Blood arsenic: Pan-India prevalence.

INTRODUCTION: Arsenic, a well-known toxic element, has become one of the biggest causes for clinical concerns among elemental toxicities. Arsenicosis has been reported from many regions of the country, especially on exposure induced by ground water contamination. The clinical effects of chronic arsenic toxicity are generally varied and its timely diagnosis and management pose a big challenge. METHODOLOGY: Our study reports analysis of blood arsenic levels in a pan-India cohort of 205,530 including 111,737 males and 93,793 females respectively. The cohort included all age groups from infants to old adults. Arsenic levels were analyzed using the analytical platform of ICP-MS touted to be the gold standard for elemental analysis. RESULT: Blood arsenic levels of ≥5 µg/L were considered high in our study. The total frequency of high arsenic cases detected in the study is 1.37%. The frequency in males was 1.47% and in females it was detected to be 1.25%. Also, maximum cases of high arsenic levels were detected to be from the state of Kerala and in cities from Mumbai. CONCLUSION: Very few studies have recorded the frequency of high arsenic levels in Indians as well as its average blood levels in a pan-India cohort. Our study has made a pilot attempt to highlight the same to generate awareness about this elemental menace in the Indian context.

Lead toxicity: An overview of prevalence in Indians.

INTRODUCTION: Elements form a basic and natural constituent of the Earth's crust and are released into the atmosphere due to many human activities like mining and manufacturing. Of all, the elements, lead toxicity is a prevailing as well as a growing concern the world over because of its ability to affect multiple clinical functions. METHODOLOGY: Blood lead levels have been analyzed in a large pan-India cohort of 222,668 comprising of 121,115 males and 101,553 females respectively. The cohort included all age groups from <2 to >55 years old. The analytical platform of Inductively Coupled Plasma-Mass Spectrometry has been used to assess lead levels. RESULT: Blood lead levels of ≥150 µg/L was considered high for analysis. The total frequency of high lead levels detected in our study was 1.16%. The frequency of males affected were higher than females, with the difference being statistically significant.. CONCLUSION: Lead being ubiquitous in its presence and also serving no biological function, has grown today to become a serious threat to human health. The high frequency of affected detected in our study raises a cause for concern. Determining its presence and the most affected geography in any country will aid in charting guidelines on controlling its release as well as exposure.

Hemoglobinopathy in India.

OBJECTIVES: Variations in hemoglobin structure as well as number of globin chains give rise to a wide spectrum of heritable disorders. As such, their detection is significant from epidemiological perspective, especially in India in which there is a large multi-cultural population with distinct geographic distribution. Although a few variants present severe clinical symptoms in homozygotes, co-existence of heterozygous mutants can lead to deleterious conditions. The aim of the present study is to provide an overview on the prevalence of different hemoglobinopathies among Asian Indians. DESIGN AND METHODS: A large cohort of samples from all regions of India was analyzed by high performance liquid chromatography (HPLC) (n=25,297) and capillary electrophoresis (CE) (n=21,219). RESULTS: Using HPLC, 8029 hemoglobin variants were detected. HbS trait was detected at the highest frequency (33.03%), principally from the Chattisgarh region. Using CE, 6524 variants were detected. HbS trait, again, represented the most common mutation (25.67%). A total of 40 variants including compound heterozygous cases were detected by HPLC and CE. CONCLUSIONS: Our report is one of the few to analyze a large cohort and report on the spectrum of hemoglobin variants in India.

National seroprevalence of Toxoplasma gondii in India.

This article reports the first national serological prevalence of Toxoplasma gondii in India. In total, 23,094 serum samples were tested for T. gondii IgG and IgM antibodies with the use of a solid-phase immunocapture ELISA. Antibodies (IgG) were found in 24.3%; IgM antibodies were detected in 2% of the samples. The lowest seroprevalences were in the northern parts of India, with the highest in the south. These data probably reflect the effects of significantly drier conditions and, therefore, a negative impact on the survivability of T. gondii oocysts.

Thyroid hormone binding protein abnormalities in patients referred for thyroid disorders.

