The effect of simvastatin and erythropoietin on renal fibrosis in rats with unilateral ureteral obstruction.

Prevention of fibrosis is a very important therapeutic strategy in the treatment of obstructive nephropathy (ON). The aim of this study is to show and compare the actions of Simvastatin (Simv) and Erythropoietin (Epo) in renal expression of nuclear factor kappa B (NFκB), transforming growth factor-ß (TGF-ß), basic fibroblast growth factor (bFGF), platelet-derived growth factor B (PDGF-B), fibronectin and development of interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). A total of 48 Sprague-Dawley rats were allocated to 4 groups of sham, Epo, Simv and control. Unilateral ureteral ligation was performed on all rats except the Sham group. For interstitial fibrosis Masson's trichrome stain and for the expression of TGF-ß, PDGF-B, bFGF, NFκB and fibronectin, immunohistochemical methods were used. In the Epo and Simv groups, expression of TGF-ß and fibronectin and staining with Masson's trichrome were less compared to the control group. In addition, fibronectin expression in the Epo group was less than the Simv group. Unlike the Simv group, NFκB and bFGF expression in the Epo group were less when compared to the control group. Consequently, it was seen that both Epo and Simv prevented fibrosis in ON. Epo was superior in this effect by suppressing the expressions of NFκB and bFGF more effectively than Simv. Based on this finding, Epo might be a better agent than Simv in the prevention of fibrosis in ON.

Primary intestinal-type adenoma of the vagina arising directly from endocervical-type adenosis: a case report.

BACKGROUND: Tubular or villous adenomas are common neoplasms of the gastrointestinal tract. Other locations where these adenomas are found, including the female genital tract, are very rare. A literature review documents that only eight cases of tubular or villous adenomas found within the vagina have been published. CASE: A 25-year-old, Caucasian woman presented with a history of primary infertility and postcoital bleeding. Gynecologic examination revealed a polypoid mass attached to the lateral wall of the vagina, approximately 2 cm above the introitus. The polypectomy specimen was a soft, tan, polypoid mass measuring 2 x 1 x 0.8 cm in size. Microscopically, the lesion was identical to pure tubular adenomas of the large intestine. Positive immunohistochemical staining for cytokeratin (CK) 20, CK 7, CEA and Cdx2 were identified. CONCLUSION: An intestinal-type adenoma should be included in the differential diagnosis of a vaginal polypoid mass lesion in women. Our review of the literature presents the risk of malignant transformation.

Fine-needle aspiration cytology of metastatic oligodendroglioma: case report and literature review.

BACKGROUND: Systemic metastasis of a glial tumor is a rare event. However, metastatic cases are anticipated to increase due to prolongation of survival as a result of the development of new treatment modalities. The possibility of metastasis should be considered in patients with a history of a glial tumor rather than a second primary tumor. Fine-needle aspiration cytology is one of the diagnostic procedures primarily applied for confirmation of metastasis in cases with a known primary focus. Therefore, comprehensive knowledge of diagnostic cytomorphologic findings is required in these cases. CASE REPORT: We report a young woman with oligodendroglioma metastasizing to the cervical lymphatic chain 5 years after initial diagnosis. Fine-needle aspiration cytology revealed a highly cellular smear with dispersed single cells and loosely cohesive cell clusters showing rosette-like features on a clean background. The relatively monotonous tumor cells were small sized and had round nuclei with moderate anisonucleosis and scant cytoplasm without extensions. Diagnostic confirmation was made by excisional biopsy and demonstration of 1p19q codeletion on tissue section by fluorescence in situ hybridization. CONCLUSION: A brief review of the literature with an emphasis on the cytologic features of metastatic oligodendroglioma and differential diagnosis with respect to other metastatic small round cell tumors is provided.

Malignant lymphoma associated with Behçet's disease: A report of 2 cases.

