Microsatellite analysis provides efficient confirmation of fetal trophoblast isolation from maternal circulation.

Fetal trophoblasts can be found in maternal circulation from an early stage of pregnancy and thus provide a potential source of DNA for non-invasive prenatal diagnosis. We have developed a two-step method for trophoblast isolation between the 8th and 12th week of pregnancy. Blood was sampled from 14 women undergoing termination of pregnancy or spontaneous abortion. Immunomagnetic beads precoated with HLA class I and II, and with anti-cytokeratin-18 monoclonal antibodies, were used to remove CD8+ and other maternal cells, and to select for fetal trophoblasts, respectively. Microsatellite analysis was performed on DNA extracted from the isolated, maternal, paternal and placental cells after PCR amplification. Recovery of the trophoblasts was confirmed in 13/14 cases (93%) by the identification of an identical microsatellite pattern for fetal and placental cells. Further evidence was the presence of heterozygous alleles of both maternal and paternal origin. The correct prediction of gender in all five male fetuses was an additional confirmation of trophoblast recovery. We conclude that trophoblasts can be effectively isolated from maternal blood in the first trimester, and by using polymorphic microsatellite markers to confirm sample purity, this method has potential future application in prenatal diagnosis.

Multimodal cancer chemotherapy during the first and second trimester of pregnancy: a case report.

This paper reports treatment with combined chemotherapy during pregnancy. A 39-year-old woman with breast cancer was given adjuvant chemotherapy including cyclophosphamide, methotrexate and 6-fluorouracil from the 6th to the 24th week of gestation. The possibility of teratogenic effects on the fetus was explained to the patient however she refused to terminate the pregnancy. A 30-week male infant with only a minor malformation was delivered. The authors reviewed the literature regarding chemotherapeutic agents given during the first trimester of pregnancy. Most cytotoxic drugs have teratogenic effects on experimental animal subjects. However, actual data on human fetuses are sparse because of the variety of therapeutic regimens and the rarity of administering chemotherapy during pregnancy. The long-term effects of exposure to cytotoxic drugs in utero, needs further research.

Serum soluble CD23 and TNF-alpha in women with spontaneous abortion in the first trimester.

The present study was designed to investigate the participation of sCD23 and TNF-alpha in pregnant women in the first trimester. One hundred and forty-one patients were enrolled in the study. Women were classified into two groups. Serum sCD23 and TNF-alpha were measured in 73 normal pregnant women in the first trimester (Group I) and in 68 women with spontaneous abortion (Group II). We found that the mean values of TNF-alpha levels were higher in women with normal pregnancy than in women with spontaneous abortion (p < 0.05), whereas sCD23 levels of women in group II did not differ statistically from the controls. These results sustain the opinion that women with spontaneous abortion seem to have reduced TNF-alpha levels. However, determination of these immunological parameters provides no useful clinical information about disease activity and management.

Disposition of pesticides and toxicants in the human reproductive system in cases of acute poisoning.

The aim of this study was to estimate the penetration of some of the pesticides and toxicant substances in the human reproductive system. This knowledge is valuable because of the possible adverse influence of these substances on the human reproduction system and the development of the foetus during pregnancy. The existing data is mainly concerned with the results of experimental studies on animals or epidemiological studies. Here we report data concerning the disposition of several toxic xenobiotics (pesticides and solvents) in the tissues of the human reproductive system as well as in other organs and glands. Data was collected from cases of acute poisonings and derived mostly from autopsy materials. Xenobiotics were found to penetrate sampled tissues such as the testes, ovaries, epididymis, uterus, thyroid gland, as well as other human tissues. Further studies will clarify and confirm peculiarities of the penetration of a wide range of substances in various body tissues and will be the base of the estimation of the role of these toxicants in human reproductive ability and the outcome of pregnancy in humans.

A pilot study on concurrent platinum chemotherapy and intracavitary brachytherapy for locally advanced cancer of the uterine cervix.

