Cervical cancer screening practices in HIV positive females - a missing link in health care delivery in Pakistan.

Objectives: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001). CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.

Prevalence of Human Papilloma virus in potentially malignant oral disorders is a risk factor for development of early dysplasia-A cytological investigation.

Objective: The proposed study was planned to screen Human Papilloma Virus (HPV) status in potentially malignant oral disorders (PMOD) and correlated HPV positivity with cytological changes in oral smears. Methods: This descriptive cross-sectional study was conducted at University of Health Sciences Lahore, Pakistan from April 2020 to April 2021. Oral smears from N=162 patients with PMODs were taken by the Cytobrush and Manual Liquid Based Cytology was performed followed by p16 antibody detection on immunohistochemistry and HPV-DNA detection by conventional polymerase chain reaction (PCR). The cytological changes were categorized according to the updated Bethesda Classification system 2014. SPSS was used to analyze data and p-Value of <0.05 was considered as statistically significant. Results: Out of total N = 162 patients, the most prevalent lesion [39% (n=63)] was lichen planus. Fifty six percent (n=90) of the patients were habitual chewers and 43% (n=70) were smokers. Pap staining of oral smears revealed atypical squamous cells of undetermined significance (ASCUS) in 45% (n=69) cases and in 2 % (n=4) of the samples diagnosis of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) was made. A total of 37% cases showed HPV positivity by polymerase chain reaction (PCR) while positive p16 expression was observed in 24% of the cases. ASC-H and ASCUS category showed significant association with HPV positivity (p=0.003). Conclusion: Early detection of PMODs by adopting minimally invasive cytological techniques and screening for HPV infection in local population is pivotal to reduce the morbidity and mortality associated with the advanced disease and carcinoma.

Anticancer genes (NOXA, PAR-4, TRAIL) are de-regulated in breast cancer patients and can be targeted by using a ribosomal inactivating plant protein (riproximin).

BACKGROUND: Anticancer genes are an endogenous defense against transformed cells as they impose antineoplastic effects upon ectopic expression. Profiling the expression of these genes is fundamental for exploring their prognostic and therapeutic relevance in cancers. Natural compounds can upregulate anticancer genes in malignant cells and thus be useful for therapeutic purposes. In this study, we identified the expression levels of anticancer genes in breast cancer clinical isolates. In addition, the purified and sequenced plant protein (riproximin) was evaluated for its potential to induce anticancer genes in two breast cancer cell lines. METHODOLOGY: Expression profiles of three anticancer genes (NOXA, PAR-4, TRAIL) were identified by immunohistochemistry in 45 breast cancer clinical isolates. Breast cancer cells were exposed to riproximin and expression of the anticancer genes was determined by microarray, real-time PCR and western blot methodologies. Lastly, a bioinformatic approach was adopted to highlight the molecular/functional significance of the anticancer genes. RESULTS: NOXA expression was evenly de-regulated among the clinical isolates, while PAR-4 was significantly down-regulated in majority of the breast cancer tissues. In contrast, TRAIL expression was increased in most of the clinical samples. Expression levels of the anticancer genes followed a distinct trend in accordance with the disease severity. Riproximin showed a substantial potential of inducing expression of the anticancer genes in breast cancer cells at transcriptomic and protein levels. The bioinformatic approach revealed involvement of anticancer genes in multiple cellular functions and signaling cascades. CONCLUSION: Anticancer genes were de-regulated and showed discrete expression patterns in breast cancer patient samples. Riproximin effectively induced the expression of selected anticancer genes in breast cancer cells.

Copy number variations and protein expression of Cyclin E1 and Epithelial cell transforming sequence 2 genes predict the chemotherapeutic response in patients with serous ovarian carcinoma.

Background & Objectives: Serous ovarian carcinoma (SOC) is characterized by extreme genomic instability, chromosomal rearrangements and copy number variations (CNVs) leading to the development of early metastasis and chemo-resistance. The present study was designed to observe the role of CNVs of Cyclin E1 (CCNE1) and Epithelial cell transforming sequence- 2 (ECT2) genes and their encoded proteins in predicting the chemotherapeutic response in SOC patients. Methods: This observational analytical study was conducted at University of Health Sciences, Lahore, Pakistan from December 2019 till June 2022.The study included twenty-five SOC patients with resectable ovarian tumors and twenty-five control subjects. The patients were followed-up for six months for their response to chemotherapy. The CNVs in CCNE1 and ECT-2 genes were determined by real time PCR while serum levels of encoded proteins were determined in controls and cases, before and after six months of treatment, through ELISA. The response to chemotherapy was categorized as sensitive or resistant based on serum CA-125 levels and radiological scans. Results: The copy number variations in CCNE1 and ECT2 genes showed association with the clinic-pathological characteristics and chemotherapy response. Statistically significant difference was found between the mean pre-chemotherapy protein levels of CCNE1 in cases than controls (p-value <0.001) and between the mean pre and post-chemotherapy protein levels of CCNE1 and ECT2 (p-value <0.001) in SOC patients. Conclusion: The copy number variations of CCNE1 and ECT2 genes and their protein expression are positively associated with chemotherapeutic response in SOC patients.

