Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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Two familial cases of myelodysplastic syndrome (MDS) are reported, one of whom had an abnormal karyotype of 45, XY, -7 (monosomy 7). Case 1 was a 60-year-old woman developed dizziness and nasal bleeding. She was treated with blood transfusion alone. About 11 months after diagnosis, she died of pneumonia. Case 2 was a 22 year-old man, who was the son of case 1, developed febrile disease because of recurrent skin and oral mucosa infections. He had a partial response to low-dose of cytarabine. Thirteen months after diagnosis, he died of severe pneumonia. Both cases were diagnosed as having refractory anemia with excess of blasts due to peripheral blood and bone marrow findings. Both patients had pancytopenia, erythroid hyperplasia in bone marrow, marked dyserythropoiesis, recurrent infectious diseases and severe pneumonia that resulted in death. These symptoms resembled to those reported for monosomy 7 syndrome. Familial MDS with monosomy 7 is rarely reported. These cases are of interest to investigate hereditary factors of MDS.
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PMID:[Myelodysplastic syndrome developed in a mother and her son whose bone marrow karyotype showed monosomy 7]. 884 1

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.
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PMID:The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation. 1241 88

On May 19, 2004, azacitidine (5-azacytidine; Vidaza(trade mark); Pharmion Corporation, Boulder, CO, http://www.pharmion.com) for injectable suspension received regular approval by the U.S. Food and Drug Administration (FDA) for the treatment of all subtypes of myelodysplastic syndrome (MDS). This report summarizes the basis for this approval. Effectiveness was demonstrated in one randomized, controlled trial comparing azacitidine administered s.c. with best supportive care (observation group) and in two single-arm studies, one in which azacitidine was administered s.c. and in the other in which it was administered i.v. The dose of azacitidine, 75 mg/m2/day for 7 days every 28 days, was the same in all three studies. In the randomized trial, study participants were well matched with respect to age, sex, race, performance status, MDS subtype, and use of transfusion during the 3 months before study entry. Patients in the observation arm were permitted by protocol to cross over to azacitidine treatment if their disease progressed according to prespecified criteria. During the course of the study, more than half of the patients in the observation arm did cross over to the azacitidine treatment arm. The primary efficacy end point was the overall response rate. Response consisted of complete or partial normalization of blood cell counts and of bone marrow morphology. The response rate in the azacitidine arm was about 16%; there were no responses in the observation arm. The response rates in the two single-arm studies were similar (13% and 19%). The responses were sustained, with median durations of 11 months and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients.
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PMID:FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. 1579 20

PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this Phase I study was to evaluate the safety, tolerability, biologic activity and pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous dosing schedule in patients with primary refractory or relapsed acute myeloid leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK monotherapy was ineffective could receive PTK/ZK combined with standard induction chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated according to standard bone marrow and peripheral blood criteria. At 1000 mg b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and anorexia were observed. Other adverse events related to PTK/ZK were dizziness, weakness, fatigue, diarrhea and pruritus; these were generally mild and reversible. Pharmacokinetic data showed that steady state was reached by day 14, there was no accumulation with repeat dosing and there was no significant increase in exposure at steady state beyond the maximum tolerated dose (MTD). Complete remission was observed in five of 17 AML patients treated with PTK/ZK combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally b.i.d. The drug is generally well tolerated and can be given in combination with chemotherapy for patients with MDS and AML.
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PMID:Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. 1661 23

A 16-year-old female patient presented with complaints of malaise, dizziness, syncope, and nausea of 1-week duration. On dermatologic examination there were telangiectasias, atrophic areas, and poikiloderma with both hypopigmentation and hyperpigmentation on the neck and the proximal parts of the thighs. The bone marrow biopsy specimen showed hypocellularity and dysplastic megakaryocytic and erythroid elements, findings consistent with hypocellular myelodysplastic syndrome, which was further confirmed by cytogenetic studies. Thereafter, she was referred for allogeneic bone marrow transplantation.
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PMID:Dyskeratosis congenita associated with hypocellular myelodysplastic syndrome: a case report. 1787 35

