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At least 595 records · Page 33Linked to original sources
PubMed1990

Hemodynamic and metabolic correlates in adipose tissue: pathophysiologic considerations.

Research efforts investigating the pathophysiology of adipose tissue have often focused separately on either the metabolic or cardiovascular components of an expanding fat mass. However, the growth and development of the fat cells and their vasculature are closely interrelated, a fact that has been established through more than a century of diverse studies of adipose tissue. Recently, the prevalence of obesity in the United States has stimulated investigations into the cardiovascular and metabolic correlates occurring with excessive lipid deposition and subsequent adipose tissue expansion. These investigations have resulted in conclusive evidence that, from a cardiovascular perspective, obesity results in an elevated blood volume and cardiac output, accompanied by an expansion of adipose water space, whereas from a metabolic aspect, the disease is characterized by adipocyte enlargement and associated alterations in metabolic pathways and hormonal responsiveness. Because these separate areas of research have independently shown interdepot differences in perfusion requirements and metabolic adaptations during the transition from the lean to obese state, adipocyte expansion may be partially dependent on the pattern of vascularity. This hypothesis is discussed by examining the integral relationship between the cardiovascular system and adipocyte metabolism, hopefully providing new insight into control of the pathophysiological processes of an expanding adipose organ.

Adipose Tissue↗
PubMed2001

Characterization of the effects of antiangiogenic agents on tumor pathophysiology.

A variety of strategies have been proposed to control tumor growth and metastasis by inhibiting tumor angiogenesis. To optimally combine such antiangiogenic approaches with conventional therapy, improved methods are needed to characterize the underlying pathophysiologic changes. The objective of the current work was to demonstrate the utility of a combination of recently developed immunohistochemical and image analysis techniques in quantitating changes in tumor vasculature and hypoxia. Murine MCa-35 mammary carcinomas were frozen after administration of two COX-2 inhibitors: meloxicam and celecoxib (Celebrex). Total blood vessels were visualized using anti-CD31 staining, perfused vessels by intravenous injection of DiOC7, and tumor hypoxia by EF5 uptake. Although both agents produced similar reductions in tumor volume compared with untreated tumors, varied effects on tumor vasculature and hypoxia were noted. Meloxicam reduced total vessel numbers significantly, whereas celecoxib had no effect. Both drugs substantially increased perfused vessel densities. Although mean hypoxic marker uptake was unchanged from matched controls, intratumor EF5 heterogeneities were significantly different between drugs. The results suggest that COX-2 inhibitors can have varying effects on tumor pathophysiology. Successful use of these drugs to enhance radiation response will likely require optimization of drug choice, dose schedule, and direct physiologic monitoring.

Angiogenesis Inhibitors↗
PubMed1989

Plasma volume in resistant hypertension: guide to pathophysiology and therapy.

It might be expected that the tremendous increase in available antihypertensives would eliminate resistant hypertension by allowing many alternatives to its treatment. In spite of this, resistant hypertension remains a common problem due, the authors feel, to a poor understanding of the pathophysiology of this condition, particularly an understanding of whether plasma volume expansion mediates resistance to antihypertensive therapy. The authors evaluated the status of plasma volume as a major determinant of response to therapy in nine patients with resistant hypertension. Measuring plasma volume using I125 radiolabeled albumin, they found eight patients with elevated plasma volumes and one patient with a contracted plasma volume at the time of presentation with resistant hypertension. In all eight patients with plasma volume expansion, aggressive diuretic therapy allowed goal blood pressure to be achieved. The patient with plasma volume contraction achieved goal blood pressure with vasodilator therapy. Plasma volume expansion is common in resistant hypertension and it mediates resistance to therapy. Measurement of plasma volume gives the clinician important insight into the pathophysiology of resistant hypertension and increases the likelihood of successful management of the resistant hypertensive patient.

Adult↗
PubMed1998

Current concepts in the pathophysiology of abnormal pain perception in fibromyalgia.

