THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

OBJECTIVE: To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. DESIGN: Prospective study SETTING: Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait SUBJECTS: Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. RESULTS: 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. CONCLUSION: Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

The impact of urbanization on tropical mangroves (Fortaleza, Brazil): evidence from PAH distribution in sediments.

This investigation represents the first environmental diagnosis of the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in sediments from a tropical mangrove in Fortaleza, northeastern Brazil. Sediment cores from six sampling stations in the Cocó and Ceará Rivers were retrieved in June-July 2006 to determine 17 priority PAHs. The total PAH concentrations (Sigma(PAHs)) ranged from 3.04 to 2234.76 microg kg(-1)(Cocó River) and from 3.34 to 1859.21 microg kg(-1) (Ceará River). These levels are higher than those of other cities with more industrial development. PAH concentrations did not reach probable effect levels (PELs). However, from 4.5 to 87.5% of individual PAH concentrations can occasionally cause adverse biological effects for aquatic organisms. The PAH molecular ratios indicate that the PAHs in the sediment core were derived mainly from petroleum, wood, and charcoal combustion (pyrogenic source), and that atmospheric deposition and urban runoff may serve as important pathways for PAH input to the sediment. Clearly, the Sigma(PAHs) in sediments collected in the Cocó and Ceará Rivers indicate that ongoing pollution is more severe than past pollution.

Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer?--experience at Kuwait University.

OBJECTIVES: This prospective study was undertaken to evaluate nuclear matrix protein (NMP22) compared to urine cytology in the detection of bladder cancer and also to determine whether indexing suspicious cytology to NMP22 could enhance the clinical utility of cytology. METHODS: Cytological findings of voided urine collected prior to a cystoscopic biopsy were correlated with urine NMP22 assay in 46 patients attending the urology clinic in Mubarak Al-Kabeer Hospital. The patients were clinically categorized into newly diagnosed cases of transitional cell carcinoma (TCC), recurrent TCC, TCC in remission and controls. RESULTS: Using histological diagnosis as the gold standard the sensitivity and specificity of NMP22 were 78% and 43% respectively and of cases with malignant urine cytology were 30% and 87% respectively. If suspicious and malignant cytology were combined as positive results the sensitivity increased significantly to 87% while the specificity decreased but not significantly to 74%. Suspicious or malignant cytology enhanced by positive NMP22 gave a sensitivity of 70% and specificity of 87% neither of which was significantly different from cytology alone. There were three false positive cases on cytology and 13 false positive cases on NMP22 assay. There were three false negative cytology and five false negative NMP22 cases but only one was false negative for both, resulting in a high sensitivity (96%) but low specificity (30%) if either positive NMP22 or malignant or suspicious cytology was taken as a positive result. CONCLUSION: Combining NMP22 with malignant or suspicious cytological result improved sensitivity for the detection of bladder cancer but with a major decrease in specificity, suggesting a potential role in screening rather than diagnosis.

Bradycardia and hypotension associated with fomepizole infusion during hemodialysis.

UNLABELLED: We report a case of hypotension and bradycardia associated with intravenous fomepizole infusion. CASE REPORT: A 59-year-old man presented to hospital 10 hours after ethylene glycol ingestion with ataxia, slurred speech, metabolic acidosis, heart rate 70/min, blood pressure 160/100 mmHg. Treatment with hemodialysis and fomepizole began 7.5 hours after admission. Severe bradycardia (29/min) and hypotension (69 mmHg systolic) occurred immediately following a 30 minute intravenous infusion of the first (19 mg/kg) fomepizole dose, but rapidly corrected with 1 mg atropine. Transient bradycardia (48/min) and hypotension (89/57 mmHg) recurred immediately after the second (10 mg/kg) fomepizole dose, also given during dialysis. DISCUSSION: Hemodialysis may cause a drop in blood pressure and heart rate; however, the close temporal relationship with fomepizole infusions, dose-related symptom intensity and recurrence with rechallenge suggest a causal relationship with fomepizole. Hemodialysis, acidosis and high initial fomepizole dose may have enhanced patient susceptibility, as a post-dialysis fomepizole dose was well tolerated. CONCLUSION: Fomepizole may precipitate bradycardia and/or hypotension during hemodialysis. Monitor vital signs closely during and immediately after infusion.

Cytomorphological and immunocytochemical study of non-Hodgkin's lymphoma in pleural effusion and ascitic fluid.

INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is often complicated by pleural effusion and ascites. The present study is an attempt to categorize the lymphomatous effusions according to the WHO classification, using archival material. METHODS: May-Grünwald-Giemsa and Papanicolaou-stained smears of 31 lymphomatous effusion specimens were reviewed. Of these, detailed cytological assessment was done on 12 pleural effusions and ten ascitic fluid specimens from 22 patients using the WHO lymphoma classification system. Immunocytochemical studies were performed in 21 specimens. RESULTS: Based on cytomorphological features, the 22 lymphomatous effusion specimens were categorized into lymphoplasmacytoid lymphoma (1), follicle centre cell (FCC) grade-1 (centrocytic) lymphoma (3), FCC grade-2 (centrocytic-centroblastic) lymphoma (3), FCC grade-3 (centroblastic) lymphoma (4), large cell immunoblastic lymphoma (4), lymphoblastic lymphoma (2), anaplastic large cell lymphoma (3) and miscellaneous types (2). Immunocytochemically, the lymphoma cells were T-cell (positive for CD3) and B-cell type (CD20 positive) in five and six cases respectively. CONCLUSION: Cytological examination of pleural effusion and ascitic fluid samples, supported by immunocytochemical studies, may be useful for the classification of lymphomas under the WHO system.

Cytomorphological spectrum in scar endometriosis: a study of eight cases.

OBJECTIVE: Endometriosis due to ectopic endometrial tissue that responds to hormonal stimulation and is extremely rare in a surgical scar appearing in 0.1% of women who have undergone Caesarean section. Fine needle aspiration cytology (FNAC) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses. METHODS: We present the cytomorphological spectrum in eight cases of abdominal wall endometriosis diagnosed by FNAC over a 6-year period (June 1998-June 2004) in Mubarak Al-Kabeer Hospital (Kuwait). The patients ranged from 27 to 56 years of age. Seven had a prior Caesarean section and one had a hysterectomy for fibroid. They presented 3-8 years later with nodules in/near the abdominal scar. Five cases presented with a painful nodule, fluctuant with the menstrual cycle. RESULTS: Cytological findings comprised epithelial clusters and fusiform stromal cells with numerous haemosiderin-laden macrophages. Mild to moderate epithelial atypia was observed in three cases. A diagnosis of endometriosis was rendered in all the eight cases and tissue was available in four cases. CONCLUSIONS: Endometriotic nodules need to be differentiated from other benign/malignant masses and evaluated for possible malignant transformation. FNAC provides a safe and effective tool for diagnosis thereby obviating the need for other procedures.

Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression.

OBJECTIVE: To study the relationship of cell death and proliferation to histologic grade and p53 expression in invasive carcinoma of the breast. STUDY DESIGN: A total of 31 cases of infiltrating duct carcinoma of the breast were randomly selected. The terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) reaction and p53 immunostaining were performed on representative paraffin-embedded tissue sections. Mitotic and apoptotic indices (MI and AI) were also measured on hematoxylin-eosin-stained sections. Histologic grade of infiltrating duct carcinoma was performed with the help of the Nottingham modification of the Bloom-Richardson system. Tumor grade and p53 overexpression were correlated with MI, AI and AI detected by TUNEL. RESULTS: There were a total of 31 infiltrating duct carcinomas of the breast, of which 13 cases were grade 1 and nine cases each were grade 2 and 3. Cells with positive TUNEL showed a strong brown nuclear positivity. TUNEL showed positivity from the periphery of the nuclear margin to the central portion. AI detected by TUNEL did not correlate with tumor grade (ANOVA, P > .05). MI was significant only in grade 1 versus grade 3 and 2 versus grade 3 carcinomas (ANOVA, P < .01). The morphologic apoptotic index was significant only in grade 1 versus grade 3 carcinomas. Nine cases showed p53 overexpression, and the rest of the cases were negative for p53 immunostaining. MI, AI and TUNEL were not significantly different in p53-negative and -positive groups. Pearson's correlation coefficient showed that AI and MI were significantly related, but there was no significant relation between AI detected by TUNEL and MI. CONCLUSION: MI is still more useful than AI or AI detected by TUNEL in differentiating various grades of carcinoma of the breast.

Cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant recipients.

