7 research outputs found
Breast Diseases: a histopathological analysis of 3279 Cases at a Tertiary Care Center in Pakistan
Objective: To know the frequency of breast diseases in Pakistani females.
Methods: A retrospective analysis of 3279 breast specimens received over a period of 4 years (1 993-1996) at the department of pathology, the Aga Khan University Hospital.
Results: Out of a total of 3279 breast specimens, common breast lesions included infiltrating duct carcinoma 37%, followed by fibro adenoma 16.95%, fibrocystic change13.96%, mastitis 6.83% and duct ectasia 5.33%. Majority of the cases of infiltrating duct carcinoma were encountered in the 5th and 6th decades of life. Tumour size was 2 or \u3e2 cms. in 93% of cases and 40% of them showed 3 or \u3e3 positive lymph nodes. Grade I tumours were 11.38%, grade 11 59.17% and grade Ill tumours 29.47%. Correlation of grade with lymph node metastases (3 or \u3e3+ve nodes) showed 15 cases (1.53%) of grade 1, 178 cases (18.25%) of grade II and 68(6.97%) cases of grade Ill tumours.
Conclusion: This study shows that in Pakistani females, the most commonly encountered lesion in carcinoma of the breast followed by the benign lesions such as fibro adenoma, fibrocystic disease & others. Breast carcinoma occurs at a younger age group with predominance of high-grade lesions and with frequent lymph node metastasis
Alternative routes for tranexamic acid treatment in obstetric bleeding (WOMAN-PharmacoTXA trial): a randomised trial and pharmacological study in caesarean section births.
OBJECTIVE: To examine the safety, efficacy and pharmacology of intravenous (IV), intramuscular (IM) and oral tranexamic acid (TXA) use in pregnant women. DESIGN: Randomised, open-label trial. SETTING: Hospitals in Pakistan and Zambia. POPULATION: Women giving birth by caesarean section. METHODS: Women were randomised to receive 1 g IV, 1 g IM, 4 g oral TXA or no TXA. Adverse events in women and neonates were recorded. TXA concentration in whole blood was measured and the concentrations over time were examined with population pharmacokinetics. The relationship between drug exposure and D-dimer was explored. The trial registration is NCT04274335. MAIN OUTCOME MEASURES: Concentration of TXA in maternal blood. RESULTS: Of the 120 women included in the randomised safety study, there were no serious maternal or neonatal adverse events. TXA concentrations in 755 maternal blood and 87 cord blood samples were described by a two-compartment model with one effect compartment linked by rate transfer constants. Maximum maternal concentrations were 46.9, 21.6 and 18.1 mg/L for IV, IM and oral administration, respectively, and 9.5, 7.9 and 9.1 mg/L in the neonates. The TXA response was modelled as an inhibitory effect on the D-dimer production rate. The half-maximal inhibitory concentration (IC50 ) was 7.5 mg/L and was achieved after 2.6, 6.4 and 47 minutes with IV, IM and oral administration of TXA, respectively. CONCLUSIONS: Both IM and oral TXA are well tolerated. Oral TXA took about 1 hour to reach minimum therapeutic concentrations and would not be suitable for emergency treatment. Intramuscular TXA inhibits fibrinolysis within 10 minutes and may be a suitable alternative to IV
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial
Background
Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.
Methods
In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.
Findings
Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.
Interpretation
Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.
Funding
London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation
Caudal duplication syndrome: a rare entity
The rare caudal duplication syndrome is a spectrum of anomalies primarily involving partial or complete duplication of organs comprising the gastrointestinal, genitourinary and distal neural tube systems. These findings are considered to be a result of aberrant embryogenesis. We hereby report a case of an adult female with complete duplication of the genital and urinary systems (urethra and bladder), hindgut and lower end of vertebral column with no functional impairment. She presented in her first pregnancy at 36 weeks gestation, in labour. To the author's knowledge this is the first case of caudal duplication syndrome with pregnancy from Pakistan.
