Biomedical subjects

K S Chen

Publications and source records attributed to K S Chen.

At least 73 records · Page 4Linked to original sources

PubMed1996

Antiplatelet and vasorelaxing actions of some aporphinoids.

A series of aporphines and oxoaporphines was tested for antiplatelet and vasorelaxing actions. (+)-N-Methylactinodaphnine, (-)-norannuradhapurine x HBr, xylopine, actinodaphnine, and N-methylnandigerine showed strong inhibition of adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Boldine, (+)-N-methylactinodaphnine, (-)-norannuradhapurine x HBr, xylopine, N-acetyllaurolitsine, N-methyllaurotetanine, actinodaphnine, N-methylnandigerine, O-methylbulbocapnine, and liriodenine showed strong inhibition of arachidonic acid (AA)-induced platelet aggregation. (+)-N-Methylactinodaphnine, fissoldine x HCIO4, (-)-norannuradhapurine x HBr, xlylopine, N-methyllaurotetanine, actinodaphnine, N-methylnandigerine, O-methylbulbocapnine, and liriodenine showed strong inhibiton of collagen-induced platelet aggregation. (-)-Norannuradhapurine x HBr, xylopine, N-methyllaurotetanine, and actinodaphnine showed strong inhibition of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)-induced platelet aggregation. (+)-N-Methylactinodaphnine, laurotetanine, N-methylactinodaphnine N-oxide, oxoglaucine, boldine, and actinodaphnine showed vasorelaxing action in rat thoracic aorta. The results are discussed on the basis of structure-activity relationships.

Adenosine Diphosphate↗

PubMed1996

Cloning, genetic mapping and expression studies of the rat Brca1 gene.

The breast cancer gene BRCA1 has previously been cloned from both human and mouse. We cloned a fragment of the rat Brca1 homologue in order to map it and explore its biological function. Partial cDNA fragments of the rat Brca1 homologue were isolated by RT-PCR. Sequence analysis revealed that the RING-finger domain is well conserved among rat, mouse and human. Rat Brca1 mRNA was expressed in most tissues studied with the highest level in testis, consistent with studies in human and mouse. Next, intron 6-containing DNA fragments were amplified by PCR from WKY and WF rat strains. The splicing sites between exon 6 and exon 7 are conserved between rat and human. Partial sequencing of the rat Brca1 intron 6 revealed a polymorphism of a pentanucleotide TTTTG repeat between the WKY and WF strains. With this intragenic microsatellite marker, we were able to map precisely the rat Brca1 gene to chromosome 10 using a genetic linkage study of (WKY x WF)F1 x WF backcross rats. Brca1 cosegregates with marker BAND3A, and is flanked by R5123 and R5842. Using this polymorphic marker, we also investigated the loss of heterozygosity (LOH) of the Brca1 microsatellite marker in carcinogen- or radiation-induced mammary carcinomas in (WF x F344)F1 female rats. No LOH or somatic microsatellite instability was detected in 18 DMBA-induced tumors studied. Only one LOH of the F344 allele was observed in 26 radiation-induced tumors tested. Ribonuclease protection assays demonstrated that Brca1 mRNA levels are similar in normal rat mammary glands and mammary carcinomas of various etiologies, including those induced by DMBA, NMU, activated-neu and activated-ras oncogenes.

Alleles↗

PubMed1996

Pulmonary actinomycosis appearing as a "ball-in-hole" on chest radiography and bronchoscopy.

A 40 year old diabetic man with pulmonary actinomycosis was admitted to hospital with recurrent haemoptysis. The chest radiograph showed an air meniscus in the left upper lobe, a rare presentation of pulmonary actinomycosis. Bronchoscopic examination revealed a mass in a cavity which has never been reported previously. He underwent lobectomy and the surgical specimen revealed sulphur granules, the typical pathological finding of actinomycosis, without evidence of fungal or mycobacterial infection.

Actinomycosis↗

PubMed1996

Cloning and chromosomal localization of the rat Stat5 and Yy1 genes.

