A study on thyroid nodules: diagnostic correlation between fine needle aspiration cytology and histopathology

This study evaluated the effectiveness of fine needle aspiration of thyroid nodules to reliably diagnose thyroid malignancy, using histopathology as the 'gold standard'. Out of 126 patients, 106 underwent surgery. The sensitivity, specificity and positive predictive value of fine needle aspiraton cytology to diagnose a papillary carcinoma in this study were 80.7%, 96.5% and 87.0% respectively. The accuracy of fine needle aspiraton cytylogy was 80.9%. Six cases that were benign by fine needle aspiraton cytology were confirmed to have malignant lesion by histopathological examination. High resolution ultrasonography could be useful in these situations for considering surgery.     

Antithyroid drug carbimazole and its analogues: synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine

Synthesis and biological activity of the antithyroid drug carbimazole (CBZ) and its analogues are described. The introduction of an ethoxycarbonyl group in methimazole and its selenium analogue not only prevents the oxidation to the corresponding disulfide and diselenide but also reduces the zwitterionic character. A structure-activity correlation in a series of CBZ analogues suggests that the presence of a methyl substituent in CBZ and related compounds is important for their antithyroid activity.     

Lipoblastoma presenting as a rapidly growing paravertebral mass and masquerading as myxoid liposarcoma on fine needle aspiration cytology

Lipoblastoma is a peculiar variant of lipoma occurring almost exclusively during infancy and early childhood. It is found most commonly in the upper and lower extremities; less common sites are head and neck, trunk, mediastinum, and retroperitoneum. It has a greater predilection for boys and commonly presents as a slowly growing soft‐tissue mass. We present here the case of a five‐ year old female child with a lipoblastoma presenting as a paravertebral mass in the right lower back which progressed rapidly in the previous six months causing diagnostic difficulty on fine needle aspiration cytology. Diagn. Cytopathol. 2016;44:426–429. © 2016 Wiley Periodicals, Inc.     

Cutaneous nocardiosis with discharging sinus clinically mimicking tuberculosis diagnosed by cytology

Nocardiosis is primarily a pulmonary infection commonly seen in immunocompromised individuals. However, lymphocutaneous nocardiosis is observed in immunocompetent individuals often after trauma. The clinical and cytomorphological features of lymphocutaneous nocardiosis closely mimic the most common infections in India such as tuberculosis and mycetoma (very common cutaneous infection with discharging sinus). As it is crucial to differentiate nocardiosis from tuberculosis, to avoid unnecessary antitubercular treatment, special stains like modified Ziehl–Neelsen stain and Gram stain can be employed to differentiate the morphology of Nocardia from tuberculosis. Fine‐needle cytology from these cutaneous lesions helps in yielding adequate material for rapid and accurate diagnosis of immediate specific antibiotic treatment. We report a rare case that presented with clinical diagnosis of tuberculosis but turned out to be nocardiosis on cytomorphology with simple and most feasible fine‐needle aspiration method of tissue diagnosis and scrape cytology.     

New Stability-Indicating RP-HPLC Method for Determination of Diclofenac Potassium and Metaxalone from their Combined Dosage Form

A simple, precise and accurate isocratic RP-HPLC stability-indicating assay method has been developed to determine diclofenac potassium and metaxalone in their combined dosage forms. Isocratic separation was achieved on a Hibar-C₁₈, Lichrosphere-100^® (250 mm × 4.6 mm i.d., particle size 5 μm) column at room temperature in isocratic mode, the mobile phase consists of methanol: water (80:20, v/v) at a flow rate of 1.0 ml/min, the injection volume was 20 μl and UV detection was carried out at 280nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and system suitability. The method was linear in the drug concentration range of 2.5–30 μg/ml and 20–240 μg/ml for diclofenac potassium and metaxalone, respectively. The precision (RSD) of six samples was 0.83 and 0.93% for repeatability, and the intermediate precision (RSD) among six-sample preparation was 1.63 and 0.49% for diclofenac potassium and metaxalone, respectively. The mean recoveries were between 100.99–102.58% and 99.97–100.01% for diclofenac potassium and metaxalone, respectively. The proposed method can be used successfully for routine analysis of the drug in bulk and combined pharmaceutical dosage forms.     

Open source drug discovery--a new paradigm of collaborative research in tuberculosis drug development

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery.     

Mid-term clinical and health-related quality of life outcomes for the Trifecta bioprosthesis

BackgroundThe Trifecta valve has been reported to have excellent hemodynamics. Controversy exists on occurrence of patient-prosthesis mismatch (PPM) and data on mid-term outcome is sparse. Health-related quality of life (HRQoL) assessment for the Trifecta valve has not been reported before. The aim of this study was to report the mid-term clinical and HRQoL outcomes in patients undergoing Trifecta valve implantation at our institution.MethodsIn this prospective, observational study, patients undergoing an aortic valve replacement (AVR) using the Trifecta valve were included. Data collection was retrospective from prospectively collected institutional database. Clinical and echocardiographic data were collected prospectively during follow-up. Quality of life was assessed using the Short Form-36 (SF-36) questionnaire.ResultsForty-seven patients were included in the study of which 9 (19%) were women. Isolated AVR was carried out in 33 (70%) patients. In-hospital mortality and 30-day mortality were 1 (2.1%) and 2 (4.2%), respectively. With a mean indexed effective orifice area (iEOA) 0.96 ± 0.1, none of the patients had severe PPM. Moderate PPM was seen in 19%. The mean follow-up was 3 ± 1.7 years. The 5-year survival estimate was 83.2% in the overall cohort, 81.4% in the isolated and 87.5% in the concomitant procedure group. Freedom from re-operation and structural valve degeneration at 5 years was 95.7% and 97.8%. The mean physical health composite was 69.24 ± 2 and the mean mental health composite was 69.7 ± 25, indicating excellent mental and physical well-being among patients.ConclusionThe Trifecta valve provides satisfactory hemodynamics, survival and freedom from re-operation and excellent HRQoL at mid-term follow-up.     

Concomitant presence of mutations in mitochondrial genome and p53 in cancer development - a study in north Indian sporadic breast and esophageal cancer patients

Mitochondrial DNA alterations in recent years have been suggested as modifier events, providing a possible proliferative advantage to the tumor cells. In order to provide further insight into the process of tumorigenesis, a study of whole mitochondria genome was conducted in 134 tissue samples obtained from 2 unrelated cancers (tumor and adjacent normal tissues from 36 breast cancer and 31 esophageal squamous cell carcinoma (ESCC) patients) with known p53 somatic mutation background. Fifteen of 36 (41.66%) breast and 12 of 31 (38.71%) ESCC tumors were found to contain at least 1 mtDNA somatic mutation, which correlated significantly with the concomitant presence of somatic mutation in DNA binding domain of the p53 gene (Breast cancer, p = 0.006; ESCC, p = 0.002). Interestingly, mutations in the non D-loop region of the mtDNA contributed significantly (Breast cancer, p = 0.004; ESCC, p = 0.032) in comparison to the hotspot-D-Loop-region. The concomitant presence of mutations in p53 and mtDNA were also predominant in breast cancer tumors with poor prognosis, that is, with the advanced stage, grade and the ER/PR negativity. Also, the observation made was apparently well explained in 10398A bearing N haplogroup genetic background with increased presence of novel and pathogenic germline mutation in mtDNA. Our study suggests that the concomitant presence of somatic alteration in mtDNA and the DNA binding domain of the p53 gene facilitates cell survival and tumorigenesis, requiring specialized therapeutic intervention because of a possible resistance to conventional chemotherapy.