Influence of 1,25-dihydroxyvitamin D3 on human leukocyte antigen-DR expression, macrophage infiltration, and graft survival in renal allografts.

Vitamin D plays an important role in the regulation of cellular growth and cell proliferation as well as exerting immunoregulatory activities. We sought to show the influence of vitamin D on renal graft survival. Among 102 patients, 40 were treated with vitamin D (group D) and the remaining 62 cases were not, forming a control group (group C). We studied human leukocyte antigen (HLA)-DR expression on tubules, interstitial cells, peritubular capillaries (PTCs), and evaluated macrophage infiltration of the interstitium and the PTCs. Compared to group C, group D patients showed fewer acute rejection episodes. Compared to group C patients group D patients showed significantly lower degrees of tubular and interstitial HLA-DR expression as well as interstitial and PTC macrophage infiltration. In addition in the PTC, HLA-DR expression was greater and therefore PTC destruction less in group D patients (P<.001). Twenty-seven (43.5%) of 62 group C patients lost their grafts at 29.2±15 months, whereas only 7/40 (17.5%) group D patients lost their grafts at 43.2±13 months. A significant difference was noted between the two groups in regard to the time of graft loss (P<.01). Testing vitamin D therapy along with several other covariates showed an independent effect on 5-year graft survival (P<.001). These data confirmed that vitamin D therapy shows an independent positive impact on long-term graft survival, which may be explained by its immunosuppressive effects of to reduce renal HLA-DR expression and renal macrophage infiltration and in turn mitigate PTC destruction. In conclusion, these results highlighted the potential use of vitamin D in renal allograft patients.

Rapamycin prevents interstitial fibrosis in renal allografts through decreasing angiogenesis and inflammation.

Rapamycin (RPM) has antiangiogenic and antiproliferative effects on cells. The aim of this study was to evaluate the mechanism of RPM as a novel antifibrotic agent by assessing its effect on interstitial fibrosis (IF). Among 60 renal transplant recipients, group 1 patients (n=20) were treated with RPM and group 2 (n=40), with cyclosporine. The proportions of infiltrating macrophages and lymphocytes in the interstitium were evaluated in 1-year biopsies. The microvessels were highlightened with CD34. After an initial biopsy, the development of diffuse IF over 18 months was evaluated by follow-up biopsies. The mean microvessel density (MVD) was significantly lower among group 1 (69.3±16) versus group 2 (96.5±30; P<.001). The proportions of macrophages and lymphocytes were lower in group 1 compared to group 2 biopsies (P<.001 for both). Fourteen (35%) group 2 and only 2 (10%) group 1 cases developed IF over 18 months (P<.05). The mean MVD in the initial biopsy was 75.6±18 in cases that did not versus 120±28 among those who did develop IF (P<.001). The amount of interstitial inflammation was greater among patients who did compared with cases who did not develop IF (P<.01). The overall 1-, 3-, and 5-year graft survival rates for group 1 were 95%, 95%, and 89% versus 95%, 65%, and 45% for group 2 patients, respectively (P<.001). RPM-treated patients showed a lower incidence of diffuse IF, which can be explained by antiproliferative and antiangiogenic effects of RPM. In conclusion, RPM therapy displayed an independently positive impact on long-term graft survival.

The influence of tubular phenotypic changes on the development of diffuse interstitial fibrosis in renal allografts.

It has been reported that myofibroblasts are the major cells in the development of interstitial fibrosis (IF) and, therefore, chronic dysfunction in renal allografts. Our aim was two fold: first, to understand the key markers controlling tubular and glomerular epithelial-to-mesenchymal transition (EMT); second, to show the role of tubular EMT on the development of interstitial fibrosis (IF) and the role of glomerular EMT on the development of proteinuria and, therefore, graft survival. For this purpose we evaluated the vinculin- and paxillin-containing adhesion complexes and α-smooth muscle actin (α-SMA) expression on tubular cells and glomerular podocytes in first year renal allograft biopsy specimens of 74 patients. We established the proteinuric state at the time of the biopsy of all patients. Follow-up biopsy specimens of all patients were evaluated for the development of diffuse IF (≥50% of the biopsy specimen). Among 74 patients, 21 showed grade 1 and 9 showed grade 2 tubular EMT. Only 25/74 cases showed glomerular EMT. The incidence of the development of diffuse IF at 18 and 24 months after the initial biopsy and the graft loss at 5 years were higher among subjects with tubules and glomerular podocytes showing EMT (P<.001 for all). The development of IF and graft loss was significantly earlier in cases with grade 2 compared with grade 1 or no tubular EMT (P<.001 for all). The proteinuric state at the time of the biopsy showed a significant positive correlation with the glomerular EMT (P<.001). In conclusion, our results showed that renal tubular cells and glomerular podocytes can undergo epithelial-to-mesenchymal differentiation. The transformed cells with reorganized cytoskeletal features have an important role in renal allograft survival by inducing the development of diffuse IF and proteinuria.

