Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the discovery of HFE gene in 1996, considerable progress has been made concerning the iron-metabolism and its major abnormalities. Five types of hereditary hemochromatosis are actually known: type 1 (HFE gene), type 2A (HJV gene), type 2B (HAMP gene), type 3 (TfR2 gene), type 4 (SLC40A1 gene). The HFE C282Y +/+ mutation is responsible for the most frequent type of hemochromatosis in France. Various secondary causes can lead to iron-overload: associated genetic diseases, exogenous iron intake, thalassaemia and refractory anaemia, hepatic siderosis, alcoholic hepatitis, cutaneous porphyria and cirrhosis. The deleterious consequences of iron-overload are due to the interactions of the environmental factors. The role of HFE heterozygote mutations is still discussed. In clinical practice, the interpretation of a serum ferritin increase is a frequent problem that needs a careful evaluation based on the tranferrin saturation measurement. Significant increase of both these factors is in favour of an HFE C282Y +/+ hemochromatosis, after exclusion of a hepatocellular insufficiency or a refractory anaemia. Nevertheless, high ferritin is not always a marker of iron-overload. Thus, there are many disorders increasing the serum ferritin levels without iron overload : cytolysis (hepatic...), inflammatory or infectious syndromes, high alcohol intake, neoplasia... Looking for HFE mutations help to separate type 1 hemochromatosis from other conditions mainly hepatic siderosis (metabolic disorders). The identification of rare types of hemochromatosis (types 2-4) is only required in particular cases. The evaluation of the iron overload is now based on hepatic MRI determination rather than liver biopsy. Repeated phlebotomies remain the essential way to decrease the iron overload in HFE hemochromatosis and to prevent the occurrence of severe and irreversible complications (cirrhosis, arthropathies, cardiac failure, and diabetes). Because of the link established between the amount of iron-overload and the occurrence of complications and the mortality over-risk in HFE C282Y +/+ hemochromatosis, venesections must be started when serum ferritin is higher than 300 microg/l in man and 200 microg/l in woman, whatever the clinical manifestations are and obviously before the symptomatic phase of the disease.
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PMID:[Hereditary and acquired iron overload]. 1737 75

Clinical, hematological and cranial neuroimaging findings of eight cases of infantile tremor syndrome are reported. All had coarse tremors, anemia, hyperpigmentation and delayed or regression of developmental milestones. Five patients had microcytic, hypochromic anemia, three had dimorphic anemia. CT scans of two cases and MRI scans of three cases showed cerebral atrophy. One of these two CT scans, in addition, showed a small hypodensity in right basal ganglia region. Two CT scans were normal. One MRI showed hyperintense signals in frontal and periventricular white matter on T2 weighted images. The changes described are non-specific and also seen in cases of malnutrition and viral infections of CNS.
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PMID:Cranial neuroimaging in infantile tremor syndrome (ITS). 1741 98

A 55-year-old man with chronic alcoholism was first referred to us in 1992 because of spastic quadriparesis. T2-weighted images of MRI showed pontine and extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM). He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait disturbance was progressively worsened from the end of 2004 and dysuria appeared from June, 2005. Neurological examination on admission in November, 2005, showed mild impairment of recent memory, spastic paraparesis with hyperreflexia in all limbs, loss of deep sensations in lower limbs and urinary disturbance. The low serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine lesion extended to the midbrain but no abnormality was found in the spinal cord. We intramuscularly administered B12, resulting in marked improvement of both anemia and neurological symptoms. The brainstem lesion on MRI, however, was unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM and the neurological symptoms in our patient.
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PMID:[A case of alcoholic with vitamin B12 deficiency presenting central pontine and extrapontine myelinolysis on MRI]. 1751 Dec 90

