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Glomerular tuft immune reactive Ezrin surface area (EzA) and fraction of EzA to total glomerular tuft area significantly increased, indicating podocyte growth, rounding and altered cytoskeletal interactions at 1 week of STZ diabetes. Podocyte number per glomerulus (WT1+ nuclei) did not change indicating no detachment, but density decreased due to tuft hypertrophy. Treatment with PLZ or Insulin for one week, prevented increase in proteinuria and hyperglycemia but not the decrease in podocyte density. PLZ but not Insulin prevented increase in ezrin positive area in glomeruli and per podocyte. In podocytes in culture neither 25 mM glucose with or without PLZ (2.5 or 25 uM) altered Ezrin expression measured in western blots. In summary, the Ezrin positive glomerular surface area increase seen after 1 week of STZ diabetes, reflects altered podocyte morphology and cytoskeletal interactions, prevented by PLZ but not by insulin. Ezrin area increase preceded podocyte detachment and in podocytes in culture is not associated with increases in podocyte Ezrin protein expression. It is a likely precursor of shape changes in podocytes and of alterd interactions with basement membrane that contribute to detachment and thickening. Glomerular capillary tuft hypertrophy and reduced podocyte density persisted despite PLZ or insulin treatments, independently of levels of glycemia and of proteinuria.

Introduction: Estrogen receptors (ER), progesterone receptors (PR), and epidermal growth factor (HER2) are prognostic and predictive factors for breast carcinoma. We determined them by immunohistochemistry (IHC) on cell blocks from fine-needle aspirates (FNA) of metastatic breast carcinoma to axillary lymphnodes and compared them with that reported in the primary breast carcinoma (PBC) to document any change in their expression for future management. Materials and Methods: ER, PR, and HER2 by IHC and HER2 oncogene by fluorescent in-situ hybridization (FISH) were studied on cell blocks of FNA of axillary lymphnodes in 53 of 94 PBC cases from 2012 to 2016. Results: In 25 of 38 (65.8%) ER, PR negative PBC the metastasis on FNA was ER, PR+, whereas the 15 (28.3%) ER, PRPBC remained negative. In 10 of 11 (91%) of HER2-IHC+, PBC the metastatic tumor was HER2-IHC+. 7 of 32 (21.9%) HER2-IHC negative PBC were HER2-IHC+ in metastatic tumor. HER2-FISH was performed in 37 cases on FNA. Six of 37 were HER2 amplified/positive, whereas 9 and 19 remained equivocal and negative for HER2 copy number, and 3 were not interpretable. All the 6 HER2-FISH+ cases were positive by IHC. In our study, 34.2% of ER, PR+ cases of PBC became ER, PR– in the metastatic tumor and 21.9% of HER2-IHC negative PBC became HER2-IHC+ in the metastatic aspirate. Conclusion: ER, PR, and HER2 by IHC in cell blocks of metastatic lymphnodes are reliable. Change in receptor (34.2%) and HER2 status (21.9%) was documented, which is of clinical significance as these patients warrant a change of management.

Patient: Male, 54-year-old Final Diagnosis: Hepatic hemosiderosis Symptoms: Elevated liver enzymes Medication:— Clinical Procedure: Liver biopsy Specialty: Gastroenterology and Hepatology • Hematology Objective: Rare disease Background: Elevated liver enzymes is a common clinical problem with many possible etiologies, yet some are rare and can be missed. Patients with sickle cell disease (SCD) may be at risk of liver disease due to recurrent blood transfusion predisposing to viral hepatitis. Furthermore, recurrent transfusions can increase the risk of iron overload, which can create deposits in the liver, eventually resulting in chronic liver disease. Liver biopsy is an essential tool to establish a diagnosis of liver disease in many patients with unexplained elevation of liver enzymes. Recently, endosocpic ultrasound (EUS)-guided liver biopsy has been shown to be safe and effective in obtaining adequate liver tissue. However, the safety and efficacy has not been established in patients with SCD. Case Report: A 59-year-old man with SCD and beta-thalassemia minor was evaluated for persistently elevated liver enzymes (mainly cholestatic). He had a background history of treated hepatitis C virus infection. He had multiple blood transfusions in the past for sickle cell crisis. A diagnostic work-up revealed negative viral and autoimmiune serology and no evidence of biliary obstruction on abdominal imaging. The iron profile was elevated, consistent with iron overload. An EUS-guided liver biopsy confirmed a diagnosis hepatic hemosiderosis secondary to long-term blood transfusions. Conclusions: This report emphasizes the importance of careful monitoring of iron levels in patients with hematological conditions requiring long-term blood transfusions. In addition, it highlights the emerging role of EUS-guided liver biopsy as a safe and accurate alternative to percutaneous liver biopsy.

Abstract. Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein ( VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 – 2.73; p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p

strongObjective:/strongMedication resins such as Kayexalate and Sevelamer used in the setting of chronic kidney disease for the correction of hyperkalemia and hyperphosphatemia are associated with gastrointestinal mucosal injury. In this study we describe the clinico-pathological features of Resin-induced gastrointestinal mucosal injury highlighting the histo-morphological appearances and differential diagnoses. The aim of this study is to increase the awareness of pathologists and clinicians alike to an under-reported etiology and pattern of intestinal mucosal injury related to medical resin therapy which may at times pose a clinical emergency.strongMaterial and Method:/strongThe archives of the Department of Histopathology, Mubarak Al Kabir hospital were analyzed for cases of resin-induced gastrointestinal mucosal injury between 2013 and 2018.strongResults:/strongOf the 15 cases, Kayexalate crystals were identified in 7 cases, Sevelamer in 5 cases and both together were seen in 3 cases. Resin crystals were identified in the gastric antrumduodenum (3 cases), colon (9 cases in the left colon, 2 cases in the right colon) and anal canal (1 case). The histological tissue reactions included mucosal necrosis (1 case), inflammatory polyps (2 cases), mucosal ulcerations with granulation tissue formation (10 cases), perforation (1 case) , and luminal crystals (1 case).strongConclusion:/strongAccurate and timely recognition of the resin crystals in biopsy samples with clinical correlation is mandatory to avoid serious complications.

