Sideroblastic anemias are caused by a diversity of hereditary, congenital, or acquired disorders. Criteria used in describing sideroblastic anemias vary widely among standard medical textbooks and even so have been imprecisely applied in the literature. Recent discoveries concerning the basic pathophysiologic mechanisms involving the molecular biology of nuclear and mitochondrial DNA, erythroid ALA synthase (ALAS-2), and iron transport have made the classification of sideroblastic anemias very complex. We recommend a more precise evaluation and documentation of the components that characterize the sideroblastic abnormality and propose an extended classification of the sideroblastic anemias.

From the Publisher: Mathematicians, students and researchers constantly refer to various sources for different formulas, equations, etc. "The Handbook of Mathematics and Computational Science" puts up-to-date equations, formulas, tables, illustrations, and explanations in one invaluable reference volume. Fully up-to-date, this handbook will quickly become the standard reference for mathematicians and students. 545 illus.

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 77.4), diabetes mellitus (relative risk, 9.2; 95 percent confidence interval, 1.8 to 47.7), cardiac disease (relative risk, 9.9; 95 percent confidence interval, 1.9 to 51.2), and death (relative risk, 12.6; 95 percent confidence interval, 2.4 to 65.4). All nine deaths during the study occurred among the 23 patients who had begun chelation therapy later and used less deferoxamine in relation to their transfusional iron load (P < 0.001).Conclusions. The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major.

Two synthetic peptides corresponding to the N-terminal amino acids (AA) of band 3 were designed to inhibit deoxyhemoglobin S (deoxy S) polymerization through two different mechanisms. Peptide I, an N:1-15AA fragment, was employed to bind to the 2,3-diphosphoglycerate (2,3-DPG) receptor locus of single deoxy S molecules with 5-7 AA extending internally and the remaining 10-8 AA projecting external to hemoglobin (Hb) S, thereby inhibiting polymerization by steric hindrance. Peptide II consisted of two N:1-8AA + K (lysine) sequences linked by a coupler through the lysine, and it was employed to bind to the 2,3-DPG loci of two deoxy S molecules, tethering them together to form "binary hemoglobin complexes" incapable of entering the polymer chains. Decreased polymerization would result from reduction in effective concentration of deoxy S. Binding of peptides to the 2,3-DPG receptor loci was demonstrated by a progressive rightward shift in the hemoglobin oxygen binding curves as a function of increasing peptide concentrations. Inhibition of deoxy S polymerization was studied by equilibrium solubility measurements of purified, stripped solutions of Hb S. Physiologically significant inhibition was demonstrated for both peptides with near-maximum increases in solubility achieved by Peptide II at 1:1 peptide:Hb S ratios. These peptides represent a new class of inhibitors of deoxy S polymerization.

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 approximately 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.

We have previously obtained evidence that N-terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1-15AA fragment binds to the 2,3-diphosphoglycerate (2,3-DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror-image peptide, corresponding to two N:1-8AA + lysine (K) linked by coupler, binds to the 2,3-DPG loci of two deoxy S molecules, tethering them together to form "binary complexes" incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol-gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror-image peptide was a more effective inhibitor than the N:1-15AA peptide. When the mirror-image peptide was present in peptide:hemoglobin molar ratios of 0.25-1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15-25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror-image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 peptides.

Opening up an institution to total quality management requires patience, openness, a commitment to new ideas, and a commitment to the customer.

Mild hepatic iron overload has been demonstrated by magnetic susceptibility measurements in a 22-year-old man with hereditary sideroblastic erythropoiesis despite hemoglobin levels in the normal range and a normal erythropoietin level. His grandfather's sideroblastic anemia has been found to be responsive to pyridoxine; his mother's hemoglobin has persisted in the normal range but red cell volume distribution analysis demonstrated two subpopulations; 30% with estimated geometric mean of 68 fl and 70% an estimated mean of 93 fl. Red cell distribution analysis of the grandson demonstrated two microcytic subpopulations; 46% with an estimated geometric mean of 45 fl and 54% an estimated mean of 70 fl. A therapeutic regimen is outlined to reduce to normal his iron stores and to prevent the future development of excessive iron overload.

