Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limb deformity and metaphyseal abnormalities in thalassaemia major. 774 45

This report presents data on visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs), as well as neurologic, ophthalmologic and otologic assessments performed on 120 patients with beta-thalassemia major undergoing long-term DFO treatment. A total of 32 patients showed abnormal VEPs and 14 abnormal BAEPs; seven had both VEP and BAEP abnormalities; 12 had sensorineural hearing loss (SNHL); 18 had conductive hearing loss, while 14 showed a combination of SNHL and conductive hearing loss. After DFO administration was modified (taking in consideration the serum ferritin levels) patients with abnormal findings were retested. The values of 15 patients of 23 who underwent VEP examinations had been normalized. Eleven of 15 who repeated the BAEP test had also gained normal values. The audiogram had not returned to normal in any patient with SNHL. In a second repetition of the examinations, no change was observed. It is concluded that in a great percentage of thalassemics at least one of the above examinations shows abnormal values. These abnormalities are mostly reversible, and probably reflect a dysfunction of the visual or auditory system, due either to DFO neurotoxicity or to iron overload or both.
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PMID:Neurophysiological and neuro-otological study of homozygous beta-thalassemia under long-term desferrioxamine (DFO) treatment. 164 95

Red cell basic ferritin (RCBF) was measured in 62 healthy subjects with normal hearing and 224 patients with different kinds of sensorineural hearing loss, compared with serum ferritin, haemoglobin, serum iron and circadian variation in the serum iron levels. The results showed that the RCBF concentrations in most kinds of sensorineural hearing loss were significantly lower than those in normal hearing status. It is conceivable that the RCBF assay can be used to evaluate the adequacy of iron stores that are useful in times of urgent iron needs and to diagnose relative iron deficiency in those patients with some other normal laboratory assays related to iron metabolism.
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PMID:Red cell basic ferritin concentration in sensorineural hearing loss. 179 10

To determine the frequency of eye and auditory complications and their relationship to drug dosage and iron stores in patients receiving deferoxamine, we studied 52 regularly transfused patients who received deferoxamine by subcutaneous or intravenous infusion in doses from 26 to 136 mg/kg/day, and whose serum ferritin levels of 185 to 17,775 micrograms/L reflected a wide range of iron stores. Forty-nine patients (94%) had no evidence of drug-induced visual or auditory abnormalities. Symptomatic loss of vision and hearing developed in one patient; both problems improved when chelation therapy was stopped. Of the 51 symptom-free patients, one had a mild degree of macular stippling and one had a mild, bilateral, high-frequency sensorineural hearing loss. Eye and ear abnormalities in the symptom-free patients did not progress despite continuation or resumption of chelation therapy at the same dosage. Patients with ophthalmologic and audiologic abnormalities did not receive higher doses of deferoxamine and did not have lower serum ferritin levels than patients without such abnormalities. These findings demonstrate that eye and ear abnormalities during chelation therapy with deferoxamine may not occur uniformly at as high a frequency as previously reported, even in patients who receive large doses of the chelating agent or who have only modest amounts of excessive iron.
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PMID:Vision and hearing during deferoxamine therapy. 201 45

Forty-seven patients with thalassaemia have been studied to define risk factors for development of sensorineural hearing loss, and to establish guidelines for safe chelation. Sensorineural hearing loss was only present in patients who had previously received desferrioxamine (DFO). The two most significant risk factors were the maximum dose of DFO previously received (P less than 0.01), and a serum ferritin of less than 2000 micrograms/l at that time (P less than 0.001). A therapeutic index obtained from the ratio of the mean daily dose of DFO mg/kg divided by the serum ferritin identifies patients with a ratio of greater than 0.025 as at risk of sensorineural hearing loss (P less than 0.001) and can be used as a guideline for safe DFO dosage. Follow-up audiometry of the affected patients over a 2-year period indicated that adjustment of the dose to a therapeutic index of less than 0.025 resulted in the stabilization of hearing loss in seven patients and improvement in two.
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PMID:Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. 260 27

Sensorineural hearing loss was detected in nine (33%) of 27 patients with beta-thalassaemia major. All were receiving regular hypertransfusion and nightly subcutaneous infusions of desferrioxamine. A retrospective analysis of these patients was undertaken to determine the risk factors for the development of deafness. No statistically significant differences were found between the affected and unaffected groups with respect to age, ferritin levels or lengths of time that they had received desferrioxamine, but the trends were similar to those reported by other authors. However, the desferrioxamine dosage was similar in both our groups (less than 60 mg/kg a day), and lower in the affected group than other authors have reported. Two patients experienced some resolution of their deafness when their dosage of desferrioxamine was lowered. These results suggest that the ototoxic effect of desferrioxamine is dose-related and can occur at relatively low doses of the drug.
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PMID:Hearing loss attributed to desferrioxamine in patients with beta-thalassaemia major. 365 30