Background Documenting the four molecular subtypes of breast carcinoma is significant as they determine response to therapy, disease free interval and survival. Our aim was to document the subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2): namely ER + PR+ HER2+; ER + PR + HER2−; ER−PR−HER2+; and ER−PR−HER2− in metastatic breast carcinoma in pleural fluid and compare them with their expression in the primary breast tumor. Methods Over a period of 18 months, 13 cases of invasive breast carcinoma with metastases to the pleural cavity were studied for subtypes. ER, PR, and HER2 were determined by IHC in the primary breast tumor and the cell blocks of the pleural fluid with metastatic carcinoma. Results Age ranged from 33 to 75 years. The primary tumor was ER + PR + HER2+; ER + PR + HER2−; ER−PR−HER2+ and ER−PR−HER2− in 2,9,0 and two cases, respectively while the metastatic tumor in pleural fluid was ER + PR + HER2+; ER + PR + HER2−; ER−PR− HER2+ and ER−PR−HER2− in 6, 3, 3, and 1, respectively. In five cases there was complete correlation between the primary and metastatic tumor. In 7 cases with HER2- primary tumor the metastases was HER2+. One from ER + PR+ HER2− primary tumor showed triple negative expression in the metastasis. Conclusions Determining the molecular subtype in metastatic breast carcinoma is of importance as it affects the management. In our series 63% of metastatic tumors to the pleural fluid became HER2 positive and would thus require appropriate therapy. Diagn. Cytopathol. 2016;44:980–986. © 2016 Wiley Periodicals, Inc.

Context: Nonsmall cell lung carcinoma (NSCLC) is the most frequently diagnosed form of lung cancer in Kuwait. NSCLC samples from Kuwait have never been screened for epidermal growth factor receptor ( EGFR ) gene aberration, which is known to affect treatment options. Aims: This study investigated the feasibility of using fine-needle aspiration (FNA) material for mutational screening, and whether common EGFR mutations are present in NSCLC samples from Kuwait. Settings and Design: Eighteen NSCLC samples from five Kuwaitis and 13 non-Kuwaitis were included in this study. Materials and Methods: DNA was extracted from FNA cell blocks and screened for EGFR gene mutations using peptide nucleic acid (PNA)-clamp assay, and EGFR gene amplification using fluorescent in situ hybridization ( EGFR -FISH). EGFR protein expression was assessed using immunohistochemistry. Results: Five EGFR mutations were detected in five non-Kuwaiti NSCLC patients (27.8%). EGFR gene amplification was evident in 10 samples (55.5%) by direct amplification or under the influence of chromosomal polysomy. Four samples had EGFR mutations and EGFR gene amplification, out of which only one sample had coexisting EGFR overexpression. Conclusions: Given the evidence of EGFR gene alterations occurring in NSCLC patients in Kuwait, there is a need to incorporate EGFR gene mutational screen for NSCLC patients to implement its consequent use in patient treatment.

Background: Kayexalate and sevelamer are resin medications commonly used in the setting of chronic renal failure for the treatment of hyperkalemia and hyperphosphatemia respectively, are known to cause bowel ischemia, ulcerations, necrosis, pseudotumors and perforations and the incidence is higher after post-transplant. Herein we report its presence on the surface of a graft nephrectomy following a masked intestinal perforation. Case Presentation: A 30-year-old male, a renal transplant recipient for dysplastic kidney underwent graft nephrectomy due to wound infection, peri-graft collection and risk of hemorrhage from the vascular anastomotic site. Histological evaluation showed extensive acute tubular necrosis and peri-renal abscess with vegetable matter and numerous colored crystals morphologically consistent with kayexalate and sevelamer. The possibility of an underlying resin induced intestinal perforation was rendered. Conclusions: Kayexalate or sevelamer induced mucosal injury in the gastrointestinal tract could be a clinical emergency and a high index of suspicion particularly in a post-transplant setting may allow prompt recognition and surgical cure. From the pathologists’ view familiarity with the morphological appearances of these non-systemic resin medications and its histologic mimics enables accurate diagnosis and timely clinical intervention.

Objectives : Touch imprint cytology (TIC) is a reliable, cost-effective technique for the diagnosis of cancer. The aim of this study was to determine the diagnostic value and accuracy of TIC of prostate core needle biopsy (CNB) specimens in predicting the final histology in patients with suspected prostate cancer. Subjects and methods : TIC was carried out on 354 core needle biopsy specimens taken from 59 patients with suspected prostate cancer as indicated by a high prostate serum antigen (PSA) level or abnormal findings on rectal examination. All biopsies were taken under transrectal ultrasound (TRUS) guidance. Two touch imprints were prepared from each CNB. The TIC results were correlated with CNB. Results : TIC revealed evaluable results in 336/354 (94.9%) CNB specimens analyzed, with the following cytological diagnosis: malignancy in 40 (11.9%), atypical features in 47 (14%) and benign results in 249 (74.1%) specimens. Histopathological examination of the 40 CNB specimens showing malignant features on TIC confirmed the diagnosis of prostate cancer. In 24/47 (51.1%) cases with atypical cytology, histopathological assessment of the CNB specimens revealed benign features in 7 and prostatitis in 17, while high-grade prostatic intraepithelial neoplasia (HGPIN) and carcinoma were seen in 3 and 20 specimens, respectively. In 12/249 (4.8%) cases showing benign results on TIC, histopathological examination of the CNB specimens revealed an abnormal histology in the form of HGPIN in 9 (75%) and carcinoma in 3 (25%) cases. TIC accurately predicted the final histology in 336 cases with a sensitivity of 84% and a specificity of 90.8%. When excluding atypical cytology on TIC and HGPIN on CNB, the sensitivity and specificity were 93% and 100%, respectively. A strong correlation was seen between TIC and CNB (p < 0.001). Conclusions : The routine use of TIC complements CNB reports and helps to provide an immediate and reliable cytological diagnosis of prostate lesions. TIC and serial sectioning of CNB specimens significantly improve the diagnostic accuracy.

