losartan-potassium and Pancreatitis

The use of hydroxyurea for the prevention of sickle cell crises in patients with homozygous HbS disease is now well established. The beneficial effects of this compound stem from (a) selective enrichment of red cells containing an increased amount of fetal hemoglobin, which inhibits HbS polymerization, and (b) a decrease of leukocytes, platelets, and reticulocytes, which significantly limits their adherence to the vascular wall. We report the results of a clinical trial of hydroxyurea on 55 Greek-origin patients with sickle cell/beta-thalassemia and 14 patients with homozygous HbS disease who have been treated with hydroxyurea for several years. Such patients have a higher probability to benefit from hydroxyurea therapy, since in addition to its antisickling effect, the increase of gamma-chain synthesis is expected to diminish the deleterious effects of the unbound alpha-globin chains. Selection of patients and monitoring throughout the whole trial were done by the same clinicians. Quantitative expression of the clinical condition was done using a system scoring several outcome parameters. For a period of 52 months prior to starting treatment, the total score of severity for 59 evaluable patients was 1182 points (3068 patient-weeks), while for the 12,018 patient-weeks of the trial this parameter fell to only 82 points. Other observations of interest include the significant improvement of a group of patients with hepatic cholestasis, the development of leg ulcers possibly related to the treatment, and the dramatic increase of hemoglobin F, often in association with an increase of the total hemoglobin levels as a result of decreased hemolysis.

Topics: Acute Disease; Adolescent; Adult; Anemia, Sickle Cell; Antisickling Agents; beta-Thalassemia; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Erythropoietin; Female; Fetal Hemoglobin; Greece; Hemoglobins; Humans; Hydroxyurea; Leg Ulcer; Male; Middle Aged; Pancreatitis; Patient Compliance; Patient Selection; Receptors, Transferrin; Severity of Illness Index

Blood transfusions in anemic patients frequently are used for critically ill patients as a life-saving therapeutic maneuver. Jehovah's Witness (JW) patients typically refuse blood transfusions due to religious beliefs. Numerous clinical reports, in a wide spectrum of medical specialties, have shown no greater morbidity or mortality in JW patients or others who refused transfusions compared to those patients who accept transfusions. We report our experience with two JW patients who presented with severe anemia and life-threatening pancreatitis. Despite undergoing percutaneous drainages by interventional radiology (IR) for complex pancreatic collections (and other IR drainages), neither patient suffered any adverse effect from the IR procedures, even though they refused blood transfusions. Our experience suggests that IR procedures also may be successful with this more limited blood product protocol.

Topics: Adult; Anemia; Anti-Bacterial Agents; Critical Illness; Drainage; Erythropoietin; Female; Humans; Jehovah's Witnesses; Male; Middle Aged; Pancreatitis; Radiology, Interventional; Recombinant Proteins; Religion and Medicine; Tomography, X-Ray Computed; Treatment Outcome; Treatment Refusal

To evaluate the effect of pretreatment with erythropoietin (EPO) on disordered pro- and anti- inflammatory balance in rats with severe acute pancreatitis (SAP) and explore the underlying mechanisms.. Ninety healthy male SD rats were randomized equally into sham-operated group, SAP group and EPO pretreatment group. SAP model was induced in the latter two groups by retrograde injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before SAP, and normal saline was administered in the other two groups. Serum amylase activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time points after the operation. The translocation and activation of nuclear factor-κB (NF-κB) in the pancreatic tissue was detected using immunofluorescence staining, and pancreatic pathologies were evaluated.. Compared with SAP group, EPO group showed a markedly decreased activation rate of NF-κB after SAP except for 12 h (P<0.05), significantly decreased serum amylase activity at 3, 6, and 12 h (P<0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P<0.05), whereas serum IL-10 underwent no significant changes. The rats in EPO group showed an obviously milder pancreatic pathology than those in SAP group at 6, 12, and 24 h (P<0.05).. EPO can effectively inhibit NF-κB activation by regulating the inflammatory mediators and restoring the pro-and anti-inflammatory balance to alleviate SAP in rats.

Topics: Acute Disease; Animals; Cytokines; Erythropoietin; Interleukin-10; Interleukin-18; Male; NF-kappa B; Pancreatitis; Rats; Rats, Sprague-Dawley

Treatment with zidovudine has been standard therapy for patients with advanced HIV infection, but intolerance is common. Previously, management of intolerance has consisted of symptomatic therapy, dose interruption/discontinuation, and, when appropriate, transfusion. The availability of new antiretroviral agents such as didanosine as well as adjunctive recombinant hematopoietic growth factors makes additional strategies possible for the zidovudine-intolerant patient. Because all of these agents are costly, we evaluated the cost implications of these various strategies for the management of zidovudine-intolerant individuals within a population of persons with advanced HIV disease. We performed a decision analysis using iterative algorithmic models of 1 year of antiretroviral care under various strategies. The real costs providing antiretroviral therapy were estimated by deflating medical center charges by specific Medi-Cal (Medicaid) charge-to-payment ratios. Clinical data were extracted from the medical literature, product package inserts, investigator updates, and personal communications. Sensitivity analysis was used to test the effect of error in the estimation of parameters. The models predict that a strategy of dose interruption and transfusion for zidovudine intolerance will provide an average of 46 weeks of therapy per year to the average patient at a cost of $5,555/year of therapy provided (1991 U.S. dollars). The models predict that a strategy of adding hematopoietic growth factors to the regimen of appropriate patients would increase the average amount of therapy provided to the average patient by 3 weeks (6%) and the costs attributable to therapy by 77% to $9,805/year of therapy provided.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Agranulocytosis; Algorithms; Anemia; Costs and Cost Analysis; Decision Support Techniques; Didanosine; Erythrocyte Transfusion; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Pancreatitis; Quality of Life; Zidovudine

Topics: Anemia, Hemolytic; Cell Membrane; Erythropoiesis; Erythropoietin; Ethanol; Folic Acid; Hematopoiesis; Hematopoietic Stem Cells; Hepatitis; Humans; Intestinal Absorption; Iron; Megakaryocytes; Mitochondria; Mononuclear Phagocyte System; Nutrition Disorders; Pancreatitis; Pyridoxal Phosphate