Evaluation of the risk factors associated with donor specific blood transfusion.
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Biomedical subjects
Publications and source records attributed to S Vaidya.
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Clinical experience has shown that it is often difficult to identify HLA-DR antigens on peripheral blood from long-term dialysis patients, leukemic patients, or blood in poor condition due to age of specimen or delivery conditions. We have found that we can accurately detect HLA-DR antigens on peripheral blood T cells that have been activated with PHA and expanded with commercially available Interleukin 2. An advantage of this technique is that a minimal number of peripheral blood cells is required at the initiation of T-cell activation. The expansion of T cells to a number sufficient for HLA-DR analysis requires 7 to 10 days. To test the validity of this protocol, we analyzed the HLA-DR antigens on a total of 13 normal donors using both conventional techniques and activated T cells. In every case, HLA-DR detection was identical by both methods, and no false positive or negative reactions were observed. Next, we used activated T cells to analyze the HLA-DR antigens in patients that had been difficult or impossible to DR type using conventional methods. We successfully identified HLA-DR antigens on 16 of 16 bone marrow transplant candidates who were previously untypable. We also identified HLA-DR antigens in all of the eight renal dialysis patients who had been untypable on several previous occasions. Subsequent phenotypic analysis of family members for those patients confirmed that the HLA-DR antigens genetically transmitted from family were detected by this method. In summary, we consider that activated T cells can be used effectively and reliably for analysis of HLA-DR antigens for patients who are otherwise difficult to type by conventional methods.
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Serum immunoglobulin levels (IgA, IgG, and IgM) have been assayed in a representative sample of children (aged 1-7 years) with homozygous sickle cell disease and in the age/sex-matched control children with a normal haemoglobin genotype, followed from birth in a prospective cohort study. In SS disease, significant elevation of IgA occurred from the age of two years and of IgG from the age of six years. IgM levels were not significantly different in the two genotypes. The mechanisms contributing to these changes in immunoglobulins are currently unclear as is their clinical significance.
The pattern of infection was compared in 139 children with sickle cell-hemoglobin C (SC) disease and in 250 control children with a normal hemoglobin (AA) genotype ascertained at birth and followed prospectively for periods of zero to six years. Both infection incidence rates and survival curve analysis indicated highly significant increases in serious infection among children with SC disease. Respiratory infection and gastroenteritis were the most common infections, but only respiratory infections were significantly more frequent in SC disease. Pneumococcal bacteremia was confined to the SC group. No hematologic differences were apparent between SC patients with and without a history of serious infection, but infection was significantly more common in patients manifesting early splenomegaly.
The decline of fetal haemoglobin (Hb F) from birth to 6 years has been compared in a cohort of 266 Jamaican children with homozygous sickle cel (SS) disease and in 243 matched controls with a normal haemoglobin (AA) genotype. Hb F levels were significantly higher in the SS cases from 1 month onward but, unlike the normal controls, no sex difference was apparent. The Hb F levels in SS disease were significantly correlated with parental Hb F levels, suggesting that genetic factors regulating adult Hb F levels are active at earlier stages in development. Furthermore, some of these genetic determinants of Hb F production may be linked to the beta-like globin gene complex and be in linkage disequilibrium with the beta s allele.
A prospective radiological and haematological study of 182 patients with homozygous sickle cell anaemia has been undertaken to assess the prevalence and pattern of splenic opacification and relate this to the blood indices. Opacification was observed in 31% of patients. In 55% of these, the pattern was punctate, whereas in 32% it was amorphous. A curvilinear appearance was seen in the remainder. In the amorphous group, a high percentage (72%), the spleen was severely contracted. The pattern of opacification and degree of contraction was related to age. The haematological indices indicate a lower haemolytic rate in patients with splenic opacification indicating a milder disease process with a greater persistence of the splenic capillary bed.
The relationship of the clinical features of homozygous sickle cell disease in the first two years of life to the level of fetal hemoglobin at age 6 months was investigated. Mean HgbF levels were significantly lower in children manifesting early palpable splenomegaly, dactylitis, acute splenic sequestration, and in those who died. The risks of dactylitis and ASS were significantly greater in patients with lower HgbF levels. Since early splenomegaly itself may increase the risks of ASS, infection, and death, the relationship of HgbF to these features was further analyzed within the early splenomegaly group. The results suggest that a low HgbF may have a direct effect on the etiology of ASS, but any effect on infection or death is probably mediated via its relationship with the appearance of a palpable spleen. A protective effect of a high HgbF on the risk of dactylitis was demonstrated coincident with the accepted theory of its pathogenesis. Early HgbF determinations may be of value in identifying patients at high risk of serious complications during infancy.
