Refined mapping of twinning-rate quantitative trait loci on bovine chromosome 5 and analysis of insulin-like growth factor-1 as a positional candidate gene.

Twinning in cattle is a complex trait that is associated with economic loss and health issues such as abortion, dystocia, and reduced calf survival. Twinning-rate QTL have been detected previously on BTA5 in the North American Holstein and Norwegian dairy cattle populations and in a USDA herd selected for high twinning rate. In previous work with the North American Holstein population, the strongest evidence for a QTL was obtained from analysis of an extended, multiple-generation family. Using additional animals, an increased density of SNP marker association tests, and a combined linkage and linkage disequilibrium mapping method, we refined the position of this QTL in the North American Holstein population. Two sets of twinning-rate predicted transmitting abilities estimated during 2 different time periods in the North American dairy cattle population were used to provide validation of results. A total of 106 SNP and 3 microsatellites were used to scan the genomic region between 5 and 80 Mb on BTA5. Combined linkage-linkage disequilibrium analysis identified significant evidence for QTL within the 25- to 35-Mb and 64- to 70-Mb regions of BTA5. The IGF-1 gene (IGF1) was examined as a positional candidate gene and an SNP in intron 2 of IGF1 was significantly associated with twinning rate by using both data sets (P = 0.003 and P = 1.05 x 10(-6)). Replication of this association in other cattle populations will be required to examine the extent of linkage disequilibrium with the underlying quantitative trait nucleotide across breeds.

Effects of the signal transducer and activator of transcription 1 (STAT1) gene on milk production traits in Holstein dairy cattle.

A functional candidate gene approach was used to search for genes affecting milk production traits in Holstein dairy cattle. Signal transducer and activator of transcription 1 (STAT1) was chosen because of its involvement in the development of the mammary gland. Using the pooled genomic DNA sequencing approach, we identified a single nucleotide polymorphism. Genomic DNA was extracted from 1,292 sons obtained from the Cooperative Dairy DNA Repository and from 715 blood samples of daughters of 12 bulls obtained from the University of Wisconsin resource population. Daughter yield deviation data for the sons and yield deviation for the daughters were obtained for milk production traits from the USDA Animal Improvement Programs Laboratory. For the Repository population, allele C was associated with significant increases in milk fat and protein percentages. For the University of Wisconsin population, genotypes CC and CT were associated with significant increases in milk, fat, and protein yields. Results from this study are consistent with previous studies on the role of STAT1 in regulating the transcription of genes involved in milk protein synthesis and fat metabolism.

Genome screen for twinning rate QTL in four North American Holstein families.

The objective of this study was to identify twinning rate quantitative trait loci (QTL) by typing pooled samples in a preliminary screening followed by interval mapping to test QTL effects. Four elite North American Holstein half-sib sire families with high twinning rate predicted transmitting abilities (PTA) were used in this study. Chromosomes 5, 7, 19 and 23 were not genotyped as these chromosomes were scanned for QTL in these families in a previous study. DNA was extracted from phenotypically extreme sons in each sire family. Two pools were prepared from sons of sires in each phenotypic tail, two each for high and low PTA levels for twinning rates. Each pool contained DNA from 4 to 15% of all sons of the sire depending on family. A total of 268 fluorescently labelled microsatellite markers were tested for heterozygosity in sires. About 135--170 informative markers per family were genotyped using pooled DNA samples. Based on the preliminary evidence for potential twinning rate QTL from pooled typing, interval mapping was performed subsequently on 12 chromosomal regions by family combinations. Evidence of QTL for twinning rate was found in one family on BTA 21 and 29 at a chromosome-wide P<0.05 and on BTA 8, 10 and 14 with a chromosome-wide P<0.01.

Screening of persistent trophoblastic disease with various serum markers.

Eighty percent of the patients with molar pregnancy go into spontaneous remission and do not require any therapy. Serial hCG determinations can identify the 20% who will develop malignant sequelae. It does not seem appropriate to treat all patients. This study was designed to assess several serum markers, including free beta-hCG, total beta-hCG, and CA-125 in order to identify persistent trophoblastic disease. The study was performed at Doctor Zekai Tahir Burak Women's Hospital, Department of Oncology. Forty-seven patients with complete hydatidiform mole were included in the study. In the spontaneous remission group (Group I), total betahCG, CA-125 and free betahCG values were 27988.7+/-18491.6 mlU/ml, 51.7+/-74.7 U/ml and 42.35+/-28.4 mlU/ml, respectively. Patients in whom persistent trophoblastic disease had developed (Group II) the mean serum CA-125 and mean total betahCG values were lower than in group I, whereas the mean free betahCG value was higher but not significant. The mean value of free betahCG per total betahCG was found to be significantly higher in group 2. The free betahCG per total betahCG ratio seems to be a sensitive predictor of persistency of trophoblastic disease. Further prospective studies with a larger series of patients may warrant the exact predictive value of free betahCG per total hCG ratios.

