Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with beta thalassemia major may develop a specific osteoarthropathy as they approach the second and third decades of life. Twenty-five of 50 patients between the ages of 5 and 33 years had evidence of periarticular disease that consisted of dull-aching ankle pain exacerbated by weight bearing and relieved by rest. Involvement was symmetrical with mild swelling and pain on bone compression. Arthrocentesis showed no evidence of inflammation. Radiographic changes included osteopenia, widened medullary spaces, thin cortices with coarse trabeculations, and evidence of microfractures. Histologic studies confirmed the presence of microfractures and showed osteomalacia and an increase in osteoblastic and osteoclastic surface area with iron deposites at the calcification front and cement lines. The relative roles of iron overload, divalent cation metabolism, erythroid hyperplasia, or other factors in the pathogenesis of the syndrome remain unknown, and no specific therapy can be recommended at present.
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PMID:Thalassemic osteoarthropathy. 63 29

Relapsing Polychondritis (RPC) is a rare disorder of unknown etiology which affects mucopolysaccharide-rich tissues such as cartilage. A 64-year-old man developed auricular and nasal chondritis with complaints of arthralgia of the hands and cervical pain. The auricular biopsy established the diagnosis of RPC. The hematological data revealed normocytic, slightly hypochromic anemia, a persistently elevated reticulocyte count, slightly increased bilirubin, and decreased haptoglobin. The presence of hemolytic anemia was confirmed by the shortened half-life of erythrocytes and erythroid hyperplasia of the bone marrow. This case illustrates the coexistence of RPC and hemolytic anemia which has been only rarely reported. The pathogenesis of RPC is also discussed may elucidate the pathogenesis of this disease.
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PMID:A case of relapsing polychondritis associated with hemolytic anemia. 221 54

Prostaglandin E2 is known to stimulate erythropoiesis by different mechanisms. A clinical trial of prostaglandin E2 to stimulate erythropoiesis in four patients with anemia of end stage renal disease resulted in an increment in peripheral blood Burst Forming Units-Erythroid (BFU-E). This increase in erythroid progenitors returned to baseline with cessation of therapy. A significant increase in serum erythropoietin (EPO) activity was demonstrated in one patient and was noticeable in another. Side effects mainly consisted of local pain at the site of the infusion and vomiting.
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PMID:A clinical trial of prostaglandin E2 to increase erythropoiesis in anemia of end stage renal disease. A preliminary report. 637 77

The mu opioid receptor is thought to be the cellular target of opioid narcotics such as morphine and heroin, mediating their effects in both pain relief and euphoria. Its involvement is also implicated in a range of diverse biological processes. Using a mouse model in which the receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in a number of physiological functions. Mice homozygous for the disrupted gene developed normally, but their motor function was altered. Drug-naive homozygotes displayed reduced locomotor activity, and morphine did not induce changes in locomotor activity observed in wild-type mice. Unexpectedly, lack of a functional receptor resulted in changes in both the host defense system and the reproductive system. We observed increased proliferation of granulocyte-macrophage, erythroid, and multipotential progenitor cells in both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which are stress-responsive systems. Unexpected changes in sexual function in male homozygotes were also observed, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results suggest a novel role of the mu opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in pain relief.
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PMID:Altered hematopoiesis, behavior, and sexual function in mu opioid receptor-deficient mice. 912 34

Patients with sickle-cell anemia treated with hydroxyurea may have significant reduction in frequency and severity of pain episodes. However, previous clinical trials show a variable response to hydroxyurea. Criteria which can be used to select patients who are likely to respond to hydroxyurea treatment would be useful. Our laboratory has previously demonstrated an inverse linear relationship between the total number of burst-forming unit-erythroid (BFU-E) colonies and fetal hemoglobin levels in sickle-cell patients treated with hydroxyurea. In the present report, an in vitro cell culture system was established to evaluate the effects of hydroxyurea on BFU-E colony growth and induction of fetal hemoglobin production. Five Hb SS patients who were not previously treated with hydroxyurea and three Hb SS patients who failed to respond to hydroxyurea treatment were included in the study. The results show that the number of BFU-E colonies is decreased from 153.7 to 7.2 per 3 x 10(5) mononuclear cells, whereas fetal hemoglobin levels were increased from 5.1 to 19.4% in the presence of hydroxyurea in vitro in cultured erythroid progenitors, which were derived from 5 patients before treatment. The number of BFU-E colonies decreased from 153.7 to 2.0 per 3 x 10(5) mononuclear cells in the in vitro cultures obtained from serial peripheral blood samples over a 9- to 20-week period of oral hydroxyurea therapy. A simultaneous rise in fetal hemoglobin level from 10.2 to 28.6% in the peripheral blood over the same period of hydroxyurea therapy was also observed. Our results demonstrate that the increase in fetal hemoglobin levels in cells treated with hydroxyurea in vitro is comparable to the rise of fetal hemoglobin production following hydroxyurea therapy in these patients. On the contrary, these findings were not observed in three previously non-responsive sickle-cell patients. These results suggest that the changes in number of BFU-E colonies and fetal hemoglobin levels after in vitro exposure to hydroxyurea may be a useful approach to select sickle-cell patients who will respond to hydroxyurea therapy.
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PMID:BFU-E colony growth in response to hydroxyurea: correlation between in vitro and in vivo fetal hemoglobin induction. 939 88

