Massimiliano Farina - Academia.edu (original) (raw)

Papers by Massimiliano Farina

Research paper thumbnail of Alteration in the pulsatility index values of the internal carotid and middle cerebral arteries after suspension of postmenopausal hormone replacement therapy: A randomized crossover study

American Journal of Obstetrics and Gynecology, 1996

The aim of the study was to investigate the effect of the suspension of hormone replacement thera... more The aim of the study was to investigate the effect of the suspension of hormone replacement therapy on blood flow in the internal carotid and the middle cerebral arteries. Doppler ultrasonography was used to measure the pulsatility index of the internal carotid and middle cerebral arteries of 23 women. The patients were all receiving continuous transdermal estradiol replacement therapy (50 micrograms/day) with a cyclic supplementation of medroxyprogesterone acetate every second month (10 mg/day for 12 days). The duration of the study was 12 months. The patients were randomly assigned to one of two groups. The first group (11 subjects) continued therapy for the first 6 months and then suspended it for the following 6 months; the second group (12 subjects) interrupted hormone replacement therapy for the first 6 months and then resumed it for the following 6 months. The internal carotid and middle cerebral artery pulsatility index was measured at the start of the 12-month period and then every 3 months. Serum estradiol levels were measured to check compliance. A statistically significant difference was found between the internal carotid and middle cerebral artery pulsatility index values of the two groups at each of the measurements after the first one. Over the first 6 months the pulsatility index values rapidly increased in the patients kept off hormone replacement therapy and remained stable in those receiving hormone replacement therapy. After the crossover at 8 months, the pulsatility index rapidly dropped to values similar to those at baseline in the patients who resumed hormone replacement therapy and increased in those who suspended therapy. Resistance to blood flow in cerebral vessels of postmenopausal women rapidly changes after hormone replacement therapy suspension. In postmenopausal women estrogen administration should be continued to maintain the favourable variations of vascular reactivity induced by hormone replacement therapy.

Research paper thumbnail of Blood Flows in Cerebral Arteries After Suspension of Postmenopausal Hormone Replacement Therapy. A Randomized Crossover Study

Medical Science Symposia Series, 1997

Research paper thumbnail of New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

Neuro – Open Journal, 2017

Background: The pathophysiological mechanism defined "chronic cerebrospinal venous insufficiency"... more Background: The pathophysiological mechanism defined "chronic cerebrospinal venous insufficiency" (CCSVI) diagnosed using Zamboni criteria has raised a heated debate about possible correlations with several neurological disorders, but also on subjectivity of these ultrasonographic criteria used for its diagnosis. Although in 2011 new criteria have been introduced to reduce the high inter-observer variability only two studies were conducted according to the new investigation protocol. Therefore, we wanted to verify the impact of the revised protocol and its ability to meet the demand for reduction of the high heterogeneity in inter-observer agreement. Patients and Methods: Between June 2010 and June 2014, 1020 subjects (693 MS patients and 327 HCs) were prospectively screened for CCSVI by two investigators, blinded regarding the observed subject. After exclusion of discordant cases between the two examiners, 630 patients with clinically defined MS and 10 patients with CIS (clinically isolated syndrome) were matched by gender (male 38.7%, male/female 248/392) and age (mean age 44.0 years, range 18.5-77.0 years) with 315 HCs (male 43.2%, male/female 136/179-mean age 46.5 years, range 19.8-79.9 years). Results: The prevalence of CCSVI in MS subjects before the introduction of the new ECD criteria (94.3%) was observed to be significantly reduced (83.4%) after their introduction (p<0.001). In MS patients, the strength of inter-observer agreement changed from moderate (k=0.532) to good (k=0.761) before/after the revision. B-mode analysis detected only 65.7% of valvular defects. Its diagnostic accuracy was 88.6% (95% CI: 84.0%-93.2%), with a sensitivity of 83.5% (95% CI: 75.2%-89.9%), a specificity of 96.0% (95% CI: 88.8%-99.2%), a positive predictive value of 96.8% (95% CI: 91.0%-99.3%) and a negative predictive value of 80.0% (95% CI: 70.3%-87.7%). Conclusions: The new ECD criteria introduced by the revised protocol ensure, at this time, a substantial reduction of the inter-observer variability. Under this perspective, M-mode analysis is essential for its ability to identify the valvular abnormalities frequently not detectable by Bmode analysis.

