush, A John

2007-01-01

DSM-IV major depressive disorder (MDD) is a clinical syndrome notable for heterogeneity of its clinical presentation, genetics, neurobiology, clinical course, and treatment responsiveness. In an attempt to make sense of this heterogeneity, clinicians and researchers have proposed a number of MDD "subtypes" based on differences in characteristic symptoms (e.g., atypical, melancholic, psychotic), onset (e.g., early vs. late, post-partum, seasonal), course of illness (e.g., single vs. recurrent, chronic, double), and severity. This article provides a brief review of the status of several of the most common subtypes in terms of their clinical features, biological correlates, course of illness, and treatment implications.

Current pathophysiological concepts and management of pulmonary hypertension.

PubMed

Lourenço, André P; Fontoura, Dulce; Henriques-Coelho, Tiago; Leite-Moreira, Adelino F

2012-03-22

Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim of this review is to summarize recent advances in epidemiology, pathophysiology and management with particular focus on associated myocardial and systemic compromise and experimental therapeutic possibilities. PAH, currently viewed as a panvasculopathy, is due to a crosstalk between endothelial and smooth muscle cells, inflammatory activation and altered subcellular pathways. Cardiac cachexia and right ventricular compromise are fundamental determinants of PH prognosis. Combined vasodilator therapy is already mainstay for refractory cases, but drugs directed at these new pathophysiological pathways may constitute a significant advance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

β-Thalassemia Intermedia: A Clinical Perspective

PubMed Central

Musallam, Khaled M.; Taher, Ali T.; Rachmilewitz, Eliezer A.

2012-01-01

Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially increased over the past decade. Earlier studies observed that patients with β-thalassemia intermedia experience a clinical-complications profile that is different from that in patients with β-thalassemia major. In this article, a variety of clinical morbidities are explored, and their associations with the underlying disease pathophysiology and risk factors are examined. These involve several organs and organ systems including the vasculature, heart, liver, endocrine glands, bone, and the extramedullary hematopoietic system. The effects of some therapeutic interventions on the development of clinical complications are also discussed. PMID:22762026

Mounier Kuhn syndrome presenting with recurrent atelectasis.

PubMed

Quentin, Christine; Lefevre, Nicolas; Bodart, Eddy; Hanssens, Laurence

2017-09-11

Objective and importance Mounier Kuhn syndrome is usually diagnosed in adulthood, and only a few cases have been described in childhood. Clinical presentation We present the case of a seven-year-old boy suffering from recurrent pneumonia and atelectasis. Intervention Previously performed chest X-rays showed bilateral hyperinflation and tracheobronchomegaly. Chest computed tomography (CT) confirmed the presence of distal enlargement of trachea and bronchi. Tracheobronchomegaly associated with recurrent respiratory tract infections is consistent with Mounier Kuhn syndrome. Pseudomonas aeruginosa was isolated from the sputum of the patient. He was then treated according to the guidelines for P. aeruginosa management in cystic fibrosis patients considering the similarities in clinical presentations and pathophysiology of both diseases. Antibiotic treatment resulted in a remarkable reduction of events of pulmonary exacerbation and hospitalizations. There are no specific guidelines for treatment options in case of pulmonary exacerbation of Mounier Kuhn syndrome. Case reports discussing the choice and efficiency of antibiotic treatment are random. Conclusion headings We share our experience of treating pulmonary exacerbation caused by P. aeruginosa in a patient with Mounier Kuhn syndrome suggesting a possible treatment option of pseudomonas infections in this syndrome.

The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas.

PubMed

Hegyi, Péter; Rakonczay, Zoltán

2011-11-15

Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.

The kappa-opiate receptor impacts the pathophysiology and behavior of substance use.

PubMed

Mysels, David; Sullivan, Maria A

2009-01-01

There is increasing evidence that the kappa-opiate receptor, in addition to the mu-opiate receptor, plays an important role in substance use pathophysiology and behavior. As dopamine activity is upregulated through chronic substance use, kappa receptor activity, mediated through the peptide dynorphin, is upregulated in parallel. Dynorphin causes dysphoria and decreased locomotion, and the upregulation of its activity on the kappa receptor likely dampens the excitation caused by increased dopaminergic activity. This feedback mechanism may have significant clinical implications for treating drug dependent patients in various stages of their pathology.

Clinical Presentation of Ulcerative Colitis in Pakistani Adults.

PubMed

Qureshi, Mustafa; Abbas, Zaigham

2015-01-01

The aim of this study was to determine the clinical presentation and severity of ulcerative colitis (UC) in Pakistani adult patients. An observational study. Data were obtained by reviewing the medical records of patients who visited a gastroenterology clinic between 2008 and 2012. There were 54 patients diagnosed as UC. The male to female ratio was 1:1. Mean age at diagnosis of UC was 38.7 ± 11.8 years (median 36.5, range 18-64). The predominant presenting symptoms were mucus diarrhea in 49 (90.7%), gross blood in stools in 42 (77.8%), abdominal pain or cramps in 40 (74.1%) and weight loss in 15 (27.7%). Left-sided colitis was present in 23 (42.6%), pancolitis in 15 (27.8%), extensive colitis in 11 (20.4%), and proctitis in five (9.2%). The severity of UC as judged by the Mayo scoring system showed that 68.5% were suffering from moderate to severe disease while 31.5% had mild disease. The extra-intestinal manifestation were found only in seven patients; arthritis in five patients and anterior uveitis in two patients. The arthritis was unilateral and the sites were knee joint in three patients and sacroiliac joint in two patients. Ulcerative colitis presents in our adult patients may present at any age with no gender preponderance. The disease severity is moderate to severe in the majority of patients and more than half of them have left-sided colitis or pancolitis at the time of presentation. Extraintestinal manifestations were not common. Qureshi M, Abbas Z. Clinical Presentation of Ulcerative Colitis in Pakistani Adults. Euroasian J Hepato-Gastroenterol 2015;5(2):127-130.

Pathophysiology of infantile pulmonary arterial hypertension induced by monocrotaline.

PubMed

Dias-Neto, Marina; Luísa-Neves, Ana; Pinho, Sónia; Gonçalves, Nádia; Mendes, Maria; Eloy, Catarina; Lopes, José M; Gonçalves, Daniel; Ferreira-Pinto, Manuel; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

2015-06-01

Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.

Improvised explosive devices: pathophysiology, injury profiles and current medical management.

PubMed

Ramasamy, A; Hill, A M; Clasper, J C

2009-12-01

The improvised explosive device (IED), in all its forms, has become the most significant threat to troops operating in Afghanistan and Iraq. These devices range from rudimentary home made explosives to sophisticated weapon systems containing high-grade explosives. Within this broad definition they may be classified as roadside explosives and blast mines, explosive formed pojectile (EFP) devices and suicide bombings. Each of these groups causeinjury through a number of different mechanisms and can result in vastly different injury profiles. The "Global War on Terror" has meant that incidents which were previously exclusively seen in conflict areas, can occur anywhere, and clinicians who are involved in emergency trauma care may be required to manage casualties from similar terrorist attacks. An understanding of the types of devices and their pathophysiological effects is necessary to allow proper planning of mass casualty events and to allow appropriate management of the complex poly-trauma casualties they invariably cause. The aim of this review article is to firstly describe the physics and injury profile from these different devices and secondly to present the current clinical evidence that underpins their medical management.

A Web-based e-learning course: integration of pathophysiology into pharmacology.

PubMed

Tse, Mimi M Y; Lo, Lisa W L

2008-11-01

The Internet is becoming the preferred place to find information. Millions of people go online in search of health and medical information. Likewise, the demand for Web-based courses is growing. This paper presents the development, utilization, and evaluation of a Web-based e-learning course for nursing students, entitled Integration of Pathophysiology into Pharmacology. The pathophysiology component included cardiovascular, respiratory, central nervous and immune system diseases, while the pharmacology component was developed based on 150 commonly used drugs. One hundred and nineteen Year 1 nursing students took part in the course. The Web-based e-learning course materials were uploaded to a WebCT for students' self-directed learning and attempts to pass two scheduled online quizzes. At the end of the semester, students were given a questionnaire to measure the e-learning experience. Their experience in the e-learning course was a positive one. Students stated that they were able to understand rather than memorize the subject content, and develop their problem solving and critical thinking abilities. Online quizzes yielded satisfactory results. In the focus group interview, students indicated that they appreciated the time flexibility and convenience associated with Web-based learning, and also made good suggestions for enhancing Web-based learning. The Web-based approach is promising for teaching and learning pathophysiology and pharmacology for nurses and other healthcare professionals.

Advancing knowledge of right ventricular pathophysiology in chronic pressure overload: Insights from experimental studies.

PubMed

Guihaire, Julien; Noly, Pierre Emmanuel; Schrepfer, Sonja; Mercier, Olaf

2015-10-01

The right ventricle (RV) has to face major changes in loading conditions due to cardiovascular diseases and pulmonary vascular disorders. Clinical experience supports evidence that the RV better compensates for volume than for pressure overload, and for chronic than for acute changes. For a long time, right ventricular (RV) pathophysiology has been restricted to patterns extrapolated from left heart studies. However, the two ventricles are anatomically, haemodynamically and functionally distinct. RV metabolic properties may also result in a different behaviour in response to pathological conditions compared with the left ventricle. In this review, current knowledge of RV pathophysiology is reported in the setting of chronic pressure overload, including recent experimental findings and emerging concepts. After a time-varying compensated period with preserved cardiac output despite overload conditions, RV failure finally occurs, leading to death. The underlying mechanisms involved in the transition from compensatory hypertrophy to maladaptive remodelling are not completely understood. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Developing a "clinical presentation" curriculum at the University of Calgary.

PubMed

Mandin, H; Harasym, P; Eagle, C; Watanabe, M

1995-03-01

Currently, medical curricula are structured according to disciplines, body systems, or clinical problems. Beginning in 1988, the faculty of the University of Calgary Faculty of Medicine (U of C) carefully evaluated the advantages and disadvantages of each of these models in seeking to revise their school's curriculum. However, all three models fell short of a curricular structure based on current knowledge and principles of adult learning, clinical problem solving, community demands, and curriculum management. By 1991, the U of C had formulated a strategic plan for a revised curriculum structure based on the way patients present to physicians, and implementation of this plan has begun. In creating the new curriculum, 120 clinical presentations (e.g., "loss of consciousness/syncope") were defined and each was assigned to an individual or small group of faculty for development based on faculty expertise and interest. Terminal objectives (i.e., "what to do") were defined for each presentation to describe the appropriate clinical behaviors of a graduating physician. Experts developed schemes that outlined how they differentiated one cause (i.e., disease category) from another. The underlying enabling objectives (i.e., knowledge, skills, and attitudes) for reaching the terminal objectives for each clinical presentation were assigned as departmental responsibilities. A new administrative structure evolved in which there is a partnership between a centralized multidisciplinary curriculum committee and the departments. This new competency-based, clinical presentation curriculum is expected to significantly enhance students' development of clinical problem-solving skills and affirms the premise that prudent, continuous updating is essential for improving the quality of medical education.

Clinical peptidomic analysis by a one-step direct transfer technology: its potential utility for monitoring of pathophysiological status in female reproductive system disorders.

PubMed

Araki, Yoshihiko; Nonaka, Daisuke; Hamamura, Kensuke; Yanagida, Mitsuaki; Ishikawa, Hitoshi; Banzai, Michio; Maruyama, Mayuko; Endo, Shuichiro; Tajima, Atsushi; Lee, Lyang-Ja; Nojima, Michio; Takamori, Kenji; Yoshida, Koyo; Takeda, Satoru; Tanaka, Kenji

2013-10-01

To date, numerous studies have searched for candidate molecules or clinical examination methods as potential biomarkers for monitoring intractable diseases, such as carcinomas. Evidence accumulated over the past decade shows that many proteolytic peptides appear in human humoral fluids, including peripheral blood, in association with an individual's health condition. Although an analysis of the whole peptide (the 'peptidome') using mass spectrometry is thought to be one of the most powerful and promising experimental approaches, it has failed to identify biomarkers in the clinical blood samples, presumably due to the methodological limitations. In general, commonly used techniques for proteomic analysis of blood require the removal of large amounts of serum/plasma proteins prior to mass spectrometry analysis, and this step seems to have resulted in the overlooking of important biomarkers during the analytical process. Here, we provide a brief overview of a new quantitative peptidomic analysis by a one-step direct transfer technology without depletion of major blood proteins. Using this technology, we herein report experimental data on serum peptidomic analysis for patients with pregnancy-induced hypertension as a clinical model. In addition, we refer to the potential utility of this approach for the monitoring of pathophysiological status in female reproductive system disorders in general. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

The pathophysiology of pulmonary hypertension in left heart disease.

PubMed

Breitling, Siegfried; Ravindran, Krishnan; Goldenberg, Neil M; Kuebler, Wolfgang M

2015-11-01

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure leading to right-sided heart failure and can arise from a wide range of etiologies. The most common cause of PH, termed Group 2 PH, is left-sided heart failure and is commonly known as pulmonary hypertension with left heart disease (PH-LHD). Importantly, while sharing many clinical features with pulmonary arterial hypertension (PAH), PH-LHD differs significantly at the cellular and physiological levels. These fundamental pathophysiological differences largely account for the poor response to PAH therapies experienced by PH-LHD patients. The relatively high prevalence of this disease, coupled with its unique features compared with PAH, signal the importance of an in-depth understanding of the mechanistic details of PH-LHD. The present review will focus on the current state of knowledge regarding the pathomechanisms of PH-LHD, highlighting work carried out both in human trials and in preclinical animal models. Adaptive processes at the alveolocapillary barrier and in the pulmonary circulation, including alterations in alveolar fluid transport, endothelial junctional integrity, and vasoactive mediator secretion will be discussed in detail, highlighting the aspects that impact the response to, and development of, novel therapeutics. Copyright © 2015 the American Physiological Society.

Advances in the pathophysiology of pre-eclampsia and related podocyte injury

PubMed Central

Craici, Iasmina M.; Wagner, Steven J.; Weissgerber, Tracey L.; Grande, Joseph P.; Garovic, Vesna D.

2014-01-01

Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions. PMID:24573315

[Studies on clinical pathophysiology of pseudophakic/aphakic eyes--a journey of 4 decades].

PubMed

Miyake, Kensaku

2008-03-01

disruption of the aqueous barrier function, drugs used perioperatively, biocompatibility of IOL materials, and effects of preservative agents. Research on preservative agents disclosed that the preservative agent in anti-glaucoma drops more strong by induced pseudophakic CME than the anti-glaucoma agent itself. Thus, this introduced a new concept called Our desire to closely observe the endosurface of the iris, ciliary processes and anterior vitreous face, all of which are closely related to phacoemulsification techniques, posterior chamber lens fixation, and active transport of PG, led me to the development of "Posterior video technique" (Miyake-Apple View). The technique since then has been used to evaluate cataract surgical techniques, to analyze complications, to review IOL designs and fixation techniques, to pre-clinically evaluate surgical devices, and to study variations of local anatomy related to cataract/IOL surgery. The method is also useful as an educational as well as a presentational tool, and it has now been accepted world-wide. The pathogenesis of aphakic/pseudophakic CME, physiological evaluation centering on blood-aqueous barrier function, and preclinical evaluation using the Posterior video technique have all played a significant role in establishing today's safe cataract/IOL implantation surgery.

[Chronic daily headache: clinical presentation].

PubMed

Krymchantowski, A V; Moreira Filho, P F

2000-06-01

Chronic daily headache (CDH) represents a group of any headache disorder that occurs on a daily or near daily basis, for longer than 6 months. Even though it is a common problem, it is not a well defined disorder, resulting in controversies regarding its identification, description and approach. Three hundred patients, 232 women and 68 men, ages 16 to 86 (mean 38 years old for the women and 42 for the men), attending a headache center and fulfilling the proposed criteria for CDH (Silberstein et al.) and presenting headache 28 days per month were retrospectively studied. The clinical features allowed the primary headache diagnosis, before the transformation into daily presentation as: transformed migraine (TM ) in 271 patients (90,3%), chronic tension-type headache (CTTH) in 26 patients (8,7%) and new daily persistent headache (NDPH) in 3 patients (1%). Among the TM patients, the most observed presentation was pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with a progressive onset. The association with nausea and phonophobia was demonstrated in 60% and 32% of the patients respectively. The association with photophobia and sleep disturbances, as well as the occurrence of intermittent headache attacks, was different among male and female patients. With regard to the CTTH patients, pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with sleep disturbances and no associated symptoms, was the predominant presentation.

Group 2 Pulmonary Hypertension: Pulmonary Venous Hypertension: Epidemiology and Pathophysiology.

PubMed

Clark, Craig B; Horn, Evelyn M

2016-08-01

Pulmonary hypertension from left heart disease (PH-LHD) is the most common form of PH, defined as mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≥15 mm Hg. PH-LHD development is associated with more severe left-sided disease and its presence portends a poor prognosis, particularly once right ventricular failure develops. Treatment remains focused on the underlying LHD and despite initial enthusiasm for PH-specific therapies, most studies have been disappointing and their routine clinical use cannot be recommended. More work is urgently needed to better understand the pathophysiology underlying this disease and to develop effective therapeutic strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of biological sex on the pathophysiology of the heart

PubMed Central

Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

2014-01-01

Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. PMID:23763376

Effects of biological sex on the pathophysiology of the heart.

PubMed

Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

2014-02-01

Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. © 2013 The British Pharmacological Society.

THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET

PubMed Central

Schmidt-Erfurth, Ursula; van Lookeren Campagne, Menno; Henry, Erin C.; Brittain, Christopher

2017-01-01

Purpose: Geographic atrophy (GA) is an advanced, vision-threatening form of age-related macular degeneration (AMD) affecting approximately five million individuals worldwide. To date, there are no approved therapeutics for GA treatment; however, several are in clinical trials. This review focuses on the pathophysiology of GA, particularly the role of complement cascade dysregulation and emerging therapies targeting the complement cascade. Methods: Primary literature search on PubMed for GA, complement cascade in age-related macular degeneration. ClinicalTrials.gov was searched for natural history studies in GA and clinical trials of drugs targeting the complement cascade for GA. Results: Cumulative damage to the retina by aging, environmental stress, and other factors triggers inflammation via multiple pathways, including the complement cascade. When regulatory components in these pathways are compromised, as with several GA-linked genetic risk factors in the complement cascade, chronic inflammation can ultimately lead to the retinal cell death characteristic of GA. Complement inhibition has been identified as a key candidate for therapeutic intervention, and drugs targeting the complement pathway are currently in clinical trials. Conclusion: The complement cascade is a strategic target for GA therapy. Further research, including on natural history and genetics, is crucial to expand the understanding of GA pathophysiology and identify effective therapeutic targets. PMID:27902638

An atypical presentation of cardiac tamponade and periorbital swelling in a patient with eosinophilic granulomatosis with polyangiitis: a case report.

PubMed

Keefe, Alexandra C; Hymas, Joseph C; Emerson, Lyska L; Ryan, John J

2017-09-24

Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated. We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. She was found to have significant hypereosinophilia and cardiac tamponade physiology. A biopsy confirmed extensive infiltration of both lungs and pericardium by eosinophils. She did not have any anti-neutrophil cytoplasmic antibodies. Eosinophilic granulomatosis with polyangiitis diagnosis does not require the presence of anti-neutrophil cytoplasmic antibodies. Anti-neutrophil cytoplasmic antibody-positive and anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis may present with different clinical phenotypes, perhaps suggesting two distinct disease etiologies and distinct pathophysiology.

Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease

PubMed Central

How, Joan; Zhou, Amy; Oh, Stephen T.

2016-01-01

Myeloproliferative neoplasms (MPNs) are the most common underlying prothrombotic disorder found in patients with splanchnic vein thrombosis (SVT). Clinical risk factors for MPN-associated SVTs include younger age, female sex, concomitant hypercoagulable disorders, and the JAK2 V617F mutation. These risk factors are distinct from those associated with arterial or deep venous thrombosis (DVT) in MPN patients, suggesting disparate disease mechanisms. The pathophysiology of SVT is thought to derive from local interactions between activated blood cells and the unique splanchnic endothelial environment. Other mutations commonly found in MPNs, including CALR and MPL, are rare in MPN-associated SVT. The purpose of this article is to review the clinical and molecular risk factors for MPN-associated SVT, with particular focus on the possible mechanisms of SVT formation in MPN patients. PMID:28246554

Toward a more precise, clinically--informed pathophysiology of pathological laughing and crying.

PubMed

Lauterbach, Edward C; Cummings, Jeffrey L; Kuppuswamy, Preetha Sharone

2013-09-01

Involuntary emotional expression disorder (IEED) includes the syndromes of pathological laughing and crying (PLC) and emotional lability (EL). Review of the lesion, epilepsy, and brain stimulation literature leads to an updated pathophysiology of IEED. A volitional system involving frontoparietal (primary motor, premotor, supplementary motor, posterior insular, dorsal anterior cingulate gyrus (ACG), primary sensory and related parietal) corticopontine projections inhibits an emotionally-controlled system involving frontotemporal (orbitofrontal, ventral ACG, anterior insular, inferior temporal, and parahippocampal) projections targeting the amygdala-hypothalamus-periaqueductal gray (PAG)-dorsal tegmentum (dTg) complex that regulates emotional displays. PAG activity is regulated by glutamatergic NMDA, muscarinic M1-3, GABA-A, dopamine D2, norepinephrine alpha-1,2, serotonin 5HT1a, 5HT1b/d, and sigma-1 receptors, with an acetylcholine/GABA balance mediating volitional inhibition of the PAG. Lesions of the volitional corticopontine projections (or of their feedback or processing circuits) can produce PLC. Direct activation of the emotional pathway can result in EL and the laughing or crying of gelastic and dacrystic epilepsy. A criterion-based nosology of PLC and EL subtypes is offered. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pathophysiology and classification of primary graft dysfunction after lung transplantation

PubMed Central

Morrison, Morvern Isabel; Pither, Thomas Leonard

2017-01-01

The term primary graft dysfunction (PGD) incorporates a continuum of disease severity from moderate to severe acute lung injury (ALI) within 72 h of lung transplantation. It represents the most significant obstacle to achieving good early post-transplant outcomes, but is also associated with increased incidence of bronchiolitis obliterans syndrome (BOS) subsequently. PGD is characterised histologically by diffuse alveolar damage, but is graded on clinical grounds with a combination of PaO2/FiO2 (P/F) and the presence of radiographic infiltrates, with 0 being absence of disease and 3 being severe PGD. The aetiology is multifactorial but commonly results from severe ischaemia-reperfusion injury (IRI), with tissue-resident macrophages largely responsible for stimulating a secondary ‘wave’ of neutrophils and lymphocytes that produce severe and widespread tissue damage. Donor history, recipient health and operative factors may all potentially contribute to the likelihood of PGD development. Work that aims to minimise the incidence of PGD in ongoing, with techniques such as ex vivo perfusion of donor lungs showing promise both in research and in clinical studies. This review will summarise the current clinical status of PGD before going on to discuss its pathophysiology, current therapies available and future directions for clinical management of PGD. PMID:29268419

Retinal vein occlusion: pathophysiology and treatment options.