Rat beta-casein gene expression is controlled in part by the positively acting factor Stat5 and the negatively acting factor Yy1. Partial cDNAs encoding the SH2 domain of rat Stat5a and Stat5b and the zinc finger domain of rat Yy1 have been cloned by an RT-PCR based approach. The nucleotide sequences encoding the SH2 domain of rat Stat5a and Stat5b are 75% homologous. The rat Yy1 cDNA is 95% homologous to its human and mouse counterparts in the zinc finger domain-encoding region. Using fluorescence in situ hybridization, we have localized Stat5a to rat chromosome band 10q32.1 and Yy1 to rat chromosome band 6q32.

Amino Acid Sequence↗

PubMed1996

Superinfection with hepatitis C virus in hemodialysis patients with hepatitis B surface antigenemia: its prevalence and clinical significance in Taiwan.

A survey of hepatitis B surface antigen (HBSAG) and antibodies against hepatitis C virus (anti-HCV) in 173 patients undergoing hemodialysis in Taiwan revealed that 15 (9%) patients were positive for both HBSAG and anti-HCV, 106 (61%) were positive for anti-HCV alone, and 14 (8%) were positive for HBSAG alone. Most HBSAg positivity was acquired before the onset of hemodialysis. Anti-HCV positivity, however, was mainly acquired via the hemodialysis procedure. Patients with dual markers were younger (43.7 +/- 3.3 years old, p = 0.0274), had the longest period on hemodialysis (6.6 +/- 1.3 years, p < 0.001), and more severe liver dysfunction. When compared with those who were negative for both markers, patients with both HBSAG and anti-HCV had an increased incidence of chronicity (5/15 vs. 2/38; p < 0.05), ultrasonographic cirrhosis (5/15 vs. 1/38; p < 0.05), and clinical decompensation (2/15 vs. 0/38; p < 0.05). Their risk for developing ultrasonographic cirrhosis and clinical decompensation was also greater than that of patients with anti-HCV alone (5/15 vs. 8/106 and 2/15 vs. 2/106; p < 0.05 for both). The presence of HBSAG alone, however, did not increase the incidence of liver dysfunction. The presence of anti-HCV alone was only associated with a greater elevation of serum alanine aminotransferase (44.2 +/- 5.5 vs. 19.1 +/- 2.5 U/l; p < 0.05) and an increased incidence of chronicity (30/106 vs. 2/38; p < 0.05). Our results indicate that a high prevalence of HCV superinfection impose a significant risk on a large population of HBSAG-positive hemodialysis patients in Taiwan. As the coexistence of anti-HCV and HBSAG is associated with more severe liver dysfunction, it is urgent to devise effective methods to prevent HCV circulation in a hemodialysis environment-especially in a hepatitis B virus endemic area such as Taiwan.

Adolescent↗

PubMed1996

Diminution of T cells with gamma delta receptor in the peripheral blood of allergic asthmatic individuals.

BACKGROUND: T cells are shown to regulate allergy and asthma. They are heterogeneous by virtue of surface receptor subtypes (alpha beta and gamma delta receptors), however, their pathophysiological roles in asthma are unclear. OBJECTIVE AND METHODS: The present study employed flow cytometric analysis to compare the size of T-cell subsets and eosinophils present in the peripheral blood of healthy, allergic and allergic asthmatic individuals. RESULTS: Current results demonstrated that the percentages of gamma delta T cells declined from 4.1% in healthy to 3.2% in the allergic subjects and to a significantly lower (P = 0.01) 2.4% in allergic asthmatics. The absolute numbers of circulating gamma delta T cells also were diminished in a similar fashion such that healthy individuals had a significantly higher mean cell count (91.8 x 10(3)/mL) than did allergic asthmatics (47.8 x 10(3)/mL) (P = 0.0266). In contrast, alpha beta T cells were comparable in the healthy, allergic, and allergic asthmatic populations (65.3%, 65.8% and 69.4%, respectively); the differences were not statistically significant. On a populational basis, the proportion of individuals having both gamma delta T cells < or = 4.1% and eosinophils > or = 2.1% was the lowest in the healthy population (30.8%), but was elevated in the allergic group (85.7%) as well as in the allergic asthmatic group (86.6%). However, on an individual basis, those who had reduced gamma delta T cells did not have consistently higher eosinophil counts or IgE level. CONCLUSION: It was concluded that no significant correlation existed between the levels between gamma delta T cells and eosinophils or between gamma delta T cells and IgE present in the peripheral blood. This report, for the first time, documents that allergic asthmatics have reduced gamma delta T cells with reciprocally elevated eosinophil numbers in their peripheral circulation. However, it does not indicate that the reduction of gamma delta T cells directly correlates with the predominance of eosinophils of IgE levels in the diseased populations. The pathophysiological role of gamma delta T cells in allergic diseases awaits further exploration.