Parathyroid carcinoma is an uncommon malignancy and the probability of an intrathyroidal location is low. Fine needle aspirations (FNA) of these presumably “thyroid nodules” can lead to misinterpretation because of the similarities in cytological features of parathyroid and thyroid lesions. Despite limitations, USG guided FNA cytology remains the first line of investigation. We report a case of intrathyroidal parathyroid carcinoma presenting with hypercalcemia and elevated serum parathormone. Cytological findings attributed it to a possible parathyroid lesion and histopathology revealed a parathyroid carcinoma. It is reported due to its rare occurrence on FNA along with brief literature review.

Exclusive reports on fine needle aspiration (FNA) cytodiagnosis of T-cell-rich B-cell lymphoma (TCRBCL) are scarce in literature. This report reflects the diagnostic difficulties associated with cytodiagnosis of this rare variant of diffuse large B-cell lymphoma. The study is based on 11 cases with age ranging from 16 to 63 years and a median of 50 years. Male to female ratio was 6:5. Ten cases presented with lymphadenopathy and one had lymphadenopathy as well as extranodal solid tumor. The initial cytodiagnosis was suggestive of TCRBCL in one case, TCRBCL/Hodgkin's lymphoma (HL) in three cases, TCRBCL/HL/anaplastic large cell lymphoma (ALCL) in two cases, TCRBCL/ALCL in one case, and TCRBCL/non-Hodgkin lymphoma (NHL) T-cell/ALCL in one case. There was also a cytologically diagnosed HL case, which on review turned out to be HL/TCRBCL. Histopathological diagnosis was HL in all these nine cases. There were two histologically diagnosed TCRBCL cases during this period, with cytodiagnoses of NHL other than TCRBCL in one and HL in the other. While highlighting the difficulties associated with the cytodiagnosis of TCRBCL, this study conveys a word of caution that adequate immunocytochemical studies should be performed before diagnosing this rare neoplasm with a varied cytomorphology. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.

In the present study, the expression of estrogen receptor (ER)α and ERβ isoforms in ER-positive (MCF7, T-47D and ZR-75-1) and ER-negative (MDA-MB-231, SK-BR-3, MDA-MB-453 and HCC1954) breast cancer cell lines was investigated. ERα mRNA was expressed in ER-positive and some ER-negative cell lines. ERα Δ3, Δ5 and Δ7 spliced variants were present in MCF7 and T-47D cells; ERα Δ5 and Δ7 spliced variants were detected in ZR-75-1 cells. MDA-MB-231 and HCC1954 cells expressed ERα Δ5 and Δ7 spliced variants. The ERβ1 variant was expressed in all of the cell lines and the ERβ2 variant in all of the ER-positive and some ER-negative cell lines (MDA-MB-231, MDA-MB-453 and SK-BR-3). MCF7, ZR-75-1, MDA-MB-453, HCC1954 and T-47D cells expressed ERβ5. All cell lines expressed an ERα 66-kDa protein band, and some expressed the truncated 42-kDa variant. ERβ1 was detected in all of the cell lines in addition to a 38–44 kDa variant. The results indicate that breast cancer cell lines widely used in research and reported as being ER-negative express ERα and/or ERβ mRNA and protein.

OBJECTIVE To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance.

Psammoma bodies (PBs) are believed to represent a process of dystrophic calcification over nonviable and dying tissues. Light microscopic and ultrastructural observations suggest that PB formation follows the intracellular assembly of precursor substances and their calcification leading to death of tumor cells and their release. It may also be the result of local secretion of precursor substances like collagen by tumor cells into extracellular space and their calcification. In an earlier reported study, we demonstrated the extracellular localization of various precursor forms of PBs and of irregular calcification in fine-needle aspiration (FNA) smears of papillary thyroid carcinoma (PTC). In this report, we describe a PTC case with intracellular formation precursor substances for calcification and their release from the well-preserved neoplastic cells before undergoing calcification. Ultrasound-guided FNA smears from a small nodule in the left lobe of thyroid in a 40-year-old woman revealed a PTC with numerous intracytoplasmic targetoid bodies, which were magenta colored in MGG stain. On their release from the neoplastic cells, these targetoid precursor bodies were found to be forming pools of matrix material, some of which showed evidence of calcification. The cytologic findings were confirmed by histopathology of the tumor in the thyroidectomy specimen. For the first time, we demonstrate through cytomorpholgy the intracytoplasmic formation of targetoid bodies as precursor substances for calcification and their release from well-preserved cells in PTC. We suggest that the calcification in PTC may not necessarily be taking place over nonviable and dying cells. Diagn. Cytopathol. 2008;36:809–812. © 2008 Wiley-Liss, Inc.

Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level. Diagn. Cytopathol. 2007;35:329–337. © 2007 Wiley-Liss, Inc.

Objective: The aim of this work was to study the effect of 7 days of strict glycemic control with insulin on glomerular function and structure in streptozotocin (STZ)-diabetic rats. Materials and Methods: Three groups of adult male Fischer rats were studied: controls (n = 15), diabetics (n = 15), and insulin-treated diabetics (n = 15). Diabetes was induced by treating the rats with STZ (55 mg/kg i.p.). One week after the induction of diabetes, blood glucose, protein excretion rate (PER), glomerular filtration rate (GFR), and renal plasma flow (RPF) were estimated in each group. Furthermore, morphometric analysis was performed to estimate the tuft volume and changes in mesangial matrix area. The results are expressed as the mean ± SEM. Results: STZ diabetes caused significant increases in GFR (0.89 ± 0.1 to 1.21 ± 0.1 mL/min/100 g; p < 0.01) and RPF (1.78 ± 0.37 to 3.32 ± 0.6 mL/min/100 g; p < 0.05). Furthermore, the diabetic rats had higher glomerular volumes but mesangial matrix areas similar to controls. Insulin treatment prevented the increases in blood glucose (4.5 ± 0.2 mM), PER (66.1 ± 7.8 mg/day), GFR (0.6 ± 0.07 mL/min/100 g), and RPF (1.72 ± 0.36 mL/min/100 g), but did not prevent glomerular hypertrophy (21.7% increase), but induced mesangial matrix expansion (25% increase). Conclusions: Insulin prevented the diabetes-induced hyperfiltration and proteinuria, but did not prevent glomerular growth, and induced mesangial expansion. Hyperglycemic episodes could be partly responsible for persistent glomerular growth and accelerated mesangial growth.