Evaluation of therapeutic potential of ivermectin against complete Freund's adjuvant-induced arthritis in rats: Involvement of inflammatory mediators.

Rheumatoid arthritis is a chronic systemic inflammatory disease with genetic manifestations. According to recently published case reports, patients taking corticosteroid medication for the management of rheumatoid arthritis develop strongloidiasis and are at high risk of developing associated infections. This study explored the antiarthritic role of ivermectin, a drug used in the treatment of strongyloides and to compare its results with dexamethasone. Thirty-two male Wistar rats were randomly divided into four groups: control, diseased, dexamethasone, and ivermectin groups. Rheumatoid arthritis in all rats except the control group was induced by using complete Freund's adjuvant. After 7 days of rheumatoid arthritis induction, animals were treated with dexamethasone 5 mg/kg and ivermectin 6 mg/kg. Body weight, visual arthritic score, total leukocyte count, differential leukocyte count, proinflammatory genes, and histopathological findings were used to assess the effects of ivermectin on rheumatoid arthritis. Treatment with ivermectin showed a significant reduction in inflammatory cells levels, body weight, and visual arthritic score, indicating an improvement in the degree of inflammation as compared with the diseased group. Treatment with ivermectin and dexamethasone significantly reduced the augmentation in the mRNA expression levels of IL-17, TLR-2, TNF, and NF-κB as a result of arthritic development. Ivermectin treatment also showed a significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to dexamethasone, a corticosteroid used for the treatment of rheumatoid arthritis. Ivermectin has significant antiarthritic properties and can be a novel treatment agent for the management of rheumatoid arthritis patients suffering from strongyloidiasis.

Chrysin Is Immunomodulatory and Anti-Inflammatory against Complete Freund's Adjuvant-Induced Arthritis in a Pre-Clinical Rodent Model.

Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund's adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.

Oral Squamous Cell Carcinoma Clinico-pathological features in relation to Tumor Stage; AJCC 2018 perspective.

Objective: To investigate the association between clinicopathological findings and tumor stage according to AJCC 2018 guidelines in patients suffering from Oral squamous cell carcinoma (OSCC). Methods: A descriptive study was conducted from January 2019 to January 2020 at King Edward Medical University and University of Health Sciences on a total of 49 patients enrolled after obtaining written informed consent. Clinical and radiographic findings were recorded. Pathological reporting was done using AJCC 2018 cancer staging guidelines. Association between clinicopathological features with tumor stage and grade was assessed using Chi-square and Kruskal-Wallis test. Result: Mean age of the patients was 46.1 ± 10.6 years. Most of the tumors were of well differentiated type (49%) and moderately differentiated (40.8%) with predominant clinical stage III in 42.9% & IV in 44.9 % and primary tumor stage pT2 28.6% & pT3 36.7%. Significant difference was seen for primary tumor stage in relation to age, gender, depth of invasion, primary site, and size of tumor (p < 0.01). For clinical stages, significant difference was observed in the age, gender, size of tumor, nodal metastasis, and anatomical tumor site (p < 0.01). Conclusion: Application of 8th Edition AJCC guidelines identifies the importance of the latest classification with strong association of latest stage criteria with age, gender, site of primary tumor, tumor thickness, depth of invasion, nodal metastasis and size of largest lymph node involved, and Level of Lymph node involved (level III & V) in a subset of patients from a developing country.

Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan.

