bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophilic fibrohistiocytic lesion of bone marrow associated with monoclonal gammopathy and osteolytic lesions
Authors: Nagler A. , Ben‐Arieh Y. , Brenner B. , Tatarsky I. , Pollack S.
Published: February 2007

We describe a 63‐year‐old male patient with severe osteoporosis, multiple lytic bone lesions, and monoclonal gammopathy (IgGλ). Whereas the tentative diagnosis in this case was multiple myeloma, bone marrow trephine biopsies of the iliac crest and from an osteolytic lesion of the tibia both showed a peculiar infiltrate consisting of numcrous clongated mast cells, eosinophils, and some plasma cells and lymphocytes. The bone marrow lesions fit the diagnosis of eosinophilic fibrohistiocytic lesion of bone marrow (EFHBM). The patient had no abnormality that could be related to a known allcrgic disease, and no relationship to drug hypersensitivity could be established. The features of the bone marrow infiltrate and its association with monoclonal gammopathy may suggest a linkage between EFHBM and the monoclonal gammopathy.
The mechanisms of sulfonylurea‐induced immune hemolysis: Case report and review of the literature
Authors: Kopicky Joyce A. , Packman Charles H.
Published: February 2007

Chlorpropamide, a sulfonylurea antidiabetic drug, was found to be the etiologic agent in a patient with immune hemolytic anemia. Hemolysis was severe, and ceased promptly when the drug was discontinued. The direct antiglobulin test was positive for complement, and the indirect antiglobulin test was also positive when the drug, patient serum, and fresh serum complement were all present. In this patient, and in four other patients described in the literature, hemolysis was mediated by the immune complex mechanism. In reports of two other patients taking a sulfonylurea drug, a milder form of hemolysis was mediated by the hapten mechanism. Sulfonylurea drugs are widely used. Since immune complex‐mediated hemolysis in these patients is dramatic, it is not likely to be missed. However, the slower, milder hemolysis mediated by the hapten mechanism may be more common than is realized. Such patients may have only mild anemia and a near‐normal reticulocyte count, making the diagnosis difficult. It is thus important to consider drug‐immune hemolysis in patients who become anemic while taking sulfonylurea drugs.
Hepatitis B vaccination of 113 hemophiliacs: Lower antibody response in anti‐LAV/HTLV‐III‐positive patients
Authors: Zanetti A. R. , Mannucci P. M. , Tanzi E. , Moroni G. A. , De Paschale M. , Morfini M. , Carnelli V. , Tirindelli M. C. , De Biasi R. , Ciavarella N. , De Rosa V. , Rodeghiero F. , Colombo M.
Published: February 2007

One‐hundred thirteen adults and children with hemophilia or other congenital bleeding disorders were vaccinated against the hepatitis B virus. Each patient was given three subcutaneous injections of the vaccine at monthly intervals and then a fourth booster dose 14 months after the first. The vaccine was highly immunogenic, since 111 of 113 patients (98%) produced anti‐HBs (10 mlU/ml or more). After the first three vaccine doses and after the booster dose, ten anti‐LAV/HTLV‐III‐positive hemophiliacs produced anti‐HBs but had a lower average titer than anti‐LAV/HTLV‐III‐negative hemophiliacs. Of the 23 patients treated with concentrates in the 15 month postvaccination period only, none acquired HBV infection. Of the 50 patients treated with concentrates also in the 6 month prevaccination period, one developed hepatitis B. In summary, the vaccine was highly immunogenic in both children and adults with hemophilia; anti‐LAV/HTLV‐III‐positive patients responded to the vaccine, but the average anti‐HBs response was lower; no case of hepatitis B occurred in patients treated with concentrates only in the postvaccination period.
Megakaryocytic colony formation (CFU‐Meg) in essential thrombocythemia: Quantitative and qualitative abnormalities of bone marrow CFU‐Meg
Authors: Klmura Hideo , Ishibashi Toshiyuki , Sato Tadashi , Matsuda Shin , Uchida Tatsumi , Kariyone Shigeo
Published: February 2007

For the purpose of examining the mechanisms for the overproduction of megakaryocytes and platelets in essential thrombocythemia (ET), marrow megakaryocytic colony‐forming units (CFU‐Meg) were characterized using a methylcellulose culture system in nine patients with ET, and they were compared with those of 16 control subjects and four patients with secondary thrombocytosis (ST). The number of CFUMeg per 105 cells in ET was significantly higher (p< 0.001) than that in the controls (5.8 times of the controls) or that in ST. ET showed endogenous CFU‐Meg (58 ± 16% of the total CFU‐Meg) that could form megakaryocytic colonies without phytohemagglutinin‐stimulated leukocyte‐conditioned medium (PHA‐LCM) as a source of Meg‐CSA. The controls and the patients with ST revealed no endogenous CFU‐Meg. The dose‐response studies with PHA‐LCM revealed that CFU‐Meg from ET are highly sensitive to low concentrations of PHA‐LCM compared to CFU‐Meg from the control and ST.

