Diagnostic value of oxidative stress markers in patients presenting with primary dysmenorrhea to the emergency department.

Background and Aim: Primary dysmenorrhea (PD) is a common presentation for emergency departments. This study investigates the diagnostic value of oxidative stress and ischemia markers in patients with PD. Materials and Methods: The participants were classified into the PD group (patients with PD) and the control group (healthy volunteers). Thiol/Disulfide Homeostasis (TDH) parameters (Ds, Disulfide; NT, Native Thiol; TT, Total Thiol) and serum ischemia modified albumin (IMA) levels of the groups were measured. The Numeric Rating Scale (NRS) was used for pain assessment. Bivariate correlation analysis was performed to test the relationship between NRS and oxidative stress parameters. A P < 0.05 was considered significant. Results: A total of 135 patients (PD group, n = 83; Control group, n = 52) were included in the study. PD group had statistically higher oxidant biomarkers (Ds level, Ds/NT ratio and Ds/TT ratio) and lower antioxidant biomarkers (NT/TT ratio) compared to the control group (p = 0.001; 0.003; 0.002, and 0.002, respectively). Serum IMA level in the PD group was higher than in the control group (P = 0.000). There was a positive correlation between IMA and NRS score (r = 0.342, P < 0.01), but no correlation was found between the other oxidative stress parameters and NRS. Conclusions: PD is characterized by increased oxidative stress and ischemia in the endometrium, which can be detected by TDH parameters and serum IMA. NRS score in PD patients is positively correlated with serum IMA level, which suggests IMA level can be valuable to determine the severity of endometrial ischemia and pain in patients with PD.

Lesional activation of Tc 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.

BACKGROUND: Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils. OBJECTIVES: To determine pathological changes in BD skin lesions related to the complex genetic predisposition. METHODS: We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation. RESULTS: We found that in BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs). CONCLUSIONS: In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response.

Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. OBJECTIVES: We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. METHODS: Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. RESULTS: In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. CONCLUSIONS: The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.

DICER1 Hotspot Mutations in Pleuropulmonary Blastoma: A Case Series From a Tertiary Center.

Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and DICER1 hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6-83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9-216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on DICER1 gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on DICER1 gene among the largest series of Turkish children with PPB.

Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case-control study.

BACKGROUND: Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. OBJECTIVES: To investigate the association of variants of the MEFV gene with a complex HS phenotype. METHODS: Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. RESULTS: The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001). CONCLUSIONS: The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

The relationship between preoperative CEA and CA19-9 status and patient characteristics and lymph node involvement in early-stage colon cancer.

OBJECTIVE: Colon cancer is a primary human cancer that accounts for approximately one-tenth of all cancers and is one of the three most common cancers in incidence and mortality. This study investigated the relationship between serum preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), patient characteristics and lymph node (LND) involvement in early-stage colon cancer. PATIENTS AND METHODS: A total of 154 patients who had undergone surgery for early-stage colon cancer were included in this study. Patient demographics regarding age and gender, laboratory parameters, tumor size, and tumor laterality were recorded. CEA and CA19-9 positivity was defined as patients whose tumor markers were above the cut-off values, and patients were grouped according to CEA and CA19-9 positivity. Patients were compared according to the CEA and CA19-9 status and pathological LND involvement. RESULTS: We found that patients in the CEA (+) and CA19-9 (+) groups were significantly older than the others. Our study detected LND involvement in histopathological examination in 25% of patients. LND pathological participation was significantly higher in the CEA (+) CA19-9 (+) group, and being age 65 years or older was found to be a risk factor for pathological LND involvement. CONCLUSIONS: Clinicians should pay more attention to LND involvement when both CEA and CA19-9 are elevated preoperatively in early-stage colon cancer patients. Preoperative CEA and CA19-9 status of patients is important in predicting LND involvement and, as a result, the prognosis of these patients.

Laparoscopy for sigmoid colon and rectal cancers in septuagenarians: a retrospective, comparative study.

