Publications by authors named "Charu Agarwal"

34 Publications

The effect and correlation of smoking with platelet indices, neutrophil lymphocyte ratio and platelet lymphocyte ratio.

Hematol Transfus Cell Ther 2020 Sep 13. Epub 2020 Sep 13.

IBS Ashwani Hospital, Faridabad, Haryana, India.

Introduction: Smoking is associated with the occurrence and progression of cardiovascular diseases, inflammatory disorders and malignancies.

Objective: To study the platelet indices, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in smokers and their correlation with smoking pack-years.

Method: A total of 110 smokers and 110 non-smokers were included. The smokers were grouped into three groups: mild (<5 pack-years), moderate (5-10 pack-years) and heavy (>10 pack-years). The platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were noted. The NLR and PLR were calculated and the statistical analysis was made using the Student's T-test, Analysis of Variance (ANOVA) and Spearman's correlation coefficient.

Results: The platelet count, PCT and PDW were significantly higher with mean values: 218.56 ± 121.31 vs 203.23 ± 80.35 (p-value = 0.038), 0.27 ± 0.10 vs 0.26 ± 0.10 (p-value = 0.041) and 12.54 ± 1.45 vs 11.99 ± 1.70 (p-value = 0.001) in smokers and non-smokers, respectively. The PLR differed significantly with mean values: 119.40 ± 84.81 in smokers and 181.99 ± 313.09 in non-smokers, with a p-value of 0.045. A significant positive correlation was found between pack-years of smoking and platelet count and PLR with the Pearson correlation coefficient of 0.250 and 0.198 and p-values, 0.008 and 0.037, respectively. The Platelet Count, PCT, MPV and PDW varied significantly between mild, moderate and heavy smoker groups, with p-values of 0.045, 0.010, 0.015 and 0.017, respectively.

Conclusion: The platelet indices and inflammatory markers NLR and PLR are derived from routine blood investigations, which are easily available and inexpensive. The monitoring of platelet indices, along with the PLR, can be used as early predictors of morbidity in smokers.
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http://dx.doi.org/10.1016/j.htct.2020.07.006DOI Listing
September 2020

Granular Cell Tumor Breast Masquerading as a Malignancy Cytologically: a Rare Case Presenting a Diagnostic Dilemma.

Indian J Surg Oncol 2020 Jun 26;11(2):321-324. Epub 2020 Mar 26.

Department of Surgery, ESIC Medical College, Faridabad, Haryana India.

Granular cell tumor (GCT) also known as Abrikossoff's tumor is an uncommon soft tissue tumor of neurogenic origin. GCT of the breast accounts for < 0.1% of breast tumors and 6% of all reported cases of granular cell tumor. Although GCT is a benign tumor, malignant GCT can be seen in 1% v of the cases. GCT of the breast is diagnostically challenging as it can imitate carcinoma clinically and radiologically but need to be differentiated from breast malignancy since they have totally different approach in treatment and prognosis. GCT has a great ability to mimic a variety of lesions from benign histiocytic to malignant epithelial/mesenchymal lesions, thereby presenting a diagnostic challenge to the practicing cytopathologist. We report a case of GCT of breast cytologically masquerading as a malignancy in a 45-year-old female. Although, fine needle aspiration (FNA) is a first-line diagnostic tool, the present case reemphasizes the role of histopathology as the gold standard for a definite diagnosis clubbed with ancillary techniques like immunohistochemistry and special stains.
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http://dx.doi.org/10.1007/s13193-020-01055-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260310PMC
June 2020

Evaluation of Tumor infiltrating lymphocytes in breast carcinoma and their correlation with molecular subtypes, tumor grade and stage.

Breast Dis 2020 ;39(2):61-69

Department of Community Medicine, ESIC Medical College, Faridabad, Haryana, India.

Background: Tumour infiltrating lymphocytes (TILs) exhibit the local immune response directed against tumor growth and metastasis. TILs have emerged as a tool to assess immune-reactivity in various malignancies including colon, ovary, lung, bladder, breast etc as well as independent marker of favourable prognosis in many tumors. TILs in breast cancer (BC) play a role in tumor response to therapy in the adjuvant and neoadjuvant settings, especially in triple-negative cancers.

Material & Methods: This cross sectional study comprised of 101cases of invasive breast carcinoma. For each case, a representative 5 μm H&E stained section was selected and the clinicopathological details were recorded. To establish the molecular subtype of breast cancer, immunohistochemistry for ER, PR and Her2neu was done. Both stromal (sTIL) and intratumoral (iTIL) TILs were assessed based on the recommendations of the International TIL Working Group (ITILWG).

Results: A statistically significant difference was observed in the mean sTIL as well as iTIL scores and tumor grade, size, molecular type and lymph node metastasis. A signification correlation was observed between stromal TIL and tumor grade, lymph node metastasis, molecular subtype and mitosis. Intratumoral TIL showed a significant correlation with tumor size, mitosis, tumor grade, distant metastasis, stage and lymph node metastasis. Moreover, stromal and intratumoral TIL showed a highly significant correlation with each other.