A cohort study of sickle cell disease from birth has allowed observations on the disease without the symptomatic selection inherent in previous series. The development of haematological indices from birth to 6 years in male and female infants with homozygous sickle cell (SS) disease is presented and compared with values in age and sex matched controls with a normal haemoglobin (AA) genotype previously presented elsewhere. In SS disease total haemoglobin levels fell rapidly from birth to a plateau at 3-6 months before falling again to 15 months after which no age related change occurred. Mean cell haemoglobin concentration fell from birth to lowest values at 15-18 months before increasing to reach the level present at birth by the age of 5 years. Red cell counts fell rapidly after birth to a plateau at 2 months, increased slightly to 6 months and then fell steadily throughout the remaining period of the study. The men cell volume and mean cell haemoglobin also fell rapidly after birth reaching the lowest values by 6 months and then increased progressively. Female patients showed significantly higher MCV from 4 to 8 months and significantly higher haemoglobin levels from 15 months to 4 1/2 years. Compared to AA controls, SS patients manifested significantly lower levels of haemoglobin from 2 weeks, and red cell counts from 1 month, and significantly higher levels of MCHC from 4 months to 3 years, MCV from 8 months to 5 years, and serum iron levels from 1 to 4 years. Children with SS disease were partially protected from iron deficiency in early childhood, perhaps by increased intestinal absorption of iron, and the associated increase in intracellular haemoglobin concentration might be disadvantageous during this high risk period.
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Haematological indices, including total haemoglobin, mean cell haemoglobin concentration, red cell count, mean cell volume, mean cell haemoglobin, reticulocytes, and serum iron values, in a cohort of 243 randomly selected Negro children with normal haemoglobin genotype, followed from birth to 5 years, are reported. Total haemoglobin fell rapidly from high levels at birth to a plateau at 2-6 months; a secondary fall occurred after 6 months and a gradual increase after 18 months. The red cell count also fell rapidly, but increased after 2 months to a plateau and then slowly declined from age 1-5. Mean cell volume and mean cell haemoglobin fell continuously from birth to the lowest values at 15 months and then progressively increased to the age of 5 years. Serum iron levels were low at one year of age (mean 9.7 mumol/l) increasing slowly by age 4 and sharply by age 5. Mean cell haemoglobin concentration fell gradually to 1-1 1/2 years and then increased progressively to age 5. Values for Hb, MCHC, MCV, and MCH were consistently and often significantly lower in males before the age of 2 years, compatible with greater depletion of iron stores. Serum iron values were generally lower in males but there was no sex difference at one year when highly significant differences in Hb, MCHC, MCV, and MCH occurred. The cause of sex differences in early haematological development is currently unclear.
In white members of our panel who have been repeatedly typed, close association between the HLA-D and DR specificities was observed. The typings were concordant with both haplotypes in 71% of the North American white panel. In American Indians concordance was observed in 47%, and in American black panel members in only 24%. One-way MLC reactions between individuals matched for both HLA-DR and D were very low (15.8%). MLC reactions between individuals who were DR matched but D mismatched were found to be generally strong, with a mean DNV of 72.3%. It was concluded that the HLA-DR matching predicted the outcome of mixed lymphocyte culture reactions only when the individuals tested were matched also for HLA-D.
135 children with homozygous sickle-cell (SS) disease diagnosed at birth have been followed for 1--5 years. Severe bacterial infections were confined to those in whom the spleen was first palpable at or before 1 year of age and were commonest in those in whom the spleen was first palpable at or before age 6 months. Regular follow-up of children with SS disease diagnosed at birth will identify children particularly at risk of severe infections.
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This study aimed to determine the contribution of the underlying dentine and the enamel-dentine junction to measurements of mineral loss from enamel recorded using quantitative light fluorescence (QLF). Sixteen square blocks (5 x 5 mm) were cut from the labial surfaces of extracted bovine incisor teeth. A dental drill was used to remove dentine and the enamel-dentine junction from half of each specimen. All specimens were embedded in epoxy resin and ground to produce a smooth, flat enamel surface. Half of the enamel surface of the block, perpendicular to where the dentine had been removed, was demineralised for 72 h prior to undertaking QLF measurements from the enamel surface to compare fluorescence loss from different areas of the block. QLF readings taken from lesions with no underlying dentine or enamel-dentine junction were very similar to readings from lesions with underlying dentine. A comparison of the two data sets demonstrated a linear relationship with a gradient of 0.95 and a y intercept of -1.24 (r(2) = 0.936). From these data, the underlying dentine and enamel-dentine junction did not influence mineral loss in enamel measured using QLF.