Flow cytometric analysis of childhood leukemias

Objective: To collect demographic data for childhood (less than 15 years) leukemias in Karachi, describe the accuracy of the cell surface markers routinely used in the flow cytometric analysis of leukemic cells and arrive at an ideal panel of antibodies for analyzing leukemic samiples. Materials and Methods: Data from 62 consecutive cases of childhood leukemias referred to the Department of Pathology, Aga Khan University Hospital. (AKUH) between January 1995 and December 1998 was analyzed using Epi Info Version 6. Flow cytometry on all samples was performed using standard protocols. Results: The mean age of patients was 8.2 years and 49 (79%) were males. Fifty (81%) had acute lymphoblastic leukemias of which 50% were CD1O positive and 24% CD10 negative Pre-B cell leukemias. Among all Pre B cell All 98% were positive for CD19, 96% for CD22, 89% for HLA-DR and 67% for CD10. Of the 10 AML cases, 100% were positive for CD33, 90% for CD13, 80% for CD19 and 70% for HLA-DR. Conclusion: The mean age in this study population was significantly higher and percentage of CD10 positive Pre-B All is lower than that in the West. Both these factors might be responsible for the poorer prognosis of these patients. It is not possible to specify a minimum or maximum panel of antibodies that should be used for phenotyping all cases of childhood leukemias. A certain degree or redundancy is essential in any panel of antibodies used for flow cytometry of leukemias

Epidermal Growth Factor Receptor (EGFR) as a Prognostic Marker: an Immunohistochemical Study on 315 Consecutive Breast Carcinoma Patients

Objective: To assess the independent and interdependent prognostic value of epidermal growth factor receptor (EGFR) in carcinoma of breast in female population. The Type I family of growth factor receptors includes epidermal growth factor receptor (EGFR also known as EGFRI). Methods: The expression of EGFR protein was analysed immunohistochemically on 315 tumour specimens of infiltrating ductal carcinoma of breast. These patients also had axillary lymph nodes sampling. Results: Overexpression and/or amplification of EGFR was observed in 70 (22.00%) tumours. Eleven (16%) were grade I, 43 (61%) grade II and 16 (23%) grade Ill tumours. Axillary lymph node metastasis had significant correlation with intensified positivity of EGFR (p\u3c 0.05). Significant number of EGFR positive patients developed local recurrence and distant metastases to brain, liver and bone (p\u3c 0.05). EGFR positivity showed significant correlation with the disease free and overall survival (p\u3c 0.05). At a median follow-up of48 (4 years) months in EGFR positive patients, the overall survival was 3.39 years and disease free survival was 2.86 years. EGFR negative tumour patients showed a better survival. In this group the overall survival was 4.62 years and the disease free survival was 4 years. Conclusion: EGFR analysis can be a useful indicator for the selection of patients who are at the high risk, for hormonal therapy decisions and can be useful as a target for new treatment modalities

Antimicrobial, hemolytic and thrombolytic activities of some new N-substituted-2-({5-[(1E,3E)F-4-(1,3-benzodioxol- 5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-yl}sulfanyl) propanamides

Purpose: To synthesize and evaluate the bioactivity of some N-substituted-2-({5-[(1E,3E)-4-(1,3- benzodioxol-5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-yl}sulfanyl)propanamides (9a-o) of the alkaloid piperine (1) extracted from P. nigrum (black pepper).Methods: Extract 1 was subjected to basic hydrolysis to obtain piperic acid (2). The heterocyclic 1,3,4- oxadiazole ring was synthesized from 2 through the formation of an ester and carbohydrazide. A series of electrophiles, 8a-o, were synthesized in the presence of 10 % Na2CO3. The final compounds, 9a-o, were synthesized by stirring 5-[(1E,3E)-4-(1,3-benzodioxol-5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-thiol (5) and 8a-o in LiH/DMF. Spectral analysis was performed using infrared (FTIR), proton nuclear magnetic resonance (1H-NMR) and electron impact mass spectrometry (EI-MS) to determine the structures of 9a-o. Antimicrobial activity was evaluated as zone of inhibition by disc diffusion method. Hemolytic and thrombolytic activities were determined by measuring absorbance before and after incubation of blood cells with test compound.Results: Compound 9d strongly inhibited Bacillus subtilis and Escherichia coli with zone of inhibition values of 16 mm for each. The reference drug, rifampicin, showed zone of inhibition of 21 and 23 mm against B. subtilis and E. coli, respectively. Compound 9a strongly inhibited Aspergillus niger with a zone of inhibition of 18 mm compared to the reference drug, fluconazole, with a zone of inhibition of 19mm.Conclusion: The newly synthesized compounds are more active antimicrobial agents than piperine. Compounds 9a and 9d are the most active.Keywords: Piper nigrum, Piperine, Propanamide, Hemolytic, Thrombolytic, Black peppe

