137 results on '"Reddy, SB"'
Search Results
52. Successful treatment of pyoderma vegetans with doxycycline.
- Author
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Reddy SB, Wang S, and Graham LV
- Abstract
Competing Interests: Dr Graham has grant support from 10.13039/100004319Pfizer and Argenx and is a consultant for Argenx and Clarivate. Author Reddy and Dr Wang have no conflicts of interest to declare.
- Published
- 2022
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53. Surgical evaluation in children <3 years of age with drug-resistant epilepsy: Patient characteristics, diagnostic utilization, and potential for treatment delays.
- Author
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Perry MS, Shandley S, Perelman M, Singh RK, Wong-Kisiel L, Sullivan J, Gonzalez-Giraldo E, Romanowski EF, McNamara NA, Marashly A, Ostendorf AP, Alexander A, Eschbach K, Bolton J, Wolf S, McGoldrick P, Depositario-Cabacar DF, Ciliberto MA, Gedela S, Sannagowdara K, Karia S, Shrey DW, Tatachar P, Nangia S, Grinspan Z, Reddy SB, Shital P, and Coryell J
- Subjects
- Child, Child, Preschool, Cross-Sectional Studies, Electroencephalography methods, Humans, Prospective Studies, Retrospective Studies, Seizures surgery, Time-to-Treatment, Treatment Outcome, Drug Resistant Epilepsy diagnosis, Drug Resistant Epilepsy surgery, Epilepsy diagnosis, Epilepsy surgery
- Abstract
Objective: Drug-resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group., Methods: The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross-sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young., Results: The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty-nine percent were seizure-free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001)., Significance: There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections., (© 2021 International League Against Epilepsy.)
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- 2022
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54. Venous thromboembolism in benign esophageal surgery patients: potential cost effectiveness of Caprini risk stratification.
- Author
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Perez SA, Reddy SB, Meister A, Pinjic E, Suzuki K, and Litle VR
- Subjects
- Aftercare, Anticoagulants therapeutic use, Cost-Benefit Analysis, Heparin, Low-Molecular-Weight adverse effects, Humans, Patient Discharge, Postoperative Complications chemically induced, Postoperative Complications prevention & control, Risk Assessment methods, Risk Factors, Venous Thromboembolism etiology, Venous Thromboembolism prevention & control
- Abstract
Background: The Caprini risk assessment model (RAM) stratifies surgical patients for prescription of post-discharge extended heparin prophylaxis to reduce post-operative venous thromboembolism (VTE) events. The average cost for treatment of a VTE event is $15,123. The 30-day post-operative VTE rate after benign esophageal procedures is < 0.8% per the Society of Thoracic Surgeons database. We hypothesized that the financial cost of selective extended prophylaxis in patients undergoing surgery for benign esophageal disease would exceed the cost of treating these rare events and therefore use of risk stratification for extended prophylaxis would not be beneficial., Methods: All patients undergoing operations for benign esophageal pathology from July 2014 to May 2019 were reviewed. Patients designated as moderate or high risk for VTE were prescribed a 10- or 30-day post-operative course of extended prophylaxis with low-molecular weight heparin (LMWH). VTE and adverse bleeding events were recorded for the 60-day post-operative period. The cost of LMWH was provided by the institution pharmacy., Results: Records from 154 patients were eligible for review. Caprini RAM was used for all patients with the following distribution of risk categories: low = 64.9% (100/154); moderate = 31.8% (49/154); and high = 3.2% (5/154). The average cost of extended prophylaxis at discharge for the moderate-risk group was $121.23, while the high-risk group was $446.46. There were no 60-day VTE or adverse bleeding events recorded., Conclusions: The majority of patients undergoing surgical therapy were at low risk of post-operative VTE event, with only 35% requiring extended VTE prophylaxis at time of discharge. When compared with the average cost of treatment for a VTE event, the cost of extended prophylaxis per patient in moderate or high-risk groups is substantially lower. In the era of cost-containment, risk stratification and extended prophylaxis may reduce healthcare costs and warrant future investigations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)
- Published
- 2022
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55. Underrepresented Populations in Pediatric Epilepsy Surgery.
- Author
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Armour EA, Yiu AJ, Shrey DW, and Reddy SB
- Subjects
- Child, Electroencephalography, Humans, Magnetic Resonance Imaging, Treatment Outcome, Epilepsies, Partial, Epilepsy epidemiology, Epilepsy surgery
- Abstract
As awareness of pediatric epilepsy increases, accompanied by advancements in technology and research, it is important to identify certain types of patients that are overlooked for surgical management of epilepsy. Identifying these populations will allow us to study and elucidate the factors contributing to the underutilization and/or delayed application of surgical interventions. Demographically, African-American and Hispanic patients, as well as patients of certain Asian ethnicities, have relatively lower rates of undergoing epilepsy surgery than non-Hispanic and white patients. Among patients with epilepsy, those with higher odds of seizure-freedom following surgery are more likely to be referred for surgical evaluation by their neurologists, with the most common diagnosis being lesional focal epilepsy. However, patients with multifocal or generalized epilepsy, genetic etiologies, or normal (non-lesional) brain magnetic resonance imaging (MRI) are less likely be to referred for evaluation for resective surgery. With an increasing number of high-quality imaging modalities to help localize the epileptogenic zone as well as new techniques for both curative and palliative epilepsy surgery, there are very few populations of patients and/or types of epilepsy that should be precluded from evaluation to determine the suitability of epilepsy surgery. Ultimately, a clearer understanding of the populations who are underrepresented among those considered for epilepsy surgery, coupled with further study of the underlying reasons for this trend, will lead to less disparity in access to this critical treatment among patients with epilepsy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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56. Publisher Correction to: Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth.
- Author
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Reddy SB, Nagy N, Rönnberg C, Chiodi F, Lugaajju A, Heuts F, Szekely L, Wahlgren M, and Persson KEM
- Published
- 2021
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57. Direct contact between Plasmodium falciparum and human B-cells in a novel co-culture increases parasite growth and affects B-cell growth.
- Author
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Reddy SB, Nagy N, Rönnberg C, Chiodi F, Lugaajju A, Heuts F, Szekely L, Wahlgren M, and Persson KEM
- Subjects
- B-Lymphocytes parasitology, Coculture Techniques, Humans, B-Lymphocytes metabolism, Malaria, Falciparum parasitology, Plasmodium falciparum growth & development
- Abstract
Background: Plasmodium falciparum parasites cause malaria and co-exist in humans together with B-cells for long periods of time. Immunity is only achieved after repeated exposure. There has been a lack of methods to mimic the in vivo co-occurrence, where cells and parasites can be grown together for many days, and it has been difficult with long time in vitro studies., Methods and Results: A new method for growing P. falciparum in 5% CO
2 with a specially formulated culture medium is described. This knowledge was used to establish the co-culture of live P. falciparum together with human B-cells in vitro for 10 days. The presence of B-cells clearly enhanced parasite growth, but less so when Transwell inserts were used (not allowing passage of cells or merozoites), showing that direct contact is advantageous. B-cells also proliferated more in presence of parasites. Symbiotic parasitic growth was verified using CESS cell-line and it showed similar results, indicating that B-cells are indeed the cells responsible for the effect. In malaria endemic areas, people often have increased levels of atypical memory B-cells in the blood, and in this assay it was demonstrated that when parasites were present there was an increase in the proportion of CD19 + CD20 + CD27 - FCRL4 + B-cells, and a contraction of classical memory B-cells. This effect was most clearly seen when direct contact between B-cells and parasites was allowed., Conclusions: These results demonstrate that P. falciparum and B-cells undoubtedly can affect each other when allowed to multiply together, which is valuable information for future vaccine studies.- Published
- 2021
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58. Type 2 diabetes is associated with failure of non-operative treatment for sternoclavicular joint infection.
- Author
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Reddy SB, Mizelle J, Sterbling HM, Lin B, Litle VR, and Suzuki K
- Abstract
Background: A standardized treatment algorithm for sternoclavicular joint infection management is lacking in the literature. While major risk factors for sternoclavicular joint infection, including immunosuppression, rheumatoid arthritis, type 2 diabetes, indwelling catheters, and intravenous drug use have been identified, clear association with treatment outcome has not been established. As our safety net hospital treats a patient population with high incidence of intravenous drug use, we sought to identify risk factors associated with failure of non-operative management of sternoclavicular joint infection., Methods: We conducted a retrospective cohort study, reviewing charts of patients diagnosed with sternoclavicular joint infection between January 2001 and December 2017 to collect demographic information as well as clinical risk factors and treatment patterns. A chi-square test was performed to determine any association between clinical variables and management, as well as relation to treatment outcome., Results: The study cohort consisted of 35 patients with diagnosis of sternoclavicular joint infection and complete follow-up. Intravenous drug use was prevalent, seen in 45.6% (16/35) of subjects, though there was no association with failure of non-operative management (P=0.50). Operative management was the initial treatment for 25.7% (9/35) of subjects and was associated with abscess on presentation (P=0.03). Failure of non-operative management was seen in 26.9% (7/26). Type 2 diabetes was associated with failed initial non-operative management, present in 42.9% (3/7) of patients (P=0.03) experiencing failure., Conclusions: This study constitutes the largest series of sternoclavicular joint infection with intravenous drug use. While intravenous drug use was not associated with failure of non-operative management, we observed that type 2 diabetes is associated with failure of non-operative management and could be considered in determining management of sternoclavicular joint infection patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1897). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)
- Published
- 2020
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59. Complete response to avelumab and IL-15 superagonist N-803 with Abraxane in Merkel cell carcinoma: a case study.
