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)

Based on preclinical studies demonstrating synergy between gallium and hydroxyurea, we evaluated the efficacy and toxicity of continuous intravenous gallium nitrate in combination with oral hydroxyurea in patients with refractory non-Hodgkin's lymphoma. Fourteen patients, median age 64 years (range 53-89), with stage III or IV low- or intermediate-grade lymphoma were treated with gallium nitrate and hydroxyurea in combination for 7 days at four different dose levels: (a) gallium nitrate, 200 mg/m2/day; hydroxyurea, 500 mg/day; (b) gallium nitrate, 250 mg/m2/day; hydroxyurea, 1,000 mg/day; (c) gallium nitrate, 300 mg/m2/day; hydroxyurea, 1,000 mg/day; and (d) gallium nitrate, 350 mg/m2/day, hydroxyurea, 1,000 mg/day. All patients had progressive disease and had been heavily pretreated. Six of 14 patients had objective tumor regression following treatment (one complete response, one near-complete response, and four partial responses) with a median duration of response of 7 weeks (range 3-38 weeks). An additional four patients had minor responses. Responses occurred at all dose levels and in both low- and intermediate-grade histologic subtypes. The predominant toxicities encountered were anemia and reversible nephrotoxicity. Combination gallium nitrate and hydroxyurea has significant activity in lymphoma and is well tolerated even by elderly patients. Because of the lack of cross-resistance to other drugs and the potential synergistic antineoplastic activity, gallium nitrate and hydroxyurea should be further evaluated in combination with other chemotherapeutic agents.
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PMID:Evaluation of continuous-infusion gallium nitrate and hydroxyurea in combination for the treatment of refractory non-Hodgkin's lymphoma. 912 95

The authors performed a phase II trial of the VIG regimen (vinblastine, ifosfamide, and gallium nitrate) in patients who had advanced ovarian cancer who were refractory to cisplatin and/or carboplatin and whose disease had progressed after paclitaxel-based therapy. This was a heavily pretreated population, with five patients having received two to three prior chemotherapy regimens and six patients having received more than six prior chemotherapy regimens, with an average of 21 therapy cycles per patient. Fourteen patients were treated with vinblastine, 0.08 mg/kg intravenously on days 1 and 2; ifosfamide, 900 mg/m2 intravenously on days 1 through 5 with standard mesna uroprotection; and gallium nitrate administered as a continuous intravenous infusion at 225 mg/m2 per 24 hours x 120 hours. Granulocyte colony-stimulating factor (G-CSF) was administered subcutaneously at 5 microg/kg/day beginning on day 7 until day 13. Five of 14 patients achieved a partial response for an overall response rate of 36% (95% confidence interval, 14%-68%). The median response duration was 14 weeks. Toxicity was primarily hematologic, with anemia and leukopenia being most significant. There were no treatment-related deaths. Further evaluation of this regimen in a less heavily pretreated population is warranted.
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PMID:Vinblastine, ifosfamide, gallium nitrate, and filgrastim in platinum- and paclitaxel-resistant ovarian cancer: a phase II study. 962

A 40-year-old woman presented with asymptomatic gross hematuria caused by the nutcracker phenomenon. Despite treatment with hemostatic agents and injection of silver nitrate into the renal pelvis, the hematuria had continued, and severe anemia (hematocrit 17%) had developed. We performed expandable metallic stent (EMS) placement across the left renal vein. Although mild hematuria continued, the anemia resolved after this interventional radiotherapy. EMS placement is a minimally invasive therapy for the nutcracker phenomenon.
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PMID:Expandable metallic stent placement for nutcracker phenomenon. 1009 99