Objective: The aim of this study was to determine the incidence of squamous cell abnormalities in cervical cytology in Mubarak Al-Kabeer Hospital, Kuwait, and to document any change in the pattern of these lesions. Materials and Methods: Over a 13-year period (1992–2004), 86,434 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional Pap smears were first examined by cytotechnicians and finally reported by cytopathologists. The smears were classified according to the modified Bethesda system. The age of presentation of squamous cell abnormalities in Kuwaiti women was analyzed. Results: Smears from 83,052 (96.09%) patients were found satisfactory for reporting while the remaining 3.9% was unsatisfactory. Atypical squamous cells of undetermined significance (ASCUS) were seen in 1,790 (2.2%) cases, atypical glandular cells of undetermined significance (AGUS) in 630 (0.8%) cases, low grade squamous intraepithelial lesion including human papillomavirus changes (LSIL) in 824 (1.0%) cases, high grade squamous intraepithelial lesion (HSIL) in 189 (0.2%) cases, and carcinoma in 79 (0.1%) cases of which 44 (0.05%) were squamous cell carcinoma. A comparison of average cases/annum during the study period revealed a significant increase in ASCUS from 1.13 to 2.83% (p < 0.001) and AGUS from 0.33 to 1.08% (p < 0.001). However, the percentage of LSIL, HSIL and carcinoma detected in Pap smears remained the same. Conclusion: A significant linear trend (p < 0.001) was observed in satisfactory smears, ASCUS and AGUS over the years. However, no significant change was found in the detection of LSIL, HSIL and carcinoma. A reduction in the age of LSIL/HSIL and an increasing trend in the number of Kuwaiti women over the years was also observed which makes screening of young women essential in Kuwait.

Summary 1 The purpose of this study was to examine the effect of inhibition of the formation of cytochrome P450 metabolites of arachidonic acid with 1-aminobenzotriazole (ABT) on the development of hypertension and end-organ damage in spontaneously hypertensive rats (SHR) chronically treated with nitric oxide synthesis inhibitor l-NAME (SHR-l-NAME). 2 Administration of l-NAME in drinking water (80 mg l−1) to SHR for 3 weeks significantly elevated mean arterial blood pressure (MABP) (223 ± 4 mmHg) as compared to SHR controls drinking regular water (165 ± 3 mmHg). The administration of ABT (50 mg kg−1 i.p. alt diem) for 6 days significantly attenuated elevation of blood pressure in SHR-l-NAME (204 ± 4 mmHg). 3 l-NAME-induced increase in urine volume and protein was significantly lower in ABT-treated animals. 4 The impaired vascular responsiveness to noradrenaline and isoprenaline in the perfused mesenteric vascular bed of SHR-l-NAME-treated animals was significantly improved by ABT treatment. 5 Morphological studies of the kidneys and hearts showed that treatment with ABT minimized the extensive arterial fibrinoid necrosis, arterial thrombosis, significant narrowing of arterial lumen with marked arterial hyperplastic arterial changes that were observed in vehicle treated SHR-l-NAME. 6 In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischaemia was significantly better in ABT-treated SHR-l-NAME. 7 These results suggest that in hypertensive individuals with endothelial dysfunction and chronic NO deficiency, inhibitors of 20-HETE synthesis may be able to attenuate development of high blood pressure and end-organ damage.

Among immunocompromised individuals, hyper-infection with Strongyloides stercoralis may occur and lead to fatal strongyloidiasis. To clinicians and laboratory diagnosticians in non-endemic countries such as Kuwait, this severe infection poses a particular problem. The clinical histories and signs and symptoms of four Kuwaiti cases of S. stercoralis hyper-infection were reviewed. Each of the four was found not only to have lived in an area where S. stercoralis was endemic but also to have been treated with immunosuppressive steroids (for medical problems unrelated to the nematode infection). When they presented with undiagnosed hyper-infections their clinical features were confusing. Three of the cases, all with low eosinophil counts, died but the other, who was treated with thiabendazole, survived. In the light of these observations, healthy medical examinees who had recently moved from endemic zones were checked for asymptomatic S. stercoralis infection, both by stool examination and ELISA-based serology. Of 381 stool samples investigated over a 3-month period, 183 (48%) were found positive for helminths, 7% for S. stercoralis. Of 198 individuals from endemic zones who were screened after another medical examination, 71 (35.8%) were found positive for intestinal helminth parasites, including one (1.45%) infected with S. stercoralis. Although ELISA appear reliable in making a presumptive diagnosis of strongylodiasis, the results of such assays are not very specific and are best interpreted in conjunction with the patient's clinical status. The concurrent administration of anthelminthics to patients prescribed steroids who, because they live or have lived in an area where S. stercoralis is endemic, are at risk of infection with the nematode, should be considered.

