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Sandeep Grover

Publications and source records attributed to Sandeep Grover.

16 recordsLinked to original sources
PubMed2025

Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.

IMPORTANCE: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD. OBJECTIVE: To identify genetic risk loci and cardiovascular risk factors with AS-specific associations. DESIGN, SETTING, AND PARTICIPANTS: This was a genomewide association study (GWAS) of AS adjusted for CAD with participants from the European Consortium for the Genetics of Aortic Stenosis (EGAS) (recruited 2000-2020), UK Biobank (recruited 2006-2010), Estonian Biobank (recruited 1997-2019), and FinnGen (recruited 1964-2019). EGAS participants were collected from 7 sites across Europe. All participants were of European ancestry, and information on comorbid CAD was available for all participants. Follow-up analyses with GWAS data on cardiovascular traits and tissue transcriptome data were also performed. Data were analyzed from October 2022 to July 2023. EXPOSURES: Genetic variants. MAIN OUTCOMES AND MEASURES: Cardiovascular traits associated with AS adjusted for CAD. Replication was performed in 2 independent AS GWAS cohorts. RESULTS: A total of 18 792 participants with AS and 434 249 control participants were included in this GWAS adjusted for CAD. The analysis found 17 AS risk loci, including 5 loci with novel and independently replicated associations (RNF114A, AFAP1, PDGFRA, ADAMTS7, HAO1). Of all 17 associated loci, 11 were associated with risk specifically for AS and were not associated with CAD (ALPL, PALMD, PRRX1, RNF144A, MECOM, AFAP1, PDGFRA, IL6, TPCN2, NLRP6, HAO1). Concordantly, this study revealed only a moderate genetic correlation of 0.15 (SE, 0.05) between AS and CAD (P = 1.60 × 10-3). Mendelian randomization revealed that serum phosphate was an AS-specific risk factor that was absent in CAD (AS: odds ratio [OR], 1.20; 95% CI, 1.11-1.31; P = 1.27 × 10-5; CAD: OR, 0.97; 95% CI 0.94-1.00; P = .04). Mendelian randomization also found that blood pressure, body mass index, and cholesterol metabolism had substantially lesser associations with AS compared with CAD. Pathway and transcriptome enrichment analyses revealed biological processes and tissues relevant for AS development. CONCLUSIONS AND RELEVANCE: This GWAS adjusted for CAD found a distinct genetic risk profile for AS at the single-marker and polygenic level. These findings provide new targets for future AS research.

Humans↗
PubMed2024

Effect of antiepileptic drug monotherapy on endogenous sex hormonal profile in men and women with epilepsy.

OBJECTIVE: To assess the alterations of endogenous sex hormone profiles in patients with epilepsy (PWE) on different antiepileptic drug (AED) monotherapies compared to healthy controls and drug naïve PWE (DNPWE). METHODS: Four databases MEDLINE, EMBASE, SCOPUS, and CENTRAL were searched for analytical observational/intervention studies on the assessment of endogenous sex hormones in PWE compared to healthy controls and DNPWE. Two researchers reviewed the title/abstract, and full-text articles for the selection of the studies independently. Extracted data included information on study details, participant demographics, interventions, method of assessment and study results. The study outcomes were used to calculate the standard mean differences (SMD) and 95% confidence interval (CI) as effect size for assessing differences in the endogenous sex hormone levels between the treatment group and control/DNPWE. RESULTS: Among 5888 publications retrieved, 33 studies were included. Enzyme-inducing AEDs (EIAEDs) such as phenytoin (men: SMD = 1.36; 95%CI = 1.06,1.66) and carbamazepine (men: SMD = 0.71; 95%CI = 0.39, 1.04 and women: SMD = 0.54; 95%CI = 0.25, 0.83) and weak-EIAED oxcarbazepine (men: SMD = 0.62; 95%CI = 0.26,0.99) increased the SHBG levels in PWE compared to control. The same trend was observed when comparing it to DNPWE. No significant changes in SHBG were observed for non-EIAEDs valproic acid, lamotrigine and levetiracetam in men. Lamotrigine significantly reduced SHBG in women (SMD = -0.50; 95%CI = -0.85, -0.16) compared to controls. Testosterone (T) levels were significantly reduced for both carbamazepine (SMD = -0.39; 95%CI = -0.67, -0.11) and valproic acid (SMD = -0.48; 95%CI = -0.74, -0.21) treated men compared to control. SIGNIFICANCE: Our findings emphasize the importance of screening the endogenous sex hormonal profile in PWE on AED monotherapies to evaluate the associated endocrine-related perturbations which may impact reproductive functions.

Humans↗
PubMed2006

Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa.

