Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pathophysiology”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2001

Epidemiology and pathophysiology of Alzheimer's disease.

Researchers in Alzheimer's disease (AD) have made remarkable strides in the past 2 decades in characterizing the disorder, understanding its pathophysiology, and developing models for assessing treatment. With these successes and the promise of others to come, researchers and policy makers alike are keeping a nervous eye on the "demographic clock," which predicts that with the aging of the US population (and indeed the world), a massive increase in the number of AD cases and related dementias will emerge, flooding our medical care system and overwhelming our ability to care for these patients and their caregivers. This article explores some of the data underlying the explosion of AD and discusses the clinical disorder, its manifestations, and our advances in understanding the underlying pathobiology. Our growing knowledge of AD pathophysiology will lead us to the development of more effective medications to slow the progression or even prevent the emergence of this dreaded disorder.

Age Distribution↗
PubMed2002

Epidemiology and pathophysiology of peripheral arterial disease.

Evidence that both asymptomatic and symptomatic peripheral arterial disease (PAD) represent an independent risk for cardiovascular morbidity and mortality has triggered a resurgence in epidemiologic and clinical interest in PAD. Between 8 and 12 million people in the United States are presumed to have PAD, and as the US population ages the incidence of PAD is expected to increase. Epidemiologic studies have shown that the prevalence of PAD among men and women is similar, and autopsy studies of young adults have shown a high frequency of advanced atherosclerotic lesions in distal abdominal aorta by the second decade of life. The pathophysiology of PAD is complex and has not been studied thoroughly. Additional research to understand the pathophysiologic mechanisms in disease-specific circulatory beds is crucial for the advancement of medical therapy for PAD.

Arteriosclerosis↗
PubMed2005

New insight into the pathophysiology of lipid abnormalities in type 2 diabetes.

Lipid abnormalities in patients with type 2 diabetes are likely to play an important role in the development of atherogenesis. These lipid disorders include not only quantitative but also qualitative abnormalities of lipoproteins which are potentially atherogenic. The main quantitative abnormalities are increased triglyceride levels, related to an augmented hepatic production of VLDL and a reduction of both VLDL and IDL catabolism, and decreased HDL-Cholesterol levels due to an accelerated HDL catabolism. The main qualitative abnormalities include large VLDL particles (VLDL1), relatively rich in triglycerides, small dense LDL particles, increase in triglyceride content of LDL and HDL, glycation of apolipoproteins and increased susceptibility of LDL to oxidation. Moreover, although plasma LDL-cholesterol level is usually normal in type 2 diabetic patients, LDL particles show significant kinetic abnormalities, such as reduced turn-over, which is potentially harmful. The pathophysiology of lipid abnormalities in type 2 diabetes is not yet totally explained. However, insulin resistance and the "relative" insulin deficiency, observed in patients with type 2 diabetes, are likely to play a crucial role since insulin has an important function in the regulation of lipid metabolism. In addition, it is not excluded that adipocytokines, such as adiponectin, could play a role in the pathophysiology of lipid abnormalities in type 2 diabetes.

Atherosclerosis↗
PubMed2001

Multiple system atrophy: new developments in pathophysiology and therapy.

There have been substantial advances in the last five years in understanding the basic and clinical pathophysiology underlying multiple system atrophy (MSA). Identification of glial cytoplasmic inclusions has been the most important organizing principle for further elucidation of underlying mechanisms. Recently, several unexpected developments at the clinical level have been reported. In this article, we will focus on two of these: (1) the recognition that substantial autonomic function is retained in MSA but not modulated appropriately, and (2) a potent pressor effect from ingestion of water, which cannot be explained by currently understood physiologic and pathophysiologic mechanisms. In some patients, water has elicited a 50% increase in blood pressure and been more therapeutically effective than any available pressor drug. By careful coordination of the pressor effect of water and the depressor effect of carbohydrate-rich food, many patients with MSA can now have their blood pressure controlled without pharmacological intervention.

Journal Article↗
PubMed2003

Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease.

