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Biomedical subjects

J J Marx

Publications and source records attributed to J J Marx.

At least 91 records · Page 5Linked to original sources
PubMed1994

Erythropoietic activity and iron metabolism in autologous blood donors during recombinant human erythropoietin therapy.

The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 U kg-1 body weight twice weekly during a 3 week period) on variables of erythropoiesis and iron metabolism in 62 autologous blood donors, of whom 32 received rhEPO (epo group) and 30 did not (control group). Patients donated only 2 units of blood and received oral iron in order to restrict phlebotomy-induced decrease of iron stores. Pre-phlebotomy haemoglobin concentration (14.0 +/- 0.8 g dl-1) was completely regenerated in the epo group at surgery (13.7 +/- 1.3 g dl-1); haemoglobin concentration in the control group fell from 13.5 +/- 1.4 g dl-1 to 11.6 +/- 1.4 g dl-1 after the phlebotomies and did not improve during the pre-operative phase. Total erythropoietic activity expressed as serum transferrin receptor concentration (sTfR) showed a 4-fold increase from 3.8 +/- 0.9 micrograms ml-1 to 14.9 +/- 4.8 micrograms ml-1 in the epo group. Effective erythropoietic activity measured by absolute reticulocyte count, however, declined after the fourth rhEPO injection in the epo group. Serum ferritin was lower in the epo group, but no differences in serum iron, transferrin concentration and transferrin saturation were observed between the groups. A marked increase in free erythrocyte protoporphyrin (FEP) was observed in the epo group, whereas FEP levels in the controls remained within normal ranges. Despite oral iron supplementation and the limited number of phlebotomies, the effect of rhEPO therapy in autologous donors is restricted by iron depletion.

Aged↗
PubMed1994

Red blood cell transfusions for total hip replacement in a regional hospital. A six-year analysis.

To evaluate changes in the need for homologous blood and to assess the impact of autologous blood transfusion, red cell transfusions in unilateral total hip replacement surgery, performed electively in the period 1986-1991, were studied in a regional hospital. Transfusion data, perioperative blood loss and post-operative haemoglobin concentration of 495 patients were analysed. From 1986 to 1991, the percentage of patients not transfused with homologous blood increased from 18.5 to 45.5%. After the introduction of an autologous blood transfusion programme in 1987, 116 of 430 patients (27.0%) donated autologous blood. No increase in the percentage of autologous donors was observed during the study. Most common reasons for nonparticipation were the patient's age, doctors' underordering and logistic limitations. 81.9% of autologous donors had total hip replacement surgery without homologous transfusions. Mean blood loss reduced significantly from 1,373 +/- 781 ml in 1986 to 958 +/- 582 ml in 1991 (p < 0.001). Transfusion requirement in the nonautologous patients fell from 2.6 +/- 1.8 units in 1986 to 1.4 +/- 1.4 units per patient in 1989 and increased thereafter to 2.2 +/- 2.1 units in 1991 (p < 0.01) and showed a strong correlation with blood loss (r = 0.58; p < 0.001). No changes in postoperative haemoglobin concentration were observed throughout the study. In conclusion, collection of autologous blood is effective, albeit still underutilized, to reduce homologous blood requirement. The close correlation between blood loss and transfusion requirement accentuates the role of surgical practice in the reduction of homologous transfusions.

Aged↗
PubMed1994

Collection of autologous blood before elective hip replacement. A comparison of the results with the collection of two and four units.

The need for allogeneic blood can be reduced effectively with the use of preoperatively donated autologous blood. However, this collection also results in the waste of autologous blood in a considerable number of patients. In order to reduce overcollection, we requested that the amount of autologous blood donated before a total hip replacement be decreased from four units to two units. We then compared the amount of allogeneic blood required for fifty patients who had donated two units of autologous blood with that of fifty historical controls who had donated four units. The patients were matched for sex, initial hemoglobin concentration, and blood loss. There was no significant difference in the percentage of autologous donors who received additional allogeneic blood; 20 per cent (ten) of the patients who had donated two units and 16 per cent (eight) of the patients who had donated four units required allogeneic blood (p = 0.12). Eighteen autologous units from the patients who had donated two units and fifty-one units from the patients who had donated four units were discarded. The erythropoietic response, measured by the increase in the reticulocyte count, was comparable for the two groups. Iron stores, measured as the serum ferritin concentration, were lower after the drawing of four units (33 +/- 39 micrograms per liter) compared with after the drawing of two units (49 +/- 29 micrograms per liter) (p = 0.03). The donation of two units of blood does not increase the exposure to allogeneic blood compared with the exposure after the donation of four units by patients who are going to have a total hip replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

The effect of recombinant human erythropoietin on hemostasis, fibrinolysis, and blood rheology in autologous blood donors.