PubMed

Karia, Niral

2010-07-30

This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.

Pathophysiology of motor dysfunction in a childhood motor neuron disease caused by mutations in the riboflavin transporter.

PubMed

Menezes, Manoj P; Farrar, Michelle A; Webster, Richard; Antony, Jayne; O'Brien, Katherine; Ouvrier, Robert; Kiernan, Matthew C; Burns, Joshua; Vucic, Steve

2016-01-01

Brown-Vialetto-Van Laere (BVVL) syndrome is a progressive motor and sensory neuronopathy secondary to mutations in SLC52A2 encoding the riboflavin transporter type 2 (RFVT2). The phenotype is characterized by early childhood onset hearing loss and sensory ataxia followed by progressive upper limb weakness, optic atrophy, bulbar weakness and respiratory failure. To gain further insight into disease pathophysiology and response to riboflavin supplementation, the present study investigated whether axonal ion channel or membrane abnormalities were a feature of BVVL. Axonal excitability studies and clinical assessments were prospectively undertaken on six patients with BVVL secondary to riboflavin transporter deficiency type 2 (age range 10-21 years) at baseline and after 12 months of riboflavin (1000 mg daily) therapy. At baseline, depolarizing and hyperpolarizing threshold electrotonus was 'fanned out' and superexcitability was increased, while the resting current-threshold gradient and refractoriness were significantly reduced in BVVL patients when compared to controls. Mathematical modeling suggested that functional alterations of myelin underlay these findings with an increase in myelin permeability. Riboflavin therapy resulted in partial normalization of the axonal excitability findings, paralleled by maintenance of muscle strength. The present study established that abnormalities in myelin permeability at the paranode was a feature of BVVL and were partially normalized with riboflavin therapy. This study reveals a novel pathophysiological process for motor nerve dysfunction in BVVL. It also indicates that nerve excitability studies may be further developed in larger cohorts as a potential biomarker to identify treatment response for BVVL patients. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

The hypertension of Cushing's syndrome: controversies in the pathophysiology and focus on cardiovascular complications.

PubMed

Isidori, Andrea M; Graziadio, Chiara; Paragliola, Rosa Maria; Cozzolino, Alessia; Ambrogio, Alberto G; Colao, Annamaria; Corsello, Salvatore M; Pivonello, Rosario

2015-01-01

Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of in-vivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first 'Altogether to Beat Cushing's syndrome' workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome.

Clinical linguistics: its past, present and future.

PubMed

Perkins, Michael R

2011-11-01

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the results of a survey of articles published in Clinical Linguistics & Phonetics between 1987 and 2008 which shows, for example, a consistent primary focus on phonetics and phonology at the expense of grammar, semantics and pragmatics. I also trace the gradual broadening of the discipline from its roots in structural linguistics to its current reciprocal relationship with speech and language pathology and a range of other academic disciplines. Finally, I consider the scope of clinical linguistic research in 2011 and assess how the discipline seems likely develop in the future.

Acute pathophysiological processes after ischaemic and traumatic brain injury.

PubMed

Kunz, Alexander; Dirnagl, Ulrich; Mergenthaler, Philipp

2010-12-01

Ischaemic stroke and brain trauma are among the leading causes of mortality and long-term disability in the western world. Enormous endeavours have been made to elucidate the complex pathophysiology of ischaemic and traumatic brain injury with the intention of developing new therapeutic strategies for patients suffering from these devastating diseases. This article reviews the current knowledge on cascades that are activated after ischaemic and traumatic brain injury and that lead to progression of tissue damage. Main attention will be on pathophysiological events initiated after ischaemic stroke including excitotoxicity, oxidative/nitrosative stress, peri-infarct depolarizations, apoptosis and inflammation. Additionally, specific pathophysiological aspects after traumatic brain injury will be discussed along with their similarities and differences to ischaemic brain injury. This article provides prerequisites for understanding the therapeutic strategies for stroke and trauma patients which are addressed in other articles of this issue. Copyright © 2010 Elsevier Ltd. All rights reserved.

Clinical Physiology: A Successful Academic and Clinical Discipline is Threatened in Sweden

ERIC Educational Resources Information Center

Arheden, Hakan

2009-01-01

Clinical physiologists in Sweden are physicians (the majority with a PhD degree) with thorough training in system physiology and pathophysiology. They investigate patients in a functional approach and are engaged in basic and applied physiology teaching and research. In 1954, clinical physiology was founded as an independent academic and clinical…

Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology.

PubMed

Jennings, Brett L; Sahan-Firat, Seyhan; Estes, Anne M; Das, Kanak; Farjana, Nasreen; Fang, Xiao R; Gonzalez, Frank J; Malik, Kafait U

2010-10-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study showing that angiotensin II-induced vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice (1000 μg/kg per day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased vascular reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor 2,3',4,5'-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1(-/-) mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3',4,5'-tetramethoxystilbene, which prevents both cytochrome P450 1B1-dependent and -independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases.

CYTOCHROME P450 1B1 CONTRIBUTES TO ANGIOTENSIN II-INDUCED HYPERTENSION AND ASSOCIATED PATHOPHYSIOLOGY

PubMed Central

Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Gonzalez, Frank J.; Malik, Kafait U.

2010-01-01

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study that angiotensin II-induced vascular smooth muscle cell growth is dependent on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg/min) or mice (1000 μg/kg/day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor, 2,3′,4,5′-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1-/- mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3′,4,5′-tetramethoxystilbene which prevents both cytochrome P450 1B1-dependent and independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases. PMID:20805442

The Clinical Presentation of Oral Potentially Malignant Disorders.

PubMed

Mccormick, Neal J; Thomson, Peter J; Carrozzo, Marco

2016-02-01

Early detection of oral cancer improves survival rates significantly, however, the incidence of oral cancer has continued to rise in the UK - between 2002-2012, it increased by more than 30%. There is currently no national screening programme for oral cancer, so undertaking a full examination of the oral mucosa during routine dental appointments is vital. Although strong evidence is still lacking, oral cancer is thought to be preceded by oral potential malignant disorders (OPMDs) or oral precancerous diseases. These mainly present as white/red lesions within the mouth and their clinical appearance can be challenging to diagnose accurately, which can lead to them being misdiagnosed as negligible problems. Dentists must keep up to date with OPMDs detection and ensure they are capable of correctly recognising lesions that carry a potential risk. This paper aims to provide a brief overview on OPMDs, highlighting potentially malignant disorders as they may present to the practitioner, showing their typical clinical appearance, and suggesting differential diagnosis and clinical management in dental practice.

Retinal vein occlusion: pathophysiology and treatment options

PubMed Central

Karia, Niral

2010-01-01

This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms. PMID:20689798

Theophylline-Induced Seizures: Clinical and Pathophysiologic Aspects

PubMed Central

Nakada, Tsutomu; Kwee, Ingrid L.; Lerner, Alfred M.; Remler, Michael P.

1983-01-01

The clinical features and management of theophylline-induced seizures are not well appreciated in spite of their unique aspects. These seizures tend to occur in neurologically intact patients and leave no or only minor neurologic sequelae if controlled early. They begin with focal motor seizures with or without secondary generalization and are followed by stupor or coma. They are responsive only to adjustment of theophylline dosage. Should the motor phenomenon persist, it takes the form of epilepsia partialis continua. Extensive workup for a structural brain lesion may be unrewarding. The electroencephalogram typically shows periodic lateralized epileptiform discharges, which may provide a diagnostic clue. PMID:6858124

Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies.

PubMed

Voulgari, Christina; Papadogiannis, Dimitrios; Tentolouris, Nicholas

2010-10-21

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.

Clinical presentation of postnatal and non-postnatal depressive episodes.

PubMed

Cooper, Carly; Jones, Lisa; Dunn, Emma; Forty, Liz; Haque, Sayeed; Oyebode, Femi; Craddock, Nick; Jones, Ian

2007-09-01

The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

Herpes zoster - typical and atypical presentations.

PubMed

Dayan, Roy Rafael; Peleg, Roni

2017-08-01

Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

[Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

PubMed

Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

2014-08-01

Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury.

PubMed

Sahuquillo, Juan; Vilalta, Anna

2007-01-01

neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.

Acute and chronic fluid misdirection syndrome: pathophysiology and treatment.

PubMed

Grzybowski, Andrzej; Kanclerz, Piotr

2018-01-01

To summarize our current understanding of the specific pathogenic mechanisms of the fluid misdirection syndrome and possible treatment methods. We used the PubMed web platform to find relevant studies using the following keywords: infusion misdirection syndrome, aqueous misdirection syndrome, ciliary block, ciliovitreal block, capsular block, intraoperative fluid misdirection, subcapsular fluid entrapment, acute intraoperative rock-hard eye syndrome, positive vitreous pressure glaucoma, and malignant glaucoma. Other publications were also considered as a potential source of information when referenced in relevant articles. We collected and analyzed 55 articles dated from 1951 to 2016. Acute intraoperative rock-hard eye syndrome is characterized by a very shallow anterior chamber with the absence of suprachoroidal effusion or hemorrhage and no noticeable pathology of the iris-lens diaphragm. It usually occurs during uneventful phacoemulsification, particularly in hyperopic eyes. The pathophysiology of acute fluid misdirection syndrome is based on inappropriate movement of balanced salt solution via the zonular fibers. This syndrome has also been described as occurring from hours to months, or years, after the initial surgery. The pathophysiology of malignant glaucoma is based on similar mechanisms of cilio-lenticular block of aqueous flow leading to the misdirection of aqueous posteriorly into or besides the vitreous gel. Faced with these situations, vitreous decompression is required, preferably with hyaloido-capsulo-iridectomy. In phakic eyes, concomitant cataract extraction would be desirable. We believe both of these clinical conditions should be considered as one syndrome. We suggest the term acute fluid misdirection syndrome for the cascade of events during phacoemulsification surgery. Chronic fluid misdirection syndrome better describes the nature of malignant glaucoma.

Meige's Syndrome: Rare Neurological Disorder Presenting as Conversion Disorder.

PubMed

Debadatta, Mohapatra; Mishra, Ajay K

2013-07-01

Meige's syndrome is a rare neurological syndrome characterized by oromandibular dystonia and blepharospasm. Its pathophysiology is not clearly determined. A 35-year-old female presented to psychiatric department with blepharospasm and oromandibular dystonia with clinical provisional diagnosis of psychiatric disorder (Conversion Disorder). After thorough physical examination including detailed neurological exam and psychiatric evaluation no formal medical or psychiatric diagnosis could be made. The other differential diagnoses of extra pyramidal symptom, tardive dyskinesia, conversion disorder, anxiety disorder were ruled out by formal diagnostic criteria. Consequently with suspicion of Meige's syndrome she was referred to the department of Neurology and the diagnosis was confirmed. Hence, Meige's syndrome could be misdiagnosed as a psychiatric disorder such as conversion disorder or anxiety disorder because clinical features of Meige's syndrome are highly variable and affected by psychological factors and also can be inhibited voluntarily to some extent.

Blood–brain barrier dysfunction and epilepsy: Pathophysiologic role and therapeutic approaches

PubMed Central

Marchi, Nicola; Granata, Tiziana; Ghosh, Chaitali; Janigro, Damir

2016-01-01

The blood–brain barrier (BBB) is located within a unique anatomic interface and has functional ramifications to most of the brain and blood cells. In the past, the BBB was considered a pharmacokinetic impediment to antiepileptic drug penetration into the brain; nowadays it is becoming increasingly evident that targeting of the damaged or dysfunctional BBB may represent a therapeutic approach to reduce seizure burden. Several studies have investigated the mechanisms linking the onset and sustainment of seizures to BBB dysfunction. These studies have shown that the BBB is at the crossroad of a multifactorial pathophysiologic process that involves changes in brain milieu, altered neuroglial physiology, development of brain inflammation, leukocyte–endothelial interactions, faulty angiogenesis, and hemodynamic changes leading to energy mismatch. A number of knowledge gaps, conflicting points of view, and discordance between clinical and experimental data currently characterize this field of neuroscience. As more pieces are added to this puzzle, it is apparent that each mechanism needs to be validated in an appropriate clinical context. We now offer a BBB-centric view of seizure disorders, linking several aspects of seizures and epilepsy physiopathology to BBB dysfunction. We have reviewed the therapeutic, antiseizure effect of drugs that promote BBB repair. We also present BBB neuroimaging as a tool to correlate BBB restoration to seizure mitigation. Add-on cerebrovascular drug could be of efficacy in reducing seizure burden when used in association with neuronal antiepileptic drugs. PMID:22905812

Multimedia platform for authoring and presentation of clinical rounds in cardiology

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Allada, Vivekanand; Dahlbom, Magdalena; Lapstra, Lorelle

2003-05-01

We developed a multimedia presentation platform that allows retrieving data from any digital and analog modalities and to prepare a script of a clinical presentation in an XML format. This system was designed for cardiac multi-disciplinary conferences involving different cardiology specialists as well as cardiovascular surgeons. A typical presentation requires preparation of summary reports of data obtained from the different investigations and imaging techniques. An XML-based scripting methodology was developed to allow for preparation of clinical presentations. The image display program uses the generated script for the sequential presentation of different images that are displayed on pre-determined presentation settings. The ability to prepare and present clinical conferences electronically is more efficient and less time consuming than conventional settings using analog and digital documents, films and videotapes. The script of a given presentation can further be saved as part of the patient record for subsequent review of the documents and images that supported a given medical or therapeutic decision. This also constitutes a perfect documentation method for surgeons and physicians responsible of therapeutic procedures that were decided upon during the clinical conference. It allows them to review the relevant data that supported a given therapeutic decision.

Physiology and pathophysiology of potassium homeostasis.

PubMed

Palmer, Biff F; Clegg, Deborah J

2016-12-01

Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

Clinical Linguistics: Its Past, Present and Future

ERIC Educational Resources Information Center

Perkins, Michael R.

2011-01-01

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the…

Clinical experience with caroverine in inner ear diseases.

PubMed

Ehrenberger, Klaus

2002-01-01

The glutamatergic synapses between the cochlear inner hair cells and their afferent neurons seem to be mostly involved in the pathophysiology of the cochlea. Glutamatergic neurotoxicity is characterized by a mitochondrial overproduction of free oxygen radicals damaging lipid membranes and DNA structures of the postsynaptic neuron followed by the clinical symptoms of hearing loss and tinnitus. In preclinical tests, quinoxaline derivatives antagonized these deleterious consequences of too high an amount of free radicals. Therefore the clinically available quinoxaline dione caroverine provides a new approach to a successful treatment of tinnitus, sudden hearing loss and speech discrimination disorders in presbyacusis. The results of corresponding clinical trials are presented.

Pathophysiology, Diagnosis, and Treatment of Radiation Necrosis in the Brain

PubMed Central

MIYATAKE, Shin-Ichi; NONOGUCHI, Noasuke; FURUSE, Motomasa; YORITSUNE, Erina; MIYATA, Tomo; KAWABATA, Shinji; KUROIWA, Toshihiko

2015-01-01

New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain. PMID:25744350

ORAL CLINICAL LONG CASE PRESENTATION, THE NEED FOR STANDARDIZATION AND DOCUMENTATION.

PubMed

Agodirin, S O; Olatoke, S A; Rahman, G A; Agbakwuru, E A; Kolawole, O A

2015-01-01

The oral presentation of the clinical long case is commonly an implied knowledge. The challenge of the presentation is compounded by the examiners' preferences and sometimes inadequate understanding of what should be assessed. To highlight the different opinions and misconceptions of trainers as the basis for improving our understanding and assessment of oral presentation of the clinical long case. Questionnaire was administered during the West African College of Surgeons fellowship clinical examinations and at their workplaces. Eligibility criteria included being a surgeon, a trainer and responding to all questions. Of the 72 questionnaires that were returned, 36(50%) were eligible for the analysis. The 36 respondents were from 14 centers in Nigeria and Ghana. Fifty-two percent were examiners at the postgraduate medical colleges and 9(25%) were professors. Eight(22.2%) indicated they were unaware of the separate methods of oral presentation for different occasions while 21( 58.3%) respondents were aware that candidate used the "5Cs" method and the traditional compartmentalized method in long case oral presentation. Eleven(30.6%) wanted postgraduates to present differently on a much higher level than undergraduate despite not encountering same in literature and 21(58.3%) indicated it was an unwritten rule. Seventeen (47.2%) had not previously encountered the "5Cs" of history of presenting complaint in literature also 17(47.2%) teach it to medical students and their junior residents. This study has shown that examiners definitely have varying opinions on what form the oral presentation of the clinical long case at surgery fellowship/professional examination should be and it translates to their expectations of the residents or clinical students. This highlights the need for standardization and consensus of what is expected at a formal oral presentation during the clinical long case examination in order to avoid subjectivity and bias.

Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease.

PubMed

Salerno, Fabio Rosario; Parraga, Grace; McIntyre, Christopher William

2017-01-01

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio-incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom. © 2016 Wiley Periodicals, Inc.

Ion Channels in Obesity: Pathophysiology and Potential Therapeutic Targets

PubMed Central

Vasconcelos, Luiz H. C.; Souza, Iara L. L.; Pinheiro, Lílian S.; Silva, Bagnólia A.

2016-01-01

Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation. PMID:27065858

Primary progressive aphasia: a clinical approach.

PubMed

Marshall, Charles R; Hardy, Chris J D; Volkmer, Anna; Russell, Lucy L; Bond, Rebecca L; Fletcher, Phillip D; Clark, Camilla N; Mummery, Catherine J; Schott, Jonathan M; Rossor, Martin N; Fox, Nick C; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

2018-06-01

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.

PubMed

Campos, Derbis; Monaga, Madelyn

2012-06-01

Mucopolysaccharidosis type I is one of the most frequent lysosomal storage diseases. It has a high morbidity and mortality, causing in many cases severe neurological and somatic damage in the first years of life. Although the clinical phenotypes have been described for decades, and the enzymatic deficiency and many of the mutations that cause this disease are well known, the underlying pathophysiological mechanisms that lead to its development are not completely understood. In this review we describe and discuss the different pathogenic mechanisms currently proposed for this disease regarding its neurological damage. Deficiency in the lysosomal degradation of heparan sulfate and dermatan sulfate, as well as its primary accumulation, may disrupt a variety of physiological and biochemical processes: the intracellular and extracellular homeostasis of these macromolecules, the pathways related to gangliosides metabolism, mechanisms related to the activation of inflammation, receptor-mediated signaling, oxidative stress and permeability of the lysosomal membrane, as well as alterations in intracellular ionic homeostasis and the endosomal pathway. Many of the pathogenic mechanisms proposed for mucopolysaccharidosis type I are also present in other lysosomal storage diseases with neurological implications. Results from the use of methods that allow the analysis of multiple genes and proteins, in both patients and animal models, will shed light on the role of each of these mechanisms and their combination in the development of different phenotypes due to the same deficiency.

Pathophysiology of constipation in the older adult

PubMed Central

McCrea, G Lindsay; Miaskowski, Christine; Stotts, Nancy A; Macera, Liz; Varma, Madhulika G

2008-01-01

This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described. MEDLINE (1966-2007) and CINAHL (1980-2007) were searched. The following MeSH terms were used: constipation/etiology OR constipation/physiology OR constipation/physiopathology) AND (age factors OR aged OR older OR 80 and over OR middle age). Constipation is not well defined in the literature. While self-reported constipation increases with age, findings from a limited number of clinical studies that utilized objective measures do not support this association. Dysmotility and pelvic floor dysfunction are important mechanisms associated with constipation. Changes in GI function associated with aging appear to be relatively subtle based on a limited amount of conflicting data. Additional research is warranted on the effects of aging on GI function, as well as on the timing of these changes. PMID:18461648

Brief Report: Pathophysiology of Autism: Neurochemistry.

ERIC Educational Resources Information Center

Cook, Edwin H., Jr.

1996-01-01

This paper reviews what is known about the role of neurochemicals in controlling the development of the brain and in the pathophysiology of autism. Suggested approaches to further research involve using animal models, examining effects of drugs on neurochemicals, and using such technologies as positron emission tomography and magnetic resonance…

Pathophysiology and Japanese clinical characteristics in Marfan syndrome.

PubMed

Fujita, Daishi; Takeda, Norifumi; Imai, Yasushi; Inuzuka, Ryo; Komuro, Issei; Hirata, Yasunobu

2014-08-01

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome. © 2014 Japan Pediatric Society.

Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity

PubMed Central

Chung, Woo-Baek; Youn, Ho-Joong

2016-01-01

Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline-induced cardiotoxicity and strategies for protecting the myocardium from anthracycline. PMID:27378126

Eye Tracking Dysfunction in Schizophrenia: Characterization and Pathophysiology

PubMed Central

Sereno, Anne B.; Gooding, Diane C.; O’Driscoll, Gilllian A.

