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Biomedical subjects

V R Gordeuk

Publications and source records attributed to V R Gordeuk.

At least 91 records · Page 5Linked to original sources
PubMed1991

Bioavailability of carbonyl iron: a randomized, double-blind study.

49 female blood donors with iron-deficiency anemia were treated with equal doses of iron either as carbonyl iron or ferrous sulfate in a randomized, double-blind fashion. The prevalence of side-effects was similar in the two groups. Mean values for hemoglobin concentration, mean corpuscular volume, corrected reticulocyte count, platelet count, serum iron, total iron-binding capacity, transferrin saturation or erythrocyte protoporphyrin did not differ significantly between the two groups throughout the study. After 16 weeks of therapy, the mean increase in hemoglobin iron was similar in both groups (p = 0.2). Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high, about 70% that of ferrous sulfate.

Adult↗
PubMed1991

Stage-specific ultrastructural effects of desferrioxamine on Plasmodium falciparum in vitro.

Desferrioxamine (DFO) is an iron chelator that inhibits the in vitro and in vivo growth of rodent and human malarial parasites. Previous studies with this chelator have suggested that it might interfere with the intraerythrocytic growth of Plasmodium sp. by withholding iron from any of several essential iron-dependent parasite enzymes, including those involved in CO2 fixation, mitochondrial electron transport, pyrimidine synthesis, and the reduction of ribonucleotides for DNA synthesis. We studied the ultrastructural effects of DFO on synchronized cultures of P. falciparum to identify the specific site of action of this compound. Synchronized cultures of early rings or schizonts were exposed to 100 microM DFO for up to 48 hr, and fixed and processed at regular intervals for electron microscopy. Untreated cultures and cultures exposed to DFO saturated with Fe3+ were processed at the same time. When DFO was added to synchronized cultures containing early rings, parasites developed normally until the late trophozoite stage, when all growth ceased. Ultrastructural lesions included the breakdown of the nuclear envelope into small membranous fragments and progressive vacuolization of the nucleoplasm. Other organelles, including food vacuoles and mitochondria, were not affected. The addition of DFO to synchronized cultures of schizonts had similar effects on nuclei of early schizonts, but little or no effect on mature schizonts and segmenters. Erythrocyte invasion by merozoites proceeded in the presence of the chelator. These findings support the hypothesis that DFO acts specifically during the late trophozoite/early schizont stage of parasite maturation by preventing nuclear division, an effect consistent with inhibition of the iron-dependent enzyme ribonucleotide reductase.

Animals↗
PubMed1990

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The significance of 'dry tap' bone marrow aspirations in Zimbabweans.

Of the 2880 bone marrow examinations performed in a 3-year period in patients with diverse haematological and oncological disorders, 116(4%) patients exhibited 'dry tap' on routine marrow aspiration. However, when the Jamshidi-Swaim technique of trephine bone marrow biopsy was performed in these patients, the single commonest underlying pathological cause of 'dry tap' was found to be aplastic anaemia which accounted for 56(48.3%) of the cases. The diagnostic potential of the technique and its advantages particularly in a developing country are briefly high-lighted.

Adolescent↗
PubMed1989

Homozygous alpha+ thalassaemia in Zimbabwe: an unrecognized cause of hypochromia and microcytosis.

The prevalence of probable homozygous alpha+ thalassaemia in Zimbabwe was found to be 3.25 percent in a survey of hospital patients (n = 2,000), 7.6 percent in a Batonga village (n = 66), and 5.3 percent in 16 kindreds (n = 94) investigated for iron overload. The diagnosis was based on finding a reduced mean cell volume (MCV), reduced mean cell haemoglobin (MCH), increased red cell count (RBC), and a normal Haemoglobin. These cases usually had a normal red cell distribution width (RDW), and of three discriminant functions tested the MCV2 x MCH was the most useful. Iron deficiency was excluded in the community based surveys. The importance of recognizing these changes is emphasized so that inappropriate iron therapy is not given.