Retroperitoneal fibrosis (RPF) is characterised by inflammatory fibrotic processes affecting the retroperitoneal structures. Its prevalence of 1 - 2/200,000 makes it a rare disease. To date, there are no guidelines for the diagnosis of or therapy for the disease. If untreated, the disease may be fatal. In 2006, the Department of Urology of the HELIOS Klinikum Wuppertal undertook to establish a nationwide patient registry, which would facilitate prospective therapy trials and the drafting of recommendations for diagnostic procedures. The pathogenesis of the disease is still unclear. Since some RPF-patients present with associated autoimmune diseases, autoimmune processes are suspected to play a role in causing the disease. The presence of autoantibodies and histological similarities with vasculitis support this hypothesis. Following initial general symptoms, patients display localised symptoms (flank pain, leg oedema, abdominal discomfort), caused by the displacing effect of the fibrotic plaques. Laboratory tests show elevated ESR and C-reactive protein and in some cases a moderate anaemia. Histological examinations should be undertaken to rule out the presence of malignant tumours. Radiological diagnostics (excretory urography, CT, MRI) show a retroperitoneal mass which blocks, compresses and displaces, completely or in part, the large vessels and the ureter. Initial therapy aims at restoring the function of the affected hollow organs through the application of (ureteric) stents, followed by immunosuppressive therapy. If drug therapy is unsuccessful, surgical procedures will follow to protect the ureter from compression. In some cases, ureteral replacement or an autotransplant of the kidney may be necessary. Life-long observation of the patients is necessary, as the disease may be chronic and relapsing. Interdisciplinary and nationwide cooperation is of crucial importance to further investigate this disease.
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PMID:[Retroperitoneal fibrosis]. 1751 80

A 64 year-old man was admitted to our hospital because of left leg weakness after a lot of alcohol drink. On admission, his blood pressure was 96/43 mmHg, and heart rate was 97 beats/min and regular. His laboratory data showed severe anemia, and Hb was 5.0 g/dl due to bleeding from gastric cancer. His clinical condition indicated pre-shock and we began to give him a blood transfusion immediately after admission. His neurological findings on admission were mild consciousness disturbance without aphasia, left unilateral spatial neglect, and mild monoparesis on left leg. Brain diffusion-weighted magnetic resonance images demonstrated the small hyper-intense lesions in the borderzone area between the anterior cerebral artery and the middle cerebral artery (MCA). MR angiography showed the occlusion of the right internal carotid artery (ICA) and the right MCA was fully supplied through anterior communicating artery from the left ICA. Transcranial Doppler (TCD) revealed the blunted waveform with low-resistance in the right MCA, but normal flow wave in the left MCA. We diagnosed him as having a hemodynamic brain infarction based on MRI and TCD findings. On day 5, severe anemia and pre-shock improved to Hb 8.2 g/dl and 148/78 mmHg, respectively. According to elevation of blood pressure, his neurological findings normalized. Follow-up TCD revealed that the abnormal waveform in the right MCA changed to normal. Finally we considered the stroke mechanism of this case as hemodynamic stroke based on TCD findings. Serial TCD examinations are useful to identify the hemodynamic mechanism of stroke in such case.
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PMID:[Case of hemodynamic brain infarction diagnosed by transcranial Doppler]. 1763 5

We observed a 42-year-old woman presenting with severe dysphagia secondary to paralysis of the lower cranial nerves and right phrenic nerve involvement, followed by respiratory failure. An EMG confirmed bilateral denervation of the 9th, 10th, 11th and 12th cranial nerves and right phrenic nerve. Videolaryngoscopy showed bilateral vocal fold immobility. Anemia, elevated ESR, microhematuria and C-ANCA (PR-3) antibodies were detected. Brain MRI and CSF were normal. A chest CT showed bilateral, irregular pulmonary lesions. An 18F-FDG total body scan showed diffuse hypermetabolic regions in both pulmonary bases, in the mediastinic region and in the rhinopharynx, raising the suspicion of a neoplastic process. A transthoracic biopsy disclosed nodular granulomatous aggregates with multinucleated giant cells, supporting the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy achieved complete clinical resolution and cleared the pulmonary lesions. To the best of our knowledge this is the first report of Wegener's granulomatosis presenting with neurogenic dysphagia due to lower cranial nerve palsy.
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PMID:Severe dysphagia in lower cranial nerve involvement as the initial symptom of Wegener's granulomatosis. 1765 54

