A complex haemoglobinopathy diagnosis in a family with both beta zero- and alpha (zero/+)-thalassaemia homozygosity. (1/295)

The occurrence of point mutation alpha-thalassaemia and of complex combinations of haemoglobin defects is underestimated. Haemoglobinopathies, the most frequent monogenic recessive autosomal disorder in man, occur predominantly in Mediterranean, African and Asiatic populations. However, countries of immigration with a low incidence in the indigenous population, are now confronted with a highly heterogeneous array of imported defects. Furthermore, the occurrence of severe phenotypes is bound to increase in the near future because of the endogamous growth of the ethnical minorities and the lack of prevention. We describe an Afghan family in which both partners of a consanguineous relationship are carriers of a beta- as well as an alpha-thalassaemia determinant. The combination of defects was revealed by the in vitro measurement of the beta/alpha biosynthetic ratio and was characterised at the DNA level. The molecular defects involved are the Cd5(-CT), a Mediterranean beta zero-thalassaemia mutation, and the alpha 2(zero/+)-thalassaemia AATA(-AA) polyadenylation defect. The alpha-thalassemia defect is a rare RNA-processing mutant described only twice before in heterozygous form in Asian-Indian patients. The mutation suppresses the expression of a alpha 2 gene and reduces the expression of the less efficient, 3' located alpha 1 gene as well, inducing a near alpha zero-thalassaemia phenotype. This defect is now described for the first time in the homozygous condition in one of the children who, in addition to being homozygous for the alpha-thalassaemia point mutation, is also a carrier of the beta zero-thalassaemia defect. A previously described homozygous case of the alpha (zero/+)-thalassaemia condition, caused by a similar polyadenylation defect, was characterised by a severe HbH disease. However, the patient described here present at 7 years of age with severe caries, like his beta-thalassaemia homozygous brother but without hepatosplenomegaly, haemolysis or severe anaemia. The haematological analysis revealed 9.5 g/dl Hb; 5.4 x 10(12)/I RBC; 0.33 I/I PCV; 61 fl MCV; 17.6 pg MCH and 6.2% of HbA2. The biosynthetic ratio beta:alpha was 1.6 and no HbH fraction was detectable either on electrophoresis or as inclusion bodies. The parents reported no complications during pregnancy, at birth, or in the neonatal period in rural Afghanistan. We presume therefore that the counterbalancing effect induced by the co-existing beta-thalassaemia defect could have modified a potentially severe perinatal HbH disease into a strongly hypochromic but well compensated 'alpha zero-like heterozygous' thalassaemia phenotype. The risk of a severe HbH disease, could have been easily missed in this family which was referred because of a child affected with beta-thalassaemia major.  (+info)

Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. (2/295)

OBJECTIVE: to evaluate whether oral supplementation with zinc or zinc/arginine increases the antibody response to influenza vaccine or modulates the lymphocyte phenotype in elderly subjects. DESIGN: a randomized controlled trial with two supplemented groups and one control group. SETTING: a community nursing home. PARTICIPANTS: 384 subjects aged 64-100 (mean age 82 years) examined in three separate studies. INTERVENTION: oral supplementation with zinc (400 mg/day) or zinc plus arginine (4 g/day) for 60 days starting 15 days before influenza vaccination. The control groups received vaccine only. MEASUREMENTS: haematological and nutritional indices, antibody titre against influenza viral antigens, lymphocyte phenotype. RESULTS: supplementation with zinc or zinc plus arginine increased zinc plasma concentrations restoring the age-related impairment in zinc concentrations to values found in younger people. The antibody titre against influenza viral antigens was not increased in zinc or zinc/arginine supplemented groups in comparison with subjects receiving vaccine alone. The number of CD3, CD4 or CD8 lymphocytes was not affected by zinc or zinc/arginine supplementation. CONCLUSION: prolonged supplementation with zinc or zinc/arginine restores zinc plasma concentrations but is ineffective in inducing or ameliorating the antibody response after influenza vaccination in elderly subjects.  (+info)

Assessment of laboratory tests for plasma homocysteine--selected laboratories, July-September 1998. (3/295)

Cardiovascular disease, including coronary heart disease and stroke, is the leading cause of death in the United States. Elevated plasma homocysteine (Hcy), generally defined as fasting plasma Hcy levels >15 micromol/L, is an independent risk factor for vascular diseases (1,2). It is unknown whether Hcy is a cause of or a marker for atherosclerosis. A recent statement by the Nutrition Committee of the American Heart Association concluded that until results of clinical trials are available, population-wide Hcy screening is not recommended (3). However, Hcy tests are used in the clinical setting and information on interlaboratory variation, on method variation, is limited. To assess the status of interlaboratory and intralaboratory variation for Hcy analysis, CDC conducted a study of selected laboratories during July-September 1998. This report summarizes findings from the study, which indicates a need to improve analytic precision and to decrease analytic differences among laboratories (4).  (+info)

Quality assurance programme in haematology at a teaching hospital in the eastern region of Nepal. (4/295)