In neonatal calves besides adaptations in organ function there are marked metabolic and endocrine changes. The growth hormone (GH)-insulin-like growth factor (IGF) axis is basically functioning, but needs maturation. Various metabolic and endocrine traits do not exhibit marked ontogenetic changes after the first week of life, but others remain different from the adult stage. Thus, plasma oxytocin or an oxytocin-like substance and nitrate concentrations are elevated for months. The ability to digest colostrum (C) and milk involves great alterations in structure and function of the gastrointestinal (GI) tract. C intake is important for passive immunity, provision of nutrients, minerals and vitamins, and contains biologically active substances. IGF-I, present in C in high amounts, appears to enhance GI tract development and function. For sufficient absorption not only of immunoglobulins, but also of fatty acids and fat-soluble vitamins, C should be ingested immediately after birth. The amino acid pattern and the glutamine/glutamate ratio depends greatly on whether C is fed or not. Effects on insulin, IGF-I, and IGF binding proteins depend on time-point and amounts of C fed. After the colostral period calves are almost exclusively fed milk and milk substitutes or weaned. Low iron intake, required for the production of pale meat, besides anemia causes metabolic and endocrine adaptations, such as enhanced insulin-dependent glucose utilization and appears to reduce IGF-I responses to GH. Metabolic and endocrine changes, such as insulin resistance and disturbed glucose metabolism, can be observed in part in association with high feeding intensity in veal calves.
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PMID:Endocrine and metabolic aspects in milk-fed calves. 1052 25

Regulation of HIV gene expression is crucially dependent on binding of the trans-activator protein, Tat, to the trans-activation response RNA element, TAR, found at the 5' end of all HIV-1 transcripts. Tat-TAR interaction is mediated by a short arginine-rich domain of the protein. Disruption of this interaction could, in theory, create a state of complete viral latency. A new class of small-molecule peptidomimetic TAR RNA binders, conjugates of aminoglycosides and arginine, was recently designed [Litovchick, A., Evdokimov, A. G., and Lapidot, A. (1999) FEBS Lett. 445, 73-79]. Two of these compounds, the tri-arginine derivative of gentamicin C (R3G) and the tetra-arginine derivative of kanamycin A (R4K), bind efficiently and specifically to TAR RNA. These compounds display negligible toxicity while being transported and accumulated in cell nuclei. Here we present a detailed synthesis and chemical characterization of the aminoglycoside-arginine conjugates R3G and R4K as well as GB4K, the tetra-gamma-guanidinobutyric derivative of kanamycin A. Their binding sites on TAR RNA were assigned by RNase A, uranyl nitrate, and lead acetate footprinting. The conjugates interact with TAR RNA in the widened major groove, formed by the UCU bulge and the neighboring base pairs of the upper stem portion of TAR, the binding site of Tat protein, and Tat-derived peptides (e.g., R52). Our results suggest an additional binding site of R4K and R3G compounds, in the lower stem-bulge region of TAR. The antiviral activity of the conjugates in cultured equine dermal fibroblasts infected with equine infectious anemia virus, used as a model system of HIV-infected cells, is also presented.
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PMID:Aminoglycoside-arginine conjugates that bind TAR RNA: synthesis, characterization, and antiviral activity. 1071 3

Injectable gallium (Ga) nitrate, approved in the United States for the treatment of hypercalcemia of malignancy, has been known for more than 2 decades to have immunosuppressive properties. At therapeutic doses, it has few adverse effects, although high-dose infusions may result in severe nephrotoxicity, particularly in patients who are not adequately hydrated, and severe anemia. In animal models, Ga has been shown to have efficacy in the treatment of adjuvant arthritis, type 1 diabetes, experimental autoimmune encephalomyelitis, experimental pulmonary inflammation, cardiac allograft rejection, experimental autoimmune uveitis, endotoxic shock, and systemic lupus erythematosus. Clinical trials have demonstrated efficacy in Paget's disease of bone and activity against some malignancies, including epithelial ovarian carcinoma, non-squamous cell carcinoma of the cervix, bladder cancer, and non-Hodgkin's lymphoma. Other clinical trials underway include studies of sarcoidosis and rheumatoid arthritis. Future studies should be conducted not only in other autoimmune diseases, such as multiple sclerosis, but also in graft-versus-host disease, leprosy, and acquired immunodeficiency syndrome (AIDS).
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PMID:Therapeutic uses of gallium nitrate: past, present, and future. 1132 18