Conclusion: The ITILWG recommendations are reproducible and reliable for the evaluation of sTILs and iTILs. TILs, as evaluated on Hematoxylin and eosin (H&E) slides, has been shown in numerous studies now to be a reliable, reproducible, inexpensive and readily available marker of pre-existing antitumor immunity in breast cancer. We suggest that TILs should be evaluated for each case of breast carcinoma and should be part of histopathology report.
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http://dx.doi.org/10.3233/BD-200442DOI Listing
January 2020

A Clinicopathological Correlation of International Federation of Gynecology and Obstetrics's PALM-COEIN Classification of Abnormal Uterine Bleeding: Indian Scenario.

J Midlife Health 2019 Jul-Sep;10(3):147-152

Department of Community Medicine, ESIC Medical College, Faridabad, Haryana, India.

Background: Abnormal uterine bleeding (AUB) is a common problem affecting the women of reproductive age group and may also have a significant impact on their physical, social, and emotional aspects directly affecting their quality of life. The International Federation of Gynecology and Obstetrics (FIGO) devised a universally acceptable system of nomenclature and classification, namely PALM-COEIN classification of AUB in the year 2011. The objective of the present study was to analyze the structural (PALM) and functional (COEIN) component of FIGO system in the Indian scenario.

Materials And Methods: Three hundred patients with complaints of AUB were taken. A clinical diagnosis according to PALM-COEIN system was made after thorough history and clinical examination. Additional investigations if required were done, and endometrial sampling or hysterectomy was done whichever indicated. A histological diagnosis was made, and each case was allocated a category according to PALM-COEIN classification. A clinicopathological correlation was done in the hysterectomy cases for structural causes (PALM).

Results: Leiomyoma (30%) was the most common cause of AUB closely followed by adenomyosis (29.66%) overall. The clinicopathological correlation in hysterectomy cases was good with concordance rate of 85.03%. The concordance between clinical and pathological diagnoses for AUB-L, AUB-A, AUB-M, and AUB-A, L was statistically significant with < 05 in positive cases. However, additional finding of adenomyosis was diagnosed in 48.2% of the cases apart from primary clinical diagnosis.

Conclusion: A good clinicopathological correlation was seen in the cases when classified according to PALM-COEIN classification. The system also provides for consideration of multiple etiologies contributing toward AUB both clinically and histopathologically. However, histopathology remains the cornerstone in establishing the accurate diagnosis as the cases without specific symptoms can be missed clinically.
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http://dx.doi.org/10.4103/jmh.JMH_128_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767954PMC
October 2019

IAC standardized reporting of breast fine-needle aspiration cytology, Yokohama 2016: A critical appraisal over a 2 year period.

Breast Dis 2019 ;38(3-4):109-115

Department of Pathology, ESIC Medical College & Hospital, NIT 3, Faridabad, India.

Background: Breast cytology is a significant component of the "Triple approach" for pre-operative diagnosis of breast lumps, the other two being clinical assessment and radiological imaging. The role of Fine needle aspiration cytology (FNAC) as a first line investigation in diagnosing breast lesions is well documented, however histopathology is the gold standard. Cyto-histopathological correlation is of great relevance and also increases precision.AIMS \& OBJECTIVES:The present study was conducted with the aim to categorize breast lesions according to the latest standardized reporting system proposed by International academy of cytologists (IAC) in 2016. Evaluation of diagnostic accuracy, sensitivity and specificity of FNAC in diagnosing breast lesions and cyto-histopathological correlation was planned.

Materials And Methods: All FNAs of breast lesions over a period of 2 years were included in the study. The cases were grouped into five standardized categories proposed by the International academy of cytology: Category I (Insufficient material), Category II (Benign), Category III (Atypical, probably benign), Category IV (Suspicious, probably in situ or invasive) & Category V (Malignant) respectively. Specificity, sensitivity, diagnostic accuracy, negative and positive predictive value of FNAC were calculated and cyto-histopathological correlation assessed wherever possible.

Results: Out of 468 breast lesions reported on FNAC, the category wise distribution was - Category I, II, III, IV & V accounting for 23(4.9%), 342(73.07%), 7(1.5%), 11(2.35%) and 85(18.16%) respectively. Histopathology was performed in 331/468 cases with cyto histological concordance of 98.4% and a type agreement rate of 90.9%. The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy was 98.90%, 99.16%, 97.82%, 99.58% and 99.09% respectively.

Conclusion: FNAC is a simple, reliable, cost effective, first line diagnostic procedure for all breast lumps. In collaboration with physical examination and imaging studies (triple approach), FNAC is a highly sensitive diagnostic tool. Adopting a universally acceptable standardized reporting system for breast cytology can enhance the diagnostic accuracy of FNAC.
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http://dx.doi.org/10.3233/BD-190393DOI Listing
March 2020

Medullary carcinoma of thyroid mimicking Hurthle cell neoplasm on cytology: a diagnostic dilemma.

Diagn Cytopathol 2019 Sep 13;47(9):943-947. Epub 2019 Jun 13.

Department of Pathology and ENT, ESIC Medical College & Hospital, Faridabad, Haryana, India.

