Platelet thrombus formation in eHUS is prevented by anti-MBL2.

E. coli associated Hemolytic Uremic Syndrome (epidemic hemolytic uremic syndrome, eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8. However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated. To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for fibrin(ogen) and CD41 (marker for platelets), von-Willebrand factor (marker for endothelial cells and platelets), and podocin (marker for podocytes). Electron microscopy (EM) was performed on ultrathin sections from mice and human with HUS. Injection of Stx-2 resulted in an increase of both fibrin and platelets in glomeruli, while administration of 3F8 with Stx-2 reduced both platelet and fibrin to control levels. EM studies confirmed that CD41-positive objects observed by IF were platelets. The increases in platelet number and fibrin levels by injection of Stx-2 are consistent with the generation of platelet-fibrin thrombi that were prevented by 3F8.

Uterine transplantation, abdominal trachelectomy, and other reproductive options for cancer patients.

More and more women with cancer issues are now raising fertility concerns as survival improves and childbearing is delayed. Pregnancy is no longer contraindicated in cancer patients including breast and endometrial cancer survivors. In fact, survival in patients treated for breast cancer who subsequently become pregnant is actually higher than that in patients who do not become pregnant. "Therapeutic" abortions are no longer recommended. Assisted reproductive technology (ART) have been associated with ovarian neoplasms, but the association is probably not causal. Neither ART nor hormone replacement is contraindicated in cancer patients. Our institution is very supportive of patients and the difficult decisions cancer survivors face. Using a program of counseling and close collaboration between oncologists, perinatologists, and reproductive endocrinologists, informed patients are offered every possible option, including ART and uterine transplantation, to achieve their family planning objectives.

Infection and cervical intraepithelial neoplasia.

The impact of sexually transmitted diseases (STDs) on the development of cervical intraepithelial neoplasia (CIN) has been increasingly recognized over the last 20 years. Much attention has been focused on human papillomavirus (HPV) and the potential for screening for certain HPV types alongside standard cervical cytology in the hope of identifying those females at particular risk of developing high grade CIN or invasive carcinoma. Some infections, for example herpes simplex virus (HSV), have been heavily investigated in the past as they were thought to be involved in the development of CIN but were subsequently discounted. Also discounted as causes of CIN are Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). These infections were found to be associated with higher rates of CIN in early studies but transpired to be markers for the presence of other infections and pathology and therefore not themselves directly responsible for cytological changes. The role of bacterial vaginosis (BV) is the focus of several current investigations, not only in the genesis of CIN but also in the development of other gynecological and obstetric conditions and complications. Evidence to implicate Trichomonas vaginalis (TV) in the genesis of CIN is conflicting, but there is some evidence that it may exert its influence in a similar way to that hypothesized for BV, ie via abnormal amines. It is well known that there is a high level of concordance of STDs whereby the presence of one infection greatly increases the likelihood of there being one or more others present. There may be a synergism between some infections with regard to the causation of CIN, although the evidence for this is putative. Presented here is an overview of current and previous research in the field of lower genital tract infection as it relates to the development of CIN.

Selective vessel ligation in the pelvis: an invaluable tool in certain surgical procedures.

