The Lancet Commission on precision health: equitable, data-driven health outcomes for all.
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Journal Article↗
Biomedical subjects
Nikhil Tandon
Publications and source records attributed to Nikhil Tandon.
Prevalence and functional significance of 25-hydroxyvitamin D deficiency and vitamin D receptor gene polymorphisms in Asian Indians.
BACKGROUND: Recent studies show a wide prevalence of hypovitaminosis D in Asian Indians. OBJECTIVE: The objective was to assess the functional significance of 25-hydroxyvitamin D [25(OH)D] deficiency, vitamin D receptor (VDR) gene, and parathyroid hormone (PTH) gene polymorphisms in relation to bone mineral density (BMD) in urban Asian Indians. DESIGN: Serum total calcium, inorganic phosphorus, alkaline phosphatase, 25(OH)D, intact PTH, and BMD at lumbar spine, proximal femur, and forearm were measured in 105 adult subjects. The genotyping related to VDR (BsmI, FokI, and TaqI) and PTH (BstBI and DraII) gene single-nucleotide polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The mean serum 25(OH)D concentration in the whole cohort was 9.8 +/- 6.0 ng/mL, which was inversely related with serum intact PTH values (P = 0.042). Ninety-nine (94.3%) of the 105 subjects had vitamin D deficiency with 25(OH)D concentrations < 20 ng/mL. The age- and body mass index (BMI)-adjusted BMD value at the hip was higher in subjects with serum 25(OH)D values > 9.0 ng/mL than in those with values < or = 9.0 ng/mL (0.893 +/- 0.114 compared with 0.839 +/- 0.112 g/cm2, respectively; P = 0.001). The mean forearm and spine BMD values in subjects with TT (VDR, TaqI) or bb (PTH, BstBI) genotypes were significantly higher than the values in subjects with Tt genotype and BB or Bb genotype, respectively. CONCLUSION: Functionally significant 25(OH)D deficiency affecting BMD at the hip region is prevalent in urban Asian Indians. However, variation in BMD at the spine and forearm is related to VDR and PTH gene polymorphisms rather than to vitamin D status, at least in this hypovitaminotic D population.
Adult↗
A study of growth parameters and prevalence of overweight and obesity in school children from delhi.
OBJECTIVE: (1) To assess the height, weight and body mass index (BMI) of school children from Delhi and generate percentile charts as appropriate for age, gender and socio-economic status. (2) To determine the prevalence of overweight and obesity in school children from low and upper socioeconomic status (LSES and USES respectively). DESIGN: Cross sectional evaluation of anthropometric parameters in Delhi school children (5-18 years) from different geographical zones. SETTING: Government schools (non-fee paying) and Private Schools (fee paying) in Delhi. SUBJECTS: 21485 children, 8840 (3566 boys, 5274 girls) from government schools and 12645 (6197 boys, 6448 girls) from private schools. METHODS: Subjects underwent assessment of height and weight and calculation of BMI. Children were classified as normal, overweight and obese as per IOTF guidelines. Height, weight and BMI percentile charts specific for the socioeconomic status were generated using the LMS method. Prevalence of overweight and obesity was assessed and compared between the two socio-economic groups. RESULTS: A significant difference was noted in height, weight and BMI between LSES and USES. The prevalence of overweight and obesity in USES children was 16.75 % and 5.59 % in boys and 19.01 % and 5.03 % in girls respectively. CONCLUSIONS: There is a significant disparity in anthropometric parameters between children from USES and LSES, with a high prevalence of overweight and obesity in USES children.
Adolescent↗
Thyroxine replacement therapy reverses sleep-disordered breathing in patients with primary hypothyroidism.
