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Biomedical subjects

R Tandon

Publications and source records attributed to R Tandon.

At least 19 recordsLinked to original sources
PubMed2007

Increase in weight induced by muraglitazar, a dual PPARalpha/gamma agonist, in db/db mice: adipogenesis/or oedema?

BACKGROUND AND PURPOSE: Muraglitazar, a dual PPARalpha/gamma agonist, caused a robust increase in body weight in db/db mice. The purpose of the study was to see if this increase in weight was due to oedema and/or adipogenesis. EXPERIMENTAL APPROACH: The affinity of muraglitazar at PPARalpha/gamma receptors was characterized using transactivation assays. Pre-adipocyte differentiation, expression of genes for adipogenesis (aP2), fatty acid oxidation (ACO) and sodium reabsorption (ENaCgamma and Na+, K+-ATPase); haemodilution parameters and serum electrolytes were measured to delineate the role of muraglitazar in causing weight gain vis a vis rosiglitazone. KEY RESULTS: Treatment with muraglitazar (10 mg kg(-1)) for 14 days significantly reduced plasma glucose and triglycerides. Reduction in plasma glucose was significantly greater than after similar treatment with rosiglitazone (10 mg kg(-1)). A marked increase in weight was also observed with muraglitazar that was significantly greater than with rosiglitazone. Muraglitazar increased aP2 mRNA and caused adipocyte differentiation in 3T3-L1 cells similar to rosiglitazone. It also caused a marked increase in ACO mRNA in the liver of the treated mice. Expression of mRNA for ENaCgamma and Na+, K+-ATPase in kidneys was up-regulated after either treatment. Increased serum electrolytes and decreased RBC count, haemoglobin and haematocrit were observed with both muraglitazar and rosiglitazone. CONCLUSIONS AND IMPLICATIONS: Although muraglitazar has a better glucose lowering profile, it also has a greater potential for weight gain than rosiglitazone. In conclusion, muraglitazar causes both robust adipogenesis and oedema in a 14-day treatment of db/db mice as observed in humans.

3T3-L1 Cells↗
PubMed2006

Towards a muscarinic hypothesis of schizophrenia.

Although the neurotransmitter dopamine plays a prominent role in the pathogenesis and treatment of schizophrenia, the dopamine hypothesis of schizophrenia fails to explain all aspects of this disorder. It is increasingly evident that the pathology of schizophrenia also involves other neurotransmitter systems. Data from many streams of research including pre-clinical and clinical pharmacology, treatment studies, post-mortem studies and neuroimaging suggest an important role for the muscarinic cholinergic system in the pathophysiology of schizophrenia. This review will focus on evidence that supports the hypothesis that the muscarinic system is involved in the pathogenesis of schizophrenia and that muscarinic receptors may represent promising novel targets for the treatment of this disorder.

Animals↗
PubMed2006

HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties.

In addition to forming the selective filtration barrier for the renal glomerulus, podocytes maintain glomerular capillary architecture by opposing distending hemodynamic forces. To understand the relationship of cytoskeletal properties and the mechanical characteristics of podocytes, we studied filamin expression and distribution and measured cell membrane deformability in conditionally immortalized wild-type (WT) mouse podocytes, and in podocytes derived from a mouse model of HIV-associated nephropathy (HIVAN). In the WT cells, filamin and F-actin were localized at the periphery and in prominent stress fibers. In the HIVAN cells, filamin expression was reduced, and stress fibers were sparse. In a microaspiration assay, HIVAN cells ruptured under minimal negative pressure. Atomic force microscopy demonstrated that the WT cells had a stiffness of 17 kPa, whereas the value for the HIVAN cells was 4 kPa. These results demonstrate that the mechanical properties of WT and HIVAN podocytes are markedly different in a manner that is consistent with differences in the composition and arrangement of their cytoskeletons. The mechanical properties of the WT podocytes suggest that these cells can better maintain capillary integrity than the HIVAN podocytes and implicate pathological assembly of the cytoskeleton as a mechanism of HIVAN.

Actinin↗
PubMed2006

Risk factors for postoperative cylindrical prediction error after laser in situ keratomileusis for myopia and myopic astigmatism.