Objective To study the fine needle aspiration (FNA) cytologic features of papillary thyroid carcinoma (PTC) with special reference to its tall cell variant (TCV), which is the most aggressive of the variants. Study design Fifty-four PTC cases were classified into variants, and the frequency of well-known morphologic criteria was determined. Four parameters were quantitatively analyzed based on a study of 200 consecutive neoplastic follicular cells: shape of cells, color of cytoplasm, intranuclear cytoplasmic inclusion (INCI) and nuclear grooves. Results The PTC cases included 6 TCV (> or = 30% tall cells), 8 cases with a significant tall cell component (sig. TCC) having 10-29% tall cells, 17 usual variant (UV), 17 follicular variant (FV) and 6 miscellaneous variants. TCV differed significantly from UV and FV in having a higher tall cell count, higher count of cells with reddish cytoplasm and INCI, and higher frequency of cases with lymphocytic infiltration. PTC (with significant tall cell component [TCC]) differed significantly from TCV with regard to tall cell count and lymphocytic infiltration, from UV with respect to tall cell count and monolayered sheets, and from FV with respect to tall cells, INCI, grooved nuclei, acinar formation, fire-flare appearance and giant cells. Conclusion TCV was cytologically distinct from other variants. The biologic behavior of PTC cases with significant TCC, which morphologically seem to be a group intermediate between TCV on the one hand and UV and FV on the other, however, needs to be carefully monitored.

OBJECTIVE To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS In all, 1700 men (mean age 55.6 years, range 35–94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to 10 ng/mL in Arab men.

Background Fine needle aspiration (FNA) cytologic diagnosis of toxoplasmic lymphadenitis with demonstration of a tissue cyst containing bradyzoites has been very rarely reported. Case A 17-year-old female presented with a mobile, painless, 2-cm-diameter swelling over the right suprascapular area. Clinical diagnosis was lipoma. FNA smears showed features of reactive lymphoid hyperplasia, including tingible body macrophages and groups of epithelioid histiocytes. A Toxoplasma cyst with bradyzoites was also demonstrated in a Papanicolaou-stained smear. Following FNA cytodiagnosis, serologic tests revealed a high titer of IgG and the presence of IgM-specific antibodies to Toxoplasma gondii, indicating active/recent disease. Conclusion FNA cytology is a valuable tool for the diagnosis of toxoplasmic lymphadenitis. Papanicolaou stain is appropriate for demonstration of the parasite. Serology is an excellent adjunct in clinching the diagnosis.

Background: Breast cancers with Her-2 neu gene amplification are recognized as important markers for aggressive disease and targets which respond to therapy with trastuzumab. Her-2 neu testing on histological sections is routinely performed to select patients who may benefit from anti- Her-2 neu therapy. Few reports are available which document Her-2 neu status on fine needle aspirates (FNA). Aim: This pilot study is to document expression of Her-2 neu (Cerb-B2) on cytospin smears from FNA of patients with breast carcinoma. Materials and Methods: Twenty samples of FNA already collected for diagnostic purposes from patients with primary breast carcinoma were studied for demonstration of Her-2 neu expression by immunohistochemistry (IHC), Fluorescent in-situ hybridization (FISH) and chromogenic in-situ hybridization (CISH) on cytospin smears from FNA. Their expression was compared with tissue sections where possible. Results: Good correlation was observed between Her-2 neu protein expression and gene amplification in cytospin smears. Three of five (60%) breast carcinomas cases with 2+ and 3+ staining on IHC showed gene amplification by FISH and CISH. Three of 7 (43%) and 5 of 7 (71%) cases negative/1+ staining on IHC did not show gene amplification by FISH and CISH respectively. Tissue sections from 10 cases with 2+ and 3+ staining for Her2neu by IHC showed gene amplification in 8 cases. Conclusion: Demonstration of Her-2 neu by IHC, FISH or CISH in FNA is possible and may play a role in the management of patients with advanced breast cancer or those cases where surgical resection is not advisable.

Objective: The study is aimed at demonstrating the effectiveness of intravenous immunoglobulin (IVIg) in resistant lupus nephritis. Lupus nephritis was considered resistant when it failed to show adequate clinical and laboratory response to treatment with steroid, azathioprine and pulse cyclophosphamide in combination for a period not less than 1 year. Methods: During the past 7 years 4 subjects (M = 1, F = 3) with systemic lupus erythematosus (SLE) and lupus nephritis WHO IV were selected to receive IVIg. Their age ranged from 19 to 48 years. The 3 female patients had severe extrarenal manifestations including skin rash, photosensitivity, fever, headache and severe polyarthralgia requiring large doses of analgesics. The male patient had steroid-dependent, relapsing autoimmune hemolytic anemia (AIHA) in addition to extrarenal manifestations. All subjects had microscopic hematuria, proteinuria (2–6 g/24 h), hypoalbuminemia (24–33 g/l), mild renal impairment (serum creatinine 90–160 µmol/l) and active serology for SLE. These patients had not responded satisfactorily to several courses of steroids, azathioprine and pulses of intravenous cyclophosphamide in 23–180 months. All 4 patients were started and continued on IVIg as per our protocol. Results: During the 9 months to 7.5 years of follow-up, these patients showed excellent response to IVIg. Their extrarenal symptoms had totally disappeared, serological activity subsided, proteinuria decreased (0.5–2 g/24 h), serum albumin improved (30–42 g/l) and renal function remained stable. The subject with AIHA did not suffer any further relapses and his hemoglobin remained above 110 g/l with only 10 mg of prednisolone daily. Repeat renal biopsy done in 2 patients showed definite histological reversal of active lesions. Clinical and immunological improvements might be related to the modulation of macrophage T cell function and enhancement of suppressor T cell function. Conclusion: IVIg has shown excellent therapeutic effect as an alternative drug in treatment of renal and extrarenal manifestations of SLE, which are resistant to other modalities of treatment.

BACKGROUND: Granular cell tumors are neoplasms of uncertain histogenesis, although a neural origin is favored. Most reports on the cytologic features of granular cell tumors have been on lesions from the breast or respiratory tract. However, there are only a few reports on fine needle aspiration (FNA) cytologic diagnosis of cutaneous or soft tissue granular cell tumors. CASE: A 7-year-old girl presented with a skin lesion on her right forearm of one year's duration. The FNA smears showed sheets and clusters of oval to polygonal cells with an abundant amount of granular cytoplasm. Many single, scattered cells with similar morphology were seen in the background. Immunostaining for S-100 protein showed granular cytoplasmic positivity. The tumor was diagnosed as a benign granular cell tumor. The histopathology report on the excised lesion confirmed the FNA diagnosis. CONCLUSION: The cytopathologic features of granular cell tumors presenting as skin lesions are distinctive enough to allow a correct diagnosis on FNA cytology.

