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Biomedical subjects

P B Hansen

Publications and source records attributed to P B Hansen.

At least 19 recordsLinked to original sources
PubMed1997

Is the arterial switch operation still a challenge in small centers?

OBJECTIVE: In the last years, major changes as regards timing for operation, surgical technique, and perioperative care determined a great improvement in the arterial switch operation (ASO) allowing excellent mid-term results in a few leading centers. This stimulated the widespread adoption of ASO as procedure of choice for transposition of the great arteries (TGA), even in small institutions. We reviewed our early experience with ASO in an attempt to evaluate its safety in a small center. METHODS: Since April 1992, 39 consecutive patients underwent TGA repair by ASO in our department. There were 27 patients with simple TGA, 8 with TGA and VSD and 4 with Taussig-Bing heart and aortic coarctation. Median age and weight at operation were 7 days and 3.5 kg, respectively. Neonatal repair was performed in 34 patients. In accordance with the Planché coronary classification, type I was encountered in 21 patients, type II in 4 and type III in 14. Several modifications of the original technique were used, mainly regarding coronary relocation, pulmonary artery reconstruction and approaches for associated VSD closure and aortic arch repair. RESULTS: Early mortality was 2.6% (n = 1), the only operative death being related to unsatisfactory coronary relocation. Since modified ultrafiltration was adopted, mean ICU stay decreased from 5 +/- 4 days (n = 21) to 2 +/- 1 days (n = 17) (P < 0.05). Three patients required reoperation for residual ASD and/or VSD closure. There were no late deaths. After a mean follow-up of 26 +/- 15 months all survivors are thriving and are currently asymptomatic. CONCLUSIONS: Although this series is rather small, most of the major coronary anomalies and complex anatomic associations were encountered. This experience suggests that neonatal repair of TGA by ASO can be safely accomplished even in small centers. Modified ultrafiltration appears to improve the early outcome of neonates undergoing ASO.

Cause of Death↗
PubMed1996

Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91.

OBJECTIVES: To analyse the distribution of noncytotoxic drugs reported as cause of thrombocytopenia during a 24-year period, and to draw attention to the most commonly involved drugs in modern clinical practice. DESIGN/SETTING: Retrospective study of spontaneous case reports from the Danish reporting system on adverse drug reactions. SUBJECTS: A total of 309 critically reviewed cases of drug-induced thrombocytopenia reported during the period from 1968 to the end of 1991. RESULTS: Sodiumaurothiomalate and the combination sulfamethoxazole with trimethoprim were the most commonly reported single drugs, and nonsteroid anti-inflammatory drugs were the most frequently reported category of drugs. A pronounced shift in the spectrum of causal drugs was observed due to the introduction of new drugs and alterations in drug consumption. At present, valproic acid and measlesmumps-rubella vaccine are most numerously reported. The still-growing list of thrombocytopenia-inducing agents contained 110 different drugs. At present, 20% of reported cases concern drugs not previously registered as causing thrombocytopenia in Denmark. Twenty-five per cent of all cases were caused by drugs which appeared only sporadically in the material. CONCLUSIONS: The spectrum of drugs reported as causing drug-induced thrombocytopenia is broadening and changing progressively, reflecting changes in drug consumption. The most frequently reported drugs at present are valproic acid and measlesmumps-rubella vaccine.

Adolescent↗
PubMed1995

Unexpected hepatotoxicity after priming and treatment with molgramostim (rhGM-CSF) in acute myeloid leukemia during induction chemotherapy.

The effect of supplementing induction chemotherapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in a randomized trial of 18 patients with acute myeloid leukemia (AML). Ten patients received rhGM-CSF, starting on day one to three before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Unexpected adverse effects of rhGM-CSF and chemotherapy combination included a transient decline in plasma coagulation factors II, VII, and X (5 of 5 patients) and an increased transcapillary escape rate of albumin (in 3 of 3 patients tested). The decline in coagulation factors was prevented in subsequent patients by prophylactic treatment with vitamin K. Although the small number of patients studied may not allow a definite conclusion, caution with regard to liver function should be shown in combining rhGM-CSF with intensive chemotherapy.