PURPOSE: To study the risk factors for the occurrence of cylindrical prediction error (PE) after laser in situkeratomileusis (LASIK) for myopia and myopic astigmatism. METHODS: The study was a nested case-control study. Five hundred eyes of 252 consecutive patients who underwent LASIK for myopia and myopic astigmatism on the Chiron Technolas 217C laser and completed 6 months of follow-up. There were 435 controls and 65 cases based on the postoperative refractive cylindrical PE. The probable risk factors studied included preoperative sphere and cylinder, keratometry, pachymetry, suction ring used, flap thickness, hinge centeration, optic zone, ablation depth, and intraoperative complications. RESULTS: By univariate analysis, the cylindrical PE was found to be associated with preoperative spherical equivalent higher than -6 D (chi(2)=10.83; P=0.001), preoperative sphere higher than -6 D (chi(2)=6.15, P=0.013), preoperative cylinder more than -0.75 D (chi(2)=6.61; P-value=0.010), and an optic zone less than 5.5 mm (chi(2)=19.3; P=0.001). Risk factors for postoperative astigmatism by stepwise multivariate logistic regression analysis were an optic zone of less than 5.5 mm with an odds ratio (OR) of 2.81 (95% confidence interval (CI)=1.62-4.86) and preoperative cylinder more than -0.75 D with an OR of 1.60 (95% CI=0.92-2.77). CONCLUSION: Postoperative astigmatism (as indicated by the cylindrical PE) is more likely to occur with an optic zone of less than 5.5 mm and a higher preoperative cylindrical error.

Adult↗
PubMed2006

Phacoemulsification with nondominant hand.

PURPOSE: Evaluation of on axis phacoemulsification surgery through temporal incision using nondominant hand with surgeon sitting at the head end, inpatients with against-the-rule astigmatism. METHODS: Eighty eyes of 80 patients who underwent phacoemulsification through a temporal clear corneal tunnel for age-related cataract and against-the-rule astigmatism were enrolled and divided into four equal groups. In Group 1A, the surgeon was sitting at the head end for the left eye performing surgery with the left hand (nondominant hand). In group 1B, the surgeon was seated at the temporal side and surgery was performed in the left eye with dominant right hand. In group 2A, the surgeon was sitting at the head end for the right eye and performed surgery holding the phacoemulsification hand piece in his right hand. In group 2B, the surgeon sat on the temporal side of the right eye and performed phacoemulsification with his right hand. The patients were followed up on day 7, 1 month, and 3 months. Parameters evaluated included average phaco power, effective phaco time, uncorrected and best-corrected visual acuity, keratometry, intraocular pressure, surgically induced astigmatism, pachymetry, and endothelial cell counts. RESULTS: The phaco time and phaco power among the four groups were comparable (phaco time: P=0.368; phaco power: P=0.294). The four groups were also comparable on parameters like surgically induced astigmatism (P=0.674), change in postoperative keratometric astigmatism (P=0.584), endothelial cell loss (0.921), change in ultrasonic pachymetry (P=0.476), and intraocular pressure (P=0.942). No intraoperative or postoperative complications were observed in any of the groups. The mean uncorrected visual acuity at 3 months in group 1 was 0.723+/-0.21; in group 2 it was 0.756+/-0.21; in group 3 it was 0.748+/-0.22, and in group 4 it was 0.732+/-0.23. The best-corrected visual acuity was 0.96+/-0.10, 0.97+/-0.11, 0.95+/-0.13, and 0.96+/-0.10 in the four groups at 3 months. CONCLUSION: Phacoemulsification surgery can be successfully performed with nondominant hand with a good surgical outcome. The technique gives an alternative approach where surgeon does not have to shift the position to perform on-axis phacoemulsification.

Aged↗
PubMed2006

Risk factors for perforation in microbial corneal ulcers in north India.

AIM: To identify predisposing factors leading to corneal perforation in patients with microbial keratitis. METHOD: Two groups of 60 patients each, with perforated corneal ulcers and healed/healing corneal ulcers, respectively, were recruited in a case-control study conducted in northern India. The cases and controls were matched by age and time of presentation. A standardised proforma was used to identify potential predisposing factors for demographic, social, medical, ocular, and treatment history. All participants underwent a detailed ocular examination. Corneal scrapings were performed where relevant. RESULTS: The characteristics associated with corneal perforation in microbial keratitis were outdoor occupation (p = 0.005), illiteracy (p = 0.02), excessive alcohol use (p = 0.03), history of "something falling into eye" (p = 0.003), trauma with vegetable matter (p = 0.008), vision less than counting fingers at referral (p<0.001), central location of ulcer (p<0.001), lack of corneal vascularisation (p<0.001), delay in starting initial treatment (p<0.001), failure to start fortified antibiotics (p<0.001), and monotherapy with fluoroquinolones (p = 0.002). The lack of corneal vascularisation (OR 6.4, 95% CI 4.2 to 13.5), delay in starting initial treatment (OR 35.6, 95% CI 6.9 to 68.2), and failure to start fortified antibiotics (OR 19.9, 95% CI 2.7 to 64.7) retained significance on a logistic regression model. CONCLUSIONS: This study characterises microbial keratitis cases at increased risk of corneal perforation and reinforces the need for standardised referral and treatment protocols for patients with corneal ulcer on their first contact at primary care level in the developing world.