- Author
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Drusbosky L, Nangia C, Nguyen A, Szeto C, Newton Y, Spilman P, and Reddy SB
- Subjects
- Aged, Antibodies, Monoclonal, Humanized pharmacology, Humans, Interleukin-15 pharmacology, Male, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Merkel Cell drug therapy, Interleukin-15 therapeutic use
- Abstract
Merkel cell carcinoma (MCC) is a rare aggressive form of skin cancer originating in neuroendocrine cells. The antiprogrammed death ligand 1 (PD-L1) monoclonal antibody (mAb) avelumab has been approved for treatment of MCC, but options are limited, should it be ineffective as a monotherapy. Combined therapy with low/moderate dose nab-paclitaxel and an interleukin 15 (IL-15)-based therapeutic such as the IL-15 'superagonist' N-803 may increase response by activation of the immune system. The case of a 71-year-old man diagnosed with MCC who achieved and maintained a complete response (CR) by treatment with the anti-PD-L1 mAb avelumab in combination with IL-15 superagonist N-803 and nab-paclitaxel (Abraxane) is presented. Avelumab treatment alone resulted in a response in a para-aortic lesion, but not the other tumor masses. N-803 was added, followed by nab-paclitaxel; CT showed a decrease in the size of the abdominal mass at 1 month, near resolution at 3 months and CR at 5 months. Abraxane was discontinued after the first CR on CT, and the patient continues on avelumab/N-803 treatment and maintains a CR. Combination of avelumab with low/moderate-dose chemotherapy and an immune enhancer such as N-803 may offer a viable treatment option for MCC patients for whom avelumab therapy alone was not effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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60. Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization.
- Author
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Peddu V, Shean RC, Xie H, Shrestha L, Perchetti GA, Minot SS, Roychoudhury P, Huang ML, Nalla A, Reddy SB, Phung Q, Reinhardt A, Jerome KR, and Greninger AL
- Subjects
- Betacoronavirus classification, Betacoronavirus isolation & purification, COVID-19, Coronavirus Infections genetics, Coronavirus Infections virology, Enterovirus classification, Enterovirus genetics, Enterovirus isolation & purification, Humans, Nasopharynx virology, Pandemics, Phylogeny, Pneumonia, Viral genetics, Pneumonia, Viral virology, RNA, Viral chemistry, RNA, Viral metabolism, Real-Time Polymerase Chain Reaction, SARS-CoV-2, Sequence Analysis, RNA, Superinfection virology, Betacoronavirus genetics, Coronavirus Infections diagnosis, Metagenomics, Pneumonia, Viral diagnosis, Superinfection diagnosis
- Abstract
Background: More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence., Methods: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2., Results: Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms., Conclusion: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2020
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61. Capacity-Building in the Peer Workforce: A Systems-Level Approach.
- Author
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Reddy SB, Wolf J, and Brown LD
- Subjects
- Humans, Program Development, Capacity Building, Health Workforce, Mental Health Services organization & administration
- Published
- 2020
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62. Renal manifestations of dengue viral infection.
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Eswarappa M, Reddy SB, John MM, Suryadevara S, and Madhyashatha RP
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- Acute Kidney Injury physiopathology, Acute Kidney Injury virology, Adolescent, Adult, Aged, Aged, 80 and over, Comorbidity, Female, Hematuria virology, Humans, Incidence, India epidemiology, Length of Stay, Male, Middle Aged, Myocardial Ischemia epidemiology, Proteinuria virology, Recovery of Function, Retrospective Studies, Severity of Illness Index, Young Adult, Acute Kidney Injury epidemiology, Dengue complications, Diabetes Mellitus epidemiology, Hematuria epidemiology, Hypertension epidemiology, Proteinuria epidemiology
- Abstract
Dengue-related renal manifestations such as proteinuria, hematuria in the absence of thrombocytopenia, rhabdomyolysis, and acute kidney injury (AKI) are not uncommon. There is relatively sparse data on the renal manifestations of dengue viral infection (DVI). Hence, a retrospective study was conducted to investigate the incidence, characteristics, and clinical outcome of DVI with renal manifestations. A total of 2416 patients were admitted to our hospital with the diagnosis of dengue fever during the study period from 2012 to 2015. Data were collected from the electronic medical records and were analyzed retrospectively. The disease severity was classified according to the World Health Organization criteria. The renal manifestations were divided into AKI and non-AKI groups using AKI Network (AKIN) criteria. Proteinuria was defined as urinary protein >1+ (30 mg/dL) by dipstick test. A total of 218 patients were found to have proteinuria (9.56%). Most of the patients [135 (58.44%) with renal manifestations] were aged between 15 and 30 years. Comorbid conditions including diabetes mellitus, hypertension, and ischemic heart disease were seen in 10 (4.31%), 11 (4.76%), and six (2.59%) patients, respectively. Nephrotic-range proteinuria was seen in five patients (2.16%). AKI was seen in 82 patients (3.4%); 58 (70.73%) had AKIN-I, 19 (23.17%) had AKIN-II, and five patients (6.09%) had AKIN-III. Death occurred in 11 patients (39.28%) with AKI. The incidence of renal manifestations (proteinuria, hematuria, and AKI) is high at 9.59% among patients with dengue, and those with AKI had significant morbidity, mortality, longer hospital stay, and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase health-care burden that underscores the need for clinician's alertness to this highly morbid and potentially fatal complication for optimal prevention and management.
- Published
- 2019
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63. Ectopic Thyroid Tissue: Immunohistochemistry and Molecular Analysis.
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Lin DM, Javidiparsijani S, Vardouniotis A, Buckingham L, Reddy SB, and Gattuso P
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- Adult, Aged, Amino Acid Substitution, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Blood Proteins, Female, GTP Phosphohydrolases genetics, GTP Phosphohydrolases metabolism, Galectin 3 genetics, Galectin 3 metabolism, Galectins, Humans, Immunohistochemistry methods, Male, Membrane Proteins genetics, Membrane Proteins metabolism, Middle Aged, Mutation, Missense, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Retrospective Studies, Sensitivity and Specificity, Adenocarcinoma, Follicular genetics, Adenocarcinoma, Follicular metabolism, Adenocarcinoma, Follicular pathology, Thyroid Gland metabolism, Thyroid Gland pathology, Thyroid Neoplasms genetics, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology
- Abstract
Ectopic thyroid tissue is rare and controversial. Some experts consider it to always be metastatic thyroid carcinoma, whereas others consider it benign as long as it is restricted to few follicles without cytoarchitectural features of papillary thyroid carcinoma. Immunohistochemistry (IHC) and molecular studies have not yet been performed to further characterize this entity. We retrospectively searched our pathology files for all ectopic thyroid inclusions and reviewed clinicopathologic characteristics and concurrent thyroid pathologic findings. We identified 8 cases from 7 patients. Ectopic thyroid tissue was present in the following locations: neck soft tissue: 3, thymus: 2, neck lymph nodes: 2, perihilar soft tissue: 1. All patients had histologically benign thyroid specimens. BRAFV600E (VE1) IHC, HBME-1 IHC, galectin-3 IHC, BRAFV600E allele-specific polymerase chain reaction (PCR) and NRAS/KRAS pyrosequencing were performed. To assess the sensitivity and specificity of BRAFV600E IHC compared with PCR; we tested 13 cases of primary and metastatic papillary and follicular thyroid carcinomas. All the ectopic cases were HBME-1, galectin-3, BRAFV600E (IHC, PCR), and NRAS/KRAS mutation negative (specificity=100%). Compared with PCR, BRAF IHC had 89% sensitivity and 100% specificity. Lack of common carcinoma-associated mutations supports benign nature of this entity. BRAF, HBME-1, and galectin-3 IHC are accurate and helpful when not enough tissue is available for molecular studies. IHC and molecular studies are more helpful than morphology alone in identifying benign thyroid rests.
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- 2018
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64. Dengue virus NS2 and NS4: Minor proteins, mammoth roles.
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Gopala Reddy SB, Chin WX, and Shivananju NS
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- Amino Acid Sequence, Animals, Dengue genetics, Dengue Virus chemistry, Dengue Virus genetics, Humans, Protein Structure, Secondary, Viral Nonstructural Proteins chemistry, Viral Nonstructural Proteins genetics, Dengue metabolism, Dengue Virus metabolism, Viral Nonstructural Proteins metabolism
- Abstract
Despite the ever-increasing global incidence of dengue fever, there are no specific chemotherapy regimens for its treatment. Structural studies on dengue virus (DENV) proteins have revealed potential drug targets. Major DENV proteins such as the envelope protein and non-structural (NS) proteins 3 and 5 have been extensively investigated in antiviral studies, but with limited success in vitro. However, the minor NS proteins NS2 and NS4 have remained relatively underreported. Emerging evidence indicating their indispensable roles in virus propagation and host immunomodulation should encourage us to target these proteins for drug discovery. This review covers current knowledge on DENV NS2 and NS4 proteins from structural and functional perspectives and assesses their potential as targets for antiviral design. Antiviral targets in NS2A include surface-exposed transmembrane regions involved in pathogenesis, while those in NS2B include protease-binding sites in a conserved hydrophilic domain. Ideal drug targets in NS4A include helix α4 and the PEPEKQR sequence, which are essential for NS4A-2K cleavage and NS4A-NS4B association, respectively. In NS4B, the cytoplasmic loop connecting helices α5 and α7 is an attractive target for antiviral design owing to its role in dimerization and NS4B-NS3 interaction. Findings implicating NS2A, NS2B, and NS4A in membrane-modulation and viroporin-like activities indicate an opportunity to target these proteins by disrupting their association with membrane lipids. Despite the lack of 3D structural data, recent topological findings and progress in structure-prediction methods should be sufficient impetus for targeting NS2 and NS4 for drug design., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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65. Isoxazole-tethered diarylheptanoid analogs: Discovery of a new drug-like PAR2 antagonist.