Adult↗

PubMed1996

Urinary tract tuberculosis: a 10-year experience.

Ninety-seven patients with urinary tract tuberculosis were reviewed from January 1983 to December 1993 at our hospital. Aside from two cases of military tuberculosis and three cases with coexisting active pulmonary tuberculosis, most urinary tract infections developed from a previous primary lung infection. Patients usually exhibited local symptoms. Fever, weight loss and anorexia were uncommon. Eighty-nine percent of the patients had abnormal urinalysis (hematuria and/or pyuria). Eight percent of the patients also had genital involvement, whereas 38% of these patients had normal intravenous pyelogram and urinalysis. Pyelograms disclosed abnormalities in 94% of the 97 patients and most revealed late changes, which were correlated with higher incidence of azotemia and anemia noted at diagnosis. Chemotherapy is the mainstay of treatment and at least three antituberculous drugs are required for initial therapy due to high drug resistance rate. Reconstructive surgery is warranted to salvage renal function. Except 6 patients run into maintenance hemodialysis, the renal functions of all patients remained stable during the period of follow-up, either receiving chemotherapy alone or combined surgery. Renal calcification may not represent inactive process, which requires further evaluation.

Adult↗

PubMed1995

Smith-Magenis syndrome deletion: a case with equivocal cytogenetic findings resolved by fluorescence in situ hybridization.

The availability of markers for the 17p11.2 region has enabled the diagnosis of Smith-Magenis syndrome (SMS) by fluorescence in situ hybridization (FISH). SMS is typically associated with a discernible deletion of band 17p11.2 upon cytogenetic analysis at a resolution of 400-550 bands. We present a case that illustrates the importance of using FISH to confirm a cytogenetic diagnosis of del(17)(p11.2). Four independent cytogenetic analyses were performed with different conclusions. Results of low resolution analyses of amniocytes and peripheral blood lymphocytes were apparently normal, while high resolution analyses of peripheral blood samples in two laboratories indicated mosaicism for del(17)(p11.2). FISH clearly demonstrated a 17p deletion on one chromosome of all peripheral blood cells analyzed and ruled out mosaicism unambiguously. The deletion was undetectable by flow cytometric quantitation of chromosomal DNA content, suggesting that it is less than 2 Mb. We conclude that FISH should be used to detect the SMS deletion when routine chromosome analysis fails to detect it and to verify mosaicism.

Chromosome Aberrations↗

PubMed1995

Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements.

A genomic DNA clone for 1 alpha,25-dihydroxyvitamin D-3 (1,25-(OH)2D3) 24-hydroxylase was isolated from a human chromosome 20 library. It spans 2.42 kb, containing the first two exons, the first and part of the second introns, and a 1.26 kb 5'-flanking region. Putative transcription cis-elements were revealed throughout the 5'-flanking region, including TATA box, CAAT box, GC boxes, vitamin D-responsive elements (VDRE), AP1, and AP2 sites. In a CAT reporter gene expression assay, the 24-hydroxylase promoter with its 1.2 kb 5'-flanking sequence elicits a 1,25-(OH)2D3-induced transactivation activity. Gel mobility shift assays of those putative DREs have identified that two different elements can form specific complexes with porcine intestinal nuclear extract (PINE). The specificity of VDRE-PINE complexes was verified by supershift assay with VDR-specific monoclonal antibody VXIE10B6. The proximal element VDREp (-172/-143) consists of three direct repeat half-sites, GAGTCAgcgAGGTGAgcgAGGGCG, in anti-sense orientation. The distal element VDREd (-293/-273) consists of two direct repeat half-sites, GCGTTCaccGGGTGT, also in anti-sense orientation. Both VDREs can direct a reporter gene expression using a heterologous herpes simplex virus thymidine kinase (TK) promoter in a 1,25-(OH)2D3-dependent fashion. Further characterization of these VDREs in various constructs with either a native or TK promoter suggests that both VDREs are required for the optimal induction of 24-hydroxylase expression by 1,25-(OH)2D3.

