V. Facchini

Ultrasonographic bone characteristics during normal pregnancy: Longitudinal and cross-sectional evaluation

OBJECTIVE We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

Increase of proopiomelanocortin-related peptides during subjective menopausal flushes☆

The present study reports the plasma levels of gonadotropins (luteinizing hormone, follicle-stimulating hormone), proopiomelanocortin-related peptides (adrenocorticotropic hormone, beta-endorphin, and beta-lipotropin), and cortisol in eight menopausal women experiencing frequent hot flushes. beta-Endorphin and beta-lipotropin levels were measured by radioimmunoassay after extraction and Sephadex G-75 column chromatography. Plasma levels of adrenocorticotropic hormone (after extraction), luteinizing hormone, follicle-stimulating hormone, and cortisol were measured by specific radioimmunoassay. All hormone levels showed a prompt and significant rise on occurrence of hot flushes (18 total recordings), remained high for 15 minutes, and decreased to basal levels 35 minutes later. The evaluation of the behavior pattern of single hormone levels revealed a more pronounced increase of proopiomelanocortin-related peptides and cortisol than of gonadotropins (p less than 0.01).

Genotype distribution of estrogen receptor-α gene polymorphisms in italian women with surgical uterine leiomyomas ☆

OBJECTIVE To explore a possible association between estrogen receptor-alpha (ER-alpha) gene polymorphisms and development of uterine leiomyomas. DESIGN Case-control study. SETTING University teaching hospital. PATIENT(S) 119 women with clinically and surgically diagnosed uterine leiomyomas. INTERVENTION(S) Therapeutic hysterectomy. MAIN OUTCOME MEASURE(S) Frequency and distribution of ER-alpha gene polymorphisms. RESULT(S) No statistically significant differences between controls and patients in the allele frequency and genotype distribution were found when Pvu II and Xba I restriction polymorphism sites were analyzed separately. When the two ER-alpha gene polymorphisms were analyzed in combination, five major genotypes were recognized in controls or patients; the frequency differed slightly but not significantly between groups. CONCLUSION(S) The Pvu II and Xba I polymorphisms in the ER-alpha gene do not produce different risks of developing uterine leiomyomas.

Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists.

In the present study we assessed the effects of ipriflavone in the prevention of increased bone turnover and the rapid bone loss that follows medical induced hypogonadism caused by the administration of a gonadotropin hormone-releasing hormone agonist (GnRH-A). In a double blind, placebo-controlled study, ipriflavone (600 mg/day, tdd (three divided doses)) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with 3.75 mg leuproreline acetate every 30 days, for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma bone GLA protein levels showed a substantial (P < 0.01) increase, while spine bone density and total body bone density significantly (P < 0.01) decreased after 3 and 6 months of GnRH-A administration. Conversely, in ipriflavone treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medical induced hypogonadism. Thus, ipriflavone administration can be of value in the prevention of osteopenia in women treated with GnRH-A.

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: Relevance for monitoring the response to chemotherapy and follow-up of patients

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.

Lack of correlation between amniotic fluid and maternal plasma contents of β-endorphin, β-lipotropin, and adrenocorticotropic hormone in normal and pathologic pregnancies

Reported are the concentrations of beta-endorphin, beta-lipotropin, and adrenocorticotropic hormone (ACTH) in the amniotic fluid and plasma of 40 healthy pregnant women at different stages of gestation. Moreover, the amniotic fluid levels of the three peptides were evaluated in 20 other pregnant women affected by different pathologic conditions (Cooleys disease, gestosis, diabetes, placental insufficiency, etc.). A silicic acid extraction procedure was performed on the samples. Each extract was subjected to Sephadex G-75 column chromatography, and the two fractions corresponding to beta-lipotropin and beta-endorphin were collected, freeze-dried, and assayed by two specific radioimmunoassays. Levels of ACTH were measured by radioimmunoassay directly on the extracts. Levels of beta-endorphin in amniotic fluid showed the highest values in the first trimester (173 +/- 30 fmol/ml, mean +/- SEM) but were significantly decreased in the second (75.2 +/- 14) and third trimesters (14.3 +/- 1.8). An inverse trend characterized plasma levels of beta-endorphin, which showed a progressive increase from the first trimester to term (10.4 +/- 11.1). Amniotic fluid levels of beta-lipotropin remained stable during the first (48.6 +/- 6.3) and second (54.6 +/- 11.1) trimesters, but decreased significantly in the third trimester (17.9 +/- 2.3). The plasma concentrations of beta-lipotropin showed the highest levels in the first trimester (10.9 +/- 0.9), and decreased significantly at term (8.9 +/- 1.3). Last, amniotic fluid levels of ACTH decreased from 55.3 +/- 4.75 fmol/ml in the first trimester to 12.5 +/- 1.16 in the second trimester, and rose again in the third trimester to 34.4 +/- 6.6 fmol/ml. Plasma levels of ACTH were characterized in the first two trimesters by values twice those recorded for nonpregnant women, and decreased at term to 8.9 +/- 1.4 fmol/ml. In the pregnant patients with fetuses affected by Cooleys disease (second trimester) and in those with edema-proteinuria-hypertension (EPH) gestosis (third trimester), amniotic fluid levels of beta-endorphin, beta-lipotropin, and ACTH were in the same range as those in healthy pregnant women.

