Biomedical subjects

A Cagnacci

Publications and source records attributed to A Cagnacci.

At least 19 recordsLinked to original sources

PubMed2001

Course of primary headaches during hormone replacement therapy.

OBJECTIVE: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. METHODS: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001). CONCLUSIONS: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.

Administration, Cutaneous↗

PubMed2001

Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy.

OBJECTIVE: Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated. DESIGN: Randomised, double-blind placebo controlled study. PATIENTS: Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). MEASUREMENTS: Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin. RESULTS: In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024). CONCLUSIONS: The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.

Analysis of Variance↗

PubMed2001

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women.

OBJECTIVE: The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women. PATIENTS: Twenty-two postmenopausal women of whom 14 were on hormone replacement therapy. DESIGN: After an overnight fast, at 0800 hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered randomly and in a double blind fashion. Forty-five minutes later, an oral glucose tolerance test (75 g; OGTT) was performed in 13 women. In another nine women insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Areas under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55 mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779 pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si modifications induced by melatonin were inversely related to Si values of the placebo day (r(2) = 0.538; P < 0.025). CONCLUSIONS: The present results indicate that in aged women administration of 1 mg of melatonin reduces glucose tolerance and insulin sensitivity. The present data may have both physiological and clinical implications.

Analysis of Variance↗

PubMed2001

Is voluntary abortion a seasonal disorder of mood?

BACKGROUND: Depressive mood and suicides are more frequent in women seeking voluntary abortion and occur in a seasonal rhythmic fashion. Whether voluntary abortion shows a similar seasonal rhythm was investigated in this study. METHODS: A 4-year analysis was performed on the database of the National Institute of Statistics (ISTAT) (508,130 abortions) and on the medical records of our institute (3463 abortions). The ratio of voluntary abortions to the number of vital pregnancies (terminated with birth and voluntary abortion) present at the third month of gestation (8--12 weeks) was evaluated. Analyses were carried out by the periodogram method. RESULTS: The rate of voluntary abortions showed a seasonal rhythm with an amplitude of 6.1--6.7% and peaked in May (+/-38 days). The national frequency of female suicides, obtained from the same ISTAT database, showed a similar rhythm, with an amplitude of 11.1% and maximal rate in June (+/-37 days). CONCLUSIONS: The present data show a seasonal rhythm in the rate of voluntary abortion, which is almost identical to that of female suicides. This link suggests common provocative mechanisms and may indicate common preventative measures.

Abortion, Induced↗

PubMed2001

Insulin sensitivity in women: a comparison among values derived from intravenous glucose tolerance tests with different sampling frequency, oral glucose tolerance test or fasting.

OBJECTIVE: To determine the correlation between insulin sensitivity (S(I)) obtained by the minimal model method applied to a frequently sampled (n=33) intravenous glucose tolerance test (FSIGT(33)), and values obtained by reduced FSIGTs, oral glucose tolerance test (OGTT), or fasting. DESIGN: Retrospective analysis on tests performed in prospective studies. METHODS: A total of 78 FSIGT(33), and 59 OGTT were performed in non-diabetic women of which 10 were young cyclic females in the early follicular menstrual phase, 10 were young non-obese subjects with polycystic ovary syndrome (PCOS) and 30 were in post-menopause. Some of these individuals were investigated both prior to and during specified treatments. FSIGT(33) was transformed into FSIGT(22) and FSIGT(12) by removing samples from the analysis. Values of SI derived from reduced FSIGTs or calculations performed on glucose and insulin values observed in fasting conditions and/or during OGTT were related to those of FSIGT(33). RESULTS: S(I) values derived from FSIGT(33) were highly correlated with those derived from FSIGT(22) (r=0.965) or FSIGT(12) (r=0.955), but were only weakly correlated with those derived from fasting or OGTT calculations (r below 0.5). Between-group (PCOS vs normal) or within-group (prior to and during treatment) comparisons showed that reduced FSIGTs were only slightly less powerful than FSIGT(33) in detecting differences in S(I). CONCLUSIONS: In non-diabetic women, reduced FSIGTs but not calculations based on fasting or OGTT values may be used in place of FSIGT(33) to document S(I) and its variation.