Adolescent↗
PubMed1989

A prospective analysis of 620 bone marrow examinations in Zimbabwe: preliminary observations.

Of the 1,310 bone marrow examinations performed in a 16-month period in patients with diverse haematological, oncological and other disorders, 620 had sufficient data for analysis. Seventy-nine percent were from the two main hospitals viz: Parirenyatwa and Harare Central Hospitals. Investigation for anaemia (42.6 percent), staging of malignant disease (14.4 percent) and pancytopenia (10.3 percent) formed the commonest triad of indications for requesting the examination. There were 318 (51 percent) males, mean age +/- s.d. of 33.8 +/- 22.6 years (range 6 months to 80 years); and 302 (49 percent) females, mean age +/- s.d. of 32.6 +/- 20.7 years (range 6 months to 78 years) giving a male to female ratio of 1.1:1. Of the 620 patients studied, 452 (73 percent) were adults (M:F ratio of 1:1) mean age +/- s.d. of 42.8 +/- 17.3 years (range 16-80 years); and 168 (27 percent) were children (M:F ratio of 1.1:1) mean age +/- s.d. of 7.3 +/- 4.5 years (range 6 months to 15 years). The three commonest diseases in the combined (adults and children) group were: megaloblastic anaemia (25.2 percent); acute or chronic leukaemia (19.2 percent) and iron deficiency anaemia (10.5 percent). These three diseases respectively accounted for 32 percent, 17.5 percent and 10.8 percent of the cases in the adult (16 years and over) group; whereas in the paediatric (0-15 years) group, the top three diseases were: acute leukaemia (22 percent); Hodgkins and non-Hodgkins lymphomas (14.3 percent) and retinoblastoma (13.7 percent). These preliminary observations indicate some of the commonest haematological and oncological disorders where intense research might be beneficial to the community in Zimbabwe.

Adolescent↗
PubMed1988

Interleukin 1 administration in mice produces hypoferremia despite neutropenia.

To determine whether the hypoferremic response to inflammation requires neutrophils, we administered human recombinant IL-1 to mice made neutropenic with cyclophosphamide. With single intraperitoneal injections of IL-1 the plasma iron concentrations decreased significantly in mice with either normal neutrophil counts or neutropenia. After single injections transferrin concentrations were not significantly changed, but the decrease in serum iron lowered mean transferrin saturations from a baseline of 45 to 24-30% in nonneutropenic mice, and from 99 to 70-77% in neutropenic mice. Similar changes were observed after intraperitoneal injections of Escherichia coli. 4-d continuous infusions of IL-1 also led to reductions in serum iron concentrations, but transferrin concentrations doubled. The combination of a decrease in serum iron and an increase in transferrin concentration after chronic infusion in neutropenic mice led to a greater decline in mean transferrin saturations, from a baseline of 110 to 25%. In mice not given cyclophosphamide, chronic IL-1 infusion was associated with a reduction in mean hemoglobin concentrations from 14.7 to 13.5 g/dl, consistent with restricted availability of iron for erythropoiesis associated with low saturation of transferrin. We conclude that IL-1 can decrease the serum iron despite profound peripheral neutropenia and that transferrin in a positive acute phase reactant in the mouse.

Agranulocytosis↗
PubMed1987

High-dose carbonyl iron for iron deficiency anemia: a randomized double-blind trial.

To determine if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia, high-dose Fe 600 mg three times per day (given as nontoxic carbonyl Fe) was compared with standard ferrous sulfate 60 mg Fe++ three times per day in a randomized, double-blind, 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia. In animal studies, both forms of Fe have similar bioavailability when administered in equal amounts. High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with standard FeSO4 therapy. The 10-fold larger amount of Fe resulted in a mean 1.5-fold increase in estimated Fe absorption. Both regimens corrected anemia but neither replenished storage Fe. These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given.

Adolescent↗
PubMed1986

Dietary iron overload persists in rural sub-Saharan Africa.

