Cytopathic effect of Vero cells adapted Bangladeshi strain of peste des petits ruminants (PPR) virus in cell culture.

The present study described the cytopathic effect of PPR virus presently being used in serial passages at the level of 60th in Vero cells and infected tissue culture fluid was used in this study as viral inoculum. Vero cells were grown on cover slip & were infected with tissue culture fluid at a fixed multiplicity of infection (MOI) 0.01. The infected cover slip along with control were stained with H&E stain at periodic intervals and cytopathic effect was studied with microscope. The cytopathic effect (CPE) was visible at first from 24 hpi and the Vero cells showed initial cell rounding, aggregation, and syncytial development. Development of inclusion bodies and cell degradation was noticed by 72 hpi. Complete detachment of the cell monolayer was observed by 84 hpi. It is concluded that, development of numerous inclusion bodies are the indication of well adaptation & extensive multiplication of PPRV in Vero cells.

Predicting development of ipilimumab-induced hypophysitis: utility of T4 and TSH index but not TSH.

PURPOSE: Ipilimumab, a monoclonal antibody inhibiting CLTA-4, is an established treatment in metastatic melanoma, either alone or in combination with nivolumab, and results in immune mediated adverse events, including endocrinopathy. Hypophysitis is one of the most common endocrine abnormalities. An early recognition of hypophysitis may prevent life threatening consequences of hypopituitarism; therefore, biomarkers to predict which patients will develop hypophysitis would have clinical utility. Recent studies suggested that a decline in TSH may serve as an early marker of IH. This study was aimed at assessing the utility of thyroid function tests in predicting development of hypophysitis. METHODS: A retrospective cohort study was performed for all patients (n = 308) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. Thyroid function tests, other pituitary function tests and Pituitary MRIs were used to identify those with hypophysitis. RESULTS AND CONCLUSIONS: Ipilimumab-induced hypophysitis (IH) was diagnosed in 25 patients (8.15%). A decline in TSH was observed in hypophysitis cohort during the first three cycles but it did not reach statistical significance (P = 0.053). A significant fall in FT4 (P < 0.001), TSH index (P < 0.001) and standardised TSH index (P < 0.001) prior to cycles 3 and 4 in hypophysitis cohort was observed. TSH is not useful in predicting development of IH. FT4, TSH index and standardised TSH index may be valuable but a high index of clinical suspicion remains paramount in early detection of hypophysitis.

Clinical manifestations and outcomes of COVID-19 in the paediatric population: a systematic review.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), the respiratory illness caused by severe acute respiratory syndrome coronavirus 2, has affected hundreds of thousands of people. We aim to report the distribution of cases, prevalence, and clinical, radiological, and laboratory signs and outcomes of COVID-19 in paediatric patients. Moreover, we intend to evaluate neonatal clinical outcomes. Hence, our age range of interest is 0 to 19 years. METHODS: A systematic literature review was conducted using the Medline database to identify papers published between 1 December 2019 and 9 April 2020 on COVID-19. RESULTS: The search identified 27 relevant scientific papers and letters. The review showed that the prevalence of COVID-19 in the paediatric population accounts for a small percentage of patients, whose clinical signs and symptoms are often milder than those of adults. Despite better prognosis and low mortality in children, the disease can progress to severe pneumonia in some cases, especially in the presence of co-morbidities. Children are likely to become a hidden source of infection because of their atypical presentation, and they may play a role in community transmission, leading to unfavourable outcomes. There is little evidence about intrauterine vertical transmission. As no vaccine or specific antiviral is currently available, management plans include supportive treatment. CONCLUSION: As compared with that in adults, the presentation of COVID-19 in children is mild and has a better prognosis. Sufficient evidence regarding the probability of intrauterine vertical transmission could not be found, and further studies need to be conducted to establish this relationship.

