Active rosette-forming T cells in the elderly.

The numbers and percentages of active rosette-forming T cells were measured in two age groups, to assess the effects of aging. The study included 21 healthy persons in the 20--40 age group and 25 persons without major disease in the 60--85 age group. In the younger subjects the number of rosette-forming cells (RFC) averaged 1430 +/- 463/cu mm (mean and S.D.), a count not significantly different from that in the older subjects (1443 +/- 398/cu mm). Likewise, the active RFC count in the 20--40 age group (526 +/- 185/cu mm) and that in the 60--85 age group (558 +/- 197/cu mm) were not significantly different. There was no difference for the percentage total RFC (young 78 +/- 4%, elderly 78 +/- 6%) or the percentage active RFC (young 29 +/- 7%, elderly 30 +/- 6%). For the total lymphocyte count or the B lymphocyte count, there was no difference between the two groups of subjects. It is concluded that T lymphocytes, measured as total and active rosette-forming cells, are not decreased in healthy older persons.     

Evaluation of reticulocyte parameters in iron deficiency, vitamin B(12) deficiency and beta-thalassemia minor patients

The aim of this study was to test the clinical utility of reticulocyte parameters in differential diagnosis in iron deficiency anemia (IDA), vitamin B(12) deficiency (B12) and beta-thalassemia minor (TM). We analyzed the percentage of reticulocyte, absolute reticulocyte count, mean content hemoglobin of reticulocyte (CHr), mean corpuscular volume of reticulocyte (MCVr), corpuscular hemoglobin concentration mean of reticulocyte (CHCMr), MCVr/MCV ratio, CHr/CH ratio and CHCMr/CHCM ratio in healthy donors (n = 34), iron deficiency (IDA) (n = 41), vitamin B(12) deficiency (B12) (n = 22), and TM (n = 34). This study demonstrates that the cutoff value of CHr was 25.7 as indicative of IDA (85.4% sensitivity, 97.1% specificity). CHr and MCVr may be useful for TM (cutoff value < or = 24.8 for CHr) and B12 (>102.1, cutoff value for MCVr), respectively. Sensitivity and specificity of these parameters were 90.9, 86.4% and 97.1, 82.4%, respectively. CHCMr is useful to differentiate IDA and TM from B12. While CHr was low value in microcytic groups (mean 21.8 +/- 3.3 for IDA, 21.0 +/- 2.9 for TM), it was high in B12 (mean 32.1 +/- 5.7). However, that of CHr/CH ratio was only significantly in IDA group compared with the control (P < 0.05, mean 0.98). Therefore, there are limitations regarding CHr and CHr/CH ratio differential diagnosis in microcytic and macrocytic groups. CHr, MCVr, and CHCMr are not sufficiently sensitive and specific to differentiate TM from IDA. We conclude that measurement of reticulocyte count and parameters may be a very useful implement in the diagnosis of IDA and TM.     

Circulating PIG-A mutant T lymphocytes in healthy adults and patients with bone marrow failure syndromes

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematological disorder with acquired PIG-A gene mutations and absent surface expression of proteins utilizing glycosylphosphatidylinositol (GPI) anchors. PNH often follows aplastic anemia, suggesting PIG-A mutant cells have relative dominance over normal hematopoietic cells. Somatic PIG-A mutations could arise after aplasia, or healthy persons could have rare PIG-A mutant cells that expand under selection pressure. METHODS: We developed an in vitro negative selection method to isolate GPI-deficient T lymphocytes using aerolysin, an Aeromonas toxin that binds GPI anchors and induces cell lysis. Peripheral blood mononuclear cells (PBMC) from normal adults and patients with PNH or other bone marrow failure syndromes were analyzed. RESULTS: From healthy adults, 166 T lymphocyte clones with deficient GPI-linked surface protein expression (CD55, CD59) were isolated. The mean mutant frequency (M(f)) of aerolysin-resistant clones was 17.8 +/- 13.8 per 10(6) PBMC, range 5.0-59.6 per 10(6) cells. Clones had a Class A complementation defect and distinct PIG-A mutations. Patients with PNH had elevated aerolysin-resistant M(f) values averaging 19 x 10(-2), a 10,000-fold difference. Two patients with Fanconi anemia and two others with mild aplastic anemia had M(f) values less than 15 x 10(-6), but two with recovering aplastic anemia had M(f) values of 20 x 10(-4), representing an intermediate value between normal persons and PNH patients. CONCLUSION: Identification of PIG-A mutant T lymphocytes in healthy adults suggests PNH could develop following intense negative selection of hematopoiesis, with clonal outgrowth of naturally occurring PIG-A mutant stem cells.     

Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival

A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is thought to result from increased RBC turnover, RBC survival has not been determined in subjects receiving RBV due to the complexity of the techniques commonly used to quantitate RBC life span. We recently described a simple, rapid, non-invasive technique that utilizes measurements of alveolar carbon monoxide (CO) concentration to determine RBC survival. In the present report, this method was employed to assess RBC survival in patients receiving RBV for hepatitis C. Each of the 31 measurements of RBC survival in 12 subjects with RBV-associated anemia was below the lower limit of normal (77 days), and the average survival (46 +/- 14 days) in these subjects was only about 38% of that of healthy controls (122 +/- 23 days). Five hepatitis C patients not undergoing RBV treatment had normal RBC survivals (112 +/- 17 days). While the mean reticulocyte percentage was significantly elevated in subjects treated with RBV, 59% of these measurements fell within the limits of normal. We conclude that RBV-associated anemia consistently is associated with reduced RBC survival as determined from breath CO measurements and that this reduced survival frequently is not associated with an elevated reticulocyte count.     

Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag

Pretreatment blood counts, particularly an absolute reticulocyte count ≥25×10⁹/L, correlate with response to immunosuppressive therapy in severe aplastic anemia. In recent trials, eltrombopag combined with standard immunosuppressive therapy yielded superior responses than those to immunosuppressive therapy alone. Our single institution retrospective study aimed to elucidate whether historical predictors of response to immunosuppressive therapy alone were also associated with response to immunosuppressive therapy plus eltrombopag. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with severe aplastic anemia, aged 2-82 years (median, 30 years), initially treated with immunosuppressive therapy plus eltrombopag between 2012 and 2019 (n=176) or with immunosuppressive therapy alone between 1999 and 2010 (n=240). Compared to non-responders, patients in the group of overall responders to immunosuppressive therapy plus eltrombopag had significantly higher pretreatment absolute reticulocyte counts, higher neutrophil counts and reduced thrombopoietin levels, as also observed for the group treated with immunosuppressive therapy alone. Addition of eltrombopag markedly improved the overall response in subjects with an absolute reticulocyte count between 10-30×10⁹/L from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count correlated with complete response in the groups treated with immunosuppressive therapy with or without eltrombopag, especially in adolescents aged ≥10 years and adults, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria clone did not correlate with responses to immunosuppressive therapy. Blood counts remain the best predictors of response to nontransplant therapies in severe aplastic anemia. Addition of eltrombopag to immunosuppressive therapy shifted patients with a lower absolute reticulocyte count into a better prognostic category.     

Automated analyzer evaluation of reticulocytes in bone marrow and peripheral blood of hematologic disorders

The R-3000 reticulocyte analyzer uses flow cytometry with an argon laser as its light source. This analyzer stains residual RNA with auramine O to provide a reticulocyte maturation differential. Using the R-3000, we analyzed 119 samples of bone marrow (BM) and peripheral blood (PB) from 111 patients with hematologic disorders. Parameters were reticulocytes, immature reticulocyte fraction (IRF) percentage in BM and PB, BM/PB reticulocyte ratio, and BM/PB IRF ratio. Reticulocytes and IRF percentage in BM were significantly higher than in PB (p < 0.01). There was also a good correlation between reticulocyte percentages in BM and in PB (r = 0.81). Patients were classified into a normal group (without anemia) and an anemia group. Furthermore, the anemia group was classified into three groups: group 1: cases with hematopoietic dysfunction; group 2: cases in bone marrow recovery phase after chemotherapy and hematopoietic stem cell transplantation, and hematologic disorders with bone marrow accelerative phase, and group 3: cases with ineffective hematopoiesis (myelodysplastic syndrome). The mean reticulocyte percentage of the normal group was 2.3 +/- 1.1%, which was close to the normal value in BM. The BM/PB reticulocyte ratio of group 3 was statistically higher than that of groups 1 and 2. This indicates that group 3 had ineffective erythropoiesis and that the BM/PB ratio is a useful indicator for the diagnosis of myelodysplastic syndrome.     