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Bhuniya D, Bhosale S, Reddy SB, and Reddy SN
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- Calcium metabolism, Diarylheptanoids chemical synthesis, Diarylheptanoids chemistry, Diarylheptanoids pharmacokinetics, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, HEK293 Cells, Hep G2 Cells, Humans, Isoxazoles chemical synthesis, Isoxazoles chemistry, Isoxazoles pharmacokinetics, Microsomes, Liver metabolism, Stereoisomerism, Diarylheptanoids pharmacology, Isoxazoles pharmacology, Receptor, PAR-2 antagonists & inhibitors
- Abstract
A new class of isoxazole-tethered diarylheptanoids having characteristic 1,3-syn-diol and 1,3-anti-diol chemophoric moieties, e.g. 4a-d and 5a-c respectively, have been designed and synthesized starting from d-glucose following a stereo-conserved general synthetic strategy. The isoxazole heterocycle was installed using our recently elaborated methodology deploying Magtrieve™ as a selective oxidizing agent. Two of these new analogs 4a and 5a exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin-I. In a HEK293 cell-based intracellular calcium [Ca
2+ ]i release assay, 4a and 5a, when tested at 30 μM, inhibited the trypsin agonist induced protease-activated receptor-2 (PAR2) activity by 80% and 70% respectively. IC50 of 4a (SB70) has been determined as 6 μM which is in the same range of current benchmarks for PAR2 antagonists., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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66. Factors influencing the induction of high affinity antibodies to Plasmodium falciparum merozoite antigens and how affinity changes over time.
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Tijani MK, Reddy SB, Langer C, Beeson JG, Wahlgren M, Nwuba RI, and Persson KEM
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- Adaptive Immunity immunology, Adolescent, Adult, Child, Child, Preschool, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Longitudinal Studies, Malaria, Falciparum blood, Malaria, Falciparum parasitology, Nigeria, Plasmodium falciparum physiology, Surface Plasmon Resonance, Antibodies, Protozoan immunology, Antibody Affinity immunology, Antigens, Protozoan immunology, Malaria, Falciparum immunology, Merozoites immunology, Plasmodium falciparum immunology
- Abstract
Understanding the functional characteristics of naturally acquired antibodies against P. falciparum merozoite antigens is crucial for determining the protective functions of antibodies. Affinity (measured as k
d ) of naturally acquired antibodies against two key targets of acquired immunity, EBA175 and PfRh2, was determined using Surface Plasmon Resonance (SPR) in a longitudinal survey in Nigeria. A majority of the participants, 79% and 67%, maintained stable antibody affinities to EBA175 and PfRh2, respectively, over time. In about 10% of the individuals, there was a reciprocal interaction with a reduction over time in antibody affinity for PfRh2 and an increase for EBA175. In general, PfRh2 elicited antibodies with higher affinity compared to EBA175. Individuals with higher exposure to malaria produced antibodies with higher affinity to both antigens. Younger individuals (5-15 years) produced comparable or higher affinity antibodies than adults (>15 years) against EBA175, but not for PfRh2. Correlation between total IgG (ELISA) and affinity varied between individuals, but PfRh2 elicited antibodies with a higher correlation in a majority of the participants. There was also a correlation between antibody inhibition of erythrocyte invasion by merozoites and PfRh2 affinity. This work gives new insights into the generation and maintenance of antibody affinity over time.- Published
- 2018
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67. Emphysematous Pyelonephritis Case Series From South India.
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Eswarappa M, Suryadevara S, John MM, Kumar M, Reddy SB, and Suhail M
- Abstract
Introduction: Emphysematous pyelonephritis (EPN) is a rare, life-threatening necrotizing infection of the kidney. The mortality rate for EPN is as high as 25%. We conducted a retrospective study at MS Ramaiah Hospital between January 2011 and May 2016 to observe the clinical, biochemical, and microbiological patterns of EPN at our institute., Methods: The clinical and laboratory data, imaging findings, and microbiological patterns of 51 patients chosen for the study were recorded. The data were analyzed to identify the prognostic variables that could predict the morbidity and mortality of patients with EPN, and the focus of this study was to determine risk factors for and outcomes of patients who presented with EPN and who required hemodialysis. Primary endpoints were successful treatment and all-cause mortality. Secondary endpoints included need for hemodialysis and the need for a specific treatment., Results: There was an equal incidence among both sexes (median age: 59 years). Common symptoms were abdominal pain (94.11%), fever (83.2%), dysuria (74.5%), vomiting (72.54%), frequency of micturition (68.62%), oliguria, generalized weakness (66.67%), and breathlessness (66.67%); 98.03% (n = 50) of the patients had diabetes. The most common organism cultured was Escherichia coli (37.2%). Nineteen patients (37.2%) required dialysis; their mean age was 60.25 ± 11.74 years. Male sex, diabetes mellitus, shock, high serum creatinine at presentation, and uremic symptoms showed no statistically significant association. Indefinite hemodialysis was required by 12.5% of patients. The antibiotic-treated group had a 100% success rate, whereas the Double J (DJ) stenting group (Double J stent, Biorad, India) had 96.42% success rate., Conclusion: Early diagnosis and broad spectrum antibiotics, together with an appropriately timed intervention, resulted in decreased mortality. Pain in the abdomen and renal angle tenderness were the most common clinical finding. E coli was the most found organism, and early use of broad spectrum antibiotics decreased mortality.
- Published
- 2017
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68. Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma.
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Reddy SB, Possick JD, Kluger HM, Galan A, and Han D
- Subjects
- Adrenal Cortex Hormones therapeutic use, Antibodies, Monoclonal adverse effects, Autoimmunity, CTLA-4 Antigen immunology, Female, Humans, Immunotherapy adverse effects, Ipilimumab adverse effects, Lung pathology, Melanoma drug therapy, Middle Aged, Nivolumab, Programmed Cell Death 1 Receptor immunology, Sarcoidosis etiology, Sarcoidosis prevention & control, Skin pathology, Skin Neoplasms drug therapy, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug-Related Side Effects and Adverse Reactions diagnosis, Immunotherapy methods, Ipilimumab therapeutic use, Melanoma diagnosis, Sarcoidosis diagnosis, Skin Neoplasms diagnosis
- Abstract
Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.
- Published
- 2017
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69. A highly sensitive and specific combined clinical and sonographic score to diagnose appendicitis.
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Reddy SB, Kelleher M, Bokhari SAJ, Davis KA, and Schuster KM
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- Appendectomy, Appendicitis pathology, Appendicitis surgery, Diagnosis, Differential, Emergency Service, Hospital, Female, Humans, Male, Retrospective Studies, Sensitivity and Specificity, Young Adult, Appendicitis diagnostic imaging, Ultrasonography methods
- Abstract
Background: Computed tomography (CT) scanning reduces the negative appendectomy rate however it exposes the patient to ionizing radiation. Ultrasound (US) does not carry this risk but may be nondiagnostic. We hypothesized that a clinical-US scoring system would improve diagnostic accuracy., Methods: We conducted a retrospective review of all patients (age, >15 years) who presented through the emergency department with suspected appendicitis and underwent initial US. A US score was developed using odds ratios for appendicitis given appendiceal diameter, compressibility, hyperemia, free fluid, and focal or diffuse tenderness. The US score was then combined with the Alvarado score. Final diagnosis of appendicitis was assigned by pathology reports., Results: Three hundred patients who underwent US as initial imaging were identified. Thirty-two patients with evident nonappendiceal pathology on US were excluded. In 114 (38%), the appendix was not visualized and partially visualized in 36 (12%). Fifty-seven (21.3%) had an appendectomy with 1 (1.7%) negative. Six nonvisualized appendicies underwent appendectomy, with no negative cases. Sensitivity and specificity for the sonographic score were 86% and 90%, respectively, at a score of 1.5. The combined score demonstrated 98% sensitivity and 82% specificity at 6.5, and 95% sensitivity, and 87% specificity at a score of 7.5. Sensitivity and specificity were confirmed by bootstrap resampling for validation. Area under receiver operating characteristic (ROC) curves for our new US score were similar to the ROC curve for the Alvarado score (91.9 and 91.1, p = 0.8). The combined US and Alvarado score yielded an area under the ROC curve of 97.1, significantly better than either score alone (p = 0.017 and p < 0.001, respectively)., Conclusion: Our scoring system based entirely on US findings was highly sensitive and specific for appendicitis, and it significantly improved when combined with the Alvarado score. After prospective evaluation, the combined US-Alvarado score might replace the need for computed tomography imaging in a majority of patients., Level of Evidence: Diagnostic Test, Level III.
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- 2017
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70. Antinuclear Antibody and Subserology Testing in the Evaluation of Fibromyalgia: A Teachable Moment.
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Arora N, Gupta A, and Reddy SB
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- Adult, Analgesics therapeutic use, Diagnosis, Differential, Fibromyalgia diagnosis, Fibromyalgia therapy, Humans, Male, Serologic Tests methods, Antibodies, Antinuclear immunology, Duloxetine Hydrochloride therapeutic use, Exercise Therapy methods, Fibromyalgia immunology, Patient Education as Topic methods
- Published
- 2017
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71. Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A 1 receptor antagonists and their biological evaluation.