BACKGROUND: The aim of the study is to analyze the results of laparoscopy in septuagenarians with sigmoid colon or rectal cancer. METHODS: Patients who underwent laparoscopic or hand-assisted laparoscopic sigmoid or rectal resections for cancer were retrospectively selected from the database of our institution. The study group (Lap > 70 group), contained the cancer patients over 70 years old who were treated with laparoscopy. Patients less than 70 years old who underwent a laparoscopic procedure (Lap < 70 group), and those over than 70 years old who underwent conventional surgery (Open > 70 group), were assigned to control groups. Demographics, information regarding tumors, perioperative data, pathological results, and survival in the three groups were compared. RESULTS: There were 56, 166, and 34 patients in the Lap > 70, Lap < 70, and Open > 70 groups, respectively. Patients in the Lap > 70 group were significantly older than other groups. The American Society of Anesthesiologists scores were higher, and the presence of the studied risk factors was more common in the Lap > 70 group than the Lap < 70 group. Intraoperative bleeding and the amount and number of perioperative transfusions required were less in the Lap > 70 group than in the Open > 70 group. The number of harvested lymph nodes was less in the Lap > 70 group than both study groups. Five-year survival in the Lap > 70 group was similar to that in the Lap < 70 group and significantly better than in the Open > 70 group. CONCLUSIONS: Laparoscopy for sigmoid colon and rectal cancer in patients over 70 may be feasible and safe as it is in younger patients. The present study has revealed that laparoscopy in the elderly may be superior to conventional techniques as regards some intraoperative findings and survival.

Mild and severe anal incontinence after lateral internal sphincterotomy: risk factors, postoperative anatomical findings and quality of life.

AIM: This study aims to evaluate the risk factors for incontinence after lateral internal sphincterotomy (LIS) and assess quality of life in different levels of incontinence. METHODS: All consecutive patients (n = 253) with chronic anal fissure who underwent LIS between 2003 and 2006 were retrospectively reviewed. All patients were questioned for possible anal incontinence according to the Wexner Incontinence Score (WIS). Demographics, vaginal delivery history, additional procedures and surgeon's experience were evaluated as risk factors. Endoanal ultrasound (EUS) was performed in incontinent patients to assess the thickness of the remaining internal sphincter and to evaluate any injury in the external sphincter. Quality of life was questioned with SF-36. RESULTS: Twenty-eight (11.7%) patients suffered from incontinence (mean WIS = 3.6 ± 2.5). The search for a risk factor was unsuccessful when continent and incontinent groups were compared. In subgroup analyses, patients were found to be suffering from mild (WIS <5, n = 19) or severe (WIS >5, n = 9) incontinence. Vaginal delivery history was found more often in the severely incontinent subgroup than in the continent group (p < 0.05). Also, vaginal delivery history and the additional procedures were more frequently observed in the severely incontinent subgroup than in the mildly incontinent subgroup. EUS did not find any external sphincter injury in these cases. WIS had negative correlations with the physical and mental component scores of SF-36. CONCLUSION: In our opinion, the threat for incontinence is unpredictable; however, vaginal delivery history may increase the risk of severe incontinence.

Apical lymph nodes at the root of the inferior mesenteric artery in distal colorectal cancer: an analysis of the risk of tumor involvement and the impact of high ligation on anastomotic integrity.

BACKGROUND: What level of arterial ligation is best in left-sided colon cancer and rectal cancer remains controversial. This study aims to assess the necessity and risk of high ligation from an oncological and technical perspective. METHODS: The lymph nodes at the origin of the inferior mesenteric artery (IMA) were separated as apical nodes in all patients operated for distal colorectal cancer in our department. The number and status of the nodes were prospectively assessed, and demographic and tumor-related variables were evaluated as risk factors for apical tumor invasion. Anastomotic leaks were also evaluated. RESULTS: A hundred and three patients (52 [50.5%] males, 60.3+/-12.9 years old) were included. The number of non-apical lymph nodes harvested was 14.5+/-7.1 with an additional 4.4+/-3.2 apical nodes at the high ligation site. Tumor invasion of apical nodes was observed in 6 (5.8%) patients. Two of these (1.9%) had no other positive nodes (skip metastases). Although none of the variables evaluated was found significant for predicting apical node positivity, tumor invasion was detected in 8.5 and 22.2% of patients with pT3 and pN2 cancers, respectively. Among patients, who had an anastomosis (n = 84, 81.6%), anastomotic leak was observed in 7(8.3%) and 1 (1.2%) of these patients required emergency relaparotomy. There was no mortality related to high ligation. CONCLUSIONS: High ligation of IMA may be routinely performed in patients with distal colorectal cancer, since tumor invasion of apical lymph nodes is neither rare (>5%) nor predictable, and skip metastases may also occur. This is especially true in case of an advanced disease for which apical node positivity peaks. The anastomotic leak rate is less than 10%, and mortality is low after high ligation of IMA.

Pancreatic Choristoma in a Canine Gallbladder.