An inappropriate erythropoietic response to iron deficiency anaemia in the elderly

Summary This study was carried out to clarify the features of iron deficiency anaemia in the elderly. Subjects were chosen from residents undergoing an annual health check in a home for the aged and the features of anaemia in the elderly were compared with those in middle-aged adults under 60 years old. The red cell count, red cell size and haemoglobin content in an elderly group with iron-deficiency anaemia did not differ from those in middle-aged adults. No significant differences of the serum ferritin and iron levels were noted between the two groups. Total iron binding capacity was higher in the middle-aged adults than in the elderly, while the reticulocyte count was significantly lower in the elderly group. Immature reticulocytes showing a considerable amount of residual RNA by flow cytometry with fluorescent staining were also lower in the elderly group than in the middle-aged adults. Serum erythropoietin levels in both groups were significantly higher than in non-anaemic age-matched controls and no difference in erythropoietin levels was noted between them. The ratio of the reticulocyte count to the log-transformed erythropoietin level was low in the elderly group with iron-deficiency anaemia compared with the middle-aged adults with iron deficiency anaemia. The same result was seen when the immature reticulocyte count was related to the log-transformed erythropoietin level. These findings suggest that the red cell production response to erythropoietin in the elderly with iron-deficiency anaemia might be inappropriate compared with both non-anaemic and anaemic middle-aged adults.     

Automated measurement of reticulated platelets in estimating thrombopoiesis

Abstract: We described a fully automated measurement of reticulated platelets using a fluorescent dye, auramine O, and a reticulocyte counter, the R-3000, equipped with special software. Reproducibility and linearity were shown to be good. In the normal subjects studied (n = 60), the mean value for reticulated platelets was 0.98% ± 0.41% and the mean absolute count was 2.12 ± 0.69 × 10⁹/l. The absolute count for reticulated platelets was significantly lower (p < 0.05) in patients with reduced thrombopoiesis as seen in acute myeloblastic leukemia, aplastic anemia or chemotherapy-induced thrombocytopenia and it was elevated (p < 0.05) in essential thrombocythemia and in chronic myelocytic leukemia with thrombocytosis. All 20 patients with chronic idiopathic thrombocytopenic purpura had a high percentage of reticulated platelets. The percentage of reticulated platelets was significantly increased (p < 0.05) in patients with impaired thrombopoiesis despite the reduction in the absolute count. In 2 leukemic patients, an apparent rise was noticed in the percentage of reticulated platelets which preceded by several days a progressive increase in the platelet count at the recovery phase of thrombocytopenia. The results suggest that an automated measurement of reticulated platelets can be applied to routine laboratories for clinical use.     

网织血小板测定对血小板减少疾病诊断价值的探讨

目的　探讨外周血网织血小板 (RP)数值的变化对各型血小板减少疾病的诊断价值 ;外周血RP与骨髓中巨核细胞 (MK)增生程度的关系。方法　以噻唑橙作为RNA的荧光染料 ,利用流式细胞仪测定外周血中含有RNA的RP ,并计算RP(% )及RP绝对值。结果　 (1)正常对照组 :RP(8 4±2 5 ) % ,RP绝对值为 (16 8± 6 8)× 10 9/L。 (2 )原发性血小板减少性紫癜 (ITP)和脾功能亢进症患者RP(% )显著高于正常对照组 ,而RP绝对值显著低于正常对照组 (P <0 0 1) ,在不同MK增生级别的ITP患者中 ,RP(% )、RP绝对值在各组之间均无差异 ;再生障碍性贫血患者RP(% )及绝对值均低于正常对照组 (P <0 0 5 ,P <0 0 1) ;而急性白血病、骨髓增生异常综合征患者RP(% )与正常对照组无明显差异 (P >0 0 5 ) ,但其RP绝对值明显低于正常对照组 (P <0 0 1)。 (3)上述疾病患者 ,经治疗有效者RP(% )恢复正常 ,而无效或疗效欠佳者 ,则RP(% )几无变化。结论　外周血RP测定 ,有助于血小板减少疾病的病因学诊断 ,是血小板减少疾病一有价值的诊断依据 ,也是疗效判断的监控指标。外周血RP与骨髓中MK增生的程度无相关性     

