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Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.
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PMID:The effects of anemia in hematologic malignancies: more than a symptom. 1208 53

Posttransplant erythrocytosis (PTE) is defined as a persistently elevated hematocrit to a level greater than 51% after renal transplantation. It occurs in 10% to 15% of graft recipients and usually develops 8 to 24 months after engraftment. Spontaneous remission of established PTE is observed in one fourth of the patients within 2 years from onset, whereas in the remaining three fourths it persists for several years, only to remit after loss of renal function from rejection. Predisposing factors include male gender, retention of native kidneys, smoking, transplant renal artery stenosis, adequate erythropoiesis prior to transplantation, and rejection-free course with well-functioning renal graft. Just as in other forms of erythrocytosis, a substantial number (approximately 60%) of patients with PTE experience malaise, headache, plethora, lethargy, and dizziness. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. Posttransplant erythrocytosis results from the combined trophic effect of multiple and interrelated erythropoietic factors. Among them, endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback regulation, thereby establishing a form of "tertiary hypererythropoietinemia." However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, and insulin-like growth factor 1 (IGF-1). Inactivation of the renin-angiotensin system (RAS) by an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin II type 1 AT1 receptor blocker represents the most effective, safe, and well-tolerated therapeutic modality.
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PMID:Posttransplant erythrocytosis. 1263 34

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.
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PMID:Anemia in the oncology patient: cognitive function and cancer. 1502 12

Delayed cerebral ischemia as a result of cerebral vasospasm is the most common cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH). It leads to death or permanent neurologic deficits in over 17-40% of SAH patients. The initial and main symptom of cerebral vasospasm is diffuse headache and may be accompanied with a slight increase in discomfort from neck stiffness and fever. The clinical diagnosis of cerebral vasospasm is made when the patient experiences an altered level of consciousness or a new focal neurologic deficit. There has been a great progress in identifying the patients at risk, putative mechanisms, and possible treatment options for cerebral vasospasm. However, the problem is by no means solved, mainly due to a limited understanding of the pathologic mechanisms of this complex disease. The iatrogenic factors that can increase the risk of cerebral vasospasm include prolongation of the subarachnoid clot by antifibrinolytic drugs, hypotension, inappropriate treatment of hyponatremia, hypovolemia, hyperthermia and increased intracranial pressure. Nimodipine has been shown to improve neurologic outcome and decrease the incidence of cerebral vasospasm. Triple H therapy is a treatment designed to augment cerebral blood flow for patient with cerebral vasospasm. Hypervolemic hypertension is induced with intravenous volume expansion with crystalloid or colloid to increase cardiac output and raise blood pressure. However, small randomized trials showed no clear benefit. Recently, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators has emerged as the primary intervention for treating medically refractory ischemia from cerebral vasospasm and in many centers is being used as a first-line treatment or even prophylactically. In addition, promising new treatments for cerebral vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia; however, all still need further clinical trials. Newly recognized mediators of cerebral vasospasm after SAH include endothelium-derived mediators, vascular smooth-muscle-derived mediators, proinflammatory mediators involved in blood-brain barrier disruption, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Moreover, observations in the laboratory have, in many circumstances, matched those of reported small series. Larger, prospective, randomized trials are needed to verify several hypotheses of molecular pathophysiology and clinical treatment regimens.
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PMID:Treatment of cerebral vasospasm after subarachnoid hemorrhage--a review. 1567 31

Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B12 and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.
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PMID:Treatment of iron deficiency anemia in pediatric inflammatory bowel disease. 1616 7

We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.
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PMID:L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m. 1635 63

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic lineage, and association with thrombotic or bleeding episodes. It is extremely rare in childhood and frequently presents without evident clinical signs. We describe a 3-year-old girl with severe headache and dizziness suffering from ET, who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of this patient did not exhibit spontaneous colony formation but responded to recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a sustained partial remission with platelet counts varying between 400 and 600 x 10(3)/microl.
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PMID:Long-lasting partial remission by Interferon-alpha treatment in a child with essential thrombocythemia. 1642 12

A 40-year-old black male with scleroderma lung disease presented with blurry vision and headache. His presenting hemoglobin was 22.3 g/dL and his serum erythropoietin level was surprisingly low. Although nocturnal hypoxemia was evident, his daytime resting arterial oxygen saturation was normal. The patient's symptoms of hyperviscosity improved after phlebotomy, as his hemoglobin gradually decreased to 18.3 g/dL. Repeat serum erythropoietin levels were in normal and high ranges. Patients with chronic interstitial lung disease and erythrocytosis could have normoxemia at rest and a normal or low serum erythropoietin level at the peak of erythrocytosis. A repeat sampling of serum erythropoietin and monitoring of oxygen saturation during sleep and exertion may help in diagnosis. Physicians should prescribe continuous oxygen therapy for patients with chronic interstitial lung disease and erythrocytosis, even if diurnal resting hypoxemia is absent.
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PMID:Erythrocytosis in a scleroderma patient. 1675 1

Cancer-related fatigue (CRF) is either a symptom or a syndrome depending on criteria for diagnosis. CRF is present in 20% to 30% of long-term cancer survivors and 80% to 90% during treatment and at the end of life. Assessment requires determining the presence, severity, and interference with daily activities. Different descriptors for fatigue (eg, tiredness, lack of vigor) measure different patient experiences. Associated factors such as depression, pain, insomnia, dyspnea, anemia, and deconditioning worsen CRF and should be treated if present. Associated factors that contribute to the severity of fatigue differ depending on the stage of cancer. Pharmacologic interventions include recombinant erythropoietin, psychostimulants, corticosteroid, anti-inflammatory drugs other than steroids, and L-carnitine. Advances in the management of CRF will require an understanding of the underlying mechanism before target-specific therapies can be developed.
Curr Pain Headache Rep 2006 Aug
PMID:Management of fatigue in cancer patients. 1683 40

To determine the efficacy and safety of intraperitoneal administration of darbepoetin in children with renal anemia on peritoneal dialysis, we conducted a single-arm, retrospective, two-centre study in which children were treated with intraperitoneal darbepoetin at the end of nightly intermittent peritoneal dialysis. Controls were those children treated with intraperitoneal erythropoietin six months before conversion to darbepoetin. Children were converted with the conversion factor 200 units erythropoietin=1 microg darbepoetin. Children who started with darbepoetin, started with 0.45 microg/kg/week. Nineteen children entered the study. The mean age was 6.8 years. Eight children were converted from 201 U/kg/week intraperitoneal erythropoietin to 1.0 microg/kg/week intraperitoneal darbepoetin. They were treated for a median period of 31.5 months. Median darbepoetin dose for an adequate erythropoesis over this period was 0.79 microg/kg/week. All 19 children were treated with darbepoetin for a median period of 13.4 months. The median dose for an adequate erythropoesis over this period was 0.63 microg/kg/week. The peritonitis incidence during this study was once every 25.1 months. Three children developed hypertension; one child developed headache. These complications developed after a rapid increase of hemoglobin concentration. Intraperitoneal administration of darbepoetin is effective and safe for children on peritoneal dialysis.
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PMID:Intraperitoneal treatment with darbepoetin for children on peritoneal dialysis. 1710 37


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