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1.
Malays Orthop J ; 18(1): 84-90, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38638651

ABSTRACT

Introduction: Peripheral nerve injuries (PNIs) remain an important health problem. PNIs mostly affect young men as this age group is mostly involved in road traffic accidents and other injuries at workplace. PNI can occur from foreign bodies like metal chips while working in industries using lathe machines. Among PNI's, injuries to the ulnar nerve, the brachial plexus and the median nerve are the most frequent lesions encountered. Materials and methods: This presentation is on a series of 18 cases of nerve injuries among industrial workers located from finger level up to the arm excluding the brachial plexus due to metallic foreign bodies entering while operating lathe machines over a period of two years with patients being followed-up over a one year period. Results: Mean age in this series was 31.3 years with age range 16-40 years and all were males. Two patients had more than one nerve involvement and one patient had associated vascular injury. All the patients showed functional improvement. Most common nerve injured was median nerve. Most common site for nerve injury was forearm. Combined lesions most commonly involved the ulnar and median nerves. Conclusion: Social cost of traumatic peripheral nerve injuries is significant since it has a higher incidence in young, previously healthy, and economically active people.

3.
Ann Oncol ; 32(6): 726-735, 2021 06.
Article in English | MEDLINE | ID: mdl-33794293

ABSTRACT

BACKGROUND: Plasma tumor DNA fraction is prognostic in metastatic cancers. This could improve risk stratification before commencing a new treatment. We hypothesized that a second sample collected after one cycle of treatment could refine outcome prediction of patients identified as poor prognosis based on plasma DNA collected pre-treatment. PATIENTS AND METHODS: Plasma DNA [128 pre-treatment, 134 cycle 2 day 1 (C2D1), and 49 progression] from 151 chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) patients in a phase II study of abiraterone acetate (NCT01867710) were subjected to custom targeted next-generation sequencing covering exons of these genes: TP53, AR, RB1, PTEN, PIK3CA, BRCA1, BRCA2, ATM, CDK12, CHEK2, FANCA HDAC2 and PALB2. We also captured 1500 pan-genome regions enriched for single nucleotide polymorphisms to allow detection of tumor DNA using the rolling B-allele method. We tested associations with overall survival (OS) and progression-free survival (PFS). RESULTS: Plasma tumor DNA detection was associated with shorter OS [hazard ratio (HR): 2.89, 95% confidence intervals (CI): 1.77-4.73, P ≤ 0.0001] and PFS (HR: 2.05; 95% CI: 1.36-3.11, P < 0.001). Using a multivariable model including plasma tumor DNA, patients who had a TP53, RB1 or PTEN gene alteration pre-treatment and at C2D1 had a significantly shorter OS than patients with no alteration at either time point (TP53: HR 7.13, 95% CI 2.37-21.47, P < 0.001; RB1: HR 6.24, 95% CI 1.97-19.73, P = 0.002; PTEN: HR 11.9, 95% CI 3.6-39.34, P < 0.001). Patients who were positive pre-treatment and converted to undetectable had no evidence of a difference in survival compared with those who were undetectable pre-treatment (P = 0.48, P = 0.43, P = 0.5, respectively). Progression samples harbored AR gain in all patients who had gain pre-treatment (9/49) and de novo AR somatic point mutations were detected in 8/49 patients. CONCLUSIONS: Plasma gene testing after one cycle treatment refines prognostication and could provide an early indication of treatment benefit.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Abiraterone Acetate , Biomarkers, Tumor/genetics , Gene Conversion , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Receptors, Androgen/genetics , Treatment Outcome
4.
Aust Dent J ; 65(3): 172-180, 2020 09.
Article in English | MEDLINE | ID: mdl-32562281

ABSTRACT

Temporomandibular disorder is a broad term encompassing pain and/or dysfunction of the masticatory musculature and the temporomandibular joints. Pain arising from a temporomandibular disorder is a common reason for seeking dental care. It is essential that dental practitioners are able to accurately diagnose and manage this condition. Identifying people at highest risk of developing a temporomandibular disorder and knowing which procedures are more likely to initiate or exacerbate a temporomandibular disorder, are important to reduce the likelihood of its acute and chronic presentation. The aim of this paper is to provide the dental practitioner with a clinical guideline for reference including practical tools to examine, diagnose and manage patients with temporomandibular disorder. In addition the risk profile of patients and procedures is explored to help minimize the occurrence of temporomandibular disorders and mitigate its symptoms. The scope of the dental practitioner in the management of acute and chronic temporomandibular disorders is presented, with guidance about when referral to a specialist is indicated.