Clinical paroxysmal nocturnal hemoglobinuria is the result of expansion of glycosyl-phosphatidyl-inositol-anchored protein-deficient clone in the condition of Deficient Hematopoiesis

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, clonal hematopoietic stem cell disorder in which PIG-A, gene essential for the biosynthesis of the glycosyl-phosphatidyl-inositol (GPI) anchor, is somatically mutated. Absence of GPI-linked proteins from the surface of blood cells is characteristic of the PIG-A mutant (PNH) clone and is also accountable fo certain manifestations, such as intravascular hemolysis. It is unclear how the PNH clone expands and comes to dominate hematopoiesis. In this study, CD34+ cells--committed progenitors (colony-forming cells) representing immature hematopoietic stem cells--and reticulocytes representing the differentiated erythroid cells were quantitated in peripheral blood of patients with PNH. Compared with normal controls (n = 29), CD34+ cell levels were significantly lower in PNH patients who did not have preexisting aplastic anemia (AA) (n = 12) (2.47+/-1.23 versus 4.68+/-1.05 x 106/L, mean +/- standard error; P = .022). PNH patients with precedent aplastic anemia (AA+/PNH) showed markedly low CD34+ cell levels compared with normal control subjects (0.6+/-0.29 versus 4.68+/-1.05 x 10(6)/L; P = .0001). In addition, colony-forming cells from PNH patients were significantly decreased compared with those from normal volunteers (erythroid burst-forming units, 2.8+/-1.2 versu 25.6+/-6.2/5 x 10(5) mononuclear cells; P = .0006; and granulocyte/macrophage colony-forming units, 1.2+/-0.5 versus 13.3+/-3.0/ 5 x 10(5) mononuclear cells; P = .0006). These findings occur in both aplastic and hemolytic types of PNH, suggesting hematopoietic failure in PNH. On the contrary, the numbers of reticulocytes and the reticulocyte production index of PNH patients were significantly higher than those of normal persons and comparable to those from patients with autoimmune hemolytic anemia, indicating accelerating erythropoiesis in PNH. The degree of reticulocytosis correlated well with the proportion of CD59- (PNH) reticulocytes. All of the findings suggest that in the condition of deficient hematopoiesis, the PNH clone arising from the mutated hematopoietic stem cell expands and maintains a substantial proportion of the patient's hematopoiesis.     

HIV immunosuppression and antimalarial efficacy: sulfadoxine-pyrimethamine for the treatment of uncomplicated malaria in HIV-infected adults in Siaya, Kenya

BACKGROUND: The altered immune response of persons with human immunodeficiency virus (HIV) infection could result in increased rates of antimalarial treatment failure. We investigated the influence of HIV infection on the response to sulfadoxine-pyrimethamine treatment. METHODS: Febrile adults with Plasmodium falciparum parasitemia were treated with sulfadoxine-pyrimethamine and were monitored for 28 days. HIV status and CD4 cell count were determined at study enrollment. RESULTS: Of the adults enrolled in the study, 508 attended all follow-up visits, including 130 HIV-uninfected adults, 256 HIV-infected adults with a high CD4 cell count (> or =200 cells/ micro L), and 122 HIV-infected adults with a low CD4 cell count (<200 cells/ micro L). The hazard of treatment failure at day 28 of follow-up was significantly higher for HIV-infected adults with a low CD4 cell count (20.5%) than for HIV-uninfected adults (7.7%). Anemia (hemoglobin level, <110 g/L) modified the effect of HIV status on treatment failure. When we controlled for fever and parasite density, the hazard of treatment failure for HIV-infected adults with a low CD4 cell count and anemia was 3.4 times higher than that for HIV-uninfected adults (adjusted hazard ratio, 3.38; 95% confidence interval, 1.56-7.34). CONCLUSIONS: HIV-infected persons with a low CD4 cell count and anemia have an increased risk of antimalarial treatment failure. The response to malaria treatment in HIV-infected persons must be carefully monitored. Proven measures for the control and prevention of malaria must be incorporated into the basic package of services provided by HIV/acquired immunodeficiency syndrome care and treatment programs in malarious areas.     