American Journal of HematologyVolume 39, Issue 2 p. 119-130 Review Parvovirus B19 for the hematologist John W. Harris, Corresponding Author John W. Harris Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University School of Medicine and MetroHealth Medical Center, Cleveland, OhioDivision of Hematology and Oncology, Department of Medicine, MetroHealth Medical Center, 3395 Scranton Road, Cleveland, OH 44109Search for more papers by this author John W. Harris, Corresponding Author John W. Harris Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University School of Medicine and MetroHealth Medical Center, Cleveland, OhioDivision of Hematology and Oncology, Department of Medicine, MetroHealth Medical Center, 3395 Scranton Road, Cleveland, OH 44109Search for more papers by this author First published: February 1992 https://doi.org/10.1002/ajh.2830390209Citations: 54AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Owren PA: Congenital hemolytic jaundice: The pathogenesis of the hemolytic crisis. Blood 3: 231–248, 1948. 2 Cossart YE, Field AM, Cant B, Widdows D: Parvovirus-Like particles in human sera. Lancet 1: 72–73, 1975. 3 Young N: Hematologic and hematopoietic consequences of B19 parvovirus infection. Semin Hematol 25: 159–72, 1988. 4 Risks associated with human parvovirus B19 infection. MMWR 38: 81–97, 1989. 5 Rotbart HA: Human parvovirus infections. Annu Rev Med 41: 2–34, 1990. 6 Kumar ML: Human parvovirus B19 and its associated diseases. In RA Polin, WT Speck (eds): Clinics in Perinatology, Neonatal Sepsis. Philadelphia: WB Saunders, 1991, Vol 18, pp 209–225. 7 Pattison JR, Jones SE, Hodgson J, et al.: Parvovirus infections and hypoplastic crisis in sickle-Cell anaemia [letter]. Lancet 1: 664–665, 1981. 8 Serjeant GR, Mason K, Topley JM et al.: Outbreak of aplastic crises in sickle cell anemia associated with parvovirus-Like agent. Lancet 2: 595–597, 1981. 9 Saarinen UM, Chorba TL, Tattersall P, et al.: Human parvovirus B19-Induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia. Blood 67: 1411–1417, 1986. 10 Anderson MJ, Jones SE, Fisher-Hoch SP, et al.: Human parvovirus, the cause of erythema infectiosum (fifth disease)? [letter]. Lancet 1: 1378, 1983. 11 Anderson MJ, Lewis E, Kidd IM, Hall SM, Cohen BJ: An outbreak of erythema infectiosum associated with human parvovirus infection. J Hygiene 93: 85–93, 1984. 12 van Elsacker-Niele A-MW, Anderson MJ: First picture of erythema infectiosum? Lancet 1: 229, 1987. 13 Ager EA, Chin TDY, Poland JD: Epidemic erythema infectiosum. N Engl J Med 275: 1326–1331, 1966. 14 Lauer BA, MacCormack JN, Wilfert C: Erythema infectiosum: an elementary school outbreak. Am J Dis Child 130: 252–254, 1976. 15 Shneerson JM, Mortimer PP, Vanderveide EM: Febrile illness due to a parvovirus. Br Med J 1: 1580, 1980. 16 Okabe N, Koboyashi S, Tatsuzawa O, et al.: Detection of antibodies to human parvovirus in erythema infectiosum (fifth disease). Arch Dis Child 59: 1016–1019, 1984. 17 Nunoue T, Okochi K, Mortimer PP, et al.: Human parvovirus (b19) and erythema infectiosum. J Pediatr 107: 38–40, 1985. 18 Plummer FA, Hammond GW, Forward K, et al.: An erythema infectiosum-Like illness caused by human parvovirus infection. N Engl J Med 313: 74–79, 1985. 19 Chorba T, Cocci P, Holman RC, et al.: The role of parvovirus B19 in aplastic crisis and erythema infectiosum (fifth disease). J Infect Dis 154: 383–393, 1986. 20 Anderson LJ: Role of parvovirus B19 in human disease. Pediatr Infect Dis J 6: 711–718, 1987. 21 Naides SJ: Erythema infectiosum (fifth disease) occurrence in Iowa. Am J Public Health 78: 1230–1231, 1988. 22 Evans JP, Rossiter MA, Kumaran TO, et al.: Human parvovirus aplasia: case due to cross infection in a ward. Br Med J 288: 681, 1984. 23 Cohen BJ, Courouce AM, Schwarz TF, et al.: Laboratory infection with parvovirus B19 [letter]. J Clin Pathol 41: 1027–1028, 1988. 24 Anand A, Gray ES, Brown T, et al.: Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 316: 183–186, 1987. 25 Mortimer PP, Luban NLC, Kelleher JF, Cohen BJ: Transmission of serum parvovirus-Like virus by clotting-Factor concentrates. Lancet 2: 482–484, 1983. 