Complications of radical hysterectomy: clinical experience of 115 early stage cervical cancers.

We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 rectovaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.

Leiomyosarcoma of the vagina.

Vaginal leiomyoma is uncommon and borderline leiomyoma of the vagina is an extreme rarity. Leiomyoma of the vagina may undergo malignant change to become borderline malignancy or leiomyosarcoma. A 38-year-old woman, complaining of foul vaginal discharge and dyspareunia with 2 months duration, underwent total excision of tumor. The removed tumor was diagnosed as borderline case of leiomyoma histologically. Unfortunately, she had tumor recurrence within 4 months. Thus, it was more likely that the primary diagnosis was incorrect and that the diagnosis leiomyosarcoma has been missed. She underwent total abdominal hysterectomy, bilateral salphingo-oophorectomy and total vaginectomy. The final diagnosis was leiomyosarcoma. Three months later tumor recurred again and re-excision followed by chemotherapy was performed. However, she died of her disease on her 5th month following three courses of chemotherapy.

Malignant degeneration of mature cystic teratomas.

Malignant transformation of benign cystic teratoma is rare and the most common malignancy is squamous cell carcinoma. The diagnosis is rarely made preoperatively and the prognosis is usually poor. We report 4 cases with dermoid cysts showing malignant transformation, 3 with squamous carcinoma and 1 with adenocarcinoma. The patients were within the reproductive age and underwent surgical intervention with intraoperative evaluation. Frozen section identified 2 cases with malignant transformation and staging laparotomy was performed at the initial laparotomy. One of the remaining underwent reoperation following a pregnancy termination and the other refused further surgery. None had metastases and/or capsule invasion. One had tumour rupture during excision and received combined chemotherapy following surgery. Three of the patients remain well and 1 is lost to follow-up.

Hydatidiform mole: clinical analysis of 310 patients.

OBJECTIVES: The aim of the study was to analyze the clinical characteristics, treatment and outcome of 310 patients with hydatidiform mole. METHODS: Three hundred ten patients with hydatidiform mole admitted to Dr Zekai Tahir Burak Women's Hospital between 1989 and 1994, were evaluated retrospectively according to their clinical characteristics, treatment modalities and follow-up. RESULTS: The incidence of molar pregnancy was 2.48 per 1000 deliveries and 1.84 per 1000 pregnancies. The age of the patients ranged from 14 to 45 years with a mean age of 25.29 +/- 7.40 years. In 60% of the patients, the molar pregnancy was their first pregnancy. A history of previous hydatidiform mole was found in 5.5% of the patients and eight of them had at least two previous molar pregnancies. The most common presenting symptom was vaginal bleeding (71%). Although theca-lutein cysts were found in 17.1% of the patients, only one patient underwent emergency surgery because of torsion. Dilatation and suction curettage was the first-line treatment; uterine perforation developed in two patients (0.6%). During follow-up 14.5% of patients were diagnosed as persistent cases according to serum beta-human chorionic gonadotropin (beta-hCG) levels. Complete remission was achieved with the administration of 2-8 courses of single-agent chemotherapy in 43 cases; combined chemotherapy (3-7 courses) was given to two patients who were resistant to single-agent therapy. CONCLUSION: Comparison of patients with spontaneous remission and patients with persistent trophoblastic disease with respect to age, histologic type, previous history, initial uterine size, gravidity, presence of theca-lutein cysts and initial beta-hCG levels did not reveal any of the above criteria to be prognostic for the occurrence of persistent disease.

Massive ovarian oedema: a nonneoplastic adnexal mass mistaken for a neoplasm.

Massive ovarian oedema (MOO) is an unusual clinical entity occurring in teenage girls and young women, and is thought to result from periodic and intermittent torsion of the ovarian pedicle. It is usually mistaken for an ovarian neoplasm and treated by oophorectomy. A case that underwent more radical surgery than is necessary is presented.

Vulvar syringoma exacerbated during pregnancy.