Physiological response to phlebotomies for autologous transfusion at elective hip-joint surgery

In order to study the physiological response to phlebotomies for autotransfusion, an autotransfusion program was designed for 10 patients undergoing hip-joint replacement surgery for arthrosis. 4 phlebotomies of 450 ml each were performed within 12 days. Blood samples were taken immediately before phlebotomy for blood hemoglobin (Hb), serum erythropoietin (Epo), reticulocyte count (ret) and erythrocyte 2,3-diphosphoglycerate (DPG). All 4 phlebotomies could be performed in 9/10 patients, and only 1 patient had significant symptoms (fatigue). The operation was performed 2 weeks after the last phlebotomy. None of the patients had recovered the initial Hb level at operation (24.8 +/- 9 per liter lower than initially), and they were all even more anemic after the operation (36.8 +/- 16.9 g/l lower than initially). Serum Epo increased from 13.6 +/- 7.2 IU to 30.6 +/- 12.2 (SD) IU per liter, and reticulocyte counts increased to a maximum of 3.68 +/- 1.69%. DPG increased in all patients except the one who had significant fatigue. It is concluded that the patients tolerated the phlebotomy program well but that a significant anemia developed. The compensatory increase in erythropoietin and reticulocyte count, adequate for this degree of anemia, was small compared to the increase seen at more severe anemia, indicating that there may be a role for pharmacological stimulation of erythropoiesis in blood predeposit programs.     

Flow cytometric evaluation of circulating CD34+ cell counts and apoptotic rate in children with acquired aplastic anemia and myelodysplasia

OBJECTIVE: Identification of a rapid and noninvasive test for the follow-up of aplastic anemia (AA) patients during immunosuppressive therapy (IST) to evaluate its functional effect on hematopoietic progenitors (HPC) and for early detection of progression to myelodysplasia or relapse. MATERIALS AND METHODS: Absolute count and apoptotic rate (AR) of peripheral blood (PB) CD34+ cells were evaluated by three-color flow cytometry for CD45, CD34, and annexin V in cord blood (CB), normal children, and adults, as well as in pediatric patients with AA at diagnosis and during IST, Fanconi anemia (FA), chronic immune cytopenia, and refractory anemia with excess blasts (RAEB). RESULTS: In normal subjects, the AR of PB CD34+ cells showed a progressive increase (p < 0.05), while their counts decreased (p < 0.05) from birth to adulthood. In very severe AA (vSAA) and severe AA (SAA) at diagnosis, the AR was 91.6% +/- 2.8%, higher than controls (p < 0.05), and PB CD34+ cell count was 2.6 +/- 2.4/microL. In FA patients, the PB CD34+ AR was again significantly increased (54.2% +/- 13.7%) with an absolute count of 3.7 +/- 1.2/microL. Conversely, in RAEB the AR was 11.7% +/- 3.5% and the absolute count 85.1 +/- 48.2/microL (p < 0.05). Chronic immune cytopenias did not significantly differ from controls. CONCLUSIONS: Flow cytometry evaluation of PB CD34+ AR and counts is a noninvasive and feasible first-step method for the differentiation of AA and myelodysplasia (MDS), and it might be useful for monitoring AA during IST to secure the early detection of relapse or transformation to MDS.     

Short Communication:Hemoglobin Machida [β6 (A3) Glu → Gln], a New Abnormal Hemoglobin Discovered in a Japanese Family: Structure,Function and Biosynthesis

This report describes a new abnormal hemoglobin discovered in a 43-year-old Japanese female living in Machida City, Tokyo Capital City, in October 1981. Hematological study of the propositus, who was clinically healthy, showed neither microcytic hypochromic anemia due to iron deficiency, nor hemolytic tendencies, in spite of slightly decreased serum iron and slightly increased reticulocyte count (WBC 4.3 × 10⁹/1, RBC 4.46 × 10¹²/1, Hb 13.6 g/dl, PCV 0.388 1/1, MCV 87 fl, MCH 30.8 pg, MCHC 35.2 g/dl, reticulocyte count 1.4%, total bilirubin 0.3 mg/dl, serum iron 65 μg/dl, TIBC 329 μg/dl). Target cells were not seen on peripheral blood smears. Family study disclosed that her son (10 year old) was a carrier of the same abnormal hemoglobin. He was also apparently healthy and hematologically normal.     