Research paper thumbnail of Long-term Effects of Postmenopausal Hormone Replacement Therapy on Pulsatility Index of Internal Carotid and Middle Cerebral Arteries

Menopause, 1997

ABSTRACT The authors studied the long-term effects of hormone replacement therapy (HRT) on vascul... more ABSTRACT The authors studied the long-term effects of hormone replacement therapy (HRT) on vascular resistance of internal carotid artery (ICA) and middle cerebral artery (MCA) in postmenopausal women. Twenty-five postmenopausal women participated in this 1-year, single-center, open study. Subjects received continuous estradiol 50 mu g/day via transdermal route (Estraderm TTS 50, Ciba-Geigy) with oral medroxyprogesterone acetate 10 mg/day for 12 days every second month. Subjects, who had been studied previously at baseline and at 6, 8, 22, and 24 weeks, were followed up 48 weeks after the start of treatment, Vascular resistance of ICA and MCA was assessed by pulsatility index (PI) measured by bidirectional Doppler ultrasonography. The significant reduction of PI from baseline, which had been observed by 6 weeks of treatment for both ICA and MCA, reached a maximum at approximately 22 weeks of treatment (25.3% and 24.5% reduction from baseline for ICA and MCA, respectively; p = 0.0001). Pulsatility index reductions reached after 24 weeks of treatment were maintained to 48 weeks both for MCA and ICA. Results demonstrate that in postmenopausal women, the rapid reduction of vascular resistance in ICA and MCA induced by estradiol is long-lasting.

Research paper thumbnail of RESEARCH ARTICLE Open Access Chronic cerebrospinal venous insufficiency in

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be a... more Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method: We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

Research paper thumbnail of Case Report Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

Copyright © 2015 Massimiliano Farina et al. This is an open access article distributed under the ... more Copyright © 2015 Massimiliano Farina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascular-ization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors ’ aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler...

Research paper thumbnail of Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

BMC Neurology, 2011

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be a... more Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated.

Method: We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al.

Results: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking
being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS.

Conclusion: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MSphenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower
susceptibility to autoimmune diseases and may increase its severity.

Research paper thumbnail of Nédemax® Mese (Leucoselect®, Lymphaselect®, Bromelain) in the treatment of chronic venous disease: a multicenter, observational study

Research paper thumbnail of Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy

American Journal of Obstetrics and Gynecology, 1993

primarily a result of marked hypersecretion of estradiol. Second, a literature search failed to r... more primarily a result of marked hypersecretion of estradiol. Second, a literature search failed to reveal any report of polycystic ovarian disease that resulted in such a massive secretion of estradiol as to mimic an estrogenproducing tumor. The occurrence of this case also suggests that polycystic ovarian disease should be included in the differential diagnosis of estrogen-producing neoplasms, in spite of its being a very rare cause of such excessive estradiol production. November 1993 Am J Obstet Gynecol We thank Laura Molho, MD, for the pathology reports and for preparing the photomicrographs.

Research paper thumbnail of New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study Citation

Background: The pathophysiological mechanism defined " chronic cerebrospinal venous insuf-ficienc... more Background: The pathophysiological mechanism defined " chronic cerebrospinal venous insuf-ficiency " (CCSVI) diagnosed using Zamboni criteria has raised a heated debate about possible correlations with several neurological disorders, but also on subjectivity of these ultrasono-graphic criteria used for its diagnosis. Although in 2011 new criteria have been introduced to reduce the high inter-observer variability only two studies were conducted according to the new investigation protocol. Therefore, we wanted to verify the impact of the revised protocol and its ability to meet the demand for reduction of the high heterogeneity in inter-observer agreement. Patients and Methods: Between June 2010 and June 2014, 1020 subjects (693 MS patients and 327 HCs) were prospectively screened for CCSVI by two investigators, blinded regarding the observed subject. After exclusion of discordant cases between the two examiners, 630 patients with clinically defined MS and 10 patients with CIS (clinically isolated syndrome) were matched by gender (male 38.7%, male/female 248/392) and age (mean age 44.0 years, range 18.5-77.0 years) with 315 HCs (male 43.2%, male/female 136/179-mean age 46.5 years, range 19.8-79.9 years). Results: The prevalence of CCSVI in MS subjects before the introduction of the new ECD criteria (94.3%) was observed to be significantly reduced (83.4%) after their introduction (p<0.001). In MS patients, the strength of inter-observer agreement changed from moderate (k=0.532) to good (k=0.761) before/after the revision. B-mode analysis detected only 65.7% of valvular defects. Its diagnostic accuracy was 88.6% (95% CI: 84.0%-93.2%), with a sensitivity of 83.5% (95% CI: 75.2%-89.9%), a specificity of 96.0% (95% CI: 88.8%-99.2%), a positive predictive value of 96.8% (95% CI: 91.0%-99.3%) and a negative predictive value of 80.0% (95% CI: 70.3%-87.7%). Conclusions: The new ECD criteria introduced by the revised protocol ensure, at this time, a substantial reduction of the inter-observer variability. Under this perspective, M-mode analysis is essential for its ability to identify the valvular abnormalities frequently not detectable by B-mode analysis.