Fibromyalgia is a noninflammatory rheumatic disorder characterized by chronic widespread musculoskeletal pain. Although many studies have described the pain and other clinical symptoms associated with this disorder, the primary mechanisms underlying the etiology of fibromyalgia remain elusive. This article reviews recent data supporting the links among each of three systems--the musculoskeletal system, the neuroendocrine system, and the central nervous system (CNS), all of which appear to play major roles in fibromyalgia pathophysiology--and pain in fibromyalgia, and concludes by presenting a model of the pathophysiology of abnormal pain perception in fibromyalgia which integrates the research findings described.

Central Nervous System↗
PubMed1998

Pathophysiology of aquaporin-2 in water balance disorders.

The recent identification of aquaporin water channel proteins has provided detailed information about the molecular basis for transepithelial water transport. At least five aquaporins have been identified in the kidney; they have provided detailed molecular insight into the fundamental physiology of water balance. This article focuses primarily on the physiology and pathophysiologic significance of the vasopressin-regulated water channel aquaporin-2 (AQP2) in a number of conditions where body water balance is disturbed. AQP2 is regulated by vasopressin by both short- and long-term mechanisms. Acutely, vasopressin induces exocytic insertion of AQP2 into the apical plasma membrane to increase collecting duct water reabsorption. Moreover, long-term regulation of body water balance is achieved by changes in total collecting duct levels of AQP2. Recent studies have documented that both vasopressin and vasopressin-independent regulation play important roles in this. In conditions with acquired nephrogenic diabetes insipidus (eg, lithium treatment, hypokalemia, postobstructive polyuria), AQP2 expression and targeting have been found to be markedly reduced, providing an explanation for the polyuria and the inability to concentrate urine associated with these conditions. Conversely, in conditions with water retention (eg, heart failure, pregnancy), it has been shown that AQP2 levels and plasma membrane targeting are increased. Continued analysis of aquaporins is providing detailed molecular insight into the physiology and pathophysiology of water balance disorders.

Animals↗
PubMed2006

Biomarkers in cardiovascular disease: integrating pathophysiology into clinical practice.

Biomarkers play an important role in the diagnosis, prognostic assessment, and management of patients with suspected acute coronary syndromes (ACS). Specific biomarkers identify different components of the pathophysiology of ACS: troponins are prototype markers of myocyte necrosis, natriuretic peptides reflect neurohormonal activation and hemodynamic stress, soluble CD40 ligand is an indicator of platelet activation, and C-reactive protein, myeloperoxidase, and monocyte chemoattractant protein-1 reflect various inflammatory processes. When combined, multiple biomarkers reflecting different pathophysiologic processes appear to enhance risk stratification, as compared with using individual markers alone. Advances in proteomic technology promise to identify additional novel biomarkers that facilitate diagnosis, risk stratification, and selection of therapies in ACS. In the future, it is hoped that multiple biomarker panels will form the basis of an individualized approach to the treatment of ACS, in which therapy is tailored to individual biomarker profiles.

Biomarkers↗
PubMed2000

Heterogenous patterns of sensory dysfunction in postherpetic neuralgia suggest multiple pathophysiologic mechanisms.

BACKGROUND: Postherpetic neuralgia (PHN) is considered by some investigators to be predominantly a deafferentation-type central pain syndrome; others suggest that activity of remaining peripheral nociceptors plays a critical role. The authors investigated the sensory dysfunction in subjects with PHN of varying duration and at different sites to gain further insight into the mechanisms responsible for the clinical features of neuropathic pain. In addition, the relationships between ongoing pain and pain evoked by mechanical and thermal stimuli were compared in patients with trigeminal and truncal PHN, to determine if the pathophysiologic mechanisms differed among subjects. METHODS: In 63 subjects with PHN, quantitative sensory testing was performed in the region of maximum allodynia or ongoing pain and the corresponding contralateral site. The intensity of ongoing pain was recorded. Sensory thresholds for warmth, coolness, heat pain, and cold pain were determined. Pain induced by various mechanical stimuli (dynamic, static, punctate) was rated using a numerical rating scale of 0-10. RESULTS: The mean rating of ongoing PHN pain was 7.3 +/- 2.0 (mean +/- SD). Allodynia induced by one or more mechanical stimuli was observed in 78% of subjects. A smaller subset (40%) had hyperalgesia to heat or cold stimuli. In subjects with duration of PHN of < or = 1 yr duration, but not in those with duration of > 1 yr, the intensity of ongoing pain correlated with intensity of allodynia induced by dynamic stimuli. Deficits in thresholds for heat and cold pain were observed in the affected region of subjects with PHN in the thoracic dermatomes (P < 0.005), but not in the trigeminal distribution. No relationship was observed between the thermal deficits and ongoing pain or mechanical allodynia in the groups of subjects with either trigeminal or thoracic PHN. CONCLUSION: Despite a common cause, the patterns of sensory abnormalities differ between subjects. Particular differences were noted between groups with facial or truncal PHN and between groups with recent or more chronic PHN. The observations suggest that the relative contributions of peripheral and central mechanisms to the pathophysiology of pain differ among subjects and may vary over the course of PHN.