Medullary carcinoma of thyroid (MCT) is a neuroendocrine neoplasm derived from the parafollicular cells or C cells. It constitutes 5% of thyroid carcinomas. We present a case of 36-year-old female with a left lower lobe thyroid swelling since 8 to 9 years. Swelling was smooth, nontender, and moving with deglutition. Contrast-enhanced computed tomography (CECT) findings were suggestive of malignant thyroid nodule. Fine-needle aspiration cytology (FNAC) smears were highly cellular comprising predominantly Hurthle cells arranged in sheets, clusters, and follicles with few singly scattered cells. Background was hemorrhagic with scant colloids. An impression of follicular neoplasm or suspicious of follicular neoplasm was given with an additional note mentioning that the possibility of Hurthle cell neoplasm could not be excluded. Left hemithyroidectomy was done and sections showed a well-circumscribed tumor suggestive of MCT, which was confirmed based on immunohistochemistry for calcitonin and carcinoembryonic antigen. It is difficult to differentiate MCT from Hurthle cell neoplasm. There may be cellular pleomorphism within a single aspirate, but the presence of mixed cell population is a diagnostic pointer for MCT. In the presence of predominant Hurthle cell population, distinguishing these entities by cytomorphology alone is difficult. Hence, clinical findings and histopathology with immunohistochemistry are mandatory in such cases to reach to a correct diagnosis to ensure proper management.
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http://dx.doi.org/10.1002/dc.24220DOI Listing
September 2019

A correlation between platelet indices and preeclampsia.

Hematol Transfus Cell Ther 2019 Apr - Jun;41(2):129-133. Epub 2018 Dec 31.

Employees State Insurance Corporation Medical College, Faridabad, Haryana, India.

Background: Preeclampsia is one of the major health problems causing maternal morbidity and mortality, complicating 3-8% of pregnancies. It has been suggested that the alterations in the coagulation and fibrinolysis play a role in the pathogenesis of preeclampsia. The markers of platelet activation include platelet count, platelet distribution width, mean platelet volume and plateletcrit.

Study Design: It was a case-controlled study which included a total of 60 patients (30 cases and 30 controls). Blood samples were collected and the platelet indices - platelet count, plateletcrit, mean platelet volume and platelet distribution width - were evaluated using the Sysmex XN1000 and compared between the two groups.

Results: The MPV and PDW also showed a significant difference (p>0.05) between the two groups, with a significant positive correlation with increasing blood pressure (MPV - r=+0.6126, p<0.05 and PDW - r=+0.6441, p<0.05). The PC and PCT had lower values in the preeclampsia patients, however the difference between the two groups was not statistically significant.

Conclusion: The MPV and PDW showed a significant difference between the two groups and increasing values with increasing BP. However, the PC and PCT in our study did not show a significant correlation with preeclampsia. Thus, the platelet indices, mainly the MPV and PDW, which are economical and easily available, can be reliable in the prediction and early diagnosis of preeclampsia, as well as a marker for the severity of preeclampsia.
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http://dx.doi.org/10.1016/j.htct.2018.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517612PMC
December 2018

Basaloid Squamous Cell Carcinoma of Tonsil: an Unusual and Aggressive Variant.

Indian J Surg Oncol 2019 Mar 15;10(1):80-82. Epub 2018 Oct 15.

Department of Pathology, ESIC Medical College and Hospital, Faridabad, Haryana India.

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http://dx.doi.org/10.1007/s13193-018-0816-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414582PMC
March 2019

Association of coagulation profile with microvascular complications and glycemic control in type 2 diabetes mellitus - a study at a tertiary care center in Delhi.

Hematol Transfus Cell Ther 2019 Jan-Mar;41(1):31-36. Epub 2018 Jun 11.

Department of Community medicine, Employees State Insurance Corporation (ESIC) Medical College, Faridabad, Haryana, India.

Introduction: Type 2 diabetes mellitus, characterized by insulin resistance, corresponds to approximately 90% of cases of diabetes worldwide. Hyperglycemia in diabetes contributes to hyperfibrinogenemia and activates the coagulation cascade thereby producing atherothrombotic events.

Objectives: This study was designed to evaluate the coagulation profile (activated partial thromboplastin time, prothrombin time and fibrinogen) in Type 2 diabetes and to analyze correlations between body mass index, fasting blood glucose, glycated hemoglobin and duration of diabetes with coagulation parameters.

Methods: This study included 60 type 2 diabetics and 30 controls. Diabetic patients were grouped in two sets based on the presence or absence of microvascular complications. The demographic profile and clinical details were recorded. Fasting blood glucose, glycated hemoglobin, coagulation parameters such as prothrombin time, activated partial thromboplastin time and fibrinogen along with other biochemical parameters were investigated.

Results: There were statistically significant differences in the coagulation parameters between the two groups of diabetics (with and without complications). The present study also found significant correlations between age and the duration of diabetes with and without complications and coagulation parameters such as the activated partial thromboplastin time, which was found to be significantly lower, and fibrinogen, which was found to be significantly higher in subjects with complications compared to subjects without complications.