Adult↗
PubMed2006

Detection of feline leukemia virus RNA in saliva from naturally infected cats and correlation of PCR results with those of current diagnostic methods.

A novel diagnostic test for feline leukemia virus (FeLV) RNA in saliva from naturally infected cats is described in this study. We evaluated different diagnostic tests and compared them with the widely used enzyme-linked immunosorbent assay (ELISA) for the detection of p27 in the diagnosis of FeLV. Blood samples from 445 cats were tested for the presence of provirus by real-time PCR and plasma and saliva specimens from those cats were tested for the presence of viral RNA by real-time reverse transcription (RT)-PCR and for the presence of p27 by ELISA. In comparison to conventional ELISA, the diagnostic sensitivity and specificity of the detection of salivary FeLV RNA by real-time RT-PCR were found to be 98.1 and 99.2%, respectively. Detection of viral RNA in saliva had a positive predictive value of 94.6% and a negative predictive value of 99.7%. The kappa value was 0.96, demonstrating an almost perfect agreement between both tests. Furthermore, we confirmed previous results showing that a number of cats which tested negative for the presence of p27 in plasma were in fact positive for the presence of DNA provirus in blood specimens (5.4%). However, 96.4% of these latently infected cats did not shed viral RNA in saliva; therefore, we assume that these cats are of relatively low clinical importance at the time of testing. This study shows considerable diagnostic value of the detection of saliva FeLV RNA in naturally infected cats. This new diagnostic method has advantages over the conventional ELISA, such as less invasive sample collection and no requirement for trained personnel.

Animals↗
PubMed2005

Shedding of feline leukemia virus RNA in saliva is a consistent feature in viremic cats.

The purpose of this investigation was to characterize the shedding pattern of feline leukemia virus (FeLV) RNA in saliva, and to correlate it with the proviral load in whole blood, viral load in plasma, levels of p27 in saliva and plasma, the isolation of infectious FeLV from saliva, and the titers of FeLV-specific antibodies of the IgG and IgA isotypes. We evaluated 24 experimentally FeLV-infected cats for these parameters using real-time RT-PCR and PCR, cell culture assay and sandwich ELISA. We observed that shedding of viral RNA in saliva was a consistent feature in viremic cats. Latently FeLV-infected cats, displaying a very low proviral load, did not shed infectious virus in saliva, but occasionally shed viral RNA. Consequently, salivary shedding of FeLV RNA may not necessarily indicate a transmission potential for susceptible cats. This study also confirmed previous results from our laboratory, showing that a negative result for p27 in plasma, or for viral RNA in plasma or saliva does not exclude FeLV infection, considering that blood cells from those cats contained provirus. We also showed that FeLV RNA and DNA were stable for more than 64 days in saliva samples stored at room temperature. We conclude that the detection of FeLV RNA in saliva may be a useful indicator of viremia, and that the detection of salivary viral RNA by RT-PCR could become a reliable tool for the diagnosis of FeLV infection, which is facilitated by the low invasive method of collection of the samples.

Animals↗
PubMed2005

Corneal topographic response to intraocular pressure reduction in patients with vernal keratoconjunctivitis and steroid-induced glaucoma.

PURPOSE: To study the corneal topographic response to IOP reduction in vernal keratoconjunctivitis (VKC) with steroid-induced glaucoma. METHODS: A total of 42 eyes of 21 patients with VKC and steroid-induced glaucoma (Group I) and 66 eyes of 33 patients with VKC without glaucoma (Group II) underwent an evaluation by Orbscan topography. In eyes with glaucoma, the IOP was controlled medically and the corneal topography was repeated at 3 months to evaluate effect on corneal parameters. RESULTS: The mean baseline IOP was 36.40+/-13.08 mmHg in Group I, 14.67+/-4.62 mmHg in Group II (P<0.0001). The IOP after treatment at 3 months follow-up was 15.00+/-5.41 mmHg in Group I (P<0.0001). In Group I, the mean maximum Sim K decreased from 44.86+/-3.21 D to 43.87+/-2.62 D (P=0.031) and mean posterior corneal elevation decreased from 64.9+/-22.36 microm to 35.7+/-28.91 microm at 3 months after reduction of IOP (P=0.001). There was a significant positive correlation between the reduction in the IOP and the decrease in the posterior corneal elevation (r=0.664, P=0.001). CONCLUSION: Eyes with VKC with and without glaucoma have similar corneal topography. Increased IOP associated with steroid-induced glaucoma and VKC may contribute to an increase in the corneal curvature and posterior corneal elevation. These changes may be reversed by a reduction in the IOP with medical therapy.