BACKGROUND AND PURPOSE: Anecdotal reports suggest that sleep-disordered breathing (SDB) is common among patients with primary hypothyroidism. This study was undertaken to determine the prevalence of SDB and to evaluate the effect of thyroxine replacement therapy on SDB in patients with primary hypothyroidism. PATIENTS AND METHODS: Fifty consecutive newly diagnosed, untreated symptomatic patients with primary hypothyroidism (age: 34+/-11 years; males: 21 [42%]) were prospectively studied. Physical examination, anthropometry, fasting blood glucose and serum lipids were performed in all patients at baseline. Polysomnography was done at baseline in all patients and was repeated after adequate thyroxine replacement in those who had SDB. RESULTS: SDB defined as apnea-hypopnea index (AHI) > or =5 was present in 15 patients (30%) at baseline and was reversible in 10 of the 12 patients evaluated following thyroxine replacement therapy (P=0.006). Thyroxine replacement therapy was associated with improvement in findings that reflect a compromised upper airway, such as macroglossia (4 [33%] vs. 1 [8%]; P=0.083), myoedema (5 [42%] vs. 1 [8%]; P=0.046) and facial puffiness (10 [83%] vs. 1 [8%]; P=0.003). CONCLUSIONS: Reversible SDB is common among patients with primary hypothyroidism. Changes in upper airway anatomy resulting from hypothyroidism probably contribute to the development of SDB in these patients.
Adult↗
Genetic association, post-translational modification, and protein-protein interactions in Type 2 diabetes mellitus.
Type 2 diabetes mellitus is a complex disorder with a strong genetic component. Inherited complex disease susceptibility in humans is most commonly associated with single nucleotide polymorphisms. The mechanisms by which this occurs are still poorly understood. Here we focus on analyzing the effect of a set of disease-causing missense variations of the monogenetic form of Type 2 diabetes mellitus and a set of disease-associated nonsynonymous variations in comparison with that of nonsynonymous variations without any experimental evidence for association with any disease. Analysis of different properties such as evolutionary conservation status, solvent accessibility, secondary structure, etc. suggests that disease-causing variations are associated with extreme changes in the value of the parameters relating to evolutionary conservation and/or protein stability. Disease-associated variations are rather moderately conserved and have a milder effect on protein function and stability. The majority of the genes harboring these variations are clustered in or near the insulin signaling network. Most of these variations are identified as potential sites for post-translational modifications; certain predictions have already reported experimental evidence. Overall our results indicate that Type 2 diabetes mellitus may result from a large number of single nucleotide polymorphisms that impair modular domain function and post-translational modifications involved in signaling. Our emphasis is more on conserved corresponding residues than the variation alone. We believe that the approach of considering a stretch of peptide sequence involving a polymorphism would be a better method of defining the role of the polymorphism in the manifestation of this disease. Because most of the variations associated with the disease are rare, we hypothesize that this disease is a "mosaic model" of interaction between a large number of rare alleles and a small number of common alleles along with the environment, which is little contrary to the existing common disease common variant model.
Diabetes Mellitus, Type 2↗
Vitamin D and bone mineral density status of healthy schoolchildren in northern India.
BACKGROUND: Current data on the prevalence of vitamin D deficiency in India are scarce. OBJECTIVE: We assessed the calcium-vitamin D-parathyroid hormone axis in apparently healthy children from 2 different socioeconomic backgrounds in New Delhi, India. DESIGN: Clinical evaluation for evidence of vitamin D deficiency was carried out in 5137 apparently healthy schoolchildren, aged 10-18 y, attending lower (LSES) and upper (USES) socioeconomic status schools. Serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and immunoreactive parathyroid hormone were measured in 760 children randomly selected from the larger cohort. Bone mineral density of the forearm and the calcaneum was measured in 555 children by using peripheral dual-energy X-ray absorptiometry. RESULTS: Clinical evidence of vitamin D deficiency was noted in 10.8% of the children. Children in the LSES group had a significantly (P < 0.01) lower 25(OH)D concentration (10.4 +/- 0.4 ng/mL) than did those in the USES group (13.7 +/- 0.4 ng/mL). Concentrations of 25(OH)D <9 ng/mL were seen in 35.7% of the children (42.3% in LSES; 27% in USES; P < 0.01). Boys had significantly (P = 0.004) higher 25(OH)D concentrations than did girls. There was a significant negative correlation between the mean serum immunoreactive parathyroid hormone and 25(OH) D concentrations (r = -0.202, P < 0.001). Mean forearm bone mineral density was significantly (P < 0.01) higher in the USES group than in the LSES group. CONCLUSION: A high prevalence of clinical and biochemical hypovitaminosis D exists in apparently healthy schoolchildren in northern India.