With the introduction of long-term subcutaneous administration of deferoxamine (DFO), there has been a decline in the morbidity and mortality of transfusion-dependent beta-thalassemia patients. However, since the use of subcutaneous DFO is hindered by poor compliance, long-term i.v. DFO therapy has been attempted in order to improve compliance, prevent excessive iron accumulation and extend survival. Thirteen patients (aged 5.4-18.4 years) were started on i.v. home administration of DFO (100 mg/kg per day) via an exteriorized, tunneled right atrial catheter (Hickman type). After a median follow-up of 36 months, the mean ferritin levels had dropped significantly (5,117 +/- 1,737 to 1,816 +/- 1,062 micrograms/l. P = 0.0001). None of the patients developed new endocrine or cardiac diseases due to iron overload. Patients beginning therapy at an early age (< or = 11 years) showed a tendency for improved growth parameters at the end of the treatment period. Two patients developed moderately high frequency sensorineural hearing loss. One patient developed a right atrial thrombus. The line infection rate was low (1.7 episodes per 1,000 patients days). In view of the grave prognosis for iron overloaded patients and the fact that oral chelators are not yet readily available, we recommend this form of therapy for the young, noncompliant beta-thalassemia patient, despite the occasional complications observed.
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PMID:Long-term intravenous deferoxamine treatment for noncompliant transfusion-dependent beta-thalassemia patients. 804 54

Structure and composition of stereocilia cross-links were investigated cytochemically in normal and hydropic cochleas of the guinea pig. The electron-dense markers colloidal thorium and cationized ferritin were used for visualization. Side links as well as tip links were visualized using both markers. Cationized ferritin allowed a better visualization of the delicate cross-link substructure than did colloidal thorium. Following digestion with neuraminidase, cross-link reactivity for colloidal thorium was virtually abolished. However, the basic structure of the cross-links could still be observed as a result of routine post-fixation and contrast staining. In both 3- and 6-month hydropic cochleas glycocalyx reactivity of the stereocilia appeared to be unaltered, provided that stereocilia were still present. However, loss of cross-links of the outer hair cells - resulting in disarrangement of the stereociliary bundles - was observed in hydropic cochleas. Our results suggest that cross-links are a separate morphological and cytochemical entity, which is different from the glycocalyx. Furthermore, loss of stereocilia cross-links, with concomitant disarrangement of the outer hair cell stereociliary bundle, appears to be one of the early pathological features of surgically induced endolymphatic hydrops, which might be responsible for permanent sensorineural hearing loss.
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PMID:Structure and composition of stereocilia cross-links in normal and hydropic cochleas of the guinea pig. 850 69

Eighty eight (88) beta-thalassemic patients undergoing regular transfusion- chelation therapy with desferrioxamine (DFO) were studied for ENT problems from 1988 to 1993, as DFO has been implicated for auditory neurotoxicity. The mean age of the patients was 9.66 +/- 3.1 years, their pre-transfusion haemoglobin level was 9 +/- 2 g/dl, serum ferritin level was 2065 +/- 898 ng/ml and the daily DFO dose was 50.7 +/- 9.5 mg/kg for 5 days/week. The ENT study included, ENT examination, pure tone audiometry, speech audiometry, tympanometry, tone decay test and ABR. During this 6-year study 24/88 (27%) patients developed bilateral or ipsilateral sensorineural hearing loss in high tone frequencies, sometimes exceeding 80 dB, which was attributed to DFO toxicity. Therefore, a reduction or temporary withdrawal of DFO followed. After this intervention 12/24 patients recovered almost completely, 7/24 remained stable and 5/24 presented aggravation of their hearing loss. This study confirms the DFO induced auditory neurotoxicity and the necessity of periodical audiology control of beta-thalassemic patients for prompt diagnosis and management of this complication.
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PMID:Sensorineural hearing loss in children with thalassemia major in Northern Greece. 876 95

A 58-year-old woman developed slowly progressive hearing loss, anosmia, and unsteady gait. She had neither repeated episode of headache nor a past history of neurosurgical operation or head injury. Neurological examination revealed anosmia, moderate degree of sensorineural hearing loss. She showed loss of caloric response bilaterally. No nystagmus was found. Romberg sign was present. No cerebellar ataxia was noted in the finger-to-nose or the heel-to-knee test. No adiadochokinesis was noted. Deep tendon reflexes were increased in both upper and lower extremities. Sensation was intact. She showed disturbance of the righting reflex in the tilt-table examination. CSF were under normal pressure, xanthochromic with siderophages. CSF total protein and ferritin level were elevated. T2-weighted image (TE4000/TR100) of high field strength magnetic resonance imaging (MRI) showed marginal hypointensity of the brain stem, the Sylvian fissures, the tips of temporal lobes, anterior cerebellar surfaces and the entire spinal cord. Angiography of the cerebral vessels and spinal arteries failed to identify the source of bleeding. It seemed likely that she had lost bilateral vestibular and auditory functions caused by hemosidelin deposition to her eighth nerves which are often affected by this disorder. Her disturbance of gait and station was apparently similar to cerebellar ataxic gait, however, she did not have limb ataxia. The electronystagmogram revealed marked degree of vestibular dysfunction (VOR) and relative sparing of cerebellar function (OKN). Her disturbance of the righting reflex in the tilt-table examination and the characteristic feature of her Romberg sign with directional preponderance also indicate that the bilateral loss of vestibular functions, i.e., vestibular ataxia caused her dysequilibrium syndrome. It is our impression that vestibular ataxia might precede cerebellar ataxia commonly reported so far.
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PMID:[A case of superficial siderosis of the central nervous system with bilateral vestibular dysfunction]. 936 92


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