M. Salih Deveci

Serum leptin levels in patients with nonalcoholic steatohepatitis

OBJECTIVE:Leptin is a peptide hormone that mainly regulates food intake and energy expenditure of human body. A close correlation between serum leptin levels and the percentage of body fat stores is well known. Nonalcoholic steatohepatitis (NASH) is a common disorder which causes serum liver enzyme elevation. In this study, the serum leptin levels were investigated in patients with NASH to determine a possible role in the pathogenesis and in patients with chronic viral hepatitis to ascertain the effect of hepatic inflammation on serum leptin level.METHODS:Forty-nine patients (38 men, 11 women) with NASH diagnosed by biopsy, 32 patients with biopsy-proven chronic viral hepatitis (21 men and 11 women), and 30 healthy adults (17 men, 13 women) enrolled in the study. Fasting blood samples were obtained, and serum leptin levels were measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.RESULTS:The mean serum leptin levels (±SEM) were 6.62 ± 0.71, 4.24 ± 1.0, and 4.02 ± 0.46 ng/ml in NASH, chronic hepatitis, and the control group, respectively. Mean serum leptin level in the NASH group was significantly higher than those in the other groups tested. BMI was also slightly higher in the NASH group when compared to the other groups (26.7 ± 0.3, 23.7 ± 0.6, and 24.6 ± 0.3, respectively). There was a significant correlation between BMI and serum leptin levels when all the subjects were evaluated together (NASH, hepatitis, and control groups, r= 0.337, p= 0.012) but not in the NASH group when evaluated alone (r= 0.238, p= 0.1). Of the predisposing factors for NASH, obesity was observed in 24% of patients and hyperlipidemia in 67%. Serum cholesterol and triglyceride levels were significantly higher in the NASH group than those in controls (p < 0.05). It has been detected that most of these patients consumed high amounts of fat in their dietary habits.CONCLUSIONS:The serum leptin levels were significantly higher in patients with NASH, while they were not affected by chronic hepatitis. This elevation is out of proportion to BMI of these patients and may be related to hyperlipidemia in most. Elevated serum leptin levels, therefore, may promote hepatic steatosis and steatohepatitis.

Evaluation of sericin/collagen membranes as prospective wound dressing biomaterial.

Sericin, a silk protein, has high potential for use in biomedical applications. In this study, wound dressing membranes of Sericin (S) and Collagen (C) were prepared by glutaraldehyde cross-linking at S/C; 2:1, 1:1, 1:2, and 0:1 weight ratios. They were stable in water for 4 weeks. However, increasing the proportion of sericin had decreasing effect on the membrane stability. Water swelling property of membranes was enhanced with sericin. The highest water swelling was obtained in 1:1 group (9.06 g/g), but increasing collagen or sericin content in the membranes had a diminishing effect. Highest water vapor transmission rate was obtained with 1:2 group (1013.80 g/m(2)/day). Oxygen permeability results showed that 1:2 (7.67 mg/L) and 2:1 (7.85 mg/L) S/C groups were better than the other groups. While sericin decreased the tensile strength and elongation of membranes, it increased modulus. Sericin also increased brittleness of membranes, but their UTS range (24.93-44.92 MPa) was still suitable for a wound dressing. Membranes were not penetrable to microorganisms. Cytotoxicity studies showed that fibroblasts and keratinocytes attached and gained their characteristic morphologies. They also proliferated on membranes significantly. After 1 week of subcutaneous implantation, a fibrous capsule formed around all membranes with an acute inflammation. Sericin containing membranes showed signs of degradation (at 2nd week), while collagen only membranes remained largely intact. Eventually, sericin containing membranes degraded in 3 weeks with moderate inflammatory response. Overall results suggest that sericin/collagen membranes would be favorable as wound dressing material when sericin ratio is less than or equal to the collagen component.

Relationship between Postoperative Recurrence Rate and Eosinophil Density of Nasal Polyps

Objectives Nasal polyps develop as a result of chronic inflammation, mostly accompanied by pronounced eosinophil leukocyte infiltration. In this study we aimed to investigate the relationship between eosinophil density in nasal polyps and the postoperative recurrence rate of this disease. Methods Forty-two patients who underwent endoscopic sinus surgery for massive nasal polyposis by one surgeon were included in the study. The eosinophil leukocyte densities in nasal polyps were determined retrospectively on histologic slides by use of computer-assisted image analysis software. The patients were assigned to group 1, in whom nasal polyps contained up to 3 eosinophils per 1,000 urn2, and group 2, in whom nasal polyps contained 4 or more eosinophils per 1,000 um2. The postoperative recurrence rates of nasal polyps were compared in the two groups. Results There were 20 patients in group 1 and 22 patients in group 2. Postoperative polyp recurrence was detected in 5 of 20 patients (25.0%) in group 1 and in 18 of 22 patients (81.8%) in group 2 during the 30-month postoperative follow-up period (p < 0.05). Conclusions The eosinophil density of nasal polyps can be used to get an estimate of the postoperative recurrence risk. Eosinophil-rich nasal polyps have a higher postoperative recurrence rate.

