Hydroxyurea is an antineoplastic agent commonly used to treat essential thrombocytosis. We report the case of a 50-year-old woman who was incidentally detected to have essential thrombocytosis after suffering an episode of cerebrovascular accident with faciobrachial monoparesis. She was subsequently initiated on hydroxyurea. Within seven weeks of therapy, the patient noticed irregular hyperpigmented patches over her feet, hands and perioral region, with bluish-grey longitudinal bands on all 20 nails. Hydroxyurea-induced hyperpigmentation and melanonychia are not commonly reported. To the best of our knowledge, this is only the third published report of hydroxyurea-induced hyperpigmentation and melanonychia involving all 20 nails. Physicians need to be aware of such mucocutaneous side effects to avoid misdiagnosis and unwarranted fear in patients. The decision to discontinue the intake of the drug depends heavily on the future risk of thrombotic events.
Female ; Humans ; Hydroxyurea ; adverse effects ; therapeutic use ; Hyperpigmentation ; chemically induced ; Middle Aged ; Nail Diseases ; chemically induced ; Nails ; drug effects ; Stroke ; drug therapy ; Thrombocytosis ; drug therapy ; Treatment Outcome

Background: Founder mutation is a heritable genetic alteration observed with high frequency in a geographically and culturally isolated population where one or more ancestors becomes the forebearer of the altered gene. The current study reports two founder mutations in the BRCA1 gene in the Nepalese people. Methods: Germline BRCA testing in all surface epithelial ovarian cancers and the selected case of breast, prostate, and pancreatic cancers has been the standard practice from 2016 to 2021. One thousand one hundred thirtythree probands were screened for germline BRCA variants by next generation sequencing. The variants were classified as per the American Society of Medical Genetics and Genomics recommendations. Pathogenic (class V) and likely pathogenic (class IV) were considered clinically relevant and utilized for cascade screening. Results: Nepalese population made up a subcohort of 5.12% (58/1,133) of probands tested for germline BRCA1/2 variants. Twenty-seven of these 58 tested harbored pathogenic genetic alterations in BRCA1/2 genes, with 23 being BRCA1 mutant. Sixteen of 23 BRCA1 mutant cases shared one common pathogenic mutation c.2214_2215insT (p.Lys739Ter) (NM_007294.4). Additionally, a second highly recurrent mutation in BRCA1 gene c.5068A>T (p.Lys1690Ter) (NM_007294.4) was noted in six patients from this population. Conclusions The overwhelming abundance of the above two variants in a geographically confined population confers these two genetic alterations a status of founder mutations amongst the people of Nepal. A more extensive population-based study to reaffirm these findings will help establish a dual site-specific germline testing similar to the “Multisite-3-assay” in Ashkenazi Jews as the primary screening tool, especially in a resource-constrained environment.

SMARCA4/BRG1-deficient lung adenocarcinoma (SD-LUAD) is being recognized as a distinct subtype based on subtle differences in its clinical, morphological, and immunophenotypic attributes compared to other non–small cell lung carcinomas. We present here a case of SD-LUAD with curious thyroid transcription factor 1 (TTF1) expression in a morphologically heterogenous lung adenocarcinoma. The better differentiated area showed preservation of TTF1 expression, and a poorly differentiated tumor had loss of TTF1 expression with universal BRG1 loss.

AIMTo study the occurrence of Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome (KFS).

METHODSBlood and semen samples were collected from azoospermic patients with KFS (n = 14) and a control group of men of proven fertility (n = 13). Semen analysis was done according to World Health Organization (WHO) guidelines. Blood samples were processed for karyotyping, fluorescent in situ hybridization (FISH) and measurement of plasma follicle stimulating hormone (FSH) by radioimmunoassay. To determine Y chromosome microdeletions, polymerase chain reaction (PCR) of 16 sequence tagged sites (STS) and three genes (DFFRY, XKRY and RBM1Y) was performed on isolated genomic DNA. Testicular fine needle aspiration cytology (FNAC) was done in selected cases.