In a survey of 505 rural Zimbabweans, iron overload was found almost exclusively among men who consumed traditional beer brewed in steel drums. Among drinkers aged over 45 years, 23 of 111 men (21%) had high serum ferritin and a transferrin saturation of over 70%, a combination that indicates a risk of liver disease and other pathological effects from excess body iron. Iron overload, which is reported to be decreasing among urban Africans, may remain a public health issue in rural areas where more than 80% of the people of sub-Saharan Africa live.

Adult↗
PubMed1986

Iron therapy for hepatic dysfunction in erythropoietic protoporphyria.

Erythropoietic protoporphyria, caused by an inherited deficiency of ferrochelatase, results in increased free protoporphyrin concentrations in erythrocytes and plasma. Cutaneous photosensitivity is the primary clinical manifestation, but in some patients, protoporphyrin accumulation in the liver may lead to fatal hepatic failure. No treatment exists for this lethal complication. We report the case of a patient with erythropoietic protoporphyria and abnormal results of liver function tests in whom oral iron therapy led to a substantial decrease in free erythrocyte and stool protoporphyrin levels with return of liver function to normal. Iron therapy should be considered for preventing potentially fatal hepatic failure in patients with erythropoietic protoporphyria.

Administration, Oral↗
PubMed1986

Hyperferremia in immunosuppressed patients with acute nonlymphocytic leukemia and the risk of infection.

Hypothesizing that any effect of an increased serum iron and transferrin saturation on the risk of bacterial infection would be particularly important in immunosuppressed patients, we reexamined the effect of hyperferremia on bacterial growth in vitro and studied the pattern and prevalence of hyperferremia in patients receiving treatment for acute nonlymphocytic leukemia (ANLL). Growth of inocula of Escherichia coli and Staphylococcus aureus was significantly greater (1.3- to 5.8-fold) in fresh or heat-inactivated sera obtained from 10 healthy volunteers 3 hours after oral ingestion of ferrous sulfate (mean +/- SEM transferrin saturation 95% +/- 3%) than before (transferrin saturation 34% +/- 10%). Similarly, in heat-inactivated serum samples obtained from six patients with various malignancies, growth of E. coli was significantly greater (2.3- to 5.5-fold) with the elevated transferrin saturation (97% +/- 3%) present 1 to 7 days after receiving chemotherapy than with the normal transferrin saturation (33% +/- 9%) present before. In a prospective evaluation of serial serum iron studies in 12 patients receiving treatment for ANLL, five patients had normal serum iron concentrations initially, but in each patient the transferrin saturation was elevated after receiving chemotherapy, usually to greater than 90% for greater than 15 days in conjunction with prolonged, profound granulocytopenia and fever.

Acute Disease↗
PubMed1986

Carbonyl iron therapy for iron deficiency anemia.

To determine if elemental carbonyl iron powder is safe and effective therapy for iron deficiency anemia, 20 nonanemic and 32 anemic volunteers were studied. Single doses of 1,000 to 10,000 mg of carbonyl iron (15 to 150 times the 65 mg of iron in the usual dose of ferrous sulfate) were tolerated by nonanemic volunteers with no evidence of toxicity and only minor gastrointestinal side effects. Anemic volunteers (menstruating women who had previously donated blood) were treated with several regimens providing 1,000 to 3,000 mg of carbonyl iron daily in one to three doses for 8 to 28 days. After 12 weeks anemia was corrected in 29 of 32 patients, and serum ferritin was greater than 12 micrograms/L in 14. Hemoglobin regeneration proceeded at a rate similar to that described for therapy with oral iron salts and parenteral iron dextran. There was no evidence of hematologic, hepatic, or renal toxicity, but mild gastrointestinal side effects occurred in a majority of anemic volunteers. Carbonyl iron is an effective, inexpensive treatment for iron deficiency anemia, is accompanied by tolerable side effects and may have an advantage over therapy with iron salts by substantially reducing or eliminating the risk of iron poisoning in children.