Herein we report 2 cases of malignant lymphoma associated with Behçet's disease. Case 1, a 53-yearold man, was diagnosed as Behçet's disease at the age of 26 years, and was treated with cyclophosphamide and prednisolone. At 45 years of age, bilateral enlarged lymph nodes were observed in the patient's neck. Evaluation of a lymph node biopsy specimen showed Hodgkin's disease and chemotherapy was administered. Due to disease recurrence 7 years later, chemotherapy and radiotherapy were administered. Case 2, a 67-year-old male, was diagnosed as Behçet's disease at age 44 years and began colchicine treatment. At 60 years of age a mass in his left tonsillar fossa was noted. Evaluation of a left tonsil biopsy specimen showed malignant lymphoma. Radiotherapy and chemotherapy were subsequently administered. At the time this report was written both patients were disease-free. Malignant lymphoma associated with Behçet's disease is rare-only 17 cases have been published. In addition to the presented cases, the literature regarding malignant lymphoma associated with Behçet's disease is reviewed.

Effect of rosiglitazone on cisplatin-induced nephrotoxicity.

AIM: Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity. METHODS: Eighteen male Sprague-Dawley rats weighing 150-200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis-Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically. RESULTS: Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p<0.05) and group 2 (p<0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p>0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p<0.05). However, there were no significant differences between groups 1 and 2 (p>0.05). CONCLUSION: This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.

Metastasis of adenocarcinoma of the gall bladder to an endometrial polyp detected by endometrial curettage: case report and review of the literature.

SUMMARY: Polyps are the most common benign lesions in the endometrium. Metastasis to the endometrial polyp from a distant primary tumor is rare. Breast carcinoma is the most frequent extragenital cancer that metastasizes to the endometrial polyp. We report the case of a 63-year-old with metastatic gall bladder adenocarcinoma involving endometrial polyps detected by endometrial curetting. It was the first sign of her metastatic disease. After this diagnosis, bone metastases were detected during radiologic screening. Gastrointestinal tumor metastasis to an endometrial polyp is a very rare event, but if a patient with a known primary extragenital tumor has abnormal vaginal bleeding, the possibility of metastasis should be included in the differential diagnosis.

[Arthroplasty for the treatment of joint degeneration caused by ochronosis in two cases]. / Iki olguda okronozise bagli eklem dejenerasyonunda artroplasti uygulamalari.

Ochronosis is a rare metabolic disease caused by the deficiency of the homogentisic acid oxidase enzyme. With increasing age, accumulation of pigment deposits of homogentisic acid in the joint cartilage results in ochronotic osteoarthritis. We presented two female patients, with ages 55 and 60 years, who underwent staged bilateral uncemented total hip and bilateral cemented total knee arthroplasty, respectively, for osteoarthritis caused by ochronosis. Both patients had no significant complaints at final follow-up examinations made 12 months and 10 months after the second operation in the hip and knee, respectively. Plain radiographs did not show any abnormality in the components of the prostheses. Histopathologic examination of surgical specimens showed brown-black pigment deposits in the connective tissue and cartilage tissue.

Intrathoracic malignant peripheral nerve sheath tumor with angiosarcoma in a child with NF1.

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon in children and adolescents but occur more frequently in NF1 patients. Angiosarcomatous differentiation in MPNSTs is a rare entity with poor prognosis. We report on a 13-year-old boy with intrathoracic angiosarcoma arising in MPNST associated with NF1.

Clinicopathologic features, cellular differentiation, PCNA and P53 expressions in gastrointestinal stromal tumors.