Understanding of the pathophysiology of Parkinson disease (PD) has advanced rapidly over the last two decades through basic and clinical studies using modern neuroanatomical, clinical assessment, neuropathological and functional brain imaging methods. Two interacting processes determine the development of functional impairment, neuronal degeneration with selective denervation of specific regions and compensatory responses, which oppose the effects of denervation. The clinical manifestations of PD, at least in early stages, reflect selective degeneration of dopamine neurons in the substantia nigra projecting through the nigrostriatal pathway to the caudal putamen with compensatory changes in this and related systems. Positron emission tomography with specific ligands for the dopamine system is a powerful tool for analysis of both degenerative and compensatory processes in the pathophysiology of Parkinson disease in vivo and can be used to confirm the diagnosis of dopamine deficient Parkinson disease.

Dopamine↗
PubMed2002

LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance.

Proteinase inhibitors are important negative regulators of proteinase action in vivo and are thus involved in several pathophysiological processes. Starting with the isolation of two new peptides from human blood filtrate, we succeeded in cloning a cDNA encoding the precursor protein for a novel 15-domain Kazal-type-related serine proteinase inhibitor. Two of the 15 domains almost exactly match the Kazal-type pattern, whereas the other 13 domains exhibit only four instead of six cysteine residues. Since the corresponding gene is expressed in several lympho-epithelial tissues, we termed this inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). For three of the 15 LEKTI domains, we demonstrated a significant trypsin-inhibiting activity. Recent results of another group show a relation between mutations within the LEKTI gene and the severe congenital disorder Netherton syndrome. In this review article, we give an overview of the already known data on the structure, processing, gene expression, and pathophysiological role of LEKTI.

Amino Acid Sequence↗
PubMed2000

Molecular biology and pathophysiological aspects of plasma cholesteryl ester transfer protein.

Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins. Since CETP regulates the plasma levels of HDL cholesterol and the size of HDL particles, CETP is considered to be a key protein in reverse cholesterol transport, a protective system against atherosclerosis. CETP, as well as plasma phospholipid transfer protein, belongs to members of the lipid transfer/lipopolysaccharide-binding protein (LBP) gene family, which also includes the lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein. Although these four proteins possess different physiological functions, they share marked biochemical and structural similarities. The importance of plasma CETP in lipoprotein metabolism was demonstrated by the discovery of CETP-deficient subjects with a marked hyperalphalipoproteinemia (HALP). Two common mutations in the CETP gene, intron 14 splicing defect and exon 15 missense mutation (D442G), have been identified in Japanese HALP patients with CETP deficiency. The deficiency of CETP causes various abnormalities in the concentration, composition, and functions of both HDL and low density lipoprotein. Although the pathophysiological significance of CETP in terms of atherosclerosis has been controversial, the in vitro experiments showed that large CE-rich HDL particles in CETP deficiency are defective in cholesterol efflux. Epidemiological studies in Japanese-Americans and in the Omagari area where HALP subjects with the intron 14 splicing defect of CETP gene are markedly frequent, have shown an increased incidence of coronary atherosclerosis in CETP-deficient patients. The current review will focus on the recent findings on the molecular biology and pathophysiological aspects of plasma CETP, a key protein in reverse cholesterol transport.

Animals↗
PubMed2000

Myoclonic seizures combined with partial seizures and probable pathophysiology of secondary bilateral synchrony.

OBJECTIVE: We report on a patient who showed an unusual transition from complex partial seizures to a combination of myoclonic seizures and partial seizures, and then to isolated myoclonic seizures. The pathophysiological mechanism of the myoclonic seizures in this uncommon condition was studied. METHODS: The interhemispheric small time differences were estimated in the ictal EEG discharges of myoclonic seizures for differentiation between primary and secondary bilateral synchrony. The estimation was performed by coherence and phase analysis based on the two-dimensional autoregressive model. RESULTS: The estimated interhemispheric time differences were at most 27.4 ms. The ictal activity of the myoclonic seizures was suggested to originate from a cortical focus in the right hemisphere, which was also the origin of the partial seizures. CONCLUSION: The patient was considered to have an unusual type of myoclonic seizures with a probable pathophysiological mechanism of secondary bilateral synchrony.

