Overview of benign and malignant prostatic disease in Pakistani patients: A clinical and histopathological perspective

Background: To present the overall clinical and histological perspective of benign and malignant prostatic disease as seen in our practice in the Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan.Materials and Methods: All consecutive prostate specimens (transurethral resection or TUR, enucleation, needle biopsies) received between July 1, 2012 and December 31, 2012 were included in the study.Results: Of the total of 785 cases, 621 (79.1%) were TUR specimens, 80 (10.2%) enucleation specimens, and 84 (10.7%) needle biopsies. Some 595 (75.8%) were benign, while 190 (24.2%) were malignant. Mean weight of BPH specimens was 19 grams and 43 grams for TUR and enucleation specimens respectively. Almost 67% of adenocarcinomas were detected on TUR or enucleation specimens. Of the above cases, 41.7% were clinically benign while 58.3% were clinically malignant. The average volume of carcinoma in all cases ranged between 60 to 65%. The average number of cores involved in needle biopsies was 5. In general, higher Gleason scores were seen in TUR/enucleation specimens than in needle biopsies. Overall, in all types of specimens, commonest Gleason score was 7, seen in 74 (38.9%) cases, followed by Gleason score 9 seen in 47 (24.7%) cases. Out of the 63 needle biopsies with carcinoma, radical prostatectomy was performed in 16 cases (25.4%).Conclusions: Benign prostatic hyperplasia (BPH) is extremely common and constitutes the bulk of prostate specimens. TMajority of prostatic carcinomas are still diagnosed on TUR or enucleation specimens. These included both clinically benign and clinically malignant cases. The volume of carcinoma in these specimens was quite high indicating extensive disease. Gleason scores were also generally high compared with scores from needle biopsies. Commonest Gleason score in all type of specimens was 7. Pathologic staging was possible in very few cases since radical prostatectomies are rarely performed

Involvement of thromboxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 mM) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0.65 mM) and calcium channel blockers, diltiazem (IC50 = 13 mM) and verapamil (IC50 = 18 mM). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 mM), a cyclooxygenase inhibitor (indomethacin; IC50 = 0.2 mM) and inhibitor of TLCK, herbimycin A with IC50 value of 5 mM. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 mM. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways

Financial Development and Output Volatility Nexus: The Role of Financial Sector Instability

This research study explores the influence of financial sector development on output volatility. Particularly, the role of financial sector instability is modeled to provide a better understating of financial sector development and output volatility nexus. The empirical analysis is based on cross-sectional panel datasets for 180 countries from 1971 through 2020. In addition to Random and Fixed Effects models, the 2-SLS and GMM techniques were used for empirical analysis. Country analyses produce mixed results but show a considerable beneficial result. The results suggest that financial sector volatility increases output volatility. While financial development, on the other hand, is critical in protecting output from instability. Trade openness and inflation have also been controlled for their impact on output volatility. Trade openness, like financial stability, decreases production volatility. Inflation, as a monetary phenomenon, tends to amplify output volatility

Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by disease-modifying antirheumatoid drugs in the adjuvant-induced arthritic rat

In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti-inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte–macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity

A Study of the Organizational Stress among Public Sector Secondary School Teachers in Punjab

The aim of the study was to find out the factors which create stress among public sector secondary school teachers to determine the stressors being faced by the secondary school teachers. The study was related to the secondary schools of public sector in Punjab. Punjab province is comprised of 9 divisions. Due to limited time and resources, the study was delimited to public sector secondary schools of Lahore division. The study adopted descriptive survey design using a sample of 1000 teachers drawn from 100 secondary schools from public sector in Lahore division. From each school 10 teachers were randomly selected. One rating scale was developed to collect data for the study. The percentage, mean, standard deviation and t-test were applied as descriptive and inferential statistics to analyze the collected data. In the light of the results and conclusions of the study, it may be recommended that unwanted sounds and noise may be minimized in the school environment, trainings be imparted to the staff, workload should be equally distributed and necessary facilities should be provided at schools

A Study of the Organizational Stress among Public Sector Secondary School Teachers in Punjab

The aim of the study was to find out the factors which create stress among public sector secondary school teachers to determine the stressors being faced by the secondary school teachers. The study was related to the secondary schools of public sector in Punjab. Punjab province is comprised of 9 divisions. Due to limited time and resources, the study was delimited to public sector secondary schools of Lahore division. The study adopted descriptive survey design using a sample of 1000 teachers drawn from 100 secondary schools from public sector in Lahore division. From each school 10 teachers were randomly selected. One rating scale was developed to collect data for the study. The percentage, mean, standard deviation and t-test were applied as descriptive and inferential statistics to analyze the collected data. In the light of the results and conclusions of the study, it may be recommended that unwanted sounds and noise may be minimized in the school environment, trainings be imparted to the staff, workload should be equally distributed and necessary facilities should be provided at schools