2011-01-01

Eye tracking dysfunction (ETD) is one of the most widely replicated behavioral deficits in schizophrenia and is over-represented in clinically unaffected first-degree relatives of schizophrenia patients. Here, we provide an overview of research relevant to the characterization and pathophysiology of this impairment. Deficits are most robust in the maintenance phase of pursuit, particularly during the tracking of predictable target movement. Impairments are also found in pursuit initiation and correlate with performance on tests of motion processing, implicating early sensory processing of motion signals. Taken together, the evidence suggests that ETD involves higher-order structures, including the frontal eye fields, which adjust the gain of the pursuit response to visual and anticipated target movement, as well as early parts of the pursuit pathway, including motion areas (the middle temporal area and the adjacent medial superior temporal area). Broader application of localizing behavioral paradigms in patient and family studies would be advantageous for refining the eye tracking phenotype for genetic studies. PMID:21312405

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

PubMed

Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

2017-05-10

Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

PubMed Central

Sibmooh, Nathawut; Fucharoen, Suthat

2017-01-01

Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

Intravascular hemolysis and the pathophysiology of sickle cell disease

PubMed Central

Kato, Gregory J.; Steinberg, Martin H.; Gladwin, Mark T.

2017-01-01

Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non–oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias. PMID:28248201

Arterial hypertension in the female world: pathophysiology and therapy.

PubMed

Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

2016-04-01

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.

A novel small animal extracorporeal circulation model for studying pathophysiology of cardiopulmonary bypass.

PubMed

Fujii, Yutaka; Shirai, Mikiyasu; Inamori, Shuji; Takewa, Yoshiaki; Tatsumi, Eisuke

2015-03-01

Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECCcauses damage to blood components and is non-physiologic, its pathophysiology has not been fully elucidated. This is because difficulty in clinical research and animal experiments keeps the knowledge insufficient. Therefore, it is desirable to have a miniature ECC model for small animals, which enables repetitive experiments, to study the mechanism of pathophysiological changes during ECC. We developed a miniature ECC system and applied it to the rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb) concentration, serum cytokines (TNF-α, IL-6, IL-10), biochemical markers (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing whether the rat ECC model is comparable to the human ECC. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride), and roller pump. Priming volume of this system is only 8 ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group (n = 7). Blood samples were collected before, 60 and 120 min after initiation of ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10 g/dL, respectively. The levels of the inflammatory and biochemical markers and the W/D ratio were significantly elevated in the ECC group, indicating some organ damages and systemic inflammatory responses during ECC. We successfully established the ECC for the rat. This miniature ECC model could be a useful approach for studying the mechanism of pathophysiology during ECC and basic assessment of the ECC devices.

Present status of yellow fever: memorandum from a PAHO meeting.

PubMed

1986-01-01

An international seminar on the treatment and laboratory diagnosis of yellow fever, sponsored by the Pan American Health Organization (PAHO) and held in 1984, differed from previous meetings on yellow fever because of its emphasis on the care and management of patients and because the participants included specialists from several branches of medicine, such as hepatology, haematology, cardiology, infectious diseases, pathology and nephrology. The meeting reviewed the current status of yellow fever and problems associated with case-finding and notification; features of yellow fever in individual countries of Latin America; health services and facilities for medical care as they relate to diagnosis and management of cases; prevention strategies for and current status of immunization programmes; clinical and pathological aspects of yellow fever in humans; pathogenesis and pathophysiology of yellow fever in experimental animal models; clinical and specific laboratory diagnosis; treatment of the disease and of complications in the functioning of individual organ systems; prognosis and prognostic indicators; and directions for future clinical and experimental research on pathophysiology and treatment.

Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success

PubMed Central

Fengler, Karl; Rommel, Karl Philipp; Okon, Thomas; Schuler, Gerhard; Lurz, Philipp

2016-01-01

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success. PMID:27621771

The hypertension of Cushing's syndrome: controversies in the pathophysiology and focus on cardiovascular complications

PubMed Central

Isidori, Andrea M.; Graziadio, Chiara; Paragliola, Rosa Maria; Cozzolino, Alessia; Ambrogio, Alberto G.; Colao, Annamaria; Corsello, Salvatore M.; Pivonello, Rosario

2015-01-01

Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of in-vivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first ‘Altogether to Beat Cushing's syndrome’ workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome. PMID:25415766

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

PubMed Central

Koulouras, Vasilios; Papathanakos, Georgios; Papathanasiou, Athanasios; Nakos, Georgios

2016-01-01

Acute respiratory distress syndrome (ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the “sponge lung” - and the “shape matching” -model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients’ response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort. PMID:27152255

Spontaneous Pneumomediastinum: Case Presentation to a College Student Health Clinic

ERIC Educational Resources Information Center

Spotts, P. Hunter

2017-01-01

The author describes a case of spontaneous pneumomediastinum (SPM) in a 19-year-old man presenting to a college student health clinic. The author also provides a review on SPM, including clinical manifestations, diagnostic evaluation, and management.

Pathophysiological Progression Model for Selected Toxicological Endpoints

EPA Science Inventory

The existing continuum paradigms are effective models to organize toxicological data associated with endpoints used in human health assessments. A compendium of endpoints characterized along a pathophysiological continuum would serve to: weigh the relative importance of effects o...

Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system.

PubMed

Cai, Anping; Li, Liwen; Zhou, Yingling

2016-01-01

In past decades, growing evidence from basic and clinical researches reveal that small guanosine triphosphate binding protein ras homolog gene family, member A (RhoA) and its main effector Rho-associated kinase (ROCK) play central and complex roles in cardiovascular systems, and increasing RhoA and ROCK activity is associated with a broad range of cardiovascular diseases such as congestive heart failure, atherosclerosis, and hypertension. Favorable outcomes have been observed with ROCK inhibitors treatment. In this review, we briefly summarize the pathophysiological roles of RhoA/ROCK signaling pathway on cardiovascular system, displaying the potential benefits in the cardiovascular system with controlling RhoA/ROCK signaling pathway.

Neurobiology of the premonitory urge in Tourette syndrome: Pathophysiology and treatment implications

PubMed Central

Cavanna, Andrea E.; Black, Kevin J; Hallett, Mark; Voon, Valerie

2017-01-01

Motor and vocal tics are relatively common motor manifestations identified as the core features of Tourette syndrome. Although traditional descriptions have focused on objective phenomenological observations, such as anatomical location, number and frequency of tics, patients’ first-person accounts have consistently reported characteristic subjective correlates. These sensory phenomena are often described as a feeling of mounting inner tension or urge to move (“premonitory urge”), which is transiently relieved by tic expression. This paper reviews the existing literature on the clinical and neurobiological aspects of the premonitory urge in patients with Tourette syndrome, with focus on its pathophysiology and possible treatment implications. PMID:28121259

Arterial hypertension after age 65: from epidemiology and pathophysiology to therapy Do we know where we stand?

PubMed

Gąsowski, Jerzy; Piotrowicz, Karolina; Messerli, Franz H

2018-01-01

Arterial hypertension is a prevalent disease with great harming potential. After the age of 55 years the remaining lifetime risk of hypertension amounts to 90%. Despite the constant advances some important issues such as the cut-off blood pressure for the initiation of antihypertensive therapy or the therapeutic goal are debated. In this review, we present - based on the available literature - the current concepts concerning the pathophysiology, epi-demiology and antihypertensive therapy in patients aged 65 years or older. The pathophysiology of hypertension in older patients in principle rests on stiffening of large conduit arteries, which leads to greater systolic and lower diastolic blood pressure. This in most older patients results in isolated systolic hypertension. Additionally most of these patients have low-renin hypertension. Data from large-scale clinical trials indicate that therapy of such individuals with thiazide-like diuretics and long-acting dihydropiridine calcium channel blockers as first-line medications reduces risk of complications. Based on results of recently published trials, meta-analyses, and prospective observations, the optimal on-treatment blood pressure values for most older hypertensive patients should be set within the 130-139 mmHg range. At present, lower values of standard office blood pressure in this group of patients have not been shown to be associ-ated with additional benefits, and may be associated with a greater risk of adverse events. In conclusion, we recommend that for most patients aged 65 years or more, standard office systolic blood pressure should be cautiously reduced to within 140 and 130 mmHg, preferably with a thiazide-like diuretic, long acting dihydropiridine calcium channel blocker or their combination.

Poststroke Seizures and Epilepsy: Clinical Studies and Animal Models

PubMed Central

Kelly, Kevin M.

2002-01-01

Poststroke seizures and epilepsy have been described in numerous clinical studies for many years. Most studies are retrospective in design, include relatively small numbers of patients, have limited periods of follow-up, and report a diversity of findings. Well-designed clinical trials and population studies in the recent past addressed several critical clinical issues and generated important findings regarding the occurrence of poststroke seizures and epilepsy. In contrast, the pathophysiologic events of injured brain that establish poststroke epileptogenesis are not well understood, and animal modeling has had limited development. Reviews of several important clinical studies and animal models that hold promise for a better understanding of poststroke epileptogenesis are presented. PMID:15309107

Fibrocartilaginous embolic myelopathy: demographics, clinical presentation, and functional outcomes.

PubMed

Moore, Brittany J; Batterson, Anna M; Luetmer, Marianne T; Reeves, Ronald K

2018-05-25

Retrospective cohort study. To describe the demographics, clinical presentation, and functional outcomes of fibrocartilaginous embolic myelopathy (FCEM). Academic inpatient rehabilitation unit in the midwestern United States. We retrospectively searched our database to identify patients admitted between January 1, 1995 and March 31, 2016, with a high probability of FCEM. Demographic, clinical, and functional outcome measures, including Functional Independence Measure (FIM) information was obtained by chart review. We identified 31 patients with findings suggestive of FCEM (52% male), which was 2% of the nontraumatic spinal cord injury population admitted to inpatient rehabilitation. The age distribution was bimodal, with peaks in the second and sixth-to-seventh decades. The most common clinical presentation was acute pain and rapid progression of neurologic deficits consistent with a vascular myelopathy. Only three patients (10%) had FCEM documented as a diagnostic possibility. Most patients had paraplegia and neurologically incomplete injuries and were discharged to home. Nearly half of the patients required no assistive device for bladder management at discharge, but most were discharged with medications for bowel management. Median FIM walking locomotion score for all patients was 5, but most patients were discharged using a wheelchair for primary mobility. Median motor FIM subscale score was 36 at admission and 69 at discharge, with a median motor efficiency of 1.41. FCEM may be underdiagnosed and should be considered in those with the appropriate clinical presentation, because their functional outcomes may be more favorable than those with other causes of spinal cord infarction.

Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease.

PubMed

Roos, Cornelis J; Quax, Paul H A; Jukema, J Wouter

2012-02-01

Patients with obesity and diabetes mellitus are at increased risk for cardiovascular events and have a higher cardiovascular morbidity and mortality. This worse prognosis is partly explained by the late recognition of coronary heart disease in these patients, due to the absence of symptoms. Early identification of coronary heart disease is vital, to initiate preventive medical therapy and improve prognosis. At present, with the use of cardiovascular risk models, the identification of coronary heart disease in these patients remains inadequate. To this end, biomarkers should improve the early identification of patients at increased cardiovascular risk. The first part of this review describes the pathophysiologic pathway from obesity to coronary heart disease. The second part evaluates several mediators from this pathophysiologic pathway for their applicability as biomarkers for the identification of coronary heart disease.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

PubMed

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-06-07

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology

PubMed Central

Ghadri, Jelena-Rima; Wittstein, Ilan Shor; Prasad, Abhiram; Sharkey, Scott; Dote, Keigo; Akashi, Yoshihiro John; Cammann, Victoria Lucia; Crea, Filippo; Galiuto, Leonarda; Desmet, Walter; Yoshida, Tetsuro; Manfredini, Roberto; Eitel, Ingo; Kosuge, Masami; Nef, Holger M; Deshmukh, Abhishek; Lerman, Amir; Bossone, Eduardo; Citro, Rodolfo; Ueyama, Takashi; Corrado, Domenico; Kurisu, Satoshi; Ruschitzka, Frank; Winchester, David; Lyon, Alexander R; Omerovic, Elmir; Bax, Jeroen J; Meimoun, Patrick; Tarantini, Guiseppe; Rihal, Charanjit; Y.-Hassan, Shams; Migliore, Federico; Horowitz, John D; Shimokawa, Hiroaki; Lüscher, Thomas Felix; Templin, Christian

2018-01-01

Abstract Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy. PMID:29850871

Neuroimaging Insights into the Pathophysiology of Sleep Disorders

PubMed Central

Desseilles, Martin; Dang-Vu, Thanh; Schabus, Manuel; Sterpenich, Virginie; Maquet, Pierre; Schwartz, Sophie

2008-01-01

Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modern neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans. Citation: Desseilles M; Dang-Vu TD; Schabus M; Sterpenich V; Maquet P; Schwartz S. Neuroimaging insights into the pathophysiology of sleep disorders. SLEEP 2008;31(6):777–794. PMID:18548822

Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies.

PubMed

Ghosh, Raktim K; Ball, Somedeb; Prasad, Vinita; Gupta, Anjan

2016-12-01

Heart failure (HF) is a burgeoning chronic health condition affecting more than 20million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Severe mitral stenosis with atypical presentation: hemorrhagic pleural effusion--a case report and literature review.

PubMed

Albalbissi, Kais A; Burress, Jonathan W; Garcia, Israel D; Iskandar, Said B

2009-02-01

Mitral stenosis is a well-described valvular heart disease. We report a 68-year-old patient with an unusual presentation of mitral stenosis. He presented with recurrent episodes of hemorrhagic pleural effusion. Afterwards, an extensive atrial thrombosis complicated his course of illness. We will discuss how the clinical presentation of mitral stenosis is mainly dictated by the underlying pathophysiology of the disease. Also, the need for anticoagulation in the setting of mitral stenosis is often linked to the presence of atrial fibrillation. We will discuss the independent risk factors for thromboembolism in the setting of mitral stenosis. Finally, a review of the current recommendation for anticoagulation is conferred.

Emergency Department Referrals for Adolescent Urgent Psychiatric Consultation: Comparison of Clinical Characteristics of Repeat-presentations and Single-presentation.

PubMed

Roberts, Nasreen; Nesdole, Robert; Hu, Tina

2018-01-01

a) to examine the demographic and clinical characteristics of repeat-presentations to an adolescent urgent psychiatric clinic, and b) to compare them with single-time presentation. This 18-month retrospective study compared repeat-presenters to age and gender matched single-time presenters. Demographic variables included age gender and ethnicity. Clinical variables included reason for referral, family history, diagnosis, recommendations and compliance. Data were analyzed using descriptive statistics, McNemar's Chi-square tests for matched pairs, and conditional logistic regression. Of 624 assessments 24% (N=151) were repeat-presentations. Compared with single-presentation, repeat-presentation group had a higher proportion of Aboriginal youth (X2 (1) = 108.28 p < 0.01), a higher proportion in special educational placement (X2 (1) = 6.82, p < 0.01), a higher proportion with a family history of anxiety disorders (X2 (1) = 10.62, p = 0.01) and substance use disorder (X2 (1) = 18.99, p < 0.01). Conditional logistic regression results suggested that repeat-presentation group had higher odds of past hospital admission (OR: 3.50, p < 0.01) higher odds of family history of mood disorders (OR: 4.86, p < 0.01) and of antisocial disorders (OR: 4.97, p = 0.02), and lower odds of recommendation compliance (OR: 0.10, p < 0.01). Repeat-presentations for urgent psychiatric consultation constitute a quarter of referrals to the urgent psychiatric clinic. Identifying and addressing factors that contribute to repeat-presentations may, assist in improving treatment compliance by ensuring focused interventions and service delivery for these youth. In turn, this will improve access to the limited urgent services for other youth.

Ultrasound monitoring of the treatment of clinically significant knee osteoarthritis.

PubMed

Vojtassak, J; Vojtassak, J

2014-01-01

The study presented an ultrasound (US) monitoring of treatment as a new imaging US method with the results of therapy of clinically significant knee osteoarthritis. X-ray is widely used for knee osteoarthritis classification, which does not involve the evaluation of the soft tissue. High frequency and high resolution US of joints (arthrosonography, echoarthrography) assess not only morphologic but also functional changes in the knee joint. In the prospective study, 110 patients with clinically significant knee osteoarthritis were treated non-operative. US examination and US monitoring of therapy was performed during 24 weeks therapy period. A remission of pathomorphologic (marginal osteofytes) and pathophysiologic (effusion in anterior knee and Baker´s cyst) attributes were evaluated according the US classification. Pathomorphologic attributes changes showed a static state, without remission or progression. Pathophysiologic attributes changes showed a remission during the study period. The highest remission was in the first three weeks, 60 % anterior knee effusion and 62 % Baker´s cyst. At the end of study, no changes from the initial US grade was observed in 16 % of effusion in anterior knee and 22 % of Baker´s cyst. Therapeutic resistant Baker´s cyst was present at the end of study in 36 %. We demonstrated a new method - US monitoring of therapy, which can objectivize the efficiency of treatment of clinically significant knee osteoarthritis. We would recommend US monitoring of therapy for the routine use in orthopedic clinical praxis (Tab. 6, Graph 3, Fig. 3, Ref. 15).

Effects of ADMA upon Gene Expression: An Insight into the Pathophysiological Significance of Raised Plasma ADMA

PubMed Central

Smith, Caroline L; Anthony, Shelagh; Hubank, Mike; Leiper, James M; Vallance, Patrick

2005-01-01

Background Asymmetric dimethylarginine (ADMA) is a naturally occurring inhibitor of nitric oxide synthesis that accumulates in a wide range of diseases associated with endothelial dysfunction and enhanced atherosclerosis. Clinical studies implicate plasma ADMA as a major novel cardiovascular risk factor, but the mechanisms by which low concentrations of ADMA produce adverse effects on the cardiovascular system are unclear. Methods and Findings We treated human coronary artery endothelial cells with pathophysiological concentrations of ADMA and assessed the effects on gene expression using U133A GeneChips (Affymetrix). Changes in several genes, including bone morphogenetic protein 2 inducible kinase (BMP2K), SMA-related protein 5 (Smad5), bone morphogenetic protein receptor 1A, and protein arginine methyltransferase 3 (PRMT3; also known as HRMT1L3), were confirmed by Northern blotting, quantitative PCR, and in some instances Western blotting analysis to detect changes in protein expression. To determine whether these changes also occurred in vivo, tissue from gene deletion mice with raised ADMA levels was examined. More than 50 genes were significantly altered in endothelial cells after treatment with pathophysiological concentrations of ADMA (2 μM). We detected specific patterns of changes that identify pathways involved in processes relevant to cardiovascular risk and pulmonary hypertension. Changes in BMP2K and PRMT3 were confirmed at mRNA and protein levels, in vitro and in vivo. Conclusion Pathophysiological concentrations of ADMA are sufficient to elicit significant changes in coronary artery endothelial cell gene expression. Changes in bone morphogenetic protein signalling, and in enzymes involved in arginine methylation, may be particularly relevant to understanding the pathophysiological significance of raised ADMA levels. This study identifies the mechanisms by which increased ADMA may contribute to common cardiovascular diseases and thereby indicates

The pathophysiology of chronic constipation

PubMed Central

Andrews, Christopher N; Storr, Martin

2011-01-01

Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. The common approach to the pathophysiology of constipation groups the disorder into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. The normal process of colonic transit and defecation is discussed, and the etiology of constipation is reviewed. PMID:22114753

Biomarkers for oxidative stress: clinical application in pediatric medicine.

PubMed

Tsukahara, Hirokazu

2007-01-01

Loads of reactive oxygen species (ROS), including superoxide anion and nitric oxide, that overburden antioxidant systems induce oxidative stress in the body. Major cellular targets of ROS are membrane lipids, proteins, nucleic acids, and carbohydrates. Circumstantial evidence suggests that ROS play a crucial role in the initiation and progression of various diseases in children and adolescents. The involvement of ROS and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in young subjects and appropriate methods for its measurement remain to be defined. Recently, specific biomarkers for oxidative damage and antioxidant defense have been introduced into the field of pediatric medicine. This review is intended to provide an overview of clinical applications of oxidative stress biomarkers in the field of pediatric medicine. First, this review presents the biochemistry and pathophysiology of ROS and antioxidant defense systems. Second, it presents a list of clinically applicable biomarkers, along with pediatric diseases in which enhanced oxidative stress might be involved. The discussion emphasizes that several reliable biomarkers are easily measurable using enzyme-linked immunosorbent assay. Third, this review presents age-related reference normal ranges of oxidative stress biomarkers, including urinary acrolein-lysine, 8-hydroxy-2'-deoxyguanosine, nitrite/nitrate, and pentosidine, and the changes of the parameters in several clinical conditions, including atopic dermatitis and diabetes mellitus. New and interesting data on oxidative stress and antioxidant defenses in neonatal biology are also presented. Fourth, this review discusses the ever-accumulating body of data linking oxidative stress to disturbances of the nitric oxide system and vascular endothelial activation/dysfunction. Finally, this review describes the reported clinical trials that have evaluated the efficacy of antioxidants for oxidative-stress related diseases

Clinical Presentation and Outcome of Patients With Optic Pathway Glioma.

PubMed

Robert-Boire, Viviane; Rosca, Lorena; Samson, Yvan; Ospina, Luis H; Perreault, Sébastien

2017-10-01

Optic pathway gliomas (OPGs) occur sporadically or in patients with neurofibromatosis type 1 (NF1). The purpose of this study was to evaluate the clinical presentation at diagnosis and at progression of patients with OPGs. We conducted a chart review of patients with OPGs diagnosed in a single center over a period of 15 years. Demographic data including age, sex, NF1 status, clinical presentation, and outcome were collected. Of the 40 patients who were identified, 23 had sporadic tumors (57.5%) and 17 had NF1-related tumors (42.5%). Among the children with NF1, there was a significant overrepresentation of girls (82.3%) (P = 0.02), while among the children without NF1, there were slightly more boys (56.5%) than girls (43.5%). The presence of nystagmus was strongly associated with sporadic optic pathway gliomas. Poor visual outcome was related to tumor affecting both optic pathways, hydrocephalus at diagnosis, and optic nerve atrophy. Of the 40 patients, five died of OPG complications (12.5%) and all had sporadic tumors. Our cohort is one of the largest with OPGs and a detailed description of the clinical presentation both at diagnosis and at progression. We observed a significant difference between sporadic and NF1 optic pathway gliomas in terms of demographics, clinical presentation, and outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease Location.