Homozygous loss of activity at the breast cancerpredisposing genes BRCA1 and BRCA2 (FANCD1) confers increased susceptibility to DNA double strand breaks, but this genotype occurs only in the tumor itself, following loss of heterozygosity at one of these loci. Thus, if these genes play a role in tumor etiology as opposed to tumor progression, they must manifest a heterozygous phenotype at the cellular level. To investigate the potential consequences of somatic heterozygosity for a BRCA1 mutation demonstrably associated with breast carcinogenesis on background somatic mutational burden, we applied the two standard assays of in vivo human somatic mutation to blood samples from a manifesting carrier of the Q1200X mutation in BRCA1 whose tumor was uniquely ascertained through an MRI screening study. The patient had an allele-loss mutation frequency of 19.4 x 10(-6) at the autosomal GPA locus in erythrocytes and 17.1 x 10(-6) at the X-linked HPRT locus in lymphocytes. Both of these mutation frequencies are significantly higher than expected from age-matched disease-free controls (P < 0.05). Mutation at the HPRT locus was similarly elevated in lymphoblastoid cell lines established from three other BRCA1 mutation carriers with breast cancer. Our patient's GPA mutation frequency is below the level established for diagnosis of homozygous Fanconi anemia patients, but consistent with data from obligate heterozygotes. The increased HPRT mutation frequency is more reminiscent of data from patients with xeroderma pigmentosum, a disease characterized by UV sensitivity and deficiency in the nucleotide excision pathway of DNA repair. Therefore, this BRCA1-associated breast cancer patient manifests a unique phenotype of increased background mutagenesis that likely contributed to the development of her disease independent of loss of heterozygosity at the susceptibility locus.
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PMID:Elevated levels of somatic mutation in a manifesting BRCA1 mutation carrier. 1815 61

Azathioprine (Aza) has been proposed in the treatment of multiple sclerosis (MS) since 1971 and continues to be used in MS Clinical Centres. Recent data, suggesting its efficacy in reducing MRI lesion load and in refractory IFN-treated MS patients, has renewed interest in this drug. Its therapeutic index over other immunosuppressive agents is generally considered favourable, but concerns about a possible risk of malignancy have limited its use. On the other hand, the occurrence of unexpected adverse events (AEs) in clinical trials in recent years has aroused the interest in the safety profile of the drugs. No systematic review of AEs in patients affected by MS is available. The aim of this study is to review the safety profile of the drug in patients affected by MS, in order to support a correct management of these patients in the clinical practice. The controlled and observational clinical studies published between 1971 and 2007 have been included. The AEs have been registered in ad hoc form and the frequency has been calculated. The risk of cancer and toxicity on reproductive function has been also considered. Gastrointestinal complaints and leukopenia are the most frequent AEs of Aza therapy in MS, occurring in more than 10% of the patients, while infections, allergy, anaemia, thrombocytopenia and pancytopenia are common (>1%-<10%). Pancreatitis is not common (>0.1%-<1%). Most of them are easily managed by dosage adjustment or therapy interruption. The cancer risk increases with the treatment duration and cumulative dose. No data on reproductive toxicity in MS treated with Aza are available. The safety profile of Aza is acceptable, if strategies for management of expected AEs are adopted, following dosage and treatment duration indications, and if long-term monitoring to evaluate the risk of cancer is warranted.
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PMID:Azathioprine. Safety profile in multiple sclerosis patients. 1817 75

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.
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PMID:[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. 1817 27

A 64-year-old woman visited our hospital in December 2005 because of general malaise. Her hemoglobin level was 9.0 g/dl. Gastrointestinal fiberscopy detected a hemorrhagic gastric ulcer, which was considered as etiology of anemia. Abdominal ultrasonography showed bilateral hydronephroses and hydroureters. A urine test revealed pyuria and macroscopic hematuria, and urine culture revealed 10(8) colony-forming units of Escherichia coli per ml. Pelvic MRI showed thickening of the posterior wall and trigone of the urinary bladder. Transurethral resection was peformed, and biopsy of the mucous of the bladder gave a diagnosis of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder. Ann Arbor clinical stage was IEA. It was planned to administer irradiation at a total dose of 36 Gy to the whole bladder and part of the tumor; however, radiotherapy was discontinued at a dose of 26 Gy because of the development of pollakisuria. Pelvic MRI and pathologic examination of the urinary bladder after radiotherapy showed that the lymphoma was in complete remission; however, she received retuximab therapy at a dose of 375 mg/m2/week, 8 times additionally, because of the reduced radiotherapy. The patient has remained in complete remission for 14 months.
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PMID:[Primary mucosa-associated lymphoid tissue lymphoma of the urinary bladder successfully treated by radiotherapy and rituximab]. 1827 93


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