Angiotensinogen t235 and angiotensin-converting enzyme insertion/deletion polymorphisms associated with the development of posttransplantation diabetes mellitus in renal allograft recipients.

BACKGROUND: Genetic polymorphisms of the renin-angiotensin system (RAS) have been reported to play an important role in the pathogenesis of diabetes mellitus and hypertension. In addition, a close association has been reported between RAS and the progression of both diabetes and hypertension. But the role of RAS on the development of posttransplantation diabetes mellitus (PTDM) is not known. For this purpose we investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) with the development of PTDM. METHODS: Genotyping for ACE insertion/deletion (I/D) and AGT M235T polymorphisms was performed in 50 patients who underwent renal transplantation during a 5-year period. Group 1 consisted of 23 recipients who developed PTDM and group 2 consisted of 27 recipients that did not have PTDM. RESULTS: Of 50 patients, 13 (26%) showed the ACE DD, 21 (42%) the ACE ID, and 16 the ACE II genotype. The frequencies of AGT MM, AGT MT, and AGT TT were 0, 54%, and 46%, respectively. Compared with group 2, there were high frequencies of the AGT TT genotype in group 1 recipients (P<.001). In addition the ACE DD genotype was found significantly higher in group 1 patients compared with group 2 patients (P=.001). CONCLUSION: The high frequencies of the AGT TT genotype and ACE DD genotype in recipients may contribute to the high prevalence of PTDM. Our data suggest a synergistic effect between the ACE and AGT polymorphism in the risk of PTDM, but to support this theory a larger patient group must be studied.

Hepatic stellate cells in hepatitis C patients: relationship with the development of interstitial fibrosis in renal allografts.

The aim of this study was twofold; first, we evaluated the influence of hepatitis C virus (HCV) and iron deposition on hepatic stellate cells (HSCs), and second, we determined the influence of HSCs on the development of interstitial fibrosis (IF) in renal allografts. Thirty chronic HCV positive patients bearing renal allografts underwent liver biopsies, which were scored for iron deposition and the number of HSCs. We evaluated the density of tumor necrosis factor-alpha (TNF-alpha) in liver biopsies and the expression of transforming growth factor-beta (TGF-beta) on tubules of renal allografts from the same patients. We examined the development of IF in renal allografts at 12 and 24 months after the reference biopsy. The density of HSCs was significantly greater among patients with compared with those without iron deposits (P < .01). TNF-alpha expression was localized mainly to liver sinusoidal cells; in some cases, it was also expressed in hepatocytes. Patients with higher-grade TNF-alpha expression in the liver showed higher-grade alpha-smooth muscle antibody (alpha-SMA)-positive HSCs (P < .001). In parallel, an increasing amount of HSCs in the liver increased the incidence of IF in the renal allograft at 12 (P < .01) and 24 (P < .01) months after the reference biopsy. In addition, the expression of TGF-beta on renal allograft tubules were increased with greater grades of alpha-SMA-positive HSCs in liver (P < .01). In conclusion, HCV infection seemed to trigger the development of IF in renal allografts by augmenting TGF-beta secretion through activation of HSC.

Apoptosis and proliferation of cardiomyocytes and interstitial mononuclear cells: association with rejection and macrophage infiltration.