PubMed

Aziz, Danish Abdul; Moin, Maryum; Majeed, Atif; Sadiq, Kamran; Biloo, Abdul Gaffar

2017-01-01

To determine different clinical presentationsand disease location demarcatedby upper and lower gastrointestinal endoscopyand relevant histopathologyin children diagnosed with inflammatory bowel disease (IBD). This is 5 years (2010 to 2015) retrospective studyconducted at the Aga Khan University Hospitalenrolling65admitted children between 6 months to 15years from either gender, diagnosed with IBD on clinical presentation, endoscopy and biopsy. Different clinical presentations at the time of diagnosis were noted in different categories of the disease. All patients underwent upper and lower (up to the terminal ileum) endoscopy with multiple punch biopsies and histologic assessment of mucosal specimens. All endoscopies were done by paediatric gastroenterologists at endoscopy suite of the hospital and all specimens were reported by the pathology department. ESPGHAN revised criteria for the diagnosis of inflammatory bowel disease in children and an adolescent was used to standardize our diagnosis. Extent of disease on endoscopy and relevant histopathology of the biopsy samples were noted at the time of diagnosis. Data was summarized using mean, standard deviation, numbers and percentages for different variables. Total 56 children were enrolled according to inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%) patients were labeled as Indeterminate colitis (IC). Mean age at onset of symptoms was10.03±2.44 and mean age at diagnosis was11.10±2.36. Abdominal pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC. Patients diagnosed with indeterminate colitis(IC) had similar clinical features as in UC patients. Only 7% patients had some extra-intestinal features in the form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 ±12.89) was relatively high in

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review

PubMed Central

Mula-Abed, Waad-Allah S.; Ahmed, Riyaz; Ramadhan, Fatima A.; Al-Kindi, Manal K.; Al-Busaidi, Noor B.; Al-Muslahi, Hilal N.; Al-Lamki, Mohammad A.

2015-01-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario. PMID:26421121

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review.

PubMed

Mula-Abed, Waad-Allah S; Ahmed, Riyaz; Ramadhan, Fatima A; Al-Kindi, Manal K; Al-Busaidi, Noor B; Al-Muslahi, Hilal N; Al-Lamki, Mohammad A

2015-09-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient's history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario.

Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European Society of Cardiology.

PubMed

Vaccarino, Viola; Badimon, Lina; Corti, Roberto; de Wit, Cor; Dorobantu, Maria; Hall, Alistair; Koller, Akos; Marzilli, Mario; Pries, Axel; Bugiardini, Raffaele

2011-04-01

Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.

Comparison of three acute stress models for simulating the pathophysiology of stress-related mucosal disease.

PubMed

Saxena, Bhagawati; Singh, Sanjay

2017-05-30

Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.

Clinical presentation and treatment of septic arthritis in children.

PubMed

Moro-Lago, I; Talavera, G; Moraleda, L; González-Morán, G

The aim of this study is to determine the epidemiological features, clinical presentation, and treatment of children with septic arthritis. A retrospective review was conducted on a total of 141 children with septic arthritis treated in Hospital Universitario La Paz (Madrid) between the years 2000 to 2013. The patient data collected included, the joint affected, the clinical presentation, the laboratory results, the appearance, Gram stain result, and the joint fluid culture, as well as the imaging tests and the treatment. Most (94%) of the patients were less than 2 years-old. The most common location was the knee (52%), followed by the hip (21%). The septic arthritis was confirmed in 53%. No type of fever was initially observed in 49% of them, and 18% had an ESR (mm/h) or CRP (mg/l) less than 30 in the initial laboratory analysis. The joint fluid was purulent in 45% and turbid in 12%. The Gram stain showed bacteria in 4%. The fluid culture was positive in 17%. Staphylococcus aureus was the most common pathogen found, followed by Streptococcus agalactiae, Streptococcus pneumoniae, and Kingella kingae. Antibiotic treatment was intravenous administration for 7 days, followed by 21 days orally. Surgery was performed in 18% of cases. The diagnosis was only confirmed in 53% of the patients. Some of the confirmed septic arthritis did not present with the classical clinical/analytical signs, demonstrating that the traumatologist or paediatrician requires a high initial level of clinical suspicion of the disease. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

PubMed

van den Noort, J C; Bar-On, L; Aertbeliën, E; Bonikowski, M; Braendvik, S M; Broström, E W; Buizer, A I; Burridge, J H; van Campenhout, A; Dan, B; Fleuren, J F; Grunt, S; Heinen, F; Horemans, H L; Jansen, C; Kranzl, A; Krautwurst, B K; van der Krogt, M; Lerma Lara, S; Lidbeck, C M; Lin, J-P; Martinez, I; Meskers, C; Metaxiotis, D; Molenaers, G; Patikas, D A; Rémy-Néris, O; Roeleveld, K; Shortland, A P; Sikkens, J; Sloot, L; Vermeulen, R J; Wimmer, C; Schröder, A S; Schless, S; Becher, J G; Desloovere, K; Harlaar, J

2017-07-01

To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena. © 2017 EAN.

A Rare Clinical Presentation of Darier's Disease

PubMed Central

Ferizi, Mybera; Begolli-Gerqari, Antigona; Luzar, Bostjan; Kurshumliu, Fisnik; Ferizi, Mergita

2013-01-01

Darier's disease, also known as keratosis follicularis or dyskeratosis follicularis, is a rare disorder of keratinization. It is an autosomal dominant genodermatosis with high penetrance and variable expressivity. Its manifestation appears as hyperkeratotic papules, primarily affecting seborrheic areas on the head, neck, and thorax and less frequently on the oral mucosa. When oral manifestations are present, the palatal and alveolar mucosae are primarily affected. They are usually asymptomatic and are discovered in routine dental examination. Histologically, the lesions are presented as suprabasal clefts in the epithelium with acantholytic and dyskeratotic cells represented by “corps ronds and grains”. This paper reports a case of a 53-year-old woman that was admitted to our clinic with more than 10-year history of keratotic papules, presented on the hands and feet, nose, ears, genitalia, and whitish lesions on palatal mucosae. PMID:23573430

Proposed Pathophysiologic Framework to Explain Some ...

EPA Pesticide Factsheets

The paper proposes a pathophysiologic framework to explain the well-established epidemiological association between exposure to ambient air particle pollution and premature cardiovascular mortality, and offers insights into public health solutions that extend beyond regularory environmental protections to actions that can be taken by individuals, public health officials, healthcare professionals, city and regional planners, local and state governmental officials and all those who possess the capacity to improve cardiovascular health within the popula­tion.The foundation of the framework rests on the contribution of traditional cardiovascular risk factors acting alone and in concert with long-term exposures to air pollutants to create a conditional susceptibility for clinical vascular events, such as myocardial ischemia and infarction; stroke and lethal ventricular arrhythmias. The conceprual framework focuses on the fact that short-term exposures to ambient air particulate matter (PM) are associated with vascular thrombosis (acute coronary syndrome. stroke, deep venous thrombosis. and pulmonary embolism ) and electrical dysfunction (ventricular arrhythmia); and that individuals having prevalent heart disease are at greatest risk. Moreover, exposure is concomitant with changes in autonomic nervous system balance, systemic in­flammation, and prothrombotic/anti-thrombotic and profibrinolytic-antifibrinolytic balance.Thus, a comprehensive solution to the problem o

Faecal soiling: pathophysiology of postdefaecatory incontinence.

PubMed

Pucciani, F

2013-08-01

Passive postdefaecatory incontinence is poorly understood and yet is an important clinical problem. The aim of this study was to characterize the pathophysiology of postdefaecatory incontinence in patients affected by faecal soiling. Seventy-two patients (30 women, age range 49-79 years; 42 men, age range, 53-75 years) affected by faecal passive incontinence with faecal soiling were included in the study. Two patient groups were identified: Group 1 comprised 42 patients with postdefaecatory incontinence and Group 2 had 30 patients without incontinence after bowel movements. After a preliminary clinical evaluation, including the Faecal Incontinence Severity Index (FISI) score and the obstructed defaecation syndrome (ODS) score, all patients of Groups 1 and 2 were studied by means of endoanal ultrasound and anorectal manometry. The results were compared with those from 20 healthy control subjects. A significantly higher ODS score was found in Group 1 (P < 0.001). Endoanal ultrasound revealed a significantly diffuse thinning of the internal anal sphincter (IAS) in Group 2 (P < 0.02) with a linear relationship between signs of IAS atrophy and the FISI score (ρs 0.78; P < 0.03). Anal resting pressure (Pmax and Pm ) was significantly lower in Group 2 (P < 0.04). The straining test was considered positive in 30 (71.4%) patients in Group 1, significantly greater than in Group 2 (P < 0.01). A significantly higher conscious rectal sensitivity threshold (CRST) was found in Group 1 patients (P < 0.01). The ODS score, a positive straining test and high CRST values suggest that postdefaecatory incontinence is secondary to impaired defaecation. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

Urethral Foreign Bodies: Clinical Presentation and Management.

PubMed

Palmer, Cristina J; Houlihan, Matthew; Psutka, Sarah P; Ellis, K Alexandria; Vidal, Patricia; Hollowell, Courtney M P

2016-11-01

To review a single institution's 15-year experience with urethral foreign bodies, including evaluation, clinical findings, and treatment. In total, 27 patients comprising 35 episodes of inserted urethral foreign bodies were reviewed at Cook County Hospital between 2000 and 2015. Retrospective chart review was performed to describe the clinical presentation, rationale for insertion, management, recidivism, and sequelae. Median patient age was 26 (range 12-60). Twenty-six patients (97 %) were male, 1 was female (3%). Items inserted included pieces of plastic forks, spoons, metal screws and aluminum, pieces of cardboard or paper, staples, writing utensils such as pens and pencils, as well as coaxial cable and spray foam sealant. Reported reasons for insertion were self-stimulation, erectile enhancement, and attention seeking. Presenting symptoms included dysuria, gross hematuria, urinary retention, urinary tract infection, and penile discharge. The most common technique for removal was manual extraction with extrinsic pressure (n = 19, 54%). Other methods include endoscopic retrieval (n = 8, 23%), open cystotomy (n = 1, 3%), and voiding to expel the foreign body (n = 7, 20%). Postremoval complications included urinary tract infection (n = 7), sepsis (n = 4), urethral false passage (n = 5), laceration (n = 5), and stricture (n = 1). We present the largest single-institutional series of urethral foreign bodies to date. Urethral foreign body insertion is a relatively rare occurrence and, commonly, is a recurrent behavior. Urethral trauma related to foreign body insertion is associated with significant risk of infection and urethral injury with long-term sequelae. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Interleukin-10 in the Pathophysiology of Preeclampsia.

PubMed

Cubro, Hajrunisa; Kashyap, Sonu; Nath, Meryl C; Ackerman, Allan W; Garovic, Vesna D

2018-04-30

The pathophysiology of preeclampsia is complex and not entirely understood. A key feature in preeclampsia development is an immunological imbalance that shifts the maternal immune response from one of tolerance towards one promoting chronic inflammation and endothelial dysfunction. As a key regulator of immunity, IL-10 not only has immunomodulatory activity, but also directly benefits vasculature and promotes successful cellular interactions at the maternal-fetal interface. Here we focus on the mechanisms by which the dysregulation of IL-10 may contribute to the pathophysiology of preeclampsia. Dysregulation of IL-10 has been demonstrated in various animal models of preeclampsia. Decreased IL-10 production in both placenta and peripheral blood mononuclear cells has been reported in human studies, but with inconsistent results. The significance of IL-10 in preeclampsia has shifted from a key biomarker to one with therapeutic potential. As such, a better understanding of the role of this cytokine in the pathophysiology of preeclampsia is of paramount importance.

Blended Learning Versus Traditional Lecture in Introductory Nursing Pathophysiology Courses.

PubMed

Blissitt, Andrea Marie

2016-04-01

Currently, many undergraduate nursing courses use blended-learning course formats with success; however, little evidence exists that supports the use of blended formats in introductory pathophysiology courses. The purpose of this study was to compare the scores on pre- and posttests and course satisfaction between traditional and blended course formats in an introductory nursing pathophysiology course. This study used a quantitative, quasi-experimental, nonrandomized control group, pretest-posttest design. Analysis of covariance compared pre- and posttest scores, and a t test for independent samples compared students' reported course satisfaction of the traditional and blended course formats. Results indicated that the differences in posttest scores were not statistically significant between groups. Students in the traditional group reported statistically significantly higher satisfaction ratings than students in the blended group. The results of this study support the need for further research of using blended learning in introductory pathophysiology courses in undergraduate baccalaureate nursing programs. Further investigation into how satisfaction is affected by course formats is needed. Copyright 2016, SLACK Incorporated.

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Orthostatic hypotension: epidemiology, pathophysiology and management

NASA Technical Reports Server (NTRS)

Jacob, G.; Robertson, D.

1995-01-01

Orthostatic hypotension is characterized by low upright blood pressure levels and symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is heterogeneous, correct pathophysiologic diagnosis is important because of therapeutic and prognostic considerations. Although therapy is not usually curative, it can be extraordinarily beneficial if it is individually tailored. Management of the Shy-Drager syndrome (multiple-system atrophy) remains a formidable challenge.

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

PubMed

Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi

2017-03-15

Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tics and Tourette's: update on pathophysiology and tic control.

PubMed

Ganos, Christos

2016-08-01

To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control. The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. Tourette syndrome patients have altered awareness of volition and enhanced formation of habits. Premonitory urges are not the driving force behind all tics. The intensity of premonitory urges depends on patients' capacity to perceive interoceptive signals. The insular cortex is a key structure in this process. The trait intensity of premonitory urges is not a prerequisite of voluntary tic inhibition, a distinct form of motor control. Voluntary tic inhibition is most efficient in the body parts that tic the least. The prefrontal cortex is associated with the capacity to inhibit tics. The management of tics includes behavioral, pharmacological and surgical interventions. Treatment recommendations differ based on patients' age. The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.

Age-related pathophysiological changes in rats with unilateral renal agenesis.

PubMed

Amakasu, Kohei; Suzuki, Katsushi; Katayama, Kentaro; Suzuki, Hiroetsu

2011-06-01

Affected rats of the unilateral urogenital anomalies (UUA) strain show renal agenesis restricted to the left side. To determine whether unilateral renal agenesis is a risk factor for the progression of renal insufficiency, we studied age-related pathophysiological alterations in affected rats. Although body growth and food intake were normal, polydipsia and polyuria with low specific gravity were present at 10 weeks and deteriorated further with age. Blood hemoglobin concentrations were normal, though there was slight erythropenia with increased MCV and MCH. Although hypoalbuminemia, hypercholesterolemia, azotemia, and hypermagnesemia were manifested after age 20 weeks, neither hyperphosphatemia nor hypocalcemia was observed. Plasma Cre and UN concentrations gradually increased with age. Cre clearance was almost normal, whereas fractional UN excretion was consistently lower than normal. Proteinuria increased with age, and albumin was the major leakage protein. In addition to cortical lesions, dilated tubules, cast formation, and interstitial fibrosis were observed in the renal medulla of 50 week-old affected rats. Renal weight was increased 1.7-fold and glomerular number 1.2-fold compared with normal rats. These findings show that the remaining kidney in UUA rats is involved not only in compensatory reactions but experiences pathophysiological alterations associated with progressive renal insufficiency.

Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options.

PubMed

Bunevicius, Robertas; Prange, Arthur J

2006-01-01

Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.

Subacute Thyroiditis: Clinical Presentation and Long Term Outcome

PubMed Central

Alfadda, Assim A.; Sallam, Reem M.; Elawad, Ghadi E.; AlDhukair, Hisham; Alyahya, Mossaed M.

2014-01-01

Few studies have been reported from the Kingdom of Saudi Arabia (SA) to describe the clinical presentation and long term outcomes of subacute thyroiditis (SAT). Our aim was to review the demographic, anthropometric, clinical presentation, laboratory results, treatment, and disease outcome in Riyadh region and to compare those with results from different regions of the Kingdom and different parts of the world. We reviewed the medical files of patients who underwent thyroid uptake scan during an 8-year period in King Khalid University Hospital. Only 25 patients had confirmed diagnosis of thyroiditis. Age and gender distribution were similar to other studies. Most patients presented with palpitation, goiter, and weight change. Elevated thyroid hormones, suppressed thyroid-stimulating hormone, and elevated ESR were reported. Among those, 7 cases of SAT were recorded. β-Blockers were prescribed to 57% and nonsteroidal anti-inflammatory drugs to 29% of SAT. Long follow-up demonstrated that 85.7% of SAT cases recovered, while 14.3% developed permanent hypothyroidism. In conclusion, SAT is uncommon in the central region of SA. Compared to the western region, corticosteroid is not commonly prescribed, and permanent hypothyroidism is not uncommon. A nation-wide epidemiological study to explain these interprovincial differences is warranted. PMID:24803929

Cumulative stress pathophysiology in schizophrenia as indexed by allostatic load.

PubMed

Nugent, Katie L; Chiappelli, Joshua; Rowland, Laura M; Hong, L Elliot

2015-10-01

The etiopathophysiology of schizophrenia has long been linked to stress and the influence of stress is important in all stages of the illness. Previous examinations of perceived stress and acute stress responses may not capture this longitudinal stress pathophysiology. We hypothesized that the cumulative negative effects of stress, indexed by allostatic load (AL), would be elevated in schizophrenia, and that the AL paradigm would be relevant to our understanding of pathophysiology in schizophrenia. We assessed allostatic load in 30 patients with schizophrenia (SZ; mean age = 33; 17 males) and 20 healthy controls (HC; mean age = 35; 12 males) using 13 cardiovascular, metabolic, neuroendocrine and immune biomarkers. Participants' perceived stress over the past month, functional capacity and psychiatric symptoms were also measured. Controlling for age, SZ had significantly higher AL as compared to HC (p = 0.007). Greater AL was present in both early course and chronic SZ, and was associated with reduced functional capacity (p = 0.006) and more psychotic symptoms (p = 0.048) in SZ. Current level of perceived stress was not significantly elevated in SZ or associated with AL in either group. The higher AL found in SZ may reflect increased bodily "wear and tear", possibly caused by more chronic stress exposure or maladaptive responses to stress over time, although additional research is required to differentiate these causes. The higher AL is similarly present in early and chronic SZ, suggesting primary maladaptive stress physiology rather than secondary effects from medications or chronic illness. Copyright © 2015 Elsevier Ltd. All rights reserved.

XML-based scripting of multimodality image presentations in multidisciplinary clinical conferences

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Allada, Vivekanand; Dahlbom, Magdalena; Marcus, Phillip; Fine, Ian; Lapstra, Lorelle

2002-05-01

We developed a multi-modality image presentation software for display and analysis of images and related data from different imaging modalities. The software is part of a cardiac image review and presentation platform that supports integration of digital images and data from digital and analog media such as videotapes, analog x-ray films and 35 mm cine films. The software supports standard DICOM image files as well as AVI and PDF data formats. The system is integrated in a digital conferencing room that includes projections of digital and analog sources, remote videoconferencing capabilities, and an electronic whiteboard. The goal of this pilot project is to: 1) develop a new paradigm for image and data management for presentation in a clinically meaningful sequence adapted to case-specific scenarios, 2) design and implement a multi-modality review and conferencing workstation using component technology and customizable 'plug-in' architecture to support complex review and diagnostic tasks applicable to all cardiac imaging modalities and 3) develop an XML-based scripting model of image and data presentation for clinical review and decision making during routine clinical tasks and multidisciplinary clinical conferences.

Approach to the genetics of alcoholism: a review based on pathophysiology.

PubMed

Köhnke, Michael D

2008-01-01

Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.

Left main coronary artery disease: pathophysiology, diagnosis, and treatment.

PubMed

Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W

2018-06-01

The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.

Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features.

PubMed

Bellissimo-Rodrigues, Fernando; Bollela, Valdes Roberto; Da Fonseca, Benedito Antônio Lopes; Martinez, Roberto

2013-04-01

Paracoccidioidomycosis (PCM) is a systemic fungal disease endemic to Latin America and characterized by two clinical presentations, i.e., patients develop either acute/subacute or chronic clinical manifestations. The differences in clinical presentations are mainly dependent on the host immune response, but may also be related to demographic characteristics of some patients. In this retrospective study, 1,219 PCM cases treated between 1970 and 2009 in a university medical center, located in southeastern Brazil, were analyzed according to their clinical and demographic features. The most affected anatomical sites were lungs (63.8%) and oral mucosa (50.0%), with increasing involvement of these sites in accord with the age of the patients. Generalized lymphadenopathy (28.1%) and skin lesions (29.6%) were more frequent on the first decades of life. Involvement of the larynx (16.1%), gut (7.5%), spleen (4.7%), central nervous system (3.4%), bones and joints (2.2%), and adrenal (2.1%) were also variable according to the age of the host. The acute/subacute form of the disease accounted for 26.4% of PCM cases and, on a multivariate analysis, was inversely associated with aging (OR = 0.8 per year, P < 0.001), and directly associated with female sex (OR = 7.2, P < 0.001), mixed black and white racial background (OR = 2.3, P < 0.001) or black skin color (OR = 4.6, P < 0.001). Based on these findings, we have shown that host immune response, as well as age, gender and ethnicity may influence the clinical presentation of PCM.

Pathophysiology of spontaneous venous gas embolism

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.

1991-01-01

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy.

PubMed

Baek, Jin Hyen; D'Agnillo, Felice; Vallelian, Florence; Pereira, Claudia P; Williams, Matthew C; Jia, Yiping; Schaer, Dominik J; Buehler, Paul W

2012-04-01

Massive transfusion of blood can lead to clinical complications, including multiorgan dysfunction and even death. Such severe clinical outcomes have been associated with longer red blood cell (rbc) storage times. Collectively referred to as the rbc storage lesion, rbc storage results in multiple biochemical changes that impact intracellular processes as well as membrane and cytoskeletal properties, resulting in cellular injury in vitro. However, how the rbc storage lesion triggers pathophysiology in vivo remains poorly defined. In this study, we developed a guinea pig transfusion model with blood stored under standard blood banking conditions for 2 (new), 21 (intermediate), or 28 days (old blood). Transfusion with old but not new blood led to intravascular hemolysis, acute hypertension, vascular injury, and kidney dysfunction associated with pathophysiology driven by hemoglobin (Hb). These adverse effects were dramatically attenuated when the high-affinity Hb scavenger haptoglobin (Hp) was administered at the time of transfusion with old blood. Pathologies observed after transfusion with old blood, together with the favorable response to Hp supplementation, allowed us to define the in vivo consequences of the rbc storage lesion as storage-related posttransfusion hemolysis producing Hb-driven pathophysiology. Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients.

