Diagnostic Significance Of Bone Marrow Examination Amongst The Patients With Abnormal Haematological Parameters.

BACKGROUND: Bone Marrow examination is considered to be the most indispensable diagnostic tool for the evaluation of many neoplastic and non-neoplastic haematological disorders. After an initial assessment of suspicious cases on abnormal laboratory parameters along with the clinical presentation of the patient marrow examination is finally required for diagnosis as well as management of many haematological malignancies as it offers a clear cytological as well as histological picture of Bone Marrow aspirate and biopsy respectively. The Objective was to evaluate the significance of Bone Marrow examination in patients with abnormal haematological parameters. METHODS: A retrospective study conducted at the Pathology Department of Pak Emirates Military Hospital from (Jan-June 2022) On data from150 patients who were advised to undergo bone marrow examination due to abnormal lab parameters and peripheral smear findings after informed consent and approval from the ethics review committee, to find out the correlation of abnormal haematological parameters and aspirate findings which have led to a definitive diagnosis. Data comprising basic demographic variables (age, gender etc.), Abnormal Haematological Parameters (CBC), peripheral smear findings and Aspirate findings were analyzed using SPSS version 23.0. RESULTS: Out of 150 studied participants with abnormal haematological parameters 24 (16%) were diagnosed on bone marrow examination as acute leukaemia / Hodgkin's and Non-Hodgkin's lymphoma respectively, 13 (9%) cases of aplastic anaemia and Autoimmune HaemolyticAnaemia, 33 (22%)cases of hypersplenism, CML and multiple myeloma. While 22 (15%) cases were diagnosed with BME as CKD and reactive changes. Moreover, 22(15%) cases were found to have Iron Deficiency anaemia respectively. CONCLUSIONS: The study revealed that patients with abnormal haematological parameters should undergo bone marrow examination to ascertain the diagnosis for malignant as well as non-malignant conditions that could cause abnormal lab parameters.

Development of Simple Dissolution Methods for Felodipine and Combined Amlodipine Besylate-Indapamide Extended Release Tablets without Stationary (Felodipine) Basket.

BACKGROUND: The dissolution method for certain drugs needs specialized conditions. Dissolution testing for felodipine extended release (ER) tablets (Plendil® 5 mg) and amlodipine-indapamide fixed dose (Natrilam®, 5/1.5 mg) ER tablets requires the use of a stationary (felodipine) basket in USP Apparatus II. OBJECTIVE: The study aimed to develop simple methods for Plendil® and Natrilam® without the use of a felodipine basket. METHODS: The dissolution profiles obtained from different media and paddle speeds were used to compute miscellaneous dissolution parameters and were compared to those obtained from standard (existing) methods using a felodipine basket. RESULTS: The f1, f2, and bootstrap f2 (5th % percentile) values for Plendil® 2.47, 88.17, and 54.62, respectively, and all other dissolution factors revealed similarity between standard and the selected test method with 1% Tween 20 at 50 rpm. For Natrilam®, f1 and f2 and bootstrap f2 5.13, 72.92, and 62.67, respectively, and all other dissolution parameters showed similarity of the standard and selected test method using 0.1N HCl media having 0.38 gm/L EDTA with a sinker at 100 rpm. Release of products assumed zero-order and Weibull model, respectively. CONCLUSION: Test dissolution methods for Plendil® and Natrilam® tablets produced equivalent dissolution profiles compared to their respective standard methods with stationary basket USP Apparatus II.

Protective effect of hesperidin in Poloxamer-407 induced hyperlipidemic experimental rats.

Hyperlipidemia is one of the leading causes of, atherosclerosis, and cardiovascular disease. In this study, we evaluated the protective role of hesperidin (HES) against lipidemic stress in a hyperlipidemic model of rats. We developed a hyperlipidemic model of the rat through an i.p dose of poloxamer-407, 0.5 g/kg body weight for 3 alternative days in a week for 30 days and rats were supplemented with HES orally (100 mg/kg body weight) once daily. Bodyweight, fasting glucose, insulin, HOMA-IR index, triglyceride, cholesterol, ROS, FRAP, GSH, PMRS, AGE, MDA, PCO, AOPP, PON-1, TNF-α and IL-6, SGPT and SGOT were estimated in blood and plasma, and histopathology was done in liver tissue. Our data show that oxidative stress, inflammatory markers were increased in the P-407 treated group. Liver tissue histology also changes in the hyperlipidemic groups of rats.HES supplementation protects against P-407 induced alterations and maintains the redox homeostasis. Our results provide evidence that HES protects against lipidemic stress and redox imbalance induced by P-407 in rats.

Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity.

CONTEXT: The anti-diabetic medicine metformin has been reported as an anti-ageing drug candidate as it mimics the benefits of caloric restriction and reduces ageing-related oxidative stress in various experimental organisms. OBJECTIVE: We investigated the possible anti-oxidative role of metformin against rotenone-induced oxidative stress and cytotoxicity in erythrocytes of Wistar rats. Rotenone is a well-known inducer of oxidative stress which leads to a cellular redox imbalance. MATERIALS AND METHODS: We have co-exposed the experimental rats with rotenone (2.5 mg/kg, i.p.) and metformin (300 mg/kg, orally) for 30 days to investigate the protective effects of metformin on various rotenone-induced impaired oxidative stress biomarkers in rat erythrocytes. RESULTS: We found that a significant alleviation in the levels of rotenone-induced pro-oxidant and anti-oxidant markers following exposure of metformin. DISCUSSION AND CONCLUSIONS: Our findings suggest that metformin supplementation shows a protective role in against rotenone-induced redox imbalance and cytotoxicity in rat erythrocytes.

Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat.

Diets rich in saturated fats and cholesterol contribute to the incidence of hyperlipidaemia. An altered lipid profile is a major factor responsible for the development of CVD. Male Wistar rats were fed with a high-fat diet (HFD) (suspension (w/v) of 0.5% cholesterol, 3% coconut oil and 0.25% cholic acid for 30 days) to induce an experimental hyperlipidaemic model. High-fat diet fed rats were also supplemented with hesperidin (100 mg/kg body weight). The present study reports reactive oxygen species (ROS) production, oxidative stress parameters: malondialdehyde (MDA), protein carbonyl (PCO), oxidation of plasma protein (AOPP), and advance glycation end products (AGEs); antioxidant defence parameters: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), Paraoxonase-1 (PON-1), plasma membrane redox system (PMRS); general biochemical parameters: triglyceride, cholesterol, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT), fasting insulin, fasting glucose, homeostatic model assessment-insulin resistance (Homa-IR) index, and inflammatory biomarkers: interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Experimental hyperlipidaemia was found to be associated with significantly higher body weight (27.58%), cholesterol (140%), triglyceride (190%), and fasting glucose level (37%). Reactive oxygen species production (67%), MDA (28.9%), AOPP (31.42%), PCO (58.53%), and PMRS (156%), inflammatory markers, cytokines IL-6 and TNF-α, were elevated and GSH (50%), PON 1 (37.07%), and FRAP (26.58%) activity were significantly (P < .05) lower in the high-fat diet group. Hesperidin supplementation protected HFD-fed rats from oxidative damage. Our findings indicate that the supplementation of hesperidin provides protection against redox imbalance induced by hyperlipidaemia in rats.

Diagnostic utility of C-kit protein (CD117) expression in differentiating adenoid cystic carcinoma and polymorphous low grade Adenocarcinoma.

BACKGROUND & OBJECTIVE: To evaluate usefulness of immunohistochemical marker C-kit (CD117) in differentiating Adenoid cystic carcinoma (AdCC) from Polymorphous low-grade adenocarcinoma (PLGA) in patients of salivary gland carcinomas. AdCC is a malignant salivary gland neoplasm with poor prognosis. PLGA is a salivary gland malignancy with indolent growth pattern. Differentiating between the two entities is a diagnostic challenge. We evaluated the role of C-kit in differentiating the two. METHODS: This is a Cross sectional study. Samples of 19 tumors including 12 AdCC and 4 PLGA was evaluated at Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from December 2015 to August 2016. Immunohistochemical techniques were used to analyze the level of c-kit expression in AdCC (n = 12), polymorphous low-grade adenocarcinoma (PLGA) (n = 6). Samples were stained using monoclonal antibody against C-kit. Statistical analysis of the data was done using SPSS version 21. RESULTS: Strong diffuse cytoplasmic reactivity was observed in more than 50% of the tumor cells of AdCC whereas less than 20% of cells showed negative to weak positivity in PLGA. Hence, the difference in the expression of c-kit between AdCC and PLGA was statistically significant (p value <0.002). CONCLUSIONS: CD117 expression itself can be used as a marker in differential diagnosis of salivary gland neoplasms. However, the percentage of the CD117 immunoreactive cells and the staining intensities appeared to be important factors in distinguishing AdCC from PLGA.