Erythropoietic burst‐forming units (BFU‐E) were monitored as a control progenitor, because the patients with ET studied did not have erythrocytosis. Although five out of nine patients with ET had endogenous BFU‐E, the percentages of endogenous BFU‐E were small (4–10%). The number of BFU‐E in ET was not different from the control value. Thus, ET is associated with an enlarged CFU‐Meg compartment that shows abnormal growth patterns when cultured in vitro, while the growth abnormality of BFU‐E is small, which may underlie the hematological features of ET. The culture of CFU‐Meg should be clinically useful for differentiating ET from ST.
Analysis of cell cycle characteristics and course of the disease in ANLL
Authors: Raza Azra , Maheshwari Yogesh , Brereton William , Preisler Harvey D.
Published: February 2007

The cell cycle characteristics of a newly diagnosed patient with acute nonlymphocytic leukemia (ANLL) were studied by using intravenous bromodeoxyuridine (BrdU) and our previously described “double‐label” technique. The percentage of S‐phase cells in the bone marrow (BM) biopsy were 25 % compared to 7 % from the simultaneously obtained BM aspirate. The duration of S‐phase (Ts) was determined to be 4 hr and the total cell cycle time (Tc) was 16 hr. We demonstrated that the actual clinical course of this patient's illness corresponded well with the course predicted on the basis of these cell cycle measurements. Although he achieved aplasia in response to two successive courses of induction chemotherapy, leukemic cells repopulated the marrow, producing a rapidly rising PB white blood cell (WBC) count with a T1/2 of approximately 20 hr each time. It is likely that the resistance of this patient's leukemia to therapy was a result of the rapid proliferative rate of his leukemic cells and not due to the inability of chemotherapeutic agents to kill a large number of cells. Since the measurements can be completed within 48 hr, measuring Ts and Tc will provide a better understanding of the biological differences that exist between patients with ANLL.
Peripheral blood t‐cell subpopulations in the very low birth weight (less than 1,500‐g) infant
Authors: Ballow Mark , Cates K. Lynn , Rowe Jonelle C. , Goetz Cynthia , Pantschenko Alexander G.
Published: February 2007

The development of monoclonal antibodies to cell‐surface antigens has provided method for characterizing distinct subpopulations of T‐cells. In the present study we have quantified peripheral blood T‐cell subpopulations in premature infants born weighing less than 1,500 g (1123 ± 223 g) and ranging in gestational age from 25 to 32 weeks. The relative proportion of T4 cells in the very low birth weight (VLBW) infants was markedly higher at l week and 1 month of age (mean ± SEM; 67.5 ± 4.1 and 59.2 ± 1.6) than in adult controls (47.2 ± 1.5). The percentage of T4 cells remained elevated until 6 months of age, when it decreased to a level comparable to that in adults. In contrast, the proportion of T8 cells was significantly lower than the adult level at 1 week and 1 month of age. The T4/T8 ratio in the VLBW infants was higher at 1 week (4.3 ± 0.5) and 1 month (3.5 ± 0.2) than in adult controls (2.0 ± 0.1). Thereafter, the T4/T8 ratio decreased but was still significantly higher than that in adult controls at 6 months of age (2.6 ± 0.2). The absolute numbers of total T‐cells (T3) and T8 and T4 cells were significantly higher in VLBW infants. The numbers of T8 cells were significantly lower in the first month of life than at 3‐6 months of age. These alterations in the T‐cell subsets in the first 6 months of life suggest that postnatal T‐cell phenotypic changes in VLBW infants may parallel the T‐cell ontogenetic process which occurs during the last trimester of pregnancy in fullterm infants.
Iron status of beta thalassemia carriers
Authors: Mehta B. C. , Pandya B. G.
Published: February 2007

One hundred twenty‐four relatives (aged 17‐52 years) of 35 children with severe transfusion‐dependent beta thalassemia major were investigated for their beta thalassemia carrier status (determined by Hb‐A2 level) and iron status (determined by serum ferritin level). Forty‐eight males had beta thalassemia trait (BTT) and 18 males did not have BTT (control); 41 females had BTT and 17 females did not have BTT (control). Serum ferritin levels (mean ± SEM) of male BTT, male control, female BTT, and female control groups were 151.0 ± 27.4, 59.6 ± 16.3, 120.6 ± 36.6, and 17.2 ± 6.1 meg/liter respectively; the differences between the two male and the two female groups were statistically significant (p = 0.05 and p < 0.001). Iron deficiency (serum ferritin below 10.0 meg/liter) was present in 6.3%, 38.9%, 24.4%, and 58.8% of male BTT, male control Female BTT, and female control groups, respectively; the differences between the two male and two female groups were statistically significant (p < 0.01 and p < 0.01). Serum ferritin was over 1,000 meg/liter in four individuals with BTT (2 male and 2 female). Thus, the BTT group had better iron nutrition. This may suggest that the BTT group has an advantage in maintaining iron balance.
Case report: T‐cell acute lymphoblastic leukemia relapsing as acute myelomonocytic leukemia and terminating possibly as chronic myelocytic leukemia
Authors: Shimizu Jyoji , Hamashima Yoshihiro , Tsuda Hideo , Akiyama Yuichi , Mikawa Haruki , Ikehara Susumu
Published: February 2007

A 9‐year‐old boy suffering from T‐cell acute lymphoblastic leukemia (T‐ALL) with a mediastinal mass had a complete remission as a result of treatment. Ten months later, he developed a typical acute myelomonocytic leukemia (AMMoL) pattern. Two months after a second relapse, he showed a clinical picture that was indistinguishable from chronic myelocytic leukemia (CML).