BACKGROUND & OBJECTIVES: Thyroid hormone binding protein (THBP) abnormalities are the major cause of discordance in commonly performed total thyroxine (T4) and thyrotropin (TSH) estimations, though these do not interfere with thyroid hormone action. Determination of such abnormalities in patients showing discordant thyroid function tests (TFTs) is diagnostically important as it eliminates equivocal assessment of thyroid function and treatment especially where proper methodology for free T4 (FT4) estimation is not available. This study was undertaken to analyse the THBP abnormalities in the population attending thyroid clinic. Family members of affected patients were also screened to study the inheritance of quantitative TBG abnormalities. METHODS: Blood samples of 15000 consecutive patients over a period of 4 years (1994-1997) were tested for thyroid function. THBP abnormalities were studied using polyacrylamide gel electrophoresis autoradiography. Serum thyroxine binding globulin (TBG), free and total T4, total tri-iodothyronine (TT3) were assayed by radioimmunoassay methods. RESULTS: In our screening of 15,000 thyroid patients over a four year period, we found the presence of complete and partial TBG deficiency and TBG excess to be 1:2,500, 1:200 and 1:15,000 respectively. Our study on the families of three affected patients revealed X-chromosome linked inheritance pattern of TBG deficiency in two families and TBG excess in one family. INTERPRETATION & CONCLUSION: Our study suggests that it would be beneficial to rule out THBP abnormalities before interpreting results of TFTs, particularly when there is large discrepancy between T4 and TSH levels. In case of inherited THBP abnormalities, the family members of the affected individual should also be screened to avoid misdiagnosis and erroneous treatment in case they develop thyroid dysfunction in future.

An immunoradiometric assay for measurement of serum thyroglobulin.

A two-site immunoradiometric assay (IRMA) for estimation of serum thyroglobulin (tg) is optimized using partially purified rabbit anti-tg antibodies (ammonium sulphate precipitated) as a solid phase antibody and affinity purified 125I labeled anti-tg antibodies as a tracer. The IRMA correlated well (r = 0.93, n = 200, P < 0.001) with conventional radioimmunoassay (RIA). The inter- and intra-assay coefficient of variation were comparable for both methods. The IRMA method gave a superior sensitivity and working range (2 ng/ml, 3-1000 ng/ml) as compared to that of RIA method (6 ng/ml, 9-500 ng/ml). Using IRMA the total incubation time was curtailed to 4 h as compared to 90 h required for conventional RIA. The shelf-life of tracer antibody used in IRMA was much longer (3 months) as compared to tracer tg (3-4 wk) used in RIA. The optimized IRMA for quantitation of serum tg has superior assay characteristics as compared to RIA.

Determination of free thyroxine in serum using column chromatography & radioimmunoassay.

A simple method for measurement of free thyroxine (FT4) levels in serum by adsorption chromatography and subsequent radioimmunoassay (RIA) is described. Assay sensitivity observed by this method was 1.2 pg/ml. Intra-assay variability was 11.2 per cent for FT4 concentrations of 7.9 pg/ml (n = 10), while interassay variability was 23.3, 9.7 and 12.9 per cent respectively for concentrations of 2.66, 12.06 and 23.96 pg/ml (n = 16). Serum FT4 concentration estimated by this method in 79 euthyroid patients was found to be 10.8 +/- 3.1 pg/ml. Values of FT4 obtained in hypothyroid and hyperthyroid patients were outside the normal range. FT4 values obtained by this method correlated well with the standard Liso-phase FT4 kit (r = 0.8) as well as free FT4 index (r = 0.93).

Monoclonal antibodies to human thyroglobulin: production and characterization.

Human thyroglobulin was used as an antigen for the development of monoclonal antibodies by the hybridoma technique. Spleen cells of BALB/c mice immunized with human thyroglobulin were fused with SP2/0 mouse myeloma cells. Seven clones secreting specific monoclonal antibodies to thyroglobulin were established. Two of these monoclonal antibodies have been purified and characterized. Their equilibrium association constants (Ka) as determined by Scatchard analysis were 0.24 X 10(11) L/M and 1.4 X 10(11) L/M respectively. The specificity of both these antibodies was validated by immunohistochemical staining of human tissues (normal human thyroid, brain, salivary gland, skeletal and smooth muscle, mucous membrane, parathyroid, adrenal) obtained from autopsy material. Only follicles and follicular cells of thyroid tissue were stained by both the monoclonal antibodies. H10 I monoclonal antibody was used for constructing a standard curve for in vitro immunoassay using a solid phase ELISA technique. The minimum amount detectable was 7.8 ng/ml. Thirty six sera from patients of various thyroid disorders were evaluated using ELISA and compared with conventional RIA. A good agreement was seen (r = 0.92) between the two techniques. These specific monoclonal antibodies may prove to be valuable for in vitro immunoassays and in vivo immunoscintigraphy.