OBJECTIVE: To evaluate the possibility of replacing histologic biopsy of azoospermic testes by fine needle aspiration (FNA) for diagnostic and management purposes. STUDY DESIGN: Twenty-seven patients were examined under general anesthesia, and 53 testes were biopsied by FNA. Fifty-four testes were biopsied for histologic examination. Histology and cytology of each testis were compared to assess the discrepancy or concordance between the diagnoses. RESULTS: Twenty-seven testes showed complete concordance of cytology and histology, and 13 testes showed a mild degree of discrepancy. A severe degree of discrepancy was seen in 13 testes. In the majority of discrepant cases, FNA biopsy diagnosis was more sensitive in detecting evidence of full or advanced maturation. In one case of discrepancy, the histologic finding was Sertoli cells only, and cytology revealed focal full maturation. In vitro fertilization using sperm from this case was successful. CONCLUSION: FNA biopsy of testes in azoospermia is a fast, reliable and minimally traumatic method. The prospects for utilizing FNA biopsy material in assisted and microassisted fertilization are promising.

FNAC is a simple diagnostic tool for the initial evaluation of various deep seated pathological lesions. This study describes the applicability and practical aspects of the technique in establishing the diagnosis of spinal tuberculosis (TB) with the aid of radiographic guidance. The study was conducted in a major teaching hospital in Kuwait between the years 1985 and 1994. Twenty-nine patients (M:F = 18:11 and age range 8-72 years) with clinically and/or radiologically suspected spinal TB were seen in the Department of Cytology, Mubarak Al Kabeer Hospital. The patients were re-examined by either computed tomography (CT) scanning (n = 19) or fluoroscopy (n = 10) to localize the lesion for FNAC. FNAC smears were routinely stained with Papanicolaou and Diff Quik stains and one smear of each case was stained with Ziehl-Neelsen (Z-N) stain for acid-fast bacilli (AFB). Aspirated purulent material or syringe washings of dry aspirates were also submitted for microbiological cultures including AFB. Radiological and cytological findings were recorded in each case. Radiological findings included: bony rarefaction and destruction (93.1%), narrowed disc space (89.7%), soft tissue calcification (65.5%) and para-vertebral abscess formation (51.7%). Cytological findings included: epithelioid cell granulomas (89.7%), granular necrotic background (82.8%) and lymphocytic infiltration (75.9%). Smears were positive for AFB in 51.7% of cases. A positive AFB culture was obtained in 82.8% of cases, including all cases with positive AFB on smear by Z-N stain. Radiologically guided FNAC with AFB culture is a simple, reliable and practical approach to diagnosing spinal TB lesions. With a high diagnostic yield, it allows immediate initiation of specific treatment, helps to avoid invasive diagnostic procedures, and decreases hospitalization time.

Background: Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of this diabetic complication. Recent data indicated that a heat-shock protein (HSP) with a molecular weight of about 70 kd is expressed in wound healing and it is under the control of the hypothalamic-pituitary-adrenal axis. In view of these findings, the current study was designed to examine the influence of diabetes and the hypercortisolemic state on the expression of HSP 72/73 during wound healing. Methods: Induction of diabetes was achieved by the intravenous injection of streptozotocin at a dose of 55 mg/kg. Subcutaneously implanted polyvinyl alcohol (PVA) sponges were used as a wound healing model. Control and diabetic animals received, respectively, subcutaneous 30-day timed-release pellets of GC (200 mg) and RU 486 (25 mg). Corresponding animals received placebo pellets. Expression of HSP 72/73 within the PVA sponges was assayed with use of Western blotting and immunohistochemical techniques. Results: GCs caused a Cushing-like syndrome with weight loss and adrenal atrophy. A pronounced accumulation of constitutive HSP 72/73 was observed in the cytoplasm of various cell types including fibroblasts, macrophages, and endothelium of nondiabetic controls. The PVA sponge contents of HSP 72/73 were decreased as a function of diabetes. A similar phenomenon was seen in control animals receiving high doses of GCs. Partial normalization of the associated hyperglycemic and hypercortisolemic states of diabetes with insulin (hyperglycemia) and the GC receptor block RU 486 (hypercortisolemia) ameliorated the diabetes-related decrease in PVA sponge contents of HSP 72/73. Conclusions: The current study provides evidence that both diabetes and the hypercortisolemic state are associated with a reduction in PVA sponge content of HSP 72/73. An amelioration of these changes was achieved by the institution of RU 486 therapy. Although our data may point to the possibility that the diabetes-related decrease in HSP 72/73 is mediated at least in part by GCs, a confirmation regarding this premise awaits further investigation. (Surgery 1999;125:594-601.)

Objective: The aim of the study is to evaluate the DNA image analysis of smears in assessing spermatogenesis and to compare it to routine fine-needle aspiration cytology (FNAC). Methods: A total of 33 testicular needle aspirates from azoospermic infertile patients were blindly studied by 2 different cytologists separately; one studied the FNAC and the other evaluated the DNA contents. DNA image analysis was done on Feulgen-stained cytology smears. The generated DNA histogram was compared to cytology results. Results: Twenty-three (69.7%) testes showed complete agreement between the image analysis and cytology mainly in the presence of sperms, while 10 (30.3%) testes showed discrepancy between the DNA image analysis and cytology, mainly in the syndrome with Sertoli cells only and spermatogenic arrest. Conclusions: DNA image analysis of testicular aspirates is an objective and reliable method in assessing spermatogenesis, while cytology is a relatively subjective method and observer dependent. The discrepancy may be explained by cytologist inter- and intra-observer variability in evaluating spermatogenesis in the FNAC specimens.

