An in vitro study on spontaneous myometrial contractility in the mare during estrus and diestrus

Uterine smooth muscle specimens were collected from euthanatized mares in estrus and diestrus. Longitudinal and circular specimens were mounted in organ baths and the signals transcribed to a Grass polygraph. After equilibration time and 2 g preload, their physiologic isometric contractility was recorded for a continuous 2.0 h. Area under the curve, frequency and time occupied by contractions were studied. Differences between cycle phases, between muscle layers, and over the recorded time periods were statistically evaluated using linear mixed-effect models. In the mare, physiologic contractility of the uterus decreased significantly over time for all variables evaluated (time as covariate on a continuous scale). For area under the curve, there was a significant effect of muscle layer (longitudinal > circular). For frequency, higher values were recorded in estrus for circular smooth muscle layer, whereas higher values were seen in longitudinal smooth muscle layers during diestrus. In longitudinal layer and in diestrus, more time was occupied by contractions than in circular layer, and in estrus. This study is describing physiologic myometrial motility in the organ bath depending on cycle phase.

Prevention of postmenopausal bone loss with long-cycle hormone replacement therapy

OBJECTIVE: Postmenopausal bone loss and osteoporotic fractures can be prevented by hormone replacement therapy (HRT). However, opposed HRT may increase the risk of breast cancer above that associated with estrogen alone and in non-hysterectomized women estrogen substitution alone increases the risk of uterine cancer, which triggered renewed interest in long-cycle HRT regimens (estrogen replacement therapy with progesterone-free intervals up to 6 months). The effects on bone of such long-cycle HRT regimens are unknown. The objective of the present study was to compare the effects on bone and the endometrium of long-cycle HRT and conventional HRT. METHODS: Seventy-three healthy non-hysterectomized postmenopausal women were randomized to either conventional HRT (estradiol (E2) 2 mg/d during 12 days, E2 2 mg/d plus 1 mg/d of norethisterone acetate (NETA) during 10 days, E2 1 mg/d for 6 days) or long-cycle HRT treatment (two cycles with E2 2 mg/d during 28 days, followed by one cycle of conventional HRT and repeated every 3 months). Primary endpoint was the change in bone mineral density (BMD) at the lumbar spine (LS) over 24 months. RESULTS: BMD at LS increased significantly versus baseline in both treatment groups (conventional HRT +3.8 +/- 0.6%, long-cycle HRT +3.3 +/- 0.5%, p < 0.0001 for both) with no significant difference between treatment groups over 24 months. Similar significant BMD increases versus baseline were observed at the femoral neck, while biochemical markers of bone turnover (osteocalcin and deoxypyridinoline) were significantly decreased over 24 months. There were no endometrial or breast related adverse events reported. CONCLUSION: Long-cycle HRT may be a valid alternative to conventional HRT with regard to protection against postmenopausal bone loss.

The Hayman technique: a simple method to treat postpartum haemorrhage

Of the several uterine compression sutures described in more recent years to treat postpartum haemorrhage (PPH), the Hayman suture offers the potential advantages that can be applied faster and easier, avoiding the performance of a lower segment hysterotomy when PPH follows a vaginal delivery. Data on efficacy and safety are limited, and long-term follow-up information are lacking. We report our experience with the Hayman suture in 11 consecutive women with massive PPH. Of these, ten were successfully treated without further interventions. One woman ultimately required a hysterectomy. Postoperative course was uncomplicated in all the cases. The median follow-up time was 11 months (range 1-19). One woman conceived spontaneously 10 months after the procedure. Our results suggest that the Hayman suture is an effective and safe treatment for PPH.