Quality assurance in haematology laboratory is intended to ensure the reliability of the laboratory tests. A quality assurance programme has two main aspects, namely, internal quality control and external quality assessment. A two year experience of quality assurance in haematology laboratory at B.P. Koirala Institute of Health Sciences, Nepal, is presented here. As a part of internal quality control, test results in the laboratory were scrutinized before release on a daily basis. Inconsistent result were checked for the given values with control material. In addition, the laboratory is a participant of the 'External Haematology Quality Assurance Programme' conducted by WHO regional reference centre at AIIMS, New Delhi, India. Variations related to errors in manual and autopipetting, calibration and inter-observer differences have been noted from time to time and rectified. The programme has helped us to deliver quality service in haematology laboratory at BPKIHS.  (+info)

The preanalytic phase. An important component of laboratory medicine. (5/295)

The preanalytic phase is an important component of total laboratory quality. A wide range of variables that affect the result for a patient from whom a specimen of blood or body fluid has been collected, including the procedure for collection, handling, and processing before analysis, constitute the preanalytic phase. Physiologic variables, such as lifestyle, age, and sex, and conditions such as pregnancy and menstruation, are some of the preanalytic phase factors. Endogenous variables such as drugs or circulating antibodies might interact with a specific method to yield spurious analytic results. The preanalytic phase variables affect a wide range of laboratory disciplines.  (+info)

Dehydration of mature and immature sickle red blood cells during fast oxygenation/deoxygenation cycles: role of KCl cotransport and extracellular calcium. (6/295)

Sickle red blood cells (RBC) become dehydrated as a consequence of potassium loss. This process depends at least partly on deoxygenation and may be influenced by the presence of oxygenation/deoxygenation cycles and the frequency of cycling. In this study, sickle RBC were subjected to approximately 180 oxygenation/deoxygenation cycles during 4 hours to evaluate RBC dehydration with cycle periods more similar to in vivo cycles than those in previous studies. A continuous-flow, steady-state apparatus circulated a dilute RBC suspension through gas-permeable silicone tubing with segments that were exposed to either nitrogen or ambient oxygen. The percentage of sickling and partial pressure of oxygen were measured by means of sampling ports in the deoxygenation and oxygenation regions. The density increase (dehydration) of young (transferrin receptor-positive) and mature (transferrin receptor-negative) RBC and the requirements for calcium and chloride were evaluated. Density increase correlated with the percentage of sickled cells at the deoxygenation sampling port and was observed only in the presence of calcium, thereby implicating the calcium-dependent potassium channel (Gardos pathway). Density increase was not dependent on the presence of chloride, making it unlikely that KCl cotransport was an important pathway under these conditions. (Blood. 2000;95:2164-2168)  (+info)

Evaluation of the Abbott CELL-DYN 4000 hematology analyzer. (7/295)

A new generation hematology analyzer, Abbott CELL-DYN 4000 (CD 4000), capable of providing 26 parameters, including fully automated reticulocyte, nucleated RBC, blast, band, and immature granulocyte, and variant lymphocyte counts, was evaluated by using the National Committee for Clinical Laboratory Standards H20-A protocol and compared with the Bayer-Technicon H-2 analyzer, which is used routinely in our laboratory. A lipid interference experiment and a sample aging study also were performed. Linearity, carryover, and precision were within the limits established by the manufacturer, and satisfactory agreement was found with the H-2 analyzer. The evaluation of leukocyte differential counts indicated an excellent correlation with the manual reference method for neutrophils and lymphocytes, a good correlation for monocytes and eosinophils, and a poor correlation for basophils in samples with low counts; for basophil counts of 2% or higher, we found an improvement of the correlation coefficient. In the lipid interference experiment, only hemoglobin determination was influenced significantly on the CD 4000, but by using a new Abbott hemoglobin reagent, the interference was eliminated. The CBC and differential counts were stable and reportable up to at least 24 hours. Intrasample viability information on leukocytes provided a quality check on each individual specimen.  (+info)

Evaluation of TruCount absolute-count tubes for determining CD4 and CD8 cell numbers in human immunodeficiency virus-positive adults. Site Investigators and The NIAID DAIDS New Technologies Evaluation Group. (8/295)

A single-platform technology that uses an internal bead standard and three-color flow cytometry to determine CD4 and CD8 absolute counts was evaluated for reproducibility and agreement. Values obtained using TruCount absolute-count tubes were compared to those obtained using a two-color predicate methodology. Sixty specimens from human immunodeficiency virus type 1-infected donors were shipped to five laboratories. Each site also analyzed replicates of 14 human immunodeficiency virus type 1-infected local specimens at 6 h and again at 24 h. The interlaboratory variability was significantly less with TruCount (median difference in percent coefficient of variation [%CV] between the two methods was -8% and -3% for CD4 and CD8, respectively) than with the predicate method. Intralaboratory variability was smaller, with a median difference in %CV of -1% for both CD4 and CD8 with 6-h samples and -2% and -3% for CD4 and CD8, respectively, with 24-h samples. Use of TruCount for shipped samples resulted in a median CD4 count change of 7 cells (50th estimated percentile) when all laboratories and CD4 strata were combined. For on-site samples, the median CD4 count change was 10 CD4 cells for 6-h samples and 2 CD4 cells for 24-h samples. Individual site biases occurred in both directions and cancelled each other when the data were combined for all laboratories. Thus, the combined data showed a smaller change in median CD4 count than what may have occurred at an individual site. In summary, the use of TruCount decreased both the inter- and intralaboratory variability in determining absolute CD4 and CD8 counts.  (+info)