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Biomedical subjects

C Bulletti

Publications and source records attributed to C Bulletti.

At least 19 recordsLinked to original sources

Paracrine regulation of menstruation.

Endometrial proliferation, secretion, vascular neoformation and modification to shedding is under direct and/or indirect control of steroid hormones. The progressive modification of the endometrial architecture is due to its growth and differentiation. The new tissue regenerates monthly from a 2-5 mm to a 12-18 mm of complex tissue until it sheds under a co-ordinated network of bioactive molecules produced and activated during the menstrual cycle. The steroid hormones, the HLA-DR and integrin molecules, the intense production of several proteins, the vascular damage, and the disconnection of cell-cell and cell-matrix interaction are participating in both the endometrial preparation for embryonic implantation and the shedding and bleeding of the tissue itself. Menstruation is a process associated with damage to the epithelium, endothelium and extracellular matrix, ending on controlled bleeding, tissue dissolution and repair. Endometrial proteinases and tissue factor (TF) contribute to systemic factors to control the mechanisms of regulation of tissue dissolution, tissue shedding, and vascular bleeding during menstruation.

Animals

The hormonal control of endometrial receptivity: estrogen (E2) and progesterone.

While the number of identified substances produced by the ovary increases steadily, it remains remarkable that the sole use of exogenous estrogen (E2) and progesterone (P) can prime optimal endometrial receptivity in women whose ovaries have failed or are absent. Early work showed that a marked leeway existed in the acceptable duration of the E2-only phase of endometrial priming. Subsequently, a sequence of transformations are induced by exogenous progesterone that reproduces classical findings made in the menstrual cycle. Secretory changes in endometrial glands are best seen between the 4th and 6th day of progesterone administration (day 18-20 of an ideal cycle where progesterone exposure starts on day 15). Predecidual changes of the endometrial stroma are apparent starting on the 10th day of progesterone exposure (day 24). Contrary to earlier belief, even maximal alterations in the plasma E2 to progesterone ratio fails to alter the endometrial morphology of either glands or stroma. More recently it has been recognized that E2 and progesterone also affect uterine contractility. It has been postulated that excessively high levels of E2 may increase uterine contractility and adversely affect implantation rates in in-vitro fertilization (IVF). Exogenous progesterone has been shown to exert utero-relaxing effects and it has been hypothesised that progesterone supplementation before embryo transfer (ET) may improve receptivity in IVF.

Androgens

Synchronization of endogenous and exogenous FSH stimuli in controlled ovarian hyperstimulation (COH).

We have previously observed that exogenous oestradiol can delay the intercycle increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH that follows discontinuation of exogenous oestradiol peaks after 3 days. We have now studied the possibility of using exogenous oestradiol to synchronize the increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG) treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged 35.1+/-6.3 years (mean+/-SD) undergoing ovarian stimulation received 2 mg of oestradiol valerate twice daily starting on day 25 of the previous menstrual cycle until the first Tuesday following menses. Ovarian stimulation was initiated 3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and luteinizing hormone (LH) (mean+/-SEM) were 566+/-53 (pmol/l), 3.8+/-0.4 (IU/l) and 5.5+/-0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean+/-SEM) had increased to 6.7+/-0.7 and 6.9+/-0.7 (IU/l) respectively while oestradiol decreased to 251+/-29 (pmol/l). The mean number (+/-SEM) of HMG ampoules used was 25.1+/-2.7 and treatment lasted 11.3+/-0.9 days. Five women became pregnant for a pregnancy rate (ongoing) of 19 (15)%. If all women aged >40 years (six women who did not become pregnant) were excluded from analysis the pregnancy rate (ongoing) was 24 (19%). These results indicate that exogenous oestradiol can safely be used for the synchronization of endogenous and exogenous FSH stimuli in COH. This approach provides the practical advantage of permitting an advanced timing of the onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are not used, which improves treatment convenience for patients and team members alike. Further development of this model may enable control of the onset of natural cycles which may find practical applications for timing assisted reproductive techniques (intrauterine insemination or in-vitro fertilization) in the natural cycle.

Adult

The first uterine pass effect.