RESULTSY chromosome microdeletions spanning the azoospermia factor (AZF)a and AZFb loci were found in four of the 14 azoospermic patients with KFS. Karyotype and FISH analysis revealed that, of the four cases showing Y chromosome microdeletion, three cases had a 47,XXY/46,XY chromosomal pattern and one case had a 46,XY/47,XXY/48,XXXY/48,XXYY chromosomal pattern. The testicular FNAC of one sample with Y chromosome microdeletion revealed Sertoli cell-only type of morphology. However, no Y chromosome microdeletions were observed in any of the 13 fertile men. All patients with KFS had elevated plasma FSH levels.

CONCLUSIONPatients with KFS may harbor Y chromosome microdeletions and screening for these should be a part of their diagnostic work-up, particularly in those considering assisted reproductive techniques.

Adolescent ; Adult ; Chromosome Deletion ; Chromosomes, Human, Y ; Electrophoresis, Gel, Two-Dimensional ; Genetic Loci ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Klinefelter Syndrome ; complications ; genetics ; Male ; Mosaicism ; Oligospermia ; etiology ; genetics ; Seminal Plasma Proteins ; genetics ; Sequence Tagged Sites

[Objective] To explore the application of Quality by Design (QbD) tools in assessing geographical variations of Phyllanthus emblica (P. emblica) from five distinct Indian states. [Methods] In the current experiment, the Box-Behnken design with a reduced quartic model and 105 runs was employed with the use of the Design Expert software for randomized response surface mapping. Three different extraction methods (Soxhlet, maceration, and sonication) along with three solventst [distilled water, methanol, and water-methanol mixture (50 : 50 v/v)] were considered in the present study. The anti-oxidant activities, total flavonoid content (TFC), and total phenolic content (TPC) in the P. emblica were determined and analysed by gas chromatography-mass spectrometry (GC-MS) to identify the major components. [Results] The QbD overlay plot showed that the extractive value of the P. emblica was no less than 30% w/w, 2,2-diphenyl-1-picrylhydrazyl (DPPH) no less than 60% mcg/mL (micrograms per millilitre), TFC no less than 75 mg QE/g (milligrams of quercetin equivalents per gram), and TPC no less than 80 mg GAE/g (milligrams of gallic acid equivalents per gram). Moreover, the GC-MS data confirmed the presence of variation in the bioactives of P. emblica extracts. [Conclusion] The model was significant in describing the variation in extractive value, DPPH, TFC, and TPC. The QbD approach may tend to prioritize thoroughness in the extraction process, ultimately resulting in improved quality in the extracted products.

Objectives: This is a diagnostic test research study to evaluate the various existing methods of thyroid examination and their comparison with the novel modified Rose method. It also aims to measure inter-examiner variation in clinical findings based on the level of education and training, as compared to ultrasonography. Methodology: This cross-sectional study was conducted at a tertiary care hospital with 83 patients presenting to surgery OPD with neck swelling. Each patient was examined by one trained Junior Resident and a Surgery Consultant with all the four methods and with ultrasonography. Data was analysed by Stata-14, agreement between the two categorical variables was assessed by Kappa. In case of continuous variable agreement was assessed by Intra class correlation and Bland-Altman plot. Results: Modified Rose method by the consultant has the highest sensitivity (98%) and diagnostic odds (210) as compared to others but its specificity ranges from 46.7-91.1% to diagnose retro-sternal extension of a goiter. It has 93.98% agreement for identification of nodules. It has a high specificity (Consultant - 100%, Resident - 95.5%) with relatively lower sensitivity (Consultant - 94%, Resident - 86.8%) to diagnose solitary thyroid nodule (STN) but the sensitivity and specificity for diagnosing a multinodular goitre (MNG) was high. However, the highest sensitivity to diagnose STN was highest with Crile’s method, but specificity was low. Lahey’s method was a better clinical method to palpate lymph nodes compared to the other three. Conclusion Examination in modified Rose’s position is a better method of clinical examination of thyroid especially in patients with occult substernal extension. Lahey’s method is a better method to examine cervical lymph nodes.