25-Hydroxyvitamin D 2↗
Glycaemic control and microvascular complication among patients with youth onset diabetes in India using differing types of insulin and methods of glucose monitoring.
We assessed whether insulin types and monitoring methods were relevant to glycaemic control, microvascular complications as well as costs of management in 208 patients with youth onset diabetes in India. The type of insulin and monitoring method used made no difference to the glycaemic and complication status. Cost considerations support bovine insulin use along with urine glucose monitoring as an appropriate approach to diabetes self care in developing countries.
Adolescent↗
Phosphaturic mesenchymal tumor: a case report.
Osteomalacia induced by tumor is a rare phenomenon in which the resection of tumor is followed by dramatic amelioration of clinical signs and symptoms. We hereby report a case of a 66 years old male who presented with features of osteomalacia in which the characteristic clinical presentation was associated with the phosphaturic mesenchymal tumor, mixed connective tissue variant. The case is reported for its rarity.
Aged↗
Residual goitre in the postiodization phase: iodine status, thiocyanate exposure and autoimmunity.
OBJECTIVE: This study was done to assess goitre prevalence, thyroid functional status and cause of residual goitre among school children in the postsalt iodization phase in India. DESIGN: A cross-sectional study in which, 14762 school children in the age group of 6-18 years, from different States and Union territories of India, were evaluated for goitre prevalence, urinary iodine and thiocyanate excretion, functional status of the thyroid as well as serological and cytopathological markers for thyroid autoimmunity. MEASUREMENTS: Urinary iodine (wet ashing method), urinary thiocyanate (colourimetric method), serum thyroxine [in-house radioimmunoassay (RIA)], serum TSH (IRMA), antithyroid microsomal and antithyroglobulin antibodies (haemagglutination method) were estimated. Fine-needle aspiration cytology was performed in all goitrous subjects giving consent. RESULTS: The overall goitre prevalence was 23% (27.1% girls; 17.8% boys, P < 0.001). Subjects belonging to poor socio-economic strata had significantly higher goitre prevalence. Median urinary iodine excretion (UIE) in goitrous subjects (2-53 micromol/l) was significantly higher than in controls (2-24 micromol/l; P < 0.001). Levels of UIE observed among goitrous subjects showed no relationship with the presence or absence of thyroid dysfunction or with thyroid antibody status. High titres (> or = 1:1600) of TMA were present more often in goitrous subjects (6.08%) than nongoitrous controls (0.34%; P < 0.001) and in girls (7.3%) than boys (2.35%; P < 0.001). TMA positivity were significantly more among goitrous subjects with thyroid dysfunction than in euthyroid subjects. Significantly higher median urinary thiocyanate (USCN) excretion was observed in goitrous subjects (0.75 mg/dl) compared to controls (0.64 mg/dl; P < 0.001) and goitrous girls compared to goitrous boys. USCN excretion of goitrous subjects and controls showed no relationship with functional or thyroid antibody status in various groups. CONCLUSIONS: Persistent, albeit reduced prevalence of goitre, despite adequate iodine prophylaxis, suggests existence of additional factors in goitrogenesis in India. Thyroid autoimmunity can explain only a part of the goitre prevalence. The role of goitrogens in residual goitre prevalence is brought forth.
Adolescent↗
Rare association of xanthoma disseminatum with skeletal involvement.
A ten-year-old boy presented with a 2.5-year history of painful shoulder and hip joints, 1.5 years of yellow-brown papules and plaques on the face, flexures and trunk, and 6 months of polyuria and polydipsia. Skin biopsy revealed histological and immunohistochemical features typical of xanthoma disseminatum. Lytic bone lesions were seen in the femur and pelvis and sclerotic changes in the humerus on X-ray. Diabetes insipidus was also diagnosed
Biopsy↗
Familial aggregation of autoimmune thyroiditis in first-degree relatives of patients with juvenile autoimmune thyroid disease.