Subject(s)
Dentists , Temporomandibular Joint Disorders , Facial Pain/diagnosis , Facial Pain/etiology , Facial Pain/therapy , Humans , Professional Role , Temporomandibular Joint , Temporomandibular Joint Disorders/diagnosis , Temporomandibular Joint Disorders/therapy
5.
J Neurosci Rural Pract ; 11(2): 329-332, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32367989

ABSTRACT

Background Neurological patients who are ventilator-dependent occupy scarce beds in the hospitals for prolonged periods of time. Most, if not all, can be discharged on home mechanical ventilation (HMV). However, due to lack of insurance and state support, it remains prohibitively expensive for the vast majority of those who require it most. Materials and Methods The authors discuss three patients admitted in the Department of Neurosurgery between January and August 2019, who were discharged on HMV after remaining on ventilator support for prolonged period in the hospital. Each patient was discharged with two units (one as standby) of AgVa home ventilator (AgVa Healthcare; New Delhi, India), one Ambu-bag, one pulse oximeter, and one backup power supply unit capable of supplying power to ventilator for a minimum of 24 hours. All the equipment were given free-of-cost through donations by hospital staffs and other donors. All patients were followed up telephonically from their homes and the incidence of complications, ventilator malfunction, and additional cost of HMV on the families were ascertained. Observation and Results Of the three patients, two were male and one female. Age ranged from 12 to 17 years. The duration of in-hospital ventilator support prior to discharge on HMV varied from 1 to 5 years. There was no insurance cover available for any of the patients with all expenses being "out of pocket." The equipment cost Indian Rupees (INR) 115,700 (USD 1,615: two units of AgVa home ventilator costing INR 100,000 [USD 1,396], one Ambu-bag costing INR 1,100 [USD 15], one pulse oximeter costing INR 1,600 [USD 22], and one backup power supply unit costing INR 13,000 [USD 182]). Discharge on HMV was planned on specific request from patients' families and informed consent was taken from all. All patients had tracheostomies. Mode of HMV was pressure support ventilation in all. Telephonic follow-up ranged from 1 to 7 months. The cost of disposables was INR 100 per month (USD 0.7) for all the patients. No complications occurred in any patient. There was no incidence of ventilator-associated pneumonia (VAP) or ventilator malfunction. Conclusions Availability of cost-effective indigenous ventilator like AgVa home has made HMV possible, even for poor patients with neurological diseases, and has the potential to improve quality of life, decrease VAP rates, and free up scarce ventilator beds in hospitals. Longer-term follow-up in larger number of patients will improve the data on safety and feasibility in developing countries like India.

6.
Childs Nerv Syst ; 35(8): 1423-1427, 2019 08.
Article in English | MEDLINE | ID: mdl-31073682

ABSTRACT

BACKGROUND: IgG4-related disease is an autoimmune process that presents with tumefactive lesions characterized by storiform fibrosis, a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, obliterative phlebitis, and often elevated serum IgG4 levels. Central nervous system IgG4-related disease is very rare and usually occurs in the form of hypertrophic pachymeningitis or hypophysitis. Presentation as a large solitary meningioma-like mass with overlying hyperostosis in a young adult has not been reported before. CASE SUMMARY: A 16-year-old male presented with focal seizures for 5 months. Imaging showed a large, extra-axial, and contrast-enhancing mass lesion in the left frontoparietal region with focal calvarial thickening. Histopathology revealed a fibrosclerotic lesion involving dura with a polymorphic infiltrate of plasma cells, mature lymphocytes, histiocytes, and occasional eosinophils. Immunohistochemical workup excluded the possibilities of meningioma, lymphoproliferative neoplasms, and histiocytic lesions. Majority of plasma cells were IgG4+ rendering a diagnosis of IgG4-related disease. Further serological and imaging workup did not reveal any evidence of systemic involvement. His serum IgG4 levels were normal. Considering a gross total resection of the lesion, no further treatment was given and the patient has been asymptomatic since. CONCLUSION: IgG4-related lesions of the CNS are under-recognized and accurate diagnosis, especially in those with isolated CNS disease and normal serum IgG4 levels, necessitates robust histopathological and laboratory workup to exclude mimics. They may occur as large dural masses with hyperostosis and differentiation from lymphoplasmacyte-rich meningiomas, in particular, can be challenging. While steroids are the mainstay of treatment in IgG4-related disease, surgical resection may be curative in solitary lesions presenting with compressive symptoms.