Conclusion: Clinical tests for prothrombin time, activated partial thromboplastin time and fibrinogen are relatively inexpensive and readily available. The present study shows that shortened prothrombin time, activated partial thromboplastin time and increased fibrinogen levels might be useful hemostatic markers in diabetic patients, especially in those at high-risk for thrombotic complications.
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http://dx.doi.org/10.1016/j.htct.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371197PMC
June 2018

Masood's and Modified Masood's Scoring Index: An Evaluation of Fine Needle Aspiration Cytology of Breast Lesions with Histopathological Correlation.

Acta Cytol 2019 13;63(3):233-239. Epub 2019 Feb 13.

Department of Pathology, ESIC Medical College, Faridabad, India.

Objective: As fine needle aspiration cytology (FNAC) is the primary tool for evaluation of breast lesions, it is essential to segregate lesions with low and high risk of malignancy. To address this, Masood proposed a cytological scoring system for categorization, Masood's Scoring Index (MSI), which was modified later (Modified Masood's Scoring Index [MMSI]). This study analyses the effectiveness of MMSI over MSI and assesses the concordance between cytological scoring and histopathology.

Study Design: All breast FNACs over a period of 2 years were categorized based on MSI and MMSI by 2 reviewers independently. The agreement rate along with specificity, sensitivity, positive predictive value, negative predictive value and diagnostic accuracy were calculated. Correlation and concordance analyses between cytological and histopathological categories were conducted.

Results And Discussion: Out of 415 cases of breast FNACs, histopathology was available for 310 for which MSI and MMSI were evaluated. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 95, 100, 100, 97.6 and 98.3%, respectively. The difference between the concordance rate of MSI and of MMSI for various cytological categories was found to be statistically significant.

Conclusion: MMSI has a better concordance with histopathological diagnosis than MSI. MMSI can serve as a uniform standardized scoring system for breast cytology for better categorization of proliferative breast diseases.
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http://dx.doi.org/10.1159/000496139DOI Listing
June 2019

Are all Granulomatous Mastitis Cases Tuberculous?: A Study on the Role of Cytology in Evaluation of Granulomatous Mastitis.

Turk Patoloji Derg 2019 ;35(2):128-133

Department of Pathology, ESIC Medical College and Hospital, NIT 3, FARIDABAD, INDIA.

Objective: Granulomatous mastitis is a rare inflammatory condition of the breast clinically mimicking breast carcinoma and pyogenic abscess, thereby creating a diagnostic dilemma. Tuberculous mastitis is a rare clinical entity accounting for approximately 3% of all mammary lesions. All cases of granulomatous mastitis diagnosed cytologically over a period of 3 years were evaluated to ascertain the cases with tuberculous etiology.

Material And Method: Fine needle aspiration cytology of the breast lump was performed and all the cytological parameters were evaluated. Wherever histopathology was available, the diagnosis was confirmed on Hematoxylin & Eosin stained sections and the Ziehl Neelsen (ZN) stain was applied.

Results: A total of 10 cases of granulomatous mastitis were diagnosed on cytology during the 3-year period. On cytological smears, four cases showed presence of ill-formed granulomas and one case had scattered epithelioid histiocytes; however, the rest of the cases had well-formed granulomas. Finally, four out of ten cases were labeled as tuberculous mastitis based on the ZN stain/Tuberculosis-Polymerase chain reaction (TB-PCR) and the other six cases were granulomatous mastitis.

Conclusion: Cytology plays a significant role in the diagnosis of granulomatous mastitis. This study re-emphasizes the role of the cytopathologist in the accurate and early diagnosis of these lesions so that unnecessary surgery can be avoided, and also highlights the fact that all granulomatous mastitis cases are not tuberculous.
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http://dx.doi.org/10.5146/tjpath.2018.01442DOI Listing
September 2019

A critical appraisal of the Milan system for reporting salivary gland cytology (MSRSGC) with histological correlation over a 3-year period: Indian scenario.

Diagn Cytopathol 2019 May 12;47(5):382-388. Epub 2018 Nov 12.

Department of Pathology, ESIC Medical College, Faridabad, Haryana, India.

Background: Fine needle aspiration cytology (FNAC) is the first line investigation for pre-operative diagnosis of salivary gland lesions, but due to its inherent limitations remains a challenge for the cytopathologists. The recently proposed international risk stratification scheme, the Milan System for Reporting Salivary Gland Cytology (MSRSGC) aims to promote and standardise the communication between cytopathologist and clinician thereby improving patient care.

Methods: A retrospective study of all salivary gland cytology cases was performed over a 3-year period, reviewed by pathologists and categorised into 1 of the 6 diagnostic categories according to MSRSGC, namely, non-diagnostic, non-neoplastic, atypia of undetermined significance (AUS), benign neoplasm, and salivary gland neoplasm of undetermined significance (SUMP), suspicious for malignancy (SFM), and malignant neoplasm. Cyto- histological correlation was done wherever possible. Risk of malignancy (ROM) was calculated for each diagnostic category.