Gastrointestinal stromal tumors: A clinicopathologic and risk stratification study of 255 cases from Pakistan and Review of Literature

Purpose: To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. Material and Results: We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletcher\u27s consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasota\u27s algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. Conculsion: Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category

ANALYSIS OF BLOOD CIRCULATING SERUM BIOMARKERS FOR THE DIAGNOSIS OF BREAST CANCER

Introduction: Breast cancer is the most common neoplasm in women and the second leading cause of cancer-related mortality in females worldwide. Breast cancer is the second most common type of cancer (after lung cancer), and the fifth most common cause of cancer death. Objectives of the study: The main objective of the study is to assess the blood circulating serum biomarkers for the diagnosis of breast cancer. Methodology of the study: This cross sectional study was conducted at DHQ teaching hospital Sahiwal during February 2018 to November 2018. Breast cancer notifications were confirmed and characterized by postal questionnaire sent to treating clinicians (consultant, or General Practitioner if details not provided by the volunteer), which was designed to ascertain clinical and histological data on diagnosed cases (date of diagnosis, histology, nodal status, staging, grade, prognosis, ER, PR and HER2 status). Results: The results indicates that CTC, CEA and ALP are the best indicating serum biomarkers for the diagnosis and progression of breast cancer. Mean, median and SD shows that there is a significant relationship in these serum biomarkers. Conclusion: It is concluded that biomarkers are the useful tool for the analysis of progression of breast cancer in females. Key words: Diagnosis, Breast, Cancer, Female

Symptomatic surgically treated non-neoplastic cysts of the central nervous system: a clinicopathological study from Pakistan

Objective: To report clinicopathologic features of symptomatic surgically removed non-neoplastic cysts of the central nervous system (CNS). Study Design: Case series. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2003 to 2012. Methodology: All non-neoplastic CNS cysts reported during the study period were retrieved and reviewed. Age, gender, location, histologic type and clinical features were noted. Results: A total of 124 cysts were diagnosed in the study period. These included 44 epidermoid cysts (mean age 30.5 ± 13.8 years), 35 colloid cysts (mean age 31 ± 13.2 years), 32 arachnoid cysts (mean age 24.8 ± 20.2 years), 6 dermoid cysts, 3 enterogenous cysts and Rathke\u27s cleft cysts each and 1 ependymal cyst. All cyst types mainly presented in young adults in both genders with signs and symptoms of a mass lesion. Conclusion: Non-neoplastic cyst mainly presented like a CNS mass lesion in young adults. Epidermoids were the most common type of these cysts in the present series followed by the colloid and the arachnoid cysts

PHENOTYPIC AND GENOTYPIC CHARACTERISTICS OF PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 3 IN PEDIATRIC POPULATION IN PAKISTAN

OBJECTIVE: To determine the phenotypic and genotypic characteristics of progressive familial intrahepatic cholestasis (PFIC) type 3 in Pakistani children in a hospital setting. METHODS: This cross-sectional observational study was conducted at department of Pediatrics Gastroenterology & Hepatology, The Children’s Hospital Lahore, Pakistan from October 2020 to March 2021. Patients of either sex under 16 years of age presenting with jaundice, pruritus, neonatal cholestasis or with chronic liver and gamma glutamyl transferase >100 IU/ml were included in the study after taking informed consent by parents. For Molecular genetics 2ml blood in EDTA was sent to an international laboratory free of cost on research basis. Reports were assessed and levels were noted and genetic coding was also recorded. Data was entered and analyzed in SPSS version 22. Molecular data was interpreted with the help of clinical geneticist. RESULTS: Out of 34 children, 14 (41.2%) were males and 20 (58.8%) were females. Mean age of children was 6.71±3.10 years. Consanguinity was noted in 32 (94.1%) parents having positive family history in 24 (70.6%) cases. The most common mutation was c. 1783C>T p.(Arg595*),  noted in 12 (35.3%) cases, followed by c. 2861G>T p.(Gly954 ASP) [8 (23.5%) cases], c. 153G>A p.(Trp51) [3 (8.8%) cases], c. 1714 C>T p.(Gln572*) c. 1906C>T p. (Gln636), c. 3220G>A p.(Gly1074Arg, c. 3433del p. (val1145Leufsx7)  in 2 (5.9%) cases each, c. 3859 C>T p.(1287Argext*) c. 88-91del p.(Lys30gly fsx7) and c. 1429c>T p. (Gln477) in one (2.9%) case each. CONCLUSION: Children with PFIC type 3 have variable phenotypic and genotypic presentation