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Koul S, Ramdas V, Barawkar DA, Waman YB, Prasad N, Madadi SK, Shejul YD, Bonagiri R, Basu S, Menon S, Reddy SB, Chaturvedi S, Chennamaneni SR, Bedse G, Thakare R, Gundu J, Chaudhary S, De S, Meru AV, Palle V, Chugh A, and Mookhtiar KA
- Subjects
- Adenosine A1 Receptor Antagonists chemical synthesis, Adenosine A1 Receptor Antagonists pharmacokinetics, Animals, Carbon-13 Magnetic Resonance Spectroscopy, Chromatography, Liquid, Drug Design, HEK293 Cells, Humans, Hypoxanthines chemical synthesis, Hypoxanthines pharmacokinetics, Male, Mass Spectrometry, Proton Magnetic Resonance Spectroscopy, Radioligand Assay, Rats, Rats, Wistar, Adenosine A1 Receptor Antagonists chemistry, Adenosine A1 Receptor Antagonists pharmacology, Hypoxanthines chemistry, Hypoxanthines pharmacology
- Abstract
Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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72. Development of Plasmodium falciparum specific naïve, atypical, memory and plasma B cells during infancy and in adults in an endemic area.
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Lugaajju A, Reddy SB, Wahlgren M, Kironde F, and Persson KE
- Subjects
- Adolescent, Adult, Antibodies, Protozoan blood, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Immunoglobulin G blood, Immunoglobulin M blood, Infant, Infant, Newborn, Pregnancy, Uganda, Young Adult, B-Lymphocyte Subsets immunology, Immunologic Memory, Plasmodium falciparum immunology
- Abstract
Background: B-cells are essential in immunity against malaria, but which sub-sets of B-cells specifically recognize Plasmodium falciparum and when they appear is still largely unknown., Results: Using the flow cytometry technique for detection of P. falciparum specific (Pf+) B-cells, this study for the first time measured the development of Pf+ B cell (CD19+) phenotypes in Ugandan babies from birth up to nine months, and in their mothers. The babies showed increases in Pf+ IgG memory B-cells (MBCs), atypical MBCs, and plasma cells/blasts over time, but the proportion of these cells were still lower than in the mothers who displayed stable levels (5, 18, and 3%, respectively). Pf+ non-IgG+ MBCs and naïve B-cells binding to P. falciparum antigens were higher in the babies compared to the mothers (12 and 50%). In ELISA there was an increase in IgG and IgM antibodies over time in babies, and stable levels in mothers. At baby delivery, multigravidae mothers had a higher proportion of Pf+ IgG MBCs and less Pf+ naïve B-cells than primigravidae mothers., Conclusions: In newborns, naïve B-cells are a major player in recognizing P. falciparum. In adults, the high proportion of Pf+ atypical MBCs suggests a major role for these cells. Both in infants and adults, non-IgG+ MBCs were higher than IgG MBCs, indicating that these cells deserve more focus in future.
- Published
- 2017
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73. Molecular profiling of a case of advanced pancreatic cancer identifies an active and tolerable combination of targeted therapy with backbone chemotherapy.
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Johnson B, Vanderwalde A, Javadi N, Feldman R, and Reddy SB
- Abstract
Typical survival with common 1(st)-line regimens for pancreatic cancer range from 6-11 months. We report a case of a patient with stage IVB pancreatic adenocarcinoma treated with gemcitabine and erlotinib who stopped therapy after 3 months without achieving a response due to intolerance. To decide upon additional treatment options, molecular analysis was performed on liver metastasis which revealed KRAS, FBXW7, APC, and ATM mutations, with thymidylate synthase (TS) negativity and PD-1 positivity. Based on this profile of TS negativity and ATM mutation, a combination strategy was devised consisting of capecitabine, oxaliplatin, bevacizumab and vorinostat. The patient had a near complete response to therapy with this regimen. In refractory metastatic pancreatic cancer, responses of this magnitude are rarely seen. To our knowledge, this represents the first demonstrated activity of this combination in the metastatic setting which could prompt further investigation of its use in large scale clinical trials.
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- 2016
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74. The Skin Cancer Objective Structured Clinical Examination (SCOSCE): A multi-institutional collaboration to develop and validate a clinical skills assessment for melanoma.
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Garg A, Biello K, Hoot JW, Reddy SB, Wilson L, George P, Robinson-Bostom L, Belazarian L, Domingues E, Powers J, Jacob R, Powers M, Besen J, and Geller AC
- Subjects
- Adult, Biopsy, Needle, Cohort Studies, Curriculum, Dermoscopy methods, Education, Medical, Undergraduate methods, Female, Humans, Immunohistochemistry, Male, Prospective Studies, Schools, Medical, Students, Medical statistics & numerical data, United States, Young Adult, Clinical Competence, Dermatology education, Melanoma diagnosis, Physical Examination methods, Skin Neoplasms diagnosis
- Abstract
Background: Assessing medical students on core skills related to melanoma detection is challenging in the absence of a well-developed instrument., Objective: We sought to develop an objective structured clinical examination for the detection and evaluation of melanoma among medical students., Methods: This was a prospective cohort analysis of student and objective rater agreement on performance of clinical skills and assessment of differences in performance across 3 schools., Results: Kappa coefficients indicated excellent agreement for 3 of 5 core skills including commenting on the presence of the moulage (k = 0.87, 95% confidence interval 0.77-0.96), obtaining a history for the moulage (k = 0.84, 95% confidence interval 0.74-0.94), and making a clinical impression (k = 0.80, 95% confidence interval 0.68-0.92). There were no differences in performance across schools with respect to 3 of 5 core skills: commenting on the presence of the moulage (P = .15), initiating a history (P = .53), and managing the suspicious lesion (P value range .07-.17). Overall, 54.2% and 44.7% of students commented on the presence of the moulage and achieved maximum performance of core skills, respectively, with no difference in performance across schools., Limitations: Limitations include overall sample size of students and schools., Conclusion: The Skin Cancer Objective Structured Clinical Examination represents a potentially important instrument to measure students' performance on the optimal step-by-step evaluation of a melanoma., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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75. Novel flow cytometry technique for detection of Plasmodium falciparum specific B-cells in humans: increased levels of specific B-cells in ongoing infection.
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Lugaajju A, Reddy SB, Rönnberg C, Wahlgren M, Kironde F, and Persson KE
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- Erythrocyte Membrane parasitology, Humans, Malaria, Falciparum diagnosis, Malaria, Falciparum immunology, Protozoan Proteins immunology, Reproducibility of Results, B-Lymphocytes parasitology, Flow Cytometry methods, Malaria, Falciparum parasitology, Parasitology methods, Plasmodium falciparum isolation & purification, Quantum Dots therapeutic use
- Abstract
Background: Malaria caused by Plasmodium falciparum is still a major health threat in endemic areas especially for children below 5 years of age. While it is recognized that antibody immunity plays an important role in controlling the disease, knowledge of the mechanisms of sustenance and natural boosting of immunity is very limited. Before, it has not been possible to investigate malaria specific B-cells directly in flow cytometry, making it difficult to know how much of a B cell response is due to malaria, or how much is due to other immunological stimulators., Methods: This study developed a technique using quantum dots and schizont extract made from ghosts of infected erythrocytes, to be able to investigate P. falciparum specific B-cells, something that has never been done before., Results: Major differences in P. falciparum specific B-cells were found between samples from immune (22.3 %) and non-immune (1.7 %) individuals. Samples from parasite positive individuals had the highest proportions of specific B-cells (27.9 %)., Conclusion: The study showed increased levels of P. falciparum-specific B-cells in immune individuals, with the highest levels in active malaria infections, using a new technique that opens up new possibilities to study how these cells are sustained in vivo after natural infections. It will also be useful in vaccine studies.
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- 2015
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76. Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens.
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Reddy SB, Anders RF, Cross N, Mueller I, Senn N, Stanisic DI, Siba PM, Wahlgren M, Kironde F, Beeson JG, and Persson KE
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- Adolescent, Adult, Child, Child, Preschool, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Infant, Male, Middle Aged, Surface Plasmon Resonance, Young Adult, Antibodies, Monoclonal immunology, Antibodies, Protozoan immunology, Antibody Affinity, Antigens, Protozoan immunology, Merozoites immunology, Plasmodium falciparum immunology
- Abstract
Background: Malaria is a major global cause of deaths and a vaccine is urgently needed., Results: We have employed the P. falciparum merozoite antigens MSP2-3D7/FC27 and AMA1, used them in ELISA, and coupled them in different ways using surface plasmon resonance (SPR) and estimated affinity (measured as kd) of monoclonal as well as naturally-acquired polyclonal antibodies in human plasma. There were major differences in kd depending on how the antigens were immobilized and where the His-tag was placed. For AMA1 we could see correlations with invasion inhibition. Using different immobilizations of proteins in SPR, we could see only moderate correlations with levels of antibodies in ELISA, indicating that in ELISA the proteins were not uniformly bound and that antibodies with many specificities exist in natural immunisation. The correlations between ELISA and SPR were enhanced when only parasite positive samples were included, which may indicate that high affinity antibodies are difficult to maintain over long periods of time. We found higher kd values for MSP2 (indicating lower affinity) compared to AMA1, which might be partly explained by MSP2 being an intrinsically disordered protein, while AMA1 is globular., Conclusions: For future vaccine studies and for understanding immunity, it is important to consider how to present proteins to the immune system to achieve highest antibody affinities.
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- 2015
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77. Neutrophilic Fixed Drug Eruption.