While developing the technique of abdominal radical trachelectomy for conservative cervical cancer management, the vascular supply of the uterus was thoroughly examined. The question of how many vessels the uterus requires to ensure its viability arose. Following an abdominal radical trachelectomy for stage IB cervical carcinoma, blood supply of the body of the uterus is successfully maintained by only the two infundibulopelvic vessels (n= 34). Pregnancy has resulted following this technique (n= 2). Selective ligation of the pelvic vasculature has been utilized in the abdominal radical trachelectomy procedure. The objectives of this study were to investigate the vasculature of the infundibulopelvic and broad ligaments, to assess the contribution of the ovarian and uterine vessels to overall uterine perfusion, and to consider the clinical applications of selective pelvic vessel ligation. Ten fresh dissections of the infundibulopelvic vessels, broad ligaments of benign total abdominal hysterectomy, and bilateral salpingo-oophorectomy specimens were performed. Perfusion index (PI) and oxygen saturation (O(2)Sat) measurements using a modified probe were taken at specified intervals at the uterine cornu during ten routine benign abdominal hysterectomies to assess the contribution of the ovarian and uterine vessels to overall uterine perfusion and the concepts studied were utilized in certain gynecological procedures. The ovarian/infundibulopelvic vessels course medially through the broad ligament toward the uterine cornu and consistently give off a branch to the ovary on its lateral border. In addition, further vessels were noted to run laterally from the uterine cornu along the ovarian ligament to the medial aspect of the ovary. PI and O(2)Sat measurements imply that the uterine and ovarian vessels contribute almost equally to uterine perfusion. Clinical application by selective ligation of the pelvic vasculature has been utilized in certain gynecological procedures often prone to torrential life-threatening uterine hemorrhage. Selective temporary ligation of the uterine and ovarian vessels has proven useful in the surgical management of chemoresistant gestational trophoblastic disease, in the Strassman procedure, fertility-sparing surgery in ruptured cornual ectopic pregnancies, and unrelenting postpartum hemorrhage. Of the six supplying vessels (ovarian, uterine, and vaginal) to the uterus only two (ovarian or uterine or a combination thereof) are required for uterine viability.

Bacterial vaginosis and cervical intraepithelial neoplasia--cause or coincidence?

Evidence regarding a causal relationship between bacterial vaginosis and cervical intraepithelial neoplasia has so far been incomplete and conflicting. To determine whether bacterial vaginosis is associated with cervical intraepithelial neoplasia a retrospective study was conducted at the Genitourinary Medicine Clinic at Southlands Hospital, Shoreham-by-Sea, UK. Three hundred patients who presented to the clinic with a first diagnosis of genital warts in the absence of other sexually transmitted diseases were recruited. Results of cervical cytology and where abnormal, histology on colposcopically directed punch biopsies were collected. Bacterial vaginosis was diagnosed by the detection of clue cells on Gram-staining of a high vaginal swab, positive amine test, vaginal pH above 4.5 and the presence of characteristic vaginal discharge. Odds ratio showed an increased prevalence of cervical intraepithelial neoplasia associated with bacterial vaginosis. The results suggest that a prospective cross sectional study should be performed to formally test the hypothesis that bacterial vaginosis predisposes to cervical intraepithelial neoplasia.

Is bacterial vaginosis associated with cervical intraepithelial neoplasia?

Previous research has produced conflicting results regarding the association of bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN). These studies have been weakened in their conclusions mainly by failure to adequately control for the presence of sexually transmitted infections (STIs). One proposed mechanism suggesting that carcinogenic nitrosamines acting either independently or via human papilloma virus (HPV) has not been fully tested previously. We undertook a prospective, case-controlled, cross-sectional study where the presence of STIs, in particular human papillomavirus (HPV) which is known to be associated with the development of CIN, was controlled for. Women with BV were not found to have CIN more frequently than women with normal vaginal flora and the quantities of nitrosamines produced by women with BV did not differ significantly from women without BV. We thus found that BV is not associated with CIN.

Abdominal radical trachelectomy: a new surgical technique for the conservative management of cervical carcinoma.

Traditionally radical hysterectomy has formed the mainstay of treatment for early stage cervical carcinoma. More recently radical trachelectomy and laparoscopic lymphadenectomy have been introduced to allow preservation of fertility. We present a new approach to fertility-sparing surgery, namely abdominal radical trachelectomy. The technique is similar to a standard radical hysterectomy and lymphadenectomy. In our technique the ovarian vessels are not ligated and, following lymphadenectomy and skeletonisation of the uterine arteries, the cervix, parametrium and vaginal cuff are excised. The residuum of the cervix is then sutured to the vagina and the uterine ateries re-anastomosed.