Low day 3 luteinizing hormone values are predictive of reduced response to ovarian stimulation

The aim of the present work was to evaluate whether low day 3 luteinizing hormone (LH) values in the presence of normal follicle stimulating hormone (FSH) are predictive of poor response to ovarian stimulation. Two groups of women undergoing ovarian stimulation and differing only in the day 3 LH concentration (<3 mIU/ml, study group, n=30; >3 mIU/ml, control group, n=45) were retrospectively analysed. Study group patients developed a lower oestradiol peak (703+/-388 versus 955+/-400 ng/ml; P = 0.005) and a lower number of follicles >15 mm diameter at the time of human chorionic gonadotrophin (HCG) administration (2.6+/-1.3 versus 3.6+/-1.8; P=0.004) than the control group. Conversely, a similar ratio of oestradiol: follicles >15 mm diameter was observed (256+/-118 versus 269+/-93; P=0.563). The number of follicles >10 mm at the time of HCG administration appeared to be lower in the study group, but this difference was not statistically significant (6+/-3.9 versus 7.8+/-4.3). Our data indicate that day 3 LH values <3 mIU/ml are predictive of poor response to ovarian stimulation.      

Relationship between MUC5AC and altered expression of MLH1 protein in mucinous and non-mucinous colorectal carcinomas

The main purpose of this study was to examine the expression of mucins and mismatch repair proteins in colorectal carcinomas. The immunohistochemical distribution of apomucins MUC2, MUC5AC, and the expression of MLH1 and MSH2 proteins were examined in 76 mucinous and 60 non-mucinous colorectal carcinomas. MUC2 was noted in all mucinous carcinomas, whereas MUC5AC was present in 41 cases only (54%). In non-mucinous carcinomas, MUC2 was expressed in 61.7% of the tumors; by contrast, MUC5AC was present in 20% of the cases. The expression level of apomucins was significantly different in mucinous and non-mucinous lesions (p<0.001). Twenty-seven (35.5%) of the mucinous carcinomas showed no MLH1 expression, whereas 11 (18.3%) of the non-mucinous tumors did. This difference was statistically significant (p<0.005). Altered expression of MSH2 protein was never observed. The lack of MLH1 expression was considerably more frequent in carcinomas with secretion of MUC5AC (p<0.005). Our study has demonstrated this close relationship by immunohistochemical methods. In summary, our data show: (1) differences in the expression of mucins between mucinous and non-mucinous tumors; (2) a high frequency of altered MLH1 protein expression (35.5%) in mucinous carcinomas; (3) a significant relationship between the presence of MUC5AC and the altered expression of MLH1 protein in colorectal carcinomas.     

NMR studies of the inclusion complex between β-cyclodextrin and paroxetine

A ¹H and ¹³C NMR study on the inclusion complex of paroxetine with β-cyclodextrin was carried out in order to define the stoichiometry of the association and its strength. Proton and carbon chemical shift measurements of paroxetine and β-cyclodextrin were performed at several molar ratios and temperatures, allowing the determination of a 1:1 stoichiometry and an association constant value of the order of 2 × 10³ for the paroxetine–β-cyclodextrin complex. Overhauser effects in the rotating frame were also measured, and the experimental interproton distance constraints have been used for molecular model building of the complex. The obtained model indicates that the benzodioxolyl moiety of paroxetine is deeply inserted in the cavity of the cylindrical structure of β-cyclodextrin, while the fluoro-phenyl ring lays above the wider rim.     