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Waldman L, Reddy SB, Kassim A, Dettloff J, and Reddy VB
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- Adult, Anti-Infective Agents adverse effects, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Antifungal Agents adverse effects, Drug Eruptions etiology, Female, Fluconazole adverse effects, Humans, Metronidazole adverse effects, Naproxen adverse effects, Pregnancy, Pregnancy Complications chemically induced, Drug Eruptions pathology, Neutrophils pathology, Pregnancy Complications pathology
- Abstract
Fixed drug eruption (FDE) is a cutaneous reaction to a medication that recurs in the same fairly localized site with each exposure to the offending drug. The classical histopathologic findings in FDE consist of an interface dermatitis with predominantly lymphocytic inflammatory cell infiltrate. An unusual case of FDE in a 27-year-old pregnant woman who presented with widespread lesions and a predominantly neutrophilic infiltrate on histopathologic examination is reported.
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- 2015
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78. BRCA1 alterations are associated with endometriosis, but BRCA2 alterations show no detectable endometriosis risk: a study in Indian population.
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Govatati S, Challa K, Reddy SB, Pramod K, Deenadayal M, Chakravarty B, Shivaji S, and Bhanoori M
- Subjects
- Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, India, Promoter Regions, Genetic, White People genetics, Young Adult, BRCA1 Protein genetics, BRCA2 Protein genetics, Endometriosis genetics, Polymorphism, Single Nucleotide
- Abstract
Purpose: To investigate the role of genetic variations and expression alterations of BRCA1 and BRCA2 genes in the pathophysiology of endometriosis., Methods: A genetic association study was conducted in 573 endometriosis cases and 490 controls of Indian origin. We genotyped 13 selected promoter SNPs of BRCA1 gene and 2 selected promoter SNPs of BRCA2 gene by PCR-sequencing analysis. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of BRCA1 & 2 was analyzed in the eutopic endometria of endometriosis cases and controls by western-blot and immunohistochemical analysis., Results: Our results revealed significant association between BRCA1 rs71361504 (-/GTT) SNP and endometriosis risk in Indian women (P < 0.0001), while the remaining SNPs of both BRCA1 & 2 genes showed no difference between cases and controls. Western-blot and immunohistochemical analysis revealed significantly decreased BRCA1 expression levels in eutopic endometria of patients compared with controls (P < 0.05). Furthermore, nuclear BRCA1 was frequently lost compared with cytoplasmic BRCA1 in eutopic endometria of patients. Expression of BRCA2 did not differ between patients and controls., Conclusions: BRCA1 rs71361504 SNP may modify the endometriosis risk in Indian women. In addition, decreased expression of BRCA1 may play an important role in the pathophysiology of endometriosis. The analysis of BRCA1 genetic variants and/or expression might help to identify patients at high risk for disease outcome.
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- 2015
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79. Controlling pain during orthodontic fixed appliance therapy with non-steroidal anti-inflammatory drugs (NSAID): a randomized, double-blinded, placebo-controlled study.
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Gupta M, Kandula S, Laxmikanth SM, Vyavahare SS, Reddy SB, and Ramachandra CS
- Subjects
- Adolescent, Double-Blind Method, Drug Administration Schedule, Facial Pain diagnosis, Female, Humans, Male, Pain Measurement drug effects, Placebo Effect, Treatment Outcome, Young Adult, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Facial Pain etiology, Facial Pain prevention & control, Orthodontic Appliances adverse effects, Orthodontics, Corrective adverse effects, Orthodontics, Corrective instrumentation
- Abstract
Background: Despite all the technological advances in orthodontics, orthodontic treatment still seems to involve some degree of discomfort and/or pain. Pain control during orthodontic therapy is of great concern to both orthodontists and patients. However, there has been limited research into controlling such pain., Aims: The purpose of this work was to assess patient-perceived pain following fixed orthodontic treatment and to evaluate the comparative analgesic efficacy of non-steroidal anti-inflammatory drugs for controlling pain., Methods: A total of 45 patients about to undergo fixed appliance orthodontic treatment were enrolled in this double-blind prospective study. Patients were evenly and randomly distributed in a blinded manner to one of three groups as follows: paracetamol/acetaminophen 500 mg thrice daily; placebo in the form of empty capsules; and etoricoxib 60 mg once daily. Drug administration began 1 h before initiating the bonding procedure and archwire placement, and given until the day 3. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 h after insertion of the appliance; 6 h thereafter and again at nighttime of the same day of the appointment; 24 h later and on the 2nd day at nighttime; 48 h after the appointment and on day 3 at nighttime., Results: Our results revealed that moderately intense pain is associated with routine orthodontic treatment, and that the amount of pain individuals perceive varies widely. We observed statistically significant differences in the pain control among the three groups, and that etoricoxib 60 mg proved most efficient., Conclusion: Etoricoxib 60 mg is highly efficacious for controlling pain during fixed orthodontic appliance therapy.
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- 2014
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80. Curricular factors associated with medical students' practice of the skin cancer examination: an educational enhancement initiative by the integrated skin exam consortium.
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Garg A, Wang J, Reddy SB, Powers J, Jacob R, Powers M, Biello K, Cayce R, Savory S, Belazarian L, Domingues E, Korzenko A, Wilson L, Grant-Kels JM, George P, Robinson-Bostom L, Trotter SC, and Geller AC
- Subjects
- Cross-Sectional Studies, Female, Health Knowledge, Attitudes, Practice, Humans, Intention, Male, Physical Examination, Schools, Medical, Self Efficacy, Task Performance and Analysis, Time Factors, United States, Dermatology education, Melanoma diagnosis, Skin Neoplasms diagnosis, Students, Medical psychology
- Abstract
Importance: As medical school curricula become progressively integrated, a need exists to optimize education related to the skin cancer examination (SCE) for melanoma, a relevant competency gap that influences secondary prevention efforts., Objectives: To identify curricular factors associated with medical students' confidence, intent, and performance regarding the SCE., Design, Setting, and Participants: Survey-based cross-sectional study from the Integrated Skin Exam Consortium at accredited US medical schools among a volunteer sample of second-year students representing 8 geographically varied public and private institutions. Students were administered a questionnaire to assess characteristics, curricular exposures, and educational and practical experiences related to skin cancer, as well as knowledge of melanoma risk and a detection method., Main Outcomes and Measures: Primary outcomes were confidence in performing the SCE, intent to perform an integrated skin examination, and actual performance of the SCE., Results: Physical diagnosis session and clinical encounter were most predictive of confidence in performance of the SCE (odds ratios [ORs], 15.35 and 11.48, respectively). Other curricular factors associated with confidence included instruction time of at least 60 minutes on skin cancer (OR, 6.35), lecture on the SCE (OR, 7.54), knowledge of melanoma risk (OR, 3.71), and at least 1 opportunity to observe the SCE (OR, 2.70). Physical diagnosis session and at least 4 opportunities to observe the SCE were most predictive of intent to perform an integrated skin examination (ORs, 4.84 and 4.72, respectively). Other curricular factors associated with intent included knowledge of melanoma risk (OR, 1.83), clinical encounter (OR, 2.39), and at least 1 opportunity to observe the SCE (OR, 1.95). Clinical encounter, physical diagnosis session, and at least 1 opportunity to observe the SCE were most predictive of performance of the SCE (ORs, 21.67, 15.48, and 9.92, respectively). Other curricular factors associated with performance included instruction time of at least 60 minutes on skin cancer (OR, 2.42) and lecture on the SCE (OR, 5.04)., Conclusions and Relevance: To augment the practice of the SCE among medical students, course directors may design an integrated curriculum that includes at least 60 minutes of instruction related to melanoma and the SCE, a description of the integrated skin examination as part of the physical diagnosis course, and education on high-risk demographic groups and anatomic sites specific to men and women and on the ABCDEs of melanoma, and at least 1 opportunity to observe the SCE.
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- 2014
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81. Trace elemental distribution in the scalp hair of bipolars using PIXE technique.
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Pradeep AS, Naga Raju GJ, Sattar SA, Sarita P, Prasada Rao AD, Ray DK, Reddy BS, and Reddy SB
- Subjects
- Adult, Copper analysis, Dopamine metabolism, Female, Humans, Iron analysis, Male, Middle Aged, Selenium analysis, Young Adult, Zinc analysis, Bipolar Disorder metabolism, Hair metabolism, Scalp metabolism, Trace Elements analysis
- Abstract
Trace metals play a significant role in neurological disorders. There is very limited information available on the role of macro and trace elements in bipolar disorders. The objective of this investigation was to identification, quantification of essential trace elements in the scalp hair samples of the patients and compare with those of normal subjects. We made a hypothesis about the role played by essential trace metals whose concentrations are significantly different to those of normals in the disease process. The analysis was carried out in the scalp hair samples of 26 male and 26 female patients suffering from bipolar disorder (BD) by Particle Induced X-ray Emission Technique (PIXE). The concentration of Cu (p < 0.002) was found to be higher in the hair samples of male bipolar disorder patients while the concentrations of Mn (p < 0.001), Fe (p < 0.005), Zn (p < 0.0001) and Se (p < 0.005) were found to be lower than those in normal subjects. The concentration of Cu (p < 0.0001) was higher in the hair samples of female bipolar patients but depressed levels of Fe (p < 0.005), Ni (p < 0.05), Zn (p < 0.00001) and Se (p < 0.05) were observed compared to controls. Cu/Zn ratio was found to be higher in the hair samples of male and female patients compared with normals. While the imbalance of certain trace elements leads to generation of more free radicals, the imbalance of some other trace elements causes changes in dopamine (neurotransmitter) activity. It is essential to monitor before and periodically during treatment the levels of essential trace elements for effective treatment of bipolar disorder., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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82. The Integrated Skin Exam film: an educational intervention to promote early detection of melanoma by medical students.