Dendritic cell counts in the peripheral blood of healthy adults

The normal range for adult blood dendritic cells (DC) has not been established. Blood DC counts were assayed directly from blood for 16 female and 11 male healthy adults with an age range of 22-60 years old (median, 46 years). DC were defined as lineage 1-negative/dim, CD34-negative/dim, and HLA-DR-positive within the total peripheral blood leukocyte (PBL) population. Impedance counter complete blood counts were used with flow cytometry percentages to calculate the absolute DC count and DC percentage of mononuclear cells (MNC). The normal adult ranges for DC calculated as the mean +/- 2SD were 0.16-0.68% PBL, 0.55-1.63% MNC, and 13-37 DC/microL of blood.     

Treatment of aplastic anemia with antilymphocyte globulin, high-dose methylprednisolone and androgen]

Twenty-seven patients with aplastic anemia (20 severe: 7 moderate) were treated with combined immunosuppression consisting of antilymphocyte globulin (ALG: Ahlbulin, Green Cross Co., Osaka, Japan) and high-dose methylprednisolone. Danazol or meptiostane was administered concurrently for at least 3 months. Ten of 27 patients had sustained improvement in hematopoiesis within 3 months of treatment. Three patients with hematological response had a recurrence of pancytopenia 12-36 months after the combined immunosuppressive therapy. Six patients died due to fungal pneumonia (2), hepatic failure (2), interstitial pneumonitis (1) and complication following allogeneic bone marrow transplantation (1). By life table analysis, the survival rate for all patients was 76 +/- 8% at 4 years, with 70 +/- 10% survival rate for patients with severe aplastic anemia and 100% for patients with moderate aplastic anemia. The factors predicting the good response to the therapy were a longer interval from diagnosis to the therapy and higher counts of platelet and reticulocyte at admission.     

PMN heterogeneity: long-term stability of fluorescent membrane potential responses to the chemoattractant N-formyl-methionyl-leucyl- phenylalanine in healthy adults and correlation with respiratory burst activity

Polymorphonuclear neutrophils (PMNs) were isolated from 24 healthy adults 20 to 61 years of age and the proportion of cells that demonstrated depolarization responses to the synthetic chemotaxin N- formyl-methionyl-leucyl-phenylalanine (FMLP) were enumerated using the lipophilic fluorescent cyanine dye 3,3'-di-pentyl-oxacarbocyanine [di-O- C(5)(3)] and flow cytometry. The membrane potential responses were correlated to the cells' respiratory burst capabilities as measured by nitroblue tetrazolium (NBT) reduction and/or superoxide production in response to FMLP; 40.2% +/- 15.1% (mean +/- SD) of cells depolarized to FMLP. The mean SE for duplicate determinations 1 hour apart was 3.8% (range 0.4% to 13.6%, n = 15). There was no correlation between the percentage of depolarizing PMNs and the yield of cells, the percentage of immature cells, or the circulating WBC count. There was no difference in the average age of men (34.9 +/- 9.9 years, n = 11) v women (33.8 +/- 8.5, n = 13) (mean +/- SD) studied, or in the percentage of depolarizing PMNs when men and women were compared (42.2 +/- 10.6% v 43.1 +/- 13.3%, respectively). However, there was a significant increase in the percentage of depolarizing PMNs with increasing age of women (r = .61, P less than .025) but not men (r = .03, P greater than .05). Analysis of variance revealed significantly greater person-to-person variability in the membrane potential response than in day-to-day variability in the same person (P less than .0005). The percentage of depolarizing PMNs in response to FMLP was significantly correlated with the percentage of NBT-positive cells from both purified PMNs and from whole blood (r = .849, P less than .0005, r = .857, P less than .05, respectively), and with the amount of superoxide produced, expressed as a percentage of that amount produced by cytochalasin B (cyto-B)-pretreated cells (r = .565, P less than .01). The data indicate that PMNs from healthy adults demonstrate a heterogeneous membrane potential response to the chemotaxin FMLP that correlates with the cells' oxidative responsiveness and that intersubject differences can be detected. In addition, the proportion of responsive PMNs increases with increasing age in women.     