Adult↗
PubMedDate not supplied

The antimalarial effect of iron chelators: studies in animal models and in humans with mild falciparum malaria.

In this study we explore the antimalarial effects of 3-hydroxypyridin-4-ones (CP compounds), a family of bidentate orally effective iron chelators in experimental animal systems in vivo and in vitro, and examine whether the iron chelator deferoxamine (DF) is active against human infection with P. falciparum. There was direct relation between lipid solubility of the CP compounds, which would facilitate membrane transit, and their in vivo antimalarial action, suggesting direct intracellular iron chelation as the most likely explantation for the antimalarial effect of iron chelators. Results of the double-blind, placebo controlled trial of DF in humans with asymptomatic parasitemia provided unequivocal evidence that this iron-chelating agent has antimalarial activity. Depriving the parasite of a metabolically important source of iron may represent a novel approach to antimalarial drug development. DF is a relatively ineffective intraerythrocytic chelator, and our data indicate that other orally effective iron chelators may have superior antimalarial activity in vivo. A systematic screening of available iron chelating drugs may result in the identification of potentially useful antimalarial compounds.

Animals↗
PubMedDate not supplied

Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.

To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18.3% (32/175) in the deferoxamine group and 10.7% (19/177) in the placebo group (adjusted odds ratio 1.8; 95% confidence interval 0.9-3.6; P = 0.074). At the rural study site, mortality was 15.4% (18/117) with deferoxamine compared to 12.7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24.1% (14/58) with deferoxamine and 6.8% (4/59) with placebo (P = 0.061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1.2; 95% confidence interval 0.97-1.6; P = 0.089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.

Antidotes↗
PubMedDate not supplied

Loading dose of quinine in African children with cerebral malaria.

The majority of deaths from cerebral malaria occur within 48 h after admission to hospital. Because of the possibility of inadequate treatment within this period, the use of a loading dose of quinine has been proposed. We reviewed clinical and laboratory data for 113 children with cerebral malaria, who were treated with intravenous quinine, 10 mg/kg every 8 h, at Macha Mission Hospital in rural Zambia. In 1990-1991, 39 children were not given a loading dose of quinine while, in 1992-1993, 74 children received a loading dose of 20 mg/kg. Elevated serum iron levels, as reflected in transferrin saturation, were strongly associated with higher mortality. A loading dose of quinine was associated with faster recovery from coma and enhanced clearance of parasitaemia and fever. The loading dose was also associated with trends to lower mortality and higher haemoglobin levels, but these differences were not statistically significant.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Carbonyl iron for short-term supplementation in female blood donors.

A randomized, double-blind trial of iron replacement after repeated blood donation was conducted in 75 menstruating women; 51 completed the study. Volunteers were assigned randomly to one of three treatment groups: 1) carbonyl iron (nontoxic elemental iron powder), 600 mg; 2) ferrous sulfate, 300 mg (60 mg Fe++); or 3) placebo, each given three times daily for 1 week immediately after blood donation. Blood samples obtained initially and 56 days later were tested for hemoglobin, mean corpuscular volume (MCV), free erythrocyte protoporphyrin, serum ferritin, serum iron, total iron binding capacity (TIBC), and percent saturation of TIBC. The prevalence of gastrointestinal side effects was similar in both groups taking iron. At the end of the study there was no laboratory evidence of change in iron status in women who received carbonyl iron (n = 15). In those treated with ferrous sulfate (n = 17) the mean TIBC increased (p less than 0.001), and in the placebo group (n = 19) there were decreases in mean MCV (p less than 0.01), serum ferritin (p less than 0.001), and percent saturation (p = 0.027) with an increase in mean TIBC (p = 0.004). Carbonyl iron seems to be effective for short-term iron replacement in repeat blood donors and may have the advantage of decreased or absent risk of poisoning if accidentally ingested by children.

Blood Donors↗