Previous studies have noted that acute rejection episodes (AREs) may lead to loss of cardiomyocytes in transplanted hearts. The aim of this study was twofold; first, to assess the degree of apoptotic cells and to compute the proliferation index of cardiomyocytes and mononuclear interstitial infiltrates in cardiac allografts. Second, we sought to determine whether apoptosis involved in AREs was associated with macrophage infiltration. Among 28 endomyocardial biopsies, 18 showed AREs and the remaining 10 biopsies, nonspecific changes, the control group. All biopsies were immunostained with Ki-67 and CD68 antibodies. Apoptotic cells were counted using the terminal deoxyncleotidyl transferase dUTP nick end labeling method. Apoptotic death of cardiac myocytes and interstitial mononuclear cells was significantly greater in cases of allograft rejection compared with the control group (P < .05). In addition, compared to the control group, ARE cases showed a greater proliferation index of cardiac myocytes and interstitial cells (P < .05). Macrophage infiltration was significantly greater in ARE cases and macrophage infiltration showed a linear association with both apoptosis and proliferation of myocytes and interstitial cells (P < .001). In conclusion, we verified the presence of apoptotic cell death during acute rejection in heart transplants. Apoptotic cell death was significant among interstitial cells but it was less among cardiac myocytes. Macrophage infiltration had a great influence on apoptotic cell death of myocytes and interstitial cells.

Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

Diagnosing amyloid goitre with thyroid aspiration biopsy.

OBJECTIVE: The aim of the study was to evaluate the value of fine needle aspiration biopsy of the thyroid as a tool for diagnosing amyloid goitre and assess how amyloidosis affects thyroid tissue and thyroid function. METHODS: Clinical and laboratory evaluation of 50 patients with secondary systemic amyloidosis was done, and goitre was found in 38 of them. All 38 patients underwent thyroid aspiration biopsy. Tissue samples were stained with haematoxylin and eosin, May-Grünwald-Giemsa, crystal violet and Congo red. RESULTS: Of the 38 cases of amyloid goitre, 10 showed euthyroid sick syndrome, two showed primary hyperthyroidism, two showed hypothyroidism and one showed subacute thyroiditis. The serum levels of thyroid hormones and thyroid-stimulating hormone were normal in the remaining patients. Thirty-five of the 38 patients (92%) showed amyloidosis after thyroid aspiration. One of these patients had papillary carcinoma in addition to amyloid goitre. Ten patients underwent subtotal thyroidectomy, and one patient underwent total thyroidectomy after aspiration. Microscopic evaluation revealed that the thyroid parenchyma in all patients was largely replaced with amyloid and adipose tissue. CONCLUSION: Fine needle aspiration of the thyroid is a valuable and sensitive method for diagnosing amyloid goitre, especially because it is a safe and easily performed procedure. Further, amyloid goitre has no significant influence on thyroid function even when it causes extensive parenchyma replacement.

Primary leiomyoma of the ovary in a young woman: literature review and report of a case.

Ovarian leiomyoma is a rare tumor. We present a case of ovarian leiomyoma in a 32-year-old virgin with the complaint of dysmenorrhea for six months. On magnetic resonance imaging, a 6 cm x 4 cm mass in the left ovary exhibiting hypointense signals on both T1-weighted and T2-weighted images was initially considered to be fibroma and/or thecoma. However, after surgery the pathological diagnosis of the removed tumor was leiomyoma of the left ovary. The literature on this rare tumor was also reviewed.

Among therapy modalities of end-stage renal disease, renal transplantation improves survival in patients with amyloidosis.

The aim of this study was to investigate the results of renal transplantation in amyloidosis patients compared with those on hemodialysis. We compared a group of 25 patients with systemic amyloidosis and end-stage renal disease (ESRD) treated with renal transplantation with a control group of 30 patients with systemic amyloidosis and ESRD treated with hemodialysis. Overall 1-, 2-, and 5-year survival rates were 86.9%, 82.6%, and 78.2%, respectively, for patients, who had renal transplantations versus 60.7%, 50%, and 46.4%, respectively, for patients on hemodialysis treatments (P < .001). Among the control group 15 patients died at 9.4 +/- 7.5 months after starting hemodialysis. Among transplantation group five patients died during follow-up (mean 12.3 +/- 13.6 months); the major cause of death was infection. Only 18 patients experienced recurrences after renal transplantation; their 5-year survival rate was 84.2% versus 50% for patients who had no recurrence (P < .001). Patients with amyloid recurrence also had better long-term survival rates than patients in hemodialysis group (P < .001). In conclusion amyloidotic patients maintained on chronic dialysis have a high mortality rate. Better survival was noted for patients who had renal transplantations despite recurrences. These results encourage transplantation in amyloid renal end-stage disease.

Posttransplant tubulointerstitial nephritis: clinicopathological correlation.

