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Biomedical subjects

S Pervez

Publications and source records attributed to S Pervez.

At least 19 recordsLinked to original sources

Time-integrated thyroid dose for accidental releases from Pakistan Research Reactor-1.

The two-hourly time-integrated thyroid dose due to radio-iodines released to the atmosphere through the exhaust stack of Pakistan Research Reactor-1 (PARR-1), under accident conditions, has been calculated. A computer program, PAKRAD (which was developed under an IAEA research grant, PAK/RCA/8990), was used for the dose calculations. The sensitivity of the dose results to different exhaust flow rates and atmospheric stability classes was studied. The effect of assuming a constant activity concentration (as a function of time) within the containment air volume and an exponentially decreasing air concentration on the time-integrated dose was also studied for various flow rates (1000-50000 m3 h(-1)). The comparison indicated that the results were insensitive to the containment air exhaust rates up to or below 2000 m3 h(-1), when the prediction with the constant activity concentration assumption was compared to an exponentially decreasing activity concentration model. The results also indicated that the plume touchdown distance increases with increasing atmospheric stability.

Air Movements↗

Diagnostic surgical pathology: the importance of second opinion in a developing country.

OBJECTIVE: To review the cases sent to the section of histopathology, Aga Khan Universty (AKU) for second opinion and see whether there are significant differences in the original outside diagnosis and the subsequent diagnosis submitted by us. METHODS: A retrospective study of all consecutive cases for second opinion in the form of paraffin blocks from 1st Novemver 2001 to 31st July 2002. The primary submitted diagnosis in each case was compared with the subsequent AKU diagnosis. RESULTS: The study included a total of 381 cases. However, in 45 cases (11.81%), initial histopathological diagnosis was not provided. Out of the remaining 336 cases, there were differences between the original diagnosis and the subsequent AKU diagnosis in 120 cases (35.71%). Out of these 120 cases, immunohistochemistry was performed in 65 cases (54.16%) only. CONCLUSION: In a developing country like Pakistan, where few laboratories are equipped to function as modern histopathology units, second opinion on difficult cases is very important. Worldwide, the concept of second opinion in surgical pathology is well established.

Bone and Bones↗

Cancer esophagus Karachi 1995-2002: epidemiology, risk factors and trends.

OBJECTIVE: To study the trends of cancer esophagus in Karachi South during 1995-2002 and identify risk factors. METHODS: Incident esophageal cancer cases recorded at the Karachi Cancer Registry for Karachi South, during 1st January 1995 to 31st December 2003 were reviewed. For maximum completion of data, incident cases registered from 1st January 1995 to 31st December 2002 were included for final analyses. RESULTS: The Age Standardized Incidence Rates (ASIRs) of cancer esophagus in Karachi South for males were 6.5/100,000 (1995-1997) and 6.4/100,000 (1998-2002). In females the observed rates were 7.0/100,000 (1995-1997) and 8.6/100,000 (1998-2002). CONCLUSION: In the moderately high incidence, cancer esophagus zone of Karachi, the ASIRs in males remained stable during the last decade, but in females, an upward trend was observed suggesting a progressively higher exposure to risk factors in the latter. The potential risk factors in Karachi are use of all forms of tobacco, areca nut, infrequent consumption of raw fruits and vegetables and diet deficiencies. There is a necessity to actively control the proven risk factors and address the existence of other risk factors. The primary recommended strategy for the control of cancer esophagus would therefore be legislation against tobacco and areca nut in Pakistan and public health education. The risk factors of cancer esophagus identified in this article need to be further confirmed.

Adult↗

Orbital embryonal rhabdomyosarcoma in Karachi (1998-2002).

OBJECTIVE: To study the epidemiology of ocular Rhabdomyosarcoma (ORMS) in Karachi. METHODS: Incident ORMS cases resident of Karachi, registered at Karachi Cancer Registry (KCR) during 1st January 1998 to 31st December 2002 were included in the study. The data were classified using ICD-O2; computerized with Canreg-3, and analyzed using SPSS 10.0. RESULTS: Ten cases of ORMS were reported to KCR during 1998-2002. RMS originated in the orbit in eight cases, conjunctiva in one and eyelid in one. Nine cases presented with proptosis, associated with conjunctivitis in four cases. One case presented with eyelid swelling. The crude annual incidence rate was 0.13/100,000, the age standardized rate was 0.3/100,000. The mean age of childhood cases was 10.4 years (95% CI 4.0; 16.7); and adult cases was 24.8 years (95% CI 12.8; 36.7). At presentation, eight patients were older than 10 years and three were older than 20 years. Five cases were categorized as childhood malignancies. Tumors were a TNM stage III disease at presentation in eight cases; survival at the end of one year was 70%, and at the end of two years 20%. There were no survivors at the end of three years. CONCLUSION: ORMS in Karachi is a disease with a dismal survival. It may reflect a late presentation, or shorter adult ORMS survival or a manifestation of a different genetic pattern, associated with rapid evolution and poor prognosis. Health education for the population, especially parents and health providers is essential for early ORMS diagnosis. Pediatricians, ophthalmologists and health professionals, can play a vital role. Healthcare planning should focus on capacity building for ophthalmologic screening. Cytogenetic studies are advised to determine the genetic pattern.