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Garg A, Wang J, Reddy SB, Powers J, Jacob R, Powers M, Biello K, Cayce R, Savory S, Belazarian L, Domingues E, Korzenko A, Wilson L, Grant-Kels JM, George P, Robinson-Bostom L, Trotter SC, and Geller AC
- Subjects
- Attitude of Health Personnel, Female, Health Knowledge, Attitudes, Practice, Humans, Male, Self Efficacy, Students, Medical psychology, Dermatology education, Early Detection of Cancer methods, Education, Medical, Melanoma diagnosis, Motion Pictures, Skin Neoplasms diagnosis
- Abstract
Background: Knowledge of the skin cancer examination (SCE) and its practice remain relevant competency gaps among medical students., Objective: We elaborate on a method of SCE known as the Integrated Skin Exam and discuss the development of an instructional film that illustrates its principles. We assess the tool's effect on knowledge, attitudes, and perceptions related to the SCE., Methods: Second-year students among 8 randomized schools viewed the film and completed pre-post questionnaires., Results: After viewing The Integrated Skin Exam film, students demonstrated improved melanoma knowledge, including identification of high-risk demographic groups (61% vs 42.9%, P < .001), high-risk anatomic sites in women (88.6% vs 46.5%, P < .001) and men (92.1% vs 34.8%, P < .001), and the ABCDEs of melanoma (98.4% vs 91.2%, P < .001). Students demonstrated increased confidence in the SCE (66.93% vs 16.40%, P < .001) and augmented intentions to practice it (99.05% vs 13.9%, P < .001). A greater proportion (70.4% vs 41.9%, P < .001) of students thought less than 3 minutes were required to integrate SCE into the routine examination., Limitations: Longitudinal impact of the film was not assessed., Conclusion: The Integrated Skin Exam film introduces an integrated approach to the SCE that addresses knowledge gaps, mitigates perceived barriers, and augments intention related to practice of the SCE., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)
- Published
- 2014
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83. Health status of the prisoners in a central jail of South India.
- Author
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Kumar SD, Kumar SA, Pattankar JV, Reddy SB, and Dhar M
- Abstract
Background: Health care in prisons is one of the neglected health areas in our country. Looking into the health problems of prisons will show us a way for the approach in providing the heath care for prisoners., Objectives: To assess the health status of convicted inmates of prison and to study their sociodemographic profile., Materials and Methods: A cross-sectional study was conducted among the inmates of central prison over a period of 1 year. Study population comprised of 300 convicted life-term prisoners. The inmates were interviewed using predesigned and pretested proforma. Sociodemographic data were analyzed by frequencies and percentages along with 95% confidence interval using statistical package SPSS18., Results: In health status, 29 (9.6%) inmates suffered from acute upper respiratory tract infections and 15 (5%) from acute lower respiratory tract infections. A total of 54 (18%) inmates had ascariasis. Diseases of musculoskeletal system and connective tissue contributed to 26 (8.7%) of inmates. A total of 252 (84%) prisoners had anemia. In sociodemographic profile, it was found that rural people, unmarried, illiterates, lower socioeconomic status people were more likely to have committed the crime resulting in the conviction for life., Conclusions: As there is an increase in number of prisoners and morbidities among them, there is an urgent need for prison health care services in developing countries like India and provide training to the health care providers to manage the commonly existing health problems among prisoners in the prisons.
- Published
- 2013
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84. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.
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Ichiyama K, Gopala Reddy SB, Zhang LF, Chin WX, Muschin T, Heinig L, Suzuki Y, Nanjundappa H, Yoshinaka Y, Ryo A, Nomura N, Ooi EE, Vasudevan SG, Yoshida T, and Yamamoto N
- Subjects
- Animals, Cell Line, Dengue Virus immunology, Dengue Virus physiology, Macaca mulatta, Microscopy, Electron, Antibody-Dependent Enhancement drug effects, Dengue immunology, Dengue Virus drug effects, Virus Replication drug effects, beta-Glucans pharmacology
- Abstract
Curdlan sulfate (CRDS), a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV). CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E) protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion). The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.
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- 2013
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85. Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non-responders from responders to pegylated interferon alpha-ribavirin treatment.
- Author
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Pham TN, Lin DM, Mulrooney-Cousins PM, Churchill ND, Kowala-Piaskowska A, Mozer-Lisewska I, Machaj A, Pazgan-Simon M, Zalewska M, Simon K, King D, Reddy SB, and Michalak TI
- Subjects
- 2',5'-Oligoadenylate Synthetase biosynthesis, Adolescent, Adult, Aged, Child, Cytokines biosynthesis, Female, Hepacivirus immunology, Humans, Male, Middle Aged, Prognosis, RNA, Viral blood, Toll-Like Receptors biosynthesis, Treatment Outcome, Ubiquitins biosynthesis, Young Adult, Antiviral Agents therapeutic use, Hepacivirus isolation & purification, Hepatitis C, Chronic drug therapy, Interferon-alpha therapeutic use, Lymphocytes immunology, Ribavirin therapeutic use, Viral Load
- Abstract
Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies., (Copyright © 2012 Wiley Periodicals, Inc.)
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- 2013
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86. Novel approach to utilizing electronic health records for dermatologic research: developing a multi-institutional federated data network for clinical and translational research in psoriasis and psoriatic arthritis.
- Author
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Armstrong AW, Reddy SB, and Garg A
- Subjects
- Algorithms, Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic therapy, Cohort Studies, Comorbidity, Computer Communication Networks, Hospital Information Systems organization & administration, Humans, Information Storage and Retrieval, Myocardial Infarction epidemiology, Pharmacovigilance, Psoriasis diagnosis, Psoriasis therapy, Reproducibility of Results, Translational Research, Biomedical methods, United Kingdom, Arthritis, Psoriatic epidemiology, Biomedical Research methods, Electronic Health Records statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Psoriasis epidemiology
- Abstract
The implementation of Electronic Health Records (EHR) in the United States has created new opportunities for research using automated data extraction methods. A large amount of information from the EHR can be utilized for clinical and translational research. To date, a number of institutions have the capability of extracting clinical data from EHR to create local repositories of de-identified data amenable to research queries through the Informatics for Integrated Biology and the Bedside (i2b2) platform. Collaborations among institutions sharing a common i2b2 platform hold exciting opportunities for research in psoriasis and psoriatic arthritis. With the automated extraction of patient-level data from multiple institutions, this novel informatics network has the ability to address high-priority research questions. With commitment to high-quality data through applied algorithms for cohort identification and validation of outcomes, the creation of Psoriasis and Psoriatic Arthritis Integrated Research Data Network (PIONEER) will make a significant contribution to psoriasis and psoriatic arthritis research.
- Published
- 2012
87. Acoustic wave immunosensing of a meningococcal antigen using gold nanoparticle-enhanced mass sensitivity.
- Author
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Reddy SB, Mainwaring DE, Kobaisi MA, Zeephongsekul P, and Fecondo JV
- Subjects
- Equipment Design, Equipment Failure Analysis, Micro-Electrical-Mechanical Systems instrumentation, Nanotechnology instrumentation, Reproducibility of Results, Sensitivity and Specificity, Acoustics instrumentation, Antigens, Bacterial analysis, Biosensing Techniques instrumentation, Gold chemistry, Immunoassay instrumentation, Nanoparticles chemistry, Neisseria meningitidis immunology
- Abstract
Bacterial meningitis is an infection of the thin membranes covering the brain and spinal cord by a number of microorganisms including Neisseria meningitidis, which can lead to permanent neurological damage in the event of late diagnosis. Given the quick onset and severity of the disease, there is a clear need for a rapid, sensitive and specific diagnostic technique. Here, we describe the development and evaluation of an acoustic wave sensor, the quartz crystal microbalance (QCM), as a rapid immunosensor employing antibodies against the cell surface outer membrane protein 85 (OMP85) of N. meningitidis as an immobilized selective layer. These antibodies were directionally orientated as receptors by thin film deposition of structured polyvinylidene fluoride and Protein A. The sensitivity of this QCM immunosensor was further increased by conjugation of the OMP85 antigen to 50 nm gold nanoparticles providing reproducible detection of the target down to 300 ng/mL. Subsequent treatment of the QCM surface with an acidic glycine solution regenerated the immunosensor allowing each crystal to be used several times., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
88. Refining the relationship between homozygosity and the frequency of the most frequent allele.
- Author
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Reddy SB and Rosenberg NA
- Subjects
- Genetic Loci, Genetics, Population statistics & numerical data, Humans, Gene Frequency, Homozygote, Models, Genetic
- Abstract
Recent work has established that for an arbitrary genetic locus with its number of alleles unspecified, the homozygosity of the locus confines the frequency of the most frequent allele within a narrow range, and vice versa. Here we extend beyond this limiting case by investigating the relationship between homozygosity and the frequency of the most frequent allele when the number of alleles at the locus is treated as known. Given the homozygosity of a locus with at most K alleles, we find that by taking into account the value of K, the width of the allowed range for the frequency of the most frequent allele decreases from 2/3 - π(2)/18 ≈ 0.1184 to 1/3 - 1/(3K) - {K/[3(K - 1)]} Σ(K)(k = 2) 1/k(2). We further show that properties of the relationship between homozygosity and the frequency of the most frequent allele in the unspecified-K case can be obtained from the specified-K case by taking limits as K → ∞. The results contribute to a greater understanding of the mathematical properties of fundamental statistics employed in population-genetic analysis., (© The Author(s) 2011. This article is published with open access at Springerlink.com)
- Published
- 2012
- Full Text
- View/download PDF
89. High affinity antibodies to Plasmodium falciparum merozoite antigens are associated with protection from malaria.
- Author
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Reddy SB, Anders RF, Beeson JG, Färnert A, Kironde F, Berenzon SK, Wahlgren M, Linse S, and Persson KE
- Subjects
- Adolescent, Adult, Aged, Aging immunology, Antibodies, Monoclonal immunology, Antibodies, Protozoan blood, Binding Sites, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Humans, Infant, Kinetics, Malaria, Falciparum blood, Middle Aged, Protozoan Proteins immunology, Surface Plasmon Resonance, Tanzania, Young Adult, Antibodies, Protozoan immunology, Antibody Affinity immunology, Antigens, Protozoan immunology, Malaria, Falciparum immunology, Malaria, Falciparum prevention & control, Merozoites immunology, Plasmodium falciparum immunology
- Abstract
Background: Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown., Methodology/principal Findings: In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as k(d)) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up., Conclusions/significance: This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations.