Diagnosis of endometriosis with imaging: a review

Endometriosis corresponds to ectopic endometrial glands and stroma outside the uterine cavity. Clinical symptoms include dysmenorrhoea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms. Pelvic ultrasound is the primary imaging modality to identify and differentiate locations to the ovary (endometriomas) and the bladder wall. Characteristic sonographic features of endometriomas are diffuse low-level internal echos, multilocularity and hyperchoic foci in the wall. Differential diagnoses include corpus luteum, teratoma, cystadenoma, fibroma, tubo-ovarian abscess and carcinoma. Repeated ultrasound is highly recommended for unilocular cysts with low-level internal echoes to differentiate functional corpus luteum from endometriomas. Posterior locations of endometriosis include utero-sacral ligaments, torus uterinus, vagina and recto-sigmoid. Sonographic and MRI features are discussed for each location. Although ultrasound is able to diagnose most locations, its limited sensitivity for posterior lesions does not allow management decision in all patients. MRI has shown high accuracies for both anterior and posterior endometriosis and enables complete lesion mapping before surgery. Posterior locations demonstrate abnormal T2-hypointense, nodules with occasional T1-hyperintense spots and are easier to identify when peristaltic inhibitors and intravenous contrast media are used. Anterior locations benefit from the possibility of MRI urography sequences within the same examination. Rare locations and possible transformation into malignancy are discussed.

Pollakisuria in a dwarf goat due to pathologic enlargement of the uterus

Pollakisuria in adult goats can be caused by diseases of the urinary tract and by distension of parts of the genital tract leading to irritation of the bladder. Hydrometra is the most common cause of uterine distension in goats and usually can be resolved by prostaglandin injections. But other pathologies of the uterus can generate a similar syndrome. A dwarf goat was presented at the clinic with a history of chronic pollakisuria and tenesm. An initial ultrasonographic examination of the abdomen led to the suspicion of hydrometra, but treatment with injections of prostaglandin were not successful. Blood samples revealed low progesterone and high oestrogen values. A laparotomy was performed and an enlarged uterus with 1.5 L of mucous content and cystic ovaries were found and partially removed. A single solid leiomyoma was diagnosed histologically in the uterine wall. Two months later the goat's condition had deteriorated and therefore she was euthanized. Necropsy and pathohistological examination revealed the presence of a metastasized adenocarcinoma of the uterus. In this case, the pollakisuria provoqued by distension of the uterus was not caused by hydrometra, but by neoplasia. The syndrome and the pathogenesis of the adenocarcinoma in consideration of the hormonal status of the patient is discussed.

Vascular birthmarks

Vascular birthmarks can be classified into hemangioma and vascular malformations. Hemangioma are frequent tumours of early infancy demonstrating endothelial hyperplasia, a history of rapid neonatal growth and slow involution during later childhood. Treatment of hemangioma is dependent of stage and type of the lesion. Given the current availability of drugs, lasers, and other techniques to treat hemangioma safely, philosophy of "benign neglect" should not be considered anymore. Vascular malformations show a normal endothelial turnover, being present at birth and growing commensurately with the child. Exact diagnosis by employing modern diagnostic means,which are able to differentiate low-flow from high flow lesions is important for further therapeutic management. Beside conservative treatment strategies, use of laser, sclerotherapy, interventional embolization and surgical treatment are possible management options. Patients should receive multidisciplinary care in qualified vascular centres.

Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and intracardiac extension: radical resection may improve recurrence free survival

BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine malignancies. Based on the mitotic activity, a distinction is made between low and high-grade ESS. Although the overall five-year survival rate for low-grade ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a long latency period. Tumor invasion of the great vessels is extremely rare. We describe a patient with advanced low-grade ESS with tumor invasion of the infrarenal aorta and the inferior vena cava. The patient presented with a large tumor thrombus extending from the inferior vena cava into the right atrium. METHODS: Review of literature and identification of 19 patients, including our own case report, with advanced low-grade ESS with invasion of the great vessels and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients presented with an abdominal tumor mass and a tumor thrombus protruding into the inferior vena cava. The tumor thrombus extended into the right heart cavities in nine patients reaching the right atrium in four, the right ventricle in three and the pulmonary artery in two patients. There were 5 patients with an advanced primary tumor and 14 patients with an advanced recurrent tumor. Seven patients presented with synchronous metastatic disease and six patients with a pelvic tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta. Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor thrombectomy was accomplished by cavatomy or by right atriotomy after installation of a cardiopulmonary bypass. There was no peri-operative mortality and a very low morbidity. Radical tumor resections were achieved in 10 patients. The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5 years). Nine patients remained recurrence free whereas one patient suffered an asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive tumor with a high recurrence rate. Resection of an inferior vena cava tumor thrombus, even with extension into the right heart cavities, can be performed safely. Extensive radical surgery is therefore justified in the treatment of advanced tumor manifestations of a low-grade ESS potentially improving recurrence free survival.

Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of alpha-lactalbumin

Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human alpha-lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.

Two cases of trisomy 16 mosaicism ascertained postnatally

Postnatally ascertained trisomy 16 mosaicism is a rare diagnosis, with only three reported cases to date with no defined clinical phenotype. Trisomy 16 mosaicism diagnosed prenatally is common and associated with variable pregnancy outcomes ranging from stillbirth with multiple congenital abnormalities to an apparently normal newborn, making the genetic counseling very challenging. It is not clear whether uniparental disomy (UPD) 16 contributes to the phenotype, although it has been suggested that maternal UPD 16 affects the rate of intra-uterine growth retardation (IUGR) and congenital anomalies. We report on two further cases of trisomy 16 mosaicism confined to fibroblasts diagnosed postnatally. Patient 1 presented at birth with severe hypospadias, unilateral postaxial polydactyly, and different hair color with midline demarcation. His growth and development were normal at 11 months of age. Patient 2 was born with IUGR, significant craniofacial and body asymmetry, asymmetric skin hyperpigmentation, unilateral hearing loss, scoliosis, VSD, unexplained dilated cardiomyopathy, feeding difficulties, failure to thrive, and recurrent respiratory tract infections. She died at 7 months of age from respiratory failure. These two further cases of postnatally diagnosed trisomy 16 mosaicism highlight the variability of clinical features and outcome in this diagnosis. While Patient 2 presented with typical features of chromosomal mosaicism, Patient 1 had mild and transient features with essentially normal outcome, suggesting that trisomy 16 mosaicism may be under-diagnosed.

Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation

The family of Eph receptor tyrosine kinases and their membrane bound ligands, the ephrins, are involved in a wide variety of morphogenic processes during embryonic development and adult tissue homeostasis. Receptor-ligand interaction requires direct cell-cell contact and results in forward and reverse signaling originating from the receptor and ligand, respectively. We have previously shown that EphB4 and ephrinB2 are differentially expressed during the development of the adult mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of transgenic mice leads to perturbations in mammary epithelial morphology, motility and growth. To investigate the role of ephrinB2 signaling in mammary gland biology, we have established transgenic mice exhibiting conditional ephrinB2 knockout in the mammary epithelium. In homozygote double transgenic CreLox mice, specific knockout of ephrinB2 occurred in the mammary epithelium during the first pregnancy-lactating period. Abolishing ephrinB2 function led to severe interference with the architecture and functioning of the mammary gland at lactation. The morphology of the transgenic lactating glands resembled that of involuting controls, with decreased epithelial cell number and collapsed lobulo-alveolar structures. Accordingly, massive epithelial cell death and expression of involution-specific genes were observed. Interestingly, in parallel to cell death, significant cell proliferation was apparent, suggestive of tissue regeneration.

Histological assessment of testicular residues in lambs and calves after Burdizzo castration

To assess the reliability of the Burdizzo procedure for castrating calves and lambs, testicular tissue from 63 bull calves (15 intact and 48 castrated) and 69 male lambs (35 intact and 34 castrated) was collected at slaughter and assessed histologically. The bull calves were castrated at either one, four to five or 12 to 16 weeks of age and the lambs at either one or 10 weeks. There was clear evidence of spermatogenesis in testicular tissue from all the intact animals. In the samples from the calves that had been castrated at 12 to 16 weeks functional testicular tissue was completely lacking. However, there was evidence of spermatogenesis and steroidogenesis in the calves that had been castrated at one week or four to five weeks, respectively. Failure to achieve complete involution of the testicular parenchyma was observed in the majority of lambs, irrespective of the age at which they had been castrated.