The pathophysiology of hypertension in patients with obesity.

PubMed

DeMarco, Vincent G; Aroor, Annayya R; Sowers, James R

2014-06-01

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting.

The pathophysiology of hypertension in patients with obesity

PubMed Central

DeMarco, Vincent G.; Aroor, Annayya R.; Sowers, James R.

2015-01-01

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting. PMID:24732974

Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease*

PubMed Central

Masters, Seth L.; Simon, Anna; Aksentijevich, Ivona; Kastner, Daniel L.

2010-01-01

The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside. PMID:19302049

A prospective cohort study of the clinical presentation of non-traumatic osteonecrosis of the femoral head: spine and knee symptoms as clinical presentation of hip osteonecrosis.

PubMed

Hauzeur, Jean-Philippe; Malaise, Michel; de Maertelaer, Viviane

2016-07-01

To study the clinical presentation of femoral head osteonecrosis (ONFH). Publications dedicated to this aspect of ONFH are rare. Our aim was to systematically collect and describe the clinical data. A prospective survey was conducted in a cohort of ONFH recruited from a dedicated clinic for osteonecrosis. The history of symptoms, medical management, and physical findings were obtained from 88 patients suffering from 125 ONFH. Subgroups were formed: bilateral versus unilateral ONFH, radiological stages 1-2 (pre-fractured) versus fractured stage 3 versus stage 4. ONFH was bilateral in 63 %, especially in corticosteroid users and in sickle-cell cases. These patients were younger but had similar BMIs compared to the unilateral cases. The pain was mechanical in 79 % of hips and inflammatory in 21 %. Acute pain at the onset was present in 55 % of hips. The localization of this pain was variable, including in the groin, the buttocks, or diffused in the lower limbs. A limp was present in 50 % of the patients, only when one hip was painful. The physical examination of the hip was normal in 31 %, especially in stages 1-2 (55 %). The diagnosis delay was 12 months, with inadequate medical management in 51 % of patients. In ONFH cases, no typical clinical pattern was found. The clinical presentation was very variable, sometimes having spine or knee symptoms with a normal physical examination of the hip. ONFH should be systematically suspected in cases of onset of pain in the pelvis, buttocks, groin, and lower limbs.

Clinical presentation of retinoblastoma in Alexandria: A step toward earlier diagnosis.

PubMed

Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad

2017-01-01

To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.

A young man presenting with paralysis after vigorous exercise.

PubMed

Gubran, Christopher; Narain, Rajay; Malik, Luqmaan; Saeed, Saad Aldeen

2012-08-27

Thyrotoxic periodic paralysis (TPP) is a rare metabolic disorder characterised by muscular weakness and paralysis in predisposed thyrotoxic patients. Although patients with TPP are almost uniformly men of Asian descent, cases have been reported in Caucasian and other ethnic populations. The rapid increase in ethnic diversity in Western and European nations has led to increase in TPP reports, where it was once considered exceedingly rare. Correcting the hypokalaemic and hyperthyroid state tends to reverse the paralysis. However, failure to recognise the condition may lead to delay in diagnosis and serious consequences including respiratory failure and death. We describe a young man who was diagnosed with hyperthyroidism who presented with acute paralysis. The clinical characteristics, pathophysiology and management of TTP are reviewed.

[Pathophysiology of delirium].

PubMed

Nickel, B; Uebelhack, R

1977-01-01

Based on a series of known facts on clinical findings and changes in the metabolism of chronic alcoholics and delirious people the possible pathomechanism of cerebral imbalances is presented according to a synopsis. The clinical symptomatology, in particular vegetative symptoms and the coordination of reflexes - to which more attention should be paid than has been up to now - make delirium appear a diencephalic illness, the sympathicotonic and ergotropic development of which together with a preponderance of noradrenergic-adrenergic mechanisms, remains unexplained to this day.

Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

PubMed

Langer, Arielle L; Ginzburg, Yelena Z

2017-06-01

Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation.

PubMed

Lemaignen, A; Birgand, G; Ghodhbane, W; Alkhoder, S; Lolom, I; Belorgey, S; Lescure, F-X; Armand-Lefevre, L; Raffoul, R; Dilly, M-P; Nataf, P; Lucet, J C

2015-07-01

The incidence of surgical site infection (SSI) after cardiac surgery depends on the definition used. A distinction is generally made between mediastinitis, as defined by the US Centers for Disease Control and Prevention (CDC), and superficial SSI. Our objective was to decipher these entities in terms of presentation and risk factors. We performed a 7-year single centre analysis of prospective surveillance of patients with cardiac surgery via median sternotomy. SSI was defined as the need for reoperation due to infection. Among 7170 patients, 292 (4.1%) developed SSI, including 145 CDC-defined mediastinitis (CDC-positive SSI, 2.0%) and 147 superficial SSI without associated bloodstream infection (CDC-negative SSI, 2.1%). Median time to reoperation for CDC-negative SSI was 18 days (interquartile range, 14-26) and 16 (interquartile range, 11-24) for CDC-positive SSI (p 0.02). Microorganisms associated with CDC-negative SSI were mainly skin commensals (62/147, 41%) or originated in the digestive tract (62/147, 42%); only six were due to Staphylococcus aureus (4%), while CDC-positive SSI were mostly due to S. aureus (52/145, 36%) and germs from the digestive tract (52/145, 36%). Risk factors for SSI were older age, obesity, chronic obstructive bronchopneumonia, diabetes mellitus, critical preoperative state, postoperative vasopressive support, transfusion or prolonged ventilation and coronary artery bypass grafting, especially if using both internal thoracic arteries in female patients. The number of internal thoracic arteries used and factors affecting wound healing were primarily associated with CDC-negative SSI, whereas comorbidities and perioperative complications were mainly associated with CDC-positive SSI. These 2 entities differed in time to revision surgery, bacteriology and risk factors, suggesting a differing pathophysiology. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[The ice water test and bladder cooling reflex. Physiology, pathophysiology and clinical importance].

PubMed

Hüsch, T; Neuerburg, T; Reitz, A; Haferkamp, A

2016-04-01

Urodynamic studies are utilised for identification and follow-up of functional disorders of the lower urinary tract. Provocation tests are used to determine disorders which could not be revealed in standard cystometry. The ice water test is a simple test to identify neurogenic bladder dysfunction and to screen the integrity of the upper motor neuron in neurogenic bladder dysfunction. Development and significance of the ice water test is presented in this review against the background of physiology and pathophysiology of the lower urinary tract. A systematic review of PubMed and ScienceDirect databases was performed in April 2015. No language or time limitation was applied. The following key words and Medical Subject Heading terms were used to identify relevant studies: "ice water test", "bladder cooling reflex", "micturition" and "neuronal control". Review articles and bibliographies of other relevant studies identified were hand searched to find additional studies. The ice water test is performed by rapid instillation of 4-8 °C cold fluid into the urinary bladder. Hereby, afferent C fibers are activated by cold receptors in the bladder leading to the bladder cooling reflex. It is a spinal reflex which causes an involuntarily contraction of the urinary bladder. The test is normally positive in young infants during the first 4 years of life and become negative with maturation of the central nervous system afterwards by inhibition of the reflex. The damage of the upper motor neuron causes the recurrence of the reflex in the adulthood and indicates spinal and cerebral lesions. The ice water test is utilised to identify lesions of the upper motor neuron. However, in the case of detrusor acontractility the test will always be negative and can not be utilized to distinguish between neurogenic or muscular causes. Furthermore, the test is also positive in a small percentage of cases of non-neurogenic diseases, e.g. in prostate-related bladder outlet obstruction or

Pathophysiologic insights into motor axonal function in Kennedy disease.

PubMed

Vucic, Steve; Kiernan, Matthew C

2007-11-06

Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p < 0.01) and the hyperpolarizing current/threshold gradient (KD 0.42 +/- 0.01; controls, 0.37 +/- 0.01, p < 0.05) were significantly increased in KD. Strength-duration time constant correlated with the CMAP amplitude (R = 0.68) and the fasciculation frequency (R = 0.62). Threshold electrotonus revealed greater changes in response to subthreshold depolarizing (KD TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

[PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

PubMed

Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

2016-12-01

Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

PubMed

Reyskens, M; Sleurs, K; Verresen, L; Janssen, M; van den Bergh, J; van den Berg, J; Geusens, P

2015-07-01

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

Clinic exam room design: present and future.

PubMed

Freihoefer, Kara; Nyberg, Gary; Vickery, Christine

2013-01-01

This article aims to deconstruct various design qualities and strategies of clinic exam rooms, and discuss how they influence users' interaction and behavior in the space. Relevant literature supports the advantages and disadvantages of different design strategies. Annotated exam room prototypes illustrate the design qualities and strategies discussed. Advancements in technology and medicine, along with new legislative policies, are influencing the way care providers deliver care and ultimately clinic exam room designs. The patient-centered medical home model has encouraged primary care providers to make patients more active leaders of their health plan which will influence the overall functionality and configuration of clinic exam rooms. Specific design qualities discussed include overall size, location of doors and privacy curtains, positioning of exam tables, influence of technology in the consultation area, types of seating, and placement of sink and hand sanitizing dispensers. In addition, future trends of exam room prototypes are presented. There is a general lack of published evidence to support design professionals' design solutions for outpatient exam rooms. Future research should investigate such topics as the location of exam tables and privacy curtains as they relate to patient privacy; typical size and location of consultation table as it relates to patient connection and communication; and placement of sinks and sanitization dispensers as they relate to frequency and patterns of usage. Literature review, outpatient, technology, visual privacy.

New concept: cellular senescence in pathophysiology of cholangiocarcinoma.

PubMed

Sasaki, Motoko; Nakanuma, Yasuni

2016-01-01

Cholangiocarcinoma, a malignant tumor arising in the hepatobiliary system, presents with poor prognosis because of difficulty in its early detection/diagnosis. Recent progress revealed that cellular senescence may be involved in the pathophysiology of cholangiocarcinoma. Cellular senescence is defined as permanent growth arrest caused by several cellular injuries, such as oncogenic mutations and oxidative stress. "Oncogene-induced" and/or stress-induced senescence may occur in the process of multi-step cholangiocarcinogenesis, and overexpression of a polycomb group protein EZH2 may play a role in the escape from, and/or bypassing of, senescence. Furthermore, senescent cells may play important roles in tumor development and progression via the production of senescence-associated secretory phenotypes. Cellular senescence may be a new target for the prevention, early diagnosis, and therapy of cholangiocarcinoma in the near future.

A review of the clinical implications of bisphosphonates in dentistry.

PubMed

Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R

2011-03-01

Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.

[Pathophysiology and new treatment of uveitis].

PubMed

Yanai, Ryoji; Takeda, Atsunobu; Yoshimura, Takeru; Sonoda, Koh-Hei

2014-01-01

Uveitis is narrow-defined inflammation of the uvea, also clinically include all inflammatory conditions in the eye. Uveitis may occur as a consequence of various causes and background, such as autoimmune diseases, infections, and hematopoietic malignancy. We have to treat uveitis not only controlling the inflammation but also maintaining up the visual function of the eye because the most uveitis is chronic and relapsing inflammatory disorder. Behçét's disease is a systemic disease and results in loss of vision without adequate treatment. Behçét's disease was a representative of vision loss uveitis because Behçét's patient usually had treatment resistance of conventional treatment, such as colchicine and cyclosporine. However, biological therapy with TNF-α, which started from 2007, has revolutionized the treatment strategy of Behçét's disease. It is not too much to say that Behçét's patient is free from fear of vision loss by the dramatic decrease of ocular attach. Biological therapy is not approved as a treatment of uveitis except Behçét's disease. Some protracted cases of Sarcoidosis and Vogt-Koyanagi-Harada disease are resistant to corticosteroid therapy and require new treatment. In this review, we discuss the pathophysiology of uveitis and report new treatment of Behçét's disease by biological therapy.

Exploring pain pathophysiology in patients.

PubMed

Sommer, Claudia

2016-11-04

Although animal models of pain have brought invaluable information on basic processes underlying pain pathophysiology, translation to humans is a problem. This Review will summarize what information has been gained by the direct study of patients with chronic pain. The techniques discussed range from patient phenotyping using quantitative sensory testing to specialized nociceptor neurophysiology, imaging methods of peripheral nociceptors, analyses of body fluids, genetics and epigenetics, and the generation of sensory neurons from patients via inducible pluripotent stem cells. Copyright © 2016, American Association for the Advancement of Science.

Clinical presentation of neurocysticercosis-related epilepsy.

PubMed

Duque, Kevin R; Burneo, Jorge G

2017-11-01

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and a major risk factor for seizures and epilepsy. Seizure types in NCC vary largely across studies and seizure semiology is poorly understood. We discuss here the studies regarding seizure types and seizure semiology in NCC, and examine the clinical presentation in patients with NCC and drug-resistant epilepsy. We also provide evidence of the role of MRI and EEG in the diagnosis of NCC-related epilepsy. Focal seizures are reported in 60-90% of patients with NCC-related epilepsy, and around 90% of all seizures registered prospectively are focal not evolving to bilateral tonic-clonic seizures. A great number of cases suggest that seizure semiology is topographically related to NCC lesions. Patients with hippocampal sclerosis and NCC have different clinical and neurophysiological characteristics than those with hippocampal sclerosis alone. Different MRI protocols have allowed to better differentiate NCC from other etiologies. Lesions' stages might account on the chances of finding an interictal epileptiform discharge. Studies pursuing the seizure onset in patients with NCC are lacking and they are specially needed to determine both whether the reported events of individual cases are seizures, and whether they are related to the NCC lesion or lesions. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosing the pathophysiologic mechanisms of nocturnal polyuria.

PubMed

Goessaert, An-Sofie; Krott, Louise; Hoebeke, Piet; Vande Walle, Johan; Everaert, Karel

2015-02-01

Diagnosis of nocturnal polyuria (NP) is based on a bladder diary. Addition of a renal function profile (RFP) for analysis of concentrating and solute-conserving capacity allows differentiation of NP pathophysiology and could facilitate individualized treatment. To map circadian rhythms of water and solute diuresis by comparing participants with and without NP. This prospective observational study was carried out in Ghent University Hospital between 2011 and 2013. Participants with and without NP completed a 72-h bladder dairy. RFP, free water clearance (FWC), and creatinine, solute, sodium, and urea clearance were measured for all participants. The study participants were divided into those with (n=77) and those without (n=35) NP. The mean age was 57 yr (SD 16 yr) and 41% of the participants were female. Compared to participants without NP, the NP group exhibited a higher diuresis rate throughout the night (p=0.015); higher FWC (p=0.013) and lower osmolality (p=0.030) at the start of the night; and persistently higher sodium clearance during the night (p<0.001). The pathophysiologic mechanism of NP was identified as water diuresis alone in 22%, sodium diuresis alone in 19%, and a combination of water and sodium diuresis in 47% of the NP group. RFP measurement in first-line NP screening to discriminate between water and solute diuresis as pathophysiologic mechanisms complements the bladder diary and could facilitate optimal individualized treatment of patients with NP. We evaluated eight urine samples collected over 24h to detect the underlying problem in NP. We found that NP can be attributed to water or sodium diuresis or a combination of both. This urinalysis can be used to adapt treatment according to the underlying mechanism in patients with bothersome consequences of NP, such as nocturia and urinary incontinence. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology.

PubMed

Meyer, Michael Andrew

2013-01-01

Delayed post-hypoxic leukoencephalopathy is a rare clinical phenomenon usually observed in a small number of carbon monoxide poisoning survivors. A similar phenomenon is reported here in a patient who successfully recovered from a large overdose of diazepam and methadone, but then abruptly declined 3 weeks after the initial event. Magnetic resnance revealed confluent white matter hyperintensity on fluid-attenuated inversion recovery and T2 weighted sequences, and spectroscopy revealed elevated peaks in choline, creatinine, and lactate. Analysis and review of the literature suggests this phenomenon occurs on average about 19 days after the initial event. Although the pathophysiology remains obscure, it is noted here that the mean lucid interval coincides approximately with the replacement half-life for myelin related lipids and proteins.

Pathophysiology of AAA: heredity vs environment.

PubMed

Björck, Martin; Wanhainen, Anders

2013-01-01

Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

Lymphogranuloma Venereum 2015: Clinical Presentation, Diagnosis, and Treatment.

PubMed

Stoner, Bradley P; Cohen, Stephanie E

2015-12-15

Lymphogranuloma venereum (LGV) has emerged as an important cause of proctitis and proctocolitis in men who have sex with men; classical inguinal presentation is now increasingly uncommon. We report summary findings of an extensive literature review on LGV clinical presentation, diagnosis, and treatment that form the evidence base for the 2015 Centers for Disease Control and Prevention treatment guidelines for sexually transmitted diseases. Proctitis and proctocolitis are now the most commonly reported clinical manifestations of LGV, with symptoms resembling those of inflammatory bowel disease. Newer molecular tests to confirm LGV infection are sensitive and specific, but are generally restricted to research laboratory or public health settings. Doxycycline (100 mg twice daily for 21 days) remains the treatment of choice for LGV. Patients with rectal chlamydial infection and signs or symptoms of proctitis should be tested for LGV, or if confirmatory testing is not available, should be treated empirically with a recommended regimen to cover LGV infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Role of Polyamines in Asthma Pathophysiology

PubMed Central

2018-01-01

Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma. PMID:29316647

[Myocardial mechanical injury in acute ischemia: a pathophysiologic and histopathologic review].

PubMed

Rossi, L; Matturri, L

1986-03-01

The recognition of histopathologic substrates of myocardial contractile damage in human acute ischemia is still very poor, notwithstanding the impressive advances in the inherent clinical diagnostic technology and concepts. The first and foremost inotropic abnormality ensuing ischemia, easily taken for atonic in origin, actually consists of a pathologic contracture of the injured myocardium, depending upon abrupt fall of ATP, and defective extrusion calcium pump with persistence of actomyosin rigor-complexes. In sustained ischemia, further membrane damage exposes the myocell to massive calcium intrusion, with eventual precipitation of it and cell death (reperfusion stone-heart). In case of transient, "hit and run" ischemia, the "stunned" myocardium undergoes prolonged contractile abnormalities. In keeping with fundamentals in pathophysiology of contraction, ischemic myofibrils in human hyperacute infarct, showed spare I bands, accounting for contracture and followed by loss of the regular cross-striation register; then, groups of adjacent sarcomeres were seen to join into true "contraction" bands, with Z lines impinging upon A bands and obliterating the I bands. Coagulative denaturation of contractile proteins follows, presenting as irregular, amorphous degeneration stripes astride irreversibly damaged myocells. As such, these cells can be passively overstretched by the nearby functioning muscle. In turn, the fixed waviness of viable, acutely ischemic myocardium was thought to configure, histologically, the loss of ATP-dependent "plasticity" of myofilaments, in a state of contracture. The "relaxant effect" of inotropic-chronotropic-positive catecholamines, favoring diastole, has been also pointed out. The present microscopic findings are cogent to clinicopathologic problems of coronary ischemia-reperfusion, and sudden death from cardiogenic shock.

Kidney Calculi: Pathophysiology and as a Systemic Disorder.

PubMed

Shadman, Arash; Bastani, Bahar

2017-05-01

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the authors' knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan)Cytopenia in Childhood

PubMed Central

Erlacher, Miriam; Strahm, Brigitte

2015-01-01

Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings, such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia, whereas antibody-mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. By contrast, pancytopenia is frequently associated with a hypocellular bone marrow, and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita, and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition, and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC) can reliably be differentiated on a morphological level, the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC, and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pan)cytopenia, their pathophysiology, characteristic bone marrow findings, and therapeutic approaches. PMID:26217651

Hemicrania continua: Case series presenting in an orofacial pain clinic.

PubMed

Hryvenko, Iryna; Cervantes-Chavarría, Andrés R; Law, Alan S; Nixdorf, Donald R

2018-01-01

Aim of investigation Hemicrania continua (HC) is an uncommon primary headache and little is known of the characteristics of such patients managed in an orofacial pain setting. This study provides clinical features of HC, its association with other disorders, and treatment outcomes of patients managed in the TMD and Orofacial Pain Clinic at the University of Minnesota. Methods A retrospective review of patient records was undertaken. Inclusion criteria were a diagnosis of HC and confirmation at follow-up. Results Six of the 1617 new patients seen between 2015 and 2017 met the selection criteria. Four patients presented with "facial pain", one with "toothache" and one with "jaw pain". All were female with mean age 55 ± 10.5 years (range = 41-69). Headache characteristics included unilateral (R:L = 1:1) pain of moderate intensity with severe exacerbations in the distribution of V 1 (1/6), V 1  + V 2 (3/6) and V 1  + V 2  + V 3 (2/6). Lacrimation and photophobia were the most common associated symptoms. Patient presentations were complicated by multiple medical and comorbid diagnoses. All were diagnosed with temporomandibular disorder (TMD). Indomethacin alone was sufficient for adequate headache control in 2/6 patients with several add-on medications providing sustained pain relief. Conclusions Comorbid pain conditions can be expected in patients with HC presenting to orofacial pain clinics. Symptom presentation varies, and multimodal treatment approach is necessary for success.

A mixed methods evaluation of team-based learning for applied pathophysiology in undergraduate nursing education.

