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G Birgegård

Publications and source records attributed to G Birgegård.

At least 19 recordsLinked to original sources

Beta-globin mRNA increases rapidly during erythropoietin treatment.

Recombinant human erythropoietin (r-HuEpo) has an important role in the treatment of anaemic patients. Because of the high cost of r-HuEpo treatment, an early indicator of whether a patient is responding to the therapy would be valuable. Although measurement of gene expression is a promising new tool, it has not yet been established in clinical practice. The response pattern of a possible new marker, beta-globin mRNA, is compared with reticulocyte count, levels of haemoglobin, transferrin receptor and ferritin after r-HuEpo treatment. Eight healthy volunteers were stimulated with erythropoietin three times a week for four weeks and compared with five untreated control subjects. Blood samples were collected before each erythropoietin injection. Quantitative measurement of beta-globin mRNA was performed by poly(A) selection onto a manifold plastic support, coated with oligo(dT). The mRNA was reverse transcribed, followed by quantitative analysis using PCR via the 5' nuclease assay. The individuals treated with rHuEpo showed a more distinct increase in beta-globin mRNA levels than all other laboratory measurements. Beta-globin mRNA levels are therefore promising as a marker for the response to treatment with Epo.

Adult↗

Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells.

UNLABELLED: Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. RESULTS: due to the sampling (26 ml each time, three times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142 g/L (p<0.002). The 2,3-DPG mean level curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p < 0.002), the treatment group showing higher levels. CONCLUSION: treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

2,3-Diphosphoglycerate↗

The measurement of venous haematocrit in patients with polycythaemia vera.

OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.

Aged↗

Change in student attitudes to medical school after the introduction of problem-based learning in spite of low ratings.

Students' attitudes to, and opinions of, their studies at medical school were investigated with the help of a questionnaire. They were asked to what extent the medical school encouraged independent, critical thinking, problem-solving skills, decision-making, studying outside the textbook and other behaviours and skills that teachers in higher education usually put forward as important. It was found that students generally had a low opinion of the extent to which their education encouraged such virtues, mean figures ranging between 3.5 and 4.6 on a 10-grade scale. The students felt that their studies to a large extent encouraged focus on details and preparation for examinations. The questionnaire was given to the students after 2 1/2 years of traditional preclinical studies and at the end of the first clinical year. There were significant but numerically small differences for some of the items at the end of the year. However, when problem-based learning (PBL) was introduced during the first clinical year, there was a substantial change: there were now significant and numerically larger differences for seven of the nine items, even though the students were asked to give their opinion of the whole of their time at medical school on both occasions, not only of the last year. There were no other changes in the curriculum or the teaching methods other than the introduction of PBL. The change in attitudes did not depend on the student's appreciation of PBL; students' opinion of PBL was low, indicating that most of them disliked it.

Attitude↗

Preoperative autologous donation of 6 units of blood during rh-EPO treatment.

PURPOSE: To determine if donation of six units of blood in three weeks is possible with self-administered subcutaneous recombinant human erythropoietin (rhEPO) injections and oral iron treatment. METHODS: A prospective trial where a total of 32 otherwise healthy patients were phlebotomised before revision hip arthroplasty during rhEPO and oral iron treatment (ferrofumarate). Adverse events were noted and compliance was controlled. Routine laboratory tests were performed at each visit including reticulocytes and 2,3-DPG. The relative oxygen releasing capacity (RORC) and the oxygen releasing capacity (ORC) were calculated. Blood donation was postponed until the next visit if haemoglobin concentrations was < 115 g.l-1 (men) or < 105 g.l-1 (women). RESULTS: All but two patients were able to donate six units of blood with an acceptable haemoglobin concentration on the day of operation. One serious adverse event occurred when the Hb was 119 g.l-1, compared with 149 g.l-1 before treatment. During the first two weeks before phlebotomy there was no increase in Hb, the mean nadir was reached after six phlebotomies (31 g.l-1 below pre-study level), while at operation it was 19 g.l-1 below pre-study level. There was an increase in 2,3-DPG and oxygen releasing capacity after the initiation of rhEPO therapy, before the first phlebotomy. CONCLUSION: It is possible to donate six units of blood in a three week period before surgery during self-administered subcutaneous rhEPO treatment and oral iron therapy at a rhEPO dose of 60 U.kg-1 BW three times a week. It is suggested that rhEPO per se initiates a right-shift of the oxygen dissociation curve via an increased 2,3-DPG level, which could explain that some patients report subjective benefit of rhEPO in spite of no change in Hb concentration.

2,3-Diphosphoglycerate↗

Assessment of erythropoiesis following renal transplantation.

Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22) ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.

Adult↗

Iron absorption in patients with chronic uremia on maintenance hemodialysis and in healthy volunteers measured with a simple oral iron load test.

Gastrointestinal iron absorption was measured by an oral iron load test in patients with uremia on maintenance hemodialysis (n = 19), with iron overload (n = 9), iron deficiency (n = 10) and in healthy volunteers (n = 9). After an overnight fast, serum iron was measured before, and 1, 2, 4 and 6 h after administration of 100 mg ferrous chloride. Bone marrow iron was assessed after staining with Prussian blue. The study shows that iron absorption is impaired in uremic patients. Even uremic subjects with iron deficiency absorbed significantly less than normal subjects. Patients with iron overload and uremia absorbed even less, showing that the iron status of the patient influences absorption also in uremia.

Adult↗

Serum erythropoietin and erythropoiesis during six years after kidney transplantation.

We have studied serum erythropoietin (EPO) levels during 6 years after kidney transplantation in 16 patients. There was a serum EPO peak around 50 mU/ml after 5 weeks. After 3 months the serum EPO level stabilized at around 30 mU/ml. Patients with good transplant function had significantly higher serum EPO levels and normalized their hemoglobin (Hb) after a mean of 3 months. If transplant function was good, Hb was normalized even if the serum EPO was only slightly elevated. Patients with poor transplant function had lower serum EPO and Hb levels. We concluded that a good transplant function is the key to a normal erythropoiesis and that small amounts of EPO are needed to improve Hb.

Adult↗

Information to and communication with cancer patients: improvements and psychosocial correlates in a comprehensive care program for patients and their relatives.

Between 1987 and 1989, 177 cancer patients who were to receive intensive chemotherapy with curative intention, participated in a comprehensive care project with the aim of improving their total situation, and that of their relatives (n = 120). A number of steps were taken to improve, among other things, the information to, and communication with, patients and their relatives. Compared with a pre-project evaluation in 54 patients and 24 relatives, significantly lower problem scores were seen in most aspects relating to interaction with medical staff. Strong associations were seen between, on the one hand, various aspects of patient- and relative-staff interaction and, on the other, psychosocial problems, although they were weaker for problems relating to information, than for communication and control problems.

Communication↗

Treatment of erythropoietin-resistant anaemia with desferrioxamine in patients on haemofiltration.

We studied 5 anaemic patients with Hb 74 +/- 8 g/l on haemofiltration (HF) treatment. They were iron overloaded. Their serum ferritin was 2667 +/- 8 micrograms/l. All patients' haemoglobin (Hb) levels decreased after an initial response to recombinant human erythropoietin (r-HuEPO) treatment. An increase in r-HuEPO dose from 100 to 400 U/kg s.c. thrice weekly with addition of oral and intravenous iron treatment for 8 weeks arrested the fall in Hb level. However, there was no significant increase in Hb during these 8 weeks. Iron was withdrawn at week 24 and desferrioxamine (DFO) treatment (i.v. doses of 2 g thrice weekly) was added to r-HuEPO from week 26 to 36. Two weeks after DFO initiation the Hb level increased to 110 g/l. Thereafter the r-HuEPO doses were reduced from 400 to 25 U/kg within 3 months. The Hb remained stable at a level of 110 g/l during the study, i.e., 17 months after the DFO treatment. Serum ferritin levels fell at a more rapid pace during DFO treatment and continued to decrease after DFO cessation for the following 17 months. In accordance with previous observations we found a positive effect of DFO treatment on erythropoiesis in patients with anaemia and iron overload. DFO treatment should be considered in patients with iron overload and r-HuEPO-resistant anaemia.

Adult↗

A combination of granulocyte colony-stimulating factor and erythropoietin may synergistically improve the anaemia in patients with myelodysplastic syndromes.

In an attempt to obtain a synergistic effect on the hemoglobin levels in anaemic patients with myelodysplastic syndromes (MDS), granulocyte colony-stimulating factor (G-CSF) and erythropoietin (epo) were combined in a clinical phase II trial. Twenty-two patients with MDS were included in the study. G-CSF was given alone for six weeks and then in combination with epo for the following twelve weeks. Eight (38%) of 21 evaluable patients showed a significant increase in hemoglobin. One patient with a previous response and subsequent failure to epo alone improved after the addition of G-CSF. Responses were more frequent in patients with less advanced pancytopenia, lower endogenous levels of serum-epo and in those with ring sideroblasts in the bone marrow. The response frequency of 38% is higher than in any study of epo as monotherapy. Moreover, patients with ring sideroblasts, who respond poorly to epo alone, showed a response rate of 60%. Our findings suggest a synergistic in vivo effect of granulocyte-CSF and erythropoietin in patients with myelodysplastic syndromes.