This study aims to evaluate the feasibility, toxicity and efficacy of concurrent chemotherapy with platinum compounds and brachytherapy, for locally advanced carcinoma of the cervix (Stages IIA/B, IIIA). The hypothesis was that synchronous chemo-brachytherapy may be sufficient to cause down-staging of the tumour, to render it operable, and hopefully improve the prognosis. 36 women with locally advanced cervical cancer were treated with concomitant brachytherapy and chemotherapy before surgery and/or definitive external radiotherapy. All patients received two caesium-137 Selectron MDR applications, 1 week apart. The dose calculated to point A for each implant was 20-25 Gy. Chemotherapy consisting of continuous cisplatin infusion (50 mg m2) and of carboplatin (300 mg m-2) was given simultaneously with intracavitary irradiation during the first and second application, respectively. The combined therapy was followed when feasible by radical hysterectomy, pelvic lymphadenectomy and pelvic radiotherapy. Patients deemed ineligible for surgery because of poor response were given full dose external radiotherapy. 31/36 patients were treated by Wertheim hysterectomy of whom 10 had negative lymph nodes and resection margins. Definitive external radiotherapy was given in the remaining five patients. Overall, 83% were disease free at 2.8 years mean follow-up. The most frequent acute side-effects of chemobrachytherapy were nausea and vomiting. No renal toxicity was observed. Thrombocytopenia was seen in five patients and was responsible for delayed surgery in four patients. Concerning late effects, two patients developed grade 2 intestinal sequelae, two mild frequency and two vaginal stenosis. One rectovaginal and one vesicovaginal fistula developed in two patients; and a third patient had a fistula associated with tumour recurrence. Concurrent brachytherapy and chemotherapy with platinum compounds is well tolerated and effective in reducing tumour bulk before definitive local treatment (surgery or external radiotherapy), in patients with locally advanced carcinoma of the uterine cervix.

Cigarette smoking and vaginal atrophy in postmenopausal women.

The atrophy of the vaginal epithelium was studied clinically and cytologically on vaginal smears of 1638 healthy postmenopausal female non smokers and 531 healthy postmenopausal smokers (over 30 years), with a mean age of 58 years. A very strong statistically significant difference (p < 0.0001) in the atrophical vaginal changes between smokers and nonsmokers to the disadvantage of the smokers. Also a very statistically significant association (p < 0.0001) was observed between the cytological expression of the vaginal atrophy and duration at menopause of the non-smokers but no association in the cases of the smokers. Another important result of this study was that the smokers women had an early menopause (p < 0.0001), on average by 2 years sooner (mean age 48.5 years) than non-smokers (mean age 50.5 years). These results suggest that cigarette smoking has an effect on the vaginal squamous epithelium, increasing the atrophical changes and causing early menopause by mechanisms, some of which remain unclear.

Use of CA-125 in the diagnosis and management of endometriosis: influence of treatment with danazol.

OBJECTIVE: To compare CA-125 levels in endometriotic women with normal controls. PATIENTS AND METHODS: The level of the oncofetal antigen CA-125 was measured in serum samples taken from 40 women, aged 21 to 33 years. Blood samples for CA-125 from 15 endometriotic women were measured before treatment, during the last 15 days of a 6-month administration of Danazol, and 3 months after treatment, and were compared to findings in 15 women without endometriosis (from whom blood samples were taken only once). RESULTS: The CA-125 levels were significantly higher in patients with endometriosis before treatment as compared with the controls (P < .01). The administration of Danazol significantly reduced the levels of CA-125 (P < .01), and 3 months after treatment the levels of CA-125 remained significantly lower (P < .05) as compared to the respective pretreatment values. CONCLUSION: The results support the view that the determination of CA-125 levels may assist in (a) evaluating women with endometriosis and (b) treatment with Danazol.

Soluble serum interleukin-2 receptor, interleukin-6 and interleukin-1a in patients with endometriosis and in controls.

The aim of this study was to verify to what extent danazol alters cell-mediated immunity. To this end, cell-mediated immunity was studied in 10 infertile patients with endometriosis and in 10 normal controls. Nonspecific parameters studied included serum SIL-2R, IL-6 and IL-1a levels. We also investigated the effect of treatment with Danazol on the levels of SIL-2R, IL-6 and IL-1a in women with endometriosis. Blood SIL-2R, IL-6 and IL-1a levels were measured in endometriotic women before treatment, during the last fifteen days of a 6-months course of Danazol and three months after treatment. Only one blood sample was taken from 10 women without endometriosis. SIL-2R, IL-6 and IL-1a levels were higher in women with endometriosis before treatment compared with controls. Administration of the drug significantly reduced the levels of SIL-2R (P < 0.001), IL-6 (P < 0.05) and IL-1a (P < 0.01). Our findings suggest that endometriosis is a condition which induces a rise in interleukin levels. Danazol also appears significantly to reduce endometriosis-associated autoimmune abnormalities.