Several studies have shown aggregation of autoimmune thyroiditis in families by estimation of thyroid antibodies. However, the prevalence by concurrent estimation with fine-needle aspiration cytology (FNAC) and thyroid antibodies has not been previously reported. We therefore studied 222 first-degree relatives (group 1) of 71 index cases diagnosed as lymphocytic thyroiditis on FNAC and 81 family members (group 2) of 23 goitrous children diagnosed as colloid goiter on FNAC for comparison. Successful FNAC conducted in 122 group 1 subjects revealed lymphocytic thyroiditis in 51 (42%), whereas lymphocytic thyroiditis was diagnosed in only 5 goitrous subjects (13%) in group 2. Among group 1 subjects with FNAC-proven lymphocytic thyroiditis, antithyroid peroxidase (TPO) antibodies were found in 35 (67%), while in anti-TPO antibody positive goitrous relatives of group 1, lymphocytic thyroiditis was found in 36 (78%). Eight new cases of overt hypothyroidism and 45 new cases of subclinical hypothyroidism were diagnosed among group 1 subjects. Our study suggests: (1). familial clustering of autoimmune thyroiditis; (2). if only FNAC or thyroid antibodies is used for diagnosis of autoimmune thyroiditis in children, 22%-33% of cases are likely to be missed; and (3). serum thyrotropin (TSH) should be offered to all first-degree relatives of patients with juvenile autoimmune thyroiditis.
Adolescent↗
Thoracoscopy: the preferred method for excision of mediastinal parathyroids.
Mediastinal exploration to resect ectopic parathyroid is required in approximately 2% of all cases of hyperparathyroidism. Traditionally, it has been performed through a midsternotomy or thoracotomy. A few reports about thoracoscopic resection of mediastinal parathyroid were published recently. We report here successful video-assisted thoracoscopic resection (VATS) of a mediastinal parathyroid and present a review of all previously reported cases. A 42-year-old woman presented with spontaneous fracture of the left femur and hypercalcemia. She had previously undergone cervical parathyroidectomy for primary hyperparathyroidism. A computed tomography (CT) scan of the chest and a technetium scan showed ectopic mediastinal parathyroid. The patient underwent successful thoracoscopic resection of ectopic parathyroid. A total of 26 patients were reviewed, 21 in the English literature and 5 in others. Of the 21 patients reported in the English literature, 16 had primary hyperparathyroidism (1 degrees HPT), whereas 5 had secondary hyperparathyroidism (2 degrees HPT). All but 3 patients had undergone previous cervical exploration. Ectopic mediastinal parathyroid was localized preoperatively in all by CT scans of the chest and nuclear scans. All 21 patients had successful thoracoscopic resection. All but 3 had parathyroid adenoma. Postoperatively, serum calcium (Ca ), phosphate (PO4 ), and parathormone (PTH) values returned to normal in all patients. Age and sex of the patient, type of hyperparathyroidism (1 degrees or 2 degrees ), size of the gland, its location within the anterior mediastinum, the approach used to resect it (right or left thoracoscopic), and final histopathology of the resected gland (adenoma or hyperplasia) had no bearing on the success of thoracoscopic resection. The data seem to suggest that thoracoscopic resection of mediastinal parathyroid is a less-invasive, effective, and safe procedure. Accurate preoperative anatomic localization by CT and nuclear scans of the chest is the key to success.
Adult↗
Immunogenetics of autoimmune diseases in Asian Indians.
The HLA class II molecules play a critical role in the processing and presentation of specific peptides derived from autoantigens of pancreatic beta cells or gluten for T cell scrutiny in IDDM and CD. In the present study, extended DR3-positive haplotypes associated with autoimmunity in northern Indian patients have been reported. The haplotype A26-B8-DR3 was the most common autoimmunity-favoring haplotype encountered among these patients. This association is, indeed, unique to Indian autoimmune patients, as it replaces the otherwise most commonly associated Caucasian haplotype A1-B8-DR3 (AH8.1) in this population. Further, CD patients revealed 100% association with DQB1*0201 along with DQA*0501 (97%) either in cis or trans configuration.
Asian People↗
Cytologic characterization of postiodization residual goiter in schoolchildren by fine needle biopsy.
OBJECTIVE: To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. STUDY DESIGN: A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. RESULTS: The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. CONCLUSION: The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.
Adolescent↗
Academic medicine and health improvements in India.
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Career Choice↗
Inhaled insulin.
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Administration, Inhalation↗