Serum soluble interleukin-2 receptor assay in epithelial ovarian cancer.

Preoperative serum soluble interleukin-2 receptor (sIL-2R) and CA 125 levels were measured in 183 patients with ovarian masses undergoing laparotomy. Serum sIL-2R levels were higher in the 54 patients with epithelial ovarian cancer than in the 129 patients with benign ovarian diseases (p < 0.0001). Elevated serum levels of sIL-2R (> or = 71 U/ml) and CA 125 (> or = 83 U/ml) were found in 79.6 and 77.8% of patients with epithelial ovarian cancer, respectively. Serum sIL-2R and CA 125 positivity rates correlated with the FIGO stage (p = 0.0033 and p = 0.0001, respectively). Raised serum levels of sIL-2R and CA 125 were detected in 11.6 and 7.0% of patients with benign ovarian diseases, respectively. The combination sIL-2R or CA 125 had a sensitivity of 88.9%, and the association sIL-2R and CA 125 had a specificity of 98.4% for epithelial ovarian cancer. As for the 16 patients with this malignancy who were serially monitored during and after chemotherapy, changes in sIL-2R and CA 125 levels correlated with the clinical course of disease in 62.3 and 94.3% of 53 instances, respectively. In conclusion, the serum sIL-2R assay could represent a useful adjunctive tool for the differential diagnosis of ovarian masses, while it seems to be of limited benefit for monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer.

Correlation of CA125 and CA19-9 serum levels with clinical course and second-look findings in patients with ovarian carcinoma

CA125 and CA19-9 levels were serially evaluated in blood samples from 21 patients during and after integrated surgical and chemotherapeutic treatment for ovarian carcinoma. Serial measurement of CA125 and CA19-9 correlated with clinical course of disease in 89.7 and 72.7% of instances, respectively. The decrease of serum CA125 and/or CA19-9 in the normal range at the end of chemotherapy does not exclude the presence of residual disease, which can be accurately evaluated only by second-look laparotomy. Serum CA125 and/or CA19-9 can raise some months before clinical and ultrasonographic detection of recurrence. CA125 is the most reliable marker in ovarian carcinoma; however, the concomitant measurement of CA19-9 could offer some benefit in the monitoring of patients with this neoplasia.

Monitoring of hematoporphyrin injected in humans and clinical prospects of its use in gynecologic oncology.

The use of hematoporphyrin (HP) and its water soluble derivatives (HPD) as tumor localizers1 and sensitizers for phototherapy of neoplasias 2 is well documented and receiving rapidly increasing interest.

Cyclic-combined Conjugated Estrogens and Dydrogesterone in the Treatment of Postmenopausal Syndrome

We report the data concerning postmenopausal women treated either with a calcium supplement (500 mg/day, group l, n = 13) or with cyclic conjugated estrogens (0.625 mg/day) and dydrogesterone (5 mg/day) for 21 days with a 7-day free interval (n = 27, group 2) for 24 months. Withdrawal bleeding was regular, starting 1–2 days after the last treatment day and defined as light or mild. No sign of endometrial hyperstimulation was found by hysteroscopy and endometrial biopsy performed after 24 months of treatment. In group 1, constant levels of both urinary excretion of hydroxyproline and plasma osteo-calcin were observed, along with a significant (p < 0.05) decrease in vertebral bone mineral density. In group 2, both urinary excretion of hydroxyproline and plasma osteocalcin levels were significantly (p < 0.05) decreased and vertebral bone density showed a slight but significant (p < 0.05) increase. In group 1, a significant (p < 0.05) increase in serum low-density lipoprotein (LDL)-cholesterol levels was observed, whereas no modification in total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides was found. In group 2, total cholesterol and LDL-cholesterol levels significantly (p < 0.05) decreased, whereas triglycerides levels were stable throughout the study. In this group, HDL-cholesterol levels showed a significant (p < 0.05) increase. In conclusion, the regimen for cyclic combined estrogen-progestogen therapy attenuates bleeding disturbances and results in a low dropout rate. Thus, the clinical and metabolic actions, as well as the protective effects on the endometrium, make this treatment of potential interest. Further studies are required to confirm the long-term beneficial effects of this formula on cardiovascular protection and fracture rate.