Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 9-year-old boy was admitted with the diagnosis of myelodysplastic syndrome (FAB RAEB in T). The patient was treated with busulfan and cyclophosphamide and transplanted with bone marrow cells from an HLA identical sister. Cyclosporin A (CyA) and short term methotrexate (MTX) was given for prophylaxis against graft versus host disease (GvHD). The serum potassium value was observed to increase to 6.3 mEq/l during the period of CyA therapy. The serum potassium value returned to 4 mEq/l when CyA treatment was decreased to a serum concentration of less than 50 ng/ml (FPIA). On day 90 post transplantation the patient was diagnosed as relapsed. The patient was preconditioned with cyclophosphamide and total body irradiation and a second bone marrow transplantation was performed using cells from the same donor. He was treated again with CyA and short term MTX for the prevention of GvHD. Once again the patient became hyperkalemic with 6.8 mEq/l. The serum creatinine level was 0.9 mg/dl, the GFR was 52.1 ml/min, FEK was 7.1%. Pseudohypoaldosteronism or hyporeninemic hypoaldosteronism was suspected. To investigate this possibility a renin/aldosterone stimulation test was performed. We speculate that an idiosyncratic response to CyA resulted in pseudohypoaldosteronism and produced a defect in potassium secretion.
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PMID:[Hyperkalemia in a cyclosporine A-treated allogeneic bone marrow transplant recipient]. 154 16

Urinary glycosaminoglycan excretion is increased in a variety of human diseases, including malignancy. We have measured serum and urine glycosaminoglycan levels by the carbazole method of uronic acid determination in patients with myeloid leukemia or myelodysplasia. Eleven patients were studied during active disease as well as eight in complete remission. Serum levels in patients with active disease did not differ significantly from 11 healthy volunteers with no hematological disease. In contrast, the median urine level for the patients with active disease was 7.6 mg uronate/g Creatinine (Creat) compared to 2.6 for controls (p less than 0.002). Interestingly, the eight patients in complete remission also had a significant increase in uronate excretion with a median of 7.3 (p less than 0.002). These results suggest that elevated urinary glycosaminoglycan levels in leukemia are not due to impaired ability of the liver to clear circulating glycosaminoglycans or overproduction by leukemic cells. The observed increase in glycosaminoglycan excretion may be due to altered bone marrow matrix metabolism that is often not reversed by the achievement of hematologic remission.
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PMID:Serum and urine glycosaminoglycans in myeloid leukemia and myelodysplasia. 290 8

A total of 3 renal transplant recipients who were candidates for urinary diversion underwent successful transplantation using a planned program of intermittent clean catheterization. The urinary tract dysfunction was caused by a lower motor neuron neurogenic bladder, prune belly syndrome and myelodysplasia. The patients remain dry between catheterizations and maintain serum creatinine levels of 1.1, 0.8 and 0.5 mg. per cent, respectively, with a followup of 6 to 25 months. There has been only 1 urinary tract infection during 42 patient-months at risk while on self-catheterization. Pre-transplant urologic evaluation and patient education are mandatory. The ideal candidate for intermittent clean catheterization is a patient with a low pressure bladder that fails to empty and who is continent between catheterizations. Intermittent clean catheterization is a safe and effective alternative to diversion in continent transplant recipients with lower urinary tract dysfunction.
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PMID:Intermittent clean catheterization: an alternative to diversion in continent transplant recipients with lower urinary tract dysfunction. 635 11

By serially measuring serum levels of alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to renal dysfunction, acute graft-versus-host disease (GVHD) and infection as complications of the transplantation. The study involved a total of 25 patients with leukemia, myelodysplastic syndrome and aplastic anemia who received BMT in this department; one patient received re-transplantation, thus bringing the total number of transplants to 26. Twenty-four patients received BMT from HLA-identical siblings while two others received BMT from unrelated donors. Alpha-1 microglobulin was within normal limits in all patients before BMT; among various complications such as nephrotoxicity, acute GVHD and infection which took place after transplantation, a raised alpha-1 microglobulin level was found only in nephrotoxicity; however, the increase was not significant compared with the pre-transplantation level. The pre-transplantation beta-2 microglobulin level was higher than normal in some patients; it was significantly increased in all of the above complications compared with the pretransplantation level (1.57 +/- 0.57 mg/l). A significant correlation was found between the serum creatinine level and the beta-2 microglobulin level (r = 0.849) in patients with renal dysfunction. In some patients, however, the beta-2 microglobulin level increased earlier than the serum creatinine level, and this finding was considered useful for the early diagnosis of renal dysfunction following allogeneic BMT.
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PMID:Change of serum alpha-1 microglobulin and beta-2 microglobulin following allogeneic bone marrow transplantation. 753 65