Research paper thumbnail of Combined Ultrasound Technologies and Optimized Probe Design for Neck Veins Examination

Biomedical Engineering / 765: Telehealth / 766: Assistive Technologies, 2012

ABSTRACT Neck veins ultrasound (US) examination has reached a relevant level of attention due to ... more ABSTRACT Neck veins ultrasound (US) examination has reached a relevant level of attention due to the definition of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and due to various studies on different neurological disorders. Echo-Color Doppler (ECD) technology is a reliable diagnostic technique for Internal Jugular Vein (IJV) and Vertebral Vein (VV) examination. The present study considers the combination of different real-time US imaging and Doppler methods as well as a proper ultrasonic transducer design for the optimization of cervical vein scanning. Increased B-Mode diagnostic confidence and more sensitive and reliable hemodynamic analysis of the cervical venous system are shown and analyzed.

Research paper thumbnail of Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

Case Reports in Ophthalmological Medicine, 2015

To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the develo... more To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascularization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler study of the neck veins, performed in November 2014, showed an atypical left jugular insufficiency associated with homolateral hypertension of the superior ophthalmic veins. This singular case highlights the necessity to further investigate the potential role of chronic alterations of intra- and extracranial venous drainage in the disruption of choroidal flow in myopic patients.

Research paper thumbnail of Assessment of jugular endovascular malformations in chronic cerebrospinal venous insufficiency: colour-Doppler scanning and catheter venography compared with intravascular ultrasound

Objectives: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition charac... more Objectives: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition characterized by several anomalies of the azygos and/or internal jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour-Doppler (CD) sonography. Though catheter venography (CV) is considered as the gold standard for determining vascular anatomy, its uniplanar point of view does not allow an overall evaluation of endoluminal structures. This limit could be addressed by intravascular ultrasound (IVUS). The aim of this report is to evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography and CV versus IVUS in estimating the diameter and the crosssectional area (CSA) of the IJVs and in detecting jugular endoluminal malformations (JEM). Method: Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS. The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were compared with IVUS data with the Bland -Altman method. Results: The mean difference in IJV MAXD recorded by CD and IVUS was 20.5 mm. The mean difference in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA recorded by CD and IVUS was 211.2 mm 2 . JEM recorded by IVUS were detected by CD sonography and CV with 88% and 32% accuracy, respectively. Conclusions: CV was significantly inferior to CD sonography and IVUS in detecting JEM. Differences between IVUS and CD sonography in detecting JEM and in quantifying jugular diameters were not significant. The IJV CSA was underestimated by CD sonography compared with IVUS. CD sonography was proven to be important in the anatomical characterization of CCSVI, providing useful information for correct intravascular treatment.

Research paper thumbnail of Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation

BMC Neurology, 2013

Background: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using e... more Background: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs).

Research paper thumbnail of Venous Hemodynamic Insufficiency Severity Score variation after endovascular treatment of chronic cerebrospinal venous insufficiency

Phlebology: The Journal of Venous Disease, 2014

Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characte... more Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the internal jugular veins (IJVs) and/or azygos veins with disturbed flow and formation of collateral venous channels. The presence of CCSVI has been associated with multiple sclerosis (MS). Percutaneous venous angioplasty (PVA) has been proposed to improve extracranial outflow; however, a non-invasive, post-procedural follow-up outcome measure has not been established. Aim of the study: To evaluate the short-term hemodynamic follow-up of CCSVI after PVA using color Doppler ultrasound (CDU) and to investigate whether hemodynamic variation correlated with clinical variation. Materials and methods: Forty-five patients affected by MS with confirmed CCSVI underwent IJVs PVA. Venous hemodynamic (VH) parameters indicative of CCSVI and the Venous Hemodynamic Insufficiency Severity Score (VHISS) were evaluated by CDU at baseline and 3 months post-PVA. Concurrently, the MS-related disability status (EDSS) was evaluated. Results: The VH parameters and VHISS 3 months after IJVs PVA significantly decreased: the VH parameters À32.1% and the VHISS À33.8% (p < 0.001). The EDSS score 3 months after IJVs PVA was significantly lower than the baseline (À5.5%, p < 0.001). Using the median value of the VHISS variation as the cut-off, we were able to identify two groups of patients: responders, group A; and non-responders, group B. The EDSS score variation at 3 months was 0.310 in group A and 0.275 in group B (p ¼ 0.746). Conclusions: CCSVI endovascular treatment can induce an improvement in VH parameters and the VHISS. The neurological disability score (EDSS) also improved after PVA; however, there was no correlation to the VHISS variation after PVA, MS type and duration. Phlebology 0(0) 1-7

