Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxicities and antitumor activity of a new anticancer platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R), were examined in rats by single intravenous injection in comparison with those of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP). The lethal dose (LD) of DWA2114R (100 mg/kg) or CBDCA (80 mg/kg) caused a slight decrease in body weight (less than 10%) and no significant change in the levels of blood urea nitrogen and urinary sugar and protein. In contrast, a sub-LD level of CDDP (8 mg/kg) seriously decreased body weight (20%) and markedly elevated the levels of these nephrotoxicity parameters. Monitoring the numbers of peripheral blood cells for 3 weeks after the drug injection revealed that all three drugs showed severe thrombocytopenia, moderate leukopenia and slight anemia. However, CBDCA induced the most severe thrombocytopenia among these drugs. The number of platelets was reduced by 60% in rats injected with a half LD of CBDCA. A moderate reduction in platelet count (35-43%) was caused by an equitoxic dose of DWA2114R or CDDP, but abated about 3 days faster than that caused by CBDCA. Interestingly, only CDDP caused an irreversible anemia. Each drug showed a potent antitumor activity at weakly toxic doses against Walker 256 carcinosarcoma transplanted intramuscularly into rats. These results indicate that DWA2114R could be a promising new platinum anticancer agent with an improved toxicity profile.
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PMID:Toxicological and tumoricidal evaluations of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato+ ++)platinum( II) monohydrate, in rats. 190 57

The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.
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PMID:Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis. 190 54

Close on the heals of the first successful reports of recombinant human erythropoietin (rHuEPO) use in dialysis-associated anemia, concern surfaced that raising the hematocrit level could threaten both the safety and efficacy of hemodialysis. Theoretical considerations prompted the conclusion that by decreasing the plasma water space available for dialysis, removal of plasma solutes would decrease in direct proportion to the increase in hematocrit. Predictions of thrombotic disaster were also aired, citing the increase in blood viscosity expected after correction of anemia. After 18 months of widespread use of rHuEPO in the United States, clinical experience has shown that correction of anemia can be accomplished without serious impact on either safety or efficacy in both conventional and high efficiency/high dialysis. Although predialysis concentrations of creatinine, phosphate, and potassium may increase whenever the hematocrit increases substantially, the magnitude of the rise is limited. Increased predialysis solute concentrations, which may be caused by either decreased dialyzer efficiency or increased dietary intake due to improved appetite, are readily managed by increasing dialysis blood flow rate, dialyzer surface area, and dialysis time. Since these measures may have little effect on increased phosphate levels, increased administration of phosphate binders may be required. However, by way of caution, the ready dialyzability of urea renders the predialysis blood urea nitrogen (BUN), as well as urea kinetics, relatively unaffected by the change in hematocrit, thereby masking adverse effects on other solutes. Fortunately, serious thrombotic consequences have not been seen, probably because anticoagulation is adequately managed by routine increases in heparin utilization.
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PMID:Impact of erythropoietin on the dialysis prescription. 192 83

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.
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PMID:Anemia in new congenital adult type polycystic kidney mice. 194 61

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. A, C57BL/6, B6AF1, LP and C3H mice received TBI in two fractions 3 h apart at total doses of between 11 and 15 Gy. They were then transplanted with syngeneic bone marrow cells providing sufficient reconstitution to avoid hemopoietic failure. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of 51Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow 59Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis.
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PMID:Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia. 196 48

The effects of recombinant human erythropoietin (r-HuEPO) on haematological parameters were studied in rats in which uraemia and anaemia had been induced by gentamicin, an aminoglycoside antibiotic and a nephrotoxic agent. After the occurrence of slight polycythaemia, the red blood cell count, haematocrit and haemoglobin concentration decreased by 20-30% compared with those of the control (saline-injected) rats. At the end of gentamicin treatment, the endogenous serum EPO level had decreased to about 40% compared with that of control rats. Gentamicin-treated rats showed marked elevation of blood urea nitrogen, extensive tubular necrosis in the kidney and haemosiderin deposition in the spleen. In the osmotic fragility test, the fragility of erythrocytes significantly increased compared with that of control rats. These findings indicate that the anaemia induced by gentamicin is due not only to a deficiency of EPO but also to an enhancement of fragility of erythrocytes in an azotaemic environment. The administration of r-HuEPO during anaemia markedly increased red blood cell count, haematocrit and haemoglobin concentration. It is suggested that a gentamicin-treated rat is a useful and convenient anaemic model and r-HuEPO is useful for treatment of anaemia in acute renal failure.
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PMID:Effect of recombinant human erythropoietin on new anaemic model rats induced by gentamicin. 198 98