We have adopted an approach to the management of myelodysplasia patients which is contrary to that most commonly supported by the existing literature. We screen patients shortly after birth with ultrasound, urine culture and serum creatinine, and then follow patients at 3 to 6-month intervals with similar studies. Cystography and urodynamics are done only as required clinically or by a change in the sonogram. Clean intermittent catheterization is indicated for continence or medical reasons. With this approach of aggressive observation and prompt intervention, we observed a rate of renal deterioration (diminished function on renal scan or parenchymal loss on imaging studies) of 5%. Renal deterioration was associated statistically with urinary tract infections and reflux. Patients started on clean intermittent catheterization for medical indications had greater risk for renal deterioration than those started on it for continence. Renal deterioration occurred with equal frequency between patients with abnormal and normal urodynamic studies, that is urodynamics did not predict renal deterioration. Our data show a rate of renal deterioration similar to other reports. We believe that aggressive observation with prompt intervention for problems once identified represents a reasonable alternative to managing patients with myelodysplasia.
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PMID:An alternative approach to myelodysplasia management: aggressive observation and prompt intervention. 802 20

1H and 31P NMR techniques were applied to study the changes in metabolite profiles in human urine resulting from radiation exposure following the Chernobyl reactor accident. In cases of acute leukemia and different accumulated doses of external radiation (from 0.20 to 4.00 Sv), the proton spectra were classified on the basis of the peaks due to N-trimethyl groups, creatinine, citrate, glycine, and hippurate. Unidentified resonances were observed between 15.9 and 21.4 ppm in six phosphorus spectra of patients with preleukemia and acute leukemia. Characteristic spectral changes were similar for external radiation and incorporation-induced internal irradiation. The spectral patterns described may serve as a criterion of radiation injury.
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PMID:Evaluation of radiation injury by 1H and 31P NMR of human urine. 812 Dec 68

Neurological toxicity occurred in 8/219 patients treated with fludarabine (FAMP), 30 mg/m2 per day and cytosine arabinoside (Ara-C), 0.5 g/m2 per hour for 2-6 hours for 5 days, for new or relapsed acute leukemia or myelodysplasia. Two patients developed severe, progressive cerebral dysfunction that was ultimately fatal. This toxicity was similar to that seen with high-dose fludarabine therapy and was limited to patients with serum creatine > or = 2.0 mg/dl and age over 60 years, occurring in 2/9 such patients compared to 0/210 among the other patients (p < 0.005). Since FAMP is partially excreted by the kidney, toxicity in these two patients was likely due to receiving an effectively high dose of FAMP. Five patients developed peripheral neuropathy but there was no association with age, creatinine, dose of Ara-C, or number of courses. A patient, who also received intrathecal Ara-C, developed myelopathy. At this dose rate and duration of Ara-C peripheral neuropathy rarely arises, and cerebral toxicity is not seen. Neither toxicity was observed in 481 chronic lymphocytic leukemia patients treated with FAMP alone, by the same dose and schedule, suggesting that combination with Ara-C is important for the development of at least the peripheral neuropathy. The incidence of neurotoxicity with FAMP/Ara-C is low especially in comparison with high-dose Ara-C therapy (3 g/m2 over 2 hours). Cerebral toxicity can likely be decreased by dose reduction of FAMP in patients with increased creatinine and peripheral neuropathy decreased by detailed neurological examination before courses of FAMP/Ara-C.
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PMID:Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. 844 43

FK506 (Tacrolimus) is an immunosuppressive drug that blocks the activation of antigen-specific T lymphocytes, a major component in the pathogenesis of graft-versus-host disease (GVHD). This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling marrow transplantation. Additionally, a subset of patients was studied to define the pharmacokinetic profile of FK506. Twenty-seven adult patients with leukemia or myelodysplasia received FK506 starting the day before transplant at a dose of 0.04 mg/kg/d by continuous intravenous infusion. When clinically possible, FK506 was given orally in two divided doses starting at five times the daily intravenous dose. FK506 doses were adjusted to target a steady state or trough blood level between 10 to 30 ng/mL. These patients were followed for 6 months posttransplant. All patients had sustained marrow engraftment. Frequently noted adverse events included reversible renal dysfunction, diarrhea, fever, nausea, vomiting, and headache. Most patients required FK506 dose reductions associated with elevated serum creatinine. Two (7%) patients relapsed, one of whom died of the disease within the 6-month study period. A second patient died due to pulmonary mucor. Whole blood pharmacokinetic parameters indicated a half-life of 18.2 +/- 12.1 hours; volume of distribution of 1.67 +/- 1.02 L/kg; clearance of 71 +/- 34 mL/h/kg; and bioavailability of 32 +/- 24%. Eleven of 27 (41%) patients developed grade II to IV acute GVHD, including 10 grade II and one grade III. Six of 24 (25%) evaluable patients developed chronic GVHD. These data indicate that FK506 monotherapy has activity in preventing GVHD. Further studies of FK506 with lower doses to improve tolerability and in combination with other immunosuppressants to augment efficacy are warranted.
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PMID:FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation. 860 72