Treatment with recombinant human erythropoietin (rhEPO) for the anemia of end-stage renal disease has been associated with thrombotic complications. To detect prothrombotic changes in autologous blood donors given 500 U/kg rhEPO subcutaneously (twice weekly during a 3-week period), changes in variables of hemostasis and fibrinolysis and in blood rheology before and at the end of treatment were investigated. In 21 patients, platelet count increased from 272 +/- 55 x 10(9)/L to 313 +/- 55 x 10(9)/L (p < 0.05). Although activated partial thromboplastin time and protein C antigen decreased significantly during rhEPO treatment, these changes remained within normal ranges. No changes in the hemostatic variables prothrombin time, fibrinogen, factor V, von Willebrand factor antigen, antithrombin III activity, protein S antigen, and prothrombin fragments F 1 + 2 were found. Measurements of plasminogen activity, alpha 2-antiplasmin activity, tissue plasminogen activator, and plasminogen activator inhibitor-1, representing variables of fibrinolysis, were normal and constant during the study. In 5 patients no changes in red cell deformability and whole blood viscosity, corrected for differences in hematocrit, were observed. Plasma viscosity showed a slight but clinically not relevant increase in 4 out of 5 patients. The absence of evident (pro)thrombotc changes in this study confirms the safety of high-dose rhEPO therapy in autologous blood donors, who donate 2 units (i.e., 2 x 450 ml) of blood.

Aged↗
PubMed1993

Doxorubicin-mediated free radical generation in intact human tumor cells enhances nitroxide electron paramagnetic resonance absorption intensity decay.

The decay of nitroxide spin label electron paramagnetic resonance (EPR) absorption intensity was used to investigate the doxorubicin-mediated intracellular generation of free radicals. The effects of 50-500 micrograms/ml doxorubicin on human tumor cells (MCF-7, breast cancer cells, and HL-60, promyelocytic leukemia, cells) were studied by measuring 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) absorption intensity decay (TAID) at a TEMPO concentration of 10 microM. Doxorubicin accelerated the TAID in both cell lines with a detection limit of 50 micrograms/ml for MCF-7 cells and 500 micrograms/ml doxorubicin for HL-60 cells. Preincubation of cells with the iron chelating agent, deferoxamine (5 mM), partially prevented the effects of doxorubicin on the TAID. Catalase and copper, zinc-superoxide dismutase (Cu,Zn-SOD) had no influence on the effects of doxorubicin on the TAID in intact cells. However, Cu,Zn-SOD completely abolished the effects of doxorubicin on the TAID in a MCF-7 cell-free system. Our findings suggest that doxorubicin mediates the intracellular generation of O2.- and that iron is involved in this process.

Cyclic N-Oxides↗
PubMed1993

Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity.

A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study.

Adult↗
PubMed1993

Mucosal uptake, mucosal transfer and retention of iron in veal calves.

A method for studying iron absorption in humans was adapted to veal calves. Three 10-week-old calves with moderate (calves 1 and 2) or severe (calf 3) iron deficiency were given an abomasal injection of 59Fe and 51Cr and all their faeces were collected over 15 days in order to measure mucosal uptake, mucosal transfer and retention of iron. The mucosal uptake was 62.2, 53.4 and 71.8% in calves 1, 2 and 3, respectively. The iron retention measured 14 days after administration of the test dose was 57.4, 52.3 and 56.4% in calves 1, 2 and 3, respectively. Maximal plasma activity was found in all three calves between 1 1/2 and 2 h after injection of the test dose. The plasma activity decreased rapidly, with a slight increase between the 5th and the 10th hour. After 21 h, less than 0.25% of the injected dose was still present in 1 litre of plasma. Not all the 51Cr was recovered in the faeces. No 59Fe was found in the urine but some 51Cr could be detected. The results of this study show that the method described is useful for measuring the different steps of iron absorption in iron-deficient veal calves.

Anemia, Hypochromic↗
PubMed1993

An electron paramagnetic resonance study of the antioxidant properties of the nitroxide free radical TEMPO.