Growth hormone replacement therapy in growth hormone deficient children and adults: Effects on hemochrome

Several lines of evidence have suggested a role of the GH/IGF-I axis in the regulation of hemochrome. Many studies have been carried out in GH deficient children and adults about this topic, reporting predominantly a positive effect of recombinant human GH (rhGH) on red series, with no action on serum leucocytes and platelets counts. The aim of this study was to assess the impact of GH deficiency (GHD) and of rhGH replacement on blood cells count in 17 pre-pubertal children with idiopathic isolated GHD (11 males and 6 females, aged 9.1+/-0.8 yr) and in 18 patients with adult-onset GHD (12 males and 6 females, aged 47.9+/-3.0 yr). Evaluation of absolute and SD score (SDS) values of red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets and white blood cells was performed at baseline and after 12 months of rhGH treatment (0.045+/-0.001 mg/kg bw/day and 4.2+/-0.5 microg/kg bw/day for children and adults, respectively). At baseline, all patients showed low IGF-I levels. Effectiveness of rhGH therapy was documented by significant increase in height SDS, height velocity and serum IGF-I levels in children. In adults, adequacy of rhGH was demonstrated by significant increase in serum IGF-I and significant decrease in body fat. At baseline, about 25% of patients (4 of 17 children and 4 of 18 adults) showed normochromic normocytic anemia, while the other indices were normal. In 7 of the 8 anemic patients, normal levels of hemoglobin were restored on rhGH, while no change in all the other indices was observed. In conclusion, rhGH therapy at physiological doses has no effect on erythropoiesis in GHD children and adults with normal blood cells count, while in patients with normochromic normocytic anemia rhGH is able to restore normal hemoglobin levels.     

Effect of age on hematopoiesis in man

We have shown previously that the cause of anemia in healthy elderly subjects can usually not be identified. In this study, hematopoiesis was examined in 18 healthy elderly subjects with unexplained anemia and in 15 young and 15 healthy elderly individuals without anemia. No reduction in circulating testosterone was noted, making decreased androgen levels as a cause for the anemia unlikely. The 2,3 diphospho- glycerate (2,3DPG) levels in the anemic subjects were significantly higher than their corresponding controls, suggesting that the anemia was pathologic, as no increase would be expected if the low hemoglobin was a physiologic adjustment to age. The anemia was associated with a reduction in marrow normoblast and CFU-E number, but no decrease in BFU- E levels was seen. This suggests that the mechanism of the anemia is a decrease in stem cell proliferation. This could be caused by a reduction in circulating erythropoietin or a defect in end organ response. A second possibility is that a basic cellular abnormality exists. The presence of an overall reduction in hematopoiesis in anemic elderly (decreased peripheral blood counts, reduced marrow myeloid precursors, and CFU-C levels) makes this especially likely. The abnormality may be caused by a mechanism unrelated to the aging process. The fact that nonanemic elderly also have reductions in hematopoiesis suggests that age contributes to the defect.     

Limb fat to trunk fat ratio in elderly persons is a strong determinant of insulin resistance and adiponectin levels

BACKGROUND: Similar to lipodystrophy syndromes, aging results in increased visceral adiposity with loss of subcutaneous adipose tissue in the extremities. The hypothesis of this study is that the distribution of limb fat to trunk fat (LF/TF) ratio in elderly persons has a stronger correlation than trunk fat alone to insulin resistance and adiponectin levels. METHODS: Thirty-eight elderly participants were divided into an insulin-resistant (IR) group and an insulin-sensitive (IS) group. Limb fat and trunk fat were measured by dual-energy x-ray absorptiometry. Insulin resistance was measured by a hyperinsulinemic-euglycemic clamp. RESULTS: There was no significant difference between the IS and IR groups with respect to body mass index, body fat index, absolute amount of trunk fat, or percent body fat. However, the difference in LF/TF ratio between the IS (1.02 +/- 0.05) and the IR groups (0.77 +/- 0.05) was highly significantly different (p <.001). Insulin resistance had a stronger correlation to the LF/TF ratio (r = 0.61, p <.001) than to absolute trunk fat (r = -0.32, p =.051). Adiponectin levels had a strong association with the LF/TF ratio (r = 0.63, p <.001), but did not correlate to absolute trunk fat (r = -0.24, p =.18). CONCLUSIONS: The distribution of body fat (LF/TF ratio) in elderly persons is a stronger determinant of insulin resistance and adiponectin levels than is trunk fat alone. The LF/TF ratio can be a useful tool to assess insulin sensitivity in the elderly population.