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)

From 1978 to 1985, 57 myelodysplasia patients with urinary and defecatory dysfunction underwent surgical treatment by modified seromuscular ileal flap fixation to the bladder. Followup was 1 to 88 months. Bladder capacity did not decrease, and voiding time and urine flow rate significantly improved. A urinary substitute sensation appeared in 45 of 46 patients (97.8 per cent) and urinary incontinence improved in 36 of 37 (97.3 per cent). A fecal substitute sensation appeared in 31 of 46 patients (67.4 per cent) and constipation improved in 22 (47.8 per cent). Operative complications were encountered in 5 of 57 patients (8.8 per cent), including 3 cases of prolonged paralytic ileus, 1 obstructive ileus and 1 wound herniation. Modified seromuscular ileal flap fixation to the bladder appears to be indicated for patients with the lower type of neurogenic bladder with neither a low compliance bladder nor high grade vesicoureteral reflux.
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PMID:A study of functional recovery for urination and defecation in patients with myelodysplasia: a modified seromuscular ileal flap fixation to the bladder. 291 47

Between 1978 and 1985, 72 patients with urinary and defecatory dysfunction due to neurogenic bladder associated with myelodysplasia (57), spinal cord injury (11), and other causes (4) were treated with modified sero-muscular ileal flap fixation to the bladder (modified IFFB). They were followed from 1 to 88 months (mean: 36.3 months). This operative procedure was attempted to recover urinary and defecatory function. Sixty-four patients underwent urodynamic studies before and after the modified IFFB. On urodynamic evaluation, bladder capacity was not decreased, voiding time was diminished, and average urine flow rate was significantly improved after the modified IFFB. Patients who were followed at least 6 months after the modified IFFB showed the following results. Urinary substitute sensation appeared in 57 out of 59 patients (96.6%) and fecal substitute sensation in 34 (57.6%). Urinary incontinence improved in 38 out of 42 patients (90.5%), disappearing completely in 19 (45.2%). Constipation improved in 26 of 59 patients (44.1%). The upper urinary tract improved in 22 renal units, remained unchanged in 90 renal units, and deteriorated in 6 of the 118 renal units. Operative complications were encountered in 6 out of 72 patients (8.3%). The modified IFFB procedure does not appear to be suitable for the low compliance bladders with high grade VUR or for young women who desire pregnancy in the future.
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PMID:[A study of functional recovery of urination and defecation by modified sero-muscular ileal flap fixation to the bladder in patients with neurogenic bladder]. 382 27

The aims of this study were to find the prevalence of tethered cord in patients with anorectal malformations; to determine if the presence of tethered cord relates to the severity of the anorectal defect, and to certain symptoms, signs, radiologic findings, and associated anomalies; and finally to determine whether tethered cord impacted on a patient's functional prognosis and whether surgical untethering improved the patient. The authors studied 934 patients with anorectal malformations, 111 of whom had magnetic resonance imaging (MRI) of the spine. We compared patients with and without tethered cord by using parametric and nonparametric statistical tests. Tethered cord occurred in 24% of the patients. The prevalence varied according to the type of anorectal defect from 43% in the complex group to 11% in patients with rectovestibular fistula. Patients with tethered cord had a lateral sacral ratio lower than that of patients without tethered cord (0.410 versus 0.702). Tethered cord was present in 90% of patients with myelodysplasia, 60% of patients with a presacral mass, 57% of patients with sacral hemivertebrae, and 56% of patients with a single kidney. The greater number of associated anomalies a patient had, the greater the risk of having tethered cord (P < .05 for all differences). The authors noted differences between patients with and without tethered cord in the presence of voluntary bowel movements (46% versus 70%), fecal soiling (91% versus 63%), constipation (21% versus 43%), and urinary incontinence (86% versus 42%). The data indicate that patients with tethered cord have a worse functional prognosis than patients without tethered cord. However, the incontinence in our patients was also predictable based on the type of anorectal defect and the character of the sacrum irrespective of the presence of tethered cord. Eighteen patients underwent surgical untethering of the cord, and none had any significant change in bowel or urinary function postoperatively. No patient with tethered cord experienced incontinence that could be attributed to the cord defect alone. This study suggests that tethered cord occurs more frequently in patients with severe anorectal defects, sacral hypodevelopment, myelodysplasia, presacral mass, sacral hemivertebrae, or a single kidney, or in those with an anorectal defect with poor functional prognosis. At present no solid evidence supports the concept that tethered cord by itself affects the functional prognosis of patients with anorectal malformations. Also, there is no good evidence demonstrating that surgical untethering improves the prognosis.
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PMID:The tethered spinal cord in patients with anorectal malformations. 909 19