PubMed

Branney, Jonathan; Priego-Hernández, Jacqueline

2018-02-01

It is important for nurses to have a thorough understanding of the biosciences such as pathophysiology that underpin nursing care. These courses include content that can be difficult to learn. Team-based learning is emerging as a strategy for enhancing learning in nurse education due to the promotion of individual learning as well as learning in teams. In this study we sought to evaluate the use of team-based learning in the teaching of applied pathophysiology to undergraduate student nurses. A mixed methods observational study. In a year two, undergraduate nursing applied pathophysiology module circulatory shock was taught using Team-based Learning while all remaining topics were taught using traditional lectures. After the Team-based Learning intervention the students were invited to complete the Team-based Learning Student Assessment Instrument, which measures accountability, preference and satisfaction with Team-based Learning. Students were also invited to focus group discussions to gain a more thorough understanding of their experience with Team-based Learning. Exam scores for answers to questions based on Team-based Learning-taught material were compared with those from lecture-taught material. Of the 197 students enrolled on the module, 167 (85% response rate) returned the instrument, the results from which indicated a favourable experience with Team-based Learning. Most students reported higher accountability (93%) and satisfaction (92%) with Team-based Learning. Lectures that promoted active learning were viewed as an important feature of the university experience which may explain the 76% exhibiting a preference for Team-based Learning. Most students wanted to make a meaningful contribution so as not to let down their team and they saw a clear relevance between the Team-based Learning activities and their own experiences of teamwork in clinical practice. Exam scores on the question related to Team-based Learning-taught material were comparable to those

[Cardio-renal axis: pathophysiological evidences and clinical implications].

PubMed

Di Lullo, Luca; Ronco, Claudio

2017-03-01

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS acute cardio - renal syndrome is characterized by acute worsening of cardiac function leading to AKI in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury, while type 4 represent cardiovascular involvement in chronic kidney disese patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

PubMed

Ntali, Georgia; Wass, John A

2018-04-01

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

The delirium subtypes: a review of prevalence, phenomenology, pathophysiology, and treatment response.

PubMed

Stagno, Daniele; Gibson, Christopher; Breitbart, William

2004-06-01

Delirium is a highly prevalent disease in the elderly and postoperative, cancer, and AIDS patients. However it is often misdiagnosed and mistreated. This may be partly due to the inconsistencies of the diagnosis itself. Delirium is best defined currently by an association of cognitive impairment and arousal disturbance. Three subtypes (hyperactive, hypoactive, mixed) receive a definition in the literature, but those definitions may vary from author to author according to the importance they give either to the motoric presentation of the delirium or to the arousal disturbance. Our aim is to point out the inconsistencies we found in the literature, but also to identify different paths that have been explored to solve them, that is, the suggestion to emphasize the arousal disturbances in defining the subtypes instead of the motoric presentations, which seem to be more fluctuating, and because of the fluctuating course of the disease to extend the observation over a period of time, which may improve the accuracy of the diagnosis. This is not without importance from a clinical standpoint. Subtypes of delirium may be explained by different pathophysiologic mechanisms, which remain partly unexplained, and may respond to specific treatments. There is a trend to isolate core symptoms (disorientation, cognitive deficits, sleep-wake cycle disturbance, disorganized thinking, and language abnormalities) so as to distinguish them from secondary symptoms that may be correlated with the different etiologies. Our contribution is also to challenge, with new data, the accepted belief that psychotic features are quite rare in the hypoactive type of delirium. We demonstrate that delusions and perceptual disturbances, although less frequent, are present in more than half of the patients with hypoactive delirium. The psychotic features are clearly correlated with a highly prevalent rate of patients', spouses', and caregivers' distress. The mixed subtype of delirium seems to have the

Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

PubMed Central

2011-01-01

Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to

The role of abdominal compliance, the neglected parameter in critically ill patients - a consensus review of 16. Part 1: definitions and pathophysiology.

PubMed

Malbrain, Manu L N G; Roberts, Derek J; De Laet, Inneke; De Waele, Jan J; Sugrue, Michael; Schachtrupp, Alexander; Duchesne, Juan; Van Ramshorst, Gabrielle; De Keulenaer, Bart; Kirkpatrick, Andrew W; Ahmadi-Noorbakhsh, Siavash; Mulier, Jan; Ivatury, Rao; Pracca, Francisco; Wise, Robert; Pelosi, Paolo

2014-01-01

Over the last few decades, increasing attention has been paid to understanding the pathophysiology, aetiology, prognosis, and treatment of elevated intra-abdominal pressure (IAP) in trauma, surgical, and medical patients. However, there is presently a relatively poor understanding of intra-abdominal volume (IAV) and the relationship between IAV and IAP (i.e. abdominal compliance). Consensus definitions on Cab were discussed during the 5th World Congress on Abdominal Compartment Syndrome and a writing committee was formed to develop this article. During the writing process, a systematic and structured Medline and PubMed search was conducted to identify relevant studies relating to the topic. According to the recently updated consensus definitions of the World Society on Abdominal Compartment Syndrome (WSACS), abdominal compliance (Cab) is defined as a measure of the ease of abdominal expansion, which is determined by the elasticity of the abdominal wall and diaphragm. It should be expressed as the change in IAV per change in IAP (mL [mm Hg]⁻¹). Importantly, Cab is measured differently than IAP and the abdominal wall (and its compliance) is only a part of the total abdominal pressure-volume (PV) relationship. During an increase in IAV, different phases are encountered: the reshaping, stretching, and pressurisation phases. The first part of this review article starts with a comprehensive list of the different definitions related to IAP (at baseline, during respiratory variations, at maximal IAV), IAV (at baseline, additional volume, abdominal workspace, maximal and unadapted volume), and abdominal compliance and elastance (i.e. the relationship between IAV and IAP). An historical background on the pathophysiology related to IAP, IAV and Cab follows this. Measurement of Cab is difficult at the bedside and can only be done in a case of change (removal or addition) in IAV. The Cab is one of the most neglected parameters in critically ill patients, although it plays a

Chest Wall Diseases: Respiratory Pathophysiology.

PubMed

Tzelepis, George E

2018-06-01

The chest wall consists of various structures that function in an integrated fashion to ventilate the lungs. Disorders affecting the bony structures or soft tissues of the chest wall may impose elastic loads by stiffening the chest wall and decreasing respiratory system compliance. These alterations increase the work of breathing and lead to hypoventilation and hypercapnia. Respiratory failure may occur acutely or after a variable period of time. This review focuses on the pathophysiology of respiratory function in specific diseases and disorders of the chest wall, and highlights pathogenic mechanisms of respiratory failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Biomarker investigations related to pathophysiological pathways in schizophrenia and psychosis

PubMed Central

Chana, Gursharan; Bousman, Chad A.; Money, Tammie T.; Gibbons, Andrew; Gillett, Piers; Dean, Brian; Everall, Ian P.

2013-01-01

Post-mortem brain investigations of schizophrenia have generated swathes of data in the last few decades implicating candidate genes and protein. However, the relation of these findings to peripheral biomarker indicators and symptomatology remain to be elucidated. While biomarkers for disease do not have to be involved with underlying pathophysiology and may be largely indicative of diagnosis or prognosis, the ideal may be a biomarker that is involved in underlying disease processes and which is therefore more likely to change with progression of the illness as well as potentially being more responsive to treatment. One of the main difficulties in conducting biomarker investigations for major psychiatric disorders is the relative inconsistency in clinical diagnoses between disorders such as bipolar and schizophrenia. This has led some researchers to investigate biomarkers associated with core symptoms of these disorders, such as psychosis. The aim of this review is to evaluate the contribution of post-mortem brain investigations to elucidating the pathophysiology pathways involved in schizophrenia and psychosis, with an emphasis on major neurotransmitter systems that have been implicated. This data will then be compared to functional neuroimaging findings as well as findings from blood based gene expression investigations in schizophrenia in order to highlight the relative overlap in pathological processes between these different modalities used to elucidate pathogenesis of schizophrenia. In addition we will cover some recent and exciting findings demonstrating microRNA (miRNA) dysregulation in both the blood and the brain in patients with schizophrenia. These changes are pertinent to the topic due to their known role in post-transcriptional modification of gene expression with the potential to contribute or underlie gene expression changes observed in schizophrenia. Finally, we will discuss how post-mortem studies may aid future biomarker investigations. PMID

Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management

PubMed Central

McFarlane, Isabel M; Ozeri, David J; Saperstein, Yair; Alvarez, Milena Rodriguez; Leon, Su Zhaz; Koci, Kristaq; Francis, Sophia; Singh, Soberjot; Salifu, Moro

2018-01-01

The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival among patients with Sickle Cell Disease (SCD). This prolonged survival however, introduces a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics. PMID:29375934

Clinical utility of EEG in diagnosing and monitoring epilepsy in adults.

PubMed

Tatum, W O; Rubboli, G; Kaplan, P W; Mirsatari, S M; Radhakrishnan, K; Gloss, D; Caboclo, L O; Drislane, F W; Koutroumanidis, M; Schomer, D L; Kasteleijn-Nolst Trenite, D; Cook, Mark; Beniczky, S

2018-05-01

Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Content Validation of Athletic Therapy Clinical Presentations in Canada

ERIC Educational Resources Information Center

Lafave, Mark R.; Yeo, Michelle; Westbrook, Khatija; Valdez, Dennis; Eubank, Breda; McAllister, Jenelle

2016-01-01

Context: Competency-based education requires strong planning and a vehicle to deliver and track students' progress across their undergraduate programs. Clinical presentations (CPs) are proposed as 1 method to deliver a competency-based curriculum in a Canadian undergraduate athletic therapy program. Objective: Validation of 253 CPs. Setting:…

Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

PubMed

Matsumoto, Naoyuki; Kobayashi, Naoki; Uda, Natsu; Hirota, Miwako; Kawasaki, Hiroshi

2018-03-15

Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

[Outlook for clinical hemorheology].

PubMed

Stoltz, J F

1996-01-01

Harvey may be considered to be the precursor of modern hemorheology, but it was not until the pioneering work of Loewenhoeck, Poiseuille, Fahraeus and Copley that the essential role of the hemorheological properties of blood and its cellular components was recognized. Before the advent of modern hemorheology in the 70s, studies were mainly focussed on microcirculation and validation of global hemorheological equations applied to blood circulation. Parallel studies on the microrheological properties (erythrocyte deformability and aggregation) explained analytically the non-Newtonian behavior of blood, and the essential contribution of these parameters to the understanding hyperviscosity syndromes. The development of clinical hemorheology in fact started at the international conferences held in Reykjavik (1966) and Heidelberg (1969), and with the initiation of the periodical European Microcirculation (since Nancy in 1960) and Clinical Hemorheology (since Nancy in 1979) Conferences. The current main avenues of research involve flow modelling, studies of cell-cell interaction mechanisms (aggregation and adhesion), in relation to the associated pathophysiological phenomena, such as cellular activation (platelets and leukocytes in particular), gene expression linked to blood flow (e.g. endothelial cells)... Clinically and therapeutically, it is crucial that pathophysiological studies be undertaken on the relationship existing between rheological parameters and objective clinical data (local flow rates, ischemic markers, hemostatic parameters, tissue oxygen, clinical symptoms,...). The main clinical application fields are cardiovascular diseases, thrombosis, diabetes, hypercholesterolemia... Also, studies on new therapeutics or on biomaterials should also be given priority.

Pedunculated and Telangiectatic Merkel Cell Carcinoma: An Unusual Clinical Presentation

PubMed Central

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-01-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect. PMID:23723504

Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.

PubMed

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-05-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

Vitiligo: An Update on Pathophysiology and Treatment Options.

PubMed

Speeckaert, Reinhart; van Geel, Nanja

2017-12-01

The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.

Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function.

PubMed

Heine, J; Prüss, H; Bartsch, T; Ploner, C J; Paul, F; Finke, C

2015-11-19

The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits, psychiatric symptoms, movement disorders and seizures and the majority of patients respond well to immunotherapy. Pathophysiological mechanisms and clinical features are increasingly recognized and indicate hippocampal dysfunction in most of these syndromes. Here, we review the neuroimaging characteristics of autoimmune encephalitides, including N-methyl-d-aspartate (NMDA) receptor, leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) encephalitis as well as more recently discovered and less frequent forms such as dipeptidyl-peptidase-like protein 6 (DPPX) or glycine receptor encephalitis. We summarize findings of routine magnetic resonance imaging (MRI) investigations as well as (18)F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and single photon emission tomography (SPECT) imaging and relate these observations to clinical features and disease outcome. We furthermore review results of advanced imaging analyses such as diffusion tensor imaging, volumetric analyses and resting-state functional MRI. Finally, we discuss contributions of these neuroimaging observations to the understanding of the pathophysiology of autoimmune encephalitides. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Gastroesophageal reflux disease-related and functional heartburn: pathophysiology and treatment.

PubMed

Miwa, Hiroto; Kondo, Takashi; Oshima, Tadayuki

2016-07-01

Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn. The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease. New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.

Unilateral Congenital Cataract: Clinical Profile and Presentation.

PubMed

Khokhar, Sudarshan; Jose, Cijin P; Sihota, Ramanjit; Midha, Neha

2018-03-01

To study the clinical profile and presentation of children with unilateral cataract. In this hospital-based, observational, cross-sectional study, patients 15 years of age or younger who presented with unilateral cataract were recruited. Cases of cataract secondary to causes such as trauma or uveitis were excluded. Age at detection and presentation, distance from the treatment center, presenting complaints, cataract morphology, and biometry were noted for each case. A total of 76 patients were recruited. Most patients presented with complaints of leukocoria. Persistent fetal vasculature accounted for 27.6% of cases and was the most common identifiable cause of cataract in this study. Subsequently, patients were divided into two groups: no persistent fetal vasculature (control) and persistent fetal vasculature. A male predominance was noted in both groups. The mean age at detection was 27.58 ± 37.02 and 6.17 ± 8.42 months and the mean age at presentation was 55.613 ± 45.21 and 14.83 ± 17.75 months in the control and persistent fetal vasculature groups, respectively. In the persistent fetal vasculature group, a significant difference was noted in the axial length, keratometry, and corneal diameter between the affected and normal eyes (P = .027, .00176, and .0114, respectively). In the control group, this difference was observed only in keratometry readings (P = .0464). The mean distance traveled by patients to reach the treatment center was 211 km. Persistent fetal vasculature is an important and less identified cause of unilateral cataract. A significant delay is noted in the detection and presentation of unilateral cataract. [J Pediatr Ophthalmol Strabismus. 2018;55(2):107-112.]. Copyright 2017, SLACK Incorporated.

Inflammation and the pathophysiology of work-related musculoskeletal disorders.

PubMed

Barbe, Mary F; Barr, Ann E

2006-09-01

Work-related musculoskeletal disorders (MSDs) have accounted for a significant proportion of work injuries and workers' compensation claims in industrialized nations since the late 1980s. Despite epidemiological evidence for the role of repetition and force in the onset and progression of work-related MSDs, complete understanding of these important occupational health problems requires further elucidation of pathophysiological mechanisms of the tissue response, particularly in the early stage of these disorders. Results from several clinical and experimental studies indicate that tissue microtraumas occur as a consequence of performing repetitive and/or forceful tasks, and that this mechanical tissue injury leads to local and perhaps even systemic inflammation, followed by fibrotic and structural tissue changes. Here we review work linking inflammation and the development of work-related MSDs. We also propose a conceptual framework suggesting the potential roles that inflammation may play in these disorders, and how inflammation may contribute to pain, motor dysfunction, and to puzzling psychological symptoms that are often characteristic of patients with work-related MSDs.

Profiling the clinical presentation of diagnostic characteristics of a sample of symptomatic TMD patients.

PubMed

Pimenta e Silva Machado, Luciana; de Macedo Nery, Marianita Batista; de Góis Nery, Cláudio; Leles, Cláudio Rodrigues

2012-08-02

Temporomandibular disorder (TMD) patients might present a number of concurrent clinical diagnoses that may be clustered according to their similarity. Profiling patients' clinical presentations can be useful for better understanding the behavior of TMD and for providing appropriate treatment planning. The aim of this study was to simultaneously classify symptomatic patients diagnosed with a variety of subtypes of TMD into homogenous groups based on their clinical presentation and occurrence of comorbidities. Clinical records of 357 consecutive TMD patients seeking treatment in a private specialized clinic were included in the study sample. Patients presenting multiple subtypes of TMD diagnosed simultaneously were categorized according to the AAOP criteria. Descriptive statistics and two-step cluster analysis were used to characterize the clinical presentation of these patients based on the primary and secondary clinical diagnoses. The most common diagnoses were localized masticatory muscle pain (n = 125) and disc displacement without reduction (n = 104). Comorbidity was identified in 288 patients. The automatic selection of an optimal number of clusters included 100% of cases, generating an initial 6-cluster solution and a final 4-cluster solution. The interpretation of within-group ranking of the importance of variables in the clustering solutions resulted in the following characterization of clusters: chronic facial pain (n = 36), acute muscle pain (n = 125), acute articular pain (n = 75) and chronic articular impairment (n = 121). Subgroups of acute and chronic TMD patients seeking treatment can be identified using clustering methods to provide a better understanding of the clinical presentation of TMD when multiple diagnosis are present. Classifying patients into identifiable symptomatic profiles would help clinicians to estimate how common a disorder is within a population of TMD patients and understand the probability of certain

PATHOPHYSIOLOGY AND TREATMENT OF TYPE 2 DIABETES: PERSPECTIVES ON THE PAST, PRESENT AND FUTURE

PubMed Central

Kahn, Steven E.; Cooper, Mark E.; Del Prato, Stefano

2014-01-01

Normal regulation of glucose metabolism is determined by a feedback loop involving the islet β-cell and insulin-sensitive tissues in which tissue sensitivity to insulin determines the magnitude of the β-cell response. When insulin resistance is present, the β-cell maintains normal glucose tolerance by increasing insulin output. It is only when the β-cell is incapable of releasing sufficient insulin in the presence of insulin resistance that glucose levels rise. While β-cell dysfunction has a clear genetic component, environmental changes play a vital role. Modern approaches have also informed regarding the importance of hexoses, amino acids and fatty acids in determining insulin resistance and β-cell dysfunction as well as the potential role of alterations in the microbiome. A number of new treatment approaches have been developed, but more effective therapies that slow the progressive loss of β-cell function are needed. Recent clinical trials have provided important information regarding approaches to prevent and treat type 2 diabetes as well as some of the adverse effects of these interventions. However, additional long-term studies of medications and bariatric surgery are required in order to identify novel approaches to prevention and treatment, thereby reducing the deleterious impact of type 2 diabetes. PMID:24315620

The Pathophysiology of Repetitive Concussive Traumatic Brain Injury in Experimental Models; New Developments and Open Questions

PubMed Central

Brody, David L; Benetatos, Joseph; Bennett, Rachel E; Klemenhagen, Kristen C; Donald, Christine L Mac

2015-01-01

In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. PMID:25684677

Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.

PubMed

King, Jill; Pana, Zoi-Dorothea; Lehrnbecher, Thomas; Steinbach, William J; Warris, Adilia

2017-09-01

Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.

Graph theory findings in the pathophysiology of temporal lobe epilepsy

PubMed Central

Chiang, Sharon; Haneef, Zulfi

2014-01-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE. PMID:24831083

The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

"Clinical brain profiling": a neuroscientific diagnostic approach for mental disorders.

PubMed

Peled, Abraham; Geva, Amir B

2014-10-01

Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain profiling (CBP) and presents some provisional validation using clinical assessments and meta-analyses of neuroscientific publications. The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling. This involves a description of the key aspects of functional anatomy that can lead to psychopathology. These features constitute the dimensions or categories for a profile of brain disorders based upon pathophysiology. The second section describes a mapping or translation matrix that maps from symptoms and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation. We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and figures. The third section addresses the construct validity of clinical brain profiling by establishing correlations between profiles based on clinical ratings of symptoms and signs under classical diagnostic categories with the corresponding profiles generated automatically using archetypal diagnoses. We then provide further validation by performing a cluster analysis on the symptoms and signs and showing how they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis. In the fourth section, we address the construct validity of clinical brain profiling by looking for associations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in the first section, we test some particular hypotheses about double dissociations using a meta-analysis of PubMed searches. The final section concludes with perspectives for the future and outstanding validation issues for clinical

Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder

PubMed Central

Ionescu, Dawn F.; Richards, Erica M.; Zarate, Carlos A.

2014-01-01

Monoaminergic neurotransmitter (serotonin, norepinephrine and dopamine) mechanisms of disease dominated the research landscape in the pathophysiology and treatment of major depressive disorder (MDD) for more than 50 years and still dominate available treatment options. However, the sum of all brain neurons that use monoamines as their primary neurotransmitter is <20 %. In addition, most patients treated with monoaminergic antidepressants are left with significant residual symptoms and psychosocial disability not to mention side effects, e.g., sexual dysfunction. In the past several decades, there has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of MDD. Although several preclinical and human magnetic resonance spectroscopy studies had already implicated glutamatergic abnormalities in the human brain, it was rocketed by the discovery that the N-methyl-D-aspartate receptor antagonist ketamine has rapid and potent antidepressant effects in even the most treatment-resistant MDD patients, including those who failed to respond to electroconvulsive therapy and who have active suicidal ideation. In this review, we will first provide a brief introduction to glutamate and its receptors in the mammalian brain. We will then review the clinical evidence for glutamatergic dysfunction in MDD, the discovery and progress-to-date with ketamine as a rapidly acting antidepressant, and other glutamate receptor modulators (including proprietary medications) for treatment-resistant depression. We will finally conclude by offering potential future directions necessary to realize the enormous therapeutic promise of glutamatergic antidepressants. PMID:24318540

Coeliac Disease – New Pathophysiological Findings and Their Implications for Therapy

PubMed Central

Stein, Jürgen; Schuppan, Detlef

2014-01-01

Summary Coeliac disease (CD) is one of the most common diseases worldwide, resulting from a combination of environmental (gluten) and genetic (human leucocyte antigen (HLA) and non-HLA genes) factors. Depending on the geographical location, the prevalence of CD has been estimated to approximate 0.5-1%. The only treatment currently available for CD is a gluten-free diet (GFD) excluding gluten-containing cereals such as wheat, rye, and barley, and other foodstuffs with natural or added gluten. However, adherence rates and patient acceptance are often poor. Moreover, even in fully adherent patients, the diet may fail to induce clinical or histological improvement. Hence, it is unsurprising that studies show CD patients to be highly interested in non-dietary alternatives. The following review focuses on current pathophysiological concepts of CD, spotlighting those pathways which may serve as new possible, non-dietary therapeutic targets in the treatment of CD. PMID:26288589

TGF-β1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency Pathophysiology.