Subject(s)
Brain Diseases/pathology , Dura Mater/pathology , Immunoglobulin G4-Related Disease/pathology , Adolescent , Brain Diseases/diagnosis , Brain Diseases/surgery , Diagnosis, Differential , Dura Mater/surgery , Humans , Hyperostosis/etiology , Hyperostosis/pathology , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/surgery , Male , Meningeal Neoplasms/diagnosis , Meningioma/diagnosis , Meningitis/etiology , Meningitis/pathology , Skull/pathology
7.
Indian J Pathol Microbiol ; 61(3): 404-406, 2018.
Article in English | MEDLINE | ID: mdl-30004066

ABSTRACT

Paragangliomas (PGLs) are rare tumors of neural crest origin, with a malignancy rate of approximately 10% and a 5-year survival rate of <50%. We present a case of malignant PGL arising from the porta hepatis with metastasis to the portal lymph node and bilateral ovaries. PGLs arising from the porta hepatis are very rare. As per our knowledge, only three cases of hepatic duct PGL have been reported. It is important to detect it earlier because the treatment modality and prognosis of benign and malignant PGL differs and defines the prognosis of the patient.


Subject(s)
Neoplasm Metastasis/diagnosis , Neoplasms , Paraganglioma/diagnosis , Abdomen/diagnostic imaging , Adult , Female , Humans , Lymph Nodes/pathology , Ovary/pathology , Paraganglioma/genetics , Paraganglioma/pathology , Paraganglioma/surgery , Prognosis , Ultrasonography
8.
AJNR Am J Neuroradiol ; 39(4): 756-761, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29449283

ABSTRACT

BACKGROUND AND PURPOSE: Ultrasound is a standard technique to detect lymph node metastasis in papillary thyroid cancer. Cystic changes and microcalcifications are the most specific features of metastasis, but with low sensitivity. This prospective study compared the diagnostic accuracy of a predictive model for sonographic evaluation of lymph nodes relative to the radiologist's standard assessment in detecting papillary thyroid cancer metastasis in patients after thyroidectomy. MATERIALS AND METHODS: Cervical lymph node sonographic images were reported by a radiologist (R method) per standard practice. The same images were independently evaluated by another radiologist using a sonographic predictive model (M method). A test was considered positive for metastasis if the R or M method suggested lymph node biopsy. The result of lymph node biopsy or surgical pathology was used as the reference standard. We estimated relative true-positive fraction and relative false-positive fraction using log-linear models for correlated binary data for the M method compared with the R method. RESULTS: A total of 237 lymph nodes in 103 patients were evaluated. Our analysis of relative true-positive fraction and relative false-positive fraction included 54 nodes with pathologic results in which at least 1 method (R or M) was positive. The M method had a higher relative true-positive fraction of 1.46 (95% CI, 1.12-1.91; P = .006) and a lower relative false-positive fraction of 0.58 (95% CI, 0.36-0.92; P = .02) compared with the R method. CONCLUSIONS: The sonographic predictive model outperformed the standard assessment to detect lymph node metastasis in patients with papillary thyroid cancer and may reduce unnecessary biopsies.


Subject(s)
Lymphatic Metastasis/diagnostic imaging , Thyroid Cancer, Papillary/diagnostic imaging , Thyroid Cancer, Papillary/secondary , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Adult , Aged , Female , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Middle Aged , Prospective Studies , Ultrasonography/methods
9.
Heredity (Edinb) ; 120(2): 138-153, 2018 01.
Article in English | MEDLINE | ID: mdl-29225353

