Frequency of goldmann applanation tonometer calibration error checks

PURPOSE: To investigate how quickly Goldmann applanation tonometers used in clinical practice develop calibration errors, and to determine the frequency of checks required to detect these errors. MATERIALS AND METHODS: Prospective check of the calibration error of all Haag-Streit Goldmann applanation tonometers in the department at month zero, month one, and month four. The tonometers were checked according to the Haag-Streit method using a standard calibration check weight bar by two independent observers. Calibration errors were classed as +/-0.5 to 2.5 mm Hg, +/-3 to 4 mm Hg, or >+/-4 mm Hg. Tonometers with a calibration error greater than +/-2.5 mm Hg were returned to the manufacturer for re-calibration. RESULTS: At month zero 2 of 34 (5.9%), at month one 3 of 29 (10.3%), and at month four 0 of 33 (0.0%) tonometers fell within the manufacturer's recommended calibration range of +/-0.5 mm Hg. A total of 14 of 34 (41.2%) tonometers at month zero, 10 of 29 (34.5%) tonometers at month one, and 17 of 33 (51.5%) tonometers at month four were identified to have calibration errors greater than +/-2.5 mm Hg. CONCLUSIONS: Goldmann applanation tonometers are not as accurate as the manufacturer's recommended calibration error tolerance of +/-0.5 mm Hg would suggest. Calibration error of less than +/-2.5 mm Hg is clinically acceptable. Calibration error checks should be carried out once monthly and tonometers with calibration error greater than +/-2.5 mm Hg returned to the manufacturer for re-calibration. Additional checks should be made if tonometers suffer specific damage. Ideally individual ophthalmologists should check calibration before each session.     

What change detection tells us about the visual representation of shape

Many recent findings suggest that human observers are surprisingly "blind" to changes in visual displays, failing to notice when substantial scene elements are added, subtracted, or altered in successive presentations of the scene. But observers are far more sensitive to certain visual changes than others, and we suggest that which types of changes enjoy differential sensitivity can reveal a great deal about the underlying visual representations. In this study, we investigate how the human visual system represents the shape of objects by demonstrating a previously unknown influence on detection of changes in shape: the sign of contour curvature. We show that subjects are substantially more sensitive to changes in concave regions of a shape's contour than to changes in convex regions, even when these changes do not alter the number or location of parts. Further, we show that this effect is modulated by figure-ground assignment, so that changes to the same physical contour are more or less detectable, depending on the contour's perceived figural status, which determines whether the change falls in a concave or convex region. The results demonstrate a heightened sensitivity for changes at concavities that is not reducible to a sensitivity to changes in gross part structure.     

Synthesis and evaluation of N-(5-methyl-3-oxo-1,2- diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-N'-phenylureas as cholecystokinin antagonists

In the search for new cholecystokinin (CCK) ligands, ureidopyrazolines were identified in combinatorial libraries using 168 chemically diverse amines. The structure-activity relationship optimisation of this pyrazoline template 4a resulted in novel 3-oxo-1,2-diphenyl-2,3-di-hydro-1H-pyrazol-4-yl)-N'-phenylureas 5a-5o. These novel CCK ligands have shown to act as mixed CCK-A/CCK-B ligands in a [125]I-CCK-8 receptor binding assay. The best pyrazoline 5e of this series displayed an IC50 of 20 and 25 nmol/L for the CCK-A, and CCK-B receptor, respectively. In a subsequent in vivo evaluation using various behavior pharmacological assays, an anxiolytic effect of these novel diphenylpyrazolinyl ureas was found in the elevated x-maze with an ED50 of 1.7 mg/kg. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.69 mg/kg was determinated for urea 5e and the antidepressant effect had a magnitude comparable to desimipramine.     

Establishment of inherent stability of stavudine and development of a validated stability-indicating HPLC assay method

The present study describes degradation of stavudine under different stress conditions (hydrolysis, oxidation, photolysis and thermal stress), and establishment of a stability-indicating reversed-phase HPLC assay method. The drug was found to hydrolyse in acidic, neutral and alkaline conditions and also under oxidative stress. The major degradation product formed under various conditions was thymine, as evidenced through comparison with the standard and spectral studies (NMR, IR and MS) on the isolated product. Separation of drug, thymine and another minor degradation product was successfully achieved on a C-18 column utilising water–methanol in the ratio of 90:10. The detection wavelength was 265 nm. The method was validated with respect to linearity, precision (including intermediate precision), accuracy and specificity. The response was linear in the drug concentration range of 25–500 μg ml⁻¹. The mean values (±R.S.D.) of slope and correlation coefficient were 24256 (±0.679) and 0.9994 (±0.0265), respectively. The R.S.D. values for intra- and inter-day precision studies were <0.210 and <1%, respectively. The recovery of the drug ranged between 99.7 and 101.5% from a mixture of degraded samples. The method even proved to be affective on application to a stressed marketed capsule formulation.     