Key Words: Caudal duplication, Genitourinary, Gestation, Hindgut
Prognostic value of proliferating cell nuclear antigen (PCNA) in infiltrating ductal carcinoma breast
Objective: To assess the independent and interdependent prognostic value of proliferating cell nuclear antigen (PCNA) in carcinoma of breast in our female population and its association with pathologic variables and disease outcome.Design: A descriptive study.PLACE AND DURATION OF STUDY: Section of Histopathology, Department of Pathology and Microbiology, The Aga Khan University, Karachi from January 1992 to December 1997.PATIENTS AND Methods: All cases diagnosed with invasive ductal carcinomas (IDC) of breast with lymph nodes sampling were included. The expression of PCNA was analyzed on tumor specimens of IDC breast. These patients also had axillary lymph node sampling. The expression of PCNA protein was analyzed immunohistochemically by PAP technique. Patients were followed for a median duration of 48 months.Results: The percentage of PCNA positive tumor cells was estimated semi-quantitatively. Positivity was seen in every case, mean PCNA positivity was 27% (range 10-80) with a median of 28%. The \u3c25% positivity was seen in 149 (47%) cases, and \u3e25% positivity seen in 166 (53%) cases. According to the pathological grading lowest mean PCNA was seen in grade-I i.e., 26% tumor cells showed nuclear reactivity to PCNA followed by grade-II 30% and grade-III 33%. PCNA categorical expression was significantly correlated with histological differentiation, (p\u3c0.05) and tumor size (p\u3c0.01). Distant metastases were seen in\u3e25% positive cases (p\u3c0.05). PCNA expression when correlated with overall survival, showed significant correlation between categorical PCNA (p\u3c0.05). At a median follow-up of 48 months, 66% of \u3c25 PCNA positive patients died with an overall survival of 3.16 years and disease-free survival of 2.5 years, among \u3e25% PCNA positive patients 77% died with an overall survival of 2.7 years and a disease-free survival of 2.2 years.CONCLUSION: In this study PCNA proved to be an independent prognostic indicator in predicting disease-free and overall survival in breast carcinoma patients
Case Control Study of Novel Prognostic Markers and Disease Outcome in Pregnancy/Lactation-associated Breast Carcinoma
A case control study of pregnancy/lactation associated breast carcinoma (PAC) was conducted on 24 test cases with two controls per case, matching age, tumor grade, tumor size and axillary lymph nodes status. During seven years of this study, 6% of all patients with breast cancer had PAC. In this study, 67% of the test cases showed positive axillary lymph nodes compared to 49% in our series of 315 cases of non-pregnancy/non-lactating women with breast carcinoma (p \u3c 0.05). The expression of nine prognostic markers, i.e. ER, PR, p53, C-erbB-2, EGFR, Cathepsin-D, PCNA, DNA ploidy and S-phase fraction, were studied by immunohistochemistry and flow cytometry. Hormone receptor status showed a statistically significant difference between the two groups, i.e. 29% immunoreactivity in test cases compared to 58% in controls with a p value of 0.007. Among p53, C-erbB-2, EGFR and Cathepsin-D in the test group, only EGFR showed a significant correlation, i.e. 33% immunoreactivity in test cases and 19% immunoreactivity in controls (p \u3c 0.05). Higher PCNA positivity was seen in the test group compared to controls, i.e. 35% in test patients and 28% in controls (p \u3c 0.05). Metastasis to bone and liver was a common feature of test patients as compared to controls (p \u3c 0.05). After a median follow-up of 72 months, there was no significant difference in the overall survival (OS) of test cases and controls as 54% deaths were recorded in test patients and 44% in controls at the end of this study (p \u3e 0.05). In summary, in spite of some significant differences in the expression of few prognostic markers, i.e. ER/PR, EGFR, PCNA and metastatic potential, there was no significant difference in the OS of PAC vs. control group if compared stage for stage
Dietary Grape (Vitis vinifera) Seed Powder and Zn–Gly Chelate Complex for Mitigating Heat Stress in Broiler Chickens: Growth Parameters, Malondialdehyde, Paraoxonase-1, and Antibody Titer
A total of 300 day old broiler chicks (Hubbard) were assigned to 30 floor pens (10 birds per pen) under cyclic heat stress. Three diets including a control, as well as two levels of grape seed powder (GSP) and zinc (OZ) at the rates of 2.5 g/kg GSP + 50 mg/kg OZ and 5 g/kg GSP + 50 mg/kg OZ, were supplied to the broilers for 35 days. According to the results, broiler feed intake improved (p < 0.05) in GSP + OZ groups from 3–5 weeks and on an overall basis compared to the control diet. Body weight increased (p < 0.05) in GSP-5 + OZ-50 during weeks 2–5 and on an overall basis. The findings indicated that feed conversion ratio (FCR) decreased (p < 0.05) during week 5 in broilers supplemented with GSP-5 + OZ-50. The antibody titer (HI) against Newcastle disease (ND) was higher (p < 0.05) in GSP + OZ groups compared to control treatment. The value of malondialdehyde (MDA) decreased (p < 0.05) under GSP + OZ diets compared to control. Moreover, paraoxonase (PON1) was higher (p < 0.05) in GSP + OZ groups compared to untreated broilers. In conclusion, GSP + OZ positively supported growth traits, reduced MDA, and augmented PON1 and HI titer against ND in broilers exposed to heat stress