Adult↗
PubMed1995

Priming and treatment with molgramostim (rhGM-CSF) in adult high-risk acute myeloid leukemia during induction chemotherapy: a prospective, randomized pilot study.

In a randomized study of 18 adult patients with high-risk or advanced acute myeloid leukemia (AML) we investigated the effect of supplementing conventional induction chemotherapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). For comparison, a historical control group of 90 patients treated for de novo AML with conventional chemotherapy during the previous period, 1984-1990, was also analyzed. Before induction chemotherapy, 10 patients were randomized to receiving rhGM-CSF, starting on day 1 to 3 before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Fatal complications and treatment outcome did not differ between the study groups and historical controls. Nor were there any differences between the groups in terms of hematological toxicity, e.g. time to three-lineage regeneration and need for supportive therapy. However, sequential weekly bone marrow examinations revealed a prolonged reduction of the relative number of myeloid (CD33-positive) marrow cells in the rhGM-CSF treated group. Although the small number of patients studied may not permit a definite conclusion, this randomized study did not demonstrate major beneficial effects of combining rhGM-CSF with standard induction chemotherapy in high-risk patients with AML.

Adolescent↗
PubMed1995

Stimulation tests for the bone marrow neutrophil pool in malignancies.

It has been known for decades that blood neutrophilia occurs after the administration of etiocholanolone, adrenocortical steroids, and endotoxins. Neutrophil leukocytosis in general may be due to several mechanisms such as increased stimulation of the myelopoiesis, increased release from the marrow, a shift from the marginated to the circulating pool (demargination), prolongation in the peripheral half-life, and decreased migration of neutrophils from the blood to the tissue. However, the principal cause of the neutrocytosis for each of the above mentioned agents is increased release of neutrophils from the bone marrow reserves. Since a sufficient reserve capacity is a prerequisite for optimal defenses against infections, the marrow response has been used to estimate the dose of chemotherapy expected to be tolerated without life-threatening neutropenia. However, none of the above "test substances" have gained widespread use due to adverse reactions or undesirable effects on neutrophil function. Recent progress in biotechnology has developed recombinant human (rh) hematopoietic growth factors ready for clinical use. Marrow myelopoiesis is stimulated by granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage CSF (rhGM-CSF). The immediate effect, however, is mobilization of mature neutrophil granulocytes to the blood. Bone marrow cellularity seems to influence the neutrophil number mobilized during 24 hours by one subcutaneous injection of either rhG-CSF or rhGM-CSF. A recent pilot study has suggested such a "24 hour stimulation test" to predict severe neutropenia following cyclic chemotherapy. This concept is illustrated by two case reports. The "stimulation test" suggests that we may devise strategies to define patient subsets which may benefit from prophylactic growth factor administration during cyclic chemotherapy.

Bone Marrow↗
PubMed1995

Short-term rhG-CSF priming before chemotherapy does mobilize blood progenitors but does not prevent chemotherapy induced myelotoxicity: a randomized study of patients with non-Hodgkin's lymphomas.

The aim of this study was to evaluate the efficacy, safety and toxicity of short-term priming with recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately after diagnosis but before combination chemotherapy (CHOP) for non-Hodgkin's lymphomas. Of fourteen patients entering the study, seven received five days subcutaneous injection of rhG-CSF (5 micrograms/kg/day) before CHOP (CSF-group), and seven were treated with CHOP alone (control group). Blood samples were studied before and on days 1-5 during rhG-CSF priming as well as twice weekly after treatment. The number of blood and bone marrow progenitors was identified by clonogenic growth day 7, 14 and 21 of GM-CFU in semisolid medium. Blood absolute neutrophil counts increased in all rhG-CSF primed patients. The expansion of marrow myelopoiesis resulted in increased myeloid:erythroid ratios, increased bone marrow cellularity and increased numbers of myeloid progenitors both in the blood as well as the marrow. Chemotherapy induced neutropenia developed on day 9-12 in all patients independent of myeloid growth factor priming. However, neutropenia appeared earlier in the cytokine primed group (P = .0038). Five patients in the CSF-group and three patients in the control group were hospitalized with neutropenic fever, and septicemia was documented in three patients in the CSF-group. RhG-CSF induced expansion of myelopoiesis immediately before combination chemotherapy mobilized sufficient number of blood progenitors for apheresis but did not result in reduction of duration and degree of neutropenia in patients with newly diagnosed non-Hodgkin's lymphoma. Although the small number of patients prevents drawing definite conclusions, this time schedule for priming should be used with caution in the future due to an increased risk of hematologic toxicity.