26 Bartolomei Corsi O, Assi A, Morfini M, Franci R, Rossi Ferrini P: Human parvovirus infection in haemophiliacs first infused with treated clotting factor concentrates. J Med Virol 25: 165–170, 1988. 27 Woolf AD, Campson GV, Chishick A, et al.: Clinical manifestations of human parvovirus B19 in adults. Arch Int Med 149: 1153–1156, 1989. 28 Anderson MJ, Higgins PG, Davis LR, et al.: Experimental parvoviral infection in humans. J Infect Dis 152: 257–265, 1985. 29 Potter CG, Potter AC, Hatton SCR, et al.: Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (b19). J Clin Invest 79: 1486–1492, 1987. 30 Reid DM, Reid TMS, Brown T, et al.: Human parvovirus-Associated arthritis. A clinical and laboratory description. Lancet 1: 422–425, 1985. 31 White DG, Mortimer PP, Blake DR, et al.: Human parvovirus arthropathy. Lancet 1: 419–421, 1985. 32 Kardolf R, Kirschner P, Hofschneider PH, Vischer TL: Detection of parvovirus in a patient with “reactive arthritis” by in situ hybridization. Clin Rheumatol 8: 398–401, 1989. 33 Mayo DR, Vana DW Jr: Parvovirus B19 as the cause of a syndrome resembling Lyme arthritis in adults. N Engl J Med 324: 419–420, 1991. 34 Dinerman JL, Corman LC: Human parvovirus B19 arthropathy associated with desquamation. Am J Med 89: 826–828, 1990. 35 Winkelman MD: Personal communication, 1991. 36 LeFrere JJ, Courouce AM, Muller JY, et al.: Human parvovirus and purpura [letter]. Lancet 2: 730–731, 1985. LeFrere JJ, Courouce AM, Soulier JP, et al.: Henoch-Schonlein purpura and human parvovirus infection. Pediatrics 78: 183–184, 1986. 37 Mortimer PP, Cohen BJ, Rossiter MA, et al.: Human parvovirus and purpura. Lancet 2: 730–731, 1985. 38 Naides JJ, Piette WE, Veach LA, Argenyi F: Human parvovirus B19 induced vesiculopustular skin eruption. Am J Med 84: 968–972, 1988. Wright IM, Williams ML, Cohen BJ: Congenital parvovirus infection. Arch Dis Child 66: 253–254, 1991. 39 Faden H, Gary GW Jr, Korman M: Numbness and tingling of fingers associated with parvovirus B19 infection [letter]. J Infect Dis 161: 354–355, 1990. 40 Singer K, Motulsky AG, Wile SA: Aplastic crisis in sickle cell anemia. A study of its mechanism and its relationship to other types of hemolytic crisis. J Lab Clin Med 35: 721–736, 1950. 41 Chernoff AI, Josephson AM: Acute erythroblastopenia in sickle-Cell anemia and infectious mononucleosis. Am J Dis Child 82: 310: 322, 1951. 42 Lutton JD, Schmalzer EA, Rao SP, et al.: Erythroid colony studies on sickle cell anemia in hypoproliferative crisis. Am J Hematol 8: 15–19, 1980. 43 Anderson MJ, Davis LR, Hodgson J, et al.: Occurrence of infection with a parvovirus-Like agent in children with sickle cell anaemia during a two-Year period. J Clin Pathol 35: 744–749, 1982. Gowde M, Rao SP, Cohen B, et al.: Human parvovirus infection in patients with sickle cell disease with and without hypoplastic crisis. J Pediatr 110: 81–84, 1987. 44 Pardoll DM, Rodeheffer RJ, Smith RRL, et al.: Aplastic crisis due to extensive bone marrow necrosis in sickle cell disease. Arch Intern Med 142: 2223–2225, 1982. 45 Kelleher JF Jr, Luban NLC, Cohen BJ, et al.: Human serum parvovirus as the cause of aplastic crisis in sickle cell disease. Am J Dis Child 138: 401–403, 1984. 46 Nkrumah FK, Neequaye JE, Ankra-Badu G: Bone marrow in sickle cell anaemia at time of anemic crisis. Arch Dis Child 59: 561–565, 1984. 47 Goldstein AR, Anderson MJ, Serjeant GR: Parvovirus associated aplastic crisis in homozygous sickle cell disease. Arch Dis Child 62: 585–588, 1987. 48 Rao SP, Miller ST, Cohen B: Transient aplastic crisis (tAC) in patients with sickle cell disease during a six year period: Parvovirus B19 studies at diagnosis and followup. Pediatr Res 29: 875A, 1991. 49 Dameshek W, Bloom ML: The events in the hemolytic crisis of hereditary spherocytosis with particular reference to the reticulocytopenia, pancytopenia, and an abnormal splenic mechanism. Blood 3: 1381–1410, 1948. 50 Chanarin I, Barkhan P, Peacock M, et al.: Acute arrest of hematopoiesis. Br J Haematol 10: 43–49, 1964. 51 Mortimer PP: The aplastic crisis of hereditary spherocytosis due to a single transmissible agent. J Clin Pathol 36: 445–448, 1983. 52 Rao KRP, Patel AR, Anderson MJ: Infection with parvovirus-Like virus and aplastic crisis in chronic hemolytic anemia. Ann Intern Med 98: 930–932, 1983. 