The endometrial effects of vaginal progesterone have been found to be unexpectedly reliable. This has led us to suspect that a local direct vagina-to-uterus transport or first uterine pass effect was the basis of the uterine targeting of vaginal progesterone. After vaginal administration of progesterone, uterine tissue concentration has been found to exceed by more than 10-fold the levels achieved by systemic administration, despite plasma levels in the latter case that were more than seven times higher. Similar differences in systemic-to-uterine tissue level ratios have been observed between oral and vaginal administration of danazol. Originally seen as a pharmacological advantage permitting the uterine targeting of vaginally administered substances, it is possible that the first uterine pass effect plays a physiological role in the control of uterine contractile activity through the prostaglandins contained in the semen.

Administration, Intravaginal

Targeted drug delivery in gynaecology: the first uterine pass effect.

The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.

Administration, Intravaginal

Treatment strategies of the borderline ovarian tumors.

The present study was undertaken to establish the role of surgical procedures, histologic type, and stage of the tumor on the survival rate of patients with borderline ovarian tumors in a 5 to 15 years of follow-up. Data reported in the literature have shown the low malignancy of this cancer and that only the stage, but not the pathological diagnosis, is significantly influencing the survival rate of the patients. After 5 years, the survival rate of patients with tumors of stage I to stage II is 98.2% (n=567) and 81.4% (n=46), respectively, with no statistical difference. After 5 years, survival rate between tumors of stage I to stage III is 98.2% (n=567) and 79.1% (n=96), respectively (p< 0.05). The data shows that for borderline ovarian tumors, a minimally invasive surgery is warranted.

Female

The efficacy of drugs in the management of endometriosis.

STUDY OBJECTIVE: To establish the crude effects of danazol and gonadotropin-releasing hormone (GnRH) analogs in the management of endometriosis. DESIGN: Prospective case-control study. SETTING: Unit of the Pathophysiology of Reproduction outpatient department. PATIENTS: Two groups of 110 women each with endometriosis (American Fertility Society score 1-3) who received danazol and GnRH analogs, and a control group who did not receive any drugs. INTERVENTIONS: Women in the treatment groups received danazol 200 mg every 8 hours for 6 months, or a different GnRH agonist at standard dosages for 6 months. Laparoscopy was performed twice, at the time of diagnosis and just before the end of treatment (or no therapy for controls). Surgical treatment of the implants was performed at the second laparoscopy. MEASUREMENTS AND MAIN RESULTS: Samples of both eutopic and ectopic endometrium were collected during both laparoscopies. Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants, and there were no significant differences between the effects (p <0.001). Fibrosis was found after 6 months of observation in the implants in one control woman (0.9%), in 20 patients (18.2%) treated with danazol (p <0.001 vs controls), and in 4 patients (3.6%) treated with GnRH agonists (NS vs controls). A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28% of women, with poor agreement (k = 0.07). CONCLUSIONS: Fibrosis, which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium, did not appear in eutopic endometria but it was found in some endometriotic implants. Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis, but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable.

Adolescent

Adhesion formation after laparoscopic myomectomy.

STUDY OBJECTIVE: To determine the frequency of adhesion formation after myomectomy performed by operative laparoscopy or laparotomy. DESIGN: Case-control study. Setting. Academic women's hospital. PATIENTS: Thirty-two premenopausal women scheduled for myomectomy by one of two techniques. INTERVENTIONS: Surgical removal of myomata. MEASUREMENTS AND MAIN RESULTS: Of the 32 women, 16 underwent laparotomy and 16 laparoscopy. Second-look laparoscopy was performed in 28 patients, at which time adhesions were lysed. Compared with laparotomy, laparoscopy resulted in adhesions in significantly fewer patients, and in significantly lower scores when adhesions were detected. CONCLUSION: Laparoscopic removal of uterine myomata is associated with fewer adhesions than removal by laparotomy.

Adult

The Financial Impact of Laparoscopy versus Laparotomy in the Treatment of Uterine Leiomyomata

To compare the efficiency of two surgical techniques to remove uterine myomata, 120 premenopausal women were included in this case control study based on the criteria of no previous operations, size of leiomyoma, and age. Sixty patients were treated by laparoscopy (group 1) and 60 by laparotomy (group 2). The hospital stay for group 1 was shorter than that for group 2 (3.53 &plusmn; 1.33 and 7.98 &plusmn; 2.05 days, p <0.001). The rate of total complications (body temperature >38&deg; C, hemoglobin <8.5 g/100 ml, infiltration of abdominal sutures, dysuria, reduction in blood platelets) was 13% in group 1 versus 53% in group 2 (p <0.001). The mean cost for each surgical treatment was $628.71 and $652.40, respectively. The mean entire cost (surgery plus hospital stay) was $1357.23 and $2298.90, respectively (p <0.001). The savings were detectable after 9 and 52 operations, respectively, whether including all expenditures or only the cost of surgery. The cost saving of the entire treatment for 60 operations was $56,500.12.

