Detection of Human Papillomavirus in Papillary Thyroid Carcinoma and its Association with Tumor Staging and Pathologic Features.

Background: The role of human papillomavirus (HPV), as a common infection, has been evaluated in many cancers such as the cervix and squamous cell carcinoma of the head and neck. To the best of our knowledge, for the first time, the association of HPV with papillary thyroid carcinoma (PTC) and its pathologic features are investigated. Methods: A retrospective cross-sectional study was conducted from May 2014 to January 2018 in several hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Thyroid tissue specimens of patients diagnosed with PTC (n=82) and benign thyroid nodules (n=77) were collected using the consecutive sampling method. The presence of HPV in PTC, adjacent normal tissue, and benign thyroid nodules was evaluated using the polymerase chain reaction (PCR) method. The frequency of HPV positivity in PTC tissues was compared with benign thyroid nodules and adjacent normal tissue. Association of pathologic features of PTC with HPV positivity was also investigated. Data were analyzed using SPSS version 21.0, and P values less than 0.05 were considered statistically significant. Results: HPV PCR positivity was observed in 3.8% of benign thyroid nodules and 13.4% of PTC samples but in none of the adjacent normal tissues. After adjustment for age and sex, the prevalence of HPV PCR positivity in the PTC tissues was significantly more than the benign thyroid nodules (P=0.015). The prevalence was also significantly higher than the adjacent normal tissues (P<0.001). Conclusion: There was a significant association between PTC and HPV positivity. Further studies are required to determine the cause and effect of the association between these two conditions.

Expression of antiapoptotic proteins livin and survivin in pediatric AML patients, as prognostic markers.

OBJECTIVE: Survivin and livin are highly expressed in various malignancies and their expression levels may be related to unfavorable prognosis. The aim was to investigate the relationships of these two markers with some prognostic factors and with survival of the children with acute myeloid leukemia (AML). METHODS: Livin and survivin expression was investigated quantitatively by immunohistochemistry staining technique in 43 primary formalin-fixed, paraffin-embedded bone marrow blocks in pediatric age group (<18 years). RESULTS: Both survivin and livin were expressed in 81.4% of AML patients. Livin expression showed significant positive association with high level of primary WBC (p = .002). Survivin expression showed significant positive correlations with risk of relapse (p ≤ .001) and high level of primary WBC (p = .003). The relationship of overall survival (OS) of the patients with livin and survivin expression, were investigated separately in disease subtypes. Significant association was observed between survivin expression and shorter OS regardless of subtypes including acute promyelocytic (APL) (p = .01) and nonacute promyelocytic leukemia (non-APL) (p = .008). Also, significant association of livin expression with shorter OS was detected, but only in APL subgroup (p = .046). Nevertheless, in Cox regression model after adjusting for disease subtypes, stage and cytogenetics; survivin and livin showed no significant association with OS (p > .05). CONCLUSION: Livin and survivin showed significant associations with some poor prognostic factors of AML. Although survivin in both subtypes and livin in non APL subtype, showed a significant relationship with shorter OS, none of them was determined as independent prognostic factors. Further studies with larger sample size are suggested.

Expression Levels of MMP9 and PIWIL2 in Prostate Cancer: a Case-Control Study.

BACKGROUND: Prostate cancer is the second most prevalent cancer in humans. Also, this is the most common malignancy and the sixth most important cause of death in men worldwide. The most routine diagnostic test for prostate cancer is PSA test which is associated with some limitations like too many false positive results. This study intends to investigate the role of MMP9 and PIWIL2 expression levels as different biomarkers in prostate cancer biopsy specimens. This study is one of the most brilliant studies in the field of prostate cancer research for the first time focusing on the investigation of the role of two different genes in prostate cancer in biopsy specimens and on formalin-fixed paraffin-embedded tissue types in order to detect the progression and prognosis of prostate cancer patients in early stages. METHODS: Seventy formalin-fixed paraffin embedded samples (35 normal and 35 cancerous cases) were selected. Expression levels of PIWIL2 and MMP9 genes were evaluated, using real-time PCR. RESULTS: MMP9 and PIWIL2 expression levels in cancerous tissues were significantly higher than the adjacent normal tissues (p < 0.05). The survival analysis showed a significant correlation between expression level of PIWIL2 and survival rate (p < 0.05), but such correlation was not observed in case of MMP9 (p > 0.05). Higher levels of MMP9 and PIWIL2 expression were strongly related to the Gleason score and age, using Pearson's correlation co- efficient test; however, this kind of association was not evident between prostate specific antigen (PSA) and expression levels of the genes of interest. The expression level of PIWIL2 had a significant correlation with metastasis rate, but this relationship was not seen in the case of MMP9. CONCLUSIONS: The results confirmed the validity of PIWIL2 expression as a valuable prognostic biomarker for early diagnosis of prostate cancer.