Research paper thumbnail of Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis

Fertility and Sterility, 2003

Objective: There is growing evidence that suggests a direct action of gonadotropin-releasing horm... more Objective: There is growing evidence that suggests a direct action of gonadotropin-releasing hormone agonist (GnRH-a) on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on in vitro eutopic endometrial cell growth and apoptosis. Design: Prospective study. Setting: Research institute and clinical fertility center. Patient(s): Sixteen women with untreated endometriosis and 14 controls. Intervention(s): Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both. Main Outcome Measure(s): The percentage of apoptotic cells was evaluated by the acridine orangeethidium bromide technique; cell proliferation was assessed by 3 H-thymidine incorporation. Result(s): Leuprolide acetate (LA) (100 ng/mL) enhanced apoptosis in endometrial cultures from patients with endometriosis and controls, and this effect was reversed by antide 10 Ϫ7 M. Cell proliferation was down-regulated by LA at 1, 10, and 100 ng/mL in cultures from women without and with endometriosis. The addition of antide 10 Ϫ7 M reversed this inhibition. Conclusion(s): GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells. (Fertil Steril 2003;80(Suppl 2):702-7.

Research paper thumbnail of Cerebral artery blood flow in relation to age and menopausal status

Obstetrics and gynecology, 1996

To investigate vascular reactivity in women's cerebral arteries from reproductive age to post... more To investigate vascular reactivity in women's cerebral arteries from reproductive age to postmenopause. The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20-59 years. In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Menopause causes a significant increase in the PI of women's cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and...

Research paper thumbnail of The effect of tamoxifen and transdermal 17β-estradiol on cerebral arterial vessels: A randomized controlled study

American Journal of Obstetrics and Gynecology, 1998

Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN... more Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN: We studied the reactivity of both the internal carotid artery and the middle cerebral artery during a 12-month period of administration of either oral tamoxifen or transdermal estradiol or no treatment. A total of 45 healthy postmenopausal women who had undergone hysterectomy were followed up. Patients were randomly allocated to treatment with either oral tamoxifen 20 mg/day or transdermal estradiol 50 µg/day or nothing (15 patients in each group). They all underwent Doppler examinations of the internal carotid artery and middle cerebral artery at the beginning of the study and after 2, 6, and 12 months of treatment. The pulsatility index was measured. RESULTS: In the women given transdermal estradiol the pulsatility index of both the internal carotid artery and the middle cerebral artery was significantly reduced compared with that in the controls. Tamoxifen did not induce variations of pulsatility index in either artery during all the study period. The difference between the effect of the two drugs on the pulsatility index of both arteries was highly significant. CONCLUSIONS: Our findings demonstrate that tamoxifen does not cause any variation in the pulsatility index of cerebral arteries. The action of transdermal estradiol on the pulsatility index of cerebral arteries in postmenopausal women is the expression of a generalized action of estrogens on arterial vessels, and if this expression plays a role in the protective effect of hormone replacement therapy on risk of cardiovascular disease, tamoxifen treatment in healthy postmenopausal women should be considered with renewed caution. Am J Obstet Gynecol 1998;178:801-5.)

Research paper thumbnail of Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries

Fertility and Sterility

To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebra... more To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. Open, controlled study. Tertiary care units of the University of Milan, Italy. Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. The ICA and MCA pulsatility index. No variation in the pulsatility index of either artery was found in either group. A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of y...

Research paper thumbnail of Cerebral artery blood flow in relation to age and menopausal status

Obstetrics and gynecology, 1996

To investigate vascular reactivity in women's cerebral arteries from reproductive age to post... more To investigate vascular reactivity in women's cerebral arteries from reproductive age to postmenopause. The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20-59 years. In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Menopause causes a significant increase in the PI of women's cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and...