ABSTRACT

Invasive species exert a serious impact on native fauna and flora and have been the target of many eradication and management efforts worldwide. However, a lack of data on population structure and history, exacerbated by the recency of many species introductions, limits the efficiency with which such species can be kept at bay. In this study we generated a novel genome of high assembly quality and genotyped 4735 genome-wide single nucleotide polymorphic (SNP) markers from 78 individuals of an invasive population of the Javan Myna Acridotheres javanicus across the island of Singapore. We inferred limited population subdivision at a micro-geographic level, a genetic patch size (~13-14 km) indicative of a pronounced dispersal ability, and barely an increase in effective population size since introduction despite an increase of four to five orders of magnitude in actual population size, suggesting that low population-genetic diversity following a bottleneck has not impeded establishment success. Landscape genomic analyses identified urban features, such as low-rise neighborhoods, that constitute pronounced barriers to gene flow. Based on our data, we consider an approach targeting the complete eradication of Javan Mynas across Singapore to be unfeasible. Instead, a mixed approach of localized mitigation measures taking into account urban geographic features and planning policy may be the most promising avenue to reducing the adverse impacts of this urban pest. Our study demonstrates how genomic methods can directly inform the management and control of invasive species, even in geographically limited datasets with high gene flow rates.


Subject(s)
Gene Flow , Genetics, Population , Introduced Species , Passeriformes/genetics , Animals , Cities , Genomics , Polymorphism, Single Nucleotide , Population Density , Singapore , Spatial Analysis
10.
Epidemiol Infect ; 145(8): 1635-1641, 2017 06.
Article in English | MEDLINE | ID: mdl-28228179

ABSTRACT

Bats are known to be reservoirs of several medically important viruses including lyssaviruses. However, no systematic surveillance for bat rabies has been carried out in India, a canine rabies endemic country with a high burden of human rabies. Surveillance for rabies virus (RABV) infection in bats was therefore carried out in Nagaland, a north-eastern state in India at sites with intense human-bat interfaces during traditional bat harvests. Brain tissues and sera from bats were tested for evidence of infection due to RABV. Brain tissues were subjected to the fluorescent antibody test for detection of viral antigen and real-time reverse transcriptase PCR for presence of viral RNA. Bat sera were tested for the presence of rabies neutralizing antibodies by the rapid fluorescent focus inhibition test. None of the bat brains tested (n = 164) were positive for viral antigen or viral RNA. However, rabies neutralizing antibodies were detected in 4/78 (5·1%) bat sera tested, suggesting prior exposure to RABV or related lyssaviruses. The serological evidence of lyssaviral infection in Indian bats may have important implications in disease transmission and rabies control measures, and warrant extensive bat surveillance to better define the prevalence of lyssaviral infection in bats.


Subject(s)
Chiroptera , Lyssavirus/isolation & purification , Rhabdoviridae Infections/veterinary , Animals , India/epidemiology , Prevalence , Rabies/epidemiology , Rabies/veterinary , Rabies/virology , Rabies virus/isolation & purification , Rhabdoviridae Infections/epidemiology , Rhabdoviridae Infections/virology
12.
J Musculoskelet Neuronal Interact ; 16(2): 122-34, 2016 06 01.
Article in English | MEDLINE | ID: mdl-27282456

ABSTRACT

OBJECTIVES: Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. METHODS AND RESULTS: To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. CONCLUSIONS: These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma.


Subject(s)
Fracture Healing/immunology , Fractures, Open/pathology , Inflammation/pathology , Muscle, Skeletal/injuries , Tibial Fractures/pathology , Animals , Disease Models, Animal , Fractures, Open/immunology , Inflammation/immunology , Male , Muscle, Skeletal/immunology , Muscle, Skeletal/pathology , Rats , Rats, Inbred Lew , Real-Time Polymerase Chain Reaction , Tibial Fractures/immunology , X-Ray Microtomography
13.
Br J Dermatol ; 175(6): 1221-1231, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27145925