Aged↗
PubMed1995

Short-term in vivo priming of bone marrow haematopoiesis with rhG-CSF, rhGM-CSF or rhIL-3 before marrow harvest expands myelopoiesis but does not improve engraftment capability.

In an attempt to optimize bone marrow grafts for autologous transplantation 37 sequential patients suffering from various haematological diseases were treated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF) (n = 23) or granulocyte-macrophage CSF (rhGM-CSF) (n = 8) for 5 days or interleukin 3 (rhIL-3) (n = 6) for 10 days before marrow harvest. All patients were in marrow remission at study entry. In contrast to rhIL-3, the administration of rhG-CSF or rhGM-CSF caused a significant (P < 0.01) increase in blood absolute neutrophil count. An increased marrow cellularity and a rise in the myeloid:-erythroid ratio was seen in the majority of patients during therapy, and in the rhIL-3 treated group a rise in the number of megakaryocytes and increased marrow fibrosis was seen in most patients. Moreover, a median of 2-, 5- and 10-fold increase in myeloid progenitors was the result of short-term administration of rhIL-3, rhGM-CSF and rhG-CSF, respectively. However, transplantation performed with primed expanded marrow grafts did not significantly reduce the time to myeloid regeneration when compared to historical controls. In conclusion, the results demonstrate that short-term priming with haematopoietic cytokines before autologous bone marrow stem cell harvest is a safe procedure which effectively expands marrow haematopoisis without enhanced engraftment capability.

Adolescent↗
PubMed1994

[rhG-CSF treatment in cyclic neutropenia. Continuous versus intermittent rhG-CSF treatment in cyclic neutropenia].

Cyclic neutropenia is a stem-cell disorder characterized by regular 21-day cyclic fluctuations in the number of neutrophils in the blood and bone marrow. The neutropenic periods may be complicated by fever, stomatitis and severe infections. In this case report only daily continuous and later intermittent treatment with recombinant human granulocyte colony-stimulating factor (two micrograms/kg) administered subcutaneously effectively prevented recurrent infections.

Adult↗
PubMed1994

Effects of eltanolone on cerebral blood flow and metabolism in healthy volunteers.

BACKGROUND: Eltanolone is a new steroid anesthetic agent that may prove to be useful in clinical practice. The aim of the present study was to evaluate the effects of eltanolone on cerebral blood flow (CBF) and metabolism in healthy volunteers. METHODS: In a randomized cross-over study, eight subjects received intravenous eltanolone 0.6 mg/kg or its vehicle. CBF was measured with the intravenous xenon 133 technique before and 2 and 30 min after administration of eltanolone or vehicle. Cerebral metabolic rate for oxygen (CMRO2) was calculated as the product of the measured cerebral arteriovenous oxygen content difference and the blood flow. RESULTS: CBF decreased from a baseline value of 64 +/- 4 (mean +/- SD) to 42 +/- 6 ml.100 g-1.min-1 at 2 min after administration of eltanolone and only 4% after vehicle. Cerebral oxygen consumption was 4.1 +/- 0.4 ml.100 g-1.min-1 at baseline and decreased to 2.7 +/- 0.6 at 2 min after eltanolone, whereas metabolism did not change significantly after administration of vehicle. At 30 min CBF and Cerebral metabolic rate for oxygen were 16 and 10% less than baseline values, respectively. Coupling between CBF and Cerebral metabolic rate for oxygen was preserved at all measurements. After administration of eltanolone a significant decrease in mean arterial blood pressure of 6 mmHg and a period of hypoventilation were observed. This did not occur after injection of vehicle. CONCLUSIONS: Eltanolone was shown to reduce cerebral oxygen consumption and blood flow in healthy volunteers. Coupling between metabolism and flow was preserved.

Adult↗
PubMed1994

Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy.

Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance spectroscopy (MRS). Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. Spectroscopic examinations were performed with the stimulated echo acquisition mode (STEAM) method on a 1.5 T clinical whole-body imaging unit. A cubic volume of interest (VOI) was selected in the bone marrow of the left iliac bone. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)/l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur. In conclusion, the non-invasive MRS method may be a useful and reliable in vivo examination for expansion of haemopoiesis and a correspondent reduction of fat tissue in bone marrow after priming with recombinant human haemopoietic growth factors.

Adult↗
PubMed1994

Priming with recombinant human hematopoietic cytokines before bone marrow harvest expands in vivo and enhances ex vivo recovery of myeloid progenitors in short-term liquid cultures.

BACKGROUND AND AIM: Short-term liquid marrow cultures (STLMC) are a potential source for autografting. We have previously shown that the quality of such grafts from transplantation candidates may be improved by hematopoietic cytokine support, especially if purified CD34-positive progenitors are cultured. The aim of this preclinical work was to quantitate ex vivo recovery of myeloid progenitors (colony-forming units-granulocyte/macrophage [CFU-GM]) in STLMC before and after short-term, in vivo treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF), granulocyte-macrophage colony-stimulating factor (rhGM-CSF), or interleukin-3 (rhIL-3). EXPERIMENTAL SETUP: Twenty-two sequential patients in marrow remission for hematological malignancies and eligible for autologous marrow transplantation received rhG-CSF or rhGM-CSF for 5 days or rhIL-3 for 10 days before marrow harvest. Marrow samples before and after in vivo priming were studied for CFU-GM in pre- and post-STLMC. RESULTS: After priming with rhG-CSF, rhGM-CSF, or rhIL-3, the number of isolated light-density cells increased nine-, six-, and two-fold, respectively. The total number of sampled (18 mL marrow) myeloid progenitors preculture (day 7/14 CFU-GM x 10(4) increased significantly from median 0.7/1.1 before to 37.3/26.7 after priming with rhG-CSF (n = 8) and from 5.6/3.4 before to 46.6/44.9 after priming with rhGM-CSF (n = 8) but remained unchanged (3.7/1.5 to 3.6/5.7) after priming with rhIL-3 (n = 6). The number of myeloid progenitors postculture (day 7/14 CFU-GM x 10(4) per 18 mL marrow) in cytokine-supported STLMC significantly increased from median 0.3/0.6 before to 7.0/5.3 after priming with rhG-CSF and from 1.9/1.6 before to 24.4/14.4 after priming with rhGM-CSF but remained unchanged (0.4/0.6 to 0.4/0.2) after priming with rhIL-3. Cytokine-primed and purified CD34+ marrow cells may be expanded in STLMC by a cytokine-driven differentiation into late myeloid progenitors and endstage cells. CONCLUSION: In vivo priming of bone marrow cells by hematopoietic cytokines significantly increases the recovery of harvested pre- and postculture myeloid progenitors. During cytokine-supported STLMC, early myeloid progenitors may differentiate into a "very late" progenitor pool with a potential for fast marrow regeneration. The number of such progenitors in cytokine-supported short-term liquid cultures may be sufficient for fast myeloid engraftment and complete peripheral blood or marrow stem-cell support after high-dose chemotherapy.

Antigens, CD↗
PubMed1993

Hypereosinophilic syndrome treated with alpha-interferon and granulocyte colony-stimulating factor but complicated by nephrotoxicity.

A 34-year-old male with hypereosinophilic syndrome (HES) and cardiac complications was treated with recombinant human alpha-interferon (rhIFN) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the attempt to suppress the eosinophilic cell clones and stimulate the neutrophil myelopoiesis in the bone marrow, respectively. After 1 month of pretreatment with rhIFN, rhG-CSF was administered daily for 22 days. Within a few days the combined treatment with rhIFN and rhG-CSF was followed by a marked increase in absolute neutrophil count but complicated by abdominal pain and an increase in plasma creatinine and blood urea nitrogen. The renal failure persisted when rhIFN therapy was stopped but resolved after discontinuing rhG-CSF. The pathogenesis of this reversible renal involvement needs further investigation. In that hematological improvement in vivo as well as in vitro followed the administration of rhIFN and rhG-CSF, a role for combined therapy with these cytokines may be advocated. However, caution with regard to kidney function should be taken with this combination therapy.