Immunohistochemical Expression of Epidermal Growth Factor Receptor and c-Kit in Triple Negative Breast Cancer.

OBJECTIVE: To determine the frequency of immunohistochemical expression of epidermal growth factor receptor (EGFR) and c-KITin triple negative breast cancer (TNBC). STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to December 2014. METHODOLOGY: Fifty cases of triple negative breast cancer diagnosed on immunohistochemistry were included in the study. Patients'gender and age were noted. Immunohistochemistry for EGFR and c-KITwere applied and the results were recorded. The data were analyzed by using computer software programme SPSS version 19. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of 50 patients of TNBC, all patients were females. The ages of the patients ranged between 30 and 80 years with an average age of 48.9 years and standard deviation of ±10.0. Out of 50 cases, 29 cases (58%) were positive for EGFR while 15 cases (30%) were positive for c-KIT. Thirteen cases (26%) were positive for both EGFR and c-KIT. Nineteen cases (38%) were negative for both EGFR and c-KIT. CONCLUSION: EGFR expression was observed in 58% and c-KITexpression was seen in 30% of the cases. The results of EGFR expression are almost similar while those of c-KIT are different from international studies which suggest immunohistochemical differences between the studied populations.

Frequency of epstein-barr virus in classical hodgkin Lymphoma.

BACKGROUND: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. METHODS: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. RESULTS: Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. CONCLUSIONS: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.

CD 10 expression intensity in various grades and stages of urothelial carcinoma of urinary bladder.

OBJECTIVE: To evaluate CD10 expression in urothelial carcinoma of the urinary bladder and the association of immunohistochemical (IHC) CD10 expression intensity with grade and stage. STUDY DESIGN: Descriptive cross-sectional analytical study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology, Rawalpindi, from January to December 2011. METHODOLOGY: Fifty consecutive cases of urothelial bladder carcinomas, obtained through transurethral resections, were included in this study. Hematoxylin-eosin (HE) stained sections from each case were re-evaluated histopathologically according to WHO 2004 grading system. The TNM system was used for pathologic staging. On selected slides IHC CD10 marker was applied and a semiquantitative scoring for its expression based on the percentage of positive cells and intensity was performed. Data was entered and analysed on SPSS version 17. Fisher's exact test was used to compare grades, stages of urothelial carcinoma with CD 10 expression and age groups. P < 0.05 was taken as level of significance. RESULTS: Urothelial carcinoma was more common in males. The male to female ratio was 9:1. The older patients > 50 years had higher grade and stage as compared to the younger patients. All cases of high grade urothelial carcinoma showed higher positivity for CD 10. Twenty cases (86.95%) of high grade urothelial carcinoma were positive with +2 immunostaining while 3 cases (13.04 %) were positive with +1 staining. None of the tumors of stage pTa was positive for CD 10 expression. Of all patients with stage pT 1 tumor, 1 case (5.3%) was CD 10 negative and 17 cases (89.9%) were CD 10 positive having +1 staining with 5 - 50% staining and 1 case (5.3%) had +2 staining with more then 50% expression. Out of all patients with stage pT 2, no tumor was CD 10 negative, 3 (13.6%) patients were CD 10 positive with +1 staining and 19 (86.4%) with stage pT 2 tumor had stained positive with +2 staining. CONCLUSION: CD 10 expression was greater in high grade and invasive urothelial carcinomas; it may be associated with tumor progression in bladder cancer pathogenesis.

Clinicopathological evaluation of odontogenic tumours in Pakistan - a seven years retrospective study.