Journal Article

Uterine Contractility in Patients with Endometriosis

Uterine contractility was evaluated in 30 women, 16 with endometriosis and 14 controls. Two catheters were introduced into the uterine cavity, one next to the fundus and the other in proximity of internal os. They were connected to a pressure transducer that transforms mechanical events into an electrical signal, and analyzed by a system dedicated to this purpose. Data were analyzed by unpaired Student's t and McNemar tests. Frequency and amplitude of oscillations and mean pressure uterine tone were evaluated. Frequency of oscillations in the fundus (mean &plusmn; SD) were significantly higher in women with endometriosis than in controls: 21.86 &plusmn; 9.75% at 10 minutes versus 10.20 &plusmn; 5.26%, respectively (p <0.04). The mean basal pressure tone was also higher than in controls: 55.54 &plusmn; 21.04 mm Hg and 25.28 &plusmn; 19.94 mm Hg, respectively (p <0.04). Abnormal uterine contractility in women with endometriosis may be associated with a possible tubal efflux of endometrial tissue and its ectopic implants.

Journal Article

Financial impact in the Italian Health Service of laparoscopic versus laparotomic surgery for the treatment of ovarian cysts.

To assess the cost of two procedures for the removal of ovarian cysts, 200 pre-menopausal women were recruited for the surgical removal of ovarian cysts by laparoscopy (n = 100) and laparotomy (n = 100) according to case-control criteria. Patients operated by laparoscopy (mean age +/- SD 32.22 +/- 9.98 years) and laparotomy (mean age +/- SD 29.57 +/- 6.62 years) for ovarian cysts (mean diameters +/- SD 4.98 +/- 3.62 and 4.83 +/- 2.78 cm) had a post-surgical hospital stay of 3.12 +/- 0.41 and 7.25 +/- 1.08 days (P < 0.001) respectively. The total rate of complications occurring in patients operated by laparoscopy was 9 versus 53% (P < 0.001) of those operated by laparotomy; body temperature > 38 degrees C was recorded in 52/100 of patients operated by laparotomy versus 6/100 of those operated by laparoscopy. The mean cost for each pure surgical treatment performed by laparoscopy was US $498.17 versus US $642.47 when it was performed by laparotomy (P < 0.001). The laparoscopic surgical approach is more expensive in the first 36 operations, thereafter becoming cheaper. The mean of the entire overall expenditure was US $1142.08 and US $2138.72 for laparoscopy and laparotomy (P < 0.001) respectively. The entire expenditure for laparoscopy is higher than laparotomy only until eight operations. In conclusion, laparoscopy versus laparotomy has resulted in a saving of US $14,429.3 for 100 operations while the saving on entire costs was US $99,664.8.

Adult

Transforming growth factor-beta 1 in the human endometrium.

Transforming growth factor-beta 1 (TGF-beta 1) is a polypeptide involved in a variety of important physiological and pathophysiological processes such as the implantation of the embryo into the endometrium. Many factors seem to be related to this event. TGF-beta 1 is involved in many mechanisms both in endometrial and in embryonic tissues: it induces proliferation and differentiation, it regulates proteolytic activity and it modulates the maternal immune response. This study evaluated the presence of TGF-beta 1 in the endometrium during normal menstrual cycles and in the uterine fluids during induction of ovulation in the framework of an in vitro fertilization program. Immunohistochemistry was used to identify TGF-beta 1 in the endometrium and immunodot-blot to quantitate TGF-beta 1 in the uterine cavity fluid. The study shows that TGF-beta 1 is present in the endometrial tissue and its secretion is modulated during the menstrual cycle, as demonstrated immunohistochemically; its production seems to be controlled by ovarian steroids. In conclusion, TGF-beta 1 influences the growth and differentiation of the embryo, as well as the activation of embryonic proteolytic enzymes, and it modulates the maternal-embryonic immune response. Its variability in the uterine cavity is demonstrated in this study, and the underexpression of TGF-beta 1 in the uterine cavity might be responsible for failed implantation.

Cytoplasm

Dysfunctional uterine bleeding (DUB).

Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB.

Adult