PURPOSE: To determine if topical dorzolamide, as observed with the use of systemic acetazolamide and methazolamide, would be effective in treating cystoid macular edema (CME) in patients with retinitis pigmentosa (RP). DESIGN: Prospective, nonrandomized clinical trial. METHODS: setting: Institutional. patients: Fifteen patients with CME and RP. intervention: A baseline visual acuity and optical coherence tomography (OCT) measurements were obtained in all patients. Each one of them was then treated with topical dorzolamide, three times a day, for at least four weeks in both eyes. main outcome measures: Significant decrease in "foveal thickness" (more than 16%) and "foveal zone thickness" (more than 11%), as measured by OCT. RESULTS: Thirteen (87%) of 15 patients showed a significant decrease in retinal thickness in at least one eye after use of topical dorzolamide for at least four weeks. Five patients (33%) demonstrated improvement in both eyes. All patients, except one, who responded showed the effect within four weeks, but were monitored for a period of two to nine months (average 4.5 months). Four patients (31%) who showed an initial improvement in macular edema showed worsening with continued treatment. CONCLUSIONS: The present study documents the potential efficacy of topical dorzolamide for treating CME in patients with RP. We observed that some patients may show a "rebound phenomenon" with continued use of the medication; hence, there is a need for careful follow-up in patients being treated.

Administration, Topical↗
PubMed2006

Shared obsessive-compulsive disorder.

BACKGROUND: Shared psychotic disorder (folie à deux) is an uncommon entity reported mainly in the context of delusions. Obsessions and compulsions occur very rarely as shared psychopathology. MATERIAL AND METHODS: We present two sisters who manifested shared obsessive-compulsive disorder. RESULTS: Both sisters were managed in keeping with their shared obsessive-compulsive disorder leading onto a similar pattern of response. CONCLUSIONS: Shared obsessions could represent the continuum concept of obsessions and delusions, and their relationship needs to be evaluated in greater detail.

Adult↗
PubMed2006

Psychotropics in pregnancy: weighing the risks.

With increase in the use of newer psychotropics, there is a growing concern in relation to the teratogenicity. Unfortunately, it is not possible to carry out prospective studies in pregnant women and as a result physicians caring for such patients have to rely on case reports, case series, and retrospective studies. Available evidence shows that the safety of psychotropics in pregnancy is still unresolved and the decision to prescribe psychotropics in pregnancy should be taken in the light of severity of mental disease, and drugs should be prescribed only when the potential risk to the foetus from exposure is outweighed by the risk of untreated maternal disorder. In this review we discussed the current evidence of the teratogenic risks with psychotropic drugs commonly used to treat psychiatric disorders and also focused on decision making in such patients.

Abnormalities, Drug-Induced↗
PubMed2005

Abnormal distribution of red/green cone opsins in a patient with an autosomal dominant cone dystrophy.

PURPOSE: To define the distribution of the red/green and blue opsins in cones from donor eyes from an affected member of a clinically well-characterized family with an autosomal dominant form of cone dystrophy. METHODS: Tissue was fixed and processed for immunohistochemistry. Cryosections were studied by indirect immunofluorescence, using well-characterized antibodies to cone cytoplasm, rhodopsin, and cone opsins. The cone-associated matrix was also labeled with the lectin PNA. The affected donor eyes were compared to a postmortem matched normal eye. RESULTS: Electroretinogram (ERG) testing three years prior to the affected member's death showed normal rod function, while the cone b-wave amplitude was reduced 40% below the lower limit of normal. Fundus exam showed only isolated drusen within the macula. Either a normal-appearing or only nonspecific macular findings were noted in the other affected family members who were examined. Immunofluorescence studies showed that blue cone opsin was restricted to the outer segments of blue cones in the affected retina. Red/green opsins were distributed along the entire plasma membrane of these cone types, from the tip of the outer segment to the synaptic base. Cone-associated matrix displayed a heterogeneous distribution. These patterns were observed both in the macula and in the periphery of the affected retina. Cone pedicles appeared larger than normal. In contrast, rhodopsin staining appeared normal. CONCLUSIONS: The immunocytochemical data obtained suggest that the clinical manifestation of this dystrophy is associated with an abnormal distribution of cone red/green opsins. Additionally, changes in the cone pedicles could have contributed to the abnormal cone ERG in this patient.

Aged↗
PubMed2004

A novel IMPDH1 mutation (Arg231Pro) in a family with a severe form of autosomal dominant retinitis pigmentosa.