The dose dependency of germanium dioxide(GeO2)-induced nephrotoxicity was investigated experimentally in rat groups orally treated with high (150 mg/kg/day), moderate (75 mg/kg/day), or low (37.5 mg/kg/day) doses of GeO2, and in an untreated group. Renal dysfunction, indicated by the increase of blood urea nitrogen and the decrease of creatinine clearance, and systemic toxicity by weight loss, anemia, and hypoproteinemia were more apparent in rats treated with higher dose of GeO2. Urinalysis including daily urinary protein excretion did not reveal any abnormalities in any of the groups. Urinary excretion and renal-tissue content of Ge were significantly elevated in the group of the higher dose of GeO2. Light microscopically, vacuolar degeneration and depositions of granules positive for periodic acid-Schiff in distal tubules were predominant in the higher-dose group of GeO2. The present study demonstrates that GeO2-induced nephrotoxicity develops dose dependently.
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PMID:Dose dependency of germanium-dioxide-induced nephrotoxicity in rats. 201 77

Four patients with primary pulmonary hypertension, microangiopathic hemolysis, and thrombocytopenia were seen at the Charleston (WVa) Area Medical Center between 1983 and 1988. Characteristic laboratory and clinical features of these patients were the following: mild anemia, reticulocytosis, low serum haptoglobin value, microangiopathic red blood cell changes on peripheral blood smear, mild to moderate thrombocytopenia, normal clotting studies (ie, prothrombin time, partial thromboplastin time, fibrinogen), negative direct Coombs' test, negative glucose water test, normal serum urea nitrogen and creatinine levels, lack of improvement of hemolysis and thrombocytopenia in response to vasodilators or calcium channel blockers, and severe plexiform lesions in the pulmonary vasculature with fibrin deposition at autopsy. The hemolysis and thrombocytopenia probably developed as a result of flow through the fibrin deposition in the plexiform lesions in the pulmonary circulation and subsequent shearing of red blood cells and platelets.
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PMID:Primary pulmonary hypertension. Its association with microangiopathic hemolytic anemia and thrombocytopenia. 204 24

In the following study, normal blood values were performed on 58 Friesian calves (30 males and 28 females) under preexisting Moroccan management conditions. The following parameters were evaluated: pH-value, p.CO2, actual HCO3, BE, BB, RBC, WBC, PCV, Hb, MCV, MCHC, Glucose, lactate, urea, creatinine, total protein, total bilirubin, enzyme activities of AST and GGT and electrolyte-values (Na, K, Cl). The values of all parameters varied significantly with age with the exception of MCV, MCHC and K. The female calves presented higher values of act. HCO3, BE, BB, Hb, PCV and MCV than the male calves (p less than 0.01). The calves were born in mixed acidosis stage which was largely restored 24 hours later. At the weaning, the calves showed a slight metabolic acidosis with a partial respiratory compensation. The metabolic acidosis was accompanied with an increase of lactate level in blood plasma. During the first month of life, the development of an anaemia (PCV decreased) was observed. The mean values of glucose and total protein increased after colostrum intake, whereas the electrolyte values in blood plasma decreased. In general, the mean values of lactate, creatinine, urea, total bilirubin and the activities of AST and GGT decreased with age, while glucose and total protein remained nearly unchanged. The age and the sex should be taken in consideration judging the above mentioned parameters in a new born calf from birth to weaning (here: two months).
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PMID:[Hemocytological and hemobiochemical studies in black pied, clinically healthy breeding calves in Morocco]. 204 72

The authors evaluated in a group of 89 patients with monoclonal gammapathy (18 patients with monoclonal gammapathy of undermined significance, 34 patients examined at the time of diagnosis of multiple myeloma (MM) and in a group of 71 patients with MM examined in different stages of the disease) the serum beta 2-microglobulin. It was revealed that the mentioned indicator is of no differential diagnostic value, it is not related to sex nor to the immunochemical type of monoclonal immunoglobulin. A relationship of serum beta 2-microglobulin to age, serum urea and serum creatinine, to the severity of anaemia, serum albumin, sedimentation rate of red cells, degree of infiltration of bone marrow by myeloma plasmocytes and the stage of the disease, evaluated by the systems of Durie-Salmon and Medical Research Council, was found. The authors tested the importance of serum levels of this indicator for the prognosis of the disease.
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PMID:[Serum beta 2-microglobulin in multiple myeloma. I. Relation to selected indicators, clinical stage and disease prognosis]. 205 4


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