Adult↗

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 (1993-1996) 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 change 13.96%, 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 >2 cms. in 93% of cases and 40% of them showed 3 or >3 positive lymph nodes. Grade I tumours were 11.38%, grade II 59.17% and grade III tumours 29.47%. Correlation of grade with lymph node metastases (3 or >3+ve nodes) showed 15 cases (1.53%) of grade I, 178 cases (18.25%) of grade II and 68 (6.97%) cases of grade III 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.

Adult↗

DNA ploidy and S-phase fraction analyses of hyperplastic, atypical and cancerous endometrium using flow cytometry from paraffin-embedded tissues.

Atypical hyperplasia of the endometrium is an entity that needs to be clearly distinguished from other florid hyperplastic states on the one hand and from well-differentiated adenocarcinomas on the other. This may at times be difficult on pure morphological grounds. In this study, DNA ploidy and S-phase fraction of hyperplastic, atypical and cancerous endometrium were evaluated using flow cytometry from paraffin-embedded tissues. In total, 72 cases (24 hyperplastic, 24 atypical and 24 adenocarcinomas) were selected. All hyperplastic endometria showed a diploid stemline, while 2/24 atypical hyperplasias showed aneuploid (Near-diploid) peaks. Both of these cases were severely atypical and one of these, on hysterectomy, showed early invasive carcinoma. There was no significant difference in mean S-phase fractions of hyperplastic vs. atypical endometria. DNA aneuploidy was significantly more common with much higher S-phase fractions in poorly and moderately differentiated carcinomas than in well-differentiated ones. It was concluded that aneuploid (near-diploid) peaks, if ever present in atypical hyperplasias, may indicate an aggressive disease/neoplastic transformation.

Adenocarcinoma↗

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 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR also known as EGFR1). 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 III tumours. Axillary lymph node metastasis had significant correlation with intensified positivity of EGFR (p < 0.05). Significant number of EGFR positive patients developed local recurrence and distant metastases to brain, liver and bone (p < 0.05). EGFR positivity showed significant correlation with the disease free and overall survival (p < 0.05). At a median follow-up of 48 (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.

Adult↗

Clinical, pathological and molecular factors predicting axillary node involvement in primary breast cancer in Pakistani women.

BACKGROUND: Axillary lymph node involvement in primary breast cancer is one of its most important prognostic features. Thus any factors that may predict axillary lymph node involvement in this setting could be potentially helpful in treatment planning and other interventions. OBJECTIVE: The objective of this study was to evaluate clinical, pathological and immuno-histochemical markers in univariate and multivariate analysis, which may be helpful predictors of axillary lymph node involvement in breast cancer. METHOD: A retrospective analysis of 555 cases. Of these 58% had axillary nodal positivity and 42% were negative. CONCLUSION: Factors of no significance included patient's age, height, weight, age of first pregnancy, parity, marital status, menopausal status, family history of breast cancer, side of tumor. In univariate analysis the age of menarche, duration of symptoms, tumor size, site in outer quadrant, S phase and skin and nipple involvement all predicted axillary nodal involvement. The length of breast-feeding, increased intraductal component and increased PCNA were inversely proportional to nodal involvement. In multiple regression analysis however only size of the tumor, involvement of the skin and nipple and disease in the outer quadrant of breast were the factors, which assumed significance.

Axilla↗

Cancer patterns in Karachi division (1998-1999).