Incidence, patterns, risk factors, and histopathological findings of liver injury in coronavirus disease 2019 (COVID-19): a scoping review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) exhibits many extrapulmonary manifestations, including liver injury. This scoping review aimed to provide insight into the incidence, patterns, risk factors, histopathological findings, and relationship with disease severity of COVID-19-associated liver injury. Furthermore, we identified existing gaps in the research on the hepatic manifestations of COVID-19 and highlighted areas for future investigations. METHODS: A scoping review was conducted following the methodological framework suggested by Arksey and O'Mallay. Five online databases, along with grey literature, were searched for articles published until 22 May 2020, and we included 62 articles in the review. The research domains, methodological characteristics, and key conclusions were included in the analysis. RESULTS: Retrospective observational studies comprised more than one third (41.9%) of the included publications, and 77.8% were conducted on living patients. The incidence of liver injury varied widely across the studies (4.8%-78%), and liver injury was frequently associated with severe COVID-19. We identified the following risk factors for liver injury: male sex, lymphopoenia, gastrointestinal involvement, old age, increased neutrophil count, and the use of hepatotoxic drugs. Histopathological findings indicate that COVID-19 has direct cytopathic effects and causes liver function test derangements secondary to inflammation, hypoxia, and vascular insult. CONCLUSIONS: Liver injury following COVID-19 infection is common and primarily hepatocellular, with a greater elevation of aspartate aminotransferase tahn of alanine aminotransferase. However, the evidence regarding hepatic failure secondary to COVID-19 is insufficient. Standardised criteria to diagnose liver injury need to be devised. Current use of hepatotoxic drugs necessitates close monitoring of liver function.

Protective effect of black relative to white race against non-alcoholic fatty liver disease in patients with severe obesity, independent of type 2 diabetes.

Severe obesity (body mass index ⩾35 kg m-2) and type 2 diabetes (T2D) are potent and additive risk factors for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Scant available evidence indicates that black relative to white patients with severe obesity are less susceptible to NAFLD, but it is unclear if T2D abolishes this apparent racial disparity. Therefore, we compared biopsy-proven NAFLD and its progression between black (n=71) and white (n=155) patients with severe obesity stratified by presence or absence of T2D. Although prevalence of T2D was similar between races (37%, P>0.9), whites were significantly more likely than blacks to have NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis and/or cirrhosis). Importantly, T2D was associated with increased odds of NAFLD, NASH and advanced fibrosis (defined as bridging fibrosis or cirrhosis) in whites only (P<0.05). In turn, a higher proportion of blacks than whites with T2D were free of NAFLD (58 versus 22%, P<0.01). These preliminary findings question translation of the powerful interconnection between T2D and NAFLD in whites with severe obesity to blacks and point to an important role of race in the pathophysiology and treatment of these diseases.

Clinical outcomes of adjuvant chemotherapy and vaginal brachytherapy with or without pelvic radiation for surgical stage I-II uterine serous carcinoma.

OBJECTIVE(S): To evaluate the benefit of adding pelvic radiation treatment (EBRT) to vaginal cuff brachytherapy (VB) for women with early stage uterine serous carcinoma (USC) treated with adjuvant chemotherapy. MATERIALS AND METHODS: After institutional review board (IRB) approval, the authors retrospectively identified 56 patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) Stage I-II USC treated with hysterectomy, bilateral oophorectomy +/- lymphadenectomy, adjuvant chemotherapy, and radiation therapy with either VB alone (n = 33) or VB + EBRT (n = 23) between July 1998 and August 2009. RESULTS: Median age and follow-up were 68.5 years and 54 months respectively. Median VB alone surface dose was 37.5 Gy and median pelvic EBRT dose was 45 Gy. The prevalence of lower uterine segment involvement, > 50% myometrial invasion, and Stage II disease were higher for patients receiving VB + EBRT. Overall, only one vaginal recurrence was observed. Pelvic recurrence rate was 26% for VB + EBRT compared to 12% for VB alone (p = 0.179). The five-year recurrence-free survival (RFS) was 80.5% for VB vs 67.3% for VB + EBRT (p = 0.3847), and the five-year overall survival (OS) was 65.9% for VB vs 66.7% for VB + EBRT (p = 0.7159). On univariate and multivariate analysis, radiation treatment modality was not a predictor for local control or survival. CONCLUSIONS: In this cohort, there was no significant clinical benefit of adding pelvic EBRT to the adjuvant management of early stage uterine serous carcinoma. The higher prevalence of high-risk features in the VB + EBRT group may underestimate the value of this treatment. Further investigation is warranted to identify the optimal radiation treatment regiment for early stage USC treated with surgery and adjuvant chemotherapy.

Mechanism of Wound-Healing Activity of Hippophae rhamnoides L. Leaf Extract in Experimental Burns.