Adult↗

Serum erythropoietin in the diagnosis of polycythaemia and after phlebotomy treatment.

Serum erythropoietin (S-Epo) was measured with a radiommunoassay method in 36 patients with polycythaemia vera, 17 patients with secondary polycythaemia and 14 patients with relative polycythaemia. The diagnoses were made without the aid of the S-Epo values. It was found that S-Epo was below the reference range in 34/36 patients with polycythaemia vera (mean 2.1 +/- 1.0 U/l), elevated in all cases of secondary polycythaemia (mean 121.7 +/- 242 U/l) and normal in all but one of the cases with relative polycythaemia (mean 7.0 +/- 2.5 U/l). Previous studies of S-Epo levels in the differential diagnosis of polycythaemia have shown significant differences between the means of the groups but a considerable overlap. After phlebotomy treatment to normal haematocrit levels, the S-Epo levels remained subnormal in most of the polycythaemia vera patients even after 18 months at a haematocrit around 45%. Two patients who had been kept at normal haematocrit for 6 and 7 years both had subnormal S-Epo. We conclude that with an Epo assay method of high sensitivity and specificity it is possible to differentiate between different forms of polycythaemia with a high degree of certainty, even between patients with relative polycythaemia and polycythaemia vera patients. The reason why S-Epo remains low in spite of a normal haematocrit in treated polycythaemia vera patients is not known.

Bloodletting↗

Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin.

Eleven patients with chronic inflammatory arthritides and haemoglobin concentrations less than 105 g/l with symptoms from their anaemia were treated with a dose of 250 IU/kg/week of recombinant human erythropoietin for six weeks. The treatment was given as subcutaneous injections five days a week. All patients had active inflammatory disease. Nine patients responded to treatment with an increase in haemoglobin of more than 15 g/l. The mean (SD) haemoglobin concentration increased from 93.0 (8.0) g/l before treatment to 115.0 (12.0) g/l after six weeks. There was no correlation between the initial serum concentration of erythropoietin and the response. It was concluded that anaemia in chronic inflammatory arthritides responds to treatment with subcutaneous injections of recombinant human erythropoietin.

Administration, Cutaneous↗

Serum erythropoietin levels in the immediate kidney-posttransplant period.

Following successful kidney transplantation, renal anemia is gradually corrected during the first 3-4 months. Serum erythropoietin (EPO) levels are increased after the first postoperative day following grafting. In this study, the serum EPO levels in the early posttransplant phase were investigated in 8 living-donor and 7 cadaveric-kidney transplant recipients with special emphasis on the first 24 h. Despite a considerable difference in cold ischemic time of the graft in the two groups the increase in serum EPO levels was noticed at about the same time (8 h) in both groups and the first peak of serum EPO, which was observed after 24 h, reached the same level in both groups. After 9-11 days, serum EPO reached levels which usually are observed during the first months following transplantation. The EPO response seems to be blunted in relation to the degree of anemia in the early posttransplant phase.

Adult↗

Improved care of patients with small cell lung cancer. Nutritional and quality of life aspects.

A comprehensive cancer care project was carried out in Uppsala with the aim of improving the overall situation for patients treated with intensive chemotherapy with curative intent. This report gives the results in 58 patients with small cell lung cancer (SCLC), focusing on the nutritional aspects of the care and chemotherapy-related adverse effects. Responses, survival and simple nutritional parameters were compared with a historical control group (n = 81), and quality-of-life parameters with a pre-project group (n = 22). Groups were comparable with respect to pre-treatment characteristics. In contrast to the historical control group, weight, body mass index and S-albumin did not decrease during treatment in patients diagnosed during the project period. Yet, food intake in the study group was low, and for most patients below what is recommended. Survival, proportion of responses and response duration did not differ from those of the control group. Compared with the pre-project quality-of-life controls, a number of scores were more favourable for study patients (n = 36) interviewed in association with the 8th treatment course by a Swedish version of the Cancer Inventory of Problem Situations (CIPS). The global score was lower in the study group than in the pre-project group (0.80 vs 1.20, p < 0.001). Significant differences in a favourable direction were also seen in several higher order factors and miscellaneous subscales constituting the CIPS. On individual items, the study group expressed less problems with appetite/food taste in hospital, nervousness before chemotherapy and worry about adverse effects. The greatest differences in positive direction for the study group were seen within areas where the project focused on caring activities. We therefore conclude that a cancer care project with the present goals and means of intervention can improve the quality of life in patients with SCLC treated with intensive chemotherapy.

Adult↗