53 Davis LR: Aplastic crises in haemolytic anaemias: The role of a parvovirus-Like agent. Br J Haematol 55: 391–393, 1983. 54 Young N, Mortimer PP: Viruses and bone marrow failure. Blood 63: 729–737, 1984. 55 LeFrere JJ, Courouce A-M, Bertrand Y, et al.: Human parvovirus and aplastic crisis in chronic hemolytic anemias. A study of 24 observations. Am J Hematol 23: 271–275, 1986. 56 Saarinen UM, Chorba TL, Tattersall P, et al.: Human parvovirus B19 induced epidemic red cell aplasia in patients with hereditary hemolytic anemia. Blood 67: 1411–1417, 1986. 57 Takahashi M, Koike T, Moriyama Y, et al.: Inhibition of erythropoiesis by human parvovirus-Containing serum from a patient with hereditary spherocytosis in aplastic crisis. Scand J Haematol 37: 118–124, 1986. 58 Nunoue T, Koike T, Koike R, et al.: Infection with human parvovirus (b19), aplasia of the bone marrow and a rash in hereditary spherocytosis. J Infect 14: 67–70, 1987. Cohen H, Walker H, Delhanty JDA, et al.: Congenital spherocytosis, B 19 parvovirus infection and inherited interstitial deletion of the short arm of chromosome 8. Br J Haematol 78: 251–257, 1991. 59 Kelleher JF Jr, Luban NLC, Mortimer PP, et al.: Human serum parvovirus: A specific cause of aplastic crisis in children with hereditary spherocytosis. J Pediatr 152: 720–722, 1983. 60 Tomiyama J, Adachi Y, Hanada T, Matsunaga Y: Human parvovirus B 19-Induced aplastic crisis in autoimmune haemolytic anaemic [case Report]. Br J Haemat 69: 288–289, 1988. 61 Chitnavis VM, Paton G, Maker YF, Kendra Jr: B19 parvovirus induced red cell aplasia complicating acute cold antibody mediated haemolytic anaemia [case reports]. Br J Haematol 76: 433–439, 1990. 62 Duncan JR, Cappelini MD, Anderson MJ, et al.: Aplastic crisis due to parvovirus infection in pyruvate kinase deficiency. Lancet 2: 14–16, 1983. 63 Mabin DC, Chowdhury V: Aplastic crisis caused by human parvo-Virus in two patients with hereditary stomatocytosis [case reports]. Br J Haematol 76: 153–154, 1990. 64 West NC, Meigh RE, Mackie M, Anderson MJ: Parvovirus infection with aplastic crisis in patient with HEMPAS. J Clin Pathol 39: 1019–1020, 1986. 65 Crosby WH: Paroxysmal nocturnal hemoglobinuria: Report of a case complicated by an aregenerative (aplastic) crisis. Ann Intern Med 39: 1107–1117, 1952. 66 Lefrere JJ, Bourgeois H: Human parvovirus associated with eryth-Roblastopenia in iron deficiency anaemia [letter]. J Clin Pathol 39: 1277–1278, 1986. 67 Tarantino MD, Shahidi N: Pure red cell aplasia associated with parvovirus B19 (pB19) infection in iron deficiency. Pediatr Res 29: 896A, 1991. 68 Frickhofen A, Raghavachar A, Heit W, et al.: Human parvovirus infection [letter]. N Engl J Med 314: 646, 1986. 69 LeFrere JJ, Courouce A-M, Girot R, et al.: Six cases of hereditary spherocytosis revealed by human parvovirus infection. Br J Haematol 62: 653–658, 1986. 70 Bertrand Y, Lefrere JJ, Leverger G, et al.: Autoimmune hemolytic anaemia revealed by human parvovirus linked erythroblastopenia. Lancet 2: 382, 1985. 71 Saunders PWG, Reid MM, Cohen BJ: Human parvovirus induced cytopenias: a report of five cases. Br J Haematol 63: 407–410, 1986. 72 Doran HM and Teall: Neutropenia accompanying erythroid aplasia in human parvorvirus infection [case reports]. Br J Haematol 69: 281–289, 1988. 73 Hanada T, Koike K, Takeya T, et al.: Human parvovirus B19-Induced transient pancytopenia in a child with hereditary spherocytosis. Br J Haematol 70: 113–115, 1988. 74 Wodzinski MA, Lilleyman JS: Transient erythroblastopenia of childhood due to human parvovirus B19 infection [case reports]. Br J Haematol 73: 127–131, 1989. 75 Boruchoff SE, Woda BA, German AP, et al.: Parvovirus B19-Associated hemophagocytic syndrome. Arch Intern Med 150: 897–899, 1990. 76 Koch WC, Massey G, Russell CE, et al.: Manifestations and treatment of human parvovirus B19 infection in immunocompromised patients. J Pediatr 116: 355–359, 1990. 77 Morinet F, Monsuez J, Roger P, Perol Y: Parvovirus B19 associated with pseudoappendicitis [letter]. Lancet 2: 1466, 1987. 78 Smith CA, Woolf AD, Lenci M: Parvoviruses: infections and arthropathies. Rheum Dis Clin North Am 13: 249–263, 1987. 79 Balfour HH Jr, Schiff GM, Bloom JE: Encephalitis associated with erythema infectiosum. J Pediatr 77: 133–136, 1970. 