Adult↗
PubMed1994

Basic mechanisms of myocardial dysfunction: cellular pathophysiology of heart failure.

The cellular pathophysiology of myocardial dysfunction in heart failure is multifactorial. Studies of animal models and myocardium from patients with heart failure have demonstrated abnormalities of cytosolic calcium handling, myofilament calcium sensitivity, and myocyte energetics. Many of these metabolic abnormalities have been shown to be the result of alterations in the activity or number of myocyte enzymes and transport channels that are important in excitation-contraction coupling. Several innovative techniques for measuring intracellular calcium and energy metabolites and recent advances in cell biology have helped to further our understanding of the cellular pathophysiology of heart failure. Abnormalities at several levels of the excitation-contraction coupling mechanism have been shown to be responsible for both systolic and diastolic dysfunction in the failing heart.

Animals↗
PubMed1999

Recent advances in the pathophysiology and management of preterm premature rupture of the fetal membranes.

During the past few years, meaningful progress has been achieved in our understanding of the pathophysiology of preterm premature rupture of membranes. In addition, more evidence has been presented in favor of induction and delivery for rupture between 34 and 37 weeks and expectant management for rupture before 34 weeks. New approaches are being suggested to complement expectant management. The purpose of this article is to review this recent information about the pathophysiology and management of women with preterm premature rupture of membranes.

Female↗
PubMed2000

Pathophysiology of interstitial cystitis.

Despite being described over 80 years ago, interstitial cystitis remains a disease of undetermined aetiology and poor treatment outcomes. Generally agreed diagnostic criteria of this condition, which occurs primarily in females, are frequency, urgency and pain, a low-capacity hypersensitive bladder, and mucosal haemorrhages and tearing on bladder distention. Although current theories of pathophysiology are predominantly conjecture, important elements of the disease process are increased afferent and efferent neuronal activity, an excess of inflammatory mediators, increased epithelial permeability and possibly reduced bladder vascularity. Improved treatment outcome will follow a better understanding of pathophysiology.

Cystitis, Interstitial↗
PubMed1998

Pathophysiology and treatment of idiopathic hypercalciuria.

Nearly 50 years after its initial description by Dr. F. Albright, the term idiopathic hypercalciuria (IH) is still in use. The exact mechanism of hypercalciuria is still unknown despite extensive pathophysiologic investigations; recent advances represent the focus of this review. A precise definition of true IH is proposed, taking into account the various nutritional conditions influencing calcium excretion. The potential pathogenic mechanisms are discussed, and the limits of the classical Pak's pathophysiological classification are recalled. The evidence supporting the role of an increased intestinal calcium absorption, a defect in renal tubular calcium reabsorption, or an increased bone loss as a primary mechanism in IH are successively examined. Since overall available human data indicates that all three mechanisms may be found in IH, the hypothesis that a broader disorder encompassing all these various abnormalities may be involved in IH is discussed. Three global hypotheses to account for IH physiopathology are examined: a diffuse defect in fatty acid content of cell membranes, an increased expression of the vitamin D receptor of the 25(OH) vitamin D 1 alpha-hydroxylase, or of the calcium sensor receptor and a monocyte disease. Finally, the available clinical data justifying the therapeutic approaches are reviewed, and guidelines for dietary recommendations regarding calcium and also animal protein, sodium chloride, alcohol, carbohydrate, phosphate, and potassium intakes are proposed, and drug therapy indications are discussed.

Bone Diseases, Metabolic↗
PubMed1990

The pathophysiology of the anophthalmic socket. Part II. Analysis of orbital fat.