An association between human papilloma virus (HPV) infection and cervical intraepithelial neoplasia has been well established Renal transplant recipients on long term immunosuppression are prone to viral infection. It is possible that there may be an increased prevalence of papilloma virus infection and associated cervical intraepithelial neoplasia in these women. Prospective study of 42 renal transplant recipients and 41 age and parity matched controls was undertaken to determine whether HPV infection and cervical intraepithelial neoplasia (CIN) occurred more often in renal allograft recipients and to assess the relative risk. All women underwent Pap smear, colposcopy, histological examination of biopsy specimen and polymerase chain reaction for HPV 16. Cytology did not pick up HPV infection in any of the women. Colposcopy revealed HPV infection in 15 and CIN in 14 women in the immunosuppressed group and HPV in 7 and CIN in 5 women in control group. Histological evidence of HPV was found in 24 and CIN in 10 women in immunosuppressed group and HPV infection in 13 and CIN in 3 women in control group, giving an odds ratio of 6.1. More women in the immunosuppressed group had CIN of higher degree as well. PCR revealed infection by HPV 16 in 17 cases and 14 controls giving an odds ratio of 1.3. Therefore renal allograft recipients on immunosuppression should be screened by colposcopy and directed biopsy at regular intervals.

Management of prolonged pregnancy: a randomized trial of induction of labour and antepartum foetal monitoring.

BACKGROUND: The two methods of management of prolonged pregnancy, induction of labour and expectant management with foetal surveillance, have pros and cons. Therefore, we compared the induction of labour with serial antenatal foetal monitoring in the management of post-term pregnancy. METHODS: Seventy-four women with uncomplicated pregnancy at 41 weeks (287 days) of gestation were randomly assigned to undergo either induction of labour or serial antenatal foetal monitoring. Labour was induced in the latter group whenever there was evidence of foetal compromise. Antenatal monitoring consisted of the foetal kick count, non-stress test and biophysical profile. RESULTS: Fifty-seven per cent of women went into spontaneous labour by 41 weeks and 4 days (291 days) of gestation and only 14% developed foetal compromise before that. However, when the gestational age was more than 41 weeks and 4 days (291 days), the incidence of meconium staining of amniotic fluid and evidence of uteroplacental insufficiency increased significantly. The rate of caesarean section, instrumental delivery, foetal distress and duration of labour did not differ significantly between the two groups. CONCLUSION: The policy of inducing labour at 41 weeks and 4 days (291 days of gestation) in uncomplicated pregnancies is justified in our population. However, foetal monitoring should begin at 41 weeks of gestation.

Manual versus image analysis estimation of PCNA in breast carcinoma.

OBJECTIVE: To compare manual to image analysis estimation of proliferating cell nuclear antigen (PCNA) expression in paraffin sections of breast carcinomas. STUDY DESIGN: Paraffin sections of 51 breast carcinomas were stained with primary antibody to PCNA. Nuclear PCNA expression in 100 randomly selected tumor cells from marked areas was manually graded from 0 to 3. Antigen expression was also calculated by a cell analysis system (CAS-200, Becton Dickinson, Elmhurst, Illinois, U.S.A.) from marked and random microscopic fields. Obtained proliferative index (PI) from both methods was compared. RESULTS: Manually calculated PI correlated strongly with the CAS-200-calculated PI (P < .01). The highest correlation was seen between the CAS-200 PI value and manually calculated PI value using grade 2 and 3 nuclei. A particularly high correlation was noted between the number of positive nuclei and antigen staining area (P < .01) as estimated by the CAS-200. CONCLUSION: Nuclear expression of PCNA and other nuclear antigens can be accurately evaluated by an image analysis system. The speed and objectivity of such machines allow the evaluation of larger parts of tissues and provide more-representative antigen expression profiles.

Comparison of ThinPrep and conventional preparations on fine needle aspiration cytology material.

OBJECTIVE: To compare the various cytologic features on ThinPrep 2000 (TP) (Cytyc Corporation, Marlborough, Massachusetts, U.S.A.) and conventional preparation (CP) specimens from fine needle aspiration cytology (FNAC) material by a semiquantitative scoring system. STUDY DESIGN: In this prospective study a total of 71 consecutive cases were included. In each case, two passes were performed. The first pass was used for conventional preparations, with direct smears made and fixed immediately in 95% alcohol for Papanicolaou stain. For TP preparation a second pass produced material for processing in the ThinPrep 2000. The TP and CP slides were studied independently by two observers and representative slides of CP and TP compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of monolayer cells, and nuclear and cytoplasmic details by a semiquantitative scoring system. Statistical analysis was performed by Wilcoxon's signed rank test on an SPSS program (Chicago, Illinois, U.S.A.). RESULTS: TP preparations contained adequate diagnostic cells in all cases and were tangibly superior to CP preparations concerning monolayer cells, absence of blood and necrosis, and preservation of nuclear and cytoplasmic detail (statistically significant, Wilcoxon's signed rank test, P < .000). CONCLUSION: TP preparations are superior to conventional preparations with regard to clear background, monolayer cell preparation and cell preservation. It is easier and less time consuming to screen and interpret TP preparations because the cells are limited to smaller areas on clear backgrounds, with excellent cellular preservation. However, TP preparations are more expensive than CP and require some experience for interpretation.