BACKGROUND/AIMS: Gastrointestinal stromal tumors are currently defined, as specific c-kit positive primary mesenchymal tumors of the gastrointestinal tract. Although increasing tumor size and mitotic activity favours aggressive behaviour, no specific histological criteria that enable the prediction of biological behaviour have yet been identified. The purpose of this study is, (1) to determine whether cell differentiation of gastrointestinal stromal tumors could be detected through their expression of various antigens, (2) to correlate their macroscopic and histologic features with cell differentiation, p53 expression, PCNA score and clinical outcome. METHODOLOGY: 65 gastrointestinal stromal tumors were included in this study. All cases were reviewed in terms of clinical presentation and courses. The cell morphology, growth pattern, cellularity, pleomorphism, mucosal invasion, necrosis and mitotic index were evaluated. Tissue sections were immunostained with CD117, CD34, alpha-smooth muscle actin, and S-100 protein. PCNA score and p53 expressions were investigated to determine whether these could be used as prognostic indicator. RESULTS: Clinical outcome was obtained for 42 of the 65 patients. The follow-up time ranged from 1 to 240 months (median: 20 months). The tumors occurred in 34 female and 31 male patients, ranging in age from 1.5 months to 80 years (median: 53 years). Tumors were located in the stomach (19), duodenum (10), jejunum and ileum (19), the colon (5), the anorectal region (5) and in the mesentery or omentum (7). 55 tumors had spindle, 7 showed spindle and epithelioid, 3 had pure epithelioid morphology. Mitotic rate was found significantly different between probably benign 11 cases and recurrent 11 and metastatic 25 cases (p=0.001). Immunohistochemically, CD117 positivity was found 52 tumors (80%). 4 of 13 CD117 negative tumors were positive for CD34. 4 of 9 tumors showing were also a-SMA and S-100 negative. CD34 positivity was determinated in 44 tumors (67.6%). alpha-SMA reactivity was seen in 39 tumors (60%). Only 5 tumors showed S-100 protein reactivity (7.69%). Statistically, mitotic rate was found significantly different between probably benign 11 cases and recurrent 11 and metastatic 14 cases (p=0.001). Furthermore, there were significant differences between the probably benign neoplasms and recurrent or metastatic cases in following parameters; p53 expression, PCNA score, presence of necrosis and cellularity. CONCLUSIONS: GISTs could be specifically differentiated neoplasms and their some other aspects should be clarified such as relations with c-kit and other oncogenes and dual or "null" differentiation in the same neoplasm.

Prenatal diagnosis of Meckel-Gruber syndrome and Dandy-Walker malformation in four consecutive affected siblings, with the fourth one being diagnosed prenatally at 22 weeks of gestation.

We report a 23-week-old male fetus affected by Meckel-Gruber syndrome. Posterior encephalocele, post-axial polydactyly, and Dandy-Walker malformation were observed on ultrasonographic (USG) examination at 22 weeks' gestation, and lobar holoprosencephaly was demonstrated on postmortem magnetic resonance imaging (MRI) prior to autopsy. After the termination of the pregnancy, polycystic dysplastic kidneys were also noted at postmortem investigation. The proband was the product of the fourth pregnancy of a consanguineous family in which all three siblings were also similarly affected. Interestingly, both the two-year-old affected sister and 23-week-old male fetus had Dandy-Walker complex.

Aberrant centrizonal features in chronic hepatic venous outflow obstruction: centrilobular mimicry of portal-based disease.

Chronic hepatic venous outflow obstruction is characterized by centrizonal scarring but may also display features that can lead to portal tract mimicry and misdiagnosis as biliary disease, especially given elevated cholestatic liver profiles in these patients. However, these histopathologic features have not been systematically described. We graded the numbers of centrizonal arterioles, ductules, keratin 7+ hepatocytes, CD34+ microvessels, and capillarized sinusoids in 61 cases of chronic venous outflow obstruction and assessed changes in metabolic zonation by glutamine synthetase staining. Centrizonal arterioles and ductules were present in 82.0% and 72.1% of cases, respectively, and correlated with fibrosis. Centrizonal CD34+ microvessels and sinusoidal capillarization were closely associated and present in 25 (92.6%) and 26 (96.3%) of 27 cases, respectively. Centrizonal capillarized sinusoids and microvessels, which were present in all cases with advanced fibrosis, were demonstrated in 90% and 80% of the cases without significant fibrosis, respectively. The results suggest that capillarization and/or microvessel formation precede and may contribute to centrizonal scarring, whereas arterialization likely reflects vascular remodeling associated with progressive fibrosis. Centrizonal ductules were often immature, being either keratin 7+/keratin 19- (36.4%) or keratin 7-/keratin 19- (10.0%). Centrizonal keratin 7+ intermediate-phenotype hepatocytes were present in 25 (92.5%) of 27 cases. Lastly, 22 (91.7%) of 24 cases showed loss of metabolic zonation, with reversed zonation in 2 (8.3%) cases. Together, the findings indicate that vascular and lobular reorganization in chronic venous outflow obstruction may result in mimicry of central zones as portal tracts. Recognition of these changes is essential to prevent misdiagnosis of this condition as biliary tract disease.