PubMed

Serralheiro, Pedro; Soares, Andreia; Costa Almeida, Carlos M; Verde, Ignacio

2017-11-26

Chronic venous insufficiency and varicose veins occur commonly in affluent countries and are a socioeconomic burden. However, there remains a relative lack of knowledge about venous pathophysiology. Various theories have been suggested, yet the molecular sequence of events is poorly understood. Transforming growth factor-beta one (TGF-β1) is a highly complex polypeptide with multifunctional properties that has an active role during embryonic development, in adult organ physiology and in the pathophysiology of major diseases, including cancer and various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis on understanding its signaling pathways (and possible disruptions) will be an essential requirement for a better comprehension and management of specific diseases. This review aims at shedding more light on venous pathophysiology by describing the TGF-β1 structure, function, activation and signaling, and providing an overview of how this growth factor and disturbances in its signaling pathway may contribute to specific pathological processes concerning the vessel wall which, in turn, may have a role in chronic venous insufficiency.

Molecular pathophysiology of cerebral edema

PubMed Central

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity?

PubMed

Farré, R

2013-10-01

Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed. © 2013 John Wiley & Sons Ltd.

Cranial dural arteriovenous shunts. Part 4. Clinical presentation of the shunts with leptomeningeal venous drainage.

PubMed

Baltsavias, Gerasimos; Spiessberger, Alex; Hothorn, Torsten; Valavanis, Anton

2015-04-01

Cranial dural arteriovenous fistulae have been classified into high- and low-risk lesions mainly based on the pattern of venous drainage. Those with leptomeningeal venous drainage carry a higher risk of an aggressive clinical presentation. Recently, it has been proposed that the clinical presentation should be considered as an additional independent factor determining the clinical course of these lesions. However, dural shunts with leptomeningeal venous drainage include a very wide spectrum of inhomogeneous lesions. In the current study, we correlated the clinical presentation of 107 consecutive patients harboring cranial dural arteriovenous shunts with leptomeningeal venous drainage, with their distinct anatomic and angiographic features categorized into eight groups based on the "DES" (Directness and Exclusivity of leptomeningeal venous drainage and features of venous Strain) concept. We found that among these groups, there are significant angioarchitectural differences, which are reflected by considerable differences in clinical presentation. Leptomeningeal venous drainage of dural sinus shunts that is neither direct nor exclusive and without venous strain manifested only benign symptoms (aggressive presentation 0%). On the other end of the spectrum, the bridging vein shunts with direct and exclusive leptomeningeal venous drainage and venous strain are expected to present aggressive symptoms almost always and most likely with bleeding (aggressive presentation 91.5%). Important aspects of the above correlations are discussed. Therefore, the consideration of leptomeningeal venous drainage alone, for prediction of the clinical presentation of these shunts appears insufficient. Angiographic analysis based on the above concept, offers the possibility to distinguish the higher- from the lower-risk types of leptomeningeal venous drainage. In this context, consideration of the clinical presentation as an additional independent factor for the prediction of their clinical

The Effectiveness of Transcranial Brain Stimulation in Improving Clinical Signs of Hyperkinetic Movement Disorders.

PubMed

Obeso, Ignacio; Cerasa, Antonio; Quattrone, Aldo

2015-01-01

Repetitive transcranial magnetic stimulation (rTMS) is a safe and painless method for stimulating cortical neurons. In neurological realm, rTMS has prevalently been applied to understand pathophysiological mechanisms underlying movement disorders. However, this tool has also the potential to be translated into a clinically applicable therapeutic use. Several available studies supported this hypothesis, but differences in protocols, clinical enrollment, and variability of rTMS effects across individuals complicate better understanding of efficient clinical protocols. The aim of this present review is to discuss to what extent the evidence provided by the therapeutic use of rTMS may be generalized. In particular, we attempted to define optimal cortical regions and stimulation protocols that have been demonstrated to maximize the effectiveness seen in the actual literature for the three most prevalent hyperkinetic movement disorders: Parkinson's disease (PD) with levodopa-induced dyskinesias (LIDs), essential tremor (ET) and dystonia. A total of 28 rTMS studies met our search criteria. Despite clinical and methodological differences, overall these studies demonstrated that therapeutic applications of rTMS to "normalize" pathologically decreased or increased levels of cortical activity have given moderate progress in patient's quality of life. Moreover, the present literature suggests that altered pathophysiology in hyperkinetic movement disorders establishes motor, premotor or cerebellar structures as candidate regions to reset cortico-subcortical pathways back to normal. Although rTMS has the potential to become a powerful tool for ameliorating the clinical outcome of hyperkinetic neurological patients, until now there is not a clear consensus on optimal protocols for these motor disorders. Well-controlled multicenter randomized clinical trials with high numbers of patients are urgently required.

Clinical presentation, imaging findings, and prognosis of spinal dural arteriovenous fistula.

PubMed

Lee, Jookyung; Lim, Young-Min; Suh, Dae Chul; Rhim, Seung Chul; Kim, Sang Joon; Kim, Kwang-Kuk

2016-04-01

Spinal dural arteriovenous fistula (SDAVF) is a relatively common acquired vascular malformation of the spinal cord. Assessment of a SDAVF is often difficult because of non-specific findings on non-invasive imaging modalities. Diagnosis of a SDAVF is often delayed, and some patients receive unnecessary treatment and treatment delays, often resulting in a poor outcome. The aim of this study was to characterize the clinical presentation, typical imaging findings, and long-term outcome of SDAVF. Forty patients (13 women, 27 men; mean age 58.18 ± standard deviation 14.75 years) who were treated at our hospital from June 1992 to March 2014 were retrospectively reviewed. We investigated the baseline characteristics, clinical presentation, imaging findings, treatment modalities, and outcome of the patients. The most common clinical presentation was a sensory symptom (80%), followed by motor weakness (70%), and sphincter dysfunction (62.5%). Roughly one-third (32.5%) of patients had a stepwise progression of fluctuating weakness and sensory symptoms, but the most common presentation was chronic progressive myelopathic symptoms (47.5%). Thirty-four patients (85%) had T2 signal change on the spinal cord MRI, indicative of cord edema. Thirty-eight patients had typical perimedullary vessel flow voids on T2-weighted MRI. Twenty-eight patients were treated with endovascular embolization, five patients underwent surgery, and four patients underwent both. Clinical outcome was determined by severity of initial deficit (p=0.008), extent of cord edema (p=0.010), treatment failure (p=0.004), and a residual fistula (p=0.017). SDAVF causes a treatable myelopathy, so early diagnosis and intervention is essential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bile acid malabsorption in chronic diarrhea: Pathophysiology and treatment

PubMed Central

Barkun, Alan; Love, Jonathan; Gould, Michael; Pluta, Henryk; Steinhart, A Hillary

2013-01-01

BACKGROUND: Bile acid malabsorption (BAM) is a common but frequently under-recognized cause of chronic diarrhea, with an estimated prevalence of 4% to 5%. METHODS: The published literature for the period 1965 to 2012 was examined for articles regarding the pathophysiology and treatment of BAM to provide an overview of the management of BAM in gastroenterology practice. RESULTS: BAM is classified as type 1 (secondary to ileal dysfunction), type 2 (idiopathic) or type 3 (secondary to gastrointestinal disorders not associated with ileal dysfunction). The estimated prevalence of BAM is >90% in patients with resected Crohn disease (CD) and 11% to 52% of unresected CD patients (type 1); 33% in diarrhea-predominant irritable bowel syndrome (type 2); and is a frequent finding postcholecystectomy or postvagotomy (type 3). Investigations include BAM fecal bile acid assay, 23-seleno-25-homo-tauro-cholic acid (SeHCAT) testing and high-performance liquid chromatography of serum 7-α-OH-4-cholesten-3-one (C4), to determine the level of bile acid synthesis. A less time-consuming and expensive alternative in practice is an empirical trial of the bile acid sequestering agent cholestyramine. An estimated 70% to 96% of chronic diarrhea patients with BAM respond to short-course cholestyramine. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Other bile acid sequestering agents, such as colestipol and colesevelam, are currently being investigated for the treatment of BAM-associated diarrhea. CONCLUSIONS: BAM is a common cause of chronic diarrhea presenting in gastroenterology practice. In accordance with current guidelines, an empirical trial of a bile acid sequestering agent is warranted as part of the clinical workup to rule out BAM. PMID:24199211

Canine anal sac adenocarcinomas: clinical presentation and response to therapy.

PubMed

Bennett, Peter F; DeNicola, Denis B; Bonney, Patty; Glickman, Nita W; Knapp, Deborah W

2002-01-01

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.

Clinical presentations of parvovirus B19 infection.

PubMed

Servey, Jessica T; Reamy, Brian V; Hodge, Joshua

2007-02-01

Although most persons with parvovirus B19 infection are asymptomatic or have mild, nonspecific, cold-like symptoms, several clinical conditions have been linked to the virus. Parvovirus B19 usually infects children and causes the classic "slapped-cheek" rash of erythema infectiosum (fifth disease). The virus is highly infectious and spreads mainly through respiratory droplets. By the time the rash appears, the virus is no longer infectious. The virus also may cause acute or persistent arthropathy and papular, purpuric eruptions on the hands and feet ("gloves and socks" syndrome) in adults. Parvovirus B19 infection can trigger an acute cessation of red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis, or congenital anemia. This is even more likely in patients with illnesses that have already shortened the lifespan of erythrocytes (e.g., iron deficiency anemia, human immunodeficiency virus, sickle cell disease, thalassemia, spherocytosis). A clinical diagnosis can be made without laboratory confirmation if erythema infectiosum is present. If laboratory confirmation is needed, serum immunoglobulin M testing is recommended for immunocompetent patients; viral DNA testing is recommended for patients in aplastic crisis and for those who are immunocompromised. Treatment is usually supportive, although some patients may require transfusions or intravenous immune globulin therapy. Most patients recover completely.

Breech presentation: an audit project as means of pursuing clinical excellence.

PubMed

Siassakos, D; Anderson, H; Panter, K

2005-10-01

Clinical audit is an effective quality improvement process to evaluate important clinical issues. Breech presentation is such an issue due to its contribution to the rising caesarean section (CS) rate. We set out to assess the management of breech presentation using, as standards, the delivery suite protocol and national guidelines. Our first audit revealed a low success rate of external cephalic version (ECV) and deficient documentation of written consent for ECV, other aspects of care being satisfactory. The results were presented to a multidisciplinary meeting and disseminated to relevant stakeholders. A re-audit was then performed. It confirmed significant improvement in the documentation of consent for ECV. It also revealed a good detection rate of breech, optimal offer rate of ECV and good neonatal outcome. However, uptake of ECV as well as the success rate could both be improved so as to reduce the CS rate for breech presentation. We discuss options for improving the uptake and success rate for ECV.

Headache attributed to airplane travel: diagnosis, pathophysiology, and treatment - a systematic review.

PubMed

Bui, Sebastian Bao Dinh; Gazerani, Parisa

2017-08-16

Headache attributed to airplane travel, also named "airplane headache" (AH) is a headache that occurs during take-off and landing. Today, there are still uncertainties about the pathophysiology and treatment of AH. This systematic review was performed to facilitate identification of the existing literature on AH in order to discuss the current evidence and areas that remain to be investigated in AH. The systematic literature search was performed in 3 relevant medical databases; PubMed, Scopus, and Embase. The search yielded 220 papers and the papers were sorted based on inclusion and exclusion criteria established for this study. This systematic review included 39 papers. Main findings revealed that AH attacks are clinically stereotyped and appear mostly during landing phases. The headache presents as a severe painful headache that often disappears within 30 min. The pain is unilateral and localized in the fronto-orbital region. Sinus barotrauma has been considered as the main cause of AH. Nonsteroidal anti-inflammatory drugs and triptans have been taken by passengers with AH, to relieve the headache. Based on this systematic review, further studies seem required to investigate underlying mechanisms in AH and also to investigate the biological effects of nonsteroidal anti-inflammatory drugs and triptans for alleviating of AH. These studies would advance our understanding of AH pathogenesis and potential use of treatments that are not yet established.

Insight in pediatric obsessive-compulsive disorder: associations with clinical presentation.

PubMed

Storch, Eric A; Milsom, Vanessa A; Merlo, Lisa J; Larson, Michael; Geffken, Gary R; Jacob, Marni L; Murphy, Tanya K; Goodman, Wayne K

2008-08-15

Insight has emerged as a significant treatment outcome predictor in adult obsessive-compulsive disorder (OCD), with some suggesting that OCD with poor insight represents a distinct clinical subtype. Despite its clinical relevance, limited data exist on insight in pediatric OCD patients. The present study investigated the relation between poor insight and clinical characteristics among children and adolescents with OCD (N=78, ages 6-20 years). Forty-five percent of the sample (n=35) was considered to have low levels of insight into their symptoms, as determined by clinician rating on item 11 of the Children's Yale-Brown Obsessive-Compulsive Scale. Pearson product-moment correlations showed a significant, inverse relation between insight and OCD severity. Relative to the high insight group, parents of patients with low insight reported higher levels of OCD-related impairment and family accommodation. These findings suggest that OCD with poor insight may represent a distinct clinical feature that may require more intensive and multimodal treatment approaches.

Recurrent Guillain-Barré syndrome presenting stereotypic manifestations, positive antiganglioside antibodies, and rapid recovery.

PubMed

Pyun, So Young; Jeong, Jin-Ho; Bae, Jong Seok

2015-12-01

Recurrent Guillain-Barré syndrome (rGBS) has been described as a rare entity with distinct characteristics. However, little is known about rGBS in Asian group. The aim of this study was to identify the incidence and clinical course of rGBS, and to determine its clinical/pathophysiological implications. The consecutive data of 117 GBS patients were retrieved from a single university-based hospital in Korea and analyzed in terms of clinical, serological, electrophysiological aspects. A thorough review revealed that three (2.6%) of the enrolled patients had experienced more than two definite recurrent attacks of GBS. Interestingly, all three cases exhibited clinically stereotypical features, serum antiganglioside antibodies, and rapid recovery after intravenous immunoglobulin treatment. Clinical, serological, and electrophysiological features of rGBS cases were described in detail. The stereotypic presentation of each attack in this variant suggests the importance of both host and genetic factors for the clinical manifestations. In addition, the simultaneous presence of serum antiganglioside antibodies and rapid recovery implicate reversible nerve conduction failure as the mechanism of rGBS. These features are different from typical monophasic GBS and acute onset of chronic inflammatory demyelinating polyneuropathy. Copyright © 2015 Elsevier B.V. All rights reserved.

SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

PubMed

Shimano, Hitoshi; Sato, Ryuichiro

2017-12-01

Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

Central sensitization in tension-type headache--possible pathophysiological mechanisms.

PubMed

Bendtsen, L

2000-06-01

headache significantly more than placebo, while citalopram had only a slight and insignificant effect. It was concluded that the blockade of 5-HT reuptake could only partly explain the efficacy of amitriptyline in tension-type headache, and that also other actions of amitriptyline, e.g. reduction of central sensitization, were involved. Finally, the plasma 5-HT level, the platelet 5-HT level and the number of platelet 5-HT transporters were found to be normal in chronic tension-type headache. On the basis of the present and previous studies, a pathophysiological model for tension-type headache is presented. According to the model, the main problem in chronic tension-type headache is central sensitization at the level of the spinal dorsal horn/trigeminal nucleus due to prolonged nociceptive inputs from pericranial myofascial tissues. The increased nociceptive input to supraspinal structures may in turn result in supraspinal sensitization. The central neuroplastic changes may affect the regulation of peripheral mechanisms and thereby lead to, for example, increased pericranial muscle activity or release of neurotransmitters in the myofascial tissues. By such mechanisms the central sensitization may be maintained even after the initial eliciting factors have been normalized, resulting in the conversion of episodic into chronic tension-type headache. Future basic and clinical research should aim at identifying the source of peripheral nociception in order to prevent the development of central sensitization and at ways of reducing established sensitization. This may lead to a much needed improvement in the treatment of chronic tension-type headache and other chronic myofascial pain conditions.

The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders

PubMed Central

Mosconi, Matthew W.; Wang, Zheng; Schmitt, Lauren M.; Tsai, Peter; Sweeney, John A.

2015-01-01

The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD. PMID:26388713

Pathophysiology of Depression: Molecular Regulation of Melatonin Homeostasis - Current Status.

PubMed

Dmitrzak-Weglarz, Monika; Reszka, Edyta

2018-06-13

Circadian rhythm alterations resulting in disturbed sleep and disturbed melatonin secretion are flagship features of depression. Melatonin, known as a hormone of darkness, is secreted by the pineal gland located near to the center of the brain between the two hemispheres. Melatonin has an antidepressant effect by maintaining the body's circadian rhythm, by regulating the pattern of expression of the clock genes in the suprachiasmatic nucleus (SCN) and modifying the key genes of serotoninergic neurotransmission that are linked with a depressive mood. Melatonin is produced via the metabolism of serotonin in two steps which are catalyzed by serotonin N-acetyltransferase (SNAT) and acetylserotonin-O-methyltransferase (ASMT). Serotonin, SNAT, and ASMT are key melatonin level regulation factors. Melatonin acts mainly on the MT1 and MT2 receptors, which are present in the SCN, to regulate physiological and neuroendocrine functions including circadian entrainment, referred to as a chronobiotic effect. Although melatonin has been known about and refereed to for almost 50 years, the relationship between melatonin and depression is still not clear. In this review, we summarize current knowledge about the genetic and epigenetic regulation of enzymes involved in melatonin synthesis and metabolism as potential features of depression pathophysiology and treatment. Confirmation that melatonin metabolism in peripheral blood partially reflects a disorder in the brain could be a breakthrough in the standardization of measurements of melatonin level for the development of treatment standards, finding new therapeutic targets, and elaborating simple noninvasive clinical tests. © 2018 S. Karger AG, Basel.

Burn injury: review of pathophysiology and therapeutic modalities in major burns.

PubMed

Kaddoura, I; Abu-Sittah, G; Ibrahim, A; Karamanoukian, R; Papazian, N

2017-06-30

Despite a considerable decrease in their incidence worldwide, burn injuries remain one of the commonest forms of trauma and account for a weighty proportion of trauma cases in health-care emergencies around the globe. Although the latest data reveal a substantial decline in burn-related mortality and hospital admissions in the US over the past three decades, severe thermal injuries continue to trigger devastating morbidity and significant mortality while their management remains a dynamic challenge for the entire medical and paramedical community. Concrete evidence continues to be established regarding burn-associated pathophysiologic responses, and their destructive sequelae and deleterious effects in survivors at cellular, systemic as well as socio-economic level. Better understanding of these responses have contributed to advances in therapeutic strategies, improved long-term outcomes and catalyzed the reintegration of victims back into society. This paper describes the current understanding of the pathophysiology of a burn injury and characterizes both local and systemic pathophysiologic responses in terms of metabolic, hemodynamics, cardiac, renal, hepatic, gastro-intestinal, immunologic, endocrine as well as male reproductive systems in an attempt to understand the corresponding treatment modalities for this unique patient population.

Burn injury: review of pathophysiology and therapeutic modalities in major burns

PubMed Central

Kaddoura, I.; Abu-Sittah, G.; Ibrahim, A.; Karamanoukian, R.; Papazian, N.

2017-01-01

Summary Despite a considerable decrease in their incidence worldwide, burn injuries remain one of the commonest forms of trauma and account for a weighty proportion of trauma cases in health-care emergencies around the globe. Although the latest data reveal a substantial decline in burn-related mortality and hospital admissions in the US over the past three decades, severe thermal injuries continue to trigger devastating morbidity and significant mortality while their management remains a dynamic challenge for the entire medical and paramedical community. Concrete evidence continues to be established regarding burn-associated pathophysiologic responses, and their destructive sequelae and deleterious effects in survivors at cellular, systemic as well as socio-economic level. Better understanding of these responses have contributed to advances in therapeutic strategies, improved long-term outcomes and catalyzed the reintegration of victims back into society. This paper describes the current understanding of the pathophysiology of a burn injury and characterizes both local and systemic pathophysiologic responses in terms of metabolic, hemodynamics, cardiac, renal, hepatic, gastro-intestinal, immunologic, endocrine as well as male reproductive systems in an attempt to understand the corresponding treatment modalities for this unique patient population. PMID:29021720

Volvulus in term and preterm infants - clinical presentation and outcome.

PubMed

Horsch, Sandra; Albayrak, Bilge; Tröbs, Ralf-Bodo; Roll, Claudia

2016-06-01

Our aim was to assess if term and preterm infants with volvulus showed different patterns with regard to pathogenesis, clinical presentation and outcome. We reviewed the medical records and imaging data of infants aged less than six months with volvulus treated in a single surgical referral centre from 2006-2013. Volvulus was diagnosed in 19 infants, with no anatomical anomaly in three of the 12 preterm infants and one of the seven term infants. Most cases (74%) presented during the first eight days of life. Later presentations occurred exclusively in preterm infants, with only one of the five having no anatomic anomalies. Bilious vomiting was the leading symptom in six of the seven term infants, while the symptoms in preterm infants were rather nonspecific. Intestinal necrosis, with the need for bowel resection, occurred in one term (14%) infant and nine (75%) preterm infants. The clinical presentation and outcome of volvulus differed between preterm and term infants, but the rate and distribution of underlying anomalies did not differ. Symptoms in preterm infants were often nonspecific and led to a delay in diagnosis. This might have contributed to the higher rate of intestinal necrosis in preterm infants. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Human Pathophysiological Adaptations to the Space Environment

PubMed Central

Demontis, Gian C.; Germani, Marco M.; Caiani, Enrico G.; Barravecchia, Ivana; Passino, Claudio; Angeloni, Debora

2017-01-01

Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population. PMID:28824446

Human Pathophysiological Adaptations to the Space Environment.

PubMed

Demontis, Gian C; Germani, Marco M; Caiani, Enrico G; Barravecchia, Ivana; Passino, Claudio; Angeloni, Debora

2017-01-01

Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.

Interesting and unusual clinical presentations in leprosy at a referral center.