A 1.5-year-old male Siberian Husky dog was presented with a history of progressive twitching and tetraplegia. The dog was humanely destroyed and at necropsy examination an incidental intramural white lesion measuring 10 × 15 × 5 mm was observed in the gallbladder. Histologically, the mass consisted of pancreatic tissue located in the tunica adventitia of the gallbladder. Immunohistochemistry revealed that the islets of Langerhans were positive for insulin, but negative for glucagon. In addition, the dog had non-suppurative meningoencephalitis associated with canine distemper virus infection. The gallbladder lesion was consistent with pancreatic choristoma and is the first case described in a canine gallbladder.

Clinical aspects and risk factors of nosocomial Stenotrophomonas maltophilia bacteremia episodes in a Turkish intensive care unit.

Stenotrophomonas maltophilia is an important nosocomial pathogen with increasing frequency in recent years, especially in immunocompromised and clinically debilitated patients. The aim of this study is to describe the characteristics of 35 episodes of S. maltophilia bacteremia at Celal Bayar University hospital in Turkey over a 3-year period from January 2003 to December 2005. Cases were identified with microbiology laboratory records and clinical data were collected from the medical record of each patient. The source of bacteremia was central venous catheter (CVC) in 65.7% (23) and respiratory tract infection in 2.9% (1) of episodes while the source of bacteremia was unknown in 11 (31.4%) episodes of bacteremia. Factors significantly associated with mortality were age of > or =65 years, APACHE score of > or =16, the presence of the total parenteral nutrition, anemia, low creatinine clearance level and shock. The most sensitive antibiotic was found as trimethoprim-sulfamethoxazole (91.4%) in antibiotic susceptibility testing of the isolates. Susceptibilities of piperacillin-tazobactam and netilmicin which frequently used antibiotics as an empirical therapy were 62.8% and 68.6%, respectively.

Ventricular ependymoma in a German Shepherd dog.

Using magnetic resonance imaging (MRI) together with clinical, pathomorphological and immunohistological methods, a ependymoma is described in a 9-year-old German Shepherd dog, which presented with behavioural and oculocephalic responses and generalised ataxia. The ependymoma, 9 x 6 x 5mm in size, was localised intra-axially in the right interventricular foramen and hydrocephalus was observed by MRI. Microscopically, the tumour was composed of pseudorosettes, and immunohistochemical examination revealed vimentin and glial fibrillary acidic protein immunoreactivity in the neoplastic cells.

A sheeppox virus outbreak in Central Turkey in 2003: isolation and identification of capripoxvirus ovis.

Poxvirus epidemics occur almost every year and cause significant economic losses for small-scale animal producers in Turkey. In this study, the causative agent of the most recent epidemic in Central Anatolia was detected in clinical samples using electron microscopy (EM) and amplified using an in house polymerase chain reaction procedure for the first time. Additionally, the aetiological agent was isolated from a sheep and identified using EM and PCR.

Effects of rapamycin treatment on pancreatic fibrosis, cellular apoptosis and oxidative stress in experimental chronic pancreatitis model.

PURPOSE: Rapamycin reduces hepatic fibrosis by inhibiting hepatic stellate cell activation. The present study investigated whether rapamycin treatment could modify the degree of fibrosis, cellular apoptosis and oxidative stress (OS) in an experimental model of CP. METHODS: Fifty-five male, Sprague-Dawley rats weighing 200-400g were randomized into four groups. CP was induced by intraductal trinitrobenzene sulfonic acid (TNBS) infusion in group A (n = 15) and group B (n = 15). Group C (n = 15) received intraductal TNBS and was killed for histologic confirmation at four weeks. Group D (n = 10) received intraductal saline instead of TNBS. Group A and group D received oral rapamycin (2 mg/kg/d) for two weeks after CP was induced while group B received oral tap water instead of rapamycin. Blood and pancreatic tissue specimens were collected and oxidative stress parameters, fibrosis and cellular apoptosis were determined. RESULTS: Tissue and blood malondialdehyde (MDA) levels were significantly lower in rapamycin treated group compared to controls (p < 0.001). Superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities were also significantly higher in the active treatment group (p < 0.001 for both). Tissue and blood MDA, SOD, GSH-Px measurements was similar in rapamycin group and pancreatic cannulation group (p > 0.05). Histopathologic fibrosis scores were similar in rapamycin and control groups. Apoptotic cell counts tended to be lower in rapamycin treated animals. CONCLUSIONS: Administration of rapamycin alleviated OS and, in part, prevented apoptotic cell death in experimental CP, but did not reduce fibrosis.

Characterization of transforming growth factor beta superfamily, growth factors, transcriptional factors, and lipopolysaccharide in bovine cystic ovarian follicles.