Risk factors for rectal colonization with vancomycin-resistant enterococci in Shiraz, Iran.

OBJECTIVES: In order to determine the risk factors for rectal colonization with vancomycin-resistant enterococci (VRE) at the Shiraz Namazi Hospital, we performed a nested case-control study. METHODS: From December 2003 to July 2004 rectal swabs were taken from 700 randomly selected hospitalized patients every 5 days. RESULTS: A total of 99 of the 700 patients (14%) were colonized with VRE (cases) and 59 patients were colonized with vancomycin-sensitive strains (VSE), serving as controls. In the univariate analysis, history of antibiotic use (p=0.04), underlying disease (p=0.013), hemodialysis (p=0.03), use of third generation cephalosporins (p=0.04), use of vancomycin (p=0.04), and duration of vancomycin therapy longer than 7 days (p=0.02) were significantly associated with VRE colonization. In a multivariate analysis, underlying disease and the duration of vancomycin use longer than 7 days were independently associated with VRE colonization. CONCLUSION: Our study, the first on VRE carriage in Iran, demonstrates that VRE prevalence is high in Shiraz and confirms earlier observations in other countries. The identified risk factor 'use of vancomycin longer than 7 days' may be avoidable, indicating a feasible intervention strategy in the control of VRE.

Immunoglobulin and complement depositions in the liver of chronic hepatitis patients.

BACKGROUND/AIMS: Liver biopsy is a cornerstone in the management of chronic hepatitis patients. In biopsy, liver cell damage as well as severity of inflammatory cell infiltration in the parenchyma and portal tracts are evaluated. There are some other inflammatory markers such as complements (C) and immunoglobulins (Ig), which are involved in the pathogenesis of inflammation. This study was carried out to investigate the status of Ig and C depositions in the liver of chronic hepatitis cases. METHODOLOGY: Two biopsy samples were taken from patients who were scheduled for liver biopsy for chronic hepatitis. The acetone fixed sections were incubated with fluorescin-conjugated anti human IgG, IgA, IgM, C3 and C4. Ten samples of non-hepatitis control cases were provided during elective cholecystectomy. RESULTS: Deposition of IgG, IgM, and Cs were seen in the parenchyma in HBV, HCV and non viral hepatitis cases. The parenchyma of control liver did not show any deposition of IgG, IgM, and Cs. IgA was found in the parenchyma of 3 control cases. C3 deposition in the parenchyma had significant association with enzyme rising in HCV (p=0.001) and non viral groups (p=0.004). C4 deposition in the parenchyma was also associated with enzyme rising in HCV cases (p=0.01). There was an association between ALT elevations with the presence of IgM in the parenchyma in HBV (p=0.01) and HCV (p=0.03) groups. Mantel-Haenszel chi2 test (for evaluation of the effects of stage and grade) confirmed that the depositions of C3 and C4 in HCV and C3 in nonviral hepatitis have positive association with enzyme rising. CONCLUSIONS: Presence of IgM, IgG, C3, and C4 in the liver parenchyma is abnormal and may be helpful in histological evaluation in chronic hepatitis. Parenchymal (but not portal) depositions of C3 and C4 in HCV and non-viral hepatitis cases show close association with elevation of liver enzymes.

Ischemic preconditioning protects the dog kidney from ischemia-reperfusion injury.