Base Sequence↗

PubMed1995

The cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine.

OBJECTIVE: To compare the cardiovascular, pulmonary, and ocular hypotensive effects of 0.2% brimonidine tartrate with those of 0.5% timolol maleate, 0.25% betaxolol suspension, and brimonidine vehicle. DESIGN AND PATIENTS: A single-center, double-masked, randomized, crossover study of 24 young, healthy men. INTERVENTIONS: Baseline heart rate, blood pressure, respiratory rate, and intraocular pressure were recorded at hour 0. At hour 2, heart rate, blood pressure, respiratory rate, and forced expiratory volume in 1 second were measured and a 15-minute treadmill test performed. Hour 0 measurements were repeated at hour 4. On four subsequent visits, we instilled one drop of a study medication into each eye after the baseline measurements at hour 0. RESULTS: Timolol reduced resting (-5.3 to -6.5 beats/min, P < or = .004) and exercise-induced heart rate (-4.3 to -13.6 beats/min; P < or = .022) compared with brimonidine, betaxolol suspension, and brimonidine vehicle. At hour 4, brimonidine reduced resting systolic blood pressure compared with all other study medications (-5.2 to -7.3 mm Hg; P < or = .024). Timolol reduced systolic blood pressure during exercise and brimonidine reduced systolic blood pressure during recovery more than betaxolol suspension and brimonidine vehicle (-5.1 to -7.7 mm Hg; P < or = .033; and -5.4 to -6.0 mm Hg; P < or = .002, respectively). Mean respiratory rate and forced expiratory volume in 1 second were not significantly altered by any study medication. At hour 4, brimonidine lowered intraocular pressure as well as timolol and better than betaxolol suspension (-1.9 mm Hg; P < .001) or brimonidine vehicle (-1.8 mm Hg; P < .001). CONCLUSIONS: The cardiopulmonary effects of 0.2% brimonidine were limited to a slight reduction in systolic blood pressure during recovery from exercise and at 4 hours after instillation. The ocular hypotensive effect of brimonidine was comparable to that of timolol and greater than that of betaxolol suspension in this patient population.

Adrenergic alpha-Agonists↗

PubMed1995

Urologic cancers in uremic patients.

From 1981 through 1990, 21 urologic cancer cases were discovered in 21 uremic patients at our hospital. This constituted 55% (11 of 20) of the total malignancies in nondialyzed uremic patients, 41% (nine of 22) of the total in chronic hemodialysis patients, and 50% (one of two) of those in patients on continuous ambulatory peritoneal dialysis. No cases of urologic cancer were found in kidney transplant recipients. When compared with the general population, the standardized incidence ratio of kidney cancer in chronic hemodialysis patients was found to be 24.1 (P < 0.01) and that of bladder cancer was found to be 16.4 (P < 0.01). Multiple underlying renal diseases contributed to the development of the urologic cancer cases, including four analgesic nephropathy-associated transitional cell carcinoma cases, two acquired cystic kidney disease-associated renal cell carcinoma cases, two chronic pyelonephritis-associated (stone and tuberculosis) squamous cell carcinoma cases, and one xanthogranulomatous pyelonephritis-associated transitional cell carcinoma case. Uremia per se may be an important promoting factor. Hematuria (17 of 21 cases) was the most common presenting feature despite the fact that most of the patients were anuric. The clinical diagnosis of renal parenchymal tumors was based on ultrasonography (five of five cases), whereas most urothelial tumors were detected by cystoscopy or retrograde pyelography (14 of 16 cases). The survival rate of the 17 aggressively treated patients was 82% at 2 years and 45% at 5 years. We conclude that uremic patients are at greater risk of developing urologic cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Synaptic loss in cognitively impaired aged rats is ameliorated by chronic human nerve growth factor infusion.

