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PubMedDate not supplied

Assessment for depression among nursing home elders: evaluation of the MDS mood assessment.

The 30-item Geriatric Depression Scale (GDS), the GDS Short Form, and the Mood Assessments from the Minimum Data Set versions 1 and 2 were completed for 50 nursing home elders. The purpose of the study was to evaluate agreement among these measures of depression, with the GDS considered the gold standard. Although the GDS Short Form performed highly consistently with the GDS, the correlations of the MDS mood assessments with the GDS were relatively low. The results are discussed in the context of the characteristics that surround the use of the MDS, and recommendations are made for improving methods of detecting depression among nursing home elders.

Age Distribution↗
PubMed2006

Possible molecular target therapy with rapamycin in MDS.

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of rapamycin (mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable transformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone.

Bone Marrow Cells↗
PubMed1992

A case of neutrophilic dermatosis (ND) complicated by cryofibrinogenemia (CFGN) and myelodysplastic syndrome (MDS).

A case of neutrophilic dermatosis (ND) complicated by cryofibrinogenemia (CFGN) and myelodysplastic syndrome (MDS) is reported. Although the patient presented pancytopenia, the skin lesions were compatible with those of ND from the clinical and histopathological findings. Further, immunofluorescence technique revealed cryofibrinogen (CFG) deposits on the walls of the blood vessels in the skin lesion, and a high titer of CFG components was disclosed in the patient's peripheral blood. In this case, CFGN may have been associated with MDS; hence CFG deposits probably played a role, at least in part, in the skin lesion formation. This is probably the first case of ND complicated by CFGN. And careful examination of an underlying disease is recommended in association with ND and/or CFGN.

Cryoglobulins↗
PubMed1984

Bone marrow histology in myelodysplastic syndromes. II. Prognostic value of abnormal localization of immature precursors in MDS.

A study has been performed of 40 bone marrow trephine biopsies from patients with myelodysplastic syndromes (MDS). Histology, more specifically the abnormal localization of immature precursors (ALIP), cytology and karyotype analysis were correlated with survival time and the prognostic value of these factors was determined. The presence or absence of ALIP proved to be highly significant in predicting the duration of survival (P = 0.007): the presence of ALIP predisposes patients to early death with high probability of developing acute myeloid leukaemia (AML), whereas the absence of ALIP carries a better prognosis with more long-term survivors and low probability of transformation to AML. The presence or absence of ALIP was not correlated with increased mortality from infection and/or bleeding. In contrast with ALIP, the main histological parameter, we were not able to obtain statistically significant prognostic information for cytology (FAB classification) or karyotype analysis (normal or abnormal chromosomes). We conclude that bone marrow biopsy provides useful information for the prognosis of MDS and that the presence of ALIP has greater predictive value than the more commonly used parameters deduced from cytology and karyotype.

Adult↗
PubMed1986

DNA content and cell cycle analysis of bone marrow cells in myelodysplastic syndromes (MDS).

DNA distribution in bone marrow cells from 10 normal subjects and 34 patients with MDS (24 with refractory anaemia (RA) and 10 with excess blasts (RAEB] was determined by flow cytometry using a FACS III. DNA histograms were resolved into G0/1, S and G2/M compartments by fitting Gaussian distributions and the DNA content of G0/1 cells, expressed as DNA index (DI), was determined. In 19 MDS patients the DI was outside the normal range, those with RA tending to be hyperdiploid. Two patients with RAEB had a second G0/1 peak. In five cases of RA the number of cells in G0/1 was below the normal range and the mean value was significantly lower than normal for this group as a whole (P = 0 X 018). Eleven (RA) patients had a higher percentage of cells in G2/M than normal (P = 0 001). In RAEB patients there is a suggestion of increased numbers in G0/1 and a decrease in S phase and G2/M cells. All three of the deaths amongst RA patients and four out of the five deaths in RAEB patients since the beginning of this study were associated with an abnormal DI at the initial investigation.

Bone Marrow↗
PubMed1992

Extended cytogenetic follow-up of patients with myelodysplastic syndrome (MDS).

The prognostic significance of clonal karyotype status in myelodysplastic syndrome (MDS) is assessed after an extended follow-up period of 5 years. There are three karyotype, single abnormalities or multiple abnormalities at the time of referral. However, there is no correlation between the size of the abnormal clone and prognosis. Karyotype status has independent prognostic significance in 'high risk' MDS so that patients with a refractory anaemia with excess of blasts (RAEB)/RAEB in transformation (RAEB-t) and a normal karyotype survive significantly longer than those with an abnormal karyotype (P < 0.001) and do not differ significantly from patients with refractory anaemia (RA). Significant differences in survival according to karyotype status are also seen in patients with chronic myelomonocytic leukaemia (P < 0.001) but not in those with primary acquired sideroblastic anaemia and RA. Among patients studied sequentially, those who retained a normal karyotype survived significantly longer than those who developed an abnormality on follow-up (P < 0.001). The risk of leukaemic transformation was also increased in patients who presented with or subsequently developed a clonal karyotype abnormality compared with those who remained normal (P < 0.05).