OBJECTIVE: To evaluate the effects of unilateral ischemic insult and ischemic preconditioning (IPC) on renal histology in a canine model. METHODS: 30 dogs were randomized into 4 groups. In group A (5 male controls) and group B (5 female controls), ischemia was induced by clamping both left renal arteries for 40 min. Dogs in group C (10 male cases) or group D (10 female cases) underwent 5 min of arterial clamping and 10 min of declamping prior to the final 40-min ischemia induction. Renal biopsy was prepared 48 h later and microscopically examined. RESULTS: The control groups (A and B) developed 40% frank necrosis, 60% moderate injury, and there was no intact renal tissue in this group with no difference between sexes. The IPC groups (C and D) revealed 55% moderate injury and 45% normal pathology; however, there was no frank necrosis among them. Better IPC protection in the female group was not statistically significant. CONCLUSION: An IPC schedule of 5-min ischemia and 10-min reperfusion improves ischemia-reperfusion injury from subsequent prolonged ischemia in a canine model.

The effect of iodine prophylaxis on the frequency of thyroiditis and thyroid tumors in Southwest, Iran.

OBJECTIVE: To investigate the effect of the salt iodization program, which was initiated in 1989 on frequencies of thyroiditis and papillary carcinoma in Fars province of Iran, which was previously an iodine deficient area. METHODS: Four hundred and eighty-two thyroidectomy specimens belonging to the pre-iodization period from 1983 to 1988, and 466 post iodization specimens from 1998 to 2003 were re-examined for presence of lymphocytic infiltration and types of thyroid tumors. This study was carried out in Shiraz University of Medical Sciences, Iran. RESULTS: The frequency of lymphocytic infiltration in non-neoplastic specimens increased from 30-60.5% after salt iodization (p<0.001). Background of lymphocytic infiltration in neoplastic specimens also increased from 18.5-61% after iodine prophylaxis (p<0.001). The frequency of papillary carcinoma in neoplastic specimens increased from 15-43% (p=0.01) and that of follicular adenoma decreased from 69-32.5% (p<0.0001). CONCLUSION: Salt iodization is associated with an increased occurrence of histologic thyroiditis and papillary carcinoma.

The effect of zinc on healing of renal damage in rats.

BACKGROUND: Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. MATERIALS AND METHODS: Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. RESULTS: In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. CONCLUSIONS: Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

The effect of pentoxifylline on detrusor muscle contractility after partial urethral obstruction in a rat model.

PURPOSE: To evaluate the effect of pentoxifylline (PTX), a nonspecific type 4 phosphodiesterase inhibitor, on contractility of obstructed detrusor muscles. METHODS: Sixty male Sprague-Dawley rats were randomized into three groups each containing 20 animals. The control groups included rats with induced BOO which received the solvent of PTX (drinking water), the sham group included rats with intact bladder outlet which received no treatment, and the treatment group was treated with PTX after induction of BOO. Four weeks after the operation and/or treatment, animals were killed and detrusor muscle of them was evaluated for contractility parameters. RESULTS: Carbachol-induced detrusor muscle tension increased proportionally with concentration of carbachol. The maximum carbachol-inducing muscle tension was significantly higher in the sham group in comparison to the rats with BOO (P < 0.001). In the latter group, PTX treatment caused no significant improvement in the maximum carbachol-induced muscle tension compared to the control group. However, no significant difference was observed among the study groups concerning the pEC50 of carbachol (5.77 ± 0.10, 5.96 ± 0.64, and 5.84 ± 0.17 in the sham, control, and treatment groups, respectively). BOO resulted in a great but statistically non-significant (P = 0.074) decrease in electrically induced bladder contraction in comparison with the sham group. Treatment with PTX reversed this effect significantly (P = 0.023), and the obtained values were almost the same as those of the sham group. CONCLUSION: PTX improved detrusor muscle contractions in responses to electric stimulation in obstructed bladder. In contrast, no improvement was detected in contractile responses to the carbachol stimulation.

Effect of combined density gradient centrifugation on X- and Y- sperm separation and chromatin integrity.

