Elevated Fructosamine Levelsin Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.MethodsWe assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (Pao₂) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.ResultsFasting serum glucose was not significantly different between the men with AIDS (87 ± 4 mg/dL) and the healthy male volunteers (84 ± 6 mg/dL); however, A1C (6.9 ± 0.2%) and serum fructosamine levels (288 ± 15 μmol/L) were significantly higher (P < .01) in the patients with AIDS than in the normal subjects (A1C, 5.6 ± 0.1%; fructosamine, 204 ± 14 μmol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P < .01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin < 12 g/dL) or hypoxia (Pao₂ < 95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 ± 3 mg/L) and the normal subjects (22 ± 4 mg/L).ConclusionOn the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent. (Endocr Pract. 2008;14:686-690)     

Circadian Variations in Human Peripheral Blood on Days With and Without Bone Marrow Sampling and Relation to Bone Marrow Cell Proliferation

Fifteen bone marrow (BM) and venous blood circadian profiles were obtained from 13 diurnally-active, healthy men sampled every 4-5 h for 24 h. Peripheral blood (PB) was also sampled in subsets of 5 men either for 24 h immediately preceding the BM procedure or 5-6 months afterwards. Cortisol and white and red cell parameters were determined in PB. BM cell cycle distribution was investigated in parallel by flow cytometry for S-phase DNA of total mononuclear cells and subpopulations of erythroid and myeloid precursor cells. On a group basis, significant circadian rhythms were found in PB variables commonly referred to as "marker" rhythms (cortisol, total white cells [WBC], neutrophils [N], lymphocytes [L]), with acrophases less than 2 h apart between the contro l day prior to and during BM sampling. Thus, major, but relatively short-lasting physiological stress, like BM aspirations or blood sampling itself, although repeated several times over 24 h, seemed to have minor influence on these rhythms on days of the BM procedure. When comparing the times of highest or lowest values in PB with times of highest or lowest values in BM, several temporal relationships were found. Among other associations, timing of lowest values in WBC, N and L or highest values in cortisol was significantly predictive of highest values in myeloid cells occurring in the following 12 h, whereas highest values in erythroid cells occurred significantly more often in the 12 h interval beginning 4 h after the time of lowest values in WBC, L and N. The stability in the circadian rhythms of the PB variables suggests that information obtained on one day can be used to guide procedures on the next, such as BM myelotoxic chronotherapy or BM harvesting.     

Women and the Acquired Immunodeficiency Syndrome: An Interview

SPECIAL EDITOR''S NOTE: Constance B. Wofsy, MD, is Co-Director of AIDS Activities at San Francisco General Hospital and Medical Center, as well as Associate Clinical Professor of Medicine at the University of California, San Francisco; Assistant Chief, Infectious Diseases, San Francisco General Hospital; and Principal Investigator, Project AWARE (Association for Women''s AIDS Research and Education). Although she was not able to contribute an article for WOMEN AND MEDICINE on this very important subject, she kindly agreed to an interview. Both physicians and nonphysicians were asked what questions they had about the acquired immunodeficiency syndrome (AIDS) and the human immunodeficiency virus (HIV) in women.     

The Acquired Immunodeficiency Syndrome: current status

A recently recognized syndrome of acquired immunodeficiency (Acquired Immunodeficiency Syndrome-AIDS) has arisen since June 1981. It has received international attention. The clinical spectrum consists of repeated opportunistic infections, rare malignancies, and autoimmune phenomena, occurring in previously healthy adults with no history of an immunologic disorder. The population subset at risk for this syndrome appears to be predominantly homosexual American males and intravenous drug abusers with rare cases being reported in heterosexuals, hemophiliacs, and foreign patients, especially Haitians. The immunologic aberrancy in all patients described appears limited to T-lymphocyte hyporesponsiveness and imbalance of T-helper and suppressor cells. This disordered immunoregulation is a consistent finding in all reported cases and appears to predispose to the opportunistic infections and malignancies which have been associated with a 40 percent mortality. The underlying factor responsible for the immunoregulatory defect is unknown but possible etiologies include a transmissible infectious agent, drug use, chronic antigen stimulation, and spermatozoa exposure. Treatment of the associated infections and malignancies has been a frustrating endeavor as many patients respond incompletely or relapse soon after successful treatment course. Preventive measures, including patient education, physician awareness, and immunomodulating agents, are discussed.     

Cytogenetic Analysis of Bone Marrow and Peripheral Blood Samples Stored in Fixative for Several Years

We have developed a method which improves the spreading of chromosomes and permits banding analysis of cytogenetic samples of bone marrow and unstimulated peripheral blood which have been stored in fixative for up to 15 years. Metaphase cells had been harvested as usual and stored in fixative (acetic acid:methanol 1:3) at -15 C. The procedure includes 4-5 changes of fixative (acetic acid:ethanol 1:1). Next, cells are dropped onto a chilled, wet slide. The back of the slide is then rinsed with 70% ethanol and dried by ignition. C-, G-, Q-, or R-banding patterns can now be obtained with these specimens. The procedure is useful for reinvestigation of cytogenetic samples that were obtained prior to the development of banding techniques.     