Aged↗
PubMed1995

The use of r-HuEpo in the treatment of anaemia related to myelodysplasia (MDS).

One hundred and sixteen (116) anaemic patients with myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (r-HuEpo) in an open-label, multicentre, compassionate treatment trial; 100 patients received therapy for > or = 4 weeks and were evaluable for efficacy. The distribution of FAB subtypes was: 44 RA, 40 RARS, eight RAEB, two RAEB-t, one CMML, and five not specified. Mean baseline haematocrit was 24.5%, and the mean prestudy transfusion requirement in the 12 weeks immediately prior to study entry was 6.5 units. r-HuEpo treatment was initiated at a dose of 150 U/kg three times weekly, with dose escalations of 50 U/kg monthly (up to 300 U/kg 3x/week) permitted if the haematocrit failed to rise. Response to therapy was defined as either an increase in haematocrit of > or = 6 percentage points over baseline, unrelated to transfusion, or a > or = 50% decrease in transfusion requirement in the last 3 months of study treatment, compared to the baseline period (12 weeks). By these criteria, 28% (28/100) of patients responded to r-HuEpo treatment. Overall, 86% (24/28) of patients responding to therapy had baseline Epo levels < or = 100 mU/ml. Response rates by FAB subtype were: RA 39% (17/44), RARS 17.5% (7/40) and RAEB 12.5% (1/8). Additionally, a 54% (15/28) response rate was seen in RA patients with baseline Epo levels < or = 100 mU/ml. Responses to therapy were durable and generally occurred at r-HuEpo doses of 150-200 U/kg t.i.w. There were no reports of thrombosis, seizures or therapy-related hypertension. The data show that patients with MDS, especially those with the RA and RARS subtypes, can benefit from treatment with r-HuEpo. Those patients with baseline Epo levels < or = 100 mU/ml were most likely to respond to therapy.

Adult↗
PubMed2005

Optimization of transplant regimens for patients with myelodysplastic syndrome (MDS).

Myelodysplastic syndrome (MDS) is a hemopoietic stem cell disorder that is potentially curable by transplantation of normal hemopoietic stem cells. The optimum timing, however, and the best conditioning strategy have remained controversial. Both conventional and reduced-intensity/nonmyeloablative regimens have been used successfully. Among selected patients with less advanced/low-risk MDS (< 5% marrow myeloblasts), 3-year survivals of 65% to 75% are achievable with HLA-matched related and unrelated donors. Among patients with more advanced/ high-risk disease (> or = 5% marrow blasts; high International Prognostic Scoring System [IPSS] scores), the probability of post-transplant relapse ranges from 10% to 40%, and, as a result, relapse-free survival is inferior. In addition to disease stage, co-morbid conditions, pre-transplant chemotherapy, conditioning regimen, source of stem cells, and post-transplant immunosuppression affect transplant outcome. Reduced-intensity conditioning regimens are associated with a decrease in non-relapse mortality and allow for successful hemopoietic stem cell transplants even in patients 60-70 years of age. Graft-versus-host disease, both acute and chronic, and post-transplant relapse remain challenging problems.

Adult↗
PubMed2003

The WHO classification of MDS does make a difference.

The purpose of this study was to determine the facility and reliability of the World Health Organization (WHO) classification of myelodysplastic syndromes (MDSs) with several observers reviewing the same diagnostic specimens. We also wanted to determine if the WHO classification provided additional information about predictability of clinical response outcome. To accomplish these goals we reviewed 103 previously diagnosed cases of low-risk MDS. We found 92% interobserver agreement (P <.001). Sixty-four of these patients had been entered into clinical trials using growth factors by the Nordic MDS Study Group. The WHO classification reliably predicted therapeutic response to the combination of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo). The response rate differed significantly between refractory anemia with ringed sideroblasts (RARS) and refractory anemia with multilineage dysplasia and ringed sideroblasts (RCMD/RS) with regard to therapeutic response (75% versus 9%; P =.003). Also, in the group of patients with less than 5% marrow blasts, there was a difference in median survival between patients with unilineage dysplasia (51% surviving at 67 months) and those with multilineage dysplasia (median survival, 28.5 months; P =.03).