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82

Thalidomide has immunomodulatory and anti-angiogenic properties which may underlie its activity in cancer. After its success in myeloma, it has been investigated in other plasma cell dyscrasias, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Thalidomide causes responses in 30-50% of myeloma patients as a single agent, and acts synergistically with corticosteroids and chemotherapy. Thalidomide results in the reduction or elimination of transfusion-dependence in some patients with myelodysplastic syndrome. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high-grade glioma, and in some patients with colon cancer in combination with irinotecan. The drug is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation, and fatigue are common side effects, whereas peripheral neuropathy and skin rash are seen in one-third. A minority of patients experience bradycardia. Thrombotic phenomena are especially common when thalidomide is combined with chemotherapy. Adverse effects severe enough to necessitate cessation of therapy are seen in around 20% of patients. A therapeutic trial of thalidomide is essential in all patients with relapsed or refractory myeloma. In other cancers, the best way to use the drug is in the setting of clinical trials. In the absence of access to studies or alternative therapeutic options, thalidomide could be considered singly or in combination with standard therapy.
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PMID:Thalidomide in cancer. 1190 8

In the majority cases, fecal soiling in children is functional and usually associated with severe constipation. Fortunately, functional soiling is a self-limiting problem and usually disappears at puberty. Organic fecal incontinence is a consequence of congenital malformations affecting the anorectum, anal sphincters, or the spinal cord. Inability to control bowel function may be permanent, as in patients with myelodysplasia; self-limiting, as in patients who have fecal soiling after a pull-through operation for Hirschsprung's disease; or partial, as in many patients who have undergone repair of an anorectal malformation. The purpose of this report is to review the etiology, long-term outcome, and evolution of the management of different types of organic fecal incontinence in children. Knowledge of the pathophysiology of fecal incontinence has accumulated during recent decades, and this provides the basis of modern treatment modalities that have revolutionized treatment so that today most patients can be provided total or at least social continence from early childhood.
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PMID:Fecal incontinence in anorectal malformations, neuropathy, and miscellaneous conditions. 1197 59

Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.
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PMID:Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. 1289 16

In analogy to solid neoplasms, accumulating data suggest the requirement of angiogenesis also for the development and progression of hematopoietic malignancies including acute myeloid leukemia (AML). Inhibition of increased microvessel density in bone marrow (BM) might be a promising target for pharmacological interventions aimed at reducing disease activity. Among the putative inhibitors of angiogenesis, thalidomide has demonstrated a considerable efficacy in myelodysplastic syndromes (MDS) and AML with overall response rates up to 56% and 25%, respectively. Responders experienced hematologic improvements with increased hemoglobin and platelet counts resulting in temporary transfusion independence. In AML, partial responses--defined as reduction of the leukemic blast cell infiltration of at least 50% in BM--occurred in four of 20 patients after one month of thalidomide administration in a previous phase I/II study. Additionally, we observed a long-term response in one AML patient of more than 20 months, meanwhile fulfilling the criteria of complete remission. The decrease in leukemic blast infiltration in BM of responders was accompanied by a significant reduction of the microvessel density. Overall adverse events caused by the drug consisted mainly of fatigue, constipation, skin rash and polyneuropathy with a tolerable dose of 200-400 mg p.o. per day. In conclusion, thalidomide as a single agent has significant anti-leukemic activity with some evidence for anti-angiogenic effects in BM, although the precise mechanism of action remains to be elucidated.
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PMID:Thalidomide for the treatment of acute myeloid leukemia. 1456 49

Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.
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PMID:Management of thalidomide toxicity. 1533 75

On May 19, 2004, azacitidine (5-azacytidine; Vidaza(trade mark); Pharmion Corporation, Boulder, CO, http://www.pharmion.com) for injectable suspension received regular approval by the U.S. Food and Drug Administration (FDA) for the treatment of all subtypes of myelodysplastic syndrome (MDS). This report summarizes the basis for this approval. Effectiveness was demonstrated in one randomized, controlled trial comparing azacitidine administered s.c. with best supportive care (observation group) and in two single-arm studies, one in which azacitidine was administered s.c. and in the other in which it was administered i.v. The dose of azacitidine, 75 mg/m2/day for 7 days every 28 days, was the same in all three studies. In the randomized trial, study participants were well matched with respect to age, sex, race, performance status, MDS subtype, and use of transfusion during the 3 months before study entry. Patients in the observation arm were permitted by protocol to cross over to azacitidine treatment if their disease progressed according to prespecified criteria. During the course of the study, more than half of the patients in the observation arm did cross over to the azacitidine treatment arm. The primary efficacy end point was the overall response rate. Response consisted of complete or partial normalization of blood cell counts and of bone marrow morphology. The response rate in the azacitidine arm was about 16%; there were no responses in the observation arm. The response rates in the two single-arm studies were similar (13% and 19%). The responses were sustained, with median durations of 11 months and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients.
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PMID:FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. 1579 20


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