We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out of 199 patients had a positive DAT. Of these, 45 samples reacted with anti-C3d antibodies, 2 with anti-IgG and 6 with both reagents. There were significantly lower haemoglobin (Hb)-levels and higher prevalence of spleen enlargement in DAT-positive than in DAT-negative patients. Hb-levels were independently associated with DAT and age. This initial study was designed to investigate the role of intravascular haemolysis (IVH), but we found no association between IVH and either DAT result or anaemia. Because of the risk of selection bias we repeated the study using consecutive enrollment of malaria patients and were able to confirm the results in a total of 49 DAT-positive and 183 DAT-negative patients. This second study (in 1998) was designed to look at the importance of erythrophagocytosis through measurement of plasma neopterin levels and total nitrite and nitrate as markers of NO-release. Both parameters were significantly higher in DAT-positive than in DAT-negative patients (P < 0.001), indicating that complement binding to erythrocytes was associated with macrophage activation. Plasma levels of haptoglobin, interleukin-10 and tumour necrosis factor-alpha did not vary between the groups. The studies support the role of complement activation and erythrophagocytosis in the pathogenesis of anaemia in falciparum malaria in African children.
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PMID:Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria. 1170 71

Babesiosis, caused by the virulent haemoprotozoan parasite Babesia canis rossi, is an important disease of dogs in South Africa. The nitric oxide metabolites, nitrate and nitrite (collectively termed reactive nitrogen intermediates or RNIs) were measured in admission sera from dogs in a babesiosis-endemic area. Five groups were prospectively studied: mild uncomplicated (n=9), severe uncomplicated (severe anaemia) (n=10) and complicated babesiosis (n=11); and two groups of healthy aparasitaemic dogs: endemic controls from the study area (n=10) and experimental dogs kept in tick-free conditions (n=10). Four measures of RNI production were studied: (i) serum RNI; (ii) serum RNI/creatinine ratio; (iii) fractional clearance of RNI (FC(RNI)); (iv) fractional excretion of RNI (FE(RNI)). Marked elevations of serum RNI occurred in only two dogs, both in the severe uncomplicated group. The highest concentration (log value 5.29 micromol/l) was in a dog that died, but concentrations in the other four dogs that died were unremarkable (0, 0.34, 1.66 and 2.64 micromol/l). Age, appetite and free serum haemoglobin were significant covariates for measures of RNI production. There were no significant differences among the babesiosis groups for serum RNI. Adjustment for creatinine had minor effects on the results. All babesiosis groups had significantly higher serum RNI and RNI/creatinine than the tick-free control group, but did not differ from the endemic controls except for the severe uncomplicated group, which had higher RNI/creatinine. The complicated group had significantly lower FC(RNI) and FE(RNI) than all other groups, except for the tick-free control group, which had similar FE(RNI). The results indicate that, in an endemic area, measures of RNI production are unlikely to be useful indicators of severity or outcome in canine babesiosis.
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PMID:Nitric oxide metabolites in naturally occurring canine babesiosis. 1177 53

To investigate the influence of iron deficiency and iron supplementation on nitric oxide (NO) production, we measured serum iron markers, serum nitrate and nitrite (NOx) concentrations, reticulocyte maturity index (RMI), and serum transferrin receptor (sTfR) levels in 369 females aged 14-19 years. RMI was analyzed by flow cytometry, sTfR concentrations were measured by enzyme immunoassay, and serum NOx levels were tested by the Griess reaction. NOx concentrations of the subjects in iron depletion phase were significantly higher than those of healthy controls. NOx concentrations increased gradually as iron deficiency progressed and were threefold higher than for the healthy controls, when the subjects attained a frank iron deficiency anemia. In particular, the NOx concentrations were 7.5-fold higher in the patients with severe iron deficiency anemia (Hb<80 g/l) than for the subjects with high hemoglobin value (Hb>or=140 g/l). The increased NOx concentrations (132.6+/-42.1 microM) observed in the group with severe anemia decreased significantly (46.3+/-15.8 microM) after hemoglobin levels were normalized by iron supplementation ( P<0.01). NOx concentrations correlated inversely with hemoglobin levels ( r(2)=0.202, P<0.01), but correlated positively with the sTfR concentrations ( r(2)=0.322, P<0.01) and the RMI ( r(2)=0.369, P<0.01). In conclusion, iron deficiency anemia increases NO production, and elevated NOx concentrations in iron deficiency anemia return to normal with iron supplementation.
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PMID:Iron deficiency anemia increases nitric oxide production in healthy adolescents. 1180 27

The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.
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PMID:Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction. 1239 48


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