80 Hall CB, Horner FA: Encephalopathy with erythema infectiosum. Am J Dis Child 131: 65–67, 1977. Van Horn DK, Mortimer PP, Young NS, Hanson GR: Human parvovirus-Associated red cell aplasia in the absence of underlying hemolytic anemia. Am J Pediatr Haematol Oncol 8: 235–239, 1986. 81 Guillot M, Lefrere JJ, Ravenet N, et al.: Acute anaemia and aplastic crisis without haemolysis in human parvovirus infection [letter]. J Clin Pathol 40: 1264–1265, 1987. 82 Hamon MD, Newland AC, Anderson MJ: Severe aplastic anaemia after parvovirus infection in the absence of underlying haemolytic anaemia [letter]. J Clin Pathol 41 1242–1246, 1988. 83 Mortimer PP, Humphries RK, Moore JG, Purcell RH, Young NS: A human parvovirus-Like virus inhibits haematopoietic colony formation in vitro. Nature 302: 426–429, 1983. 84 Young NS, Mortimer PP, Moore JG, et al.: Characterization of a virus that causes transient aplastic crisis. J Clin Invest 73: 224–230, 1984. 85 Young N, Harrison M, Moore J, Mortimer P, Humphries RK: Direct demonstration of the human parvovirus in erythroid progenitor cells infected in vitro. J Clin Invest 74: 2024–2032, 1984. 86 Ozawa K, Kurtzman G, Young N: Replication of the B19 parvovirus in human bone marrow cultures. Science 233: 883–886, 1986. 87 Ozawa K, Young N: B19 parvovirus capsid and non-Capsid proteins detected in human erythroid bone marrow cultures. J Virol 61: 2627–2630, 1987. 88 Ozawa K, Kurtzman G, Young N: Productive infection by B19 parvovirus of human erythroid bone marrow cells in vitro. Blood 70: 384–391, 1987. 89 Takahashi T, Ozawa K, Takahashi K, et al.: Susceptibility of human erythropoietic cells to B19 parvovirus in vitro increases with differentiation. Blood 75: 603–610, 1990. 90 Srivastava A, Bruno E, Briddell R, et al.: Parvovirus B19-Induced perturbation of human megakaryocytopoiesis in vitro. Blood 76: 1997–2004, 1990. 91 Kurtzman GJ, Ozawa K, Cohen B, et al.: Chronic bone marrow failure due to persistent B19 parvovirus infection. N Engl J Med 317: 287–294, 1987. 92 Kurtzman GJ, Cohen BJ, Field AM, et al.: Immune response to B19 parvovirus and an antibody defect in persistent viral infection. J Clin Invest 84: 1114–1123, 1989. 93 Kurtzman GJ, Cohen B, Meyers P, et al.: Persistent B19 parvovirus infection as a cause of severe chronic anaemia in children with acute lymphocytic leukaemia. Lancet 2: 1159–1162, 1988. 94 Smith MA, Shah NR, Lobel JS, Cera PJ, Gary GW, Anderson LJ: Severe anemia caused by human parvovirus in a leukemia patient on maintenance chemotherapy. Clin Pediatr 27: 383–386, 1988. 95 Coulombel L, Morinet F, Mielot F, Tohernia G: Parvovirus infection, leukaemia, and immunodeficiency [letter]. Lancet 1: 101–102, 1989. 96 Davidson JE, Gibson B, Gibson A, Evans TJ: Parvovirus infection, leukaemia and immunodeficiency [letter]. Lancet 1: 102, 1989. 97 Carstensen J, Ornvold K, Cohen BJ: Human parvovirus B19 infection associated with prolonged erythroblastopenia in a leukemic child [letter], Pediatr Infect Dis J 8: 56, 1989. 98 Mintzer D, Reilly R: Pure red cell aplasia associated with human immunodeficiency virus infection: response to intravenous gammaglobulin. Blood 87: 124A, 1987. 99 deMayolo JA, Temple JD: Pure red cell aplasia due to B19 infection in a man with HIV infection. B South Med J 83: 1480–1481, 1990. 100 Frickhofen N, Abkowitz JL, Safford M, et al.: Persistent parvovirus infection in patients infected with human immunodeficiency virus type 1 (hIV-1): A treatable cause of anemia with AIDS. Ann Intern Med 113: 926–933, 1990. 101 Weiland HT, Salimans MMM, Fibbe WE, et al.: Prolonged parvovirus B19 infection with severe anaemia in a bone marrow transplant recipient. Br J Haematol 71: 300, 1989. 102 Kurtzman G, Frickhofen N, Kimball J, et al.: Pure red-Cell aplasia of 10 years' duration due to persistent parvovirus B19 infection and its cure with immunoglobulin therapy. N Engl J Med 321: 519–523, 1989. 103 Belloy M, Morinet F, Blondin G, et al.: Erythroid hypoplasia due to chronic infection with parvovirus B19 [letter]. N Engl J Med 322: 633–634, 1990. 104 Knott PD, Welply GAC, Anderson MJ: Serologically proved intrauterine infection with parvovirus. Br Med J 289: 1660, 1984. 