Conception Rate Using the Select-Synch Protocol in Combination with a Lower Dose Progesterone-Releasing Intravaginal Insert (1.38 g) in Swiss Dairy Cows

Background: Synchronization programs have become standard in the dairy industry. In Switzerland, these programs are used but newly. The objective of this study was A) to estimate the pregnancy rate after a Select-Synch protocol in- cluding a low dosage of progesterone in CIDR (1.38 g). As a second step B) this pregnancy rate should be compared to cows from another Swiss study that used a Select-Synch protocol with the 1.9 g insert (Rudolph et al., 2011). Methods: A) 196 cows were included in the study. Cows received a CIDR 1.38 g and 2.5 ml of buserelin i.m. on d 0. On d 7, the CIDR insert was removed and 5 ml of dinoprost was administered i.m. On d 0 a milk sample for progesterone analysis was taken. Pregnancy was determined at or more than 35 days after artificial insemination. B) The 1.38 g group and the 1.9 g group were compared as to cow and farm factors, number of preceding AI’s, gynecological and uterine pretreat- ment and treatment itself. A forward selection procedure was used (test result considered significant if p-value  0.05). Results: A) The pregnancy rate, using the Select-Synch protocol with the CIDR 1.38 g was 44.4%. B) The CIDR 1.9 g Select-Synch group revealed a pregnancy rate of 50.4% (Rudolph et al., 2011). Significant differences between the groups were not found. Conclusion: The 1.38 g CIDR-Select-Synch protocol may be recommended for multiparous dairy cows. The pregnancy rate compared to the 1.9 g CIDR-Select-Synch protocol was 8% lower, but this difference was not significant.

Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC

BACKGROUND Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests. METHODS A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206). RESULTS There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.

Enhanced inflammatory activity of endometriotic lesions from the rectovaginal septum.

Endometriosis is characterised by the growth of ectopic lesions at multiple locations outside the uterine cavity and may be considered a collection of distinct but related conditions. The exact aetiology of endometriosis is still not clear although a role for inflammation is increasingly accepted. We therefore investigated the inflammatory activity of eutopic tissue and that of the matching ectopic lesions from different locations by measuring the genetic expression of inflammatory chemokines and cytokines. The gene expression in matching eutopic and ectopic tissue was compared, as was the gene expression in lesions from different locations. A significantly higher mRNA expression of the chemokines ENA-78 and RANTES and the cytokines IL-6 and TNF α was observed in endometriotic lesions of the rectovaginal septum (RVS) compared to that of matching eutopic tissue. Comparisons across lesion locations showed a significantly higher expression of IL-6 and TNF α in the RVS compared to lesions from either the ovaries or the peritoneum. These results show that the production of some inflammatory chemokines and cytokines is significantly increased in the ectopic endometrial tissue compared to matching eutopic tissue. Furthermore, IL-6 and TNF α are produced in significantly higher quantities in RVS lesions compared to other lesions.

Analysis of caesarean section rates over time in a single Swiss centre using a ten-group classification system.

OBJECTIVE Caesarean section (CS) rates have risen over the past two decades. The aim of this observational study was to identify time-dependent variations in CS and vaginal delivery rates over a period of 11 years. METHOD All deliveries (13,701 deliveries during the period 1999-2009) at the University Women's Hospital Bern were analysed using an internationally standardised and approved ten-group classification system. Caesarean sections on maternal request (CSMR) were evaluated separately. RESULTS We detected an overall CS rate of 36.63% and an increase in the CS rate over time (p <0.001). Low-risk profile groups were the two largest populations and displayed low CS rates, with significantly decreasing relative size over time. The relative size of groups with induced labour increased significantly, but this did not have an impact on the overall CS rate. Pregnancies complicated by breech position, multiple pregnancies and abnormal lies did not have an impact on overall CS rate. The biggest contributor to a high CS rate was preterm delivery and the existence of a uterine scar from a previous CS. CSMR was 1.45% and did not have an impact on the overall CS rate. CONCLUSION The observational study identified wide variations in caesarean section and vaginal delivery rates across the groups over time, and a shift towards high-risk populations was noted. The biggest contributors to high CS rates were identified; namely, previous uterine scar and preterm delivery. Interventions aiming to reduce CS rates are planned.