Previous reports of superoxide scavenging and ferroxidase-like activity of nitroxide free radicals have greatly increased interest in the ability of these compounds to protect cells against oxidative cellular damage. In the present study we investigated the antioxidant properties of the six membered nitroxide 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) in various assays. TEMPO (5 mM) inhibited the hydroxyl radical mediated generation of ethylene from 2-keto-4-methylthiobutyric acid to 31.2 +/- 4.0% of control values. Furthermore, we noted that TEMPO had the ability to maintain iron in its ferric form, a finding with strong implications for the interpretation of the ferricytochrome c reduction assay. TEMPO may be reduced to an electron paramagnetic resonance silent hydroxylamine by a number of pathways. TEMPO absorption intensity decay (TAID) was monitored to investigate the effects of hydrogen peroxide on Cu,Zn-SOD. TEMPO was found to effectively scavenge or suppress formation of hydroxyl radicals inside Cu,Zn-SOD. The generation of hydroxyl radical was confirmed by employing the conventional spin trapping agent DMPO. Using radical scavengers unable to penetrate the Cu,Zn-SOD enzyme (e.g., mannitol, ethanol, albumin) or compounds with access to copper within the Cu,Zn-SOD enzyme (azide and cyanide), we could not detect hydroxyl radicals outside the enzyme. Finally, since the electron paramagnetic resonance absorption intensity is directly proportional to the concentration of TEMPO spins, loss of absorption intensity provided information concerning radical-mediated processes. Therefore, the decay kinetics of TEMPO may be used as a very sensitive alternative to conventional spin traps.

Antioxidants↗
PubMed1993

Radioisotopic labels for blood cell survival studies: a review.

The different methods of labeling blood cells, in particular erythrocytes and platelets, for survival studies are reviewed. Besides the technical information about these procedures, attention is also paid to the indications of blood cell survival studies, the effective dose equivalent involved and the interpretation of the resulting data. In the final section the possibilities created by dual-labeling procedures are discussed.

Animals↗
PubMed1993

Viability of platelets collected by apheresis versus the platelet-rich plasma technique: a direct comparison.

Different platelet preparation techniques have not previously been compared directly and simultaneously with respect to in vivo platelet viability. Using a dual-label technique with 111-In and 114m-In, platelet apheresis was compared with the platelet-rich plasma (PRP) procedure with respect to platelet recovery and survival (n=4). Furthermore, a continuous flow cell separator (Cobe 2997) and an intermittent apheresis system (Haemonetics V50) were compared with each other (n=4). No differences in platelet viability were found between the PRP-platelets and the apheresis-platelets. Also no differences were found between the two apheresis systems. Although different platelet preparation methods result in a varying degree of platelet activation, no difference in platelet viability has been observed.

Adult↗
PubMed1993

The efficacy of subcutaneous recombinant human erythropoietin in the correction of phlebotomy-induced anemia in autologous blood donors.

The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3-week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 +/- 1.0 g/dL [140 +/- 10 g/L]) was completely recovered before surgery (14.0 +/- 1.6 g/dL [140 +/- 16 g/L]) in the EPO group, while a decrease from 13.8 +/- 1.1 to 12.2 +/- 1.3 g per dL (138 +/- 11 to 122 +/- 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 +/- 29 micrograms per L in the EPO group and to 54 +/- 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Increased exposure to cryptosporidia among dairy farmers in Wisconsin.

Cryptosporidium infection is an important cause of diarrhea in humans and livestock; no effective therapy is known. A self-administered questionnaire and an ELISA were used to assess the risk of exposure to cryptosporidia among 70 dairy farmers and 50 who were not dairy farmers in Wisconsin. Dairy farmers (44.3%) were more likely to be seropositive for cryptosporidia than were other persons (24.0%; relative risk = 1.9). Among dairy farmers, age > or = 50 and use of a canister method of milking were associated with seropositive status. Among persons who were not dairy farmers, feeding or milking cows was associated with being seropositive. These findings suggest that dairy farmers and other persons who have contact with cattle are at greater risk of Cryptosporidium infection than are persons who do not have such contact. Identification and avoidance of farming practices associated with Cryptosporidium infection may reduce the risk of infection among dairy farmers.

Adult↗
PubMed1993

The in vitro response of human tumour cells to desferrioxamine is growth medium dependent.