105 Brown T, Anand A, Ritchie LD, et al.: Intrauterine parvovirus infection associated with hydrops fetalis [letter]. Lancet 2: 1033–1034, 1984. 106 Wright EP, Dyson AJ, Alaily A: Infection with parvovirus during pregnancy [letter]. Br Med J 290: 241, 1985. 107 Mortimer PP, Cohen BJ, Buckley MM, et al.: Human parvovirus and the fetus [letter]. Lancet 2: 1012, 1985. 108 Brown T, Ritchie LD: Infection with parvovirus during pregnancy [letter]. Br Med J 290: 559–560, 1985. 109 Lefrere JJ, Damez Y, Courouce AM, et al.: Intrauterine infection with human parvovirus [letter]. Lancet 1: 449, 1986. 110 Gray ES, Anand A, Brown T: Parvovirus infections in pregnancy [letter]. Lancet 1: 208, 1986. 111 Bond PR, Caul EO, Usher J, et al.: Intrauterine infection with human parvovirus [letter]. Lancet 1: 448: 449, 1986. 112 Woernie CH, Anderson LJ, Tattersall P, Davison JM: Human parvovirus B19 infection during pregnancy. J Infect Dis 156: 17–20, 1987. 113 Knisely AS, O'shea PA, McMann R, et al.: Electron microscopic identification of parvovirus virions in erythroid-Line cells in fatal hydrops fetalis. Pediatr Pathol 8: 163–170, 1988. 114 Porter HJ, Khong TY, Evans MF, et al.: Parvovirus as a cause of hydrops fetalis: Detection by in situ DNA hydridisation. J Clin Pathol 41: 381–383, 1988. 115 Rodis JF, Hovick TJ Jr, Quinn DL, Rosengren SS, Tattersall P: Human parvovirus infection in pregnancy. Obstet Gynecol 72: 733–738, 1988. 116 Anderson LJ, Hurwitz ES: Human parvovirus B19 and pregnancy. Clin Perinatol 15: 273–286, 1988. 117 Caul EO, Usher MJ, Burton PA: Intrauterine infection with human parvovirus B19: A light and electron microscopy study. J Med Virol 24: 55–66, 1988. 118 Schwarz TF, Roggendorf M, Hottentrager B, et al.: Human parvo-Virus B19 infection in pregnancy [letter]. Lancet 2: 566–567, 1988. 119 Maeda H, Shimokawa H, Satoh S, et al.: Nonimmunologic hydrops fetalis resulting from intrauterine human parvovirus B-19 infection: Report of two cases. Obstet Gynecol 72: 482–485, 1988. 120 Franciosi RA, Tattersall P: Fetal infection with human parvovirus B19. Hum Pathol 19: 489–491, 1988. 121 Kinney JS, Anderson LJ, Farrar J, et al.: Risk of adverse outcomes of pregnancy after human parvovirus B19 infection. J Infect Dis 157: 663–667, 1988. 122 Anderson MJ, Khousam MN, Maxwell DJ, Gould SJ, Happerfield LC, Smith WJ: Human parvovirus B19 and hydrops fetalis [letter]. Lancet 1: 535, 1988. 123 Committee on Infectious Diseases: Parvovirus, erythema infectiosum, and pregnancy. Pediatrics 85: 131–133, 1990. 124 Hall SM, Cohen BJ, Mortimer PP, et al.: Prospective study of human parvovirus (b19) infection with pregnancy. Br Med J 300: 1166–1170, 1990. 125 Weiland HT, Vermey-Keers C, Salimans MMM, et al.: Parvovirus B19 associated with fetal abnormality [letter]. Lancet 1: 582–683, 1987. 126 Levy M, Read SE: Erythema infectiosum and pregnancy-Related complications. Can Med Asso J 143: 849–858, 1990. 127 Van Elsacker, Niele AM, Salimans MM, et al.: Fetal pathology in human parvovirus B19 infection. Br J Obstet Gynaecol 96: 768–775, 1989. 128 Bratteby LE, Garby L, Wadman B: Studies on erythrokinetics in infancy. XIII. The mean life span and the life span frequency function of red blood cells formed during foetal life. Acta Paediat Scand 57: 305, 311–320, 1968. 129 Porter HJ, Quantrill AM, Fleming KA: B19 parvovirus infection of myocardial cells [letter]. Lancet 1: 535–536, 1988. 130 Saint-Martin J, Choulet JJ, Bonnaud E, Morinet F: Myocarditis caused by parvovirus [letter]. J Pediatr 116: 1007, 1990. 131 Naides SJ, Weiner CP: Antenatal diagnosis and palliative treatment of nonimmune hydrops fetalis secondary to fetal parvovirus B19 infection. Prenatal Diagn 9: 105–114, 1989. 132 Goldflocher S, Grotsky HW, Chang C-H, et al.: Idiopathic neonatal iron storage involving the liver, pancreas, heart, and endocrine and exocrine glands. Hepatology 1: 58–64, 1981. 133 Silver MM, Beverly DW, Valberg LS, et al.: Perinatal hemochromatosis. Clinical morphologic and quantitative iron studies. Am J Pathol 128: 538–554, 1987. 134 Haddy TB, Castro OL, Rana SR: Hereditary hemochromatosis in children, adolescents and young adults. Am J Pediatr Hematol Oncol 10: 23–34, 1988. 