The local antinociceptive actions of nonsteroidal antiinflammatory drugs in the mouse radiant heat tail-flick test

BACKGROUND:While many preclinical models detect the analgesic activity of nonsteroidal antiinflammatory drugs (NSAIDs), the radiant heat tail-flick response has repeatedly been insensitive to this class of drugs. As the tail-flick test involves nociceptive processing at spinal circuits with supraspinal modulation, it seems reasonable to assume that the NSAIDs should not modify strong nociceptive stimuli, since the primary site of action of NSAIDs is likely to be in the periphery. METHODS:We injected 3–300 &mgr;g of diclofenac, dipyrone, ketorolac, lysine acetyl salicylate, and sodium salicylate intradermally into mice tails and evaluated the tail-flick response to radiant heat. These results were compared with intraperitoneally injected controls. We also evaluated the ability of naloxone to reverse the observed effects. RESULTS:Intradermal injection of each NSAID produced a dose-dependent increase in tail-flick latency. Intraperitoneal NSAIDs injection produced no antinociceptive effects. Naloxone pretreatment had no effect on the antinociceptive effects of intradermal diclofenac, ketorolac, lysine acetyl salicylate, and sodium salicylate. Naloxone completely blocked the antinociceptive effects of intradermal dipyrone. CONCLUSIONS:Local, but not systemic, administration of NSAIDs produced antinociception in the tail-flick thermal assay. The endogenous opioid system contributes to the peripheral antinociceptive effects of dipyrone, but not to that of diclofenac, ketorolac, lysine asetyl salicylate, or sodium salicylate, suggesting differences in the mechanisms of action among the NSAIDs.

Oncocytic mucoepidermoid carcinoma of the parotid gland: Report of a case with DNA ploidy analysis and review of the literature

A 44‐year‐old female presented with a painful mass in the left parotid gland. Histologic examination revealed the characteristic picture of oncocytic mucoepidermoid carcinoma (OMEC) composed mainly of sheets of oncocytic cells with uniform nuclei and eosinophilic cytoplasm, focally smaller epidermoid cells surrounding poorly formed glandular spaces, and a few cystic structures lined by well‐differentiated mucous cells with intracytoplasmic mucin. Immunohistochemical staining with antimitochondrial antibody showed granular cytoplasmic positivity in oncocytic cells. The resulting histogram for DNA ploidy analysis was of diploid type. OMEC of the parotid gland is a recently described rare neoplasm. Only six cases have been previously reported in the literature. For an accurate approach in the management of patients, OMEC should be considered in the differential diagnosis of oncocytic lesions of the parotid gland, most of which are benign.

Prognostic value of p53 protein and MK-1 (a tumor-associated antigen) expression in gastric carcinoma

BackgroundMK-1, the target molecule of FU-MK-1, is encoded by the GA733-2 gene, which is currently being used as a target in clinical trials for gastric, intestinal and biliary cancer treatment with monoclonal antibodies. Also of interest is p53, a protein that has been intensively investigated in relation to particular types of tumors, patterns of metastases, tumor stage, and prognosis.MethodsThe expression of p53 protein and MK-1 antigen was investigated in specimens from 42 patients with gastric carcinoma. The specimens were stained by the avidin-biotin peroxidase technique for immunohistochemical examination.ResultsMK-1 was positive in 21 (50%) of the 42 cases. MK-1 expression was more frequent in cardia tumors (71%), in large (>3 cm) tumors (60%–64%), and in specimens from patients with more than five metastatic lymph nodes (69%). p53 expression was present in 20 (48%) of the 42 cases. Of these 20 patients, 15 (52%) had tubular adenocarcinoma (TA) and 5 (38%) had signet ring cell carcinoma. p53 expression was more frequent in the tumors of male patients (55% vs 27%); in poorly differentiated TAs (60% vs 47% in well-to-moderately differentiated TAs); in smaller tumors (£3 cm, 72% vs 43%–50% in larger tumors); in patients with a prominent inflammatory response (61% vs 21%; P < 0.02); and in patients with lymphatic vessel invasion (77% vs 34%; P < 0.02). However, p53 expression was less frequent in the presence of more than five metastatic lymph nodes (23% vs 60% for five or fewer nodes; P < 0.05). Most patients with p53- and MK-1-positive gastric carcinomas and those more than five metastatic lymph nodes had a poor prognosis.ConclusionThe study found that the expression of both p53 and MK-1 was frequent in aggressive gastric carcinomas; however, extensive lymph node involvement (more than five nodes) was the only significant factor related to overall survival.