The present investigation was undertaken to evaluate the healing efficacy of lyophilized aqueous leaf extract of Sea buckthorn (Hippophae rhamnoides L., family Elaeagnaceae) (SBT) and to explore its possible mechanism of action on experimental burn wounds in rats. The SBT extract, at various concentrations, was applied topically, twice daily for 7 days. Treatment with silver sulfadiazine (SSD) ointment was used as reference control. The most effective concentration of the extract was found to be 5.0% (w/w) for burn wound healing and this was further used for detailed study. The SBT-treated group showed faster reduction in wound area in comparison with control and SSD-treated groups. The topical application of SBT increased collagen synthesis and stabilization at the wound site, as evidenced by increase in hydroxyproline, hexosamine levels and up-regulated expression of collagen type-III. The histological examinations and matrix metalloproteinases (MMP-2 and -9) expression also confirmed the healing efficacy of SBT leaf extract. Furthermore, there was significant increase in levels of endogenous enzymatic and non-enzymatic antioxidants and decrease in lipid peroxide levels in SBT-treated burn wound granulation tissue. The SBT also promoted angiogenesis as evidenced by an in vitro chick chorioallantoic membrane model and in vivo up-regulated vascular endothelial growth factor (VEGF) expression. The SBT leaf extract had no cytotoxic effect on BHK-21 cell line. In conclusion, SBT aqueous leaf extract possesses significant healing potential in burn wounds and has a positive influence on the different phases of wound repair.

Brain penetration effects of microelectrodes and DBS leads in STN or GPi.

OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).

Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients.

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.

Cytoprotective effect of Podophyllum hexandrum against gamma radiation is mediated via hemopoietic system stimulation and up-regulation of heme-oxygenase-1 and the prosurvival multidomain protein Bcl-2.

The radioprotective effect of a hydroalcoholic extracted material (REC-2000) from the rhizome of Podophyllum hexandrum was studied in mice exposed to lethal gamma radiation (10 Gy). The extract (REC-2000) was found to restore the hemoglobin content (14.73 +/- 0.33) and total leukocyte count (TLC) (4166.66 +/- 0.02) in lethally (10 Gy) gamma-irradiated mice on the 15th day in comparison to the radiation control mice. The hemoglobin content of the drug + radiation group was observed to be significantly (21.25%) higher than the radiation control group on the 10th day. Similarly, the TLC was significantly increased (83.33 times) in the drug + radiation group as compared to a radiation (10 Gy) only group on the 10th day. Enhanced expression of heme-oxygenase-1 and Bcl-2 protein observed by Western blotting further supports the observation of hemopoietic recovery in irradiated mice. These findings indicate that the bioactive constituents present in REC-2000 exert the radioprotective effect by modulating the hemopoietic system.

Technical Note: Evaluation of the systematic accuracy of a frameless, multiple image modality guided, linear accelerator based stereotactic radiosurgery system.

PURPOSE: To evaluate the total systematic accuracy of a frameless, image guided stereotactic radiosurgery system. METHODS: The localization accuracy and intermodality difference was determined by delivering radiation to an end-to-end prototype phantom, in which the targets were localized using optical surface monitoring system (OSMS), electromagnetic beacon-based tracking (Calypso®), cone-beam CT, "snap-shot" planar x-ray imaging, and a robotic couch. Six IMRT plans with jaw tracking and a flattening filter free beam were used to study the dosimetric accuracy for intracranial and spinal stereotactic radiosurgery treatment. RESULTS: End-to-end localization accuracy of the system evaluated with the end-to-end phantom was 0.5 ± 0.2 mm with a maximum deviation of 0.9 mm over 90 measurements (including jaw, MLC, and cone measurements for both auto and manual fusion) for single isocenter, single target treatment, 0.6 ± 0.4 mm for multitarget treatment with shared isocenter. Residual setup errors were within 0.1 mm for OSMS, and 0.3 mm for Calypso. Dosimetric evaluation based on absolute film dosimetry showed greater than 90% pass rate for all cases using a gamma criteria of 3%/1 mm. CONCLUSIONS: The authors' experience demonstrates that the localization accuracy of the frameless image-guided system is comparable to robotic or invasive frame based radiosurgery systems.

Assessment of nucleolar organizer regions (NORs) in proliferative conditions of the liver.