Brain↗
PubMed2003

Evoked potentials and transcranial magnetic stimulation in migraine: published data and viewpoint on their pathophysiologic significance.

Migraine is a disorder in which central nervous sytem dysfunction might play a pivotal role. Electroneurophysiology seems thus particularly suited to study its pathophysiology. We have extensively reviewed evoked potential and transcranial magnetic stimulation studies performed in migraineurs in order to identify their pathophysiologic significance. Publications available to us were completed by a Medline search. Retrieved and personal data were compared with respect to methodology and interpreted according to present knowledge on cortical information processing. Results are in part contradictory which appears to be method-, patient- and disease- related. Nonetheless, both evoked potential and transcranial magnetic stimulation studies demonstrate that the cerebral cortex, and possibly subcortical structures, are dysfunctioning interictally in both migraine with and without aura. These electrophysiologic abnormalities tend to normalise just before and during an attack and some of them seem to have a clear familial and predisposing character. Besides the studies of magnetophosphenes which have yielded contrasting results, chiefly because the method is not sufficiently reliable, most recent electrophysiologic investigations of cortical activities in migraine favour deficient habituation and decreased preactivation cortical excitability as the predominant interictal dysfunctions. We propose that the former is a consequence of the latter and that it could favour both interictal cognitive disturbances as well as a cerebral metabolic disequilibrium that may play a role in migraine pathogenesis. To summarize, electrophysiologic studies demonstrate in migraine between attacks a cortical, and possibly subcortical, dysfunction of which the hallmark is deficient habituation.

Brain Mapping↗
PubMed2003

Are colonic regular contractile frequency patterns in slow transit constipation a relevant pathophysiological phenomenon?

BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. AIMS: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. PATIENTS: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. METHODS: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. CONCLUSIONS: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.

Adult↗
PubMed2005

A review of the epidemiology and pathophysiology of pelvic floor dysfunction: do racial differences matter?

OBJECTIVE: To describe the current state of knowledge regarding etiology of pelvic floor dysfunction with special consideration to the effect of racial background on the epidemiology and pathophysiology of this disease. METHODS: We performed a nonsystematic review of the literature to detail the current knowledge of the etiology of pelvic floor dysfunction. Additionally, we performed a systematic search of MEDLINE, Cinahl, and the Cochrane database for English-language articles registered from January 1, 1989, to June 31, 2003, that evaluated racial differences in the epidemiology and pathophysiology of pelvic floor dysfunction. We also reviewed the references of identified articles. RESULTS: We identified 11 articles that examined the effect of racial background on stress urinary incontinence (SUI), urodynamic stress incontinence, and (or) pelvic organ prolapse. We identified 2 studies that measured the prevalence of subjective stress urinary incontinence. Six cross-sectional studies compared the prevalence of urodynamically confirmed SUI and (or) pelvic organ prolapse among different groups. White women had a higher risk of developing urodynamic stress incontinence. Three studies noted anatomical and physiological differences among the different groups. CONCLUSIONS: Both quantitative and qualitative defects in collagen (endopelvic fascia) and compromised levator ani muscle function have been identified as important etiologic factors in the development of pelvic floor dysfunction. Parity, vaginal delivery, menopause, and aging have been most clearly associated with collagen defects and levator ani muscle dysfunction. The literature suggests that white women are at increased risk for SUI. At present, there is insufficient evidence to draw any conclusions regarding the role of racial differences in pelvic organ prolapse. It is possible that differences in prevalence rates for both SUI and pelvic organ prolapse may be attributed to inherent anatomical and physiological differences among racial groups.

Aging↗
PubMed1979

Pathophysiological changes in urine and blood from calves experimentally infected with Sarcocystit cruzi.