Data input module for Birth Defects Systems Manager

The need for a computational bioinformatics infrastructure to manage the vast digital information from functional genomics and proteomics motivated us to develop Birth Defects Systems Manager (BDSM) as an open resource to facilitate analysis and discovery in developmental biology and developmental toxicity. This report describes the design, development and implementation of the data loading module of BDSM, referred to as LoadBDSM. It includes a shared data directory resource that can be granted various levels of security for different research groups or investigators to manage experimental datasets individually or in groups. LoadBDSM allows the upload of data and experiment details using controlled semantics for developmental exposure (toxicant, dosing scenario, intervention), biological sample (species, tissue, stage) and disease outcome (time, risk, phenotype). It adheres to existing controlled vocabulary plus rules of inference (ontologies) for experiment, data and metadata annotations. LoadBDSM extends the capabilities of BDSM to support the emergence of "embryo-formatics" defined here as the data, information and knowledge from genomic sciences applied to, or derived from, an embryological context. This includes, but is not limited to, delineating pathways and biological regulatory networks for specific chemicals or classes of developmental toxicants, developing novel biomarkers indicative of exposure and/or predictive of adverse effects, and integrating modern computing and information technology with data from molecular biology.     

Novel lectins from rhizomes of two Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines

Two novel lectins were purified from rhizomes of two sweet flag species, namely Acorus calamus (Linn.) and Acorus gramineus (Solandin Ait.) by affinity chromatography on mannose linked epoxy-activated Sepharose 6B. The apparent molecular mass of the lectins, as determined by gel filtration chromatography, was 56 kDa for ACL and 55 kDa for AGL. In SDS-PAGE, pH 8.3, both lectins migrated with a subunit molecular mass of 13.6 kDa and 13.5 kDa, respectively, under reducing and non-reducing conditions thus indicating the absence of disulphide linkages. Acorus lectins readily agglutinated rabbit, rat and guinea pig erythrocytes. Both ACL and AGL also reacted with RBCs from sheep, goat and human ABO blood groups after neuraminidase treatment. ACL and AGL were inhibited by mannose/glucose and their derivatives. The most effective inhibitor was methyl-alpha-D-mannopyranoside. Acorus lectins were stable up to 55 degrees C, did not require metal ions for their activity and were also affected by high concentrations of denaturants like urea, thiourea and guanidine-HCl. These lectins showed potent mitogenic activity towards mouse splenocytes and human lymphocytes. Both ACL and AGL also significantly inhibited the growth of J774, a murine macrophage cancer cell-line and to lesser extent WEHI-279, a B-cell lymphoma.     

Kawasaki disease: a decade of experience from North India

Kawasaki disease (KD) has not been frequently reported from developing countries, especially from India. In this series from a tertiary level center in North India, we report on the clinical features and management of patients with KD seen between January 1994 to November 2004. KD was diagnosed on the basis of standard diagnostic criteria. Investigations included work-up for other causes of fever along with chest X-rays, electrocardiograms, and 2-D echocardiography. Thallium scintigraphy and coronary angiography were performed in 20 and 3 cases, respectively. Sixty-nine children (49 boys and 20 girls) fulfilled the diagnostic criteria. Mean age at diagnosis was 4.9 +/- 3.0 years (range 0.3-14 years) and as many as 23 cases (33.3%) were above 5 years of age. Clustering was seen during the winter months. Extreme irritability, out of proportion to the degree of fever, was a characteristic feature. Redness of the lips and tongue was common but rash was seen only in 43 cases and lymphadenopathy in 47 cases. Thrombocytosis was present in 52.2% of the patients. Sixty-four patients received intravenous immunoglobulin. Cardiac abnormalities included extrasystoles in 1, coronary artery dilatation in 5, valvular regurgitation in 3, and perfusion defects on thallium scintigraphy in 4. There was no mortality. KD appears to occur at an older age in Indian children as compared to reports from Japan. Irritability is a characteristic clinical finding. Cardiac abnormalities are frequent during the acute stage but regress gradually. The disease needs to be considered in the differential diagnosis of all children with persistent unexplained fever.