To overcome the diagnostic dilemma in proliferative conditions of the liver which sometimes pose a problem to the working pathologist especially when the material is inadequate, a special staining technique (AgNOR) has been applied. By using this technique, nucleolar organizer regions were counted which determine the proliferative status of the cells. This prospective study included 65 cases of randomly selected liver core and fine needle aspiration biopsies. AgNOR staining was performed on formalin-fixed, paraffin-embedded tissue sections NOR dots were counted in 100 randomly selected hepatocytes at x100 oil immersion objective, and the mean count per cell was calculated for each case. Statistical analysis was done by using the Mann Whitney U test. AgNOR count results were later compared with the histologic diagnosis. The study revealed a gradual increase in mean AgNOR counts from normal liver through cirrhosis to hepatocellular carcinoma. The difference in NOR counts was significant in these three groups. The hepatocellular carcinomas were graded according to the Edmondson-Steiner histological grading system. The Grade I hepatocellular carcinomas show AgNOR counts ranging between 5-6/cell, a score which is much higher than in the normal liver, where it ranges between 1.2-2.0/cell. This technique can be used to assess the lesions where the distinction between normal liver and Grade I hepatocellular carcinoma is difficult with the use of routine methods. AgNOR counts in normal liver and chronic hepatitis cases were insignificant, but there was an appreciable difference between cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma. In view of the results of this study, the AgNOR staining method is found to be a useful diagnostic tool to differentiate between normal liver, cirrhosis and hepatocellular carcinoma and also to precisely discriminate between cases of normal liver and Grade I hepatocellular carcinoma.

Derivatization of keto fatty acids, X: Synthesis of thiazanones.

The synthesis of alkyl chain-substituted thiazanones from oxo fatty esters and a long chain aldehyde is reported. Four oxo compounds-methyl 10-oxoundecanoate, methyl 9-oxooctadecanoate, methyl 9,10-dioxooctadecanoate and octadecanal-were allowed to react with ß-mercaptopropionic acid in the presence of ammonium carbonate in benzene to give the corresponding 4-m-thiazanones in high yields. The structures of these compounds were confirmed by combustion and spectral data.

Effect of oestrogen on the incidence of drumsticks in the rabbit neutrophils.

Adult female rabbits were given daily intramuscular injections of 0.5 microgram of oestradiol diproprionate for four weeks. Weekly drum-stick counts were made from their blood smears and percent incidences of drum-sticks in the neutrophils was recorded. A highly significant increase in the drum-stick counts compared to the control animals was noted after one week's treatment with the oestrogen. Subsequent values after 2nd, 3rd and 4th week's treatment were not significantly different from values obtained from the corresponding untreated animals. It was concluded that oestrogen produces only an initial increase in the drumstick count and subsequent continued treatment neither increases nor decreases the drum-stick counts significantly.

Detection of Mycobacterium tuberculosis in paraffin embedded intestinal tissue specimens by polymerase chain reaction: characterization of IS6110 element negative strains.

Tuberculosis is still one of the most widespread infection known to mankind. Although lung is the predominant site of disease, a sizeable population in Pakistan gets intestinal disease. Clinical presentation, radiologic and endoscopic examination provide clues to the diagnosis. However, a definitive diagnosis requires biopsy material with granulomas and/or caseation complemented by acid fast staining and culture. There are many occasions when biopsy material is scanty and even in some intestinal resection cases histologic evaluation fails to confirm or rule out tuberculosis. Therefore, an investigation was conducted to assess the efficacy of PCR in the detection of mycobacterial DNA in paraffin embedded intestinal tissue. In this study 12 histologically confirmed cases of intestinal tuberculosis and 2 cases with non specific inflammation but clinically suspected for abdominal tuberculosis were selected. One case of rectal polyp was included to serve as a negative control. M. tuberculosis DNA was amplified in 8 out of 12 histologically confirmed cases and in 2 cases diagnosed with non specific inflammation. Amplified products were obtained in 6 out of 10 PCR positive specimens with IS6110 region specific primers while 4 samples were negative, suggesting the absence of insertion sequence 6110 in these strains. However, amplification was obtained in these negative specimens with a second primer pair confirming them as M. tuberculosis complex species. On the basis of this study we conclude that; (1) Processed and paraffin embedded tissue material is suitable for PCR analysis, (2) PCR assay can be used to complement the diagnosis of intestinal tuberculosis especially in situations where a definite conclusion can not be drawn by conventional methods, (3) M. tuberculosis species lacking insertion sequence 6110 element are present in our population. Therefore, several primer pair sets should be included when applying PCR for the detection of mycobacterial DNA.

Breast carcinoma in Pakistani females: a morphological study of 572 breast specimens.