135 Witzleben CL, Uri A: Perinatal hemochromatosis: entity or end result. Hum Pathol 20: 335–340, 1989. 136 Metzman R, Anand A, DeGinlio PA, Knisely AS: Hepatic disease associated with intrauterine parvovirus B19 infection in a newborn premature infant. Pediatr Gastroenterol Nutr 9: 112–114, 1989. 137 Silver MM, Cave CT, Kirpalani H: Perinatal hemochromatosis. Pediatr Pathol 9: 203–210, 1989. 138 Hardy L, Kinsely A, Hansen J, Kushner J, Kaplan J: Perinatal hemochromatosis: a study of gene linkage to the HLA locus. Clin Res 37: 321A, 1989. 139 Colletti RB, Clemmens JJW: Familial neonatal hemochromatosis with survival. J Pediatr Gastroenterol Nutr 7: 39–45, 1988. 140 Carrington D, Gilmore DH, Whittle MJ, et al.: Maternal serum α-Fetoprotein-A marker of fetal aplastic crisis during intrauterine human parvovirus infection. Lancet 1: 433–435, 1987. 141 Bemstein IM, Capeless EL: Elevated maternal serum α-Fetoprotein and hydrops fetalis in associated fetal parvovirus B19 infection. Obstet Gynecol 74: 456–457, 1989. 142 Rodis JF, Quinn DL, Gary GW Jr, et al.: Management and outcomes of pregnancies complicated by human B19 parvovirus infection: A prospective study. Am J Obstet Gynecol 163: 1168–1171, 1990. 143 Peters MT, Nicolaides KH: Cordocentesis for the diagnosis and treatment of human fetal parvovirus infection. Obstet Gynecol 75: 501–504, 1990. 144 Soothill P: Intrauterine blood transfusion for non-Immune hydrops fetalis due to parvovirus B19 infection [letter]. Lancet 336: 121–122, 1990. 145 Merlich A, Schwartz TF, Roggendorf M, et al.: Parvovirus B19-Infected erythroblast in fetal cord blood [letter]. Lancet 337: 310, 1991. 146 Sahakian V, Weiner CP, Naides, et al.: Intrauterine transfusion treatment of nonimmune hydrops fetalis secondary to human parvo-Virus B19 infection. Am J Obstet Gynecol 164: 1090–1091, 1991. 147 Morey AL, Nicolinc U, Welch CR, et al.: Parvovirus B19 infection and transient fetal hydrops [letter]. Lancet 337: 496, 1991. 148 Anderson LJ, Tsou C, Parker RA, et al.: Detection of antibodies and antigens of human parvovirus B 19 by enzyme-Linked immunosorbent assay. J Clin Microbiol 24: 522–526, 1986. 149 Schwartz TF, Roggendorf M, Hottentrager B, et al.: Immunoglobulins in the prophylaxis of parvovirus B19 infection [letter]. J Infect Dis 162: 1214, 1990. 150 Talcahashi M, Koike T, Moriyama Y, Shibata A: Neutralizing activity of immunoglobulin preparation against erythropoietic suppression of human parvovirus [letter]. Am J Hematol 37: 68, 1991. 151 Salimans MM, Holsappel S, Van de Rijke FM, et al.: Rapid detection of human parvovirus B19 DNA by dot-Hybridization and the polymerase chain reaction. J Virol Methods 12: 19, 1989. 152 Clewley JP: Polymerase chain reaction assay of parvovirus B19 DNA in clinical specimens. J Clin Microbiol 27: 2647, 1989. 153 Koch WC, Adler SP: Detection of human parvovirus B19 DNA by using the polymerase chain reaction. J Clin Microbiol 28: 65, 1990. 154 Okochi K, Mori R, Miyazaki M, et al.: Nakatani antigen and human parvovirus (b19) [letter]. Lancet 1: 160–161, 1984. 155 Courouce AM, Ferchal F, Morinet F, et al.: Human parvovirus infections in France [letter]. Lancet 1: 160, 1984. 156 Anderson MJ, Cohen BJ: Human parvovirus B19 infections in United Kingdom 1984-86 [letter]. Lancet 1: 738–739, 1987. 157 Schwarz TF, Roggendorf M, Deinhardt F: [letter]. Lancet 1: 739, 1987. 158 Cohen BJ, Buckley MM: The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 25: 151–153, 1988. 159 Gillespie SM, Cartler ML, Asch S, et al.: Occupational risk of human parvovirus B19 infection for school and day-Care personnel during an outbreak of erythema infectiosum. JAMA 263: 2061–2065, 1990. 160 Cartter ML, Farley TA, Rosengren S, et al.: Occupational risk factors for infection with parvovirus B19 among pregnant women. J Infect Dis 163: 282–285, 1991. 161 Bell LM, Naides SJ, Stoffman P, et al.: Human parvovirus B19 infection among hospital staff members after contact with infected patients. N Engl J Med 321: 485–491, 1989. Citing Literature Volume39, Issue2February 1992Pages 119-130 ReferencesRelatedInformation

Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia, who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network.