Incidentally detected renal adenomatosis in a patient with urolithiasis: a case report.

A renal epithelial tumor with a papillary or tubulopapillary pattern and a low nuclear grade is defined as a renal adenoma if its diameter is 5 mm or less. Two important issues related to the renal adenoma are the lack of exact criteria for the histopathological differentiation from a papillary renal cell carcinoma and the lack of consensus as to whether it is a precancerous lesion. Renal adenomatosis is very rarely seen entity entity characterized by multiple and usually bilateral adenomas. Innumerable adenomas, adenomatous transformations within a single tubule and adenomas measuring 7 mm or less, were detected in a 47-year-old man who underwent simple nephrectomy due to nonfunctional hydronephrosis secondary to urolithiasis. In this paper, our diagnostic approach to this fairly rare entity is discussed along with a brief literature review.

Intracerebroventricular Application of Dexmedetomidine Produces Antinociception and Does not Cause Neurotoxicity in Rats.

BACKGROUND: Alpha2 agonists contribute to pain control at the level of the medulla spinalis. Alpha2 agonists are generally added to local anaesthetics to prolong spinal or epidural anaesthesia time. AIMS: In the present study, we aimed to evaluate the antinociceptive and neurotoxic effects of dexmedetomidine given intracerebroventricularly for 5 days. STUDY DESIGN: Animal experimentation. METHODS: After intraventricular cannulation, rats (n=32) were divided into two groups (n=16 each). Rats in the dexmedetomidine group (Group D, n=16) received 3 µg (0.03 mL) dexmedetomidine and the control group (Group C, n=16) received 0.03 mL physiological serum through an intracerebroventricular catheter once a day, for 5 days. Antinociceptive, sedative, and motor effects were evaluated before the injection and for 90 min after injection. The tail-flick and hot plate tests were used to assess thermal nociceptive threshold. For histopathological evaluation, half of the rats in both groups were sacrificed on the 6(th) day and the remaining rats were sacrificed on the 21(st) day. Then the perfusion fixation method was applied. The first tissue section was obtained from the cervical spinal cord 1 cm distal to the proximal end of the spinal cord. The second sample was retrieved from the region 1 cm distal from the thoracic 13-lumbar 1 vertebra. On morphological evaluation, nonspecific changes like edema and gliosis, signs of neuronal degeneration demonstrating a severe reaction, and density of inflammatory cells were examined. RESULTS: In dexmedetomidine-administered rats, on the first day reaction times at 5, 10, and 20 min and on the other days, reaction times at 5, 10, 20, and 30 min in hot plate tests were significantly longer compared with baseline values (p<0.05). In dexmedetomidine-administered rats, on the 1(st), 4(th), and 5(th) days reaction times at 5, 10, 20, 30, and 40 min and on the 2(nd) and 3(rd) days reaction times at 5, 10, 20, and 30 min in tail-flick tests were significantly longer compared with baseline values (p<0.05). First-degree sedation lasting for 60 min and first-degree motor block lasting for 30-40 min were observed in the dexmedetomidine group. Similar rates of nonspecific changes such as edema and gliosis were seen in both groups. Signs of severe reactions such as neuronal degeneration and diffuse inflammatory cell infiltration were not encountered in any group. There was no significant difference between groups according to morphological findings of the spinal cord on the 6(th) and 21(st) days (p>0.05). CONCLUSION: We observed that intracerebroventricular administration of 3 µg dexmedetomidine produced antinociception and did not cause neurotoxicity.