Unusual features in a patient with neurofibromatosis type 1: Multiple subcutaneous lipomas, a juvenile polyp in ascending colon, congenital intrahepatic portosystemic venous shunt, and horseshoe kidney

We report a case that draws attention to a hitherto undescribed association of neurofibromatosis type 1 (NF1) with juvenile polyp, congenital intrahepatic portosystemic venous shunt, multiple subcutaneous lipomas, and horseshoe kidney. Our patient has fulfilled the National Institutes of Health consensus conference criteria for NF1 by having neurofibromas, axillary freckling, Lisch nodules, and café‐au‐lait spots. There is no family history of NF1 and his 7‐year‐old son has no stigmata of NF1. On the other hand, the patients family had a presumably dominant inheritance of horseshoe kidney: the father, proband, sister, and son of the other sister had a horseshoe kidney. The patient was investigated for mutations in the NF1 gene and PTEN, but no germline mutations were detected. The differential diagnosis for such a collection of hamartomatous, cutaneous, and vascular disorders includes the Proteus, Bannayan–Riley–Ruvalcaba, and Cowden syndromes. None of these diagnoses was convincingly confirmed in this patient.

Pericardial rhabdomyomatous spindle cell thymoma with mucinous cystic degeneration

Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour Sir: Isotalo et al. have commented on our recently published study that provided immunohistochemical evidence of mesothelial cell origin for a series of paratesticular adenomatoid tumours. In their letter Isotalo et al. refer to their own study in which they conclude that, rather than being of mesothelial cell origin, adenomatoid tumours are derived from mesenchymal cells. In this study they describe nests of epithelioid cells peripheral to aggregates of adenomatoid tumour acini. Additionally, in two cases of pseudomyxoma peritonei and two cases of testicular hydrocoele, they observed cytokeratin-positive glandlike structures within the stroma and describe a morphological transition between these epithelioid cells and adjacent stromal cells. They speculate that the epithelioid component of adenomatoid tumours develops from mesenchymal cells through a process of induction by submesothelial cells. We remain unconvinced of the validity of the conclusions Isotalo et al. drew from their data. In our own study and in a follow-up study in which we investigated calretinin expression and growth kinetics in the same series of tumours, we have demonstrated that the immunohistochemical phenotypic pro®le of the epithelioid component of both acinar and solid adenomatoid tumours is identical to that of mesothelial cell proliferations. It is highly unlikely that this would be the case if these cells were not of mesothelial cell origin, but were derived by a metaplastic process from what appear to be reactive ®broblasts. It is signi®cant that in adenomatoid tumours no cells intermediate between stromal and mesothelial (epithelioid) cells are seen. In support of this we have shown calretinin staining to be restricted to the epithelioid component of the tumour and that adjacent stroma shows no evidence of calretinin expression. This suggests that rather than being neoplastic in nature the stromal compartment arises through reactive desmoplasia, and further that the observed peripheral nests are local in®ltration by neoplastic cells. As the reactive lesions investigated by Isotalo et al. have all occurred in close proximity to mesothelial surfaces, we believe that the nests of cytokeratin-containing cells in these lesions are implanted mesothelial cells associated with reactive ®brosis. This phenomenon is frequently seen in pleural in ̄ammation and in this context is clearly not metaplastic in nature. Previous reports have shown adenomatoid tumours to have ultrastructural and immunohistochemical features of mesothelial cells and our two studies have provided additional evidence of this.

The relationship of the BRAF(V600E) mutation and the established prognostic factors in papillary thyroid carcinomas.

It has been shown that BRAFV600E mutation in papillary thyroid carcinomas (PTC) is associated both with pathogenesis and poor prognosis. In this study, we aimed to investigate the relationship of the BRAFV600E mutation and the established prognostic factors in a cohort of Turkish patients with PTC. Forty-six cases of papillary thyroid carcinoma have been evaluated for the presence of BRAFV600E mutation. BRAFV600E has been examined by restriction fragment length polymorphism. BRAFV600E mutation status has been compared with well-known histopathological and clinical prognostic parameters such as invasion of thyroid capsule, extrathyroidal extension, and the presence of lymph node and/or distant metastasis. We have found that BRAFV600E mutation was present in the majority of our cases (40/46). Considering the stage of the disease, five of the negative cases were in stage 1 while the remaining one was in stage 2. Only one BRAFV600E negative case has shown extrathyroidal extension and lymph node metastasis. All four patients with distant metastasis had BRAFV600E mutation. Statistical analyses revealed that there are no significant relationship between the BRAFV600E mutation and the established prognostic factors. We found a relatively higher BRAFV600E mutation rate in classical type PTC than in other similar studies. We think that the limited number of our cases may either weaken or mask some potentially important relationship between BRAFV600E mutation and the established prognostic factors.

Testicular (gonadal stromal) fibroma: Case report and review of the literature

A 25‐year‐old man presented with complaint of a painless enlargement in his left testis. The solid, encapsulated, circumscribed and grayish–white testicular mass displayed the characteristics of testicular fibroma histologically. It was composed of acellular collagenized plaques and hypercellular areas of fibroblastic spindle cells. Immunohistochemically, the neoplastic cells were positive for vimentin and smooth muscle actin, but not for cytokeratin, S‐100 protein, desmin, CD99/MIC2 (a protein expressed by Sertoli cells and granulosa cells) and CD34. Only 18 cases of testicular (gonadal stromal) fibroma composed exclusively of spindle cells have been reported to date. An additional case of fibroma, which lacks definite neoplastic sex cord elements, and its differential diagnosis from other mesenchymal lesions of testis are discussed here, together with other cases in the literature.