PURPOSE: To define ophthalmic findings in a family with autosomal dominant retinitis pigmentosa and a novel IMPDH1 gene mutation. DESIGN: Genetic and observational family study. PARTICIPANTS: Sixteen affected members of a family with autosomal dominant retinitis pigmentosa. METHODS: Ophthalmic examination, including best-corrected visual acuity (VA), slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, Goldmann kinetic perimetry, and electroretinography were performed. Deoxyribonucleic acid single-strand conformation polymorphism (SSCP) analysis was done. Abnormal polymerase chain reaction products identified by SSCP analysis were sequenced bidirectionally. RESULTS: All affected patients had the onset of night blindness within the first decade of life. Ocular findings were characterized by diffuse retinal pigmentary degenerative changes, marked restriction of peripheral visual fields, severe loss of VA, nondetectable electroretinography amplitudes, and a high frequency of posterior subcapsular lens opacities. Affected members were observed to harbor a novel IMPDH1 gene mutation. CONCLUSION: A novel IMPDH1 gene mutation (Arg231Pro) was associated with a severe form of autosomal dominant retinitis pigmentosa. Families affected with a severe form of this genetic subtype should be investigated for a mutation in the IMPDH1 gene.

Adolescent↗
PubMed2004

Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation.

PURPOSE: Psychophysical and electroretinographic (ERG) studies indicate that patients with Stargardt disease exhibit abnormally slow rod dark adaptation after illumination that bleaches a substantial fraction of rhodopsin. However, relatively little information is available concerning rod recovery in this disease after weaker adapting (i.e., conditioning) light. With the use of a paired-flash ERG method, properties of the derived rod response to a low-bleach (<1%) but rod-saturating conditioning flash were investigated in seven normal subjects and in five Stargardt patients with identified sequence variations in the ABCA4 gene. METHODS: In the first of two experiments, the interval between a fixed conditioning flash (67 or 670 scotopic cd s m(-2)) and a bright probe flash of fixed strength was varied to determine the falling-phase kinetics of the derived rod response to the conditioning flash. In the second, the instantaneous amplitude-intensity function for the rod response at an intermediate stage of recovery from the conditioning flash was determined by presenting a test flash of various strengths at a fixed time after the conditioning flash, and a probe flash at 200 ms after the test flash. RESULTS: The maximum peak amplitude of the dark-adapted, rod-mediated a-wave determined in Stargardt patients (211 +/- 87 microV) was on average lower than that determined in normal subjects (325 +/- 91 microV; P = 0.06). The derived rod response to the 670 scotopic cd s m(-2) conditioning flash determined in normal subjects and Stargardt patients exhibited a biphasic recovery, and the kinetics of the early stage of this recovery were similar in the two subject groups. For both normal subjects and patients, normalized amplitude-intensity functions describing the dark-adapted derived rod response exhibited half-saturation at approximately 1.5 log scotopic troland second. In both groups, the normalized amplitude-intensity function determined at approximately 2 seconds after the 67 scotopic cd s m(-2) conditioning flash and at approximately 9 seconds after the 670 scotopic cd s m(-2) conditioning flash exhibited an average desensitization (i.e., an increase of test flash strength at half-saturation) of approximately 0.5 to 0.6 log unit relative to that determined under dark-adapted conditions. CONCLUSIONS: The results indicate that, despite a reduction in the average dark-adapted maximum a-wave amplitude in the Stargardt/ABCA4 patients, the early-stage recovery kinetics of the derived rod response to a low-bleaching conditioning flash as well as the lingering rod desensitization produced by such a flash are similar to those determined in normal subjects.

ATP-Binding Cassette Transporters↗
PubMed2003

Variability of full-field electroretinogram responses in subjects without diffuse photoreceptor cell disease.

PURPOSE: To evaluate test-retest variability in electroretinogram (ERG) responses in subjects without evidence of diffuse photoreceptor cell disease. DESIGN: Cohort study. PARTICIPANTS: Forty subjects without diffuse photoreceptor cell disease. METHODS: Serial ERGs were performed on 40 subjects (mean age at the time of first ERG: 54 years; range: 38-75 years) over a period of 2 to 6 years. These subjects participated in a study by a pharmaceutical company investigating the effects of certain drugs, used for gastrointestinal disorders, on retinal function. None of the subjects showed any evidence of progressive change in retinal function related to the medications. The ERG responses that were evaluated included amplitudes and implicit times for the dark-adapted rod-isolated and rod-dominant responses, light-adapted single flash response, and both light- and dark-adapted 31-Hz flicker responses. MAIN OUTCOME MEASURES: The data were analyzed by using analysis of variance methods, and a threshold criteria for significant change with 95% confidence was calculated for implicit times and an increase or decrease in ERG amplitudes. RESULTS: The threshold for significant change varied depending on the ERG stimulus. For the dark-adapted stimuli, a significant decrease in amplitude varied from 35% to 42% as compared with a variation of 53% to 73% for a significant increase. For the light-adapted stimuli, a significant decrease in amplitude varied by 52% as compared with a variation of 109% to 110% for a significant increase. The threshold for significant change for implicit times varied from 3.0 milliseconds to 8.7 milliseconds. CONCLUSIONS: The measured test-retest variability in ERG amplitudes and implicit times in subjects without diffuse photoreceptor cell disease underscores the importance of conducting similar comprehensive studies of variability in patients with acquired and hereditary retinal diseases. These data are also of value for monitoring disease progression and in future therapeutic trials.