Administration, Topical↗
PubMed2005

Effect of moxidectin selection on the genetic variation within Cylicocyclus nassatus based on amplified fragment length polymorphism (AFLP).

Cyathostomins are among the most important intestinal nematodes of horses, yet, the literature on the molecular genetics of these worms is scarce. In this study, the technique of amplified fragment length polymorphism (AFLP) was applied to study the genetic diversity as well as to determine the effect of moxidectin selection on the population genetic diversity for Cylicocyclus nassatus, one of the most common cyathostomin species. Genomic DNAs from 30 individual male worms were used from each of two populations: an avermectin-milbemycin (AM)-naive population (Population-S) and a population derived from Population-S following 21 treatments with moxidectin (Population-Mox). Three selective primer pairs were used for each worm, yielding a total of 229 AFLP markers. Calculation of average pair wise Jaccard indices revealed a high degree of genetic variation within both populations using all three primer combinations. In addition, selection by moxidectin during a 3-year period caused a significant decrease in the level of genetic diversity as evidenced by analysis of AFLP markers for two primer combinations but not for the third. A dendrogram of relationships among individuals based on AFLP markers did not show a clear classification of individuals in separate groups. It was concluded that a high degree of genetic intrapopulation variation exists in C. nassatus and that moxidectin selection has a significant effect on the genetic composition of C. nassatus.

Animals↗
PubMed2005

Outcome of penetrating keratoplasty in patients with bilateral corneal blindness.

PURPOSE: To evaluate the outcome of penetrating keratoplasty in patients with bilateral corneal blindness. METHODS: Bilaterally blind patients who had undergone optical penetrating keratoplasty (PK) were evaluated on optical and refractive parameters and presence of complications if any. The results at 3 months, 6 months, and 1 year were compared with age-matched and indication-matched unilaterally blind controls. RESULTS: The most common indication for surgery in both the groups was the presence of a corneoiridic scar. Best corrected visual acuity of > or =6/18 was seen in five (16.66%) patients in the study group and in 11 (36.66%) patients in the control group (P = 0.14). In all, 15 (50%) grafts in the study group and six (20%) in the control group failed (P = 0.03). The most common cause of failure was graft infection (40%) in the study group and post-PK glaucoma (20%) in the control group. The percentage of graft rejection as a cause of graft failure was the same in both the groups. A composite socioeconomic status scale based on family literacy and income suggested that 70% of the cases in the study group and 30% in the control group belonged to the low socioeconomic group (P = 0.004). CONCLUSION: The outcome of optical penetrating keratoplasty in patients with bilaterally blinding corneal disease is poorer than those who are unilaterally blind. Low socioeconomic status may be a contributing factor for the poor outcome.

Adult↗
PubMed2005

Imaging of osteo-odonto-keratoprosthesis by electron beam tomography.

AIM: To describe the experience of using electron beam tomography (EBT) in imaging of osteo-odonto-keratoprosthesis (OOKP) to identify early bone and dentine loss which may threaten the viability of the eye. METHODS: Seven patients with an OOKP in one eye underwent EBT. The OOKP lamina dimensions were measured on EBT and compared to the manual measurements at the time of surgery. RESULTS: There was a high degree of resolution of the OOKP lamina noted with EBT. In particular, it identified three patients with a marked degree of thinning of the lamina edges. Two of these patients had OOKP that were allografts. The mean time from surgery to examination was 3.6 years (range 1.2-5 years) while the mean age of the patients was 56 years (range 31-79 years). CONCLUSIONS: It is important to monitor regularly the dimensions and stability of the OOKP lamina as it will help detect cases that are at risk of extrusion of the optical cylinder and consequent endophthalmitis. Prophylactic measures can then be taken to prevent such serious complications from occurring. In this series, the authors found EBT to have excellent resolution and speed and they would support regular scanning of the OOKP lamina in all patients.