骨髓单个核细胞抗体及外周血B淋巴细胞与IRP的相关性研究

采用流式细胞术双标法检测拟诊免疫相关性全血细胞减少症患者(A组)、非免疫相关性恶性血液病患者(B组)及正常人(正常对照组)的骨髓单个核细胞结合的自身抗体,同时检测B组、确诊免疫相关性全血细胞减少症(C组)及正常对照组外周血B淋巴细胞及CD5+B淋巴细胞比率;A组中16例骨髓造血细胞自身抗体阳性,阳性率88.88%;B组1例骨髓造血细胞自身抗体阳性,阳性率9.09%。C组外周血B淋巴细胞、CD5+B淋巴细胞比率显著高于B组及正常对照组(P均<0.05),而正常对照组外周血B淋巴细胞、CD5+B淋巴细胞显著高于B组(P均<0.05);IRP患者骨髓单个核细胞自身抗体表达显著增高,B淋巴细胞总数及CD5+B淋巴细胞数量显著增高可能是IRP发病的重要因素之一;利用流式细胞术检测骨髓造血细胞自身抗体及B淋巴细胞数可以为IRP提供科学可靠的依据,优于骨髓Coomb’s实验。     

Rate and Time of Dna Synthesis of Human Leukaemic Blasts In Bone Marrow and Peripheral Blood

Abstract. We have evaluated DNA synthesis rate (S rate) and time (T_s) and tritiated thymidine labelling index (LI) of peripheral blood (PB) and/or bone marrow (BM) leukaemic blasts (Bl) in nineteen cases of acute leukaemia (twelve non-lymphoblastic, AnLL, and seven lymphoblastic, ALL), in one case of non-Hodgkin's leukaemic lymphoma and in a case of plasma cell leukaemia.
The LI of PB-BI was significantly lower than that of BM-Bl (range 0.1-6.2% and 1.9-19.5%, respectively; P < 0.01). the S rate was higher for PB-Bl than for BM-Bl (range 3.5-11-3 and 2.5-9.5 mol × 10-¹⁸/min; P < 0.02) and the T^s of PB-Bl was shorter than that of BM-Bl (range 7.6-22.1 and 10.8-34.7 hr, respectively; P < 0.02). In eight cases where S rates of both BM-Bl and PB-Bl were available, a linear correlation ( r = 0.82; P < 0.01) was found between the two parameters. This suggests that the DNA synthetic rate is a property of the leukaemic cell line in individual patients and differs from case to case. It further indicates that the environmental influences on the DNA synthesis rate in BM or PB are always of the same order of magnitude. From the results of this study we speculate that the DNA synthesis rate of leukaemic blasts is slowed down in the BM by environmental factors such as cell density.     

New Stains for Blood and Bone Marrow Cells

Traditionally, blood and bone marrow cells have been identified based on their characteristic shapes and colors when stained with one of several panoptic stains including Wright's or Giemsa's. As questions arose regarding the origin of normal and leukemic cells, cytochemical stains were developed. These stains help identify cells on the basis of a distinctive metabolite or enzyme. As part of an ongoing tradition in which textile dyes are used for biological staining, several new stains have been applied to hematologic staining. These include C.I. basic blue 41, basic blue 141, basic blue 93, and an assymetrical polymethine dye. As additional cell-selective stains are developed, we can anticipate further improvements in our ability to identify normal and malignant hematopoietic cells.     

小鼠骨髓造血干细胞、外周血组成随年龄的变化趋势及其相关性分析

造血干细胞是具有自我更新能力并能分化为血液中各种血细胞组分的多能干细胞。近来研究显示,不同造血干细胞表面标志物标记的造血干细胞具有分化为不同血细胞的趋势,但是这种分化的内在关系仍不清楚。对小鼠CD34~-/Sca-1~+骨髓造血干细胞、外周血组成随小鼠年龄增长的变化情况进行了分析,结果显示:随着年龄的增长,骨髓中的CD34~-/Sca-1~+骨髓造血干细胞比率显著增加;而外周血各组分则随年龄变化呈现不同的趋势。对不同年龄段小鼠的骨髓造血干细胞及其他组分与外周血组分的同步分析发现,外周血中血小板密度变化趋势与CD34~-/Sca-1~+骨髓造血干细胞变化情况相关系数为0.804 8;外周血中淋巴细胞密度变化趋势与CD34~+/Sca-1~-骨髓细胞的变化情况相关系数为0.947 97;外周血中白细胞密度变化趋势与CD34~+/Sca-1~+骨髓细胞变化情况相关系数为0.763 1(大于0.9为极度相关,0.7到0.9为高度相关)。     

