Patricia Griffith

Bio: Patricia Griffith is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Thalassemia & Aplastic anemia. The author has an hindex of 11, co-authored 13 publications receiving 1602 citations.

Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major.

Abstract: Background To determine whether deferoxamine prevents the complications of transfusional iron overload in thalassemia major, we evaluated 59 patients (30 were female and 29 male; age range, 7 to 31 years) periodically for 4 to 10 years or until death. Methods At each follow-up visit, we performed a detailed clinical and laboratory evaluation and measured hepatic iron stores with a noninvasive magnetic device. Results The body iron burden as assessed by magnetic measurement of hepatic iron stores was closely correlated (R = 0.89, P<0.001) with the ratio of cumulative transfusional iron load to cumulative deferoxamine use (expressed in millimoles of iron per kilogram of body weight, in relation to grams of deferoxamine per kilogram, transformed into the natural logarithm). Each increase of one unit in the natural logarithm of the ratio (transfusional iron load to deferoxamine use) was associated with an increased risk of impaired glucose tolerance (relative risk, 19.3; 95 percent confidence interval, 4.8 to...

Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major

Abstract: To examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75, P < 0.0001) and in those with thalassemia major (R = 0.76, P < 0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76, P < 0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only ∼57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores. © 1993 Wiley-Liss, Inc.

Detection of early cardiac dysfunction in patients with severe beta-thalassemia and chronic iron overload.

Abstract: To detect early left ventricular dysfunction, we used radionuclide cineangiography to determine left ventricular ejection fraction during exercise in 24 patients with transfusion-dependent, congenital anemias, 21 of whom had severe beta thalassemia. Ejection fraction at rest was normal in 21 patients (>45 per cent) and in all patients was 53±2 per cent (mean ±S.E.M.) — not significantly different from the value in normal subjects. However, ejection fraction during exercise was normal in only 11 patients (53±3 per cent in all patients, P<0.001 as compared with the normal value). All eight patients who had received fewer than 100 transfusions but only three of 16 (19 per cent, P<0.001) who had received 100 or more transfusions had normal responses during exercise. Whereas echocardiographic fractional shortening at rest was normal in 16 of 19 patients studied, eight patients with normal fractional shortening had abnormal ejection-fraction responses to exercise. Thus, radionuclide cineangiography dur...

Cyclosporine therapy of aplastic anaemia, congenital and acquired red cell aplasia.

Abstract: We treated 22 patients with severe aplastic anaemia refractory to antithymocyte globulin (ATG) with cyclosporine, alone or in combination with prednisone. Eight patients showed significant clinical improvement, all but one to transfusion-independence. Although cyclosporine alone was effective, the addition of prednisone resulted in prompter and fuller haematologic improvement. No patient with an absolute granulocyte count less than 0.2 x 10(9)/l responded to treatment. Haematologic remissions were sustained beyond the treatment period. Of nine patients with Diamond-Blackfan syndrome, one showed a complete response to two separate courses of cyclosporine and relapse with withdrawal of therapy, and a second achieved significant reduction in corticosteroid dose without relapse; however, seven cases failed to respond. Two of three adults with acquired pure red cell aplasia recovered. A combination of cyclosporine and corticosteroids may be effective therapy in patients with aplastic anaemia who have failed ATG treatment. Occasional cases of congenital and acquired pure red cell aplasia may also respond to cyclosporine.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

Abstract: The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload

Abstract: Aims To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops.Methods and Results We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0(.)93, P <0(.)0001). Inter-study cardiac reproducibility was 5(.)0%. As myocardial iron increased. there was a progressive decline in ejection fraction (r=0(.)61, P <0(.)001). All patients with ventricular dysfunction had a myocardial T2* of < 20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0(.)79, P <0(.)002).Conclusions Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique. should reduce mortality from this reversible cardiomyopathy. (C) 2001 The European Society of Cardiology.

Role of oxidative stress in cardiovascular diseases.

Abstract: ObjectivesIn view of the critical role of intracellular Ca2+-overload in the genesis of myocyte dysfunction and the ability of reactive oxygen species (ROS) to induce the intracellular Ca2+-overload, this article is concerned with analysis of the existing literature with respect to the role of oxida

Inherited haemoglobin disorders: an increasing global health problem.

Abstract: Despite major advances in our understanding of the molecular pathology, pathophysiology, and control and management of the inherited disorders of haemoglobin, thousands of infants and children with these diseases are dying through lack of appropriate medical care. This problem will undoubtedly increase over the next 20 years because, as the result of a reduction in childhood mortality due to infection and malnutrition, more babies with haemoglobin disorders will survive to present for treatment. Although WHO and various voluntary agencies have tried to disseminate information about these diseases, they are rarely mentioned as being sufficiently important to be included in setting health care priorities for the future. It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.