Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

Plasma levels of genistein following a single dose of soy extract capsule in Indian women.

BACKGROUND & OBJECTIVE: Soy isoflavones are being used as therapy for menopausal syndrome in many countries. Marketed preparations show variability in bioavailability and there are variations in kinetics due to ethnicity and diet. Inspite of soy isoflavone being available in the Indian market there are no studies to show whether the preparation is likely to be effective in women. This study was carried out to determine circulating levels of genistein, a bioactive soy isoflavone, in Indian women after a single dose of soy extract. METHODS: Six healthy vegetarian women volunteers, between 36 and 62 yr and with a mean body mass index (BMI) 25.01+/-2.02 (kg/m2), were enrolled after an informed consent. Women with antibiotic or Soy food intake within 1 month of study were excluded. A single dose of standardized soy extract capsule containing 64.12 mg of total isoflavones (genistein content equivalent to 31.76 mg) was ingested under supervised fasting condition and multiple blood samples were collected at 0, 1, 2, 4, 6, 8 and 24 h. Genistein levels were measured by high performance liquid chromatography (HPLC) method with a detection level of 2.5 ng/100 microl of injection volume. The intra- and inter-assay coefficients of variation were < 5.32 per cent. RESULTS: Genistein was detected (10.3 to 16.2 ng/ml) in 3 volunteers in baseline samples. Within one hour genistein levels rose from 42 ng to 215 ng/ml with a maximum concentration of 117 to 380 ng/ml at 4 to 8 h. A secondary peak suggestive of enterohepatic circulation was seen between 4 and 6 h in 2 out of 6 volunteers. The mean Cmax was 315.5 +/- 57.1 ng/ml. All women had detectable levels from 25.2 to 109.3 ng/ml at 24 h. INTERPRETATION & CONCLUSION: Our study showed adequate circulating levels of genistein in Indian vegetarian women after a single dose of soy extract. Variability in plasma levels of the soy isoflavones may explain differences in responses to therapy.

Sulfa drugs: thermodynamic proton-ligand and metal-ligand stability constants.

The thermodynamic proton-ligand stability constants of sulfa drugs have been determined in different mole fractions of dioxane (0.083-0.174) at 25 and 35 +/- 0.1 degrees C. Empirical corrections to pH meter readings in mixed aqueous media have been applied. The pKa varies linearly with the mole fraction of dioxane. Numerical equations expressing this linear relationship have been obtained using the method of least squares, and relevant correlation coefficients have been calculated. The thermodynamic parameters delta G degrees, delta H degrees, and delta S degrees are calculated. The effect of solvent and the change in free energy from mixed aqueous media, delta, is discussed. The thermodynamic metal-ligand stability constants of Cu(II), Pd(II), and Ce(IV) with sulfa drugs in 50% aqueous dioxane at 35 +/- 0.1 degrees C have been determined. The effect of basicity of the ligand and the order of the stability constant is discussed.

Extraction and micro-determination of manganese(II) with oxine and aliquat 336.

A sensitive and selective method has been developed for the micro-determination of Mn(II) by the selective extraction of the yellow Mn(II)-8-hydroxyquinolinate complex with a liquid ion-exchanger, Aliquat 336, from basic medium. The molar absorptivity of the complex is 2.2 x 10(4)1.mole(-1).cm(-1) at 420 nm and the colour system obeys Beer's law in the range 0.1-3.5 ppm Mn(II) in the final solution. The composition and stability of the complex are discussed. Potential interferents have been examined and the method is applied to analysis of standard steel and bronze samples.

Ion-exchange separation and spectrophotometric determination of vanadium in environmental samples.

A selective and sensitive method for the extraction and spectrophotometric determination of vanadium(V) in microgram quantities is described. The molar absorptivity of the yellow vanadium(V)-caffeic acid-Aliquat 336 extract is 1.3 x 10(4) 1.mole(-1).cm(-1) at 370nm. The method is compared with the atomic-absorption spectrometric method and applied to the trace determination of vanadium in steel, alloys, a rock and environmental samples.

Sequential liquid-liquid extraction graphite furnace atomic absorption spectrometric (GFAAS) and spectrophotometric determination of zirconium(IV) with calixarene hydroxamic acid.

A new calixarene hydroxamic acid, 25,26,27,28-tetrahydroxy-5,11,17,23-tetrakis (N-p-chlorophenyl) calix[4]arene hydroxamic acid (CPCHA) is synthesized and used for the extraction and graphite furnace atomic absorption determination of zirconium(IV). The extract is also determined spectrophotometrically as CPCHA-SCN complex having maximum absorbance at 447 nm with molar absorptivity 9.4x10(3) l mol(-1) cm(-1). The Beer's law obeys in the range of 1.0-9.5 ppm of zirconium. The graphite atomic absorption (GFAAS) increases the sensitivity by about 50 folds. The method is applied to the trace determination of zirconium(IV) in standard samples.

An algorithmic approach to adaptive state filtering using recurrent neural networks.

Practical algorithms are presented for adaptive state filtering in nonlinear dynamic systems when the state equations are unknown. The state equations are constructively approximated using neural networks. The algorithms presented are based on the two-step prediction-update approach of the Kalman filter. The proposed algorithms make minimal assumptions regarding the underlying nonlinear dynamics and their noise statistics. Non-adaptive and adaptive state filtering algorithms are presented with both off-line and online learning stages. The algorithms are implemented using feedforward and recurrent neural network and comparisons are presented. Furthermore, extended Kalman filters (EKFs) are developed and compared to the filter algorithms proposed. For one of the case studies, the EKF converges but results in higher state estimation errors that the equivalent neural filters. For another, more complex case study with unknown system dynamics and noise statistics, the developed EKFs do not converge. The off-line trained neural state filters converge quite rapidly and exhibit acceptable performance. Online training further enhances the estimation accuracy of the developed adaptive filters, effectively decoupling the eventual filter accuracy from the accuracy of the process model.