Evaluation of antinociceptive and neurotoxic effects of intrathecal dexmedetomidine in rats.

OBJECTIVE: Dexmedetomidine has been reported to produce analgesia after intrathecal administration. In the present study the α2-adrenoceptor agonist dexmedetomidine was evaluated for its potential spinal neurotoxic effects. MATERIAL AND METHODS: Three days after intrathecal cannulation, rats were administered either dexmedetomidine (3 µg/30 µL, i.t.) or saline (30 µL, i.t.). Antinociceptive, sedative and motor effects of intrathecal administrations of dexmedetomidine or saline were evaluated during 90 min. The tail-flick and hot plate tests were used to assess the thermal nociceptive threshold. Seven days after drug administration, animals were sacrified and spinal cords were evaluated for histopathological changes by light microscopy. RESULTS: Dexmedetomidine administered intrathecally produced antinociception. Antinociception was accompanied by immediate sedation and loss of placing-stepping reflexes that lasted over 40 min in all dexmedetomidine administered rats. In all rats, microscopic examination revealed mild gliosis and minimal infiltration of inflamatory r cells in posterior white matter. Mild (total score 4-6) histopathologic lesions were seen in four animals in dexmedetomidine adminisered rats, but there was no statistically significant difference when compared with the saline administered rats. CONCLUSION: We observed that intrathecal injections of dexmedetomidine at the dose of 3 µg/30 µL produce antinociception but did not cause any histopathological sign of injury in the spinal cord.

Thymosin ß4 is a novel potential prognostic marker in gastrointestinal stromal tumors.

Thymosin beta-4 (Tß(4)) is a major actin-sequestering molecule that contributes to cell growth, differentiation, motility, survival, mitosis and angiogenesis. It is overexpressed in certain type of carcinoma and fibrosarcoma cell lines and is associated with metastatic potential. The aim of this study was to investigate the relationship between Tß(4) expression and clinicopathologic features and VEGF status in gastrointestinal stromal tumors (GISTs). Retrospectively, 60 GISTs were re-examined and immunohistochemistry for Tß(4) and VEGF was performed. Increased expression of Tß(4) and VEGF was observed in 26 (43.3%) and in 19 (31.6%) of the tumors, respectively. Tß(4) expression was positively correlated with VEGF expression (p < 0.01). Tß(4) and VEGF expression were significantly associated with tumor size (p = 0.00 and p = 0.02, respectively) and high mitosis (p = 0.03 and p = 0.00, respectively). Although Tß(4) expression was positively associated with pleomorphism (p = 0.01), VEGF expression was positively associated with necrosis (p = 0.03). Tß(4) expression was related with local recurrence and/or metastasis (p = 0.03), but VEGF expression was not (p = 0.12). We firstly demonstrate the presence of Tß(4) protein in GISTs. Our study reveals that increased expression of Tß(4) could be considered as an indicator of aggressive behavior of tumor.

Clinical, histopathological and mineralogical analysis findings of an unusual case of pneumoconiosis.

