Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.

Evaluation of Dual Trigger with Combination of Gonadotropin-Releasing Hormone Agonist and Human Chorionic Gonadotropin in Improving Oocyte-Follicle Ratio in Normo-Responder Patients.

OBJECTIVE: Our aim was to compare the efficacy of two triggering method one with dual triggering with gonadotropin-realising hormon (GnRH) agonist plus standard dosage human chorionic gonadotropin (hCG) and the other with hCG only for final oocyte maturation on oocyte/follicle ratio and pregnancy rates in normoresponders in GnRH antagonist cycles in invitro fertilization-intrastoplasmic sperm injection (IVF-ICSI). MATERIAL METHODS: In this retrospective study, all patients underwent GnRH antagonist protocol. When at least ≥3 follicles reached ≥17 mm diameter, 116 patients received dual trigger with GnRH agonist plus hCG (1mg Leuprolide acetate plus 10.000 IU uhCG) and 178 patients received uhCG (10.000 IU u hCG) for final oocyte maturation. All follicles ≥10 mm diameter were aspirated. Number of oocytes and metaphase II oocytes retrieved per aspirated follicles, implantation rate, and clinical pregnancy rate per cycle was recorded. RESULTS: There was no statistically significant difference in terms of metaphase II oocyte ratio per aspirated follicle, implantation rate and clinical pregnancy rate between the dual trigger group and hCG only group (45.7% vs. 51%; 35.4% vs.30.3% and 45%vs. 40% respectively). Oocyte/ follicle ratio was significantly higher in dual trigger group (68.2%vs 63.8% p=0,028). CONCLUSIONS: Dual triggering in normal responders with a GnRH-agonist and a standard dosage of hCG is superior to hCG only protocol in terms of oocyte/follicle ratio but does not improve metaphase II oocyte, implantation and clinical pregnancy rates in GnRH-antagonist cycles. Dual triggering method may be beneficial in patients with immature oocytes and emty follicle syndrome.

Aortic stiffness in patients with wilson's disease.

AIM: Wilson's disease (WD) presents with different phenotypes. Neurologic and liver involvement in WD are well documented. Few reports demonstrated cardiac and vascular involvement. Several studies showed an association between serum copper levels and atherosclerosis. Although WD is the prototype disease of copper metabolism, atherosclerosis has not been studied yet. The aim of this study is to assess aortic stiffness in WD. MATERIALS AND METHODS: Aortic pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx), central aortic systolic, diastolic, mean, and pulse pressures were measured using SphygmoCor (AtCor Medical) device in 32 patients with WD and 24 healthy controls. RESULTS: Patients with WD and healthy controls were similar in terms of age sex, body mass index (BMI), and liver and kiney functions. However, patients with WD were anemic and thrombocytopenic. Echocardiographic parameters including left ventricular, atrial dimensions, and systolic and diastolic functions were similar between two groups. Patients with WD and healthy controls were compared. Baseline characteristics including age, sex, and BMI did not differ between groups. Central aortic systolic, diastolic, mean, and pulse pressures were similar between the groups. AP, AIx, and PWV did not differ between groups as well. CONCLUSION: Aortic stiffness in WD was similar in healthy controls.

Serum endocan levels in patients with cardiac syndrome X.

BACKGROUND: Endocan is a recently introduced marker of endothelial dysfunction and is also associated with inflammation and atherosclerosis. To date, the relationship between cardiac syndrome X (CSX) and endocan has not been studied. The objective of this study was to compare the serum endocan levels of patients with CSX with those of control subjects. PATIENTS AND METHODS: In this study, 50 patients were included in the CSX group and 28 patients in the control group. Patients with pathological conditions that could potentially influence endothelial functions were excluded. Endocan serum concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean endocan level of the CSX group was significantly higher than that of the control group (3051.3 ± 1900.5 ng/l vs. 2088.1 ± 522.2 ng/l; p = 0.002). There was no difference between the two groups in terms of age, gender, hypertension, diabetes mellitus, dyslipidemia, and smoking status. In receiver operating characteristic (ROC) curve analysis, endocan levels greater than 2072 ng/l had a 72% sensitivity and 54% specificity (p = 0.002) for accurately predicting a diagnosis of CSX. CONCLUSION: The results of this study suggest that patients with CSX have higher endocan levels. Therefore, endocan may be valuable in helping uncover the underlying pathogenesis of CSX.

Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.

BACKGROUND: The role of carotid endarterectomy for the treatment of atherosclerotic carotid bifurcation disease is now well established. The aim of this study was to compare durability, postoperative death, stroke, minor strokes, cranial nerve injuries, neck hematomas, myocardial infarctions, or surgical defects and restenosis at the operative site following short- and mid-term duration of the advantages eversion carotid endarterectomy (E-CEA) compared to conventional carotid endarterectomy (C-CEA). PATIENTS AND METHODS: Between March 2003 and November 2012, primary CEAs were performed in 380 consecutive patients by the same surgical groups. These patients were evaluated retrospectively. C-CEA was performed in 202 patients, and E-CEA was performed in 178 patients. Carotid duplex ultrasonography was performed in all patients at 1, 6, 12 and 24 months after CEA to identify residual atherosclerotic carotid disease. RESULTS: Mean age was 67.3±13.4 years in the E-CEA group and 64.8±14.8 years in the C-CEA group. Mean cross-clamping time in the E-CEA group was 9.54±2.6 minutes and 12.62±2.7 minutes for C-CEA group (P=0.236). Three postoperative strokes occurred (one after E-CEA and two after C-CEA). In the E-CEA group and C-CEA group respectively, carotid stenosis rates were found in 4 patients (2.24%) and in 5 (2.97%) at a follow-up period of 26 months. CONCLUSION: Classical endarterectomy still remains the gold standard surgical technique for patients who are selected for coronary artery disease surgery. Nevertheless, we believe that eversion endarterectomy, which has some advantages, must be kept in mind as an alternative approach.

Protection of the spinal cord from ischemia: comparative effects of levosimendan and iloprost.

BACKGROUND: The purpose of the study was to investigate and compare iloprost and levosimendan on spinal cord ischemia in an experimental model. MATERIALS AND METHODS: The study was done in two stages. For the 4-hour short survival study, 50 New Zealand white rabbits were randomly allocated into five groups. Spinal cord ischemia was induced by clamping the aorta just below the left renal artery and just proximal to the aortic bifurcation with bulldog artery clamps. The aortic clamps were removed after 40 min and restoration of blood flow was verified visually. The groups were analyzed at 1 and 4 h after reperfusion. For the 48-hour survival study, two different groups (iloprost plus levosimendan, n = 10; saline-treated controls, n = 10) were analyzed at 24 and 48 h after reperfusion. RESULTS: The neurologic status of the animals in the treatment and sham groups was better than that in the control group both at 1 and 4 h after reperfusion. Viability index values in the levosimendan, iloprost and iloprost plus levosimendan groups were statistically higher than in the control group indicating less or no neuronal damage. DISCUSSION: The results suggest that levosimendan, as well as iloprost, may reduce ischemic damage in transient spinal ischemia and provide better neurologic outcome.

Effect of Helicobacter pylori infection and eradication therapy on interleukin-6 levels in patients with Familial Mediterranean Fever.

It is being questioned if Helicobacter pylori infection, which causes a chronic inflammatory response, can increase the frequency and severity of attacks in patients with Familial Mediterranean Fever (FMF) and if the impact of inflammatory response can be diminished by eradication of the infection. To evaluate if there is difference in interleukin (IL)-6 levels of H. pylori-positive and -negative patients both before and during FMF attacks; if there is a change in IL-6 levels following successful eradication treatment; and if MEFV gene mutations have an effect on IL-6 levels. IL-6 levels were evaluated in 47 FMF patients before and during FMF attacks. Genetic testing to determine M694V, M694I, E148Q, V726V, M680I mutations was also performed in all patients. IL-6 levels were also determined after successful eradication of the infection in H. pylori-positive patients. IL-6 levels were compared in H. pylori-positive and -negative patients, and before and after eradication treatment in patients who cleared the infection. Number of patients in tested mutation groups was not enough to compare IL-6 levels in these groups. Thirty-four patients (73.9%) were H. pylori-positive. Before FMF attack there was no statistically significant difference in IL-6 levels of H. pylori-positive and -negative groups. IL-6 levels were significantly higher in both groups during the attacks than before the attacks (p < 0.05). There was a statistically significant decline in IL-6 levels both before and during FMF attacks, following eradication therapy in patients who cleared the infection (p < 0.05). In patients with homozygous M694V mutation, IL-6 levels before and during the FMF attacks were not significantly different in H. pylori-positive and -negative groups, despite a much lower level found in H. pylori-negative group (p > 0.05). Comparisons were not performed in other mutation groups because of small number of patients in each group. C-reactive protein (CRP) and fibrinogen levels were not significantly different between the groups (p > 0.05). We believe that the observation of IL-6 levels are lower both before and during FMF attacks both in H. pylori-negative patients and in patients who cleared the infection after eradication therapy is very important in the determination of the role of eradication of H. pylori on decreasing the frequency and severity of FMF attacks. As for today, the correlation between H. pylori infection and FMF seems unlikely; however, studies evaluating the interaction of cytokines in both diseases and their relations and roles will be needed to reach better conclusions.