Adult↗
PubMed2003

Necrotizing fasciitis caused by Erysipelothrix rhusiopathiae.

A woman with diabetes mellitus type 2 had a thigh infection that drained foul-smelling pus. Necrotizing fasciitis was diagnosed surgically and histopathologically, with Erysipelothrix rhusiopathiae being the predominant organism. A pet goldfish might have been the source.

Aged↗
PubMed2002

Comparison of intraocular light scatter in carriers of choroideremia and X-linked retinitis pigmentosa.

OBJECTIVE: To compare the extent of intraocular straylight in carriers of choroideremia (CHM) and X-linked recessive retinitis pigmentosa (XLRP) to clarify further the relationship between photoreceptor cell degeneration and intraocular light scatter in retinal diseases. DESIGN: Prospective case-control study. PARTICIPANTS: Six obligate carriers of CHM, 12 obligate carriers of XLRP, and 30 age-similar control subjects with normal vision. The controls had no posterior subcapsular (PSC) lens opacities, and the carriers had minimal or no PSC lens opacities, as assessed by slit-lamp biomicroscopy. MAIN OUTCOME MEASURES: Straylight levels were measured using a van den Berg Straylightmeter. Visual acuity and Goldmann visual field area using a II/4e target were assessed for both eyes of each carrier. Electroretinogram (ERG) data were available on four of six carriers of CHM and all carriers of XLRP. The extent of retinal pigment epithelial degenerative changes was evaluated by fundus examination. RESULTS: All six carriers of CHM had typical fundus abnormalities with normal visual fields. Five of the six carriers of CHM had age-normal levels of intraocular light scatter, and one showed minimally elevated intraocular light scatter. The 12 carriers of XLRP had a spectrum of fundus abnormalities and varying severity of functional impairment as derived from visual field areas and ERG amplitudes. Seven of the 12 carriers of XLRP showed an elevated level of intraocular light scatter in at least one eye. The degree of straylight elevation above the normal mean age value was correlated significantly with both visual field area and amplitude of the maximal-intensity, dark-adapted ERG b-wave. CONCLUSIONS: The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced ERG amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels. This finding supports the hypothesis that the increased levels of intraocular light scatter observed in some patients with hereditary retinal degenerations result from subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration.

Adult↗
PubMed2002

Atypical presentation of pattern dystrophy in two families with peripherin/RDS mutations.

PURPOSE: To describe the atypical clinical presentations of pattern dystrophy (PD) in two unrelated families with novel peripherin/RDS mutations. DESIGN: Observational case reports and family genetic study with review of peripherin/RDS mutations. PARTICIPANTS: Affected and unaffected members of two families with PD. METHODS: The probands of two families, as well as other family members, underwent an ophthalmologic assessment including slit-lamp biomicroscopy, applanation tonometry, and a dilated fundus examination. Goldmann visual fields and fluorescein angiography were performed, wherever appropriate. Blood samples were obtained from affected and selected unaffected members of the families for DNA analysis. RESULTS: The proband of family 1 had an acute onset of decreased vision and a yellowish lesion in both maculae that appeared inflammatory. However, resolution of the acute lesion ultimately resulted in fundus changes more typical for PD. Moreover, the proband's sister showed more classic-appearing PD lesions. Screening of the peripherin/RDS gene for sequence variations showed a 2-bp deletion, resulting in a translational frameshift at codon 290 in affected members of the family. The proband's father, who showed this sequence variation, did not have a macular lesion. The proband of family 2 was asymptomatic and showed a fundus phenotype similar to fundus flavimaculatus. The patient had normal visual acuity and did not demonstrate a "dark choroid" on fluorescein angiography. Molecular screening showed a Gln331stop variation in the peripherin/RDS gene. CONCLUSIONS: We describe two novel mutations in the peripherin/RDS gene in two unrelated families with PD. Clinicians should recognize the atypical features that may occur in patients with PD. A suspected diagnosis of PD may be confirmed by the identification of a mutation in the peripherin/RDS gene. In isolated family members with PD, a mutation in this gene may occur even in the absence of a clinically discernible macular lesion.

Adult↗