Research paper thumbnail of Alteration in the pulsatility index values of the internal carotid and middle cerebral arteries after suspension of postmenopausal hormone replacement therapy: A randomized crossover study

American Journal of Obstetrics and Gynecology, 1996

The aim of the study was to investigate the effect of the suspension of hormone replacement thera... more The aim of the study was to investigate the effect of the suspension of hormone replacement therapy on blood flow in the internal carotid and the middle cerebral arteries. Doppler ultrasonography was used to measure the pulsatility index of the internal carotid and middle cerebral arteries of 23 women. The patients were all receiving continuous transdermal estradiol replacement therapy (50 micrograms/day) with a cyclic supplementation of medroxyprogesterone acetate every second month (10 mg/day for 12 days). The duration of the study was 12 months. The patients were randomly assigned to one of two groups. The first group (11 subjects) continued therapy for the first 6 months and then suspended it for the following 6 months; the second group (12 subjects) interrupted hormone replacement therapy for the first 6 months and then resumed it for the following 6 months. The internal carotid and middle cerebral artery pulsatility index was measured at the start of the 12-month period and then every 3 months. Serum estradiol levels were measured to check compliance. A statistically significant difference was found between the internal carotid and middle cerebral artery pulsatility index values of the two groups at each of the measurements after the first one. Over the first 6 months the pulsatility index values rapidly increased in the patients kept off hormone replacement therapy and remained stable in those receiving hormone replacement therapy. After the crossover at 8 months, the pulsatility index rapidly dropped to values similar to those at baseline in the patients who resumed hormone replacement therapy and increased in those who suspended therapy. Resistance to blood flow in cerebral vessels of postmenopausal women rapidly changes after hormone replacement therapy suspension. In postmenopausal women estrogen administration should be continued to maintain the favourable variations of vascular reactivity induced by hormone replacement therapy.

Research paper thumbnail of Blood Flows in Cerebral Arteries After Suspension of Postmenopausal Hormone Replacement Therapy. A Randomized Crossover Study

Medical Science Symposia Series, 1997

Research paper thumbnail of New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

Neuro – Open Journal, 2017

Background: The pathophysiological mechanism defined "chronic cerebrospinal venous insufficiency"... more Background: The pathophysiological mechanism defined "chronic cerebrospinal venous insufficiency" (CCSVI) diagnosed using Zamboni criteria has raised a heated debate about possible correlations with several neurological disorders, but also on subjectivity of these ultrasonographic criteria used for its diagnosis. Although in 2011 new criteria have been introduced to reduce the high inter-observer variability only two studies were conducted according to the new investigation protocol. Therefore, we wanted to verify the impact of the revised protocol and its ability to meet the demand for reduction of the high heterogeneity in inter-observer agreement. Patients and Methods: Between June 2010 and June 2014, 1020 subjects (693 MS patients and 327 HCs) were prospectively screened for CCSVI by two investigators, blinded regarding the observed subject. After exclusion of discordant cases between the two examiners, 630 patients with clinically defined MS and 10 patients with CIS (clinically isolated syndrome) were matched by gender (male 38.7%, male/female 248/392) and age (mean age 44.0 years, range 18.5-77.0 years) with 315 HCs (male 43.2%, male/female 136/179-mean age 46.5 years, range 19.8-79.9 years). Results: The prevalence of CCSVI in MS subjects before the introduction of the new ECD criteria (94.3%) was observed to be significantly reduced (83.4%) after their introduction (p<0.001). In MS patients, the strength of inter-observer agreement changed from moderate (k=0.532) to good (k=0.761) before/after the revision. B-mode analysis detected only 65.7% of valvular defects. Its diagnostic accuracy was 88.6% (95% CI: 84.0%-93.2%), with a sensitivity of 83.5% (95% CI: 75.2%-89.9%), a specificity of 96.0% (95% CI: 88.8%-99.2%), a positive predictive value of 96.8% (95% CI: 91.0%-99.3%) and a negative predictive value of 80.0% (95% CI: 70.3%-87.7%). Conclusions: The new ECD criteria introduced by the revised protocol ensure, at this time, a substantial reduction of the inter-observer variability. Under this perspective, M-mode analysis is essential for its ability to identify the valvular abnormalities frequently not detectable by Bmode analysis.