- Published
- 2012
- Full Text
- View/download PDF
90. Induction of adaptive response in human blood lymphocytes exposed to 900 MHz radiofrequency fields: influence of cell cycle.
- Author
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Sannino A, Zeni O, Sarti M, Romeo S, Reddy SB, Belisario MA, Prihoda TJ, Vijayalaxmi, and Scarfi MR
- Subjects
- Adaptation, Physiological drug effects, Adaptation, Physiological genetics, Adult, Cell Cycle drug effects, Cell Cycle genetics, Cell Proliferation drug effects, Cell Proliferation radiation effects, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Humans, Lymphocytes drug effects, Lymphocytes metabolism, Male, Micronucleus Tests, Middle Aged, Mitomycin pharmacology, Time Factors, Young Adult, Adaptation, Physiological radiation effects, Cell Cycle radiation effects, Lymphocytes cytology, Lymphocytes radiation effects, Radio Waves adverse effects
- Abstract
Purpose: To investigate the influence of cell cycle on the adaptive response (AR) induced by the exposure of human blood lymphocytes to radiofrequency fields (RF)., Materials and Methods: Human peripheral blood lymphocytes in G(0)-, G(1)- or S-phase of the cell cycle were exposed for 20 hours to an adaptive dose (AD) of 900 MHz RF at an average specific absorption rate of 1.25 W/kg and then treated with a challenge dose (CD) of 100 ng/ml mitomycin C (MMC). Un-exposed and sham-exposed controls as well as cells treated with MMC alone were included in the study. The incidence of micronuclei (MN) was evaluated to determine the induction of AR., Results: The results indicated that the cells which were exposed to AD of RF in G(0)- and G(1)-phase of the cell cycle did not exhibit AR while such a response was observed when the cells were exposed to AD of RF in S-phase of the cell cycle., Conclusions: These results confirmed the observations reported in our previous investigation where AR was observed in human blood lymphocytes exposed to AD of RF in S-phase of the cell cycle and further suggested that the timing of AD exposure of RF is important to elicit AR.
- Published
- 2011
- Full Text
- View/download PDF
91. Twisting ligature wires for lingual retainers.
- Author
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Ramana Reddy SB, Rachala MR, and Alineni KR
- Subjects
- Humans, Orthodontic Retainers, Orthodontic Wires, Technology, Dental instrumentation
- Published
- 2011
92. Discovery of a potent and selective small molecule hGPR91 antagonist.
- Author
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Bhuniya D, Umrani D, Dave B, Salunke D, Kukreja G, Gundu J, Naykodi M, Shaikh NS, Shitole P, Kurhade S, De S, Majumdar S, Reddy SB, Tambe S, Shejul Y, Chugh A, Palle VP, Mookhtiar KA, Cully D, Vacca J, Chakravarty PK, Nargund RP, Wright SD, Graziano MP, Singh SB, Roy S, and Cai TQ
- Subjects
- Administration, Oral, Animals, Inhibitory Concentration 50, Male, Molecular Structure, Rats, Rats, Wistar, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, Drug Discovery, Receptors, G-Protein-Coupled antagonists & inhibitors, Small Molecule Libraries chemical synthesis
- Abstract
GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput screening hit 1 (hGPR91 IC(50): 0.8 μM)-originally synthesized in Merck for Bradykinin B(1) Receptor (BK(1)R) program, systematic structure-activity relationship study led us to discover potent and selective hGPR91 antagonists e.g. 2c, 4c, and 5 g (IC(50): 7-35 nM; >1000 fold selective against hGPR99, a closest related GPCR; >100 fold selective in Drug Matrix screening). This initial work also led to identification of two structurally distinct and orally bio-available lead compounds: 5g (%F: 26) and 7e (IC(50): 180 nM; >100 fold selective against hGPR99; %F: 87). A rat pharmacodynamic assay was developed to characterize the antagonists in vivo using succinate induced increase in blood pressure. Using two representative antagonists, 2c and 4c, the GPR91 target engagement was subsequently demonstrated using the designed pharmacodynamic assay., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
93. Micronuclei in the blood and bone marrow cells of mice exposed to specific complex time-varying pulsed magnetic fields.
- Author
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Reddy SB, Weller J, Desjardins-Holmes D, Winters T, Keenliside L, Prato FS, Prihoda TJ, Thomas V, and Thomas AW
- Subjects
- Animals, Blood Cells cytology, Bone Marrow Cells cytology, Erythrocytes cytology, Erythrocytes radiation effects, Male, Mice, Micronucleus Tests, Time Factors, Blood Cells metabolism, Blood Cells radiation effects, Bone Marrow Cells metabolism, Bone Marrow Cells radiation effects, Electromagnetic Fields adverse effects, Micronuclei, Chromosome-Defective
- Abstract
For 8 weeks, adult CD-1 male mice were continuously exposed to complex time-varying pulsed magnetic fields (PMF) generated in the horizontal direction by a set of square Helmholtz coils. The PMF were <1000 Hz and delivered at a peak flux density of 1 mT. Sham-exposed mice were kept in a similar exposure system without a PMF. Positive control animals exposed to 1 Gy gamma radiation were also included in the study. Blood samples were collected before (time 0) and at 2, 4, 6, and 8 weeks. All mice were euthanized at the end of 8 weeks and their bone marrow was collected. From each blood and bone marrow sample, smears were prepared on microscope slides, fixed in absolute methanol, air-dried, and stained with acridine orange. All slides were coded and examined using a fluorescence microscope. The extent of genotoxicity and cytotoxicity was assessed from the incidence of micronuclei (MN) and percent polychromatic erythrocytes (PCE) in the blood and bone marrow, respectively. The data indicated that both indices in PMF-exposed mice were not significantly different from those observed in sham-exposed animals. In contrast, positive control mice exhibited significantly increased MN, and decreased percentages of PCE in both tissues. Thus, the overall data suggested that 8 weeks of continuous exposure to PMF did not induce significantly increased genotoxicity and cytotoxicity in experimental mice. Further investigations are underway using other genotoxicity assays (comet assay, gamma-H2AX foci, and chromosomal aberrations) to assess genotoxicity following PMF exposure., (2010 Wiley-Liss, Inc.)
- Published
- 2010
- Full Text
- View/download PDF
94. Induction of adaptive response in human blood lymphocytes exposed to radiofrequency radiation.
- Author
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Sannino A, Sarti M, Reddy SB, Prihoda TJ, Vijayalaxmi, and Scarfì MR
- Subjects
- Adult, Humans, Lymphocytes drug effects, Male, Mitomycin pharmacology, Nucleic Acid Synthesis Inhibitors pharmacology, Young Adult, Lymphocytes cytology, Lymphocytes radiation effects, Micronuclei, Chromosome-Defective radiation effects, Radio Waves
- Abstract
The incidence of micronuclei was evaluated to assess the induction of an adaptive response to non-ionizing radiofrequency (RF) radiation in peripheral blood lymphocytes collected from five different human volunteers. After stimulation with phytohemagglutinin for 24 h, the cells were exposed to an adaptive dose of 900 MHz RF radiation used for mobile communications (at a peak specific absorption rate of 10 W/kg) for 20 h and then challenged with a single genotoxic dose of mitomycin C (100 ng/ml) at 48 h. Lymphocytes were collected at 72 h to examine the frequency of micronuclei in cytokinesis-blocked binucleated cells. Cells collected from four donors exhibited the induction of adaptive response (i.e., responders). Lymphocytes that were pre-exposed to 900 MHz RF radiation had a significantly decreased incidence of micronuclei induced by the challenge dose of mitomycin C compared to those that were not pre-exposed to 900 MHz RF radiation. These preliminary results suggested that the adaptive response can be induced in cells exposed to non-ionizing radiation. A similar phenomenon has been reported in cells as well as in animals exposed to ionizing radiation in several earlier studies. However, induction of adaptive response was not observed in the remaining donor (i.e., non-responder). The incidence of micronuclei induced by the challenge dose of mitomycin C was not significantly different between the cells that were pre-exposed and unexposed to 900 MHz RF radiation. Thus the overall data indicated the existence of heterogeneity in the induction of an adaptive response between individuals exposed to RF radiation and showed that the less time-consuming micronucleus assay can be used to determine whether an individual is a responder or non-responder.
- Published
- 2009
- Full Text
- View/download PDF
95. Absence of genotoxic potential of 902 MHz (GSM) and 1747 MHz (DCS) wireless communication signals: In vivo two-year bioassay in B6C3F1 mice.