OBJECTIVE: To study the morphological features in breast carcinoma which have proven prognostic value. METHODS AND SETTING: A retrospective analysis of 572 mastectomy specimens received over a period of three years at the department of pathology, The Aga Khan University Hospital. RESULTS: A total of 572 mastectomy specimens were analyzed which were received over a period of three years. Most of the patients were in the 5th and 6th decades of life. The mean age at diagnosis was 48 years. The most common tumour was infiltrating ductal carcinoma (81%). Tumour size was > 2 cms. in 80% of the cases. According to Modified Bloom and Richardson system most of the tumours were in grade II (65%) followed by grade III (24%). The number of cases with > 3 lymph node metastasis was significantly higher (70%) in tumours of > 2 cms size. High grade tumours also showed increased number of lymph node involvement. CONCLUSION: In Pakistani females breast carcinoma occurs at a younger age group. They are of large size at the time of presentation and show more frequent axillary lymph node metastasis. Infiltrating ductal carcinoma is the most common type of tumour with predominance of high grade lesions.

Immunohistochemical evaluation of small round cell tumors of childhood.

OBJECTIVE: This study was done to evaluate the pediatric undifferentiated small round cell tumors with immunohistochemical staining. SETTING: The present study included consecutive cases of small round cell tumors which were diagnosed in children (< 15 years) in the section of Histopathology at the Aga Khan University Hospital, Karachi during the period of two years. METHODS: The group of undifferentiated small round cell tumors were evaluated immunohistochemically by using a panel of antibodies on sections from routinely processed, formalin fixed, paraffin embedded tissue blocks. RESULTS: The category of undifferentiated small round cell tumors included rhabdomyosarcoma (23.2%), primitive neuroectodermal tumor (17.9%), non-Hodgkin's lymphoma (16.1%), neuroblastoma (14.2%), Ewing's sarcoma (10.7%) in order of frequency. Osteosarcoma (Small cell variant), retinoblastoma and medulloblastoma comprised 1.8% each. In seven cases (12.5%), the immunohistochemical analysis was inconclusive. CONCLUSION: Immunohistochemistry is a very valuable diagnostic tool which helps in distinguishing the undifferentiated tumors especially small round cell tumors. The immunohistochemical staining needs to be performed routinely for undifferentiated tumors in diagnostic histopathology.

Central nervous system lymphomas: a histologic and immunophenotypic analysis.

OBJECTIVE: To observe the spectrum of non-Hodgkin's lymphomas involving the central nervous system including morphological subtypes and immunophenotypic status. SETTING: Retrospective analysis of eleven years (1986 to 1996) data from surgical pathology files of Department of Pathology. RESULTS: Forty-three cases of non-Hodgkin's lymphomas were diagnosed during the period of eleven years (from 1986 to 1996), all of which were diffuse types. A total of 1177 Central Nervous CNS biopsies were examined, out of which 937 cases were diagnosed as CNS neoplasms, the remaining were non-neoplastic in nature. Among 937 CNS neoplasms, 43 cases (4.6%) were reported as non-Hodgkin's lymphomas. As most of the cases were outside referrals, the primary or secondary nature of the lymphomatous process could not be assessed. Seventeen cases were intracranial, while 26 cases were spinal in location. Majority of the intracranial lymphomas were biopsied from the cerebrum (12 cases). Male to female ratio was 1:2. The median age for intracranial lymphomas was 50 years and for spinal lymphomas 29 years. There were 16 cases (37%) of diffuse large cell lymphomas; 7 cases (16%) of diffuse mixed small and large cell lymphomas; 3 cases (7%) of diffuse large cell immunoblastic lymphomas; 2 cases (4.6%) of lymphoblastic lymphomas and diffuse small non-cleaved cell lymphomas and one case of small lymphocytic lymphoma and diffuse small cleaved cell lymphoma. One case of T cell rich B cell lymphoma was also diagnosed in the thoracic spine as primary extranodal lymphoma. Eight cases were unclassifiable and in 2 cases the features were suggestive of lymphoma. Immunophenotypic analysis was performed in 20 cases, however, in 2 cases the results were inconclusive. Fifteen cases (83%) showed immunoreactivity for B cell markers and 3 cases showed T cell phenotype out of which one case was lymphoblastic lymphoma. CONCLUSION: CNS lymphomas were uncommon tumors and comprised 4.6% of the total CNS neoplasms in our study. Moreover, these CNS lymphomas accounted for 2.2% of the total non-Hodgkin's lymphomas, including both nodal and extranodal. There was a higher incidence of location of these lymphomas within the spinal cord than brain. Most of the lymphomas were of intermediate or high grade (75%) according to the working formulation. Immunophenotypical status revealed B-cell phenotype in 84% of the lymphomas, in which it was tested (JPMA 50:141, 2000).

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.