Background and Objectives: Lesions of the thyroid and breast represent the two commonest sources of frozen section in Kuwait. This study investigates the value of intraoperative cytology (IC), preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section (FS), in improving the diagnostic accuracy of such lesions. Material: Thirty-one breast masses and 45 thyroid lesions were included. Methods: In each case, diagnosis was established by (1) preoperative FNAC, (2) intraoperative IC and (3) FS. Their accuracy was compared to paraffin section diagnosis. Results: Sensitivity of FNAC, IC and FS for breast malignancy was 82.6, 95.8 and 91.7%, respectively, while for thyroid malignancy sensitivity was 68.4, 85.0 and 65%, respectively. All three had 100% specificity and 0% false-positive rates. A 100% diagnostic accuracy was achieved by combined FNAC and IC in breast, and 93.3% with combined IC and FS in thyroid lesions. Conclusion: Intraoperative IC improves the diagnostic accuracy of FNAC and FS in breast and thyroid lesions.

This study aimed to develop a new experimental model of partial ureteric obstruction in sheep. Graded obstruction of the ureter using various sized catheters (Fr 3–8) for variable durations up to 6 weeks was performed in 19 sheep. The kidneys were studied by radionuclide diuretic renography for up to 21 weeks and had histopathological examination at the end of the experiment. Catheters of Fr 3 or Fr 5 should be used to block the ureter for a minimum of three weeks to produce sufficient functional and pathological changes to be studied. The advantages and disadvantages of this model are discussed.

Objective: To report data on the evaluation of the efficacy of urine cytology in detecting BK virus (BKV). Material and Methods: Papanicolaou-stained cytospin preparations of randomly collected urine samples from 8 renal transplant (RTR) patients (5 males, 3 females, age: 23–63 years) who previously tested positive for BKV by PCR in urine or blood or both were studied. Urine sediment from 3 of the patients was processed for ultrastructural examination (EM). Renal biopsies before and after BKV detection were also evaluated. Results: The interval between renal transplant and urine cytology ranged between 2 and 5 years. Urine from females was difficult to assess due to vaginal contamination. In 2 of the 5 urine specimens from male recipients BKV-infected decoy cells were identified. Viral particles suggestive of BKV were identified on EM in 2 of the 3 specimens studied. Kidney biopsies showed morphologic features suggestive of BKV infection in 2 cases, 1 each detected on cytology and EM, respectively. Conclusion: Screening for the presence of decoy cells in urine provides a simple sensitive means for the diagnosis of BKV nephropathy in RTR.

Objective: During routine fine needle aspiration cytodiagnosis of papillary thyroid carcinoma (PTC), a number of cases are diagnosed as suspicious; or it is suggested that PTC or a neoplasm be ruled out by histopathology. Since these diagnostic labels are likely to put the clinicians in a difficult situation while planning the management, this study aims to find out how much the surgeon should read from these reports. Materials and Methods: The patients were divided into two groups. Group A included 38 cases diagnosed as PTC or suspicious of PTC. Group B included 40 cases in which it was suggested that PTC/a neoplasm to be ruled out and non-neoplastic lesions with one or more cytologic features of PTC. The two groups were compared with clinical, imaging and cytomorphologic features. Results: A significant difference was observed with respect to age between Group A and Group B (P

Introduction Calcineurin inhibitor (CNI) induced HUS, although rare, can be a serious complication of renal transplantation. Classical syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury may not be fully manifested. Methods We retrospectively analyzed our data in 950 kidney recipients under follow-up in our center (1994 – 2008). We reviewed the kidney biopsies performed for these patients to exclude conflicting diagnoses like antibody mediated rejection. Results HUS was diagnosed in 12 patients (1.26%). None of them had HUS as the original kidney disease. Cyclosporine was the primary immunosuppression in 9 and tacrolimus in 3 patients. The median day of onset was 7 days. Manifestations were anemia (100%), thrombocytopenia (75%), elevated reticulocyte count (62.5%), fragmented red blood cells (8.3%), elevated lactate dehydrogenase (LDH) enzyme (83.3%), increased fibrin degradation product (FDP) (83.3%), reduced haptoglobin level (42.9%) and hyperbilirubinemia (25%). CNI elimination was the first step in the management. Transfusion of fresh frozen plasma (FFP) was used in 10 patients and plasma exchange with FFP in the other two. All grafts recovered function. Cyclosporine or tacrolimus were reintroduction in two patients after complete clinical and laboratory recovery. Both patients developed recurrence of HUS. While the former did not the latter did recover on further treatment of HUS. Conclusion Anemia, thrombocytopenia, elevated LDH and FDP are the most frequent manifestations of HUS. Early CNI elimination and fresh plasma transfusion can revert CNI induced HUS and save the graft. Reintroduction of CNI may be deleterious to the graft and should be avoided.

A histology-based retrospective study was carried out in Kuwait to determine the frequency and type of helminthic infestation of the appendix in this predominantly desert environment. In 1,674 consecu

It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non-Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed-Sternberg (R-S)-like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine-needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty-one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin-like cells and typical R-S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnosis of HL.

The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (anNa+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001),Cinulinincreased 80% (P<.01). Kidney wet and dry weights increased 10%–12% (P<.05), and glomerular tuft area increased 9.3% (P<.001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

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-Grunwald–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.

To report data on the evaluation of the efficacy of urine cytology in detecting BK virus (BKV).Papanicolaou-stained cytospin preparations of randomly collected urine samples from 8 renal transplant (RTR) patients (5 males, 3 females, age: 23-63 years) who previously tested positive for BKV by PCR in urine or blood or both were studied. Urine sediment from 3 of the patients was processed for ultrastructural examination (EM). Renal biopsies before and after BKV detection were also evaluated.The interval between renal transplant and urine cytology ranged between 2 and 5 years. Urine from females was difficult to assess due to vaginal contamination. In 2 of the 5 urine specimens from male recipients BKV-infected decoy cells were identified. Viral particles suggestive of BKV were identified on EM in 2 of the 3 specimens studied. Kidney biopsies showed morphologic features suggestive of BKV infection in 2 cases, 1 each detected on cytology and EM, respectively.Screening for the presence of decoy cells in urine provides a simple sensitive means for the diagnosis of BKV nephropathy in RTR.