The pathophysiologic mechanisms responsible for the clinical features of the anophthalmic socket are poorly understood. Atrophy of orbital fat has been thought to be a major contributing cause of enophthalmos and the superior sulcus deformities that develop after enucleation, but it has never been demonstrated histopathologically or confirmed by scientific analysis. This study was undertaken to investigate the changes that occur in the orbital fat compartment of the anophthalmic socket in an animal model by measuring orbital soft tissue mass and evaluating adipocyte cell size. Instead of reduction in the tissue mass, a statistically significant greater weight of the fat and connective tissue compartment was found in the anophthalmic orbit by nearly 13% compared to the control orbit in the animals in the long-term group. No significant change in the mean maximal diameter of adipocytes developed 7 months after enucleation. These analyses do not support the concept that orbital fat atrophy or a reduction of metabolic activity occurs in the anophthalmic socket in this animal model. From these results and our previous findings that the circulation dynamics and blood flow to orbital tissues do not change after enucleation, we propose that the pathophysiologic basis of the problems associated with anophthalmos is a disturbance in the spatial architecture and interrelationships of the multiple tissue components of the orbit, not a change in the orbital blood flow or development of fat atrophy.

Adipose Tissue↗
PubMed1995

Pathophysiology of heart failure: neuroendocrine response.

The understanding of the pathophysiology of heart failure is an emerging science. Although the mortality rate remains high, there has been some improvement in treatment in recent years. What was once thought to be a purely hemodynamic disorder now is understood to be a disease of cellular pathophysiology. The progression of compensated ventricular dysfunction to symptomatic heart failure is marked by the activation of vasoconstrictor hormones. Norepinephrine, renin-angiotensin-aldosterone, and arginine vasopressin are secreted in response to inadequate systemic perfusion. These combine to increase preload and afterload on an already failing heart. Baroreceptor function is attenuated, allowing for the continued sympathoexecitatory state. In addition, local tissue factors mitigate against a return to normal ventricular function by down-regulation of beta receptors, stimulation of local vasoconstrictor hormone secretion, and promotion of growth. Patients in intensive care units with chronic heart failure are best managed with an understanding of how their altered physiology affects their clinical presentation.

Heart Failure↗
PubMedDate not supplied

Pathophysiology of diabetes mellitus.

As we learn more about the pathophysiology of diabetes mellitus, we find that there is more yet to be learned. This may sound like a trite statement, but in reality it is true. The following article reviews the basic pathophysiology of both type 1 diabetes mellitus and type 2 diabetes mellitus as we understand it today. It continues on to reveal the "things that go wrong" when there is too much or too little glucose available to the body organs and especially to the brain. The article points out the signs and symptoms to be aware of when the person is in the acute state of diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic coma (or state), and severe hypoglycemia. It concludes with important considerations when the individual is in one of these acute states and contributes key points related to the control of diabetes when the person is in the state of compromise.

Diabetes Mellitus, Type 1↗
PubMed1998

Using forensic autopsies to teach advanced pathophysiology.

Forensic autopsies can be used to help teach advanced pathophysiology. Currently, most faculty use commercially available slides and overheads, but these are poor substitutes for actual tissue, organs, and systems. Student participation in cadaver dissections or observation of hospital autopsies may be preferable, but these options are not always available in many schools of nursing. The forensic autopsy, however, allows students to directly observe a variety of pathologies and their sequelae, while exploring the multiplicity of factors that contribute to a person's death. In addition, students enhance their physical assessment skills and learn forensic content that can be applied to nursing practice. Bringing such real-world experiences to lectures and student assignments encourages these adult learners to actively participate in the integration of pathophysiology theory with autopsy observations.

Adult↗
PubMed1999

Pathophysiology of posttraumatic osteomyelitis.