ABSTRACT

BACKGROUND: Activity of both c-Jun and cyclin D1 is deemed critical for melanoma cell proliferation. This functionality is corroborated by frequently elevated expression and activity of these proteins in human melanomas. Correspondingly, alleviating c-Jun and cyclin D1 function is vital to the success of antimelanoma therapeutics. OBJECTIVES: To understand the role of the c-Jun N-terminal kinase (JNK) signalling pathway in melanoma cell proliferation and survival. METHODS: The effect of JNK inhibitors SP600125 and JNK-IN-8 on the proliferation and survival of genetically highly representative human melanoma cell lines was studied in assays of proliferation and apoptosis. Changes in c-Jun and cyclin D1 protein and mRNA levels in response to JNK and mitogen-activated protein kinase kinase (MEK) inhibition were investigated through immunoblotting and quantitative reverse-transcription polymerase chain reaction. The effects of JNK and MEK inhibitors on cell-cycle distribution were assessed by flow cytometry. RESULTS: We demonstrate the requirement of JNK signalling in melanoma cell proliferation and survival. While JNK inhibition suppressed the expression and activity of c-Jun, it failed to suppress cyclin D1 levels. Consistently with its inability to downregulate cyclin D1, JNK inhibition failed to induce G1 arrest. In contrast, the blockade of MEK-extracellular signal-regulated kinase (ERK) signalling, although unable to suppress c-Jun activity and expression, paradoxically abated cyclin D1 levels and triggered G1 arrest. This previously unreported dual disconnect between JNK-cyclin D1 and ERK-c-Jun levels was confirmed by concomitant JNK and BRAF inhibition, which suppressed both c-Jun and cyclin D1 levels and exhibited a heightened antiproliferative response. CONCLUSIONS: Dual disjunction between JNK-cyclin D1 and ERK-c-Jun signalling forms the basis for further investigation of combined JNK and MAPK signalling blockade as a more effective therapeutic approach in human melanoma.


Subject(s)
JNK Mitogen-Activated Protein Kinases/metabolism , Melanoma/mortality , Skin Neoplasms/mortality , Anthracenes/pharmacology , Cell Proliferation , Cyclin D1/metabolism , Humans , Melanoma/pathology , Protein Kinase Inhibitors/pharmacology , Signal Transduction/physiology , Skin Neoplasms/pathology , Tumor Cells, Cultured
14.
Cell Death Dis ; 7: e2135, 2016 Mar 10.
Article in English | MEDLINE | ID: mdl-26962685

ABSTRACT

MITF (microphthalmia-associated transcription factor) is a frequently amplified lineage-specific oncogene in human melanoma, whose role in intrinsic drug resistance has not been systematically investigated. Utilizing chemical inhibitors for major signaling pathways/cellular processes, we witness MITF as an elicitor of intrinsic drug resistance. To search kinase(s) targets able to bypass MITF-conferred drug resistance, we employed a multi-kinase inhibitor-directed chemical proteomics-based differential affinity screen in human melanocytes carrying ectopic MITF overexpression. A subsequent methodical interrogation informed mitotic Ser/Thr kinase Aurora Kinase A (AURKA) as a crucial regulator of melanoma cell proliferation and migration, independent of the underlying molecular alterations, including TP53 functional status and MITF levels. Crucially, assessing the efficacy of investigational AURKA inhibitor MLN8237, we pre-emptively witness the procurement of a molecular program consistent with acquired drug resistance. This involved induction of multiple MAPK (mitogen-activated protein kinase) signaling pathway components and their downstream proliferation effectors (Cyclin D1 and c-JUN) and apoptotic regulators (MITF and Bcl-2). A concomitant AURKA/BRAF and AURKA/MEK targeting overcame MAPK signaling activation-associated resistance signature in BRAF- and NRAS-mutated melanomas, respectively, and elicited heightened anti-proliferative activity and apoptotic cell death. These findings reveal a previously unreported MAPK signaling-mediated mechanism of immediate resistance to AURKA inhibitors. These findings could bear significant implications for the application and the success of anti-AURKA approaches that have already entered phase-II clinical trials for human melanoma.


Subject(s)
Apoptosis , Aurora Kinase A/metabolism , Drug Resistance, Neoplasm , Melanoma/metabolism , Microphthalmia-Associated Transcription Factor/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism , Signal Transduction , Aurora Kinase A/antagonists & inhibitors , Aurora Kinase A/genetics , Azepines/pharmacology , Cell Line, Tumor , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Humans , Melanoma/drug therapy , Melanoma/genetics , Melanoma/pathology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Mitogen-Activated Protein Kinase Kinases/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Pyrimidines/pharmacology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
15.
Phys Chem Chem Phys ; 17(29): 19465-73, 2015 Jul 15.
Article in English | MEDLINE | ID: mdl-26146342

ABSTRACT

Herein, we report the synthesis, separation and characterisation of the E- and Z-isomers of dipyrrolyldiphenylethene to study their emission behaviour in the aggregation state and solid state. The E-isomer showed pronounced aggregation induced emission (AIE) whereas the Z-isomer showed crystallization induced emission (CIE). The present study explains that the emission behaviour (AIE/CIE) is dependent on the inter/intra molecular interactions between the molecules. The study also confirms that restriction of intramolecular rotation (RIR) is the main cause of AIE/CIE in olefinic luminogens Tetraphenylethylene (TPE) type systems rather than E/Z isomerisation.