We reported 37 patients with myelodysplastic syndromes (MDS) of refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts who were treated with cyclosporin A (CyA)/thalidomide combination therapy. Of them, 19 patients (19/37, 51.4%) achieved a hematologic improvement and erythroid response (HI-E); 9 patients (9/29, 31.0%) achieved hematologic improvement and platelet response (HI-P) and 7 patients (7/33, 21.2%) achieved hematologic improvement and neutrophil response (HI-N). 15 of 32 (46.9%) transfusion-dependent patients achieved independence from transfusion. The median response duration of HI-E, HI-P and HI-N were 88 (4-108) weeks, 78 (8-84+) weeks and 78 (10-84+) weeks, respectively. Some patients presented with I or II grade hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rash or sense of numbness. Therefore, CyA combined with thalidomide appears to be useful and is relatively well-tolerated for patients with MDS.
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PMID:Cyclosporin A and thalidomide in patients with myelodysplastic syndromes: Results of a pilot study. 2059 81

This study reports an unusual case in which myelodysplastic syndrome presented bilateral sudden sensorineural hearing loss as the first symptom of the disease. The aural symptoms and signs such as tinnitus, dizziness, and hearing impairment of a hematologic disease are common. However, sudden hearing loss as the first manifestation of a hematologic disease is extremely rare. A 76-year-old woman presented with bilateral sudden hearing loss. The patient was found to have myelodysplastic syndrome during a workup for her hearing loss. Unfortunately, the patient's hearing loss did not improve after the medical treatment.
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PMID:Bilateral sudden sensorineural hearing loss as an initial presentation of myelodysplastic syndrome. 2293 15

Myelodysplastic syndrome (MDS) with eosinophilia is a rare condition and has yet to be classified under the 2008 World Health Organization classification. However, reports have described the prognostic significance of chronic persistent eosinophilia in MDS. Here, we report a case of a 67-year-old woman who was admitted to the hospital in July 2007 with generalized weakness, dizziness, and dyspnea on exertion persisting for 5 years. In the initial investigation, eosinophilia (22.1%) in peripheral blood and an increased proportion of eosinophils (5.6%) in normocellular bone marrow with dysplastic megakaryocytes and erythroid cells were noted. Eosinophilia was continuously detected during follow-up over 3 years. In a second bone marrow examination in August 2010, hypercellular bone marrow with similar features was observed. These findings led to the diagnosis of MDS with chronic persistent eosinophilia. To increase awareness of the prognostic significance of MDS with chronic eosinophilia, here we report a slow-progressing case of MDS with chronic persistent eosinophilia lasting over 6 years.
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PMID:A case of myelodysplastic syndrome with marked eosinophilia showing favorable prognosis. 2408 44

A 57-year-old man with high-risk myelodysplastic syndrome underwent umbilical cord blood transplantation. He began receiving steroids on day 14 for acute graft-versus-host disease, and experienced dizziness on day 75 during gradual dose reduction. Multiple hemorrhages were observed in the cerebrum, cerebellum, and brainstem. His bleeding increased, and he underwent a brain biopsy on day 91. Subsequently, he was diagnosed with central nervous system vasculitis (CNSV) on the basis of the observed aggregation of mature CD3+ lymphocytes around small vessels and vascular wall invasion by lymphocytes and macrophages. After receiving high-dose steroid therapy, cerebral hemorrhage stopped; however, dysphasia occurred on day 113 and the patient died of cerebral edema on day 128. Toxoplasma DNA and tachyzoites were detected in the brain biopsy specimen during additional examinations; therefore, we suspected that the toxoplasmosis was related to the onset of CNSV. CNSV is a rare, rapidly progressing disease that may present as a fatal post-transplantation central nervous system complication. Investigating the causes of CNSV, including CNSV associated with toxoplasmosis, is critically important for improving the prognosis of patients with CNSV.
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PMID:[Toxoplasmosis-associated central nervous system vasculitis accompanied by multiple cerebral hemorrhages developing subsequent to cord blood transplantation]. 3084 78

A 57-year-old man with a history of diabetes and coronary artery disease was referred to haematology for the evaluation of anaemia in the setting of non-cardiac chest pain, fatigue, dyspnoea and dizziness. Previous investigations into these recurrent symptoms focused on a re-evaluation of his known ischaemic heart disease, which required multiple percutaneous interventions with stenting several years ago. In the year leading up to his referral, the patient required two transfusions during separate hospitalisations. Previously, his chronic anaemia was attributed to chronic inflammation because of unrevealing micronutrient and endoscopic evaluations. The patient underwent a bone marrow biopsy, which demonstrated normal karyotype myelodysplastic syndrome with ringed sideroblasts. This patient was found to have favourable cytogenetics and low-risk disease. His anaemia and associated symptoms improved with the administration of an erythroid-stimulating agent. Now 75 years old, he has remained on single-agent therapy for 10 years without need of transfusion.
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PMID:Low-risk myelodysplastic syndrome managed with an erythroid-stimulating agent for 10 years. 3226 7


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