Immunohistochemical Estrogen receptor determination in human Breast carcinoma: correlation with histologic differentiation and age of the patients

An immunohistochemical assay for the measurement of estrogen receptor (ER) has been evaluated on 290 consecutive human breast biopsy and mastectomy specimens in the year 1992 at The Aga Khan University Hospital laboratories. Immunohistochemical localization of estrogen receptor on frozen/paraffin section was scored in a semi-quantitative fashion incorporating both the intensity and the distribution of specific staining. Histologic grading of the tumour was performed according to Bloom’s method. In this study, 21% of the tumours were estrogen receptor negative, 15% were weak positive, 25% intermediate positive and 39% strong positive. Fifty percent of the well differentiated tumours showed strong ER positivity against 27% of the poorly differentiated tumours. Seventy eight percent of all negative estrogen receptors were in patients younger than 50 years of age (pre-menopausal group), while 52% of strong estrogen receptor positivity was observed in patients older than 50 years (post- menopausal). This study demonstrates the value of immunohistochemical method to determine the ER status in patients with advanced breast cancer

Spinal cord compression: Histologic spectrum of lesions

Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal cord compression. Modem imaging techniques have revolutionized the procedure of localizing lesions pre¬senting with signs and symptoms of spinal cord compression. As a result, these lesions are more accessible for fine needle aspiration and biopsy. A quick diagnosis is possible if cytologic preparation is made. Similarly, intraoperative frozen section facility not only provides rapid diagnosis, but also offers oppor tunity of appropriate management decision there and then. Histology in many cases needs help of special stains and immunocytochemistry. This study looks at the histologic spectrum of these lesions, gender distribution and age range in Pakistani population

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

Comparison of Recurrence Rate of Wrist Ganglion Between Seton and Open Surgical Excision in Military Hospitals of Pakistan

Objective: To evaluate the recurrence following open surgical excision and Seton placement in treating symptomatic wrist ganglions in Military Hospitals in a six-month follow-up study. Study Design: Quasi-experimental study Place and Duration of Study: Department of General Surgery, Combined Military Hospital, Bahawalpur Pakistan, Combined Military Hospital, Dera Nawab Sahib Pakistan and Pakistan Airforce Force Hospital, Shorkot Pakistan, from Jun 2015 to Dec 2020. Methodology: The patients were divided into two groups after informed consent. A consultant general surgeon carried out every procedure. The findings were recorded on a uniform proforma, and recurrence was recorded at ten days, six weeks and six months for both groups. Results: The mean age of the patients was 29.45±8.13 years in Group-A (Seton-Group) and 28.56±8.32 years in Group-B (OpenSurgery). There was no difference in the recurrence rates between the Seton-Group (n=7, 4.35%) and Open Surgery-Group (n=2, 4.65%, p=0.931). Conclusion: Seton insertion for treating Ganglions of the wrist is a simple, economical and cosmetic procedure which can be done in the outpatient department. It is a safe alternative to open resection for successful treatment of the wrist Ganglion. Keywords: Ganglion, Open surgery, Recurrence, Seton, Wrist

Pharmacological Evaluation and Synthesis of New Sulfonamides Derivatives Based on 1,4-Benzodioxane

We report here the synthesis of a series of N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide and its N-substituted derivatives with benzyl chloride and ethyl iodide. Initially, 2,3-dihydrobenzo[1,4]dioxine-6-sulfonyl chloride (1) was subjected to react with various aryl amines (2a-e) to afford parent compounds N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (3a-e). At second step, these parent compounds were reacted with benzyl chloride (4) and ethyl iodide (5) as to synthesize N-benzyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (6a-e) and N-ethyl-N-aryl-2,3-dihydrobenzo[1,4]dioxine-6-sulfonamide (7a-e) in the presence of lithium hydride and N,Nꞌ-dimethylformamide respectively. FT-IR, Nuclear Magnetic Resonance (1H-NMR) and Mass Spectrometry (MS) techniques were used to investigate the structures of these synthesized compounds. A fingerprinted study was conducted against some enzymes like butyrylcholin-esterase (BChE), acetylcholinesterase (AChE) and lipoxygenase (LOX). This study revealed that most of them demonstrated a moderate activity against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) however promisingly a good activity against lipoxygenase enzyme was observed. Finally, an antimicrobial and hemolytic activities of these sulfonamides were probed which confirmed that the parent sulfonamides 3b have the proficient antimicrobial activities, while the derivatives 6a, 7a, 7b and 7c explored a good activity against the selected panel of bacterial and fungal species. All the compounds were further computationally docked against (LOX), (BChE) and (AChE) enzymes and these interaction highlighted the importance of sulfonamides in the inhibition of the target enzymes

Dose optimization of β-lactams antibiotics in pediatrics and adults:A systematic review

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses