Familial Cervical Cancer: Case Reports, Review and Clinical Implications

We report three Dutch families with familial clustering of (pre)neoplastic cervical disease, review the literature on familial risks of cervical intraepithelial neoplasia (CIN) and cervical cancer, and discuss possible practical guidelines for women with a family history of cervical cancer. Daughters and sisters of women with cervical cancer have been reported to have a relative risk of 1.5-2.3 to develop this type of cancer. From a practical clinical point of view, we suggest that as in women with an increased non-genetic risk to develop cervical cancer (e.g. because of immunosuppressive therapy) increased surveillance to detect this tumour should be considered in women with an increased risk based on family history. Cessation of smoking should be advised. As the use of condoms at least prevents HPV re-infection its use can be recommended as a way to lower the cervical cancer risk. Future studies to determine the genetic contribution to the development of cervical cancer should include the paternal family history of cancer and, because genetic predisposition might express itself as a higher risk to develop precursors of cervical cancer, carcinoma in situ and CIN grade II-III

Abnormal vaginal bleeding in women of reproductive age: a descriptive study of initial management in general practice

<p>Abstract</p> <p>Background</p> <p>Abnormal vaginal bleeding (AVB) in women of reproductive age is a common reason for consulting a general practitioner. Nevertheless, how general practitioners (GPs) choose to initially manage AVB is largely unknown, as is the prevalence of underlying pathology of AVB in primary care.</p> <p>Methods</p> <p>To investigate the initial diagnostic procedures and treatment for AVB used in general practice, we performed a descriptive study based on computerised medical records. New consultations for AVB in 2000 and 2001 were selected. Patient characteristics, diagnostic procedures and treatment were analysed.</p> <p>Results</p> <p>In total, 270 new consultations were included. The majority of patients (75%) consulted the GP for AVB only once. GPs performed diagnostic procedures in 54% of all consultations. Overall, additional diagnostic procedures revealed abnormalities in 11% of women. However, the diagnostic procedures implemented by the GPs varied widely per bleeding type and contraceptive use. Anaemia was found in 36% of 45 women tested. Uterine fibroids were found in 41% of 27 women examined by ultrasound. Medication was prescribed in 34% of all consultations. A gynaecological referral was registered in 4% of all contacts.</p> <p>Conclusion</p> <p>Initially, GPs tend to follow a policy of expectant management in women of reproductive age with AVB. However, when additional diagnostic procedures were performed, anaemia and uterine fibroids were found in a considerable number of women.</p

Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization

Funding This work was supported by a grant from the European Union, MSCA joint doctoral project MoGlyNet [675527].Peer reviewedPublisher PD

Mature Religiosity Scale: Validity of a New Questionnaire

In order to validate a new questionnaire, the Mature Religiosity Scale (MRS), it was presented to a sample of 336 persons, of which 171 were parishioners and 165 outpatients of Christian mental health clinics. A first version of this questionnaire was designed by studying both psychi- atric/psychological and theological literature. Validity and reliability were studied by including other questionnaires, among them the Spiritual Well-Being Scale (SWBS), the Duke Religion Index, the Religious/Spiritual Coping (RCoPE) and the State-Trait Anxiety Inventory (STAI). The results indicate that 16 items of the 19-item questionnaire make up one factor with good internal consistency, which is measured by Cronbach’s alpha. This factor was used as the Mature Religiosity Scale in this study. out of correlations with other validated scales and correlations with characteristics of known groups this scale proved to have good validity. The Mature Re- ligiosity Scale is suitable for use in both mental healthcare and pastoral care. It is designed and validated for these two groups, giving direction to professional communication about faith and meaning of life

Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts

Funding: This work was supported by the European Union Program Grant CVDIMMUNE [037227], CARDIMMUN [601728] and Marie Sklodowska Curie Actions joint doctoral project MoGlyNet [675527]. Acknowledgments: We would like to thank Raghed Halawani with help of quantifying histological images.Peer reviewedPublisher PD

Vascular remodeling and intimal hyperplasia in a novel murine model of arteriovenous fistula failure

ObjectiveThe arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient outward remodeling and intimal hyperplasia (IH) formation from which the exact mechanism is largely unknown. A suitable animal model is of vital importance in the unraveling of the underlying pathophysiology. However, current murine models of AVF failure do not incorporate the surgical configuration that is commonly used in humans. Because the hemodynamic profile is one of the key determinants that play a role in vascular remodeling in the AVF, it is preferable to use this same configuration in an animal model. Here we describe a novel murine model of AVF failure in which the configuration (end-to-side) is similar to what is most frequently performed in humans.MethodsAn AVF was created in 45 C57BL/6 mice by anastomosing the end of a branch of the external jugular vein to the side of the common carotid artery with interrupted sutures. The AVFs were harvested and analyzed histologically at days 7, 14, and 28. Identical veins of unoperated-on mice served as controls. Intravenous near-infrared fluorescent fluorophores were used to assess the patency of the fistula.ResultsThe patency rates at days 7, 14, and 28 days were 88%, 90%, and 50%, respectively. The mean circumference increased up to day 14, with a maximum 1.4-fold increase at day 7 compared with the control group (1.82 ± 0.7 vs 1.33 ± 0.3 mm; P = .443). Between days 14 and 28, the circumference remained constant (2.36 ± 0.2 vs 2.45 ± 0.2 mm; P = .996). At 7 days after surgery, the intimal area consisted mainly of an acellular layer that was structurally analogous to a focal adherent thrombus. Starting at 14 days after surgery, venous IH increased significantly compared with the unoperated-on group (14 days: 115,090 ± 22,594 μm2, 28 days: 234,619 ± 47,828 μm2, unoperated group: 2368 ± 1056 μm2; P = .001 and P < .001, respectively) and was mainly composed of cells positive for α-smooth muscle actin. We observed leukocytes in the adventitial side of the vein at all time points.ConclusionsOur novel murine AVF model, which incorporates a clinically relevant configuration of the anastomosis, displays similar features that are characteristic of failing human AVFs. Moreover, our findings suggest that coagulation and inflammation could both potentially play an important role in the formation of IH and subsequent AVF failure. Near-infrared fluoroscopy was a suitable alternative for conventional imaging techniques. This murine AVF-model is a valuable addition to the AVF animal model arsenal.Clinical RelevanceThe autologous arteriovenous fistula is considered the preferred choice for vascular access in hemodialysis. However, this type of vascular access suffers from a high failure rate, of which the exact pathophysiology is poorly understood. The use of a clinically relevant murine model provides us with a tool to unravel the pathophysiology and also to develop new therapeutic strategies that can improve the patency of the arteriovenous fistula in hemodialysis patients