Results: Out of a total of 150 salivary FNAC cases, histopathology was available for 64 cases. The sensitivity of FNAC was 81.8%, specificity was 100% while the diagnostic accuracy was 96.9%. The positive and negative predictive values were 100% and 96.4% respectively. The ROM for non-diagnostic, non-neoplastic, AUS, benign neoplasm, SUMP, SFM, and malignant categories were 0%, 10%, 50%, 2.5%, 50%, 100%, and 100% respectively.

Conclusion: MSRSGC fulfils the critical need for a uniform, internationally acceptable reporting system with ROM specified for each category. However, large scale multi centre studies need to be conducted before its reliability and validity is proven.
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http://dx.doi.org/10.1002/dc.24109DOI Listing
May 2019

Encapsulated Follicular Variant of Papillary Thyroid Carcinoma Arising in a Follicular Adenoma: a Diagnostic Dilemma.

Indian J Surg Oncol 2018 Sep 13;9(3):414-417. Epub 2018 Aug 13.

2Department of ENT, ESIC Medical College, Faridabad, Haryana India.

Papillary thyroid carcinoma (PTC) arising within follicular adenoma is a rare histological subset of papillary carcinoma. A 24-year-old female (euthyroid and asymptomatic) presented with a solitary mass in the right lobe of thyroid for 2 years. Fine-needle aspiration cytology (FNAC) suggested features of hyperplasia of thyroid. Hemithyroidectomy was performed. Histopathological examination revealed two distinct areas and was reported as encapsulated variant of papillary carcinoma along with follicular adenoma. Papillary carcinoma was confirmed by positive immunohistochemistry for HBME-1. CT head and neck region ruled out metastasis and the patient was kept on follow-up. There have been reports of medullary and papillary carcinomas occurring together; however, there is a paucity of literature on co-existing follicular neoplasm and papillary carcinoma. We hereby report a rare case of follicular variant of papillary carcinoma arising within follicular adenoma of the thyroid.
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http://dx.doi.org/10.1007/s13193-018-0801-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154354PMC
September 2018

Intracranial chondrosarcoma: Series of three cases with varied and unusual presentations.

Indian J Pathol Microbiol 2018 Apr-Jun;61(2):294-296

Department of Pathology, PGIMER Dr. RML Hospital, New Delhi, India.

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http://dx.doi.org/10.4103/IJPM.IJPM_179_17DOI Listing
October 2018

Solitary nodular lesion on forehead in a 56-year-old woman.

Indian J Dermatol Venereol Leprol 2019 Sep-Oct;85(5):555-558

Department of Pathology, ESIC Medical College, Faridabad, Haryana, India.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_1141_16DOI Listing
February 2020

Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

J Food Sci 2018 Mar 13;83(3):700-710. Epub 2018 Feb 13.

Inst. of Wood Based Products and Technologies, Univ. of Sopron, Bajcsy-Zsilinszky u. 4, Sopron 9400, Hungary.

Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids. The influence of 3 independent factors (time, input power, and methanol concentration) was evaluated on the extraction of total phenols (TPC), flavonoids (TF), ferric reducing ability of plasma (FRAP) and the overall yield. A face-centered central composite design was used for statistical modelling of the response data, followed by regression and analysis of variance in order to determine the significance of the model and factors. Both the solvent composition and the time significantly affected the extraction while the sonication power had no significant impact on the responses. The response predictions obtained at optimum extraction conditions of 15 min time, 130 W power, and 80% methanol were 314.822 mg GAE/g DW of TPC, 28.173 mg QE/g DW of TF, 18.79 mM AAE/g DW of FRAP, and 10.86% of yield. A good correlation was observed between the predicted and experimental values of the responses, which validated the mathematical model. On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses. Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis.

Practical Application: Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control.
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http://dx.doi.org/10.1111/1750-3841.14075DOI Listing
March 2018

Apocrine carcinoma of breast: A rare entity posing cytological challenge.

Diagn Cytopathol 2017 Dec 21;45(12):1156-1158. Epub 2017 Sep 21.

Department of Surgery, ESIC Medical College, Faridabad, Haryana, India.

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http://dx.doi.org/10.1002/dc.23819DOI Listing
December 2017

A rare tumor of salivary gland: Diagnostic Dilemma on fine needle aspiration cytology.

J Cytol 2017 Apr-Jun;34(2):107-109

Department of Pathology, PGIMER, Dr. RML Hospital, New Delhi, India.

Salivary gland cytopathology is a diagnostically challenging area with overlapping cytomorphological features between benign, malignant, and metastatic tumors. We report the case of 45-year-old male who presented with two swellings in right retroauricular and infraauricular region along with a palpable single right cervical lymph node. On ultrasonography of the neck, a possibility of malignant lesion was given. Contrast enhanced computed tomography of the head showed a large well-defined space occupying lesion in right temporooccipital region eroding the skull bone with both extra and intracranial extension. Fine needle aspiration was performed from both swellings and cervical lymph node. Based on cytological features and clinicoradiological examination, a possibility of metastasis from epithelial malignancy (adenocarcinoma) was suggested. The retroauricular region swelling was excised, and a diagnosis of salivary duct carcinoma was given on histopathology. In this article, we discuss the diverse presentation, cytomorphological features, and differential diagnosis of this rare salivary gland tumor.
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http://dx.doi.org/10.4103/0970-9371.203576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398016PMC
May 2017

Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology.