- Author
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Ziemann C, Brockmeyer H, Reddy SB, Vijayalaxmi, Prihoda TJ, Kuster N, Tillmann T, and Dasenbrock C
- Subjects
- Animals, Biological Assay, Environmental Exposure, Erythrocytes radiation effects, Female, Male, Mice, Micronucleus Tests, Survival Rate, Time Factors, Cell Phone, Radio Waves adverse effects
- Abstract
Purpose: The aim of the present investigation was to determine the incidence of micronuclei in peripheral blood erythrocytes of B6C3F1 mice that had been chronically exposed to radiofrequencies (RF) used for mobile communication., Materials and Methods: 'Ferris wheels' were used to expose tube-restrained male and female mice to simulated environmental RF signals of the Global System for Mobile Communications (GSM, 902 MHz) or Digital Cellular System (DCS, 1747 MHz). RF signals were applied to the mice for 2 hours/day on 5 days/week for two years, at maximal whole-body-averaged specific absorption rates of 0.4, 1.3, and 4.0 W/kg body weight. Concurrent sham-exposed mice, cage controls, and positive controls injected with mitomycin C were included in this investigation. At necropsy, peripheral blood smears were prepared, and coded slides were stained using May-Grunwald-Giemsa or acridine orange. The incidence of micronuclei was recorded for each mouse in 2000 polychromatic and 2000 normochromatic erythrocytes., Results: There were no significant differences in the frequency of micronuclei between RF-exposed, sham-exposed, and cage control mice, irrespective of the staining/counting method used. Micronuclei were, however, significantly increased in polychromatic erythrocytes of the positive control mice., Conclusions: In conclusion, the data did not indicate RF-induced genotoxicity in mice after two years of exposure.
- Published
- 2009
- Full Text
- View/download PDF
96. Herpesviruses in chronic and aggressive periodontitis patients in an Indian population.
- Author
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Bilichodmath S, Mangalekar SB, Sharma DC, Prabhakar AK, Reddy SB, Kalburgi NB, Patil SR, and Bhat K
- Subjects
- Adolescent, Adult, Age Factors, Child, Cytomegalovirus isolation & purification, Dental Plaque virology, Female, Herpesvirus 1, Human isolation & purification, Herpesvirus 2, Human isolation & purification, Herpesvirus 4, Human isolation & purification, Humans, India, Male, Middle Aged, Periodontal Attachment Loss virology, Periodontal Pocket virology, Young Adult, Aggressive Periodontitis virology, Chronic Periodontitis virology, Herpesviridae classification, Herpesviridae Infections virology
- Abstract
Many recent studies have assessed the prevalence and role of herpesviruses in the etiopathogenesis of periodontal diseases, which has led to the realization of intricate interactions between viruses and bacteria within periodontal pockets. It has also been shown that the occurrence of herpesviruses may vary depending upon the age of the patient and the race of the population studied. Thus, the present study aimed at detecting herpes simplex virus type 1 and 2 (HSV 1 and 2), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in periodontal pockets of Indian patients with chronic and aggressive periodontitis. Subgingival plaque samples (n = 33) were collected from 19 randomly chosen chronic periodontitis and 14 aggressive periodontitis patients. Herpesviruses were detected using multiplex polymerase chain reaction technique. Chronic periodontitis patients revealed presence of HSV-1 in 19 (100%) samples, HSV-2 in 3 (15.7%), EBV in 15 (78.9%) and HCMV in 5 (26.31%) samples. Samples from aggressive periodontitis patients showed the presence of HSV-1 in 8 (57.14%), EBV in 4 (28.57%) and HCMV in 1 (7.14%), whereas HSV-2 was not detected in any specimen. In this population, herpesviruses were found more frequently in chronic periodontitis than in aggressive periodontitis patients and their prevalence may vary according to the age and race of the patient.
- Published
- 2009
- Full Text
- View/download PDF
97. Tirapazamine: a novel agent targeting hypoxic tumor cells.
- Author
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Reddy SB and Williamson SK
- Subjects
- Animals, Antineoplastic Agents adverse effects, Antineoplastic Agents chemistry, Cell Hypoxia drug effects, Clinical Trials as Topic, Humans, Neoplasms metabolism, Tirapazamine, Treatment Outcome, Triazines adverse effects, Triazines chemistry, Antineoplastic Agents therapeutic use, Neoplasms drug therapy, Neoplasms pathology, Triazines therapeutic use
- Abstract
Background: Tumor hypoxia remains one of the greatest challenges in the treatment of solid tumors, as cancer cells in these regions are resistant to killing by radiation therapy and most anticancer drugs. Tirapazamine (TPZ) is a newer class of cytotoxic drugs with selective toxicity towards hypoxic mammalian cells., Objective: This article reviews the mechanism of action, toxicity and antitumor activity of the drug and provides insights into factors that may have contributed to the disappointing results in some of the Phase III trials. It also identifies the need to explore dependable markers of tumor hypoxia and limit future trials of this agent to patients who have significant populations of hypoxic tumor cells., Methods: We reviewed all clinical trials published to date and present a summary of the results. There are also several ongoing studies, the results of which are pending and may yet impact the clinical use of the drug., Results/conclusion: Despite the very promising results obtained in various preclinical studies and early-Phase clinical trials, several Phase III trials have failed to demonstrate any survival benefit of adding TPZ to chemotherapy or radiation therapy in non-small cell lung cancer or head and neck cancer. Several clinical trials have yet to be completed and reported.
- Published
- 2009
- Full Text
- View/download PDF
98. Multiple squamous cell carcinomas of the skin after therapy with sorafenib combined with tipifarnib.
- Author
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Hong DS, Reddy SB, Prieto VG, Wright JJ, Tannir NM, Cohen PR, Diwan AH, Evans HL, and Kurzrock R
- Subjects
- Aged, Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Biopsy, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell secondary, Carcinoma, Squamous Cell pathology, Diagnosis, Differential, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Kidney Neoplasms drug therapy, Kidney Neoplasms secondary, Niacinamide analogs & derivatives, Phenylurea Compounds, Pyridines therapeutic use, Quinolones therapeutic use, Receptors, Vascular Endothelial Growth Factor, Skin Neoplasms pathology, Sorafenib, Antineoplastic Agents adverse effects, Benzenesulfonates adverse effects, Carcinoma, Squamous Cell chemically induced, Pyridines adverse effects, Quinolones adverse effects, Skin Neoplasms chemically induced
- Abstract
Background: Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor., Observations: We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date., Conclusions: Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors.
- Published
- 2008
- Full Text
- View/download PDF
99. Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection.
- Author
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Pham TN, King D, Macparland SA, McGrath JS, Reddy SB, Bursey FR, and Michalak TI
- Subjects
- Adult, Antiviral Agents therapeutic use, Base Sequence, Cells, Cultured, Female, Follow-Up Studies, Hepacivirus genetics, Hepacivirus metabolism, Hepatitis C blood, Hepatitis C drug therapy, Hepatitis C genetics, Hepatitis C, Chronic blood, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic genetics, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, RNA, Viral blood, Time Factors, Viral Load, Viral Nonstructural Proteins blood, Virus Replication, B-Lymphocytes virology, CD4-Positive T-Lymphocytes virology, CD8-Positive T-Lymphocytes virology, Hepacivirus growth & development, Hepatitis C immunology, Hepatitis C, Chronic immunology, Monocytes virology
- Abstract
Background & Aims: Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C., Methods: Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA-positive and -negative strands and, in selected cases, nonstructural protein 5A display and HCV variants., Results: All subtypes of immune cells investigated support HCV replication in both forms of infection, although significant differences were found between patients, and virus loads in the cells were greater in CHC than in occult infection. Although HCV RNA occurred at a comparable frequency in all cell subtypes in CHC, monocytes contained the greatest loads. In contrast, B cells tended to carry the highest virus quantities in occult infection, whereas monocytes appeared to be the least frequently infected. Detection of HCV nonstructural protein 5A and HCV variants that were not found in plasma confirmed virus replication in different immune cell types., Conclusions: This work documents that the immune system supports HCV replication regardless of clinical appearance of infection and identifies immune cells that are reservoirs of HCV in symptomatic and occult infections.
- Published
- 2008
- Full Text
- View/download PDF
100. The effect of ibuprofen on bleeding during periodontal surgery.
- Author
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Shiva Prasad BM, Vijaya M, Reddy SB, Patil SR, and Kalburgi NB
- Subjects
- Adult, Bleeding Time, Gingival Hemorrhage etiology, Humans, Pain, Postoperative prevention & control, Premedication, Single-Blind Method, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Blood Loss, Surgical, Ibuprofen adverse effects, Periodontium surgery
- Abstract
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used medications for both medical and dental ailments. These drugs have been shown to increase bleeding during surgeries, which may prompt practitioners to discontinue their use before surgical procedures. The aim of the present study is to assess the effect of a common NSAID, ibuprofen, on bleeding during periodontal surgery., Materials and Methods: The study group consisted of 10 patients who were scheduled to undergo periodontal surgery of similar type, complexity, and duration. Each subject acted as control as well as case group. The case group consisted of 10 surgeries in which patients were administered ibuprofen prior to surgery, whereas ibuprofen was not administered in control group. Bleeding time was measured at first visit and prior to first and second surgeries. The volume of blood loss during each surgery was measured by subtracting the amount of water used for irrigation from the total volume of fluid collected in the portable aspirator at the end of the surgery., Results: The result showed a statistically significant (P < 0.05) increase in intraoperative bleeding during periodontal surgery when ibuprofen was preadministered. In addition, there was statistically significant (P < 0.05) increase in bleeding time., Conclusion: Ibuprofen taken prior to periodontal surgery increases intraoperative bleeding and should be administered cautiously before periodontal surgeries.
- Published
- 2008
- Full Text
- View/download PDF
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