Two 8-week experiments were conducted to determine the relationships between nutritional stress and pathophysiological changes in male Holstein calves infected with Sarcocystis cruzi. Calves were infected by oral inoculation with 200 000 S. cruzi sporocysts. In the first experiment weight gain reduction was greatest in inoculated calves during weeks 4 and 5 after inoculation. Feed intake was reduced during the 5th week. Erythrocyte count was reduced during week 5 and haemoglobin was reduced during week 6. The 24-h excretion of urinary and urea nitrogen from the inoculated calves was increased by treatment. In the 2nd experiments, both the feed-restricted and inoculated calves lost weight during weeks 4 and 5; feed intake was lower from week 5 to 8 inclusive. Urine volume from inoculated calves was lower during week 8. Lower urine excretions of sodium and potassium resulted from S. cruzi inoculation. There was a non-significant trend for higher urinary zinc excretion in the inoculated group during week 4. Urine nitrogen excretion from inoculated calves was higher during week 6. The urinary excretion of 3-methylhistidine from the inoculated calves was higher during week 4 and excretion of guanine was higher during weeks 4, 5 and 8. S. cruzi has several specific pathophysiological effects on calves beyond those induced by nutritional stress.

Animals↗
PubMed1984

Studies on the pathophysiology of chronic ovine haemonchosis in Merino and Scottish blackface lambs.

An experiment was conducted to examine, under laboratory conditions, the pathophysiology of chronic ovine haemonchosis. In the present study, groups of Merino and Scottish Blackface lambs were maintained on a low plane of nutrition and infected with 50 Haemonchus contortus larvae/kg live weight. The parasitized lambs along with respective breed controls were examined over a 27-week period. In addition to the body weight, haematological and parasitological parameters, erythrokinetic, metabolic, digestibility and nitrogen balance studies were conducted in the early stages of the infection. The results demonstrated that a low level of infection with H. contortus in lambs on a poor plane of nutrition caused the development of a normochromic normocytic anaemia which was associated with a modest but significant increase in abomasal blood loss and slightly elevated erythropoiesis in both breeds relative to the controls. The level of anaemia, hypoproteinaemia and pathophysiological changes were more marked in the Merino lambs and they also had higher faecal egg counts than the Blackface lambs.

Anemia↗
PubMed2003

Contributions from brain imaging to the elucidation of pathophysiology of bipolar disorder.

Over the past two decades, brain-imaging studies have examined the mechanisms possibly involved in the pathophysiology of bipolar and unipolar mood disorders. The available findings suggest subtle anatomical changes in sub-regions of the prefrontal cortex, medial temporal lobe and cerebellum, and functional abnormalities in brain circuits inter-connecting these same brain regions and the striatum in patients suffering from bipolar disorder. 1H magnetic resonance spectroscopy (MRS) studies reported decreased N-acetyl aspartate (NAA) levels in the dorsolateral prefrontal cortex, and 31P-MRS studies found abnormalities in membrane phospholipids in frontal and temporal regions in bipolar individuals. Few studies have utilized in-vivo receptor imaging to study bipolar patients. Even though preliminary findings from cross-sectional studies indicate anatomical, neurochemical, and functional brain abnormalities in bipolar patients in key regions involved in mood regulation, the relationship of such abnormalities with illness phase and their clinical relevance needs further investigation. The potential for utilization of brain-imaging tools to elucidate the pathophysiology of bipolar disorder is still largely unrealized, and it is anticipated that important new developments in this area will come about over the next years and beyond.

Bipolar Disorder↗
PubMed2006

Pathophysiology and therapy for haemoglobinopathies. Part II: thalassaemias.

Thalassaemias result from mutations of the globin genes that cause reduced or absent haemoglobin production and thus interfere with the critical function of oxygen delivery. They represent the most common single-gene disorders, with 4.83% of the world population carrying globin gene variants. Reduced or absent alpha-globin (alpha-thalassaemia) or beta-globin (beta-thalassaemia) leads to anaemia and multifaceted clinical syndromes. In this second of two reviews on the pathophysiology of haemoglobinopathies, we describe the clinical features, pathophysiology and molecular basis of alpha- and beta-thalassaemias. We then discuss current targeted therapies, including the new oral iron chelators, which, along with chronic transfusions, constitute the mainstay of symptomatic therapy for the majority of patients. Finally, we describe potentially curative therapies, such as bone marrow transplant, and discuss some of the outstanding research studies and questions, including the upcoming field of gene therapy for beta-thalassaemia. An accompanying article on haemoglobinopathies (Part I) focuses on sickle cell disease.