To obtain new information concerning the behaviors, and in turn the structures, of gels formed from mixtures of S and A hemoglobins, their physical properties have been characterized by stress relaxation with a rotational rheometer. The variables manipulated were (1) initial total hemoglobin concentration, (2) mole fraction of hemoglobin S present in the mixture, (3) hemoglobin A as intact tetramer only or as both tetramer and hybridized hemoglobin AS, (4) annealing time, (5) shear history, (6) temperature, and (7) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin SA gels were less solid than those of pure S of similar initial hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by shear history, annealing time, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin SA gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. The presence of hemoglobin A with hemoglobin S results in polymers and gels that differ from those found in pure hemoglobin S. Pathophysiologic implications of these findings for sickle cell disorders are proposed.

Between March 1982 and October 1987, 375 fields in 187 patients with AIDS-related Kaposi's Sarcoma were treated in the Department of Radiation Oncology at the University of California in San Francisco (UCSF). Field sizes ranging from 2 x 2 cm to total skin received doses of 8 Gy in a single fraction to 15-40 Gy in 5-10 fractions. Seventy-four percent of the patients have died. Response to treatment was achieved in over 90% of treated fields, with a median time to progression of 21 months and an actuarial freedom from relapse at 6 months of 69% (97 patients alive). There was no difference in outcome regardless of the fractionation regimen used. Severe reactions were noted in 17% of treated fields, but this incidence was significantly lower when a single fraction of 8 Gy was used (p less than 0.001). Radiation therapy plays an important palliative role in this devastating disease. This review supports the use of a single 8 Gy fraction for all Kaposi's Sarcoma lesions of the skin. Further data regarding single fraction therapy for lesions of other sites are needed.

The physical properties of deoxyhemoglobin S gels formed from solutions at concentrations and temperatures approaching those in vivo have been characterized by stress relaxation using a rotational rheometer. Gels were annealed in the rheometer and then subjected to a constant shear strain; thereafter the stress sustained was followed with time. Gels with solid-like behavior held stress indefinitely, and were characterized by yield temperature (the temperature at which stress decreased). Gels with less solid behavior were unable to hold target stress, and were characterized by yield stress (maximum stress attained) and equilibrium stress (final stress held). The samples were ultracentrifuged to calculate pellet and polymer masses. The solidity of the gels, as measured by yield temperature or yield stress, was related to the initial hemoglobin concentration, pellet and polymer masses, shear history, temperature, and the temperature and time of annealing. Solidity increased significantly with time when gels were annealed at 37 degrees C, whereas, when annealed at 25 degrees C, no or minimal increases in solidity were noted. Studies suggest that polymerization occurs rapidly and is completed early in or before the gel annealing period and that the increase in solidity with time of annealing is mainly due to factors other than polymer mass, i.e. alignment, increasing bond strength, water loss. The chemical activity of deoxyhemoglobin S did not affect the solidity of the formed gels. When the resultant polymer masses were comparable, gels formed from samples with albumin present (higher initial total protein concentration, but lower initial deoxyhemoglobin S concentration), had the same behavior as gels formed from solutions with higher initial hemoglobin S concentration. These findings demonstrate that gel annealing conditions must be standardized when comparing the rheologic behaviors of deoxyhemoglobin S gels and indicate that the gel's physical properties (influenced by polymer mass, shear history, annealing time) must be considered in understanding pathophysiology of sickling disorders.

Ear oximetry was used to monitor arterial oxygenation in seven patients who had a history of frequent admissions for sickle cell crisis and were taking narcotic analgesics. Five full-night studies and seven daytime "nap" studies were performed in which sleep state was monitored by electroencephalography, and respiratory rate and tidal volume were monitored by inductance plethysmography. For all patients the mean (+/- SEM) of the median oxygenation values was 93.3% +/- 0.4% during wakefulness and 91.4% +/- 0.8% during sleep. During wakefulness the lowest saturation was 90% +/- 0.5%; during sleep there was a fall in the lowest oxygen saturation to 86.5% +/- 0.9%. In all patients a fall in oxygen saturation was associated with a decrease in respiratory depth without a change in respiratory frequency. The results indicate that in sickle cell disease oxygen saturation is lower during sleep than during wakefulness and that hypoxemia can be attributed to a fall in tidal volume.

A hemoglobin variant was identified as hemoglobin Mobile in which valine replaces the normal aspartic acid at beta 73. Studies of its oxygen equilibria and of its interactions in gelation when mixed with hemoglobin S were carried out. Hemoglobin Mobile had an oxygen affinity lower than that of hemoglobin A, as observed by others. However, in mixtures with hemoglobin S, hemoglobin Mobile appeared to impair gelation or increase solubility to a slightly greater extent than did hemoglobin A. Beta 73 is a known site of intermolecular interactions in polymers of hemoglobin S. Our studies suggest that the impairment of hemoglobin S polymer formation by altered intermolecular interactions is significantly less in Hb Mobile than in Hb Korle-Bu in which beta 73 is asparagine.