At autopsy, massive infiltration of CML‐like cells was observed even in the thymus (190 g). These observations suggest that the leukemia in this child arose in a pluripotent stem cell capable of differentiation into both T‐lymphocytic and myelomonocytic lineages.
An autoantibody with poten antithrombin activity whose action could be inhibited by toluidine blue or methylene blue
Authors: Shojania A. Majid , Meilleur Gisele , Alvi Abdul W.
Published: February 2007

A 41‐year‐old man with posthepatitic liver cirrhosis and bleeding tendency was found to have a circulating anticoagulant with potent antithrombin activity. The thrombin time of the patient's purified fibrinogen was normal. This anticoagulant was residing in the patient's IgG fraction, and his IgG fraction could prolong the thrombin time of purified fibrinogen, suggesting that this circulating anticoagulant was an antibody. No heparin was detected in the patient's plasma. However, the antithrombin activity of this anticoagulant could be neutralized by toluidine blue or methylene blue ex vivo.
Restoration of decreased suppressor cells by vitamin B12therapy in a patient with pernicious anemia
Authors: Kubota Kazuo , Arai Toshimasa , Tamura Jun'Ichi , Shirakura Takuo , Morita Toyoho
Published: February 2007

A unique case of pernicious anemia is described. Initially, the percentage of OKT8‐positive blood cells was markedly decreased, resulting in an increase in the OKT4/OKT8 ratio. The level of OKT8‐positive blood cells was, however, returned to normal after vitamin B12therapy. The finding may propose a possible role of the imbalance of blood lymphocyte subpopulations on the pathogenesis of pernicious anemia and also a responsibility of vitamin B12for such a selective reduction in the OKT8‐positive blood cells.
Transient response of pure red cell aplasia to anti‐thymocyte globulin in a patient with T‐cell chronic lymphocytic leukemia
Authors: Hocking William , Champlin Richard , Mitsuyasu Ronald
Published: February 2007

Pure red cell aplasia (PRCA) is an unusual complication of chronic lymphoproliferative disorders. A patient with T‐cell chronic lymphocytic leukemia (T‐CLL) had severe anemia and neutropenia. Initial in vitro studies demonstrated no evidence of T‐cell suppression of erythropoiesis. Sequential bone marrow examinations demonstrated progressive red cell aplasia. In vitro studies showed that the T‐cells from the patient suppressed allogeneic but not autologous BFU‐E. Treatment with antithymocyte globulin (ATG) reduced circulating leukemic cells and produced a definite but transient improvement in erythropoiesis.
Marked hypodiploidy in blast phase chronic myelogenous leukemia: Report of a case and review of the literature
Authors: Cibull Michael L. , Thompson Mark E. , Smith Linda , Jennings C. Darrell , Doukas Michael A. , Pavlik Edward J. , Powell Deborah E.
Published: February 2007

The emergence of a near‐haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients.
Two new variants of glucose‐6‐phosphate dehydrogenase associated with hereditary non‐spherocytic hemolytic anemia: G6PD wayne and G6PD huron
Authors: Ravindranath Y. , Beutler Ernest
Published: February 2007

Two new deficient variants of glucose‐6‐phosphate dehydrogenase (G6PD) causing hereditary nonspherocytic hemolytic anemia (HNSHA) are described. Both of these are unique and they have been named G6PD Wayne and G6PD Huron. Patients with G6PD Wayne underwent splenectomy and no objective improvement was noted. The patients with G6PD Huron were under medical observation for a considerable period of time without the diagnosis of G6PD deficiency being entertained because the family was of Northern European origin. Since sporadic variants of G6PD causing HNSHA show no special racial predilection, the diagnosis of G6PD deficiency should always be considered in patients with this syndrome.
Use of capillary blood for the evaluation of iron status
Authors: Lu Yuying , Lynch Sean R. , Cook James D. , Madan Nishi , Bayer William L.
Published: February 2007

The accuracy and precision of measurements of iron status made on the capillary blood from a single 75 × 1‐mm microhematocrit tube were evaluated in 301 normal volunteers. After recording the hematocrit value, a hematofluorometer was used to assay erythrocyte protoporphyrin directly on the packed red cell fraction. Values in the low normal range were 50‐100% higher than assays by an extraction technique in simultaneously collected venous blood. However, measurements in the iron deficient range were only 12 % greater. Plasma ferritin concentration was determined by using an enzyme‐linked immunoassay on 10‐μl plasma retrieved after measuring the hematocrit. Capillary values were approximately 7% higher than venous concentrations, the proportional difference being consistent throughout the measured range. When the individual measurements were combined to calculate the iron storage status of each individual, the frequency distribution of iron stores in 141 female volunteers between 18 and 36 years of age was approximately Gaussian and paralleled that calculated for women aged 18‐44 years in NHANES II. These studies demonstrate that iron status can be r'etermined accurately from the measurement of hematocrit, erythrocyte protoporphyrin, and ferritin on a single microhematocrit tube of capillary blood.
Predictive value of enzyme‐linked immunoassay platelet crossmatching for transfusion of platelet concentrates to alloimmunized recipients
Authors: Brubaker Daniel B. , Duke James C. , Romine Maxine
Published: February 2007