Surgical treatment of unilateral iliac artery occlusive disease using a retroperitoneal approach.

OBJECTIVE: We evaluated the early and late postoperative outcome of aorto/iliofemoral bypass operations using a retroperitoneal approach. METHODS: From December 1999 until the end of December 2005, unilateral aorto/iliofemoral bypass was performed on 23 patients (3 female, 20 male) for unilateral iliac occlusive disease. The average age was 57 years (range: from 45 to 68 years). Operative indications were claudication in seven patients, rest pain in 14 patients, and non-healing ulcer or gangrene in two patients. RESULTS: Surgical procedures included aortofemoral bypass in ten patients, iliofemoral bypass in 12 patients and aortoiliac bypass in one patient. Simultaneous femoropopliteal bypass was performed on seven patients. Mean follow-up period was 2.5 +/- 0.31 years. Graft patency was 100% during this period. CONCLUSIONS: A retroperitoneal approach for unilateral iliac obstructive disease is a valuable and well-tolerated alternative to conventional aortobilateral reconstruction in unilateral symptomatic aorto-iliac disease with excellent long-term outcome.

Investigation of Keyes skin biopsy instrument for cervical biopsy procedures versus Kevorkian biopsy forceps.

OBJECTIVE: We aimed to investigate the utility and efficacy of the Keyes skin biopsy instrument for cervical biopsy procedures. MATERIAL AND METHODS: A prospective clinical trial was conducted on 50 women with cervical lesions. Colposcopy-guided cervical biopsies were collected using a Keyes biopsy punch and a Kevorkian biopsy forceps and the two methods were compared with definitive histopathological examination of the specimens obtained by the loop electrosurgical excision procedure (LEEP), conization or hysterectomy. RESULTS: There were no differences in speed of collection, diagnostic value of specimens, complication rates, or sample quality. The sensitivity, specificity, positive and negative predictivity of specimens were all 100% for both methods. CONCLUSIONS: The Keyes biopsy punch was found to be a safe, rapid and accurate diagnostic tool in cervical biopsy procedures. Based on the results of this study, the use of a Keyes punch instrument can be recommended as an alternative to other cervical biopsy methods.

Management of a case of primary vaginal cancer with irreducible massive uterine prolapse--a case report.

Primary cancer of the vagina constitutes 1-2% of all malignant genital tract tumors in women. As one of the most complicated therapeutic problems in gynecological oncology, this disease had been deemed to be untreatable until the end of 1930s. Presently, as a result of technological improvements in radiotherapy and radical surgery, more favorable prognoses are known to be achieved even in advanced cases. In the present case, a woman with vaginal cancer and Stage IV massive uterovaginal prolapsus, which could not be repositioned under general anesthesia, was repositioned by surgical intervention prior to radiotherapy to avoid any potential vesicovaginal fistula formation. The cervix was bilaterally suspended to the pectineal ligaments by polypropylene mesh.

Comparison of spinal cord protection utilizing left atrial-femoral with femoral-femoral bypass in patients with traumatic rupture of the aortic isthmus.

INTRODUCTION: Postoperative paraplegia remains a dreaded complication of repair of traumatic rupture of the aortic isthmus. Claims have been made that left atrial-femoral bypass provides better spinal cord protection. To test the hypothesis that left atrial-femoral bypass is better than femoral vein-to-femoral artery bypass in regard to postoperative paraplegia, we concurrently compared the two techniques. METHODS: We compared the occurrence of paraplegia in 18 patients whose ruptures were repaired utilizing left atrial-femoral bypass with 10,000 units of systemic heparin (group A) and 72 patients with femoral-femoral bypass with heparin 300 units/kg and an oxygenator (group B) operated on between January 1995 and July 2004. RESULTS: The mortality rate was 5.6% (5/90), with no statistical difference between the two groups. Postoperative paraplegia was present in three (16.7%) group A patients and five group B (6.9%) patients. However, the specific etiology of the neurologic defect was not clear, as one patient's paraplegia was transient following a period of cardiac arrest, and four others had had neurologic injuries prior to the aortic repair. Median aortic cross-clamp times were shorter in group A (34 minutes vs. 49 minutes). No patient required reexploration for bleeding, and no patient developed a graft infection. CONCLUSIONS: Paraplegia rates were higher in the left atrial-femoral group, but the difference was not statistically significant. This occurred despite the decreased cross-clamp times in this group. In patients undergoing repair of traumatic rupture of the aortic isthmus, left atrial-femoral bypass does not provide better spinal cord protection than femoral-femoral bypass.