Adult↗
PubMed1993

Recombinant human granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes.

The purpose of this study was to improve erythropoiesis in patients with anemia due to myelodysplastic syndromes (MDS). We treated 13 patients first with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for 6 weeks, then with recombinant human erythropoietin (rhEpo) and rhGM-CSF for the next 12 weeks. Five patients had refractory anemia (RA), 3 refractory anemia with ringed sideroblasts (RAS), and 5 refractory anemia with excess of blasts (RAEB). Ten patients were transfusion-dependent at the time of inclusion. Eleven patients completed this phase II study. Five responded with an increase in hemoglobin level (3 patients) or a reduction in transfusion requirement (2 patients). We registered no response in the remaining 6 patients during treatment. Patients responding to combined treatment had relatively low concentrations of plasma Epo and plasma ferritin before treatment with rhEpo and a normal karyotype throughout the study. Long-term bone marrow cultures did not predict the response. Still, responders seemed to have a higher number of colony-forming progenitors than nonresponders. In conclusion, combined therapy with rhGM-CSF and rhEpo may stimulate hematopoiesis and correct or improve anemia in some patients with MDS.

Aged↗
PubMed1993

Blood neutrophil increment after a single injection of rhG-CSF or rhGM-CSF correlates with marrow cellularity and may predict the grade of neutropenia after chemotherapy.

The grade of neutropenia after chemotherapy seems to be correlated to the bone marrow cellularity as judged by biopsies. Prolonged blood neutropenia after sequential chemotherapy reduces dose intensity and increases the risk of severe infections. A predictive non-invasive test for marrow cellularity is needed in the attempt to predict chemotherapy-induced blood neutropenia. Thirty-one patients with haematological disorders were studied with measurements of blood absolute neutrophil counts (ANC) 24 h after a single subcutaneous injection of recombinant human granulocyte colony stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF). Before cytokine administration all patients had bone marrow biopsies performed. The median increase in blood ANC 24 h after cytokine administration was 15.9 x 10(9)/l (range 3.7-34.2) in 18 patients with normo- or hypercellular marrows and only 0.4 x 10(9)/l (range 0.0-11.2) in 13 patients with hypocellular marrows (P < 0.00001). An increase in ANC or more than 5 x 10(9)/l was predictive for normo- or hypercellular bone marrows with a sensitivity and specificity of 94% and 84%, respectively. A subsequent pilot study in selected patients with prolonged neutropenia was performed. The ANC increment in 12 cases before chemotherapy correlated to the grade of neutropenia and may predict the risk of febrile neutropenia. It is suggested that blood responsiveness to myeloid growth factors correlates with marrow cellularity and may identify outpatients with risk for severe neutropenia after cyclic chemotherapy.

Adolescent↗
PubMed1993

Different membrane expression of CD11b and CD14 on blood neutrophils following in vivo administration of myeloid growth factors.

During the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF) we studied the early and late changes of membrane antigen density on neutrophils. RhG-CSF and rhGM-CSF both caused an early transient reduction in blood neutrophilic granulocyte-concentration within the first 30 min after treatment followed by a marked later increase during the subsequent 24 h. During the early neutropenia quantitative flow cytometry showed an associated marked increase in the density of membrane CD11b from 169 x 10(3) before to 568 x 10(3) A.U. per cell induced by rhGM-CSF but a non-significant change by rhG-CSF, suggesting that different mechanisms may be responsible for the transient neutropenia. The subsequent neutrophil granulocytosis was followed by a significantly (P < 0.05) increased density of the CD14 antigen from 6.1 x 10(3) before to 15.9 x 10(3) A.U. per cell during treatment with rhG-CSF, but not by rhGM-CSF administration. These results demonstrate that the two cytokines may affect the function of neutrophilic granulocytes in different ways. The increased expression of CD11b could explain some of the side-effects during treatment with rhGM-CSF. The upregulation of CD14 induced by rhG-CSF may be clinically relevant, as CD14 is an opsonic receptor for lipopolysaccharide binding proteins, acting in the defence against Gram-negative bacterial infections.

Adult↗