Subject(s)
Pyrroles/chemistry , Stilbenes/chemistry , Crystallography, X-Ray , Models, Molecular , Molecular Structure , Pyrroles/chemical synthesis , Stereoisomerism , Stilbenes/chemical synthesis
16.
Ann Oncol ; 25(12): 2372-2378, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25281711

ABSTRACT

BACKGROUND: BRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in high-grade serous ovarian cancer, we sought to evaluate the utility of BRCA1 immunohistochemistry (IHC) in screening for BRCA1 loss by germline, somatic, and epigenetic mechanisms. PATIENTS AND METHODS: Patients with advanced high-grade serous ovarian cancer who had previously undergone germline BRCA1 testing were identified. Samples from each tumor were stained for BRCA1 and reviewed independently by two pathologists blinded to BRCA status. Tumors with abnormal BRCA1 IHC and wild-type germline testing underwent further evaluation for somatic BRCA1 mutations and promoter hypermethylation. McNemar's test was used to determine the association of BRCA1 IHC with germline BRCA1 mutations and BRCA1 loss through any mechanism. Kaplan-Meier methods were used to estimate overall survival (OS), and the log-rank test was used to assess differences between groups. RESULTS: Inter-rater reliability between the two pathologists on BRCA IHC interpretation was very good (kappa coefficient 0.865, P = 0.16; McNemar's test). BRCA1 IHC was abnormal in 36% (48/135) of cases. When compared with germline BRCA1 status, BRCA1 IHC had a high negative predictive value (95.4%) but a low positive predictive value (PPV, 52.1%). When accounting for promoter hypermethylation and somatic mutations as alternative methods of BRCA1 loss, the PPV rose to 87.5%. Five-year OS rate was 49.6% [95% confidence interval (CI) 26.3% to 69.3%] for patients with germline BRCA1 mutations, 50.4% (95% CI 27.5% to 69.5%) for germline wild-type BRCA1 and abnormal IHC, and 52.1% (95% CI 38.4% to 64.2%) for germline wild-type BRCA1 and normal IHC (P = 0.92). CONCLUSIONS: BRCA1 IHC interpretation was a highly reproducible and accurate modality for detecting germline, somatic, or epigenetic mechanisms of BRCA1 loss. These results support further development of BRCA1 IHC as a potential biomarker for BRCA1 loss in high-grade serous ovarian cancer.


Subject(s)
Epigenesis, Genetic , Genes, BRCA1 , Germ-Line Mutation , Ovarian Neoplasms/genetics , Adult , Aged , Aged, 80 and over , DNA Methylation , Female , Humans , Immunohistochemistry , Middle Aged , Promoter Regions, Genetic
17.
Am J Physiol Cell Physiol ; 305(7): C761-75, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-23885064

ABSTRACT

Volumetric muscle loss (VML) results in a large void deficient in the requisite materials for regeneration for which there is no definitive clinical standard of care. Autologous minced muscle grafts (MG), which contain the essential components for muscle regeneration, may embody an ideal tissue engineering therapy for VML. The purpose of this study was to determine if orthotopic transplantation of MG acutely after VML in the tibialis anterior muscle of male Lewis rats promotes functional tissue regeneration. Herein we report that over the first 16 wk postinjury, MG transplantation 1) promotes remarkable regeneration of innervated muscle fibers within the defect area (i.e., de novo muscle fiber regeneration); 2) reduced evidence of chronic injury in the remaining muscle mass compared with nonrepaired muscles following VML (i.e., transplantation attenuated chronically upregulated transforming growth factor-ß1 gene expression and the presence of centrally located nuclei in 30% of fibers observed in nonrepaired muscles); and 3) significantly improves net torque production (i.e., ∼55% of the functional deficit in nonrepaired muscles was restored). Additionally, voluntary wheel running was shown to reduce the heightened accumulation of extracellular matrix deposition observed within the regenerated tissue of MG-repaired sedentary rats 8 wk postinjury (collagen 1% area: sedentary vs. runner, ∼41 vs. 30%), which may have been the result of an augmented inflammatory response [i.e., M1 (CCR7) and M2 (CD163) macrophage expression was significantly greater in runner than sedentary MG-repaired muscles 2 wk postinjury]. These findings support further exploration of autologous minced MGs for the treatment of VML.