As a cause of graft dysfunction, tubulointerstitial nephritis (TIN) seems to be the third most common pathology after rejection and cyclosporine nephrotoxicity. Among 540 needle biopsies obtained from 280 renal transplant patients between 1996 and 1999, acute TIN was detected in 23 patients (8%). The cause of acute TIN was secondary to bacterial infection in 17 patients and secondary to cytomegalovirus (CMV) infection in three patients. The remaining three cases showed granulomatous pyelonephritis due to Mycobacterium tuberculosis (n = 2) and Candida albicans (n = 1). During follow-up, 13 of 23 patients (56.5%) showed at least one acute rejection episode. The average number of urinary tract infection (UTI) episodes in the 23 patients was 1.4 +/- 07. We observed that the number of UTI episodes showed a significant association with the development of chronic allograft nephropathy (P = .03) and graft loss (P < .01). Twelve patients (52.2%) lost their grafts during 5 years posttransplantation. Only 6 of 17 patients with bacterial TIN lost their graft at a mean time of 52.5 +/- 14 months. But all patients with CMV TIN or granulomatous TIN lost their grafts at a mean time of 31 +/- 3.1 months and 39 +/- 3 months, respectively (P < .05). In conclusion, these results support the pathological role of tubulointerstitial nephritis as a pathway of graft rejection or renal allograft deterioration among recipients after transplantation.

Does colchicine have an antifibrotic effect on development of interstitial fibrosis in renal allografts of recipients with familial Mediterranean fever?

Colchicine, which has been reported to inhibit fibrosis, has been successfully used to treat fibrotic disorders, such as liver cirrhosis, scleroderma, and idiopathic pulmonary fibrosis. We hypothesized that besides its ability to prevent amyloid deposition, colchicine may prevent the development of interstitial fibrosis (IF) in amyloidosis patients who had undergone renal transplantation. We evaluated the influence of colchicine therapy on the development of IF in 25 patients with systemic amyloidosis secondary to familial Mediterranean fever (group 1). Twenty-five nonamyloidotic patients who did not receive colchicine therapy served as controls (group 2). The incidences of recurrence and development of IF in the first, second, and third years after transplantation were evaluated from follow-up allograft biopsies. Only four patients showed amyloid recurrence in their renal allografts. IF developed in 44% (11/25) of group 1 patients and 80% (20/25) of group 2 patients during the 36 months posttransplantation (P < .01). Development of IF in the first, second, and third years posttransplantation was significantly greater among group 2 recipients than group 1 recipients (P < .01). The overall 1-, 2-, and 3-year graft survival rates for group 1 recipients were 96%, 92%, and 80%, and those for group 2 recipients were 96%, 88%, and 60%, respectively. Our results support the thesis that colchicine therapy may help prevent the development of interstitial fibrosis in renal allografts.

De novo glomerulonephritis in renal allografts with hepatitis C virus infection.

The purpose of this study was to examine the influence of hepatitis C virus (HCV) infection on the occurrence of posttransplant de novo glomerulonephritis (GN). Of 165 patients selected for the study, 44 were HCV positive and 121 HCV negative. Light and immunofluorescence microscopy were performed on all biopsies and clinical and laboratory findings reviewed. Fifteen (34%) of the 44 HCV positive patients showed de novo GN (4 membranous, 11 membranoproliferative) at a mean of 47 +/- 22 months. But only 8 (6.6%) of 121 HCV negative patients showed de novo GN (5 anti-glomerular basement membrane nephritis in recipients with Alport's disease, 2 membranous GN, 1 membranoproliferative GN) at a mean of 60 +/- 39 months. The risk of development of de novo GN was higher among patients with HCV infection (P < .001). The presence of de novo GN in HCV positive patients impaired graft survival compared with HCV positive patients without de novo GN (P < .01). The incidence of recurrence of primary disease, mainly focal segmental glomerulosclerosis, membranous glomerulonephritis, membranoproliferative glomerulonephritis, and IgA nephropathy, was higher in HCV negative patients (29%) compared with HCV positive patients (6.8%; P = .001), namely, 50%, 57.6%, 25%, and 69%, respectively. In conclusion, HCV infection showed a strong influence on the development of de novo GN. For this reason, it is important to follow HCV positive recipients with a renal biopsy even when there are no significant clinical or laboratory findings.

Angiotensin-converting enzyme and endothelial constitutive nitric oxide synthase polymorphisms in Turkish renal transplant population and possible influence on renal artery atherosclerosis and graft survival.