Some evidence has shown that platelet crossmatching is useful in multitransfused patients with hypoplastic bone marrows who are refractory to platelet therapy through alloimmunization. Several immunoglobulin binding assays other than enzyme‐linked immunospecific assay (ELISA) have been studied previously. We performed 51 ELISA crossmatches on six patients receiving single donor platelets. One bone marrow transplant patient receiving 33 single donor HLA matched (related and unrelated) was also studied. Effectiveness of transfusion was closely monitored by patient evaluation and corrected platelet count increment (CCI) at 1‐2 and 18‐24 hours posttransfusion. We found the ELISA method very sensitive, specific, and predictive, 85, 96, and 95.6% respectively in the 51 crossmatches studied in six patients with either leukemia, solid tumors, or aplastic anemia. However, variation existed among individual recipients, with sensitivity ranging from 70‐100%. The distribution of true positives and negatives and false positives and negatives in the 33 crossmatches performed in the bone marrow transplant patient differed significantly (X2 − 101.2; P < 0.001) from single donor recipients. The specificity in the 51 crossmatches on the six patients was also significantly different from the 33 crossmatches performed in the bone marrow transplant (96 vs 74%). This suggests individual variation occurs as well as differences in diseases and bone marrow suppressive agents affecting platelet crossmatching.
Nonclonal hemopoietic progenitors in a G6PD heterozygote with chronic myelogenous leukemia revealed after long‐term marrow culture
Authors: Hogge Donna E. , Coulombel Laure , Kalousek Dagmar K. , Eaves Connie J. , Eaves Allen C.
Published: February 2007

When marrow cells from Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) patients are placed into long‐term culture, Ph‐positive progenitor numbers typically decline rapidly. Karyotypically normal cells derived from persisting, but previously undetectable, precursors can then frequently be demonstrated. To investigate the origin of these cytogenetically normal progenitors, longterm cultures were established with marrow from a girl with CML who was also heterozygous for the glucose‐6‐phosphate dehydrogenase (G6PD) enzyme variants A and B as shown by studies of her skin fibroblasts. Erythroid and granulocytic colonies generated in methylcellulose assays of fresh marrow from this patient were all Phpositive and expressed the enzyme G6PD‐A as found in the mature blood cells. In assays of 4‐ and 6‐ week‐old long‐term cultures, numbers of progenitors present were low and most were Ph‐positive, but some (2/11) were Ph‐negative. G6PD analysis showed that a similar proportion was not part of the neoplastic clone (4/30 were G6PD‐B and 26/30 were G6PD‐A). Thus, long‐term marrow culture in conjunction with G6PD analysis was able to reveal the presence of a nonclonal hemopoietic progenitor population in a CML patient where such cells would not otherwise have been detected. This approach may offer a novel strategy for the demonstration and selection of populations of normal hemopoietic progenitors in other patients where the malignant cells cannot be distinguished by chromosome analysis.
Severe thrombocytopenia in iron deficiency anemia
Authors: Berger Mark , Brass Lawrence F.
Published: February 2007

Mild‐to‐moderate thrombocytopenia has been reported as an occasional finding in patients with iron deficiency. The present case describes a multiparous woman who presented with increased menorrhagia, severe anemia (3.0 g/dl) and thrombocytopenia (9,000 platelets/mm3). Her bone marrow examination showed iron deficiency, megakaryocytopenia, and erythroid hypoplasia but no other evidence of a primary marrow disorder. Her symptoms, the thrombocytopenia and the megakaryocytopenia, resolved with iron replacement. This case demonstrates the profound degree to which thrombopoiesis can be affected in iron deficiency.
Screening for sickle cell trait: The veterans administration national sickle cell program
Authors: Meyer Leo M. , Adams Junius G. , Steinberg Martin H. , Miller Inez E. , Stokes Norma
Published: February 2007

Results of the Veterans Administration Sickle Cell Program for a period of 10 years are presented. We screened 370,250 patients; 404,341 attended educational sessions, and 38,347 had individual counseling sessions. Sickle cell trait was present in 6.4% of patients, and HbC trait was present in 1.8%. The clinically significant disorders HbSC disease, sickle cell anemia, and sickle β thalassemia were present in 0.41% of individuals screened. A large number of uncommon variants were detected. The program enhanced the awareness of and the approach to evaluation of hemoglobinopathies.
Spontaneous hemoperitoneum in two patients with myeloproliferative disorders
Authors: Storniolo Anna Maria , Fitzgerald Denis B. , Rowe Jacob M. , Olson John P.
Published: February 2007

Spontaneous hemoperitoneum developed in two patients with hitherto undiagnosed myeloproliferative disorders. No other known etiology could be attributed to the two patients described. The report of these two patients suggests that the diatnosis of a myeloproliferative disorder should be considered in the evaluation of patients with spontaneous hemoperitoneum.
Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: Spontaneous recovery from the neutrophil abnormalities during early childhood
Authors: Yasui Kozo , Yamazaki Munehiro , Miyagawa Yukiaki , Komiyama Atsushi , Akabane Taro
Published: February 2007

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8‐month‐old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N‐formyl‐methionyl‐leucyl‐phenylalanine (3H‐FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (< 3 SD) as compared with those of control cells of 52,000 ± 6,000 (mean ± SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.
Refractory aplastic anemia: Concomitant therapy with antithymocyte globulin and high‐dose corticosteroids
Authors: Pulver Kerry P. , Flaum Morris A.
Published: February 2007