Subject(s)
Muscle Development , Muscle, Skeletal/transplantation , Muscular Atrophy/surgery , Regeneration , Tissue Engineering/methods , Animals , Biomarkers/metabolism , Biomechanical Phenomena , Disease Models, Animal , Extracellular Matrix/metabolism , Gene Expression Regulation , Male , Motor Activity , Muscle Contraction , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Atrophy/genetics , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Rats , Rats, Inbred Lew , Recovery of Function , Time Factors , Transforming Growth Factor beta1/metabolism , Transplantation, Autologous
18.
J Cutan Aesthet Surg ; 6(1): 4-11, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23723597

ABSTRACT

Cosmeceuticals are topical cosmetic-pharmaceutical hybrids that enhance the beauty through constituents that provide additional health-related benefit. Cosmeceuticals are commonly used for hyperpigmentation. These disorders are generally difficult to treat, hence the need for skin lightening agents including, cosmeceuticals. These agents selectively target hyperplastic melanocytes and inhibit key regulatory steps in melanin synthesis. With the recent safety concern regarding use of hydroquinone, the need for alternative natural, safe and efficacious skin lightening agents is becoming all the more necessary and the article attempts to look at other alternative cosmeceuticals available or maybe upcoming in the future. We carried out a PUBMED search using the following terms "cosmeceuticals, hyperpigmentation, skin lightening agents." We cited the use of various agents used for the treatment of hyperpigmentation, mainly melasma and post-inflammatory hyperpigmentation. We describe the safety and efficacy of these agents and their advantage over the conventional therapy.

19.
Br J Neurosurg ; 27(2): 181-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23298376

ABSTRACT

BACKGROUND: Vasospasm plays a major role in the morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). The preliminary studies suggest that statins protect against cerebral vasospasm. OBJECTIVE: The aim of the study was to determine the role of simvastatin in preventing clinical vasospasm and improving functional outcome in patients with aSAH. METHODS: All patients with aSAH admitted within 96 h of ictus were randomized to receive either Simvastatin or placebo - 80 mg/day for 14 days. Thirty eight patients were recruited in the study- 19 received Simvastatin and 19 placebo. All the patients underwent surgical clipping of the aneurysm. The primary outcome of the study was the development of clinical cerebral vasospasm. The secondary outcomes included Glasgow Outcome Score (GOS), Modified Rankin Scale (MRS) and Barthel Index Score (MBI) at follow-up at 1, 3 and 6 months. RESULTS: 16% of the patients in the simvastatin group had high Middle Cerebral Artery velocities (> 160 cm/sec) on transcranial Doppler on one or more than one day during the study duration as compared to 26% of the patients in the placebo group (p = 0.70). Neurological deterioration occurred in 26% and 42% of the patients in simvastatin group versus placebo group, respectively (p = 0.31). There was an improvement in the functional outcome in the simvastatin group at 1, 3 or 6 months in the follow-up; however, this difference was not statistically significant. CONCLUSIONS: There was benefit of simvastatin in terms of reduction in clinical vasospasm, mortality or improved functional outcome, however, this was not statistically significant.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Subarachnoid Hemorrhage/surgery , Vasospasm, Intracranial/prevention & control , Double-Blind Method , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Subarachnoid Hemorrhage/complications , Treatment Outcome , Vasospasm, Intracranial/complications
20.
Indian J Surg ; 75(Suppl 1): 388-90, 2013 Jun.
Article in English | MEDLINE | ID: mdl-24426625

ABSTRACT

An obturator hernia is a rare variety of abdominal hernia that presents with a confusing clinical picture. We present a case of 74-year-old woman who admitted to our hospital because of abdominal distention, abdominal pain, and vomiting for 3 days. Incarcerated intestinal obstruction due to the right-sided obturator hernia was found preoperatively. Perforation of the small bowel due to incarceration was noted during laparotomy. Bowel resection and anastomosis were done. She was recovered after 15 days of postoperative care. In this case report, we emphasize that preoperative high index of suspicion is required for diagnosis and treatment.

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