BACKGROUND: The purpose of the study was to analyse the clinicopathological spectrum of benign and malignant odontogenic tumours (OT) in Pakistan. MATERIALS AND METHODS: This retrospective study was carried out at the Armed Forces Institute of Pathology (AFIP) Rawalpindi. Seven years archival records of histologically diagnosed odontogenic tumours, both benign and malignant, were collected and the lesions re-diagnosed histologically in accordance with the WHO classification of head and neck tumours (2005). Clinical as well as histological data were analysed and frequency of each type of OT was calculated using computer software programme SPSS (version 17). Mean tumour size was calculated and Chi-square test was applied to find associations of age, gender and site with each histological type of tumour. RESULTS: Only 1.7% of the odontogenic tumours diagnosed in this said period were malignant while the remaining 98.3% were benign. Amongst benign lesions, ameloblastoma was the most common (61.3%) type while primary intraosseous squamous cell carcinoma (1.7%) was the only reported malignant tumour. Mean age of the affected patients was 31.7±16.7 years with posterior mandible as the commonest site involved. CONCLUSIONS: Our study revealed ameloblastoma and primary intraosseous squamous cell carcinoma as the commonest diagnosed benign and malignant tumours respectively. There was a significant difference in age and site of origin of different types of OT at the time of their presentation. However, all the tumours showed male predominance.

Spectrum of liposarcomas-a study of 106 cases.

BACKGROUND: Liposarcoma is a malignant tumour that arises in fat cells in deep soft tissue. This study was conducted to access the spectrum of liposarcomas METHODS: This descriptive study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi from 1st January 2008 to 31st December, 2012 and included all the cases diagnosed as liposarcomas. Records of the malignant tumors of soft tissue that presented during this period were analysed and out of this spectrum of liposarcomas were studied. RESULTS: A total of 19367 malignant tumours were diagnosed during study period. Out of these, 615 were malignant soft tissue tumours. Out of these 106 cases were liposarcoma with an overall frequency of 0.54% of the malignant neoplasm and 17.24% of soft tissue sarcomas .The age ranged from 26-85 years. Out of these 106 cases 77 were male and 29 were female with a male to female ratio of 2.6:1. The most common tumour seen was pleomorphic liposarcoma (42.5%) followed by myxoid liposarcoma (22.6%), dedifferentiated liposarcoma (19.8%) and well differentiated liposarcoma (15.1%). Fifty five (51.9%) of liposarcomas originated in lower extremity, the second most commonly involved site was upper extremity (22.6%) CONCLUSION: Pleomorphic Liposarcoma is the commonest liposarcoma of extremities and their frequency is much high in our population.

GLIMPSE: a rapid decision framework for energy and environmental policy.

Over the coming decades, new energy production technologies and the policies that oversee them will affect human health, the vitality of our ecosystems, and the stability of the global climate. The GLIMPSE decision model framework provides insights about the implications of technology and policy decisions on these outcomes. Using GLIMPSE, decision makers can identify alternative techno-policy futures, examining their air quality, health, and short- and long-term climate impacts. Ultimately, GLIMPSE will support the identification of cost-effective strategies for simultaneously achieving performance goals for these metrics. Here, we demonstrate the utility of GLIMPSE by analyzing several future energy scenarios under existing air quality regulations and potential CO2 emission reduction policies. We find opportunities for substantial cobenefits in setting both climate change mitigation and health-benefit based air quality improvement targets. Though current policies which prioritize public health protection increase near-term warming, establishing policies that also reduce greenhouse gas emissions may offset warming in the near-term and lead to significant reductions in long-term warming.

A direct sensitivity approach to predict hourly ozone resulting from compliance with the National Ambient Air Quality Standard.

In setting primary ambient air quality standards, the EPA's responsibility under the law is to establish standards that protect public health. As part of the current review of the ozone National Ambient Air Quality Standard (NAAQS), the US EPA evaluated the health exposure and risks associated with ambient ozone pollution using a statistical approach to adjust recent air quality to simulate just meeting the current standard level, without specifying emission control strategies. One drawback of this purely statistical concentration rollback approach is that it does not take into account spatial and temporal heterogeneity of ozone response to emissions changes. The application of the higher-order decoupled direct method (HDDM) in the community multiscale air quality (CMAQ) model is discussed here to provide an example of a methodology that could incorporate this variability into the risk assessment analyses. Because this approach includes a full representation of the chemical production and physical transport of ozone in the atmosphere, it does not require assumed background concentrations, which have been applied to constrain estimates from past statistical techniques. The CMAQ-HDDM adjustment approach is extended to measured ozone concentrations by determining typical sensitivities at each monitor location and hour of the day based on a linear relationship between first-order sensitivities and hourly ozone values. This approach is demonstrated by modeling ozone responses for monitor locations in Detroit and Charlotte to domain-wide reductions in anthropogenic NOx and VOCs emissions. As seen in previous studies, ozone response calculated using HDDM compared well to brute-force emissions changes up to approximately a 50% reduction in emissions. A new stepwise approach is developed here to apply this method to emissions reductions beyond 50% allowing for the simulation of more stringent reductions in ozone concentrations. Compared to previous rollback methods, this application of modeled sensitivities to ambient ozone concentrations provides a more realistic spatial response of ozone concentrations at monitors inside and outside the urban core and at hours of both high and low ozone concentrations.