Although syringoma of the eyelids and the cheeks are well known and defined, vulvar syringoma is a rare clinical variant of this benign eccrine tumor. A case of syringoma of the vulva exacerbated during pregnancies with regression in the periods in between is presented. Histopathological examination showed typical features of syringomas. Only 20 patients with vulvar syringoma have been previously reported in the literature.

The importance of endometrial fluid collection in postmenopause.

OBJECTIVE: We sought to determine the importance of postmenopausal endometrial fluid collection, which has almost invariably been accepted as a finding of a malignant process. METHODS: Out of 1,500 postmenopausal patients admitted to our center mainly for their postmenopausal symptoms, endometrial fluid collection was detected in 15 cases during transvaginal pelvic ultrasonographic evaluations. These patients were evaluated with cervical smears as well as endocervical and endometrial curretages. The fluid collections were aspirated and measured. RESULTS: The mean age and mean menopausal age were 51.7 +/- 1.3 and 5.7 +/- 9.8 years, respectively. Six of the patients were already on hormone replacement therapy. Nine were asymptomatic and the others had vaginal discharge and pelvic pain. Ten patients had normal findings on pelvic examination, and in the others benign cervical polyps, previous cervical amputation, cervical erosion, and nabothian cysts were detected. The volume of the directly measured fluid was 7.9 +/- 4.0 cm3. The cervical smears, the cytological examinations of the fluids, the colposcopic examinations and the endocervical curretages were negative, and the histopathological evaluation of the endometrial curretage specimens revealed no premalignant or malignant disease, but blood and fibrin in 1 patient, inactive endometria in 9 patients, proliferative endometria in 4 patients and senile cystic atrophy in 1 patient. CONCLUSION: Although there was no malignancy in our series, the conflicting results of the limited number of studies made us cautious and we still consider that postmenopausal patients with endometrial fluid collection may be at risk for gynecologic cancers and that every effort should be made in order to rule out such a condition.

Medical treatment of squamous hyperplasia and lichen sclerosus of the vulva.

OBJECTIVE: To evaluate the efficacy of medical treatment in patients with lichen sclerosus (LS), squamous hyperplasia (SH) and lichen sclerosus with associated squamous hyperplasia. METHODS: Forty-eight patients with non-neoplastic epithelial disorders of the vulva, SH in 23 (47.9%), LS in 20 (41.6%) and LS with associated SH in five (10.5%) were diagnosed and treated in our clinic. Patients with LS were treated with 2% testosterone ointment. Topical fluorinated corticosteroids was the treatment of choice in patients with SH. Patients with LS with associated SH were treated with topical fluorinated corticosteroid application followed by testosterone propionate ointment. RESULTS: The clinical response rate of SH to first-line therapy was 95.6% with a correlation of 90.5% with histological reversal; this rate was 80% with a histological correlation of 81.3% in LS. The remission rates of SH and LS patients following a full course of therapy were 100% and 90%, respectively. In LS with associated SH patients, 90% responded to standard therapy with a remission rate of 100% after completion of a full course of therapy. CONCLUSION: Medical therapy of lichen sclerosus and squamous hyperplasia was very effective with a good clinical and histologic correlation.

Postmenopausal vulvar pruritus--colposcopic diagnosis and treatment.

Vulvar pruritus is a common symptom in post-menopausal women and treatment is easy if the diagnosis is duly recognized. The purpose of this study is to show the importance of colposcopic examination and directed biopsies in 27 post-menopausal women with pruritus. Biopsy sites were selected by colposcopy. The prevalence of vulvar pruritus, vulvar pathologies, vulvar dystrophies and vulvar intraepithelial lesions (VIN) were 2.18%, 1.49%, 0.94% and 0.07% respectively. Vulvar dystrophies were treated by topical steroids and success rate was 100%. All patients with vulvar pruritus need examination under colposcopy to define optimal therapy and to exclude atypia or malignancy.

Chronic pelvic pain in adolescent women. Diagnostic laparoscopy and ultrasonography.

OBJECTIVE: To evaluate the correlation of preoperative pelvic examination and ultrasonography with the laparoscopic findings in 45 adolescent women with chronic pelvic pain. STUDY DESIGN: Between January 1, 1989, and December 31, 1992, 45 adolescent women underwent diagnostic laparoscopy following a detailed clinical workup for evaluation of chronic pelvic pain. RESULTS: Thirty-five of 45 pelvic examination findings correlated with the laparoscopic findings. The predictive values of normal and abnormal findings at pelvic examination were 42.8% and 93.5%, respectively. Ultrasonography (US) correlated with laparoscopy in 39 of 45 cases. The predictive value of normal findings at US was 60%, and that of abnormal findings was 94.2%. When both pelvic examination and US were normal, 50% of cases were abnormal at laparoscopy. However, laparoscopy revealed abnormality in 100% of patients with abnormal pelvic examinations and abnormal US findings. CONCLUSION: Clinical evaluation of chronic pelvic pain, when combined with US, is highly predictive but needs confirmation, best provided by laparoscopy.