BACKGROUND: Genetic mutations, peritoneal metastasis and frequent development of chemoresistance worsen the prognosis of ovarian carcinoma. OBJECTIVE: The objective of the study is to determine mutations in cancer susceptibility genes in relation with chemotherapy response. METHODS: In this follow up descriptive study, 47 consenting female patients diagnosed with surface epithelial ovarian cancer were observed for six months after completion of chemotherapy to see the treatment response. For genetic analysis, the DNA extraction was done and the genomic regions of different exons of BRCA1/2, PALB2, CHEK2, BAP1, CTNNB1, HOXB13, and PIK3CA were amplified using gene specific primers followed by Sanger Sequencing. RESULTS: 86.7% of the patients were sensitive to chemotherapy whereas 13.3% showed resistance. Genetic variants of BRCA1 in 7%, BRCA2 in 4.7%, PIK3CA in 9.3%, PALB2 in 7%, CHEK2 in 2.3%, BAP1 in 2.3%, and CTNNB1 in 2.3% of the patients were found. There was also a significant association between TNM stage and the treatment response (p< 0.01). Of the patients with no mutations, 90.9% showed chemosensitivity as opposed to 70% in mutations group. CONCLUSION: Our study exhibits the pivotal role of genetic analysis in predicting the treatment response and paving pathway for patient tailored targeted therapy in Pakistani population.

Nimbolide attenuates complete Freund's adjuvant induced arthritis through expression regulation of toll-like receptors signaling pathway.

Nimbolide is an active constituent of Azadirachta indica and is known for its anti-inflammatory, anti-oxidant, immune-modulatory, and anti-cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll-like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra-dermally into the sub-plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll-like receptors, IL-17, IL-23, HSP70, and IFN-γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non-steroidal anti-inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll-like receptors pathway in rheumatoid arthritis.

Challenges in screening of sexually transmitted viral infections of the female genital tract: Where do we stand? - A scoping review.

Globally more than a million sexually transmitted infections occur daily, and over 53 000 [47,000-60,000] women aged 15 and over were living with human immunodeficiency virus / acquired immunodeficiency syndrome in Pakistan by the year 2020. This situation becomes graver when the sexually transmitted infections exist as co-infections while remaining undiagnosed or under-diagnosed. Additionally, herpetic or papillomavirus lesions are more recurrent, more extensive and have more serious consequences in human immunodeficiency virus-positive patients. Literature shows a dramatic increase in morbidity and mortality due to the occurrence of malignancies in genital co-infections. There is a key concern that every single adolescent female living in Pakistan is at a high risk of acquiring viral sexually transmitted infections along with malignancy of the cervix. As such, the health and future of this age group is already imperilled. Needless to mention that the practice of routine cervical screening and diagnostic laboratory services offered to a common woman in Pakistan have been less than satisfactory for decades. Therefore, to meet the minimum expectations regarding the Millennium Development Goals for sexual and reproductive health and rights 2030, it has now become imperative for the health sector to develop and implement scientific and community-based policies for comprehensive and multidisciplinary diagnostic strategies leading to early and effective management of viral sexually transmitted infections and subsequent neoplasia.

Immunohistochemical Expression Of Matrix Metalloproteinase-1 (MMP-1) in Different Types Of Breast Carcinoma And Its Comparison With ER/PER and HER2/neu.

BACKGROUND: Breast cancer is a complex disease that comprises of various biological sub-types with different natural history. Matrix metalloproteinase-1(MMP-1) expression has been reported to inversely correlate with the survival. The current study was conducted to classify breast cancer into four subtypes based on IHC, to assess the immunohistochemical expression of MMP-1 in primary breast carcinoma, to compare its expression with ER/PR and HER2/neu. METHODS: A descriptive study was conducted on 100 mastectomy specimens of breast carcinoma after being fixed in 10% formalin at Department of Histopathology, University of Health Sciences Lahore. Sections were taken on frosted slides for H&E and on lysine coated slides for immunohistochemistry (IHC). Haematoxylin and eosin (H&E) and IHC for oestrogen receptor/progesterone receptor (ER/PR), HER2/neu and Matrix metalloproteinase (MMP-1) were performed according to protocol. RESULTS: The mean age was 48.4411.79 Years (ranging 25 to 90 years). 97 cases were of Invasive ductal carcinoma (IDC) type, two showed the features of invasive lobular carcinoma and only one case was found to be of mucinous type, 19 cases were found to be in grade I, 74 in grade II and seven cases were in grade III. Breast cancer has been classified into four major groups based on IHC profile ER/PR and HER2/neu expression. The groups were: Triple positive, ER/PR+, HER2-, ER/PR-, HER2/neu+ and triple negative) cases. Among 100 cases of breast cancer, 9 were of triple positive type, (ER/PR +, HER2/neu+), 28 cases were of ER/PR +, HER2- type, 19 were ER/PR-, HER2/neu +ve and 44 cases were of triple negative type (ER/PR-, HER2/neu-ve). 13 cases were of score 1 MMP-1out of which 7 (25.0%) were ER/PR+, HER2-, 1 (5.3%) case was ER/PR-, HER2/neu +ve and 5 (11.4%) cases were triple negative. Among 30 cases of MMP-1 score 4, 5(55.6%) cases were of triple positive type, 3 (10.7%) cases were of ER/PR +, HER 2/neu-ve type, 12(63.2%) cases were of ER/PR-, HER 2/neu+ve type, and 10 (22.7%) cases were of triple negative type. A significant p-value of <0.05 was obtained. CONCLUSIONS: Among four IHC based subtypes, most frequent were triple negative breast cancers which showed high IHC score of MMP-I which is reported to be an important marker for metastatic potential in breast carcinoma.