In the present study, we assessed the synaptic changes in aged impaired and unimpaired rats, and the effect of exogenous human nerve growth factor administration on behavioral activity and synaptic density. Human nerve growth factor was administered into the rat ventricles with a cannula connected to an osmotic pump in adult, aged impaired and unimpaired rats. Behavioral performance was evaluated in the Morris water maze. Aged impaired rats had an 18 +/- 4% decrease in the number of synaptophysinimmunoreactive presynaptic terminals as compared to aged unimpaired rats. After a continuous four-week human nerve growth factor, the aged impaired rats displayed a significant 16 +/- 3% increase in the number of synaptophysin-immunoreactive presynaptic terminals in the frontal cortex, as compared to aged impaired rats treated with vehicle. This increase correlated with an improvement in water maze performance (r = -0.74, P < 0.001). Measurements of synaptophysin-immunoreactive presynaptic terminals in other cortical and subcortical regions did not show any statistically significant difference or correlations among the various groups. These results support the possibility that nerve growth factor mediates the induction of other trophic factors which, in turn, might potentially produce a sprouting response of non-cholinergic fibers that ameliorate the cognitive deficits in impaired, aged rats.

Aging↗

PubMed1995

Hepatocellular carcinoma with metastasis to right atrium--a report of three cases.

Hepatocellular carcinoma (HCC) is one of the most common neoplasma in Taiwan. The tumor itself has the tendency of extension into the venous system, such as to the portal vein, hepatic vein and inferior vena cava (IVC), but intra-atrial metastasis is unusual. Antemortem diagnosis was difficult before the availability of two-dimensional echocardiography (2-DE). Sometimes, the first symptoms and signs are cardiogenic manifestations such as dyspnea on exertion, syncope, edema of the lower legs, and shock. Clinicians may mistakenly make the wrong diagnosis of heart failure. Because of this, we hereby report three cases of HCC with right intra-atrial metastasis to raise the physician's awareness. All three cases initially presented as right side heart failure. Imaging study revealed hepatocellular carcinoma with right intra-atrial metastasis. Two of the three cases died within one month after diagnosis.

Aged↗

PubMed1995

Induction and relief of nasal congestion in ferrets infected with influenza virus.

Susceptible ferrets intranasally infected with influenza virus consistently responded with maximal nasal secretion of virus, febrile reaction, and influx of inflammatory cells into nasal lumen on day 2 post infection (d.p.i.). Polymorphonuclear leucocytes were the earliest predominant cell, followed by monocytes/macrophages while lymphocytes were maintained as a minor population throughout the 7-day period. Nasal congestion level, continuously monitored by computer aided active anterior rhinomanometry, was reproducibly maximal at 2 d.p.i., diminished in intensity the next day and returned to the basal level within 7 d.p.i. Nasal congestion was effectively relieved by a single intranasal dose of 0.1% oxymetazoline or 0.2% phenylephrine, or a single intragastric administration of pseudoephedrine. Intranasal delivery of a single dose of 1% pyrilamine relieved nasal congestion while 0.8% ipratropium bromide and 30% cimetidine were ineffective. These results suggested that nasal congestion is regulated by alpha-adrenergic receptors in the mucosal vasculature or by H1 histamine receptor, but is unaffected by inhibitors of nasal secretion regulated by the cholinergic nervous system. The present study indicates that the infectious rhinitis ferret model provides a reproducible nasal congestion pattern that can be objectively measured by a refined active anterior rhinomanometric system. This labour intensive measurement, however, makes it difficult either to conduct a large population animal study or to use it for a rapid throughput screening of new drugs. The temporal relation between the influx of inflammatory cells into the nasal lumen and the onset of nasal congestion underlies the model's relevance to the exploration of the pathogenic mechanism(s) during viral rhinitis.