Cytologic grading and DNA image cytometry of breast carcinoma on fine needle aspiration cytology smears.

OBJECTIVE: To correlate the cytologic grade of breast carcinoma with DNA image cytometry (ICM) and nuclear area on fine needle aspiration cytology (FNAC) smears. STUDY DESIGN: In this prospective study, FNAC material from 28 breast carcinomas were studied for cytologic grade and DNA ICM. Breast carcinomas were classified as grade 1-3 (low to high). DNA histograms were classified by the modified Auer method. Degree of hyperploidy (DH), ploidy balance (PB) and nuclear area (NA) were measured on Feulgen-stained smears by a CAS 200 image cytometer. Cytologic grade was correlated with DNA ICM findings and NA. RESULTS: There were 3 cytologic grade 1, 13 grade 2 and 12 grade 3 breast carcinomas. Seven of eight cases of hypertetraploid aneuploidy were grade 3 tumors. All cytologic grade 1 tumors were diploid. There were significant differences in DH, PB and NA in different grades of breast carcinoma (one-way ANOVA). CONCLUSION: DNA image cytometry in combination with cytologic grading might offer additional information for the characterization of breast carcinomas diagnosed by FNAC. These observations are of particular interest with the introduction of preoperative chemotherapy.

Maternal zinc indices and small babies.

BACKGROUND: Maternal zinc deficiency has been reported to be associated with foetal growth retardation. This study aimed to determine if zinc deficiency is associated with foetal growth retardation in south Indian women. METHODS: A prospective study was undertaken to evaluate the maternal zinc indices in those bearing small-for-gestational age babies and in those with appropriate-for-gestational age babies. Zinc levels in plasma, red blood cells and white blood cells in both groups were assayed in 65 patients with small-for-gestational age babies (regardless of cause) and 51 women with appropriate-for-gestational age babies. RESULTS: There was no significant difference in the mean (SD) plasma [67.5 (9) v. 70.67 (13.9)], red blood cell [47.26 (5.8) v. 45.69 (8.2)] and white blood cell [55.61 (10.5) v. 54.77 (12.4)] zinc levels in mothers who gave birth to small-for-gestational age babies and those who delivered appropriate-for-gestational age babies. The presence of predisposing factors for intrauterine growth retardation also did not influence the maternal zinc levels. CONCLUSION: Maternal zinc levels were not associated with intrauterine growth retardation in our population.

Aspiration pneumonia. Strategies for early recognition and prevention.

Aspiration is the result of dysfunction during the oral, pharyngeal, or esophageal stage of deglutition. Depending on the type of aspirate, the resultant lung injury may include chemical or bacterial inflammation or obstruction of the airways. Tools for evaluation include roentgenography, upper GI tract studies, bronchoscopy, and esophageal pH studies. Medical management is primarily supportive. Because aspiration pneumonia has a high morbidity rate, prevention involving early recognition and modification of predisposing factors whenever possible is critical for improving outcomes.

Detection of CIN by naked eye visualization after application of acetic acid.

A prospective study was undertaken to determine the sensitivity and specificity of acetic application to the cervix followed by naked eye visualization as a screening test for detection of cervical intraepithelial neoplasia. Three hundred and seventy two sexually active woman in the reproductive age group were studied. All the women underwent Papanicolaou test, acetic acid test and colposcopy. One hundred and seventy five woman were acetic acid test negative, 197 women were acetic acid test positive. The sensitivity of acetic acid test was 72.4%, specificity 54% and false negative rate 15.2%, as compared to papanicolaou test which had a sensitivity of 13.2%, specificity of 96.3% and false negative rate of 24.4%. The advantage of the acetic acid test lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening programme in developing countries.