The Local Blood Flow in Human Bone Marrow in Leukemia and Neoplastic Diseases as Determined by the Clearance Rate of Radioiodide (I131) 1

Petrakis, Nicholas L.; Masouredis, S. P.; Miller, Philip; Cordes, Fauno L.

doi:10.1172/jci102821

Cited by 25 publications

(11 citation statements)

References 6 publications

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“…The degree of anemia present in these patients could not be correlated with the mean pressures or the pulse pressures in the marrow. These pressure data confirm the increased vascularity in the marrow in some forms of leukemia as has been previously demonstrated by the clearance of I13' from the marrow (7).…”

Section: Resultssupporting

confidence: 90%

Bone Marrow Pressure in Leukemic and Non-Leukemic Patients

Petrakis¹

1954

J. Clin. Invest.

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It has been a frequent observation that many patients with leukemia and multiple myeloma bleed freely through the marrow needle at the time of bone marrow aspiration although hemorrhagic tendencies may not be present clinically. In addition , throbbing bone pain and bone tenderness are not infrequently observed in these patients (1). Such clinical observations suggest that some degree of pressure elevation may be present in the marrow cavity in these diseases. It was believed of interest to determine the pressure relationships within the human marrow cavity under a variety of physiologic stimuli. MATERIALS AND METHODS The marrow pressures of 14 patients with neoplastic diseases having essentially normal marrows, as determined by microscopic examination, and of 10 patients with leukemia and one patient with multiple myeloma were determined by means of recording strain gauges attached to clinical bone marrow needles. The patients were studied under resting but not basal conditions, without previous sedation. The pressure in both the sternal and iliac crest marrows was measured in most patients, either simultaneously or serially. The sternal site was at the level of the second interspace, and the iliac crest at a site two centimeters posterior to the anterior superior iliac spine. The usual precautions of sterility and local procaine anesthesia of skin and periosteum were employed. A bonded SR4 wire resistance strain gauge and recording apparatus developed for clinical pressure measurements by Bierman and Jenkins (2) were employed for pressure determinations. The gauge was connected directly to the bone marrow needle after the needle and gauge chamber had been filled with heparin-saline solution. The saline within the manometer was equalized with the ambient pressure, after which the chamber was sealed. The output of the strain gauge was connected to a strain indicator and photographically recorded with a multiple channel recording oscilloscope. The Turkel-Bethell bone marrow needle employed in these studies had a 14-gauge bore and was equipped with a trephine stylette which made it useful for removing bony spicules which frequently entered the needle during its implantation. After implantation, the needle was filled with heparin-saline solution, care being exercised to exclude air bubbles. It was found necessary to premedicate the patients with 50 to 100 mg. of heparin intravenously shortly before the studies to prevent clotting within the needle in the marrow. Smaller amounts of heparin were used in patients with leukemia, or completely omitted where manifest bleeding tendencies existed. A modified strain gauge strapped over the lower chest cage was utilized as a pneumotachometer, and a single lead EKG tracing was made in each patient for pulse de-terminations. The marow pressure, respiratory rate and amplitude, and EKG record were simultaneously recorded photographically. The marrow pressures were studied with the patients at rest in supine position, during exaggerated respiration, coughing, Valsalva and Mueller...

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Section: Resultssupporting

confidence: 90%

Bone Marrow Pressure in Leukemic and Non-Leukemic Patients

Petrakis¹

1954

J. Clin. Invest.

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“…Petrakis et al (1953) noted increased marrow blood £ow in patients with acute leukaemia or multiple myeloma and with hyperplastic marrows; this was later con¢rmed by Lahtinen et al (1982), who studied patients with leukaemia. The underlying notion is that enhanced leucopoiesis would be accompanied by an increased marrow blood £ow, while decreased leucopoiesis would be paralleled by a reduced blood supply to the marrow.…”

Section: Marrow Blood £Ow During Altered Haemopoiesismentioning

confidence: 80%

“…Early studies of marrow blood £ow relied on invasive procedures likely to perturb its microenvironment (Petrakis et al 1953, BrÔnemark 1959, Michelsen 1969. Early studies of marrow blood £ow relied on invasive procedures likely to perturb its microenvironment (Petrakis et al 1953, BrÔnemark 1959, Michelsen 1969.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Blood flow to the haemopoietic bone marrow

Iversen

1997

Acta Physiologica Scandinavica

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In order to maintain an adequate haemopoiesis, the bone marrow is dependent on a sufficient blood supply. Our understanding of the regulation of marrow perfusion remained patchy for several decades, mainly because of technological difficulties. Recent advances in methodology have permitted more detailed analyses of bone marrow perfusion. Enhanced stimulation of erythropoietic or leucopoietic activity leads to increased blood flow to the bone marrow. There is evidence that this vasodilatory effect is mediated by the cytokines erythropoietin and granulocyte colony-stimulating factor; however, a direct link has yet to be firmly established. The presence of receptors for several other cytokines on vascular endothelial and smooth muscle cells suggests that these may also have a regulatory role. The vasodilating factor nitric oxide (NO) regulates bone marrow blood flow both under normal conditions and during accelerated haemopoiesis, and NO is possibly induced via activation of cytokine receptors. There are conflicting reports as to how catecholamines affect marrow vascular tone. Although there is firm evidence that the bone marrow vasculature is innervated, no definite role of this innervation in vasoregulation has been documented. Advances in bone marrow/blood stem cell transplantation technology and the development of other therapeutic strategies for bone marrow failure may in part be dependent on optimization of the blood supply to the haemopoietic bone marrow.

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“…Blood flow to leukaemic marrow is greater than to marrow in patients with solid tumours (Petrakis, Masouredis, Miller & Cordes, 1953), and pressor amines may increase radioiodine 131I clearance from the marrow fourfold. After a few days on the infusions patients were in a better physical state, with a fall in blast count, transfused and often receiving antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.

Harris¹,

Potter²,

Bunch³

et al. 1979

Brit J Clinical Pharma

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1 The pharmacokinetics of cytosine arabinoside were studied after a single i.v. bolus of 2 mg/kg ara‐C in patients with newly diagnosed untreated AML, using a bioassay and GC‐MS method to measure the plasma concentrations. 2 Most patients showed a bi‐ or tri‐phasic decline in plasma concentrations with time. Plasma clearance was 3.9 to 18.1 l/min as measured by the GC‐MS method, and terminal half‐lives varied from 7‐ 107 min. 3 There was poor correlation of the GC‐MS assay with the bioassay, probably because the latter was interfered with by the release of endogenous nucleosides from blasts after after ara‐C. 4 Plasma concentrations were measured by GC‐MS during continuous infusions in 14 patients. Plasma clearances were much lower than after a bolus, 0.39 to 5.25 l/min. 5 There was no correlation of response (remission or fall in peripheral blast count) with exposure to ara‐C calculated from infusion dose, clearance and duration of infusion. 6 This study shows that ara‐C pharmacokinetics varies markedly from patient to patient and that there is a wide range in the plasma concentrations associated with therapeutic response.

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The Local Blood Flow in Human Bone Marrow in Leukemia and Neoplastic Diseases as Determined by the Clearance Rate of Radioiodide (I131) 1

Cited by 25 publications

References 6 publications

Bone Marrow Pressure in Leukemic and Non-Leukemic Patients

Bone Marrow Pressure in Leukemic and Non-Leukemic Patients

Blood flow to the haemopoietic bone marrow

Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.

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