Airway Resistance↗

PubMed1995

[A study on sex hormones in gingival crevicular fluid and black pigmented bacteria in subgingival plaque of pregnant women].

Gingivitis is one of the most common oral diseases. It is caused by dental plaque and by the factors produced/released from it. The black pigmented bacteria in subgingival dental plaque are thought to be the periodontopathogens. Prevotella intermedia and Porphyromonas gingivalis have been shown to be closely associated with human gingivitis. Prevetella intermedia can use female sex hormones such as progesterone or estradiol as a source of nutrients. In pregnant women, the concentrations of progesterone and estradiol are markedly increased in serum and both are accumulated and found in the gingival tissue. The purpose of this study was to test levels of female sex hormones in gingival crevicular fluid and to observe the relationship between hormones and black pigmented bacteria in subgingival plaque. The results showed that the amount of progesterone found in the gingival crevicular fluid and percentage of black pigmented bacteria in subgingival plaque of pregnant women were markedly higher than in the postpartum stage. The percentage of black pigmented bacteria was positively correlated with the progesterone level, pregnancy and the severity of the gingivitis. Severity of the gingivitis was positively correlated with both the plaque index and the percentage of black pigmented bacteria in subgingival plaque.

Adult↗

PubMed1995

Somatic gene transfer of NGF to the aged brain: behavioral and morphological amelioration.

Primary fibroblasts modified to secrete nerve growth factor (NGF) were implanted into the nucleus basalis magnocellularis (NBM) of aged memory impaired rats. The NGF-producing fibroblasts survived for 6 weeks following transplantation and continued expressing NGF mRNA through the duration of the experiment. A significant amelioration of the memory impairment and a significant increase in size and number of low-affinity NGF receptor (p75)-positive neurons in the basal forebrain were observed. Implantation of NGF-producing cells into normal young adult rats resulted in a transient but significant memory impairment and hypertrophy of low-affinity NGF receptor-positive neurons. These results show that naturally occurring age-related memory loss can be reversed by grafting cells engineered to secrete NGF directly to the NBM, and that either cholinergic hyper- or hypofunction may lead to cognitive impairments.

Aging↗

PubMed1995

The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps within the Smith-Magenis microdeletion critical region in 17p11.2.

The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed.

Animals↗

PubMed1995

Human recombinant erythropoietin and phlebotomy in the treatment of iron overload in uremic patients.

Six chronic hemodialysis patients suffering from iron overload (serum ferritin ranged between 2053-15704 mu g/L) were treated with human recombinant erythropoietin (EPO) alone for eighteen months. An initial rapid decrease of serum ferritin was observed in all six patients when the loading dose of EPO was given. Three patients (Cases 4, 5, 6) who suffered from chronic blood loss maintained a continuous decline of serum ferritin in the subsequent stage of maintenance dose EPO therapy, however, the decrease of serum ferritin became sluggish under a maintenance dose in the other three patients (Cases 1, 2 and 3). The serum ferritin eventually decreased to a satisfactory level (975-1761 mu g/L) in Cases 4, 5 and 6, whereas it remained high (4232-8196 mu g/L) in Cases 1, 2, and 3 who had higher basal levels of serum ferritin (5641-15704 mu g/L) and a plateau of response under a maintenance dose of EPO. These three patients were then treated with EPO and phlebotomy. Their serum ferritin decreased quickly from 6752 +/- 1264 mu g/L to 2454 +/- 482 mu g/L after six months of phlebotomy therapy; it was a dramatic improvement in contrast to the stagnant response under a maintenance dose of EPO alone. Our experience indicates that EPO therapy alone has its limitations in treating severe iron overload. Although there is an initial rapid decrease of serum ferritin during the period of the loading dose, the response might become stagnant during the period of maintenance dose. Phlebotomy effectively eliminated the excessive iron stores in these refractory cases. Therefore, we suggest that phlebotomy be considered in severe iron overload if a stagnant response is observed under a maintenance dose EPO therapy.

Adult↗