Diagnostic accuracy, sensitivity, specificity and positive predictive value of fine needle aspiration cytology (FNAC) in intra oral tumors.

OBJECTIVE: The objective of this study was to establish the diagnostic accuracy, specificity and sensitivity of fine needle aspiration cytology(FNAC) for intra-oral tumors, comparing with histopathology as the gold standard. MATERIALS AND METHODS: Forty cases of FNA cytology from intraoral tumors was performed in AFID along with the demographic data and clinical information and then diagnosed at AFIP, Rawalpindi. Then the cytology results obtained per FNAC were compared with the histopathological biopsy results of the same lesions. The following variables were recorded for each patient: Age, gender, site of biopsy, diagnosis. The data were entered and analyzed using Open-epi version 2.0. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Cohen Kappa was further applied to compare the agreement between the biopsy and FNAC diagnoses. A p-value of <0.05 was considered as statistically significant. RESULTS: Among the total patients included in the study there were 24 males and 16 females, with a ratio of 1.5:1. Age of the patients ranged from 24 to 80 years with a mean of 52 years. A total of six sites were aspirated from the oral cavity with maximum (11) aspirates taken from alveolar ridge. The results of FNAC revealed that there were 32 malignant and 8 benign aspirates. Confirmation through histopathological analysis came for 31/32 malignant cases while one was falsely given positive for malignancy on FNAC. Among a total of 40 cases, 31(77%) cases diagnosed were found to be malignant and remaining 9(23%) were benign. The FNAC results revealed 32 malignant and 8 benign lesions. Histopathology of the subsequent surgically excised specimen showed malignant lesions in 31(77%) and benign in 9(23%) patients. As a whole, it was found that the absolute sensitivity for intra oral FNAC was 100% and specificity 89% with positive predictive value of 97% and negative predictive value of 100%. CONCLUSION: Cytological diagnosis was almost corroborative with final histopathological diagnosis in all cases, with very few exceptions, exhibiting high diagnostic accuracy.

Spatially refined aerosol direct radiative forcing efficiencies.

Global aerosol direct radiative forcing (DRF) is an important metric for assessing potential climate impacts of future emissions changes. However, the radiative consequences of emissions perturbations are not readily quantified nor well understood at the level of detail necessary to assess realistic policy options. To address this challenge, here we show how adjoint model sensitivities can be used to provide highly spatially resolved estimates of the DRF from emissions of black carbon (BC), primary organic carbon (OC), sulfur dioxide (SO(2)), and ammonia (NH(3)), using the example of emissions from each sector and country following multiple Representative Concentration Pathway (RCPs). The radiative forcing efficiencies of many individual emissions are found to differ considerably from regional or sectoral averages for NH(3), SO(2) from the power sector, and BC from domestic, industrial, transportation and biomass burning sources. Consequently, the amount of emissions controls required to attain a specific DRF varies at intracontinental scales by up to a factor of 4. These results thus demonstrate both a need and means for incorporating spatially refined aerosol DRF into analysis of future emissions scenario and design of air quality and climate change mitigation policies.

Diagnostic challenges and role of immunohistochemistry in metastatic liver disease.