Bone marrow transplantation is possible for only a minority of patients with severe aplastic anemia. There has been successful treatment in some patients with immunosuppressive agents: high‐dose 6‐methylprednisolone, antilymphocyte globulin, and antithymocyte globulin. We report the successful treatment oftwo patients with severe aplastic anemia with the simultaneous adminstration of antithymocyte globulin and high‐dose 6‐methylprednisolone after failure with antithymocyte globulin and low‐dose corticosteroids.
Hermansky‐pudlak platelets: Further studies on release reaction and protein phosphorylations
Authors: Rendu Francine , Maclouf Jacques , Launay Jean‐Marie , Boinot Catherine , Levy‐Toledano Sylviane , Tanzer Joseph , Caen Jacques
Published: February 2007

Platelets from a patient with the Hermansky‐Pudlak syndrome were studied. These platelets had decreased amounts of serotonin and adenine nucleotides, and a decreased number of mepacrine‐labeled dense bodies. β‐Thromboglobulin and acid hydrolases contained in alpha‐granules and lysosomes respectively were present in normal amount. Platelets in platelet‐rich plasma did not respond to collagen, but arachidonic acid and ionophore A 23187 induced normal aggregation and normal thromboxane (TX) synthesis. Alpha‐granule release was found impaired and remained subnormal even with high doses of inducers. In response to thrombin aggregation, release and TX synthesis of isolated metrizamide gradient platelets were found at lower than normal levels. Phosphorylation of P20 and P43 proteins was normal. Only a combination of ADP plus thrombin could restore a normal aggregation, with normal alpha‐granule and lysosome release and normal TX synthesis. These results indicated that in the absence of dense bodies: 1) the release of other granules is impaired; 2) the TX synthesis is delayed except when induced by arachidonic acid and A 23187 ionophore; 3) the absence of dense bodies could be compensated for by the addition of ADP which restores the impaired release reaction and TX formation; and 4) P20 and P43 polypeptides were phosphorylated as rapidly as those in normal platelets.
Severe acute thrombocytopenia following infusion of plasma containing anti P1A1
Authors: Nijjar Tirath S. , Bonacosa Ines A. , Israels Lyonel G.
Published: February 2007

An 18‐year‐old girl with a preoperative platelet count of 216,000/cmm received 3 units of stored plasma at the time of surgery. Within 6 hours her platelet count had fallen to 5,000/mm3 and hemorrhagic manifestations appeared. One of the plasma donors was found to be P1A1 negative with an anti P1A1 antibody. The recipient, who was P1A1 positive, recovered normal platelet counts by day 8 post plasma infusion.
Concomitant occurrence of disseminated intravascular coagulation and factor VIII inhibitor in a patient with prostatic cancer
Authors: Singal Usha , Mammen Eberhard F.
Published: February 2007

An 86‐year‐old man, diagnosed as having carcinoma of the prostate, stage D, was admitted to the hospital. Soon after admission, he developed bleeding from various sites, including intravenous puncture sites and gastrointestinal and urinary tracts. A clinical diagnosis of disseminated intravascular coagulation (DIC) was made, which was corraborated by laboratory data. A factor VIII inhibitor of 12.5 Bethesda units was also identified in the patient's plasma. Concomitant occurrence of disseminated intravascular coagulation and an acquired factor VIII inhibitor has not been reported previously.
Formation and disappearance of pocked erythrocytes: Studies in human subjects and laboratory animals
Authors: Buchanan George R. , Holtkamp Christine A. , Horton Jureta A.
Published: February 2007

The pocked or “pitted” RBC count is being increasingly utilized as a test of splenic function. Since little is known about patterns of formation and removal of the characteristic organelles in the pocked RBC, we performed serial pocked RBC counts following splenectomy in six patients and in three animal species (dogs, rats, and rabbits). In the patients, pocked RBC counts began to rise within 1 week following splenectomy and reached a plateau (40‐60%) by 60‐100 days. Similar results were obtained following splenectomy of dogs, except that the plateau value was less. Pocked RBCs in splenectomized rats rose initially, but after the sixth week there was a progressive decline in their numbers; splenosis or accessory spleens were not visualized at autopsy. Rabbits had only a slight and inconsistent rise in pocked RBCs after splenectomy. When the rate of removal of pocked RBCs from the circulation was determined by transfusion of blood from splenectomized dogs in eusplenic animals, the pocked RBC count rapidly decreased within 3 to 6 hours. Pocked RBCs did not disappear when crosstransfused into a splenectomized recipient animal. Prior treatment of the recipient dog with either corticosteroids or vincristine did not affect the pattern of removal of pocked RBCs. We conclude that pocked RBCs rise slowly following splenectomy, disappear rapidly from the circulation in the presence of a normal spleen, and vary in pattern of rise and peak levels following splenectomy of different laboratory animals.
Philadelphia chromosome‐positive acute leukemia: Morphologic and clinical correlations
Authors: Helenglass Gilla , Testa Joseph R. , Schiffer Charles A.
Published: February 2007

Twenty‐eight adult patients with Philadelphia chromosome positive (Ph+) acute leukemia were studied to determine if additional chromosomal changes were related to specific morphologic and clinical features. Twenty patients had chronic myeloid leukemia in blast crisis (CML‐BC), three had Ph+ de novo acute nonlymphocytic leukemia (ANLL), and five had de novo acute lymphoblastic leukemia (ALL). Chromosomal abnormalities in addition to a single Ph were noted in 90% of patients with CML‐BC and included a second Ph (five patients), +8 or duplication of part of 8q (five patients), dicentric isochromosome 17 (two patients), and +19 (two patients). Octaploidy with 4 Ph was seen in one patient with megakaryoblastic transformation. One of two patients with a progranulocytic blast crisis had a t(15;17) abnormality. Hypodiploidy was noted in 4 of 20 patients with CML‐BC. Each of the four patients had prominent extramedullary manifestations of blast crisis. All had received intensive chemotherapy prior to the detection of hypodiploidy, and the cytogenetic findings were similar to those often seen in patients with therapy‐related leukemia. An inv(3)(q21q26) was noted in two patients (one CML‐BC, one de novo Ph+ ANLL), one of whom had hypolobulated micromegakaryocytes. Additional cytogenetic abnormalities in de novo Ph+ ANLL (especially +19) were similar to those in CML‐BC. In contrast, the additional karyotypic changes in de novo Ph+ ALL (eg, +4, –7, –20, markers) were those commonly seen in ALL without a Ph and were generally different from those seen in CML‐BC.
Nonleukemic granulocytic sarcoma of the heart: A report of a fatal case
Authors: Foucar Kathy , Foucar Elliott , Willman Cheryl , Horvath Andrew , Gerety Richard L.
Published: February 2007

We report the clinical and pathological features of a cardiac fatality caused by granulocytic sarcoma in a young adult man with no evidence of leukemia involving bone marrow or peripheral blood. At autopsy, walls of the four cardiac chambers were massively infiltrated by tumor, resulting in a cardiac weight of almost three times normal. Routine cytochemical stains plus immunoperoxidase staining for OKM1 confirmed the diagnosis. Although subclinical cardiac infiltrates are commonly detected at autopsy in patients with acute nonlymphoblastic leukemia (ANLL), massive cardiac granulocytic sarcoma in the absence of bone marrow disease has not been previously described. Cytochemical and immunological methods of diagnosing granulocytic sarcoma in fixed tissues are reviewed.
Modulation of monocyte Mo2 surface antigen expression by exposure to respiratory syncytial virus
Authors: Baumann M. A. , Paul C. C. , Stokes C. , Bernstein J. M.
Published: February 2007

The Mo2 antibody recognizes a monocyte‐specific cell surface antigen of unknown function. Upward modulation of Mo2 surface epitope density was demonstrated in response to 72‐hr culture of monocytes with respiratory syncytial vcirus (RSV), but this was not seen after culture with phytohemagglutinin or other respiratory viruses. Monoclonal antibody probes for RSV proteins were used to demonstrate probable replication of RSV proteins in peripheral blood monocytes and pulmonary alveolar macrophages. These data provide possible clues to the biologic role of the Mo2 antigen.
Essential thrombocythemia associated with recurrent abortions and fetal growth retardation
Authors: Falconer John , Pineo Graham , Blahey Walter , Bowen Tom , Docksteader Brian , Jadusingh Inderman
Published: February 2007

Essential thrombocythemia (ET) is one of the myeloproliferative disorders characterized by an elevated platelet count, usually greater than 1,000 × 109/L. It may be associated with either hemorrhagic or thrombotic tendencies. Although it usually affects older people, we have recently encountered two young women with ET who had a total of six spontaneous abortions before the end of the first trimester. During her most recent pregnancy, one of the patients underwent plateletpheresis on four separate occasions before the 12th week. She reached 34 weeks but demonstrated evidence of fetal growth retardation and pre‐eclampsia. At delivery there were scattered villus infarcts in the placenta. Based on this patient and previous reports in the literature, we postulate that the spontaneous abortions, fetal growth retardation, and pre‐eclampsia may be related to the thrombocytosis and suggest that the use of antiplatelet agents throughout pregnancy should be seriously considered in such cases.
Should platelets be radiolabelled in plasma medium?
Authors: Tsan Min‐Fu , Hill‐Zobel Robin L.
Published: February 2007

Because of the low labelling efficiency of platelets with In‐111 oxine in plasma containing media, most investigators have labelled platelets in plasma‐free media. However, labelling of platelets with In‐111 oxine in plasma‐free media may result in either: 1) irreversible damage leading to rapid clearance from the circulation and permanent hepatic sequestration; or 2) reversible damage with transient hepatic sequestration without affecting the in vivo survival. Since human platelets can be labelled with In‐111 oxine in plasma in sufficient efficiency for routine clinical use, they should be labelled in plasma whenever possible. The use of newer In‐111 chelates, tropolone and mercaptopyridine‐N‐oxide, which label platelets with high efficiency in plasma as well as in plasma‐free media, may offer another alternative.
Megakaryocyte progenitors in the bone marrow and peripheral blood of patients with myeloproliferative diseases
Authors: Grossi Alberto , Vannucchi Alessandro M. , Rafanelli Daniela , Vannucchi Letizia , Ferrini Pierluigi Rossi
Published: February 2007