Research paper thumbnail of Long-term Effects of Postmenopausal Hormone Replacement Therapy on Pulsatility Index of Internal Carotid and Middle Cerebral Arteries

Menopause, 1997

ABSTRACT The authors studied the long-term effects of hormone replacement therapy (HRT) on vascul... more ABSTRACT The authors studied the long-term effects of hormone replacement therapy (HRT) on vascular resistance of internal carotid artery (ICA) and middle cerebral artery (MCA) in postmenopausal women. Twenty-five postmenopausal women participated in this 1-year, single-center, open study. Subjects received continuous estradiol 50 mu g/day via transdermal route (Estraderm TTS 50, Ciba-Geigy) with oral medroxyprogesterone acetate 10 mg/day for 12 days every second month. Subjects, who had been studied previously at baseline and at 6, 8, 22, and 24 weeks, were followed up 48 weeks after the start of treatment, Vascular resistance of ICA and MCA was assessed by pulsatility index (PI) measured by bidirectional Doppler ultrasonography. The significant reduction of PI from baseline, which had been observed by 6 weeks of treatment for both ICA and MCA, reached a maximum at approximately 22 weeks of treatment (25.3% and 24.5% reduction from baseline for ICA and MCA, respectively; p = 0.0001). Pulsatility index reductions reached after 24 weeks of treatment were maintained to 48 weeks both for MCA and ICA. Results demonstrate that in postmenopausal women, the rapid reduction of vascular resistance in ICA and MCA induced by estradiol is long-lasting.

Research paper thumbnail of RESEARCH ARTICLE Open Access Chronic cerebrospinal venous insufficiency in

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be a... more Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method: We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

Research paper thumbnail of Case Report Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

Copyright © 2015 Massimiliano Farina et al. This is an open access article distributed under the ... more Copyright © 2015 Massimiliano Farina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascular-ization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors ’ aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler...

Research paper thumbnail of Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

BMC Neurology, 2011

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be a... more Background: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated.

Method: We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al.

Results: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking
being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS.

Conclusion: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MSphenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower
susceptibility to autoimmune diseases and may increase its severity.

Research paper thumbnail of Nédemax® Mese (Leucoselect®, Lymphaselect®, Bromelain) in the treatment of chronic venous disease: a multicenter, observational study

Research paper thumbnail of Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy

American Journal of Obstetrics and Gynecology, 1993

primarily a result of marked hypersecretion of estradiol. Second, a literature search failed to r... more primarily a result of marked hypersecretion of estradiol. Second, a literature search failed to reveal any report of polycystic ovarian disease that resulted in such a massive secretion of estradiol as to mimic an estrogenproducing tumor. The occurrence of this case also suggests that polycystic ovarian disease should be included in the differential diagnosis of estrogen-producing neoplasms, in spite of its being a very rare cause of such excessive estradiol production. November 1993 Am J Obstet Gynecol We thank Laura Molho, MD, for the pathology reports and for preparing the photomicrographs.

Research paper thumbnail of New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study Citation

Background: The pathophysiological mechanism defined " chronic cerebrospinal venous insuf-ficienc... more Background: The pathophysiological mechanism defined " chronic cerebrospinal venous insuf-ficiency " (CCSVI) diagnosed using Zamboni criteria has raised a heated debate about possible correlations with several neurological disorders, but also on subjectivity of these ultrasono-graphic criteria used for its diagnosis. Although in 2011 new criteria have been introduced to reduce the high inter-observer variability only two studies were conducted according to the new investigation protocol. Therefore, we wanted to verify the impact of the revised protocol and its ability to meet the demand for reduction of the high heterogeneity in inter-observer agreement. Patients and Methods: Between June 2010 and June 2014, 1020 subjects (693 MS patients and 327 HCs) were prospectively screened for CCSVI by two investigators, blinded regarding the observed subject. After exclusion of discordant cases between the two examiners, 630 patients with clinically defined MS and 10 patients with CIS (clinically isolated syndrome) were matched by gender (male 38.7%, male/female 248/392) and age (mean age 44.0 years, range 18.5-77.0 years) with 315 HCs (male 43.2%, male/female 136/179-mean age 46.5 years, range 19.8-79.9 years). Results: The prevalence of CCSVI in MS subjects before the introduction of the new ECD criteria (94.3%) was observed to be significantly reduced (83.4%) after their introduction (p<0.001). In MS patients, the strength of inter-observer agreement changed from moderate (k=0.532) to good (k=0.761) before/after the revision. B-mode analysis detected only 65.7% of valvular defects. Its diagnostic accuracy was 88.6% (95% CI: 84.0%-93.2%), with a sensitivity of 83.5% (95% CI: 75.2%-89.9%), a specificity of 96.0% (95% CI: 88.8%-99.2%), a positive predictive value of 96.8% (95% CI: 91.0%-99.3%) and a negative predictive value of 80.0% (95% CI: 70.3%-87.7%). Conclusions: The new ECD criteria introduced by the revised protocol ensure, at this time, a substantial reduction of the inter-observer variability. Under this perspective, M-mode analysis is essential for its ability to identify the valvular abnormalities frequently not detectable by B-mode analysis.

