Report of fertility in a woman with a predominantly 46,XY karyotype in a family with multiple disorders of sexual development.

CONTEXT: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X). PATIENTS: A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis. RESULTS: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage. CONCLUSIONS: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.

Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women.

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.

Adjuvant therapy after radical surgery of cervical cancer: Zagreb experience.

The results of the analysis of the treatment of 72 patients with carcinoma of the uterine cervix are presented. Seventy-two patients with Stage IB1 carcinoma of the cervix underwent a radical hysterectomy and pelvic lymphadenectomy. The low-risk group includes the patients without unfavourable prognostic factors that were treated by surgery alone. The high-risk group included women with pelvic node metastases, clinical tumour size greater than 3.0 cm, depth of stromal invasion greater than 1/3 of the cervical wall, Grade 3 tumours and the presence of lympho-vascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks following surgery. Thirty-four patients (47.2%) were in the low-risk group and thirty-eight patients (52.8%) were in the high-risk group. Locoregional recurrences were diagnosed in three cases (8.8%) in the surgery group and in four patients (10.5 %) assigned to postoperative radiotherapy. The incidence of distant metastases was 2.9% in the group treated by surgery alone and 5.3% in the group treated by surgery and radiotherapy. Overall survival at five years was 91.2% in the low-risk group and 89.5% in the high-risk group of patients. Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, which emphasizes the value of whole pelvic radiation in patients with one or more unfavourable prognostic factors after radical surgery in Stage IB1 cervical cancer

[Alternative hormone therapy in postmenopause]. / Alternative hormonskomu lijecenju u postmenopauzi.

Despite the fact that hormonal combination used in huge Wpmen's Health Initiative (WHI) is not common all over the world, and treated population is, because of age, in risk per se, study results have consternated not only lay users, but prescribers too. Namely, increased cancer, stroke and coronary heart disease risk associated with long term use of postmenopausal hormone therapy (HT) have rapidly declined the number of women treated with HT (either estrogen alone or estrogen plus progestogen). Considering recent position statements from leading organizations dealing with menopause, individualization of therapy and lower dosage HT becomes the state of the art. Not only WHI, but also results of other studies published during past few years, have induced curiosity for non-estrogen containing treatments in climacteric medicine. This review shows not only mandatory list of possibilities, but also emphasises which of the alternative and complementary treatments are evidence based regarding published randomized controlled trials.

Possible role of bacterial and viral infections in miscarriages.

OBJECTIVE: To determine the role of infections in miscarriages. Chorionic villi from aborted material were subjected to cytogenetic evaluation and analyzed for the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, human cytomegalovirus (HCMV), adeno-associated virus (AAV), and human papillomaviruses (HPV). DESIGN: Retrospective study. SETTING: University hospital and academic research institution. MAIN OUTCOME MEASURE(S): Karyotyping and detection of bacterial and viral DNA by means of polymerase chain reaction (PCR) in placenta specimens. RESULT(S): In 54 (50%) of 108 samples the karyotype was normal, in 38 (35%) samples it was abnormal, and in 16 (15%) samples karyotype was undetermined. No U. urealyticum, M. hominis, HCMV, or AAV-2 DNA was detected, while C. trachomatis DNA was detected in one (1%) and HPV DNA in eight (7%) samples. No significant correlation of HPV-positive findings with karyotype status was established. CONCLUSION(S): Our findings do not support a role of C. trachomatis, U. urealyticum, M. hominis, HCMV, or AAV infections in miscarriages during the first trimester of pregnancy. However, further investigation should be made to determine a possible involvement of HPVs in the development of genetic abnormalities of the fetus and in miscarriages.