Ultrasonographic appearance of fallopian tube carcinoma.

Preoperative diagnosis of tubal carcinoma is difficult and a diagnosis cannot usually be established until the time of operation. However, since prognosis is strictly related to the stage of the neoplasm, it is very important to be familiar with the clinical and imaging characteristics of primary fallopian tube carcinoma in order to make an early and accurate diagnosis. This report presents the ultrasonographic features of three cases of fallopian tube carcinoma and reviews the literature on the subject.

Preoperative assessment of myometrial invasion of endometrial carcinoma by transvaginal ultrasonography.

Preoperative transvaginal ultrasonographic evaluation of myometrial invasion was performed in 33 patients with endometrial cancer and compared with histologic findings. TVU was remarkably precise in predicting deep myometrial invasion (accuracy 91.7%) but superficial myometrial invasion (sensitivity 20%). TVU was highly accurate in patients with tumours limited to the endometrium (sensitivity 100%) and the sensitivity of TVU in distinguishing nil or superficial versus deep invasion was 87.8%. TVU appears to be an efficient, economic, and practical tool for this purpose, however its limitation leads to more complex imaging techniques, especially in patients in whom preoperative irradiation or conservative management is planned.

How does negative clinical evaluation of ovarian carcinoma after full course of chemotherapy correlate with second-look laparotomy findings?

Surgical reexploration was performed in 46 patients with epithelial nonmucinous ovarian adenocarcinoma requiring adjuvant chemotherapy whose initial therapy consisted of optimum debulking and surgical staging. All patients were placed on CAP (cisplatinum, Adriamycin, cyclophosphamide) chemotherapy for at least six courses until proved to be clinically disease free (mainly CA-125 below 35 U/ml and normal ultrasonography or computerized tomography). All women underwent second-look laparotomy (SLL) after completion of adjuvant therapy. We classified SLL findings in five categories, namely, no evidence of disease, cytological evidence of disease, histological evidence of disease, macroscopic evidence of disease (< 2 cm), and bulky tumor (> 2 cm). SLL demonstrated 14 (30%) patients with disease. Of these, five cases had histological evidence of disease and nine had macroscopic disease; however, we found no patient with persistent disease larger than 1.5 cm. No patient in stage I demonstrated disease at SLL. All cases with macroscopic disease and three cases with histological disease were initially in stage III. We found that about one third of cases who were clinically free of disease had persistent disease at the completion of chemotherapy. Hence, we conclude that routine SLL is still of importance in the management of patients with epithelial ovarian adenocarcinoma except those with stage I disease.

Malignant mixed müllerian tumor of the fallopian tube.

Primary malignant mixed müllerian tumor of the fallopian tube is uncommon. Only 37 cases of malignant mixed müllerian tumor of the fallopian tube have been reported to date and of these only 16 contained heterologous components (mesodermal mixed tumor). This rarity made us report a case of malignant mixed müllerian tumor of the fallopian tube containing heterologous components which was operated on in our gynecologic oncology department. Postoperatively the patient was placed on six courses of adjuvant chemotherapy consisting of cis-platinum, adriamycin and cyclophosphamide (PAC). Second look laparotomy was performed after completion of chemotherapy. Presently, she is doing well, at two months follow-up, with no evidence of disease.

Accuracy of pipelle endometrial sampling in endometrial carcinoma.

In this prospective study, we compared the histological results of Pipelle endometrial sampling (PES) with that of hysterectomy to examine whether endometrial sampling with the Pipelle device can accurately diagnose endometrial carcinoma. PES was performed in 26 patients with known endometrial carcinoma whose initial therapy consisted of hysterectomy. Discomfort and pain during the biopsy were reported to be mild by 22 patients, moderate by 3 patients and severe by only 1 patient. All of the samples were found to be adequate. Twenty-four of 26 PES confirmed endometrial carcinoma, a correlation of 95%, and the histological grade reported on PES agreed with that of hysterectomy specimens in 87.5% of the patients. On the other hand, the tumor grade in the specimens obtained at dilation and curettage correlated with hysterectomy specimens in 95% of the patients. We conclude that Pipelle is an accurate device in patients with endometrial carcinoma.