The purpose of this study was to examine the effect of inhibition of Ras-GTPase mediated signalling on the development of hypertension and end-organ damage in spontaneously hypertensive rats chronically treated with nitric oxide synthesis inhibitor L-NAME (SHR-L-NAME). Administration of L-NAME in drinking water (80 mg/L) for 3 weeks significantly elevated mean arterial blood pressure (MABP) (223 +/- 4 mmHg) as compared to that of SHR controls (165 +/- 3 mmHg). The administration of Ras-GTPase inhibitor FPTIII (232 ng/min) to SHR-L-NAME during the last 6 days significantly attenuated high blood pressure (192 +/- 4 mmHg). Morphological studies of the kidneys and hearts showed that treatment with FPTIII minimized the extensive arterial fibrinoid necrosis, arterial thrombosis, narrowing of arterial lumen with marked arterial hyperplastic arterial changes that were observed in vehicle treated SHR-L-NAME. L-NAME-induced increase in urine volume and protein was also significantly lower in FPTIII-treated animals. The impaired vascular responsiveness to isoprenaline in the perfused mesenteric vascular bed of SHR-L-NAME-treated animals was significantly attenuated by FPTIII treatment. In isolated per-fused hearts, recovery of left ventricular function from a 40 min of global ischemia was significantly better in FPTIII-treated SHR-L-NAME. Treatment with FPTIII also significantly reduced expression of cardiac sodium-hydrogen exchanger-1 (NHE-1) which was elevated in SHR-L-NAME. These data indicate that inhibition of Ras-GTPase-mediated signalling can attenuate end-organ damage during severe hypertension and endothelial dysfunction. (c) 2005 Elsevier Ltd. All rights reserved., The purpose of this study was to examine the effect of inhibition of Ras-GTPase mediated signalling on the development of hypertension and end-organ damage in spontaneously hypertensive rats chronically treated with nitric oxide synthesis inhibitor L-NAME (SHR-L-NAME). Administration of L-NAME in drinking water (80 mg/L) for 3 weeks significantly elevated mean arterial blood pressure (MABP) (223+/-4 mmHg) as compared to that of SHR controls (165+/-3 mmHg). The administration of Ras-GTPase inhibitor FPTIII (232 ng/min) to SHR-L-NAME during the last 6 days significantly attenuated high blood pressure (192+/-4 mmHg). Morphological studies of the kidneys and hearts showed that treatment with FPTIII minimized the extensive arterial fibrinoid necrosis, arterial thrombosis, narrowing of arterial lumen with marked arterial hyperplastic arterial changes that were observed in vehicle treated SHR-L-NAME. L-NAME-induced increase in urine volume and protein was also significantly lower in FPTIII-treated animals. The impaired vascular responsiveness to isoprenaline in the perfused mesenteric vascular bed of SHR-L-NAME-treated animals was significantly attenuated by FPTIII treatment. In isolated perfused hearts, recovery of left ventricular function from a 40 min of global ischemia was significantly better in FPTIII-treated SHR-L-NAME. Treatment with FPTIII also significantly reduced expression of cardiac sodium-hydrogen exchanger-1 (NHE-1) which was elevated in SHR-L-NAME. These data indicate that inhibition of Ras-GTPase-mediated signalling can attenuate end-organ damage during severe hypertension and endothelial dysfunction.

Introduction BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. Patients and methods We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. Results No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 ± 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 ± 58 (87 to 285) μmol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 ± 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) μmol/L, which is better than the renal function at diagnosis. Conclusion The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Introduction: Intracytoplasmic lumens (ICL) with or without magenta material and transgressing vessels are features of Hurthle cell neoplasms (HCN). After detection of intracytoplasmic colloid inclusions (CIs) including targetoid (magenta) body-like structures in the Hurthle cells (HC) in a case of Hashimoto's thyroiditis (HT), we reviewed cases of HT, thyroid neoplasms, hyperplastic nodules (HN) and colloid goitres to determine the frequency of these structures. Further, an attempt was made to find out the significance of CIs. Methods: FNA smears of 120 HT, 101 colloid goitres, 11 HN, and 76 neoplastic goitres were examined. The presence of CIs and empty ICL were noted in epithelial cells in these lesions. An attempt was made to find out the difference between HT with and without CIs in respect of various cytomorphologic features. The groups were compared using the Fisher's exact test of probability. Results: The CIs were present in 36 (30.0%) of HT, 26 (34.2%) of neoplastic goitres, 3 (27.3%) of HN, and 4 (4.0%) colloid goitres. As compared to colloid goitres, CIs were present in a significant higher number of cases in HN (P = 0.0202), neoplastic goitres (P

To study the fine needle aspiration (FNA) cytologic features of papillary thyroid carcinoma (PTC) with special reference to its tall cell variant (TCV), which is the most aggressive of the variants.Fifty-four PTC cases were classified into variants, and the frequency of well-known morphologic criteria was determined. Four parameters were quantitatively analyzed based on a study of 200 consecutive neoplastic follicular cells: shape of cells, color of cytoplasm, intranuclear cytoplasmic inclusion (INCI) and nuclear grooves.The PTC cases included 6 TCV (or = 30% tall cells), 8 cases with a significant tall cell component (sig. TCC) having 10-29% tall cells, 17 usual variant (UV), 17 follicular variant (FV) and 6 miscellaneous variants. TCV differed significantly from UV and FV in having a higher tall cell count, higher count of cells with reddish cytoplasm and INCI, and higher frequency of cases with lymphocytic infiltration. PTC (with significant tall cell component [TCC]) differed significantly from TCV with regard to tall cell count and lymphocytic infiltration, from UV with respect to tall cell count and monolayered sheets, and from FV with respect to tall cells, INCI, grooved nuclei, acinar formation, fire-flare appearance and giant cells.TCV was cytologically distinct from other variants. The biologic behavior of PTC cases with significant TCC, which morphologically seem to be a group intermediate between TCV on the one hand and UV and FV on the other, however, needs to be carefully monitored.