Spectrophotometric determination of sulphacetamide.

A new rapid selective spectrophotometric method for the determination of sulphacetamide is described. The drug forms a orange-yellow colored complex with Cerium(IV) in sulfuric acid media which is extracted into ethyl acetate. The complex exhibits a maximum absorbance at 440 nm with a molar absorptivity of 3 x 10(2) 1 mol-1 cm-1. The system obeys Beer's law in the concentration range of 0.07-1.1 mg of sulphacetamide. The various parameters for the optimum extraction conditions are discussed. The method is applied to the determination of sulphacetamide in dosage forms.

Thermodynamic ionization constants of antihypertensive drugs.

The thermodynamic ionization constants (pKa) of indapamide, clonidine and methyldopa have been determined at 25 degrees C and 35 degrees C by pH titration technique. The pKa varies linearly with mole fraction of dioxane. The thermodynamic parameters have been calculated.

Congenital adrenal hyperplasia 11beta-hydroxylase deficiency: two cases managed with bilateral adrenalectomy.

This series describes two patients with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency. The first patient, a ten-year-old with XX genotype, reared as a male, presented with resistant hypokalaemia and hypertension. The second patient, a 23-year-old with XY genotype, presented with bilateral adrenal masses and resistant hypertension. Both the patients were offered bilateral adrenalectomy. These two patients are described with a discussion on the role of bilateral adrenalectomy in the management of difficult cases of congenital adrenal hyperplasia. The association of myelolipoma and testicular rests with this condition is also discussed.

Autoimmune hypophysitis: a single centre experience.

INTRODUCTION: Autoimmune hypophysitis (AH) is a rare primary autoimmune inflammatory disorder involving the pituitary gland. METHODS: A retrospective analysis of the clinical features and outcome of patients diagnosed with AH between 1988 and 2006, was carried out. RESULTS: 15 patients (14 females and one male) with AH were identified. Three patients presented in the peripartum period. Headache, vomiting and visual field defects, suggestive of an expanding sellar mass, were the most common presenting symptoms (67 percent). The most common deficient hormone was adrenocorticotropic hormone (ACTH) (67 percent), followed by thyroid stimulating hormone (53 percent) and gonadotropins (40 percent). Imaging revealed a definite, enhancing sellar mass in 87 percent of the patients and stalk thickening in 33 percent of the patients. Three patients underwent surgery. On serial monitoring, the sellar mass regressed or disappeared spontaneously without any immunosuppressive treatment in the other ten patients with a definite sellar mass. CONCLUSION: We report a higher female to male ratio and a lower incidence of peripartum cases in our series. Symptoms of mass effect were the most common presentation, while ACTH was the most commonly-deficient hormone. Surgery was rarely needed, and most patients experienced a spontaneous resolution of the mass.

The role of percutaneous renal biopsy in clinical nephrology.

Percutaneous renal biopsy provides the cornerstone for our understanding of the diseases of the kidney. Recent advances in biopsy techniques, such as the use of real-time ultrasonography and the biopsy gun, have made this procedure easier, increased the yield of diagnostically adequate tissue, and may result in a lower complication rate as well. Despite these improvements, the role of biopsy in the treatment of individual patients remains controversial. Even in diseases such as nephrotic syndrome and systemic lupus erythematosus, where biopsy findings have been used to categorize outcome events, it is unclear whether the biopsy provides more accurate information than can be obtained from less invasive procedures or from empiric therapy. Renal biopsy, however, does remain the best method for evaluation of renal dysfunction in renal allograft recipients. The role of fine-needle aspiration cytology in the management of transplant rejection remains to be established.

Stability of total nutrient admixtures in a dual-chamber flexible container.

The stability of total nutrient admixtures (TNAs) prepared from dextrose and amino acid injections commercially packaged in a dual-chamber container and a safflower-soybean oil fat emulsion was studied. The admixtures studied were divided into two groups. Group 1 admixtures represented 14 combinations of Aminosyn II, dextrose, and Liposyn II. Group 2 admixtures represented 10 combinations of Aminosyn II with Electrolytes, dextrose, and Liposyn II. Amino acid concentrations of 7, 8.5, and 10%, dextrose concentrations of 10, 20, 40, and 50%, and 10 and 20% fat emulsion were used. After the amino acid and dextrose injections were mixed in their original container (Nutrimix, Abbott Laboratories), the fat emulsion was added. One of two combinations of electrolytes and trace metals was then added. Multivitamins were added to each TNA just before 24-hour storage at room temperature (25 +/- 4 degrees C). Admixtures were tested initially and at the conclusion of storage periods of 24 hours at room temperature or nine days at 5 degrees C followed by 24 hours at room temperature. Measurements of pH, emulsion particle size, and weight percent of oil particles larger than 5 microns in diameter (HIAC) were made after visual inspection of each admixture. In selected admixtures, concentrations of individual amino acids and dextrose were determined by chromatographic techniques initially and at the conclusion of storage. The TNAs retained a uniform milk-like appearance throughout both storage periods. The pH values, particle size, HIAC measurements, and amino acid and dextrose concentrations remained essentially unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergenic agent in contact dermatitis from Holigarna ferruginea.

9 of 10 patients who developed dermatitis following contact with Holigarna ferruginea and 5 of 35 asymptomatic volunteers showed a positive patch test reaction to 2% W/V acetone extract of the plant's resinous exudate. 6 albino rats were sensitized following 3 weekly applications of the same extract. Laccol (3-heptadecadienyl catechol) was identified as the active principle in the exudate.