Adult↗
PubMed2005

Primary amyloidosis presenting with predominant lymphnodal masses.

A 50 year young farmer presented with clinical features of bilateral carpal tunnel syndrome and generalized lymphadenopathy including paratracheal and retroperitoneal lymphodes. The histological diagnosis confirmed primary amyloidosis of lymphnodes. Presentation of primary amyloidosis as lymphnodal mass with deposition of amyloid in carpal tunnel is extremely rare and can only be diagnosed by histochemistry. The clinical response to drugs is variable and needs surgical intervention for decompressive therapy which can improve the symptoms of carpal tunnel syndrome.

Amyloidosis↗
PubMed2004

Predicting the rate of cognitive decline in aging and early Alzheimer disease.

OBJECTIVES: To determine prognostic factors affecting the course of Alzheimer disease (AD) and to determine the role of region-specific brain volumes as predictors of cognitive decline. METHODS: Longitudinal data from 166 normal elderly individuals and 59 early AD patients were analyzed. Brain volumes were extracted from MRI scans using semiautomated recursive segmentation methods. Prognostic factors were considered significant if they had a significant effect on the rate of cognitive decline. RESULTS: In multivariate analysis, higher Clinical Dementia Rating Scale (CDR) score at entry was a significant prognostic factor for an increased rate of cognitive decline. Significant prognostic factors within the baseline CDR = 0 group were base rate of progression and percent total high signal intensity (HSI), percent ventricular, and percent CSF volumes. Base rate of progression, family history, and percent ventricular volume were significant prognostic factors within the CDR = 0.5 group and APOE had a marginally significant effect on the rate of cognitive decline in the CDR = 1 group. CONCLUSIONS: Percent total HSI, ventricular, and total CSF volume measures can independently predict the rate of cognitive decline and improve the predictive power of statistical models that use only clinical data. Brain volumetric measures from MRI can be used to estimate the rate of cognitive decline even among normal elderly individuals and thus may aid in the prediction of time of onset of disease.

Age of Onset↗
PubMed2004

Evaluation of a larval development assay (DrenchRite) for the detection of anthelmintic resistance in cyathostomin nematodes of horses.

A larval development assay (LDA, DrenchRite) was evaluated to determine the effectiveness of this method in detecting anthelmintic resistance in cyathostomin nematodes of horses. A total of 15 horse farms from Georgia and South Carolina (USA) and Population S ponies from the University of Kentucky (USA) were included in this study. Nematode eggs were extracted from pooled fecal samples and placed into the wells of a DrenchRite plate for testing against thiabendazole (TBZ), levamisole (LEV) and 2 ivermectin (IVM) analogs (IVM-1, IVM-2). After a 7-day incubation larvae in each well were counted and data were analyzed by logistic regression. Resistance status of each farm for different drugs was determined in a separate study using a fecal egg count reduction test. LDA were performed on the 15 farms once, however, the Population S cyathostomins were assayed on 3 separate occasions to estimate the consistency of results between assays. Mean TBZ LC50 for oxibendazole resistant, suspected resistant and sensitive farms were 0.2015, 0.1625, and 0.1355 microM, respectively. For LEV, mean LC50 for PYR resistant, suspected resistant and sensitive farms were 1.590, 1.8018 and 1.4219 microM, respectively. All 15 farms had worms susceptible to IVM; mean LC50 for IVM-1 and for IVM-2 were 7.5727 and 87.9718 nM, respectively. A linear mixed model was fitted to the data to determine the relationship between LC50 and LC95 and resistance status for each farm. No meaningful relations were found. Consistency of assays varied between drugs, being best for TBZ and worst for LEV and IVM-1. All farms in this study had benzimidazole-resistant nematodes; therefore usefulness of DrenchRite for discriminating susceptibility versus resistance to this drug class could not be accurately assessed. Moreover, since all farms tested were sensitive to IVM and resistance to this drug class has not yet been reported in cyathostomins, it is not possible to assess accurately the usefulness of DrenchRite LDA for detecting IVM resistance at this time. Assay results for LEV suggest that LEV in a LDA does not yield data that is useful in estimating PYR efficacy in vivo. Based on results for PYR/LEV, the current high prevalence of benzimidazole resistance, no known cases of IVM resistance, and the sometimes extreme variation in results seen in many of the assays, DrenchRite LDA cannot be considered a useful tool for the diagnosis of resistance in cyathostomins of horses at present.

Animals↗