Transmucosal oxygen tension of the clitoris: a new parameter for future investigations of the sexual, metabolic, and cardiovascular health of women.

BACKGROUND: Several studies suggested that abnormalities in tissue perfusion of external genitalia and vagina can lead to female sexual dysfunctions (FSDs) and can be associated to metabolic and cardiovascular risk factors. However, there are some technical difficulties in assessing these abnormalities. The measurement of oxygen partial pressure is a noninvasive method to measure oxygen partial pressure (pO2) at the skin surface to assess tissue perfusion. The aim of this study was to evaluate whether transmucosal oxygen tension (TmPO2) can be measured at the mucosal surface of clitoris and whether the measurements are reliable. METHODS: TmPO2 was measured in six young healthy women by using a device to measure transcutaneous pO2 on the skin and by choosing a small sensor, usually used for newborns. The identical procedure for the detection of pO2 at the skin surface was used. RESULTS: The mean value of TmPO2 was 42.3 mmHg (range: 24.1-53.4 mmHg). All the trend curves of the TmPO2 showed the same behavior: after a stabilization time, there was a stable pO2 (plateau phase) that corresponds to the TmPO2 of the clitoris. These curves had a similar trend to those recorded at the skin surface. CONCLUSIONS: TmPO2 can be easily measured at the mucosal surface of clitoris. Large epidemiological studies in healthy and unhealthy women and in women with FSD are needed to establish both the normal range of TmPO2 and the meaning that different values of TmPO2 can have on sexual and general health of the women.

Association between low C-peptide and fragility fractures in postmenopausal women without diabetes.

PURPOSE: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. METHODS: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. RESULTS: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively). CONCLUSIONS: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes.

UNLABELLED: In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. INTRODUCTION: It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density. METHODS: Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay. RESULTS: rteen percent of the population had osteoporosis and 38% had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). CONCLUSIONS: These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.

Chemotherapy with or without estrogenic recruitment in metastatic breast cancer. A randomized trial of the Gruppo Oncologico Nord Ovest (GONO).

BACKGROUND: This phase III study was carried out to verify whether a kinetic recruitment induced with low doses of diethylstilbestrol (DES) could increase the antitumor activity of chemotherapy in patients with advanced breast cancer. PATIENTS AND METHODS: Two hundred fifty-eight women with metastatic breast cancer were randomized to receive chemotherapy consisting of cyclophosphamide 600 mg/sqm i.v., epidoxorubicin 60 mg/sqm i.v. and fluorouracil 600 mg/ sqm i.v. (CEF) on day 1 or DES-CEF (diethylstilbestrol 1 mg orally days 1-3 CEF on day 4) every 21 days. Patients were treated until progression or, if responsive, for a maximum of 10 courses. RESULTS: There were no significant differences between the two treatment arms in response rates (51.3% to CEF and 49.6% for DES-CEF); median progression-free survival (9.4 months for CEF and 11 months for DES-CEF group) or median overall survival (17.3 and 20 months for CEF and DES-CEF arms, respectively). Non-hematological toxicities were superimposable in the two arms, while DES-chemotherapy was more myelotoxic. CONCLUSIONS: This trial confirms that chemotherapy preceded by estrogenic recruitment is still in an experimental phase and that, at present, it has no role in clinical practice. Further research is needed to test the possibility of combining different mitogens in the light of new information about breast cancer cell growth.

Second-line hormonotherapy for breast cancer. Uselessness of first-line continuation.

The hypothesis that the results of second line hormonotherapy for breast cancer may be ameliorated with continuation of the first line has been explored in a randomized trial. Patients progressing under tamoxifen were randomly allocated to aminoglutethimide and hydrocortisone acetate with or without tamoxifen continuation. No difference has been observed between the two arms in terms of response rate and progression-free overall survival.

Factors predicting early response to treatment with recombinant interferon alpha-2a in chronic non-A, non-B hepatitis. Preliminary report of a long-term trial.

To evaluate cost-effectiveness and response predictors of treatment with recombinant interferon alpha-2a in chronic non-A, non-B hepatitis, 263 consecutive patients were enrolled in a multicenter long-term study. A pre-planned analysis aimed at identifying predictors of early response was carried out when all patients had completed the initial 3 months of treatment with 6 MU thrice weekly. Sixty-three percent of the patients enrolled were classified as responders. At multivariate logistic regression analysis, baseline gamma-glutamyltranspeptidase levels and cirrhosis were the only independent variables significantly associated with response. The risk of no response after 3 months of treatment was 3.9 times higher (95% confidence interval, 1.6 to 7.2) in patients with high baseline levels of gamma-glutamyltranspeptidase as compared with patients showing low baseline levels, and it was 2.0 times higher (1.1 to 3.8) in patients with cirrhosis as compared with those without it. We expect that results from this and other studies on large patient populations may help to select those patients who are more likely to benefit from interferon administration.

Treatment of advanced pancreatic carcinoma with the somatostatin analogue BIM 23014. Preliminary results of a pilot study.

Treatment of advanced pancreatic cancer has not improved substantially in recent years. The search for new agents or new therapeutic modalities may be critical for further development in the therapy of this disease. Experimental and clinical findings suggest that it might be possible to develop a new hormonal therapy for exocrine cancer of the pancreas based on new somatostatin analogues. Preliminary results indicate clinical activity and increased survival in some patients. In this study, 19 patients with advanced exocrine pancreatic carcinoma were given the somatostatin analogue BIM 23014 using a range of doses from 250 micrograms/day to 1 mg/day. One patient had a partial response, 6 patients had stable disease, and 11 had progressive disease. Six patients showed a sharp improvement in pain and performance status. Side effects were mild. Plasma levels of growth hormone were evaluated in ten patients and remained unchanged. The clinical activity observed, even if limited, warrants further investigation using more appropriate schedules and administration techniques.

In vivo manipulation of human breast cancer growth by estrogens and growth hormone: kinetic and clinical results.

Since 1983, a series of experimental and clinical studies have been carried out on the possibility of enhancing the chemotherapy effectiveness in breast cancer by expanding the fraction of cycling cells. Theoretically estrogens should recruit breast cancer cells and this fact should result in a higher killing efficiency of antiproliferative drugs. Actually it has been clearly shown, by means of the thymidine labeling index and primer-dependent alpha-DNA polymerase assay, that low doses of diethylstilbesterol are able to increase the tumor proliferative activity of human breast cancer in vivo (estrogenic recruitment). Three randomized trials have been carried out (one in locally advanced and two in metastatic breast cancer) comparing conventional polychemotherapy vs chemotherapy with estrogenic recruitment. Only limited advantages have been observed in these trials. Searching for new modalities of kinetic manipulation of tumors, recombinant human growth hormone has been employed in a pilot study: the preliminary results indicate that it largely enhances tumor proliferative activity, suggesting the possibility of employing a growth factor system to increase chemosensitivity.

Cisplatin and 5-fluorouracil in refractory breast cancer patients: a phase II study.

24 patients with a median of 3 prior chemotherapy regimens were treated in our department with cisplatin 20 mg/m2 (with pre- and posthydration) and 5-fluorouracil 200 mg/m2 i.v. on day 1-5, every three weeks. 23 patients are evaluable; one had early death. 4 patients (17%) achieved a partial response, 8 had stable disease, and 11 progressed. Toxicity observed was moderate and no renal toxicity was noted. This study therefore shows tolerable toxicity but limited usefulness of adding cisplatin to 5-fluorouracil according to this schedule in these highly pretreated patients.

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma.

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.