OBJECTIVE: A minimal cancer incidence data for Karachi, the largest city of Pakistan, is being presented here, for the years 1998-1999. The city has a population of 9,802,134; males 5,261,712 (52.6%) and females 4,540,422 (47.4%); census 1998. METHODOLOGY: A predominantly mixed (passive and active) registration system has evolved in Karachi, the data sources being the hospitals within the Karachi Division. The reported/retrieved cancer data sets at the Karachi Cancer Registry are checked, coded, computerised in an analytical format and analysed. RESULTS: The incident cancer cases registered in Karachi, during the 2-year period, 1st January 1998 to 31st December 1999 were analysed. The age-standardised incidence rate (ASR) of cancer, all sites was 132.4/100,000 for the males. Cancer of the lung 10.8%; ASR 17.3 was the most frequently recorded malignancy, followed by oral cavity 10.5%; ASR 13.2 and larynx 5.0%; ASR 7.4. The age-standardised incidence rate (ASR) of cancer, all sites was 133.0/100,000 in the females. Cancer of the breast, 32.0%; ASR 40.7 was the most frequently recorded malignancy, followed by oral cavity 8.1%; ASR 11.7 and gall bladder 3.6%; ASR 5.5. CONCLUSION: The present data has been calculated with an estimated 15-20% probable under ascertainment. Tobacco-associated cancers in Karachi were responsible for 38.3% of the tumours diagnosed amongst the males. Two principal cancers, breast and oral cavity were responsible for 40.1% of the cancers in females. A rare finding was the high incidence of gall bladder cancer in the females. At present it is difficult to determine whether this indicates a genuine high risk or a selection bias. A continuous process of cancer registration to study the trends in the incidence and an adequate cancer control program are possible and essential for Pakistan and can be based on the pattern being practiced in Karachi.

Breast Neoplasms↗

Transitional cell carcinomas of the urinary bladder. A histopathological study.

OBJECTIVE: To determine the histological grading and muscle invasion in Transitional Cell Carcinomas of the Urinary Bladder; and to evaluate whether any correlation exists between tumour grade and muscle invasion. METHOD: A Retrospective study of all consecutive cases of Transitional Cell Carcinomas of the Urinary Bladder diagnosed at Aga Khan University Hospital between 1st Jan 1997 and 31st Dec 2000. RESULTS: This study included 495 cases of Transitional Cell Carcinoma of the Urinary Bladder. M: F ratio was 4:1. Ages of patients ranged from 30 years to 87 years. Mean age in males was 59.1 years and in females 58.8 years. Forty four percent cases were Grade II, and 29.5% Grade III. None of the Grade I lesions were invasive, 10% Grade II tumours, 61.41% of Grade III and all Grade IV tumours were invasive. CONCLUSION: There is a definite correlation between advancing tumour grade and muscle invasion.

Adult↗

Cancer patterns in Quetta (1998-1999).

INTRODUCTION: Quetta, the capital of Baluchistan, is located at latitude 30.25; longitude 67.00. It has a population of 759,245; 425,474 males (56%) and 333,771 females (44%); Census 1998. The majority of residents are Persian or Baluchi speaking Baluchs. METHODOLOGY: The cancer cases from Quetta reported to the Karachi Cancer Registry were reviewed. The data included cases from the Aga Khan University Hospital (AKUH), Pathology Department (Quetta collection point) and health care facilities in Karachi. The residents of Baluchistan were ascertained and cancer cases residents of Quetta identified with the help of recorded addresses and retraceable telephone numbers. RESULTS: During a 2-year period, 1st January 1998 to 31st December 1999 the Karachi Cancer Registry received 1077 cancer notifications from Quetta. Approximately half the cases were registered from the AKUH Quetta collection point. Others were the referral patterns in Karachi. The age-standardized incidence rate (ASR) of cancer, all sites (1998-99) was 137.0 for males and 92.8/100,000 for females. The commonest cancer in the males and females was cancer of the esophagus (ICD-10 categories C15; males- ASR 25.5, 17.2%; females-ASR 23.4,23.1%). One ofthe highest in the world, for both genders. Incidence of cancer breast in the females (ICD-10 categories C50; ASR 11.8, 13.3%) was low. CONCLUSION: The cancer data from Quetta is quite distinct from the cancer pattern of Karachi. It represents only a part of the cancer burden of Quetta; nonetheless it gives a glimpse into the cancer profile of Baluchistan. The high incidence of esophageal cancer indicates an extension of the geographical limits of the esophageal cancer belt.

Female↗

Folinic acid protects against suppression of growth by methotrexate in mice.

The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean+/-SD body weight 9.64+/-0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post-MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes. Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8+/-0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one-way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short-term suppression of growth, however they could benefit from supplementation with folinic acid.

Animals↗

Significance of immunohistochemical c-ErbB-2 product localisation pattern for prognosis in human breast cancer.