Classification↗
PubMed2005

Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF.

We report long-term results of treatment of myelodysplastic syndrome (MDS) with erythropoietin and granulocyte colony-stimulating factor (G-CSF). A total of 129 patients were followed up 45 months after last inclusion in the Nordic MDS Group studies. Erythroid response rate was 39% and median response duration 23 months (range, 3-116 months or more). Complete responders showed longer response duration than partial responders (29 versus 12 months, P = .006). The International Prognostic Scoring System (IPSS) groups Low/Intermediate-1 (Low/Int-1) had longer response duration than Int-2/High (25 versus 7 months, P = .002). The time until 25% developed acute myeloid leukemia (AML) was longer in the good and intermediate predictive groups for erythroid response compared with the poor predictive group (52 versus 13 months, P = .008). Only 1 of 20 long-term responders developed AML. We assessed the effect on long-term outcome by comparing treated patients with untreated patients selected from the IPSS database using multivariate Cox regression, adjusting for major prognostic variables. There was no difference in survival (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.7-1.2; P = .55) or risk of AML evolution (OR, 1.3; 95% CI, 0.7-2.2; P = .40) between treated and untreated patients. Patients with high/intermediate probability of response and with IPSS Low/Int-1 show frequent and durable responses without adverse effects on outcome, while other patients should not be considered candidates for this treatment.

Adolescent↗
PubMed2006

CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins.

CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) are distinguished from other MDS cells and from normal hematopoietic cells by their pronounced expression of apoptotic markers. Paradoxically, trisomy 8 clones can persist in patients with bone marrow failure and expand following immunosuppression. We previously demonstrated up-regulation of c-myc and CD1 by microarray analysis. Here, we confirmed these findings by real-time polymerase chain reaction (PCR), demonstrated up-regulation of survivin, c-myc, and CD1 protein expression, and documented comparable colony formation by annexin(+) trisomy 8(-) CD34(+) and annexin(-) CD34 cells. There were low levels of DNA degradation in annexin(+) trisomy 8 CD34 cells, which were comparable with annexin(-) CD34 cells. Trisomy 8 cells were resistant to apoptosis induced by gamma irradiation. Knock-down of survivin by siRNA resulted in preferential loss of trisomy 8 cells. These results suggest that trisomy 8 cells undergo incomplete apoptosis and are nonetheless capable of colony formation and growth.

Annexins↗
PubMed1983

A clinical study of long-term administration of dextran sulfate (MDS Kowa) in patients with retinopathy.

We administered MDS at a daily dose of 1,800 mg to 25 patients with diabetic retinopathy for periods ranging from 12 to 48 months (mean: 28 months) and achieved the following results: 1) During the administration period total cholesterol, triglyceride and fibrinogen levels were all maintained at significantly lower levels. 2) Eye fundus findings showed an improvement in 38.9% no change in 47. 2% and a deterioration in 13.9% of the cases. 3) No side-effects or abnormalities in clinical findings were observed in any of the cases even though clinical tests of hepatic function, renal function, blood chemistry, and urinalysis were conducted. The above results demonstrate that MDS has a marked effect on diabetic retinopathy, especially in cases with moderate to severe symptoms during the non-proliferative stage.

Adult↗
PubMed2001

Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS).

Considerable progress has been made recently in defining and understanding the diverse members of the group of hematologic disorders now known as the myelodysplastic syndrome (MDS). New systems of classification, based on the latest cytogenetic methodologies, have generated better prognostic data, and basic research has more closely associated molecular mechanisms with clinical subgroups. The mechanisms underlying most cases of myelodysplasia appear to be an array of chromosomal abnormalities leading to suppression of normal myeloid cell differentiation and dominance of abnormal, immature cells. The process is progressive and is mediated by a variety of cytokines, potential loss of tumor suppressor genes, aberrations in signal transduction pathways, and perhaps immune mechanisms. Hypermethylation of specific DNA sequences has been implicated in the pathogenesis of MDS. Until recently, treatment options have been few, high risk, and mostly ineffective. New discoveries, particularly in the area of stimulating remaining normal myeloid cells to resume growth and differentiation, hold promise for safer treatment regimens and improved outcomes. Among the promising new agents are nucleoside analogues, such as 5-azacytidine and decitabine, which reactivate tumor suppressor gene transcription through effects on DNA methylation.

Antimetabolites, Antineoplastic↗
PubMed1993

Detection of monoclonal hematopoiesis using restriction fragment length polymorphism (RFLP) of phosphoglycerokinase (PGK) gene in a patient with hypoplastic myelodysplastic syndrome (MDS).