BACKGROUND: It has been claimed that by using different washing methods, the sperms can be separated according to size, motility, density, chromosomal content and surface markings and charge. These methods also reduce sperm chromatin deficiencies and screen the sperms before applying in assisted reproduction techniques. OBJECTIVE: This study compared simple density gradient methods and a combined method with albumin density gradient and PureSperm separation (alb/PureSperm) for sex preselection by double fluorescence in situ hybridization (FISH) versus chromomycin A3 staining to determine chromatin integrity. MATERIALS AND METHODS: 30 normal semen samples were prepared with PureSperm, albumin gradients and alb/PureSperm. All samples were then stained by FISH and chromomycin A3. The results were compared with SPSS 11.5 and the Kruskal-Wallis test. RESULTS: The proportion of X-bearing spermatozoa by PureSperm separation (47.58±5.67) and Y-bearing spermatozoa by albumin gradient (46.13±3.83) methods were slightly higher than in putative normal sperm samples (1:1), but there were no significant differences in the X- or Y- bearing spermatozoa counts among the three methods. Albumin gradient separation tended to underestimate abnormal spermatozoa compared to PureSperm and combined alb/PureSperm. CONCLUSION: Routine separation methods slightly enriched X- or Y- bearing spermatozoa, but the differences were not significant for clinical purposes. The combined alb/PureSperm method had no advantages for assessing sex ratio or chromatin integrity compared to simpler gradient methods.

Protective effect of parenteral vitamin E on ischemia-reperfusion injury of rabbit kidney.

OBJECTIVES: To evaluate the effect of parenteral vitamin E on renal ischemia-reperfusion injury. METHODS: Twenty German rabbits weighing 1.5-1.9 kg were selected and divided randomly into study and control groups. Each group contained 5 male and 5 female rabbits. Intravenous vitamin E was administered to the study group 5 minutes before left renal artery clamping and the same volume of normal saline was administered to the control group. Ischemia was maintained for 60 minutes. After 48 hours, nephrectomy was performed and kidneys were sent to the pathology laboratory. Histopathologic sections were evaluated by the pathologist and graded by the extent of tissue injury to normal, mild, and moderate to severe injury. RESULTS: Histopathologic evaluation of the sections revealed that in the control group 50% of the sections had signs of moderate to severe injury and 50% were categorized as mild injury, whereas 50% of the study group sections developed no sign of ischemia-reperfusion injury and 50% developed mild injury (P = .03). No significant correlation was found between sex and the extent of cell injury (P = .99). CONCLUSIONS: Parenteral injection of vitamin E significantly protects cells against ischemia-reperfusion injury in German rabbits.

Inferior vena cava reconstruction with a flap of parietal peritoneum: an animal study.

BACKGROUND: The development of reconstructive venous surgery has been hampered by the lack of suitable grafts. Patency rates with grafts in the venous system are commonly less satisfactory than in arterial system, mainly due to nonpulsatile flow velocity and the low pressure in veins. Grafting of the inferior vena cava may be necessary in cases of trauma and major tumor surgery involving the vein. Several types of grafts have been evaluated. Reconstruction of the vena cava with autologous vein is so time-consuming and requires extra incisions. Prosthetic material is associated with a higher risk of infection and thrombosis. We, therefore, created an animal model of inferior vena cava reconstruction using a flap of parietal peritoneum. METHODS: A tube, 5 cm in length and 1 cm in diameter, was constructed from the parietal peritoneum of the anterior abdominal wall of ten dogs. It was anastomosed end-to-end as an interposition graft to the inferior vena cava. The observation period was two months. RESULTS: Eight of ten grafts were macroscopically and venographically patent, while the other two were occluded. Eight out of ten specimens (for pathologic examination) which revealed patent lumens were completely endothelialized.No infection or other problems were noted. CONCLUSION: The peritoneum is an accessible and safe substitute for reconstruction of the inferior vena cava.

Application of amniotic membrane as xenograft for urethroplasty in rabbit.

