Leuprolide therapy for prostate cancer. An association with scintigraphic "flare" on bone scan

The scintigraphic "flare" phenomenon on bone imaging refers to an increase in intensity of tracer uptake in sites of bone metastases and/or the appearance of "new" lesions, which occur shortly after commencement of hormonal therapy or chemotherapy for breast, prostate, or lung cancer. In this study, we observed that scintigraphic flare can occur in patients with prostate cancer following treatment with the "hormone-like" luteinizing hormone releasing hormone analog, leuprolide acetate. Twenty-six patients with prostate cancer being treated with leuprolide acetate underwent serial bone scans at three-month intervals. Five (19.2%) of the 26 patients had findings consistent with a scintigraphic flare on bone scans obtained between three and six months after initiation of therapy. These scan findings should not be confused with progression of skeletal metastases.     

Human leukemia cell line K562 responds to erythroid-potentiating activity

We report that erythroid-potentiating activity (EPA), known to stimulate the proliferation of normal human erythroid precursors in vitro, has a growth-promoting effect on human K562 erythroleukemia cells and Friend mouse erythroleukemia cells. Detailed studies were carried out using an EPA produced by a human T-lymphoblast line (Mo). Although EPA has not been purified to homogeneity, several observations indicate that the factor elaborated by Mo cells that stimulates erythroleukemia cell growth is the EPA molecule. The erythroleukemia growth factor cofractionates with EPA using gel exclusion chromatography, isoelectric focusing, and ion exchange chromatography. In addition, the activities exhibit similar kinetics of heat inactivation. A granulocyte-macrophage colony-stimulating factor also elaborated by Mo cells had no effect on the growth of the erythroleukemia cells. Other sources of EPA, such as peripheral blood leukocyte-conditioned medium, preparations from urine of anemic patients, and medium conditioned by a human monocyte-like cell line, stimulated erythroleukemia cell growth. Mouse sources of EPA (termed "burst-promoting activity") stimulated mouse but not human erythroleukemia cells. The availability of cell lines apparently responsive to EPA should prove useful for examining the mode of action of this regulator of erythropoiesis.     

Omnidirectional assessment of one-handed manual strength at three handle heights

Maximal right-handed omnidirectional strengths of eleven males were measured at three handle heights of 1.5 m, 1.0 m and 0.5 m using the Tri-Axial Force measurement System. The postures of the subjects were constrained by preventing rotation of the footbase in order to ensure that the forward-backward and leftward-rightward axes of the subject remained constant relative to the measurement system. A two-way repeated measures analysis of variance revealed highly significant differences in maximal strengths between the three heights and the 614 directions of exertion measured. A highly significant interaction was found between height and direction. At all three hand heights a restricted area of great strength was found in the direction of upward and almost directly forward from the subject. A second, less powerful, but more widespread area of high strength was also found at each height. At the 1.5-m height the peak was in the backward and almost vertically downward area. At the 1.0-m height the peak was in the area of slightly downward and largely backward. At the 0.5-m height the peak was to the right of upward and backward. RELEVANCE: Very few real-life manual exertions involve forces which are purely in the sagittal, forward-backward plane, with lateral components of force usually being involved as well. The data presented extend the knowledge base about male one-handed strengths.     

Localization of protein disulfide isomerase to the external surface of the platelet plasma membrane

Protein disulfide isomerase (PDI) is an enzyme that catalyzes the formation as well as the isomerization of disulfide bonds. In this study, antibodies against PDI were used to show PDI antigen on the platelet surface by indirect immunofluorescence microscopy and by flow cytometry. The platelets were not activated, as evidenced by the absence of staining by an antibody against P-selectin. Permeabilized platelets showed little cytosolic PDI by indirect immunofluorescence microscopy, suggesting that the majority of platelet PDI is localized to the platelet surface. PDI activity against "scrambled" RNase was shown with intact platelets. The activity was inhibited by inhibitors of PDI and by an antibody against PDI. Other blood cells showed little PDI. Platelet surface PDI may play a role in the various physiological and pathophysiologic processes in which platelets are involved.     

Pulse oximetry in sickle cell disease

Patients with sickle cell disease usually have mild hypoxaemia and their oxyhaemoglobin dissociation curve is shifted to the right. It follows that oxygen saturation in sickle cell disease should be lower than normal. Most subjects in this clinic had normal oxygen saturation by pulse oximetry, however. To improve the understanding of this paradox, arterialised capillary oxygen tension (PO2) and oxygen saturation were compared with simultaneously measured pulse oximeter saturation in 20 children with sickle cell disease. In addition, the PO2 at 50% haemoglobin saturation (P50) was compared with saturation measured by pulse oximetry in all 20 patients. It was found that saturation measured by pulse oximetry was, on the whole, similar to that calculated from the sampled blood. Individual deviations were not random, however, and were partly explained by differences in P50 values. It is concluded that pulse oximetry gives variable results in patients with sickle cell disease and should be used with caution to predict arterial saturation in this patient group.     

The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters

PURPOSE: Although prostate cancer specific mortality is decreasing, there is little effect on overall mortality in this population, suggesting the possibility of an increased risk of death from nonprostate cancer related causes. Androgen deprivation therapy could adversely affect cardiovascular health. We investigated changes in lipid and glucose during androgen deprivation therapy. MATERIALS AND METHODS: We performed an exploratory analysis of pooled data from 3 prospective clinical trials aimed at achieving medical castration by comparing the gonadotropin releasing hormone antagonist abarelix, the gonadotropin releasing hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen bicalutamide. Most patients were treated in the neoadjuvant setting or because of biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were determined in 1,102 men at baseline, and on treatment days 85 and 169. In the current study men were categorized into 3 treatment groups according to the type of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate plus bicalutamide or abarelix, and statin therapy. RESULTS: Significant increases in total cholesterol, triglyceride and high density lipoprotein-cholesterol were observed in patients on leuprolide acetate or abarelix but not in patients on leuprolide acetate plus bicalutamide. Consistent changes in low density lipoprotein-cholesterol were not detected. Increased total cholesterol was usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin A1C increased from baseline to day 85 only and there were no significant changes in fasting glucose measurements. The type of androgen deprivation therapy did not affect these parameters. CONCLUSIONS: Short-term androgen deprivation therapy affects serum lipid and hemoglobin A1C independent of statin therapy.