Research paper thumbnail of Combined Ultrasound Technologies and Optimized Probe Design for Neck Veins Examination

Biomedical Engineering / 765: Telehealth / 766: Assistive Technologies, 2012

ABSTRACT Neck veins ultrasound (US) examination has reached a relevant level of attention due to ... more ABSTRACT Neck veins ultrasound (US) examination has reached a relevant level of attention due to the definition of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and due to various studies on different neurological disorders. Echo-Color Doppler (ECD) technology is a reliable diagnostic technique for Internal Jugular Vein (IJV) and Vertebral Vein (VV) examination. The present study considers the combination of different real-time US imaging and Doppler methods as well as a proper ultrasonic transducer design for the optimization of cervical vein scanning. Increased B-Mode diagnostic confidence and more sensitive and reliable hemodynamic analysis of the cervical venous system are shown and analyzed.

Research paper thumbnail of Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

Case Reports in Ophthalmological Medicine, 2015

To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the develo... more To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascularization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler study of the neck veins, performed in November 2014, showed an atypical left jugular insufficiency associated with homolateral hypertension of the superior ophthalmic veins. This singular case highlights the necessity to further investigate the potential role of chronic alterations of intra- and extracranial venous drainage in the disruption of choroidal flow in myopic patients.

Research paper thumbnail of Assessment of jugular endovascular malformations in chronic cerebrospinal venous insufficiency: colour-Doppler scanning and catheter venography compared with intravascular ultrasound

Objectives: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition charac... more Objectives: Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition characterized by several anomalies of the azygos and/or internal jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour-Doppler (CD) sonography. Though catheter venography (CV) is considered as the gold standard for determining vascular anatomy, its uniplanar point of view does not allow an overall evaluation of endoluminal structures. This limit could be addressed by intravascular ultrasound (IVUS). The aim of this report is to evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography and CV versus IVUS in estimating the diameter and the crosssectional area (CSA) of the IJVs and in detecting jugular endoluminal malformations (JEM). Method: Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS. The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were compared with IVUS data with the Bland -Altman method. Results: The mean difference in IJV MAXD recorded by CD and IVUS was 20.5 mm. The mean difference in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA recorded by CD and IVUS was 211.2 mm 2 . JEM recorded by IVUS were detected by CD sonography and CV with 88% and 32% accuracy, respectively. Conclusions: CV was significantly inferior to CD sonography and IVUS in detecting JEM. Differences between IVUS and CD sonography in detecting JEM and in quantifying jugular diameters were not significant. The IJV CSA was underestimated by CD sonography compared with IVUS. CD sonography was proven to be important in the anatomical characterization of CCSVI, providing useful information for correct intravascular treatment.

Research paper thumbnail of Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation

BMC Neurology, 2013

Background: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using e... more Background: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs).

Research paper thumbnail of Venous Hemodynamic Insufficiency Severity Score variation after endovascular treatment of chronic cerebrospinal venous insufficiency

Phlebology: The Journal of Venous Disease, 2014

Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characte... more Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the internal jugular veins (IJVs) and/or azygos veins with disturbed flow and formation of collateral venous channels. The presence of CCSVI has been associated with multiple sclerosis (MS). Percutaneous venous angioplasty (PVA) has been proposed to improve extracranial outflow; however, a non-invasive, post-procedural follow-up outcome measure has not been established. Aim of the study: To evaluate the short-term hemodynamic follow-up of CCSVI after PVA using color Doppler ultrasound (CDU) and to investigate whether hemodynamic variation correlated with clinical variation. Materials and methods: Forty-five patients affected by MS with confirmed CCSVI underwent IJVs PVA. Venous hemodynamic (VH) parameters indicative of CCSVI and the Venous Hemodynamic Insufficiency Severity Score (VHISS) were evaluated by CDU at baseline and 3 months post-PVA. Concurrently, the MS-related disability status (EDSS) was evaluated. Results: The VH parameters and VHISS 3 months after IJVs PVA significantly decreased: the VH parameters À32.1% and the VHISS À33.8% (p < 0.001). The EDSS score 3 months after IJVs PVA was significantly lower than the baseline (À5.5%, p < 0.001). Using the median value of the VHISS variation as the cut-off, we were able to identify two groups of patients: responders, group A; and non-responders, group B. The EDSS score variation at 3 months was 0.310 in group A and 0.275 in group B (p ¼ 0.746). Conclusions: CCSVI endovascular treatment can induce an improvement in VH parameters and the VHISS. The neurological disability score (EDSS) also improved after PVA; however, there was no correlation to the VHISS variation after PVA, MS type and duration. Phlebology 0(0) 1-7