A 43-year-old man with a long history of dyspnea which had progressively worsened over the preceding month is presented. He had worked in an antimony mine for 3 years. Radiologically, there were diffuse reticulonodular shadowing opacities in both lung parenchymas. Histopathologic examination of the open-lung biopsy specimen revealed alveolar spaces filled with dust-laden macrophages and amorphous proteinaceous semifluid, the latter being immunoreactive for Human Surfactant Apoprotein A, associated with marked interstitial accumulation of the similar-looking macrophages along the bronchovascular bundles and mild interstitial fibrosis. Silicotic nodules or mixed dust fibrosis were not seen. The patient was diagnosed as silicoproteinosis with unusual histopathological features because he had worked in an antimony mine for only 3 years and had 86% silica in a mineralogical analysis. Pneumoconiosis is a rare lung disease which may be confused with other interstitial lung diseases. Clinical, radiological and unusual histopathologic features of this rare case are presented and discussed with the differential diagnosis, especially of mixed dust pneumoconiosis.

Inhibition of vein graft intimal hyperplasia by periadventitial application of hyaluronic acid-carboxymethyl cellulose: an experimental study.

OBJECTIVE: Placement of an external support has been reported to prevent intimal hyperplasia of vein grafts. In this study, we investigated the effect of HA/CMC on intimal hyperplasia in a rabbit model. DESIGN: Right jugular vein to common carotid artery bypass grafting was performed in 24 female New Zealand white rabbits (2.5-3.0 kg). Animals were divided into two groups: control group (n=12) and HA/CMC group (n=12). Absorbable membrane barrier was wrapped around vein grafts in HA/CMC group. In control group, no material was applied following venous graft bypass. RESULTS: At 1 month, in the vein grafts supported with the HA/CMC membrane neointimal thickening was significantly less (109 microm [IQR, 78-166]) compared to the unsupported control grafts (220 microm [IQR; 101-312]; p<0.001). Medial thickening in the HA/CMC group (128 microm [IQR, 101-181]) compared to unsheathed control grafts (182 microm [IQR, 131-255] p<0.001) was also significantly less. CONCLUSION: Periadventitial placement of HA/CMC as an absorbable membrane inhibits intimal hyperplasia of vein bypass grafts in a rabbit model.

Serum endostatin levels and regenerative capacities of normal and cirrhotic livers following partial hepatectomy in mice: the response to different resection sizes.

BACKGROUND: Angiogenesis has an important role in liver regeneration. Antiangiogenic response in remnant liver following resection and its relationship to regeneration is not well known. The aim of this study was to investigate the effect of hepatectomy size on serum endostatin levels, and the effect of endostatin levels to liver regeneration after partial hepatectomy in normal and cirrhotic mice. MATERIALS AND METHODS: Sixty noncirrhotic and 36 carbon tetrachloride-induced cirrhotic mice were included in the study. Noncirrhotic mice were randomly divided into four main groups: sham, 20%, 40%, and 70% hepatectomy groups. Similarly, cirrhotic mice were randomly divided into three main groups: sham, 20%, and 40% hepatectomy groups. The mice in each group were further divided into two subgroups to compare serum endostatin levels and liver regeneration indexes on days 1 and 14. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum endostatin level was measured to evaluate antiangiogenic response. RESULTS: Serum endostatin levels on the first day and 14th day increased significantly in correlation with the hepatectomy size, both in normal mice and cirrhotic mice (P < 0.05). In normal mice with high regeneration indexes that underwent 40% and 70% hepatectomies, there was a significant increase in serum endostatin levels on the 14th day compared with the first day (P < 0.05). However, the increase in mice that underwent 20% hepatectomies was not significant. After 20% and 40% hepatectomies, first day serum endostatin levels were significantly higher in cirrhotic mice compared with normal mice (P < 0.05), which was independent of regeneration. Nevertheless, after 40% hepatectomies, 14th day serum endostatin levels were significantly lower in cirrhotic mice compared with normal mice, attributable to the limited regeneration capacity of cirrhotic liver (P < 0.05). Regeneration capacity of cirrhotic liver was low at all times. CONCLUSIONS: The current study suggests that there is a significant relationship between serum endostatin levels and regeneration capacity after hepatectomy in normal mice. On the other hand, following resection of cirrhotic liver, regeneration capacity is depressed and high endostatin levels are independent of hepatic regeneration.