OBJECTIVES: Uroepithelium repair has always been the subject of discussion in urology surgeries. Using human amniotic membrane allograft has already proved to be useful in other fields. In this study, we use amniotic membrane to repair uroepithelium injuries in rabbits. METHODS: Twenty healthy rabbits underwent surgery to induce a 10-mm incision, 10 mm from the meatus on ventral part of the urethra. Then a 5 x 10 mm patch of amniotic membrane was sutured to the incised urethra. All of the rabbits were catheterized for a week and then the patches were removed. The rabbits were studied for a month for any signs of infection and fistula formation. RESULTS: All samples revealed complete re-epithelialization of reconstructed urethra by transitional epithelium. There was one case of infection and following fistula (5%). There were two cases of urethral strictures (10%). CONCLUSION: The result from this study suggests that amniotic membrane is an inexpensive, easy, and biodegradable graft with very little antigen effect which seems to be the ideal solution for urethroplasty.

Effect of intraurethral captopril gel on the recurrence of urethral stricture after direct vision internal urethrotomy: Phase II clinical trial.

OBJECTIVE: The purpose of this study is to evaluate the effect of intraurethral captopril gel as an antifibrotic agent on patients with urethral stricture. MATERIALS AND METHODS: In the first phase of clinical trial, 13 rabbits were included and local side-effects of captopril gel were evaluated. In the second phase, 56 patients were enrolled from April 2004 to January 2006. After internal urethrotomy the patients were classified into three patient groups: (i) received placebo gel (group I); (ii) received 0.1% captopril gel (group II); and (iii) instilled 0.5% captopril gel intraurethrally (group III). RESULTS: In phase I, no significant local side-effects were seen in the urethra of rabbits. In phase II, the mean age of the patients was 39.5 and the mean follow-up duration was 16 months. The most common etiology of the urethral stricture in the patients was iatrogenic (35.7%), most of their strictures had a depth of 0.5 cm or less (67.8%), and the length of most strictures was between 1 and 2 cm (41.1%). The patients' maximum urine flow increased more in groups II and III, than in group I (P < 0.04, P < 0.05, respectively). The recurrence rate was less in groups II and III than in group I (P < 0.05). In terms of the maximal urine flow and recurrence rate, no significant difference was seen between group II and group III (P = 0.13, P = 0.21, respectively). CONCLUSION: Captopril gel is a safe, effective and non-toxic agent for decreasing the recurrence rate of the urethral stricture after internal urethrotomy. However, more studies, including more cases and a longer follow up, are needed to prove the effect of captopril gel on patients' urethra.

Can thymic tissue induce tolerance to kidney allografts?

INTRODUCTION: The aim of this study was to investigate the beneficial effect of donor thymic tissue to induce tolerance in thymokidney allografts, transplanted to thymectomized cross-bred canines. MATERIALS AND METHODS: Seven pairs of transplant donors and recipients were selected from 3- to 4-month-old cross-bred canines with major histocompatibility complex (MHC) mismatches. Recipients underwent partial thymectomy 4 weeks before transplantation and received an autologous thymic graft under the renal capsule, which had been engrafted in the donors 3 months before transplantation (thymokidney). Successful engraftment with evidence of thymocyte development in the donors was determined by gross and histologic examination at the time of transplantation. Biopsy specimens were obtained at the transplant day and 3 months after transplantation and were studied histologically for evidence of hyperacute or acute rejection. RESULTS: At 90 days after the operation, all 7 juvenile thymic grafts had developed with normal thymic structure under the renal capsule. Hyperacute rejection was not observed in allografts, and all of them were functioning until the end of follow-up; however, all of the allografts showed acute cell-mediated rejection 3 months after transplantation. CONCLUSION: No tolerance was induced by vascularized donor thymokidneys in MHC-mismatched canines. The advantages of tolerance over chronic immunosuppression are so great that a potentially tolerogenic approach such as thymic transplantation would seem worthy of further investigations on large animal models. To evaluate the beneficial effects of thymic tissue in tolerance induction, utilizing a short course, low-dose adjuvant immunosuppressant to this regimen and/or application of in-bred MHC-matched canines is suggested.