Research paper thumbnail of Gonadotropin-releasing hormone agonist induces apoptosis and reduces cell proliferation in eutopic endometrial cultures from women with endometriosis

Fertility and Sterility, 2003

Objective: There is growing evidence that suggests a direct action of gonadotropin-releasing horm... more Objective: There is growing evidence that suggests a direct action of gonadotropin-releasing hormone agonist (GnRH-a) on endometrial growth. Consequently, our purpose was to evaluate the effect of GnRH-a on in vitro eutopic endometrial cell growth and apoptosis. Design: Prospective study. Setting: Research institute and clinical fertility center. Patient(s): Sixteen women with untreated endometriosis and 14 controls. Intervention(s): Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA), antide, and a combination of both. Main Outcome Measure(s): The percentage of apoptotic cells was evaluated by the acridine orangeethidium bromide technique; cell proliferation was assessed by 3 H-thymidine incorporation. Result(s): Leuprolide acetate (LA) (100 ng/mL) enhanced apoptosis in endometrial cultures from patients with endometriosis and controls, and this effect was reversed by antide 10 Ϫ7 M. Cell proliferation was down-regulated by LA at 1, 10, and 100 ng/mL in cultures from women without and with endometriosis. The addition of antide 10 Ϫ7 M reversed this inhibition. Conclusion(s): GnRH-a appears to have a direct effect by enhancing the apoptotic index and decreasing the cell proliferation in endometrial cells. (Fertil Steril 2003;80(Suppl 2):702-7.

Research paper thumbnail of Cerebral artery blood flow in relation to age and menopausal status

Obstetrics and gynecology, 1996

To investigate vascular reactivity in women's cerebral arteries from reproductive age to post... more To investigate vascular reactivity in women's cerebral arteries from reproductive age to postmenopause. The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20-59 years. In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Menopause causes a significant increase in the PI of women's cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and...

Research paper thumbnail of The effect of tamoxifen and transdermal 17β-estradiol on cerebral arterial vessels: A randomized controlled study

American Journal of Obstetrics and Gynecology, 1998

Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN... more Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN: We studied the reactivity of both the internal carotid artery and the middle cerebral artery during a 12-month period of administration of either oral tamoxifen or transdermal estradiol or no treatment. A total of 45 healthy postmenopausal women who had undergone hysterectomy were followed up. Patients were randomly allocated to treatment with either oral tamoxifen 20 mg/day or transdermal estradiol 50 µg/day or nothing (15 patients in each group). They all underwent Doppler examinations of the internal carotid artery and middle cerebral artery at the beginning of the study and after 2, 6, and 12 months of treatment. The pulsatility index was measured. RESULTS: In the women given transdermal estradiol the pulsatility index of both the internal carotid artery and the middle cerebral artery was significantly reduced compared with that in the controls. Tamoxifen did not induce variations of pulsatility index in either artery during all the study period. The difference between the effect of the two drugs on the pulsatility index of both arteries was highly significant. CONCLUSIONS: Our findings demonstrate that tamoxifen does not cause any variation in the pulsatility index of cerebral arteries. The action of transdermal estradiol on the pulsatility index of cerebral arteries in postmenopausal women is the expression of a generalized action of estrogens on arterial vessels, and if this expression plays a role in the protective effect of hormone replacement therapy on risk of cardiovascular disease, tamoxifen treatment in healthy postmenopausal women should be considered with renewed caution. Am J Obstet Gynecol 1998;178:801-5.)

Research paper thumbnail of Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries

Fertility and Sterility

To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebra... more To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. Open, controlled study. Tertiary care units of the University of Milan, Italy. Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. The ICA and MCA pulsatility index. No variation in the pulsatility index of either artery was found in either group. A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of y...

Research paper thumbnail of Cerebral artery blood flow in relation to age and menopausal status

Obstetrics and gynecology, 1996

To investigate vascular reactivity in women's cerebral arteries from reproductive age to post... more To investigate vascular reactivity in women's cerebral arteries from reproductive age to postmenopause. The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20-59 years. In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Menopause causes a significant increase in the PI of women's cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and...