BACKGROUND: Renal transplant recipients are prone to accelerated atherosclerosis secondary to immunosuppressants, which may decrease graft survival. We sought to analyze the effects on renal graft survival of atherosclerotic degeneration in the renal artery and the influence of angiotensin-converting enzyme (ACE) endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms. METHODS AND PATIENTS: Thirty three renal transplant recipients (25 men) of mean age 28.4 +/- 9.6 years, received organs from 11 living related donors and were followed for at least 36 months. Genotyping was performed for the insertion/deletion ACE (I/D), angiotensin (AGT) (M-->T, 235), angiotensine 1 receptor (A-->C, 1166), angiotensin 2-receptor (A-->G, 1223), and ecNOS (b-->a, intron4) gene polymorphisms. Renal artery biopsies were performed during transplantation surgery to analyze the presence of atherosclerosis. RESULTS: Pathological examination indicated that 18 donor specimens and nine recipient specimens had atherosclerotic degeneration. Survival analysis (36 months) indicated that graft survival rates of recipients who had atherosclerosis in the renal artery and who received an organ from donors with an atherosclerotic renal artery were shorter than in their counterparts (P = .02, P = .04, respectively). Comparison of genetic variations of recipients revealed that CC/TC variation of AGT was higher in patients with atherosclerosis (81% vs 53%, P = .03). There was no significant difference between groups in means of other gene polymorphisms. CONCLUSION: Renin-angiotensin system gene polymorphism analysis of patients in renal transplantation waiting list may provide information about allograft survival and posttransplant atherosclerotic degeneration at graft vasculature of young transplant recipients.

Seronegative systemic lupus erythematosus: etiology of nephrotic syndrome and acute renal failure in early postpartum period.

Systemic lupus erythematosus (SLE) is an autoimmune syndrome that occurs most commonly in women during their reproductive years. Nephritis is known to be one of the most serious complications of SLE. Lupus nephropathy is frequently associated with ANA and anti-dsDNA antibodies. Rarely, serological markers may be initially absent, and in many cases, they become positive after sometime. We present a 28-year old, otherwise healthy female who admitted to our clinic with edema, hypertension, proteinuria and acute renal failure following her fourth delivery. Serum immunological markers were negative and renal biopsy showed histopathological changes consistent with systemic lupus erythematosus as the etiology of nephrotic syndrome. A dramatic therapeutic response was achieved by pulse steroid and cyclophosphamide treatment following oral steroid therapy. In women with new onset nephrotic syndrome or renal function deterioration in postpartum period, even if the patient is asymptomatic or seronegative, it is crucial to exclude SLE for a rapid diagnosis and prompt treatment in the case of lupus nephritis. Renal biopsy is of diagnostic importance in such cases in which there is no other clinical, biochemical and serological evidence of the disease.

HPV and p53 expression in epithelial ovarian carcinoma.

OBJECTIVES: Human papillomavirus is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear. This study aimed to determine the presence of human papillomavirus (HPV) in ovarian cancer tissues along with the expression of tumor suppressor gene p53. We also investigated any possible association of HPV with p53 gene mutations in ovarian carcinoma. METHODS: Archived human ovarian cancer tissues (n = 40 cases of epithelial ovarian cancer) embedded in paraffin blocks were used. Controls were 32 non-malignant ovarian tumor tissue blocks. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the presence of HPV and p53 expression, respectively. RESULTS: Of the total, 37.5% (n = 15) of malignant and 28.1% (n = 9) of benign ovarian tumors were positive for HPV (OR: 1.5 CI: 0.5-4.1, p = 0.4). The difference was not statistically significant. However, p53 was detected in 72.5% (n = 29) of malignant cases compared to 37.5% (n = 12) of benign cases (OR: 4.3 CI: 1.6-11.9, p = 0.003). Furthermore, a positive correlation between HPV and p53 expressions in ovarian cancer tissue samples was detected (r = 0.47, p = 0.001). CONCLUSIONS: HPV does not seem to be a major component in the development of ovarian carcinoma, nevertheless HPV positivity seems to contribute to the pathogenesis in at least some ovarian carcinoma cases by way of interaction with tumor suppressor p53.

Association of helicobacter pylori infection with nutritional status in hemodialysis patients.

The presence of Helicobacter pylori (HP) infection may adversely influence outcome in renal transplant candidates because of its strong association with gastrointestinal disorders. We examined the association between HP infection and nutritional parameters in symptom-free hemodialysis patients and assessed prospectively the nutritional changes in patients who received therapy for the disease. The 163 study patients, including 114 men and 69 women of mean age 41.5 +/- 12.9 years on dialysis for 67.2 +/- 47.6 months, were selected from among the group who underwent routine endoscopic evaluation according to our renal transplant protocol. Patients with active peptic ulcer, acute gastritis, chronic inflammatory disease, malignancy, or diabetes mellitus were excluded. Endoscopy results revealed normal findings in 60 (group 1), gastritis in 86 (group 2), or gastritis with HP in 17 patients (group 3). Group 3 patients received a 2-week course of triple therapy (omeprazole, amoxicillin, clarithromycin). The patient groups were compared for nutritional metrics (albumin, phosphorus, interdialytic weight gain [IDWG], body mass index [BMI]), inflammatory indices (CRP, fibrinogen), and iPTH levels. Group 3 patients were observed to be malnourished when compared with groups 1 and 2, namely abnormal values of albumin (P <.0001), phosphorus (P <.009), IDWG (P <.03), and BMI (P <.02). Repeat endoscopy revealed a 94% rate of eradication of HP with increased levels of albumin and phosphorus in group 3. Although symptom-free hemodialysis patients with HP-associated gastritis displayed a state of malnutrition; its eradication improved the nutritional status. Therefore, the presence of HP infection should be sought and its eradication mandatory for this patient population.

The renin-angiotensin system and endothelial nitric oxide synthase gene polymorphisms and cyclosporine toxicity in renal transplant patients.

Although cyclosporine has improved graft survival, the toxicity of the drug frequently causes problem for renal transplant patients. Cyclosporine displays deleterious effects due to direct toxicity to the nephrons and vasoconstriction of afferent arterioles, effects that may be due to increased angiotensin II and decreased nitric oxide activity. We sought to examine the relation between cyclosporine toxicity and the RAS (angiotensin-converting enzyme, angiotesinogen, angiotensin 1 and 2 receptors, and ecNOS) gene polymorphisms in 111 renal transplant patients. Retrospectively, we correlated the results of graft biopsies from these 111 patients, with the cumulative drug doses (mg), mean blood levels (mg/mL), mean daily doses (mg), and mean doses (mg/kg/d) of cyclosporine. Overall 125 patients (38 women, 87 men) were enrolled in the study. Their mean age was 34.47 +/- 11.04 years. Twenty patients displayed cyclosporine toxicity on graft biopsy; 91 showed no evidence of the disorder. We could not find any relation between cyclosporine toxicity and gene polymorphisms (P >.05), although the mean mg/kg/d dose was significantly high among cyclosporine toxicity group (P =.028, RR = 1.42). In recent studies angiotensin II and nitric oxide have been suggested to be related to cyclosporine toxicity; however, our results failed to reveal an association between cyclosporine toxicity and angiotensin II or nitric oxide-related gene polymorphisms.

Primary carcinoid tumor of the ovary: a case report.

Primary ovarian carcinoid tumors are rare. A 47-year-old woman presented to our emergency room with lower abdominal pain. Physical examination, pelvic ultrasonographic evaluation and abdominal computed tomography revealed a 10-cm mass in the right ovary containing cystic and solid components, as well as calcifications typical of a dermoid cyst. At laparotomy, a smooth-surfaced, firm and mobile right adnexal mass with solid and cystic portions was detected. Initially, right salpingo-oophorectomy was performed. Frozen-section examination identified the mass as a sex cord stromal tumor containing a mature cystic teratoma. Based on this finding, total abdominal hysterectomy, left salpingo-oophorectomy, omentectomy, appendectomy were performed, and the pelvic-paraaortic lymph nodes were also removed. All histological findings in the right ovary were similar to the features of cystic teratoma and trabecular carcinoid tumor. Examination of the resected lymphatic, omental, and appendiceal tissue indicated no tumoral invasion. The diagnosis was ovarian carcinoid Stage IA. Serum testing post-surgery revealed that the levels of cancer antigen (CA) 19-9 and CA125 were 18.5 u/ml and 10.5 u/ml, respectively. The patient was discharged on postoperative day 5. The report describes the clinicopathologic and immunohistochemical features of a primary ovarian carcinoid that contained a mature cystic teratoma.