Analysis of Isocitrate dehydrogenase (IDH) mutation in Gliomas: A call for neurosurgeons and pathologists in Pakistan.

Tumours of the central nervous system, though not very common, pose a serious health burden owing to their high mortality rate. Glial tumours are the commonest type of brain tumours in Pakistani population. Diagnosis of gliomas has been greatly revolutionised over the past few years with integration of immunohistochemistry and molecular subtyping in the World Health Organisation's updated 2016 classification of glial tumours. One of the major changes was incorporation of isocitrate dehydrogenase mutation detection that is considerably a significant prognostic and predictive marker. The published data on isocitrate dehydrogenase mutation in the local population is hard to find. The current narrative review was planned to briefly describe the international trends regarding frequency of isocitrate dehydrogenase mutation in gliomas, its predictive and prognostic significance and its impact on accurate diagnosis leading to a targeted therapeutic approach for patients.

Doctor of Science (D.Sc.): Time to move towards Higher Doctorate Degrees.

The present most modern and highly advanced 21'st century is the era of science and technology. In human history, universities are the basic birthplace of higher education, research, and innovation and play a significant role in the countries' performance, prosperity, and economic progress. Worldwide, there is a swift shift in the pattern of biological, environmental, economic, and educational systems. This broader change is rotating around the higher academia and its allied innovative research impact. The leading universities develop a culture and curricula as per need and demand and produce knowledge and skills-based professional graduates. The universities prepare graduates to keep in view their country's requirements and compete with their peers at international levels. Moreover, worldwide, universities are transforming towards higher doctorate degrees (D.Sc / S.Dc) to provide an elevated helipad to the applicant to compete in this modern and highly advanced era. The higher doctoral degree, D.Sc, is earned 6-8 years after the post Ph.D. The candidates with higher academic titles, professional skills, and innovative research could compete and achieve top-ranked positions worldwide. Many universities worldwide, including the United States of America, the United Kingdom, Australia, and New Zealand, promote D.Sc degree programs in various science disciplines, including medical sciences. This manuscript explores the dynamics of a higher doctorate and its significance, need, and demand in academia to compete globally.

Rare Variant of Adult Rhabdomyosarcoma Presenting as a Palatal Swelling.

A 26-year-old male was referred to the Department of Oral and Maxillofacial Surgery of a tertiary care hospital in Lahore with chief complaint of painless swelling on the right palate of 40 days duration. Clinical differential diagnosis included squamous cell carcinoma, Ewing sarcoma, fibrosarcoma, neuroblastoma and rhabdomyosarcoma. Computed tomography scan revealed hypodense mass with necrotic changes. Histological examination of the excised tumor revealed malignant neoplasm arranged in fascicles and bundles comprising of spindle cells with pleomorphic, hyperchromatic nuclei and increased atypical mitosis. Immunohistochemical analysis showed negative staining with Cytokeratin, S100, CD34, Stat6, h-Caldesmon and EMA while the tumour cells were positive for desmin, myogenin, smooth muscle actin, CD-99 and MyoD1 thus confirming the diagnosis of spindle cell rhabdomyosarcoma.

Immunohistochemical expression of MUC4 in different grades of head and neck squamous cell carcinoma.

OBJECTIVE: To determine immunohistochemical expression of Mucin 4 in head and neck squamous cell carcinoma and its different histological grades among patients reporting to various tertiary care hospitals in an urban setting. METHODS: The descriptive study was conducted at the Department of Oral Pathology / Morbid Anatomy and Histopathology, University of Health Sciences, Lahore, Pakistan, from January to July 2017 and comprised cases of head and neck squamous cell carcinoma. Histological diagnosis and grading was done for each case. Haematoxylin and eosin stain followed by immunohistochemistry was done. Relation of Mucin 4 expression with tumour types was explored. SPSS 20 was used for statistical analysis. RESULTS: Of the 63 samples, 40(63.5%) were from male patients. The overall mean age of the patients was 53±3.77 years. Mucin 4 expression was positive in 47(74.6%) cases. Of them, 16(34%) had grade 1 tumour, 28(59.6%) had grade 2 and 3(6.4%) had grade 3 tumour. There was a significant relation (p=0.03) between tumour grades and intensity of Mucin 4 expression. CONCLUSIONS: Upregulation of Mucin 4 in tumour tissue with no expression in normal epithelium was found and loss of Mucin 4 expression with increase in tumour grade was noted.

Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6, TNF-α, NF-ĸB, and COX-2 levels, and upregulation of TFF-2 levels.

Oxyresveratrol, an active ingredient of Artocarpus lakoocha, is known to possess anti-inflammatory and immunomodulatory properties. Current study investigates the immunomodulatory effect of oxyresveratrol in mouse model of ethanol-induced ulcer. Anti-ulcer effect was determined using histopathological evaluation (H&E staining) and different tests like, gastric ulcer scoring, ulcer index, total acid secretion, and gastric pH. The mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor-kappaB (NF-ĸB), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and trefoil factor 2 (TFF-2) were evaluated using reverse transcription polymerase chain reaction (RT-PCR). The data showed marked percentage inhibition of erosion, hemorrhage, fibrinoid necrosis, inflammatory infiltrate, and ulcer in low (30 mg/kg b.w.) and high dose (50 mg/kg b.w.) groups of oxyresveratrol. Treatment with oxyresveratrol inhibited ulcer score and ulcer index as compared with disease control group. Oxyresveratrol significantly increased gastric pH (P < 0.001) and attenuated total acid (P < 0.001) secretion. RT-PCR analysis showed significant suppression in the mRNA expression levels of IL-6 (P < 0.001), TNF-α (P < 0.01), NF-ĸB (P < 0.001), and COX-2 (P < 0.05) in oxyresveratrol treated groups, while COX-1 expression levels were found unaltered. Treatment with oxyresveratrol significantly elevated (P < 0.01) the expression levels of cytoprotective TFF-2 levels. Similar Immunomodulatory and anti-ulcer effects were found with ranitidine treatment, which was used as a reference drug. In conclusion, oxyresveratrol possess significant anti-ulcer property which might be attributed to attenuated expression levels of IL-6, TNF-α, NF-ĸB, and COX-2 and elevated expression levels of TFF-2.

Histopathological Changes in Arsenic Kushta Induced Nephrotoxicity in Wistar Rats.

OBJECTIVE: To determine the nephrotoxic effects of arsenic kushta (Kushta Sam-ul-Far) in Wistar rats. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Morbid Anatomy and Histopathology, University of Health Sciences, Lahore from May to August 2014. METHODOLOGY: This experimental study was conducted on 48 healthy Wistar rats, each weighing 200 - 250 grams. The rats were randomly divided into 4 experimental groups each containing 12 rats. Group I was taken as control given flour pellets. Group II was given single dose (180 mg/kg) of arsenic kushta for 2 weeks. Group III received 150 mg/kg of arsenic kushta for 12 weeks; whereas, group IV was also given 150 mg/kg of arsenic kushta for 12 weeks along with 75 mg of BSA (bovine serum albumin). Histopathological changes in glomeruli, tubules and interstitium were noted in the kidney. RESULTS: Mesangial proliferation, thickening of basement membrane, necrosis, and interstitial edema were mainly observed in all the above groups except group I which served as control. These changes were seen in greater severity in high dose groups and the group given BSA injection along with kushta (group III, IV). CONCLUSION: Herbo-mineral preparations of arsenic kushta are nephrotoxic in rats and may have similar toxic effects in human beings.

Enabling the disabled: Call for intercepting disability surge in Pakistan.

Muscular dystrophies have always been marginalized culturally and socially, particularly in underdeveloped and developing countries. Pakistan is facing significant dearth of "appropriately" trained neurologists and neuromuscular pathologists. A careful and methodical link between clinical, pathological and molecular analysis must be established before making a diagnosis in such cases. Increased collaboration between local and international neurology societies may add value to collaborative neuromuscular research and education in Pakistan, both in community and health sectors. These goals are all achievable but require persistence, dedicated workforce, and positive efforts to meet them.

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis

ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

MCM - 2 and Ki - 67 as proliferation markers in renal cell carcinoma: A quantitative and semi - quantitative analysis.

INTRODUCTION/BACKGROUND: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. MATERIAL AND METHODS: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. RESULTS: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. CONCLUSION: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.