Multiple Chromosome Abnormalities Following Bone Marrow Transplant for Chronic Myelogenous Leukemia

A 44-year-old female was diagnosed in the chronic phase of chronic myelogenous leukemia (CML) and was confirmed to be Philadelphia chromosome positive by a bone marrow cytogenetic study. No additional cytogenetic abnormalities were found. The patient's cell counts were initially well controlled with hydrox-yurea. She then received an unrelated 6 of 6 HLA matched allo-geneic bone marrow transplant (BMT) from a male donor. The patient underwent myeloablative therapy with thiotepa and five fractions of total body radiation prior to the transplant. About four weeks after transplantation, the patient developed biopsy-proven graft-versus-host disease of the skin and GI tract. A blood sample was drawn at that time for cytogenetic analysis. Among 34 analyzed cells, 22 were normal male donor cells. The remaining 12 cells did not have the t(9;22), but had numerous structural abnormalities. While many cells were missing an X chromosome, other abnormalities, including deletions, rearrangements, dicentrics, acentric fragments, rings and marker chromosomes were non-clonal. No clinical evidence of progression from CML chronic phase was found, suggesting that the non-clonal abnor-malities were therapy related.     

Changes in Thyroid Function in Ethiopian and Non-Ethiopian Israeli Patients With Human Immunodeficiency Virus Infection or Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether human immunode ficiency virus (HIV) infection or its treatment is a risk fac tor for thyroid dysfunction and whether thyroid function changes over time in 2 distinct subpopulations with HIV or acquired immunodeficiency syndrome (AIDS) in Israel: Ethiopian immigrants and Israeli patients.MethodsSerum thyroid-stimulating hormone (TSH) and free thyroxine levels were determined in HIV carriers undergoing follow-up at the Hadassah-Hebrew University Medical Center HIV clinic in Jerusalem, Israel, and these thyroid measurements were correlated with clinical and laboratory variables pertaining to their disease, including disease duration, drug therapy, viral load, CD4 count, low density lipoprotein cholesterol, and creatine kinase. Serum samples stored at − 20°C from the time of referral were tested as well.ResultsWe recruited 121 consecutive patients with HIV or AIDS for this study: 60 Ethiopians and 61 Israeli patients. Of the 121 patients, 4 (3%) had abnormal thyroid function—subclinical hypothyroidism in 2, overt hypothy roidism in 1, and overt hyperthyroidism in 1. Previously stored serum samples were available for 60 of the 121 patients and revealed 2 additional patients with subclini cal hypothyroidism, whose TSH has normalized in the subsequent test. Throughout the follow-up period of 3.2 ± 1.9 years, the mean TSH level remained unchanged in the Israeli cohort but significantly declined in the Ethiopian cohort.ConclusionThyroid function abnormalities were uncommon in these Israeli patients with HIV or AIDS. This finding does not support the need for routine thyroid func tion tests in this patient population. The decline in TSH level in the Ethiopian population over time probably repre sents a shift from an iodine-deficient to an iodine-sufficient country. (Endocr Pract. 2012;18:882-886)     

Cytometry and Time-Dependent Variations in Peripheral Blood and Bone Marrow Cells: A Literature Review and Relevance to the Chronotherapy of Cancer

By flow cytometry of individual cells, multiple cell properties can be analyzed. Such parameters may be important in relation to cytotoxic treatment of cancer. For example, DNA measurements will answer questions regarding cell kinetics. Myelosuppression is the major dose-limiting toxicity during cancer treatment. Therefore, the study of cell cycle parameters in bone marrow cells is highly relevant. However, inattention to the existence and potential importance of biological rhythms may introduce artifacts and misleading results. The literature of rhythms in hematology is reviewed. Time-dependent variations in hematological variables have been extensively studied and rhythms have been described for all kinds of blood cells. Also the numbers of hemopoietic stem cells in the bone marrow undergo circadian variations. Our group has shown how such variations change with aging in mice. The relevance of time sequence studies in aging research of hemopoiesis was clearly demonstrated. In animal studies using cytometry, our group has demonstrated extensive circadian variations in cell cycle distribution of bone marrow cells, especially the DNA synthesis (S-phase). In humans a few and rather small time sequence studies of the bone marrow have been performed, so far. In this overview the clinical implications of circadian rhythms of S-phase variations measured by flow cytometry of human bone marrow cells are discussed. Male volunteers were examined every 4 h around-the-clock. The data indicated a lower proliferative activity during night, suggesting the possibility of reducing the bone marrow toxicity to cancer treatment when taking these time-dependent variations into consideration.