We studied the behavior in culture of megakaryocyte progenitor cells (CFU‐Mk) from peripheral blood (PB) and bone marrow (BM) cells in eight patients with myeloproliferative diseases (MPD). In seven patients we observed megakaryocyte (Mk) colony formation from PB cells, which were generated in the absence of any added stimulator and which did not increase after the addition of a source of Mk‐colony stimulating activity (CSA‐Mk). The number of BM CFU‐Mk was significantly higher in patients than in controls, and in seven out of eight patients the responsiveness to added CSA‐Mk was retained. Plasma obtained from six patients did not stimulate normal donors' BM target cells to form Mk colonies. These data demonstrate an expansion of the CFU‐Mk pool in MPD patients without increased plasma levels of CSA‐Mk, and suggest that PB and BM CFU‐Mk of MPD patients might have different kinetic properties.
Effects of α‐thalassemia‐2 on the developmental changes of hematological values in children with sickle cell disease from georgia
Authors: Felice A. E. , McKie K. M. , Cleek M. P. , Marino E. M. , Kutlar A. , McKie V. C.
Published: February 2007

The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of α globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (αα/αα), 64 with SS (‐α/αα), and 9 with SS (–α/–α) between the ages of 1 and 15 years. Non‐steady‐state data were excluded from these analyses. The number and organization of α globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with α globin gene numbers throughout the 15‐year age interval. On the other hand, SS children with αα/αα, –α/, –α had similar hemoglobin concentrations up to the ages of 5–10 years. Around the age of 7, the SS patients with –α/–α developed a higher Hb concentration than that of the SS (–α/αα), which in turn was higher than that of the SS (αα/αα). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (αα/αα) and the decline of Hb F % under 15%. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5‐10 years. It occurs to a smaller extent among SS (–α/αα) or not at all among SS (–α/αα) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of α globin gene numbers, the absence of Hb Bart's suggested that α‐thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of α‐thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (> 7 years) α‐thalassemia and Hb F levels exceeding 15% appear to have additive effects in diminishing the rate of hemolysis.
Malignant granular lymphoproliferation after Epstein‐Barr virus infection: Partial immunologic reconstitution with interleukin‐2
Authors: Aronson Frederick R. , Dempsey Roy A. , Allegretta Mark , André‐Schwartz Janine , Poldre Peeter A. , Hillyer Christopher D. , Parkinson David R. , Rudders Richard A. , Schwartz Robert S. , Mier James W.
Published: February 2007

This report describes a patient who developed a malignant proliferation of granular lymphocytes following Epstein‐Barr virus (EBV) infection. For many months, his illness resembled prolonged infectious mononucleosis with persistent fatigue, fever, leukocytosis, and serologic evidence of recent primary EBV infection. After approximately I year, however, he developed progressive granular lymphocytosis and extensive lymphocytic infiltration of the bone marrow and liver. Tests for EBV DNA in pre‐ and postmortem tissue samples using a sensitive DNA hybridization technique were negative. Southern blot analysis of DNA prepared from blood mononuclear cells demonstrated clonal T‐cell antigen receptor gene rearrangement. Despite increased numbers of circulating lymphocytes with the morphology and surface phenotype of normal donor natural killer (NK) cells, the patient's NK activity was consistently depressed in a standard in vitro assay. However, in vitro incubation with interleukin‐2 (IL‐2), but not with α‐ or ‐γ‐interferon, increased the NK activity of the patient's lymphocytes. Intravenous recombinant IL‐2 treatment transiently increased the patient's blood NK activity and was associated with seroconversion to EBV nuclear antigens but failed to affect the progression of his disease. Our findings indicate that clonal granular lymphocytic proliferation may develop after EBV infection and confirm the utility of DNA hybridization analysis in distinguishing monoclonal from benign immunoreactive lymphoproliferation. Furthermore, our results suggest that certain functionally inert neoplastic granular lymphocytes acquire NK activity when exposed to IL‐2.
In vitro immunoglobulin production, proliferation, and cell markers before and after antithymocyte globulin therapy in patients with aplastic anemia
Authors: Lum Lawrence G. , Seigneuret Margaret C. , Doney Kristine C. , Storb Rainer
Published: February 2007

Peripheral blood lymphocytes from 16 aplastic anemia patients were studied for in vitro biosynthesis of immunoglobulins (Ig), proliferative responses, and cell markers before and after antithymocyte globulin (ATG) treatment in an attempt to identify immune functions that would be useful in predicting responses to ATG therapy. Six of the 16 aplastic anemia patients were complete responders to ATG therapy, two were partial responders, and eight failed to respond to ATG therapy. The proportion of E+, CD4, CD8, and surface Ig‐positive cells did not correlate with in vitro lymphocyte functions nor clinical responses before or after ATG therapy. Lymphocyte proliferative responses to phytohemagglutinin, tetanus toxoid, alloantigens, or pokeweed mitogen were generally present before and after ATG therapy. When pokeweed mitogen, herpes simplex type I virus, and tetanus toxoid were used as probes to elicit in vitro Ig production using a hemolytic plaque assay, some patients had 1) B cells that failed to produce Ig, 2) T cells that failed to provide helper activity, and 3) T cells that exhibited excessive suppressor activity in the various antibody production systems. These measures of immune function, however, did not correlate with clinical responses to ATG therapy.
Erythrocyte‐oxidized glutathione transport in pyrimidine 5′‐nucleotidase deficiency
Authors: Kondo Takahito , Ohtsuka Yoshinori , Shimada Michiro , Kawakami Yoshikazu , Hiyoshi Yasuhiko , Tsuji Yoshiro , Fujii Hisaichi , Miwa Shiro
Published: February 2007

The oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5′‐nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP‐requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17‐year‐old patient and a 13‐year‐old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [3H]glycine, were incubated at 37°C, and the rate of [3H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17–3.65 nmol GSSG/ml erythrocytes/hr at 37°C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 ± 0.80 nmol GSSG/ml erythrocytes/hr; mean ± SD). The activity of γ‐glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte GSH in P5N deficiency.
Deficiency of inducible suppressor cell activity in the Chediak‐Higashi syndrome
Authors: Nair Madhavan P. N. , Gray Robert H. , Boxer Laurence A. , Schwartz Stanley A.
Published: February 2007

Peripheral blood lymphocytes from two Chediak‐Higashi syndrome (CHS) patients were examined for their 1) natural killer (NK) cell functions 2) concanavalin A (Con A)‐inducible suppressor cell activity, 3) soluble suppressor factor production, and 4) responsiveness to interferon alpha and interleukin‐2 in comparison with age‐matched normal controls. Peripheral blood lymphocytes or NK‐enriched large granular lymphocytes from Chediak‐Higashi syndrome patients showed negligible cytotoxic activity against several target cells. Although the NK activity of Chediak‐Higashi syndrome lymphocytes could not be restored to normal levels by treatment with either interferon or interleukin‐2, the percent enhancement of NK activity was higher for the patients than the controls. Soluble suppressor factor activity of culture supernates from the lymphocytes of Chediak‐Higashi syndrome patients significantly inhibited the NK activity of allogeneic, normal peripheral blood lymphocytes, whereas lymphocytes from Chediak‐Higashi syndrome patients precultured with Con A failed to suppress the cytotoxic activity of normal lymphocytes. These results demonstrate a previously unrecognized suppressor cell dysfunction in CHS patients.
Cyclosporin A for the treatment of aplastic anemia refractory to antithymocyte globulin
Authors: Bridges Ronald , Pineo Graham , Blahey Walter
Published: February 2007

Antithymocyte globulin (ATG) is an established form of therapy for severe aplastic anemia (SAA). However, in patients who do not respond to this treatment and who are not candidates for bone marrow transplantation few successful therapeutic alternatives exist. We report two such patients who have shown a therapeutic response to Cyclosporin A (CSA) (Sandimmune, Sandoz). Case 1, a 15 year old male, and Case 2, a 34 year old female, were diagnosed as having SAA in September 1984 and May 1984 respectively. Treatment with high dose Methylprednisolone (MPN) and ATG in Case 1 and MPN, ATG and Oxymetholone in Case 2 for ten days was ineffective in both cases. Case 1 developed anaphylaxis with both repeat ATG and ALG (antilymphoblast globulin), and Case 2 failed to respond to repeat ATG. Both required frequent packed cells and platelet transfusions.

At five and six months respectively following completion of ATG therapy, CSA was started at 10 mg/kg/day in divided doses orally. Renal and liver functions and CSA blood levels were followed. Within six weeks both patients exhibited a hematologic response and were no longer transfusion dependent. On maintenance therapy of 4 mg/kg/day (Case 1) and four months after discontinuing CSA (Case 2) the hematologic values are as follows: hemoglobin 160 and 130 g/L, absolute granulocyte count 3100 and 1640 × 109/L, and platelets 132 and 84 × 109/L respectively. Side effects included hypertrichosis, gingival hyperplasia and mild reversible nephrotoxicity. CSA appears to represent an effective form of therapy for patients with SAA refractory to ATG.
Hemophiliac patient's knowledge and educational needs concerning acquired immunodeficiency syndrome
Authors: Hargraves Martha A. , Jason Janine M. , Chorba Terence L. , Holman Robert C. , Dixon Gloria R. , Eastham Christine J. , Brownstein Alan P. , Heine Peggy , Agle David P. ,   Hemophilia/Aids Collaborative Study Group
Published: February 2007

The Patient Knowledge Assessment Study (PKAS) was conducted among 107 male hemophilic patients, aged 15 to 67 years, at 19 hemophilia treatment centers (HTC). Participants were given a 30‐item questionnaire concerning the cause of acquired immunodeficiency syndrome (AIDS), the groups at risk, and modes of transmission. The questionnaire included questions on the participant's status in regard to antibody to human T‐lymphotropic retrovirus, type III/lymphadenopathy‐associated virus (HTLV‐III/LAV), and the meaning of this test result. HTC health‐care providers were asked to complete a separate questionnaire containing 17 questions about information given patients concerning their HTLV‐III/LAV antibody status and its meaning. Overall, patients had a good base of knowledge about AIDS; however, there were gaps in this knowledge. Twenty‐nine percent of patients did not know that spouses of AIDS patients were at risk for AIDS; 47% did not know that sexual partners of persons with hemophilia were at risk; and 32% did not know that hemophilic children were at risk. Further, only 69% understood that antibody‐positive individuals had had contact with the AIDS virus. Identifying these and other areas of misunderstanding will provide the information needed to design educational strategies and psychosocial support programs appropriate for the hemophilic population, and which may serve as a model for other populations.