Iron chelating agents have been demonstrated to inhibit tumour cell growth. However, in vitro and in vivo results using desferrioxamine a hexadentate iron chelating agent, for anti-cancer treatment are not always in agreement. Therefore, we have studied the response of three human tumour cell lines (HL-60 promyelocytic leukaemia, MCF-7 breast cancer and HepG2 hepatoma), grown in culture medium supplemented with either human pooled (HPS) or fetal bovine serum (FBS), to desferrioxamine. Desferrioxamine, at micromolar concentrations, induced severe cytotoxicity in all tumour cell lines grown in FBS medium. When grown in HPS medium, comparable desferrioxamine cytotoxicity was observed in the millimolar range. The addition of 50% saturated human transferrin to FBS medium resulted in protection against desferrioxamine cytotoxicity. HL-60 cells were further studied for iron metabolism characteristics. HL-60 cells, grown in medium with FBS, were found to have an 8.4 fold increase in surface transferrin receptor (TfR) expression (P < 0.001) as compared with HL-60 cells grown in medium with HPS. However, iron uptake of HPS cultured HL-60 cells, after incubation with saturated human transferrin, was higher, resulting in a higher concentration of iron in HPS cultured HL-60 cells as compared with FBS cultured cells (1.72 +/- 0.02 mumol/g protein v. 1.32 +/- 0.14 mumol/g protein; P < 0.001). Using desferrioxamine it was shown that TfR expression is dependent on the biological availability of iron in the cell. Consistent with the lower iron content in FBS cultured cells, we conclude that the cytotoxicity of desferrioxamine is dependent on the ability of cells to replenish cellular iron stores from the culture medium. Cells grown in FBS medium lack this ability and are therefore more susceptible to desferrioxamine.

Biological Availability↗
PubMed1993

Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria.

We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis. The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron-dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mitochondrial electron energy-loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients. These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this failure is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient.

Adult↗
PubMed1993

The effect of porphyrins on cellular redox systems: a study on the dark effect of porphyrins on phagocytes.

Erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) are characterized by skin morbidity, induced by pro-inflammatory reactive oxygen species generated by the photosensitizing properties of protoporphyrin IX and uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the absence of light is poorly understood. We tested the hypothesis that porphyrins can interference with cellular redox systems, by studying the dark effects of protoporphyrin (PP), haematoporphyrin (HP), deuteroporphyrin (DP) and uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic oxyradical generating systems. Both in phagocytic cells and enzymatic systems, a dose-dependent inhibition of chemiluminescence was observed by all porphyrins added. Catalase and SOD-like activity of porphyrins was excluded by oxygraph and ferricytochrome c reduction. However, ferrocytochrome c oxidation was inhibited by porphyrins indicating ferrireductase-like activity. In a Fenton type reaction between H2O2 and PP, we could demonstrate the generation of .OH, or an electronically excited porphyrin species. No influence on phagocyte chemotaxis, phagocytosis and killing-capacity was observed. We conclude that porphyrins do interfere with (cellular) redox systems and can both inhibit and enhance oxygen free radical generation, dependent on the type of redox reaction. Porphyrins can thus affect cellular metabolism. Since H2O2 and PP both readily dissolve in biological membranes, their interaction in the presence of transition metals may contribute to the toxic dark effects of porphyrins as observed in patients with EPP and PCT.

Cytochrome c Group↗
PubMed1993

Inhaled aeroallergen and storage mite reactivity in a Wisconsin farmer nested case-control study.

A nested case-control study was undertaken to assess the role of antibody (Ab) to a panel of antigens associated with hypersensitivity pneumonitis in the development of lung disease among Wisconsin dairy farmers. Immunologic reactivity to a panel of inhaled allergens was assessed in the Ab+ cases and compared to the Ab+ control, Ab- control, and Ab- blue-collar control subjects by skin tests, RAST assays, and a modified American Thoracic Society questionnaire. The most prevalent allergens among the cases as determined by either skin test or RAST assays were the house dust mites (HDM) (21.6%), storage mites (11.2%), grain smuts (11.2%), Cladosporium (7.5%), Aspergillus (6.0%), and cattle (5.2%). No other allergens appeared to be different from in nonfarming populations. Of the storage mite reactors, IgE to Lepidoglyphus destructor (7 of 8) was the most frequently found, followed by Tyrophagus putrescentiae (6 of 8), Glycyphagus domesticus (5 of 8), Chortoglyphus arcuatus (5 of 8), and Acarus siro (2 of 8). L. destructor was also isolated from the farm of one of the cases. There was no difference in the total IgE levels among the groups. Reactions to HDM, storage mites, and grain smuts were significantly more frequent among the cases (p < 0.05). We conclude from this study that there is a significant increase in reactivity to certain inhaled allergens among those dairy farmers reporting barn-associated respiratory symptoms that is unrelated to past exposure to the causative agents of farmer's lung disease.

Agricultural Workers' Diseases↗