Diagn Cytopathol 2017 Jul 6;45(7):651-654. Epub 2017 Mar 6.

Department of Pathology, ESIC Medical College, Faridabad, Haryana, India.

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651-654. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/dc.23704DOI Listing
July 2017

Coincidental Finding of Beta Thalassaemia Minor in a Patient of Lacquer Thinner Poisoning Presenting as Methaemoglobinemia.

J Clin Diagn Res 2016 Nov 1;10(11):ED08-ED09. Epub 2016 Nov 1.

Associate Professor, Department of Pathology, PGIMER Dr RML Hospital , New Delhi, India .

Lacquer thinner, commonly used for removing household paints, is known to contain various aromatic hydrocarbons and naphtha; if ingested, may cause methaemoglobinemia. We report a case of 13-year-old girl who presented with episodes of vomiting, abdominal pain and numbness of limbs. Peripheral blood smear showed few fragmented erythrocytes and 10-12 nucleated red blood cells /100 white blood cells. Reticulocyte count was 15% with presence of Heinz bodies. There was a history of accidental ingestion of lacquer paint thinner. Levels of methaemoglobin were very high along with raised HbA2 levels. An impression of haemolytic anaemia, due to lacquer thinner paint poisoning, with methaemoglobinemia was given. Incidentally High Performance Liquid Chromatography (HPLC) revealed increased HbA2 levels i.e., heterozygous inheritance of beta thalassaemia minor. Patient responded well to methylene blue. Blood transfusion was performed and symptomatic treatment was given.
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http://dx.doi.org/10.7860/JCDR/2016/20625.8847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198333PMC
November 2016

Parathyroid lesions: Difficult diagnosis on cytology.

Diagn Cytopathol 2016 Aug 1;44(8):704-9. Epub 2016 Jun 1.

Department of Pathology, PGIMER, Dr. RML Hospital, New Delhi, India.

Cytology of parathyroid lesion (PL) is often confused with that of thyroid lesions. Differentiation between thyroid and PL is very difficult on cytomorphology because of their similar features and close anatomical proximity. Three cases of PLs reported on cytology in last one year were retrieved from archives of cytology department. Their cytomorphological details were studied and were correlated with the available biochemical parameters. Histopathology was available in two cases. Radiological assistance and parathyroid hormone (PTH) assessment in our cases formed the basis of diagnosing PLs on cytology. We discuss the differential diagnosis and pitfalls in cytological diagnosis of PLs. However, histopathology remains the gold standard for diagnosis. Interpretation of PLs on cytology remains problematic due to its rarity and limited available literature. The cytomorphology combined with clinical and biochemical data supported by histopathology are necessary to improve the diagnostic sensitivity of PLs. Diagn. Cytopathol. 2016;44:704-709. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/dc.23508DOI Listing
August 2016

Trichoepithelioma and Basal Cell Carcinoma with Squamous Differentiation: Is it Causal or Coincidental?

Indian J Dermatol 2015 Jul-Aug;60(4):394-6

Department of Dermatology, PGIMER, Dr. RML Hospital, New Delhi, India.

Trichoepitheliomas (TEs) are benign cutaneous tumors that occur either as solitary non-familial or multiple familial. We report a case of multiple familial trichoepithelioma (MFT) in a 55-year-old female patient and her son who came with complaints of single ulcerated mass involving the left nasolabial fold and cheek. She had multiple papules and nodules all over the face and neck since 25 years. Histopathological examination of an ulcerated lesion revealed features of basal cell carcinoma (BCC) with squamous differentiation, which was confirmed by immunohistochemistry. A skin biopsy obtained from the papule on neck showed features of TE. However, whether BCC developed independently or by transformation from TE was uncertain. Her 36-year-old son presented with similar lesions on the face and a skin biopsy showed features of TE. Though malignant transformation of TE is quite rare, awareness of the potential for evolution of carcinoma in patients with MFT is important for management of these patients.
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http://dx.doi.org/10.4103/0019-5154.160494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533542PMC
August 2015

Effect of addition of 2% chlorhexidine or 10% doxycycline on antimicrobial activity of biodentine.

J Conserv Dent 2014 May;17(3):271-5

Department of Conservative Dentistry and Endodontics, Meerut, Uttar Pradesh, India.

Aim: The purpose of this in vitro study was to determine whether the addition of 2% chlorhexidine gluconate or 10% doxycycline would enhance the antimicrobial activity of Biodentine against Staphylococcus aureus (ATCC-25923), Enterococcus faecalis (ATCC-29212), Candida albicans (ATCC-90028), and Streptococcus mutans (MTCC-497).

Materials And Methods: Three wells of 4 mm diameter and 4 mm depth on each plate were prepared on the agar medium with standardized suspensions of each microorganism. Biodentine powder mixed with 2% chlorhexidine (0.06 g) or 10% doxycycline (0.30 g) in its liquid or liquid alone was placed to fill each well. Plates were incubated at 37°C as required for microbial growth. A blinded, independent observer measured zones of inhibition. The data were analyzed using independent "t" test to compare the differences among the three cement preparations for different micro-organisms.