Clinical experience with a new type of intra-tubal device

3 types of hysteroscopic sterilization are in various stages of investigation at present: destruction of the interstitial portion of the tube with electrocoagulation or cryonecrosis, injection of sclerosing agents or liquid silicone, and mechanical devices. A nylon intratubal device measuring 4 cm long by 1 mm in diameter tested in a multicenter study was designed to prevent migration into the uterine cavity and had a nylon ring at the proximal extremity to facilitate removal of the device. The flexible middle part permitted insertion of the device without trauma. The proliferative phase of the cycle was the optimal time for insertion since the tubal orifices were most easily observed at that time. Among contraindications to use of the device were retroverted uterus, pelvic inflammatory disease, insufficiently large tubal opening, and sinuosity of the interstitial segment. 166 women aged 33.5 years of age on average and with an average parity of 2.4 children participated in a test of the method between March 1982 and February 1984. Bilateral insertion on the 1st attempt was possible for 149 women, 7 women required a 2nd attempt because of bleeding or poor visualization, and the others had functional or anatomic contraindications to use of the method. 29 insertions were done under paracervical local anesthesia and 6 under general anesthesia. Hysterographic control 1 month after insertion revealed 4 expulsions, 2 of which were bilateral. 1471 cycles without other contraception have been followed. 1 pregnancy occurred 6 months after insertion; in this case hysteroscopy showed that the device was in place. Microhysteroscopy permits a direct approach to the uterine cavity which can be done on an outpatient basis without general anesthesia. The surgical nylon of the device is inert and biocompatible, and microhysteroscopic controls have not demonstrated inflammatory tissue reactions. The flexibility of the device assures an insertion without risk of perforation. Although the method has been studies in 1471 cycles, further research is needed before conclusions can be drawn about its efficacy. Observations in 6 patients who underwent hysterectomy after use of the intratubal device showed a moderate reaction of neighboring tissue, but no evidence that the device could not be easily removed and permeability of the interstitial portion of the tubes recovered. Preliminary results support development of the method, but some difficulties in its use must still be overcome.     

Dietary soy modulation of biochemical parameters in DMBA-induced mammary tumors

The aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, by simultaneously investigating the expression of estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta), progesterone receptor (PR), apoptosis, neu, and markers of cell proliferation, such as proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The percentage of ERalpha positive tumors was 65.8% in masses from control animals, and significantly dropped to 36.8% in tumors from soy treated rats (P=0.010). The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals (P=0.066). Moreover, the percentage of cases which were both ERalpha and ERbeta positive was significantly lower (17.6%) in soy treated than in control animals (51.3%) (P=0.006). The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats (P=0.0006). There were no statistically significant differences in the percentage of tumors positively stained for neu, apoptosis, or PCNA, in control vs. soy treated rats. However, when analyzing the reciprocal correlation among the different biochemical parameters we showed that, in treated animals, the majority of ERalpha positive tumors (91.7%) were also PCNA positive (P=0.036). The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors (25 vs. 5%) (P=0.0031). Moreover, an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive (P=0.011).     

Detection of fetal cells in intrauterine lavage samples collected in the first trimester of pregnancy.

OBJECTIVES: The aim of the present study was first to evaluate the presence of fetal cells in transcervical cell (TCC) samples collected by intrauterine lavage in the first trimester of pregnancy, and then to compare different methods for the detection of these cells. METHODS: TCC samples were collected by intrauterine lavage before termination of pregnancy (TOP) from 81 pregnant women between 7 and 12 weeks of gestation. Samples of placental tissue were collected from each patient at TOP, whereas maternal peripheral blood samples were obtained in 57 cases. DNA extracted from 81 lavage and the corresponding placental samples was amplified by a polymerase chain reaction (PCR) assay using primers for SRY and HUMARA genes. All 81 lavage samples were also analysed by fluorescent in situ hybridisation (FISH) using direct-labelled probes for X chromosome alpha-satellite (DXZ1, Xp11.1-q11.1) and Y chromosome alpha-satellite (DYZ3, Yp11.1-q11.1) regions. In 57 cases, a quantitative fluorescent (QF) PCR assay, involving the use of two small tandem repeat (STR) markers (D21S11, D21S14.11) specific to chromosome 21 was employed to analyse DNA extracted from placental tissue, lavage and maternal blood samples. RESULTS: PCR analysis revealed that 40/81 placental samples were from male pregnancies. Correct sexing was achieved with the PCR technique in 30/40 (75%) lavage samples retrieved from pregnant women with male conceptuses and in all 41 (100%) samples collected from pregnancies with female fetuses. With the FISH analysis, nuclei bearing X and Y signals were observed in 32/40 cases (80%) from known male pregnancies, the rate of fetal cells ranging between 2% and 95%, whereas nuclei showing X and Y signals were not detected in any of the 41 lavage samples from known female pregnancies. Paternal peaks were present in 30/57 (52.6%) lavage samples tested by QF-PCR. CONCLUSION: The results suggest that fetal cells can be found, at a significant rate, in a very high proportion of intrauterine lavage samples. Therefore, this sampling technique can be regarded as a promising tool towards minimally invasive prenatal diagnosis. The FISH and PCR methods showed a similar efficiency in detecting fetal cells.