A clonal analysis of hematopoiesis in a hypoplastic MDS patient was performed. Monoclonal utilization of PGK gene on her two X chromosomes was detected by Southern blot analysis of the bone marrow cells using a PGK probe after methylation-sensitive restriction enzyme treatment. This is compatible with monoclonal construction of her hematopoiesis, confirming MDS nature with a progression of her morphological dysplasia in bone marrow cells. RFLP of PGK gene on X chromosome is thus useful to detect a monoclonality in hematopoietic diseases.

Adolescent↗
PubMed1999

Clofibric acid: a potential therapeutic agent in AML and MDS.

Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated by patients. We demonstrate that clofibric acid (CA) enhances the response of HL60 cells to all-trans RA and D3. Our findings and those of others in the field lead us to suggest that combination therapy using all-trans RA and CA should be considered as potential therapy for AML and MDS.

Aged↗
PubMed1992

[Megakaryoblastic leukemia which developed from therapy-related MDS with myelofibrosis].

A 56-year-old man had a leiomyosarcoma of the small intestine in 1987. After surgery, he received cyclophosphamide for 2 years. In December, 1990, he exhibited severe pancytopenia. His hematological data were as follows: Hb 7.4g/dl, ret. 0.8%, WBC 1,700/microliters with leukoerythroblastosis and 2.8 x 10(4)/microliters platelets. A bone marrow aspiration was a dry tap. A bone marrow biopsy specimen showed a hypercellular marrow with myelofibrosis, leukemic infiltration (10.2%) and slight dyserythropoiesis. Both PPO and GPIIb/IIIa reaction were positive for blast cells and atypical megakaryoblasts. A diagnosis of MDS with an abnormality in megakaryocytic lineage was made. The patient was treated with 1,25-dihydroxy-vitamin D3, however this therapy was temporary and he developed into acute megakaryoblastic leukemia (M7). This report suggested that some cases of therapy-related leukemia (TRL) mainly involve megakaryocytic lineage and are diagnosed as MDS with myelofibrosis which transform to M7. The fact that PAS stain of erythroblasts in the patient reported here was positive may suggest involvement of development of more precise immunological markers of differentiation and EM study will permit better diagnosis of TRL and may therefore facilitate new therapeutic approaches.

Chemotherapy, Adjuvant↗
PubMed2006

Angiogenesis in myelodysplastic syndromes (MDS) in Indian patients.

Angiogenesis plays an important role in the pathogenesis of haematological neoplasms and may be correlated with the prognosis. We recently evaluated the microvessel densities in trephine biopsy sections of seventeen patients of myelodysplastic syndromes (MDS). Of the 17 cases, 2 were RAEB-t, 3 were RAEB, one was RARS and 11 were of the subtype RA (FAB subtyping). The microvessel counts were measured in the bone marrow biopsy sections by immunohistochemical staining, using CD34 reactive monoclonal antibodies. MVD was significantly higher in the cases of RAEB and RAEB-t as compared to the cases of RA. The average MVD per x400 in the cases of RA was 5.7 +/- 4.7 with a median value of 4.65 (range 19) whereas it was 45.4 +/- 10.0 and 44.0 (range 27.3) respectively in RAEB and RAEB-t (p <.001), the 95% confidence interval being (2.94, 8.5) and (36.6, 54.3), for the two groups respectively. This finding may imply that subtypes of MDS with a higher tendency for converting to acute leukaemia are associated with increased angiogenesis as compared to other subtypes where the risk of progression to acute leukaemia is much lower.

Adolescent↗
PubMed1989

Myelodysplastic syndromes (MDS) in Zimbabweans--preliminary observations.

Twenty three Zimbabwean African patients who satisfied the French-American-British(FAB) diagnostic criteria for the myelodysplastic syndromes(MDS) at Godfrey Huggins School of Medicine, University of Zimbabwe, between July 1985 and June 1987 are presented. The disorders appear not to behave differently from those reported in Caucasian populations with regard to clinical and haematological features. Refractory anaemia (RA) occurred in 12 (52.2%) patients; refractory anaemia with ringed sideroblasts (RARS) in 4 (17.4%) patients; refractory anaemia with excess blasts (RAEB) in 2 (8.7%) patients; refractory anaemia with excess blasts in transformation (RAEB-T) in 3 (13.0%) patients; while chronic myelomonocytic leukaemia (CMML) was observed in 2 (8.7%) patients. In 19 cases, the disease was primary and in 4 prior exposure to myelotoxic agents resulted in secondary MDS. The clinical significance of recognising the disorders is briefly high-lighted together with our current treatment protocol.

Adult↗