There is a close relationship between hematopoietic bone marrow and bone cells. Thus, the profound derangement of hematopoiesis in myelodysplastic syndromes (MDS) might be expected to affect bone cell function. We studied the dynamic histomorphometric changes in bone in 22 MDS patients to examine this relationship and analyze the influence of hematological disease on bone remodeling. Bone-regulating hormones and histomorphometry of undecalcified transiliac bone biopsies, after double tetracycline labeling, were studied. Serum calcium, phosphorus, creatinine, alkaline phophatase, osteocalcin, iPTH, 25(OH)D3, 1,25(OH)2D3, hydroxyprolinuria, and calcium/creatinine ratio in urine were normal compared with controls. Histomorphometry showed a significant decrease in osteoblast surface (Ob.S/BS) (0.30 +/- 0.40 vs. 0.8 +/- 1.1, p = 0.031), wall thickness (W.Th), (22.03 +/- 5.5 vs. 31.8 +/- 5.8, p < 0.005), osteoclast number (N.Oc/T.Ar) (0.004 +/- 0.01 vs. 0.017 +/- 0.01, p = 0.03), mineral apposition rate (MAR) (0.16 +/- 0.15 vs. 0.53 +/- 0.19, p < 0.005), bone formation rate, surface referent (BFR/BS) (0.004 +/- 0.10 vs. 0.016 +/- 0.016, p = 0.009), and activation frequency (Ac.f) (0.06 +/- 0.07 vs. 0.21 +/- 0.23, p = 0.008). An increase in mineralization lag time (MLT) (119.2 +/- 78.6 vs. 29.6 +/- 77, p < 0.005), (mean +/- SD, unpaired Student t-test) was observed. Bone volume (BV/ TV), eroded surfaces (ES/BS), and osteoid thickness (O.Th) remained unchanged. This picture of adynamic bone with decreased mineral apposition rate and markedly decreased osteoclast number is a characteristic finding in MDS patients. Thus, bone histomorphometric finding in MDS patients show the relationships and interactions between hematopoietic and bone cells.
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PMID:Bone remodeling alterations in myelodysplastic syndrome. 889 47

We performed an open, nonrandomized, multicenter phase-II trial to evaluate the efficacy and toxicity of 1 year of treatment with the oral iron chelator deferiprone in 38 mainly nonthalassemic patients with transfusional iron overload. Initial serum ferritin varied between 996 and 11.644 micrograms/l. Patients were treated with 3-6 g of deferiprone daily. Mean urinary iron excretion (UIE) in 36 evaluable patients was 21.0 mg/24 h and was significantly higher in the patients with thalassemia than in those with myelodysplasia. Negative iron balance was achieved in 20 patients (56%). The median duration of treatment was 10 months; due to side effects and other causes only 20 patients completed 1 year of treatment. Mean serum ferritin levels decreased from 3563 micrograms/l at the start of the trial to 2767 micrograms/l at 6 months (26 patients, p < 0.004) and to 2186 micrograms/l at 12 months (20 patients, p < 0.005). Serum ferritin levels normalized in two patients who were no longer transfusion dependent. Deferiprone was clearly not effective in three patients (two with myelofibrosis, one with myelodysplasia). One patient with myelodysplasia developed agranulocytosis after 12 months of treatment; this was rapidly reversible after stopping deferiprone. Three patients had a mild and transient decrease in white blood cell count. Other side effects leading to withdrawal from the trial consisted mainly of nausea (3 patients), arthralgia (2), and skin rash (1). No clinical signs of zinc deficiency were seen, although zinc excretion was increased in three patients. No changes were seen in liver enzymes, creatinine, antinuclear factor, T-cell subsets, cardiac function, visual acuity, and audiogram. Although our results confirm deferiprone as an effective iron chelator in patients with thalassemia and in some patients with other forms of iron overload, there is still some concern about the safety of this drug, which therefore, at this time, should be used exclusively in well-controlled clinical trials.
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PMID:Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. 895 43


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