Understanding the pathophysiology of posttraumatic osteomyelitis is crucial as researchers attempt to meet the challenge of developing more effective strategies for the management and prevention of this infection. Some aspects of pathogenesis have been well described, including the important roles of the extent of soft tissue injury, bacterial attachment to necrotic bone and fixation devices, and bacterial contamination at the time of injury. More recently, the importance of early wound coverage in preventing osteomyelitis has been emphasized. Now some of the cellular interactions that promote infection and tissue damage are beginning to be understood. Trauma can have deleterious effects on host response to infection through its activation of certain cytokines. These cytokines, mainly produced by cells of the immune system, regulate the action of polymorphonuclear leukocytes, macrophages, and lymphocytes. Bacteria have been shown to use diverse tactics to initiate and maintain infection that lead to host defense impairment, decreased efficacy of antibiotics, and direct tissue damage. New insights into the pathophysiology of osteomyelitis may lead to the innovative therapeutic approaches needed to improve the standard of care for this infection.

Bone Resorption↗
PubMed1993

Intracerebral hemorrhage: pathophysiology and management.

OBJECTIVES: To review the pathophysiologic basis for intensive care management of patients with intracerebral hematoma and to present management strategies based on that analysis. DATA SOURCES: Review of English language scientific and clinical literature using BRS Colleague search. STUDY SELECTION: Pertinent literature was selected to demonstrate physiologic principles, the clinical presentation, and the natural history of intracerebral hematoma. All clinical treatment trials were reviewed. DATA EXTRACTION: Literature was reviewed to summarize physiologic principles and the results of clinical trials. The suggested medical management is based on the results of clinical trials and the applications of pathophysiologic principles. DATA SYNTHESIS: Spontaneous intracerebral hematomas acutely increase intracranial volume and reduce intracranial compliance, thus potentially increasing intracranial pressure and reducing cerebral perfusion. Therefore, any physiologic perturbation that could increase cerebral blood volume (hypercarbia, hypoxia, vasodilation) or reduce cerebral perfusion (hypotension) should be avoided. Acute hypertension may be a response to increased intracranial pressure and should be treated conservatively. Treatment of increased intracranial pressure is accomplished initially with hyperventilation, but this approach should be replaced rapidly with cerebrospinal fluid drainage alone or in combination with osmotic therapy employing diuretics, osmotic agents, or hypertonic saline to produce a state of hyperosmolality and euvolemia. Although the role of surgery remains controversial, it may be helpful in selected patients. Careful attention to pulmonary and metabolic status and to the consequences of therapy is required. Outcome is primarily determined by hemorrhage size, location, and initial level of consciousness. Stereotaxic aspiration of hematomas is a promising new therapy. CONCLUSIONS: The primary injury from intracerebral hemorrhage is exacerbated by disturbed intracranial physiology. Management should include principles that improve intracranial compliance and reduce intracranial pressure.

Brain↗
PubMed1999

Distribution and pathophysiology of acute lobar collapse in the pediatric intensive care unit.

OBJECTIVE: The high incidence of lower lobe collapse in adult intensive care patients is well described. We aimed to document the incidence and distribution of acute lobar collapse in the pediatric intensive care setting. The influence of anatomical and pathophysiological differences between the adult and pediatric respiratory tract will be considered. DESIGN: Retrospective review of chest radiograph series. SETTING: Tertiary referral center for pediatric intensive care and the Department of Diagnostic Radiology in a large teaching hospital in England. PATIENTS: Cohort of 160 patients receiving intensive care during a 2-yr period (age range, 6 days-18 yrs; median, 23 months). INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Twenty-four of 160 children (15%) developed acute lobar collapse during their intensive care unit admission. Isolated right upper lobe collapse occurred in 14 patients, right upper lobe in association with one or more other lobes in five patients, and lobar collapse other than the right upper lobe in five patients. The development of lobar collapse and, in particular, right upper lobe collapse was associated with a lower median age (no collapse, 26 months; lobar collapse, 8 months; right upper lobe collapse, 4 months). Lobar collapse was significantly associated with the requirement for mechanical ventilation during admission (chi-square, 12.18; p = .005). It was observed in association with both high and low endotracheal tube positions. CONCLUSION: The predominance of upper lobe and, in particular, right upper lobe collapse observed in pediatric intensive care patients contrasts with the high incidence of lower lobe collapse in their adult counterparts. Multiple interrelated factors are likely to be contributory and include the following: a) anatomical and physiological differences between adults and children; b) the pathophysiology of childhood respiratory disease; c) more critical positioning of endotracheal tubes in younger patients and their movement with patient positioning.

Adolescent↗