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified, including c-ErbB-2. In this study, expression of c-ErbB-2 in breast carcinoma was correlated with axillary lymph node metastases and disease outcome. The expression of c-ErbB-2 oncoprotein was analysed in 315 tumor specimens of infiltrating ductal carcinoma of breast. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. These patients also had axillary lymph nodes sampling. The expression of c-ErbB-2 oncoprotein was analysed immunohistochemically. Over expression of c-ErbB-2 were observed in 39.36% tumors. Axillary lymph node metastasis had significant correlation with intensified positivity of c-ErbB-2. C-ErbB-2 positive patients did show resistance to chemotherapy when compared for recurrence and distant metastases following surgery (p< 0.05). At a median follow-up of 48 months in c-ErbB-2 positive patients, the overall survival was 3.0 years and disease free survival was 2.5 years. c-ErbB-2 negative tumor patients showed a far better survival. In this group the overall survival was 4.44 years and the disease free survival was 3.78 years. These findings reinforce the view that c-ErbB-2 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.

Breast Neoplasms↗

DNA ploidy analyses in 218 consecutive Pakistani breast cancer patients: does it add anything?

An analysis was made to evaluate the significance of DNA ploidy in the biology and prognosis of breast carcinoma. This was done by estimating the correlation of DNA ploidy with other established prognostic markers of breast cancer, namely tumor size, tumor grade, lymph node metastasis and S-phase fraction. From 1995 up to year 2000 ploidy analysis was performed on 218 consecutive cases of infiltrating breast carcinoma by flow cytometry using formalin fixed paraffin embedded material. From the laboratory record, data regarding other pathological variables was retrieved. No correlation could be found between DNA ploidy and tumor grade, nor could there be found a correlation with tumor size. For lymph node metastasis there was a significant difference between the proportion of aneuploids and diploids having metastasis in more than 4 lymph nodes. However, no significant difference was found in axillary lymph node positive and negative groups when number of positive lymph nodes was not taken into account. The mean value of S-phase fraction for the aneuploids and the diploids was also insignificantly different. In conclusion DNA ploidy alone did not add much to predict tumor behaviour in terms of known pathologic variables.

Adult↗

Technetium-99m direct radiolabeling of lanreotide: a somatostatin analog.

Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide 99mTc. Labeling was accomplished by reduction of the cysteine bridge, which provided sulfhydryl groups for chelation with 99mTc. Stannous chloride was used as reducing agent, while tartrate acted as transchelating agent. Lanreotide (100 microg), stannous chloride dihydrate (100 microg) and tartaric acid (64 microg) were dissolved in acetate/acetic acid buffer (pH 2.8). After overnight (approximately 18 h) incubation, approximately 444 MBq (12 mCi) 99mTc was added and kept in boiling water for 30 min. More than 97% labeling efficiency was confirmed by RP-HPLC, ITLC-SG and C18 cartridge analysis. Radiolabeling results in one major peak when analyzed by reverse-phase HPLC. The stability of the 99mTc-peptide bond was evaluated by cysteine challenge studies.

Chromatography, High Pressure Liquid↗

Evaluation and reinforcement of the correlation of S-phase fraction with nodal metastases, tumor grade and tumor size in breast carcinoma patients in Pakistan.

The aim of this study was to evaluate the S-phase fraction (SPF) of tumors in breast cancer patients in Pakistan. Its association with the traditional morphological prognostic markers, i.e., axillary lymph node metastasis, tumor size and grade, was also studied. Flow cytometry was used to estimate SPF on breast cancer tissues from 166 patients reported at the Aga Khan University Hospital between the years 1997 and 2000. Univariate analysis was done to find any association between SPF and the aforesaid variables. For the ease of analysis, the cases were subdivided into two categories depending on the SPF value, i.e., <10% (low-risk group) and > or = 10% (high-risk group). The mean and median SPF values were 21.45% and 20.035%, respectively, with a range of 3.26% to 54.30%. Twenty-six (15.66%) of the cases had SPF <10%, 57 (34.34%) had SPF from 10%-20%, and 83 (50%) had SPF >20%. A significant correlation between SPF and nodal metastasis was observed (p = 0.0111), but not between SPF and the number of lymph nodes involved when metastatic cases were subdivided into <4 lymph node-positive cases and > or =4 lymph node-positive cases. Significant correlations were also found between SPF and tumor grade (p = 0.0244), as well as between SPF and tumor size (p = 0.048). In conclusion, DNA flow cytometric analysis of SPF carried out in our laboratory could reasonably predict the chances of lymph node metastasis, tumor grade and size in breast cancer patients, thus proving to be an important prognostic marker in the Pakistani setting. This requires further investigations regarding the survival of patients so as to evaluate its capacity of predicting the outcome of Pakistani patients.

Adenocarcinoma↗