The process of transformation of growing bovine follicles into cysts is still a mystery. Local expression of proteins or factors, including transforming growth factor ß, growth factors, and transcription factors, plays a central role in mammals. Therefore, in abattoir-derived cystic ovarian follicles and follicular fluid, the role of some transforming growth factor ß superfamily proteins, insulinlike growth factor-1 (IGF-1) and GATA-4 and GATA-6, were investigated. The relationship between intrafollicular lipopolysaccharide (LPS) and etiopathogenesis of ovarian cysts was also assessed. Data on the preovulatory follicle and the largest follicle (F1) were compared. The number of intrafollicular LPS-positive samples and LPS concentrations were higher in cysts. Immunohistochemical staining was mildly positive for IGF-1, inhibin alpha, and GATA-4 in thecal cells. Staining for anti-Müllerian hormone (AMH), growth differentiation factor-9, bone morphogenetic protein-6 (BMP-6), and GATA-6 was insufficient for their quantitation, and oocytes could not be stained for any of the proteins tested in the cystic follicles. Expression of BMP-6, inhibin alpha, and IGF-1 was moderately higher in granulosa cells of F1 follicles, and all the proteins were moderately expressed in granulosa cells in preovulatory follicles. However, loss of GATA-6 staining was significant in F1 follicles. Intrafollicular progesterone, IGF-1, and AMH concentrations in cysts and F1 follicles were significantly higher than those in preovulatory follicles. Western blot analyses revealed that follicular fluid inhibin-α was strongly expressed, whereas expression of growth differentiation factor-9, BMP-6, GATA-4 and GATA-6 was lower in cysts than in preovulatory follicles. Also, high intrafollicular AMH concentration and low BMP-6 expression were closely associated with cystic degeneration and atresia. In conclusion, immunohistochemical loss of BMP-6 and GATA-6 in the granulosa cells together with high intrafollicular LPS levels may play important roles in disruption of the ovulatory mechanism and steroidogenic reactions in type 2 cyst. Also, high intrafollicular AMH concentration along with low BMP-6 expression may be used as indicators of the bovine degenarative ovarian follicles.

Evaluation of the patellofemoral joint with kinematic MR fluoroscopy.

OBJECTIVE: The aim of this study was to evaluate the diagnostic effectiveness of kinematic magnetic resonance fluoroscopy (KMRF) on patients with patellofemoral incongruency. MATERIALA AND METHODS: 17 patients (20 knees) and 10 healthy volunteers (20 knees), all men (mean age 29.4 years, S.D. 9, range 16-50), were included to our study. Only male subjects were studied because of potential biomechanical differences between sexes. KMRF was used to perform kinematic MR imaging of patellar alignment and tracking in 10 healthy subjects and 17 patients with a provisional clinical diagnosis of abnormal patellofemoral joints. The patellofemoral joints were examined with the knee in different angles of active flexion. At each knee position, real time kinematic and axial MRF image was used to focus on the sagittal plane, followed by an axial image focused through the middle of the patella. Three angles were measured: patellar tilt angle (PTA), sulcus angle (SA) and congruence angle (CA). RESULTS: Five patterns of malalignment were identified and studied. Two patellofemoral joints were normal, 10 had lateralization of the patella, 2 had patellar tilt, 2 had lateralization and patellar tilt (i.e. excessive lateral pressure syndrome) and 4 had medialization of the patella. CONCLUSION: KMRF is an effective method in evaluating patellofemoral incongruency. Short time duration of investigation, ability to get nearly real time images, suitable temporal contrast resolution and investigation from very different angles of knee are important advantages of the method.

The role of L-arginine and neutrophils on incisional wound healing.

Although arginine plays an important role in many aspects of inflammation and wound healing, the mechanism is not clear. We aimed to evaluate the effect of L-arginine administration on wound healing and neutrophil activity and on the interaction of these effects. Sixteen rats were divided into two groups: control group and L-arginine group. L-arginine was given intraperitoneally. The rats underwent incisional wounding and were killed on the 7th day of wounding. Blood neutrophil counts, neutrophil adhesivity index, tensile strengths and hydroxyproline level of skin were determined, histopathological and electron microscopical evaluation of healing was performed. Wound scores in the control group were significantly lower (p < 0.05). Hydroxyproline and collagen levels of skin were significantly increased in the L-arginine group (p < 0.05). Blood neutrophil counts and neutrophil adhesivity index in the L-arginine group were significantly increased (p < 0.05), as were the inflammatory cells in the skin. L-arginine may be used during the first phase of healing to induce inflammation in high risk patients.