Humans↗
PubMed2006

Serial changes in urinary proteome profile of membranous nephropathy: implications for pathophysiology and biomarker discovery.

Membranous nephropathy is one of the most common causes of primary glomerular diseases worldwide. The present study adopted a gel-based proteomics approach to better understand the pathophysiology and define biomarker candidates of human membranous nephropathy using an animal model of passive Heymann nephritis (PHN). Clinical characteristics of Sprague-Dawley rats injected with rabbit anti-Fx1A antiserum mimicked those of human membranous nephropathy. Serial urine samples were collected at Days 0, 10, 20, 30, 40, and 50 after the injection with anti-Fx1A (number of rats = 6; total number of gels = 36). Urinary proteome profiles were examined using 2D-PAGE and SYPRO Ruby staining. Quantitative intensity analysis and ANOVA with Tukey post-hoc multiple comparisons revealed 37 differentially expressed proteins among 6 different time-points. These altered proteins were successfully identified by MALDI-TOF MS and classified into 6 categories: (i) proteins with decreased urinary excretion during PHN; (ii) proteins with increased urinary excretion during PHN; (iii) proteins with increased urinary excretion during PHN, but which finally returned to basal levels; (iv) proteins with increased urinary excretion during PHN, but which finally declined below basal levels; (v) proteins with undetectable levels in the urine during PHN; and (vi) proteins that were detectable in the urine only during PHN. Most of these altered proteins have functional significance in signaling pathways, glomerular trafficking, and controlling the glomerular permeability. The ones in categories (v) and (vi) may serve as biomarkers for detecting or monitoring membranous nephropathy. After normalization of the data with 24-h urine creatinine excretion, changes in 34 of initially 37 differentially expressed proteins remained statistically significant. These data underscore the significant impact of urinary proteomics in unraveling disease pathophysiology and biomarker discovery.

Biomarkers↗
PubMed2000

Chronic pancreatitis--new pathophysiological concepts.

The pathophysiology of chronic pancreatitis has been a controversial topic of discussion for decades. None of the concepts proposed up until now have been able to elucidate the course of the disease in a conclusive matter. However, with the growth of new techniques in cell and molecular biology and the ability to create genetically modified cell systems and animals, many new and potentially important mechanisms have been discovered in recent years. This article will review these new pathophysiological aspects in chronic pancreatitis, which include growth factor overexpression, inflammatory mediator activation, deregulated immune response and altered nerve growth with specific neuroimmune interactions.

Animals↗
PubMed2002

[Craniocerebral trauma--new pathophysiological and therapeutic viewpoints. 1: Management of the acute phase].

AIM: As there is only few evidence-based knowledge in the treatment of head trauma, the aim of this work was to demonstrate the close relationship between pathophysiology and clinical treatment modalities during the primary phase of head trauma. METHODS: Review article. DISCUSSION: Cerebral hypoxia represents the main source of secondary brain injury. Depending on severity and duration, there results an irreversible brain damage. Under clinical conditions, the continuous monitoring of cerebral perfusion pressure (CPP) allows an estimation of the risk for cerebral hypoxia and the beginning of causal therapy. The priority of treatment lies in normalization of arterial O2 and increase in cerebral blood flow (CBF). In case of unchanged autoregulation of CBF, a decrease of CPP is followed by vasodilation with increase of cerebral blood volume (CBV) and a increase of CPP leads to a decrease of CBV by vasoconstriction. The usual shift of autoregulation on the right side after trauma requires CPP-values > 70 mmHg in the initial posttraumatic phase as there exists the most probable risk of hypoxia. The therapy of elevated ICP > 20 mmHg is oriented on CPP. A decrease in ICP under load of CPP has to be avoided. Beyond it, there is a need of origin of ICP-increase. CONCLUSIONS: The priority of initial treatment after head trauma lies in the individual optimization of CBF by maintenance of adequate CPP and cerebrovascular resistance. Afterwards, there will be performed a goal-directed treatment being based on the differentiation of the varying subgroups of head trauma and their related pathophysiology, what leads to the required treatment strategy. For this reason, it is necessary to put in the traditional treatment option by means of the multimodal monitoring as soon as possible.

Brain↗