Results: All Biodentine samples inhibited microbial growth. The highest mean diameters of zone of inhibition for all the micro-organisms were found around Biodentine/chlorhexidine (13.417) followed by Biodentine alone (12.236) and Biodentine/doxycycline (11.25).

Conclusion: In conclusion, adding 2% chlorhexidine gluconate in liquid of Biodentine enhanced the antimicrobial activity of Biodentine against all the tested micro-organisms except Candida albicans, while addition of 10% doxycycline decreased the antimicrobial activity of Biodentine. The differences were significant statistically (P < 0.05).
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http://dx.doi.org/10.4103/0972-0707.131795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056401PMC
May 2014

Ustilago maydis phosphodiesterases play a role in the dimorphic switch and in pathogenicity.

Microbiology (Reading) 2013 May 8;159(Pt 5):857-868. Epub 2013 Mar 8.

Department of Biology, Program on Disease Evolution, University of Louisville, Louisville, KY 40208, USA.

Components of the cAMP (cyclic AMP) signalling cascades are conserved from fungi to humans, and are particularly important for fungal dimorphism and pathogenicity. Previous work has described two phosphodiesterases, UmPde1 and UmPde2, in Ustilago maydis which show strong phosphodiesterase activity. We further characterized the biological function(s) of these phosphodiesterases in U. maydis. Specifically, we examined their possible role(s) in regulation of the cAMP-dependent protein kinase A (PKA) pathway and their roles in filamentous growth and pathogenicity. We found that UmPde1, which shares 35 % similarity with Cryptococcus neoformans Pde1, also displays functional homology with this enzyme. UmPde1 complements the capsule-formation defect of C. neoformans strains deleted for Pde1. In U. maydis, the cell morphology of the umpde1 deletion mutant resembled the multiple budding phenotypes seen with the ubc1 mutant, which lacks the regulatory subunit of PKA. Interestingly, on low-ammonium medium, umpde2 deletion strains showed a reduction in filamentation that was comparable to that of ubc1 deletion strains; however, umpde1 deletion strains showed normal filamentation on low-ammonium medium. Furthermore, both the ubc1 deletion strain in which the PKA pathway was constitutively active and the umpde1 deletion strains were significantly reduced in pathogenicity, while the umpde2 deletion strains showed a trend for reduced pathogenicity compared with wild-type strains. These data support a role for the phosphodiesterases UmPde1 and UmPde2 in regulating the U. maydis cAMP-dependent PKA pathway through modulation of cAMP levels, thus affecting dimorphic growth and pathogenicity.
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http://dx.doi.org/10.1099/mic.0.061234-0DOI Listing
May 2013

Haplo-insufficiency for different genes differentially reduces pathogenicity and virulence in a fungal phytopathogen.

Fungal Genet Biol 2012 Jan 28;49(1):21-9. Epub 2011 Nov 28.

Department of Biology, Program on Disease Evolution, University of Louisville, Louisville, KY 40208, USA.

The main determinant of pathogenicity in Ustilago maydis is the b-mating locus, where establishment of heterozygosity is sufficient to cause galls/tumors on maize plants. However, matings between haploids where one partner contains a mutation, in e.g., the smu1 gene, encoding a Ste20-like PAK kinase, often show reduced mating and pathogenicity compared to wild type. Here we show that similarly, diploids lacking one copy of smu1, are reduced in production of aerial hyphae, but do not show significantly-reduced virulence. Haplo-insufficiency was also observed for additional genes. UmPde1 is a cyclic phosphodiesterase involved in cAMP turnover as part of the cAMP-dependent PKA pathway. Hsl7 plays a role in cell length and in the filamentous response to low ammonium in haploid cells. Diploids deleted for one copy of either the pde1 or hsl7 genes had reduced or increased production of aerial hyphae, respectively, and both were severely impaired in virulence compared to wild type diploids. rho1 and pdc1 are two genes essential for cell viability in haploids. These genes also displayed haplo-insufficiency for pathogenesis. rho1/Δrho1 diploid cells were defective in pheromone production and detection, aerial hyphae induction, and were avirulent. In contrast, pdc1/Δpdc1 diploid cells only failed to produce tumors when applied to maize whorls. We predict the haplo-insufficiency of most of these signaling components is due to stoichiometric imbalance of the respective gene products with their interacting partners, thereby impairing virulence-induction mechanism(s). Further investigation of the bases for such haplo-insufficiency as well as of additional genes displaying this phenotype will provide important insights into fundamental aspects of development in this organism as well as inter-nuclear communication and genetic control.
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http://dx.doi.org/10.1016/j.fgb.2011.11.007DOI Listing
January 2012

High-performance liquid chromatographic enantioseparation of (R,S)-fluoxetine using Marfey's reagent and (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester as chiral derivatizing reagents along with direct thin-layer chromatographic resolution and isolation of enantiomers using L-tartaric acid as mobile phase additive.