PubMed

Tayshetye, Pritam U; Pai, Vivek V; Khanolkar, Subhash A; Rathod, Vikram; Ganapati, Ramaswamy

2013-10-01

Leprosy is a disease of declining global endemicity but is still an important health-care problem in India. Pure neural leprosy is an important subset of presentations of leprosy in India. Leprosy is a known disease of the skin and nerves, but cases of pure neural involvement are relatively less. We hereby present 10 cases of pure neural leprosy in which the diagnosis of leprosy was difficult with routine methods. The study was conducted at the main referral center and satellite clinics of our organization. A retrospective analysis of patient records for the last four years was undertaken to identify patients presenting with predominantly neurological manifestations and uncommon presentations including those without skin lesions. The medical records of the patients were used as source of data. All the patients were subjected to a detailed clinical examination and bacteriological examination with slit-skin smears. Investigations like nerve biopsy, electromyography, and nerve conduction studies were done in patients with diagnostic difficulties. Patients presented with neurological symptoms like paresthesias (60%), diminished sensations (40%), nonhealing ulcers (30%), and blisters (20%). All except one had thickened nerves on clinical examination. Slit-skin smear was negative in all but one patient. Nerve biopsy confirmed the diagnosis of leprosy in seven cases. Pure neural leprosy is difficult to diagnose with routine methods. The diagnosis should be considered, especially by neurologists and dermatologists, who are more likely to see such patients with predominant neural manifestations. The diagnosis should be confirmed with nerve biopsy to prevent delay in therapy and associated complications.

Suprasellar ganglioglioma presenting with diabetes insipidus in a young boy: a rare clinical presentation.

PubMed

Gupta, Ruchika; Suri, Vaishali; Arora, Raman; Sharma, Mehar C; Mishra, Shashwat; Singh, Manmohan; Sarkar, Chitra

2010-02-01

Gangliogliomas are rare tumors composed of an admixture of glial and neuronal components. These usually occur in young patients, who present with therapy-resistant seizures. Clinical presentation of ganglioglioma with diabetes insipidus is extremely rare with only one case reported earlier in the available literature. Due to this rarity, ganglioglioma is not considered in the differential diagnosis in a patient with diabetes insipidus. A 7-year boy presented with polyuria, polydipsia, and progressive visual loss for 18 months. Investigations revealed diabetes insipidus. Radiographic studies of the brain showed a solid and cystic mass in the suprasellar region effacing the third ventricle. Intraoperatively, diffuse thickening of bilateral optic nerves and optic chiasma was noted and a diagnosis of optic glioma was considered. A biopsy of the mass was taken, which on histopathological examination showed features of ganglioglioma. The patient was referred for further radiotherapy but was lost to follow-up. Diabetes insipidus as a presenting symptom of ganglioglioma is extremely rare. This benign tumor should be kept in mind in patients with central diabetes insipidus and a suprasellar mass lesion. This report describes the second such case in the literature.

Early onset marfan syndrome: Atypical clinical presentation of two cases

PubMed Central

Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

2015-01-01

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

PubMed

Bradshaw, Michael J; Venkatesan, Arun

2016-07-01

Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

Mechanistic approach to the pathophysiology of target organ damage in hypertension from studies in a human model with characteristics opposite to hypertension: Bartter's and Gitelman's syndromes.

PubMed

Calò, L A; Maiolino, G

2015-07-01

Extensive studies using Bartter's/Gitelman's syndrome patients have provided insights into the angiotensin II (Ang II) signaling pathways involved in the regulation of vascular tone and cardiovascular-renal remodeling. The renin-angiotensin-aldosterone system is activated in these syndromes, however, patients do not develop hypertension and cardiovascular remodeling and clinically manifest conditions opposite to hypertension. The short- and the long-term signaling of Ang II remains an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications. The long-term signaling of Ang II is involved in the pathophysiology of cardiovascular-renal remodeling and inflammatory responses in which the balance between RhoA/Rho kinase pathway and NO system plays a crucial role. In this brief review, the results of our studies in Bartter's and Gitelman's syndromes are reported on these processes. The information obtained from these studies can clarify, confirm or be used to extend the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could offer further chances to identify additional potential significant targets of therapy.

Revitalizing pathology laboratories in a gastrointestinal pathophysiology course using multimedia and team-based learning techniques.

PubMed

Carbo, Alexander R; Blanco, Paola G; Graeme-Cooke, Fiona; Misdraji, Joseph; Kappler, Steven; Shaffer, Kitt; Goldsmith, Jeffrey D; Berzin, Tyler; Leffler, Daniel; Najarian, Robert; Sepe, Paul; Kaplan, Jennifer; Pitman, Martha; Goldman, Harvey; Pelletier, Stephen; Hayward, Jane N; Shields, Helen M

2012-05-15

In 2008, we changed the gastrointestinal pathology laboratories in a gastrointestinal pathophysiology course to a more interactive format using modified team-based learning techniques and multimedia presentations. The results were remarkably positive and can be used as a model for pathology laboratory improvement in any organ system. Over a two-year period, engaging and interactive pathology laboratories were designed. The initial restructuring of the laboratories included new case material, Digital Atlas of Video Education Project videos, animations and overlays. Subsequent changes included USMLE board-style quizzes at the beginning of each laboratory, with individual readiness assessment testing and group readiness assessment testing, incorporation of a clinician as a co-teacher and role playing for the student groups. Student responses for pathology laboratory contribution to learning improved significantly compared to baseline. Increased voluntary attendance at pathology laboratories was observed. Spontaneous student comments noted the positive impact of the laboratories on their learning. Pathology laboratory innovations, including modified team-based learning techniques with individual and group self-assessment quizzes, multimedia presentations, and paired teaching by a pathologist and clinical gastroenterologist led to improvement in student perceptions of pathology laboratory contributions to their learning and better pathology faculty evaluations. These changes can be universally applied to other pathology laboratories to improve student satisfaction. Copyright © 2012 Elsevier GmbH. All rights reserved.

Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.

PubMed

Kolkka-Palomaa, M; Jääskeläinen, S K; Laine, M A; Teerijoki-Oksa, T; Sandell, M; Forssell, H

2015-11-01

Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by burning pain often accompanied with taste dysfunction and xerostomia. The most compelling evidence concerning BMS pathophysiology comes from studies on the somatosensory system using neurophysiologic or psychophysical methods such as blink reflex, thermal quantitative sensory testing, as well as functional brain imaging. They have provided convincing evidence for neuropathic involvement at several levels of the somatosensory system in BMS pain pathophysiology. The number of taste function studies trying to substantiate the subjective taste disturbances or studies on salivary factors in BMS is much more limited, and most of them suffer from definitional and methodological problems. This review aims to critically evaluate the existing literature on the pathophysiology of BMS, paying special attention to the correctness of case selection and the methodology used in published studies, and to summarize the current state of knowledge. Based on the recognition of several gaps in the current understanding of the pathophysiology of BMS especially as regards taste and pain system interactions, the review ends with future scenarios for research in this area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Idiopathic granulomatous mastitis: a heterogeneous disease with variable clinical presentation.

PubMed

Baslaim, Muna M; Khayat, Hind A; Al-Amoudi, Shefaa A

2007-08-01

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast disease that presents with variable local manifestations. We describe here the different management protocols based on the clinical presentation of these patients. A retrospective review of 20 histopathologic confirmed cases of IGM seen over a period of 10 years was performed. The median age was 34 years (age range: 21-45 years). All were married, parous with history of breast feeding. Ill-defined mass mimicking carcinoma was the commonest presentation (70%); however, with the presence of signs of inflammation like pain (55%), redness (40%), and peau d'orange (40%), an inflammatory process appeared more likely. Axillary lymph node enlargement was infrequently seen (40%). Radiologic findings (mammography and ultrasound) were nonspecific. Histopathology showed the characteristic lobular distribution of granulomatous inflammation in all cases. Surgically, 7 patients had abscess drainage with open biopsy, and 7 patients had lumpectomy. Six patients with diffuse breast involvement were diagnosed by core needle biopsy only. Microbial cultures showed no growth. Antibiotics were given empirically when signs of inflammation where present. Two patients needed further abscess drainage followed by persistent sinus excision 3-6 weeks later. The median follow-up was 24 months (range: 15-42 months). Seventeen patients (85%) were recurrence-free, and 3 patients (15%) were lost to follow-up. Management of IGM cases needs to be tailored according to the clinical presentation. Precise radiologic and pathologic data interpretation by a multidisciplinary breast team will facilitate diagnosis and minimize unnecessary intervention.

All That Glitters Yellow Is Not Gold: Presentation and Pathophysiology of Bile Cast Nephropathy.

PubMed

Pitlick, Mitchell; Rastogi, Prerna

2017-10-01

Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one. In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy. One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline. Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.

Pathophysiological relationships between heart failure and depression and anxiety.

PubMed

Chapa, Deborah W; Akintade, Bimbola; Son, Heesook; Woltz, Patricia; Hunt, Dennis; Friedmann, Erika; Hartung, Mary Kay; Thomas, Sue Ann

2014-04-01

Depression and anxiety are common comorbid conditions in patients with heart failure. Patients with heart failure and depression have increased mortality. The association of anxiety with increased mortality in patients with heart failure is not established. The purpose of this article is to illustrate the similarities of the underlying pathophysiology of heart failure, depression, and anxiety by using the Biopsychosocial Holistic Model of Cardiovascular Health. Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal axis, autonomic dysregulation, and activation of cytokine cascades and platelets. Patients with heart failure and depression or anxiety may exhibit a continued cycle of heart failure progression, increased depression, and increased anxiety. Understanding the underlying pathophysiological relationships in patients with heart failure who experience comorbid depression and/or anxiety is critical in order to implement appropriate treatments, educate patients and caregivers, and educate other health professionals.

Neurofascin-155 IGG4 Neuropathy: Pathophysiological Insights, Spectrum of Clinical Severity and Response To treatment.

PubMed

Garg, Nidhi; Park, Susanna B; Yiannikas, Con; Vucic, Steve; Howells, James; Noto, Yu-Ichi; Mathey, Emily K; Pollard, John D; Kiernan, Matthew C

2018-05-01

Sensorimotor neuropathy associated with IgG4 antibodies to neurofascin-155 (NF155) was recently described. The clinical phenotype is typically associated with young onset, distal weakness, and in some cases, tremor. From a consecutive cohort of 55 patients diagnosed with chronic inflammatory demyelinating polyneuropathy, screening for anti-NF155 antibodies was undertaken. Patients underwent clinical assessment, diagnostic neurophysiology, including peripheral axonal excitability studies and nerve ultrasound. Three of 55 chronic inflammatory demyelinating polyneuropathy patients (5%) tested positive for anti-NF155 IgG4. Patients presenting with more severe disease had higher antibody titers. Ultrasound demonstrated diffuse nerve enlargement. Axonal excitability studies were markedly abnormal, with subsequent mathematical modeling of the results supporting disruption of the paranodal seal. A broad spectrum of disease severity and treatment response may be observed in anti-NF155 neuropathy. Excitability studies support the pathogenic role of anti-NF155 IgG4 antibodies targeting the paranodal region. Muscle Nerve 57: 848-851, 2018. © 2017 Wiley Periodicals, Inc.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.

PubMed

Michalakis, Stylianos; Becirovic, Elvir; Biel, Martin

2018-03-07

The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca 2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

PubMed Central

Biel, Martin

2018-01-01

The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application. PMID:29518895

A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome

PubMed Central

Blondonnet, Raiko; Constantin, Jean-Michel; Sapin, Vincent; Jabaudon, Matthieu

2016-01-01

Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care. PMID:26980924

Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine.

PubMed

Jones, B A; Gores, G J

1997-12-01

Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.

Common pathophysiological mechanisms involved in luteal phase deficiency and polycystic ovary syndrome. Impact on fertility.

PubMed

Boutzios, Georgios; Karalaki, Maria; Zapanti, Evangelia

2013-04-01

Luteal phase deficiency (LPD) is a consequence of the corpus luteum (CL) inability to produce and preserve adequate levels of progesterone. This is clinically manifested by short menstrual cycles and infertility. Abnormal follicular development, defects in neo-angiogenesis or inadequate steroidogenesis in the lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and polycystic ovary syndrome (PCOS) are independent disorders sharing common pathophysiological profiles. Factors such as hyperinsulinemia, AMH excess, and defects in angiogenesis of CL are at the origin of both LPD and PCOS. In PCOS ovulatory cycles, infertility could result from dysfunctional CL. The aim of this review was to investigate common mechanisms of infertility in CL dysfunction and PCOS.

Translational neuropathic pain research: A clinical perspective.

PubMed

Bouhassira, D; Attal, N

2016-12-03

Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. Copyright © 2016. Published by Elsevier Ltd.

The Hypoxic Testicle: Physiology and Pathophysiology

PubMed Central

Reyes, Juan G.; Farias, Jorge G.; Henríquez-Olavarrieta, Sebastián; Madrid, Eva; Parraga, Mario; Zepeda, Andrea B.; Moreno, Ricardo D.

2012-01-01

Mammalian spermatogenesis is a complex biological process occurring in the seminiferous tubules in the testis. This process represents a delicate balance between cell proliferation, differentiation, and apoptosis. In most mammals, the testicles are kept in the scrotum 2 to 7°C below body core temperature, and the spermatogenic process proceeds with a blood and oxygen supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, pathologies such as varicocele or testicular torsion and environmental exposure to low oxygen (hypoxia) can result in changes in blood flow, nutrients, and oxygen supply along with an increased local temperature that may induce adverse effects on Leydig cell function and spermatogenesis. These conditions may lead to male subfertility or infertility. Our literature analyses and our own results suggest that conditions such as germ cell apoptosis and DNA damage are common features in hypoxia and varicocele and testicular torsion. Furthermore, oxidative damage seems to be present in these conditions during the initiation stages of germ cell damage and apoptosis. Other mechanisms like membrane-bound metalloproteinases and phospholipase A2 activation could also be part of the pathophysiological consequences of testicular hypoxia. PMID:23056665

Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy.

PubMed

Mariotte, Eric; Azoulay, Elie; Galicier, Lionel; Rondeau, Eric; Zouiti, Fouzia; Boisseau, Pierre; Poullin, Pascale; de Maistre, Emmanuel; Provôt, François; Delmas, Yahsou; Perez, Pierre; Benhamou, Ygal; Stepanian, Alain; Coppo, Paul; Veyradier, Agnès

2016-05-01

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13; activity <10%). We aimed to investigate the association between mechanisms for ADAMTS13 deficiency and the epidemiology and pathophysiology of thrombotic thrombocytopenic purpura at initial presentation. Between Jan 1, 1999, and Dec 31, 2013, we did a cross-sectional analysis of the French national registry for thrombotic microangiopathy to identify all patients with adult-onset thrombotic microangiopathy (first episode after age 18 years) who had severe ADAMTS13 deficiency at presentation. ADAMTS13 activity, anti-ADAMTS13 IgG, and ADAMTS13 gene mutations were investigated by a central laboratory. We collected patients' clinical data for correlation with their ADAMTS13 phenotype and genotype. We used logistic regression analysis to identify variables significantly associated with idiopathic thrombotic thrombocytopenic purpura, as measured by estimated odds ratios (ORs) and 95% CIs. This study is registered with ClinicalTrials.gov, number NCT00426686. We enrolled 939 patients with adult-onset thrombotic thrombocytopenic purpura, of whom 772 (82%) patients had available data and samples at presentation and comprised the cohort of interest. The prevalence of thrombotic thrombocytopenic purpura in France was 13 cases per million people. At presentation, 378 (49%) patients had idiopathic thrombotic thrombocytopenic purpura, whereas 394 (51%) patients had disease associated with miscellaneous clinical situations (infections, autoimmunity, pregnancy, cancer, organ transplantation, and drugs). Pathophysiologically, three distinct forms of thrombotic thrombocytopenic purpura were observed: 585 (75%) patients had autoimmune disease with anti-ADAMTS13 IgG, 166 (22%) patients had acquired disease of unknown cause and 21 (3%) patients had inherited disease (Upshaw-Schulman syndrome) with

Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology.

PubMed

Bisogni, Valeria; Rossi, Gian Paolo; Calò, Lorenzo A

2014-06-01

The glicyrrhizic acid, contained in licorice, has a mineralcorticoid-like effect. Chronic excess intake of licorice induces the rare syndrome of "apparent mineralcorticoid excess", due to the inhibitory effect of glicyrrhizic acid on 11 β-hydroxysteroid dehydrogenase type 2 determining clinical/biochemical manifestations as resistant hypertension, metabolic alkalosis and severe hypokalemia. We report a typical clinical case of licorice abuse to emphasize the importance of a detailed anamnesis, which is essential for the diagnosis, avoid unnecessary and expensive investigations, and reduce the duration of hospitalization. We also provide an appraisal of the pathophysiology of "apparent mineralcorticoid excess" syndrome, still an often forgotten or unrecognized cause of hypokalemia and hypertension.

Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

PubMed Central

2011-01-01

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented. PMID:21917147

Surfer's myelopathy: a rare presentation in a non-surfing setting and review of the literature.

PubMed

Maharaj, Monish M; Phan, Kevin; Hariswamy, Soumya; Rao, Prashanth J

2016-09-01

Surfers myelopathy can be a rapidly devastating disease and little is known surrounding the pathophysiology of the condition. Although the classical pattern of illness has been well reported, it has never been observed in a non-surfing setting. A 51-year-old demolition worker presented with acute non-traumatic myelopathy. Clinical examination revealed sensory loss to the level of L2. T2-MRI and MRI-DWI revealed a hyperintense signal suggestive of an ischaemic event. A diagnosis of surfer's myelopathy was made and he was commenced on steroid therapy. Following steroid therapy and fluid management the patient was discharged after 6 days with minor anaethesia but significant overall neurological improvement. Diagnosis of SM requires a thorough history, clinical examination and imaging (MRI, MRI-DWI). The patient should be admitted early and investigated. The use of rehabilitation services may be useful if available.

Evaluation of Asperger Syndrome in Youth Presenting to a Gender Dysphoria Clinic

PubMed Central

Reisner, Sari L.; Edwards-Leeper, Laura; Tishelman, Amy

2016-01-01

Abstract Purpose: There is evolving evidence that children and adolescents with gender dysphoria have higher-than-expected rates of autism spectrum disorder (ASD), yet clinical data on ASD among youth with gender dysphoria remain limited, particularly in North America. This report aims to fill this gap. Methods: We conducted a retrospective review of patient chart data from 39 consecutive youth ages 8 to 20 years (mean age 15.8 years, natal male: n = 22, natal female: n = 17) presenting for evaluation at a multidisciplinary gender clinic in a large U.S. pediatric hospital from 2007 to 2011 to evaluate the prevalence of ASD in this patient population. Results: Overall, 23.1% of patients (9/39) presenting with gender dysphoria had possible, likely, or very likely Asperger syndrome as measured by the Asperger Syndrome Diagnostic Scale (ASDS). Conclusion: These findings are consistent with growing evidence supporting increased prevalence of ASD in gender dysphoric children. To guide provision of optimal clinical care and therapeutic intervention, routine assessment of ASD is recommended in youth presenting for gender dysphoria. PMID:26651183

Evaluation of Asperger Syndrome in Youth Presenting to a Gender Dysphoria Clinic.

PubMed

Shumer, Daniel E; Reisner, Sari L; Edwards-Leeper, Laura; Tishelman, Amy

2016-10-01

There is evolving evidence that children and adolescents with gender dysphoria have higher-than-expected rates of autism spectrum disorder (ASD), yet clinical data on ASD among youth with gender dysphoria remain limited, particularly in North America. This report aims to fill this gap. We conducted a retrospective review of patient chart data from 39 consecutive youth ages 8 to 20 years (mean age 15.8 years, natal male: n = 22, natal female: n = 17) presenting for evaluation at a multidisciplinary gender clinic in a large U.S. pediatric hospital from 2007 to 2011 to evaluate the prevalence of ASD in this patient population. Overall, 23.1% of patients (9/39) presenting with gender dysphoria had possible, likely, or very likely Asperger syndrome as measured by the Asperger Syndrome Diagnostic Scale (ASDS). These findings are consistent with growing evidence supporting increased prevalence of ASD in gender dysphoric children. To guide provision of optimal clinical care and therapeutic intervention, routine assessment of ASD is recommended in youth presenting for gender dysphoria.

Physiology and pathophysiology of K(ATP) channels in the pancreas and cardiovascular system: a review.

PubMed

Seino, Susumu

2003-01-01

K(ATP) channels are present in pancreatic and extrapancreatic tissues such as heart and smooth muscle, and display diverse molecular composition. They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX). Recent studies on genetically engineered Kir6.2 knockout mice have provided a better understanding of the physiological and pathophysiological roles of Kir6.2-containing K(ATP) channels. Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion. Kir6.2/SUR2A mediates the effects of K(ATP) channels openers on cardiac excitability and contractility and contributes to ischemic preconditioning. However, controversy remains on the physiological properties of the K(ATP) channels in vascular smooth muscle cells. Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone. This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels.

Hypertensive crisis. Clinical presentation, comorbidities, and target organ involvement.

PubMed

Al-Bannay, Rashed; Husain, Aysha A

2010-08-01

To evaluate the clinical presentation and comorbidities of hypertensive crisis in our own population. In this cohort based study, we investigate the clinical presentation and comorbidities of hypertensive crisis by evaluating the data collected between January and April 2009. We included 154 patients admitted with systolic and diastolic blood pressure of >179 mm Hg and >119 mm Hg (based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria) in the Department of Internal Medicine, Salmaniya Medical Complex, Kingdom of Bahrain. In the study population, 64.3% had hypertensive urgency (blood pressure elevation without end organ damage) and 35.7% had hypertensive emergency (blood pressure elevation with end organ damage). The mean age group was 45-65 years (56% of the study population) and more men were affected than women (100:54). Shortness of breath and neurological deficits had a strong statistical association with hypertensive emergency, and headache and blurring of vision had the same tendency toward hypertensive urgency. Diabetes mellitus was an independent risk factor for hypertensive crisis. Most of the studied patients were known hypertensive. Diabetes mellitus is powerful predictor for hypertensive crisis. Dyspnea and neurological deficits have significant statistical correlation with hypertensive emergencies.

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

PubMed Central

2018-01-01

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770