The prevalence of anaemia in patients with cancer lies between 10 and 40%, depending on the type of tumor and chemotherapy. Anaemia has a significant impact on the quality of life, along with pain or disease progression. There are multiple causes but the physiopathology resembles that of inflammatory anaemia. The following mechanisms can be distinguished: a resistance of the erythroid precursor cells (BFU-e, CFU-e) to erythropoietin, an inappropriately decreased renal erythropoietin secretion for a given haemoglobin value and alterations of the iron metabolism leading to a functional iron deficiency. Recombinant human erythropoietin (r-hu-EPO) is safe and efficient in the treatment of anaemia of chronic renal failure and rheumatoid arthritis. In oncology different phase I and II studies have demonstrated an efficacy (increase of haemoglobin, decrease of transfusion requirements) in about 50% of all adult patients. A response to a subcutaneous r-hu-EPO treatment with a relatively high posology of 150 U/kg three times a week can be expected after one to two months. No single reliable parameter will predict a response to the r-hu-EPO treatment. Several phase III studies confirm that anaemia in cancer patients undergoing chemotherapy (notably with cisplatin) can be corrected in 40 to 60% of all cases and that the haemoglobin increase improves the quality of life. Finally, recent clinical trials suggest that an early r-hu-EPO treatment might prevent the occurrence of anaemia secondary to chemotherapy. Several parameters will have to be specified such as the precise definition of the groups at risk, the appropriate haemoglobin level to initiate a r-hu-EPO treatment, its optimal posology, as well as the role of the iron substitution and its route of administration. The impact of the r-hu-EPO treatment on the quality of life of cancer patients constitutes a priority for future studies, which will have define the exact role of r-hu-EPO in oncology management.
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PMID:[Tumor anemia. Overview of the role of human recombinant erythropoietin (r-hu-EPO) in treatment of tumor anemia]. 1006 75

Hydroxyurea (HU) is a widely used cytotoxic agent that is known to induce fetal hemoglobin (HbF) production and is presently used to ameliorate the severity of pain episodes in patients with sickle cell anemia (HbSS). Previously we have shown that HU inhibits growth of burst forming unit-erythroid (BFU-E) colonies in a dose-dependent manner, while fetal hemoglobin levels were increased. In the present report, we extended our analysis demonstrating the number of S phase cells is significantly higher for HbSS patients that respond to HU therapy. Studies were completed in vitro using erythroid progenitors derived from umbilical cord samples or peripheral blood from patients with HbS-hereditary persistence of fetal hemoglobin (HbS-HPFH) or HbSS disease. The effect of HU on (a) S phase erythroid progenitors, (b) BFU-E colony growth, (c) HbF levels in BFU-E colonies, and (d) total cellular RNA synthesis was analyzed in vitro for the three groups. The level of S phase erythroid progenitors was similar for all three groups and BFU-E colony growth was inhibited 92-94% for all samples in a dose-dependent manner. The HbF levels were increased in BFU-E colonies from HbSS patients (control, 4.0% +/- 1.15% vs. +HU, 22.67% +/- 2.03%) whereas HbF levels were decreased in BFU-E colonies derived from umbilical cord samples (control, 80% +/- 9.07% vs. +HU, 35.7% +/- 4.81%) or HbS-HPFH patients (control, 49.67% +/- 3.84% vs. +HU, 23.3% +/- 0.88%). Total RNA synthesis measured by 3H-uridine incorporation increased with increasing concentrations of HU; however, actinomycin D inhibited HU-induced RNA synthesis. These results suggest that HU can inhibit an active globin gene without preference and that newly synthesized RNA is under transcriptional control mechanisms.
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PMID:Mechanism for fetal hemoglobin induction by hydroxyurea in sickle cell erythroid progenitors. 1107 40

In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.
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PMID:Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia. 1198 48

The switch from embryonic to fetal then to adult hemoglobin synthesis is a unique phenomenon during early human development. Fetal hemoglobin (Hb F) is known to interfere with polymerization of Hb S in erythrocytes. Several pharmacologic agents such as 5-azacytidine, myleran, hydroxyurea, erthropoietin, and butyrates enhance fetal hemoglobin production and have been used in hemoglobinopathy patients to ameliorate severe pain episodes and reduce severe anemia. Among these, hydroxyurea is the agent of choice because of its safety and ease of administration. One of the primary cellular mechanisms involved in pharmacologic induction of Hb F synthesis is rapid regeneration of erythroid precursors following the cytoreduction phase of certain pharmacologic agents. Molecular mechanisms involving changes in chromatin structure and/or transcription factor binding have been demonstrated for gamma gene induction by butyrate. Identifying the proteins involved in gamma gene activation by various compounds may offer a new strategy for gene therapy to cure hemoglobinopathy disorders.
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PMID:Pharmacologic induction of fetal hemoglobin synthesis: cellular and molecular mechanisms. 1267 46

High fetal hemoglobin (HbF) levels inhibit the polymerization of sickle hemoglobin (HbS) and reduce the complications of sickle cell disease. Pharmacologic agents that can reverse the switch from gamma- to beta-chain synthesis--gama-globin chains characterize HbF, and sickle beta-globin chains are present in HbS--or selectively increase the proportion of adult erythroid precursors that maintain the ability to produce HbF are therapeutically useful. Hydroxyurea promotes HbF production by perturbing the maturation of erythroid precursors. This treatment increases the total hemoglobin concentration, reduces the vaso-occlusive complications of pain and acute chest syndrome, and attenuates mortality in adults. It is a promising beginning for pharmacologic therapy of sickle cell disease. Still, its effects are inconsistent, trials in infants and children are ongoing, and its ultimate value--and peril--when started early in life are still unknown.
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PMID:Hydroxyurea treatment for sickle cell disease. 1280 65


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