Biomed Chromatogr 2010 Nov;24(11):1152-8

Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India.

Chiral assay of enantiomers of fluoxetine was achieved in pharmaceutical formulations using direct and indirect methods. L-tartaric acid was used as a mobile phase additive in thin-layer chromatography; the enantiomers were separated and isolated and were used to determine the elution order in HPLC. (R,S)-flouxetine was derivatized with (S)-N-(4-nitrophenoxycarbonyl)phenylalanine methoxyethyl ester [(S)-NIFE], Marfey's reagent and 1-fluoro-2,4-dinitrophenyl-L-methionine amide (FDNP-L-Met-NH₂. The diastereomers were separated using RP-HPLC. The effect of flow rate and TFA concentration on resolution was studied. The diastereomers obtained by derivatization with FDNP-L-Met-NH₂ were also separated by RP-TLC.
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http://dx.doi.org/10.1002/bmc.1421DOI Listing
November 2010

Reversed-phase liquid chromatographic resolution of diastereomers of protein and non-protein amino acids prepared with newly synthesized chiral derivatizing reagents based on cyanuric chloride.

Amino Acids 2011 Feb 18;40(2):403-9. Epub 2010 Jun 18.

Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667, India.

Two new chiral monochloro-s-triazines (MCT) were synthesized [viz N-(4-chloro-6-piperidinyl-[1,3,5]-triazine-2-yl)-L-leucine amide and N-(4-chloro-6-piperidinyl-[1,3,5]-triazine-2-yl)-L-leucine) (CDR 1 and 2, respectively)] by the nucleophilic displacement of chlorine atoms in s-triazine moiety. One of the Cl atoms was replaced with piperidine, and the second Cl atom in the 6-piperidinyl derivative was replaced with amino acid amide (viz L-Leu-NH(2)) and amino acid (L-Leu). These reagents were characterized and used as CDRs for chiral separation of protein and non-protein amino acids, and were separated on a reversed-phase C(18) column. The reaction conditions were optimized for the synthesis of diastereomers using one MCT reagent. The separation method was validated for limit of detection, linearity, accuracy, precision, and recovery.
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http://dx.doi.org/10.1007/s00726-010-0650-zDOI Listing
February 2011

Application of (S)-N-(4-Nitrophenoxycarbonyl) phenylalanine methoxyethyl ester as a chiral derivatizing reagent for reversed-phase high-performance liquid chromatographic separation of diastereomers of amino alcohols, non-protein amino acids, and PenA.

Amino Acids 2010 Jul 28;39(2):549-54. Epub 2010 Jan 28.

Department of Chemistry, Indian Institute of Technology, Roorkee, 247667, India.

Indirect enantioresolution of 15 primary and secondary amino group containing compounds (amino alcohols, non-protein amino acids, PenA) was done using the reagent (S)-N-(4-Nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE] by reversed-phase high-performance liquid chromatography. The diastereomeric derivatives were analyzed under reversed-phase conditions using linear gradient. The detection was at 205 nm and sharp peaks were obtained. The reagent used is comparatively economic than the other derivatizing reagents. Method validation was also done.
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http://dx.doi.org/10.1007/s00726-010-0472-zDOI Listing
July 2010

Two phosphodiesterases from ustilago maydis share structural and biochemical properties with non-fungal phosphodiesterases.

Front Microbiol 2010 29;1:127. Epub 2010 Nov 29.

Department of Biology, Program on Disease Evolution, University of Louisville Louisville, KY, USA.

The dependence of Protein Kinase A (PKA) activity on cAMP levels is an important facet of the dimorphic switch between budding and filamentous growth as well as for pathogenicity in some fungi. To better understand these processes in the pathogenic fungus Ustilago maydis, we characterized the structure and biochemical functions of two phosphodiesterase (PDE) genes. Phosphodiesterases are enzymes involved in cAMP turnover and thus, contribute to the regulation of the cAMP-PKA signaling pathway. Two predicted homologs of PDEs were identified in the genome of U. maydis and hypothesized to be involved in cAMP turnover, thus regulating activity of the PKA catalytic subunit. Both umpde1 and umpde2 genes contain domains associated with phosphodiesterase activity predicted by InterPro analysis. Biochemical characterization of recombinantly produced UmPde1 (U. maydis Phosphodiesterase I) and UmPde2 demonstrated that both enzymes have phosphodiesterase activity in vitro, yet neither was inhibited by the phosphodiesterase inhibitor IBMX. Moreover, UmPde1 is specific for cAMP, while UmPde2 has broader substrate specificity, utilizing cAMP and cGMP as substrates. In addition, UmPde2 was also found to have nucleotide phosphatase activity that was higher with GMP compared to AMP. These results demonstrate that UmPde1 is a bona fide phosphodiesterase, while UmPde2 has more general activity as a cyclic nucleotide phosphodiesterase and/or GMP/AMP phosphatase. Thus, UmPde1 and UmPde2 likely have important roles in cell morphology and development and share some characteristics with a variety of non-fungal phosphodiesterases.
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http://dx.doi.org/10.3389/fmicb.2010.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109409PMC
July 2011