OBJECTIVE: To evaluate the role of Immunohistochemistry (IHC) in the diagnosis of metastatic liver disease, with a descriptive, cross-sectional study at the Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi. MATERIAL AND METHODS: A total of 130 cases of metastatic liver disease were retrieved from the tumor registry data. Eosin-haematoxylin stained sections and Immunohistochemistry panels applied to ascertain the site of primary tumor were evaluated. The panels of detailed immunohistochemical markers were applied. Frequency and percentages were calculated for qualitative variables. Mean and standard deviations were calculated for quantitative variables. RESULTS: Males were 87 (67%) and were females 43 (33.07%). The most common site of primary was in GIT (45%), followed by neuroendocrine carcinoma and gall bladder. The other less common sites were lung, breast, ovary and thyroid. CONCLUSION: There is no specific singular panel of immunohistochemistry markers which can be used in all cases of metastatic liver tumors. The best use and selection of IHC markers depend upon morphological features, clinical history and results of other relevant investigations.

Determination of her-2/neu by chromogenic in situ hybridization on borderline (2+) immunohistochemistry cases in carcinoma breast.

OBJECTIVE: To determine the HER-2/neu status by chromogenic in situ hybridization (CISH) on tissue specimens with a borderline (2+) immunohistochemistry (IHC) score in carcinoma breast by a descriptive, cross-sectional study in the Histopathology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jun 2008 to Dec 2009. METHODS: Tissue block specimens from 50 consecutive patients having HER-2/neu score of borderline (2+) on IHC assay were tested for HER-2/neu gene amplification by CISH. Mean and standard deviation were calculated for quantitative variables like age and HER-2/neu gene copy signal/clusters by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like type of carcinoma and results of HER-2/neu by CISH (amplified/nonamplified). RESULTS: HER-2/neu gene amplification by CISH was found in 10 (20%) out of 50 patients with borderline (2+) IHC score. All CISH amplified cases belonged to invasive ductal carcinoma type. No significant correlation was noted between type of carcinoma and HER-2/neu gene amplification. CONCLUSION: Chromogenic in situ hybridization (CISH) is a practical, cost-effective and reliable method for analysis of HER-2/neu borderline (2+) cases which may be candidates for Herceptin therapy.

Epidemiological and excision margin status of Basal cell carcinoma--three years Armed Forces Institute of Pathology experience in Pakistan.

OBJECTIVE: The rationale of this study is to analyze the demographic distribution and clearance of excision margin in basal cell carcinoma among patients diagnosed at AFIP Rawalpindi. MATERIALS AND METHODS: Records of a total of 235 cases diagnosed from January 2005 to December 2007 were retrieved from our tumour registry. The following variables were recorded for each patient: age, gender, site of biopsy, type of biopsy (incisional vs excisional) and status of clearance of surgical margins. The data was analyzed using SPSS version 17.0. RESULTS: Among the total of 235 cases, 125 (53.2%) were males and 110 (46.8%) were females (1.2:1). The ages ranged from 32 to 90 years with mean age of 60.0 + 11.7, with a general age-dependent increase. The nose was the most frequent site (28.9%), followed by the eye, including the orbit (24.7%), and the cheek (20.4%). Among the type of biopsies, 140 (59.6%) were excisional and 95 (40.4%) were incisional. With the former, the excision margins were reported as clear in 82 (34.9%) cases and involved in 55 (23.4%) cases. CONCLUSION: Basal cell carcinoma (BCC) appears to be on the rise in our part of world. Careful clinical assessment, and complete excision with the help of frozen sections can avoid recurrence.

Area of influence (AOI) development: fast generation of receptor-oriented sensitivity fields for use in regional air quality modeling.

An approach is developed and tested to extend discrete, source-based sensitivity results to provide a complete set of information for source-air quality impacts, including inversion of those results to develop receptor-oriented source-impact sensitivities. First, the decoupled direct sensitivity analysis method in 3D (DDM-3D) is used to calculate a finite number of forward sensitivities from discrete points. These results are then interpolated using tessellation to provide complete fields of forward, emissions-based sensitivities, i.e., how emissions in any one grid cell within the domain impact any other cell. Receptor-oriented sensitivities are then found by inverting the set of forward sensitivities and can be used to identify the area of influence (AOI). This economically provides results similar to what would be found using an adjoint model. The present approach is computationally less intensive than adjoint modeling for a large number of receptors, and provides both source-oriented and receptor-oriented pollutant response fields that can be used for air quality management and health impact analyses. The forward sensitivity interpolation procedure, as well as the receptor-oriented sensitivities, is evaluated using data withholding.