Administration, Oral↗

PubMed2000

Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.

OBJECTIVE: Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli. METHODS: Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol. RESULTS: Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol. CONCLUSIONS: Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

Administration, Cutaneous↗

PubMed2000

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy.

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.

Antioxidants↗

PubMed2000

Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement.

OBJECTIVE: In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement. DESIGN: Prior to and after 2 months of transdermal oestradiol (50 microg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion. PATIENTS: Fourteen healthy postmenopausal women. MEASUREMENTS: Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test). RESULTS: Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0. 457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day. CONCLUSIONS: Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.

Catecholamines↗

PubMed2000

Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women.

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 micrograms/day of 17 beta-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection. Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 +/- 21.6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.

Arginine↗

PubMed1999

Effect of prolonged administration of transdermal estradiol on flow-mediated endothelium-dependent and endothelium-independent vasodilation in healthy postmenopausal women.

In 15 postmenopausal women with no cardiovascular risk factors, hormone replacement with transdermal estradiol (50 microg/day for 2 months) did not enhance flow-mediated endothelium-dependent vasodilation, reduce endothelium-independent vasodilation, and did not modify the pulsatility index and blood flow of the brachial artery. The present data do not support a positive effect of replacement with transdermal estradiol on vessel vasodilation in healthy, postmenopausal women.

Administration, Cutaneous↗

PubMed1999

Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men.

In this study it was investigated whether the oral administration of melatonin (1 mg) in comparison to placebo was able to reduce blood pressure, vascular reactivity, and catecholamines in men, as previously reported in young women. The administration of melatonin significantly reduced blood pressure, the pulsatility index in the internal carotid artery, and catecholamines levels within 90 minutes. The effect of melatonin on the artery pulsatility index was related to baseline values, being greater in men with higher baseline values. The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implications.

Adult↗

PubMed1999

Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances. Influences of socio-economic and personality factors.

OBJECTIVES: To clarify the effect exerted by hormone replacement therapy (HRT) versus socio-economic and personality factors in improving postmenopausal mood disorders. STUDY DESIGN: The effect of the 1-year administration of systemic hormone replacement therapy (HRT; n = 22) or a vaginal cream of estriol (n = 14) versus no treatment (n = 26) was evaluated on mood states of anxiety, depression, somatization and inadequacy, as evaluated by the symptom rating test (SRT) scale. Results were correlated with the woman socio-economic status, and her capability to cope with daytime distresses, as evaluated by the Coping Style questionnaire. RESULTS: A spontaneous decline of all SRT scores, except that of inadequacy, was observed in the group with no treatment. In comparison HRT induced a greater improvement of only the SRT score of inadequacy (P < 0.01) and to a lesser extent of anxiety (P < 0.06). Similarly, vaginal estriol induced a greater decline of the SRT score of inadequacy (P < 0.01). Multiple regression analysis showed that modifications of the total SRT score and the SRT score of anxiety were related mainly to socio-economic factors, while those of the SRT score of depression were related only to the coping style of the woman. The decline of somatization was related only to time since the menopause while, the reduction of the SRT score of inadequacy was only the consequence of therapy, either systemic or local. CONCLUSIONS: In a 1-year period improvement of post-menopausal psychological discomfort, is spontaneous and independent of therapy. Only symptoms of inadequacy are improved by the hormonal therapy. Likely, the perceived menopausal 'losses' make the woman to feel inadequate and the use of sex-related hormones is capable to improve this feeling.

Adaptation, Psychological↗

PubMed1999

Rhythmic variation in the rate of ectopic pregnancy throughout the year.

OBJECTIVE: This study was conducted to determine whether the incidence of ectopic pregnancy follows a seasonal rhythm of occurrence. STUDY DESIGN: A retrospective analysis was performed on 15,639 pregnancies reported in a single department in 5.5 years (January 1992-June 1997). For each pregnancy the time of conception was estimated from medical records. Frequencies of conceptions that terminated in birth, spontaneous abortion, legally induced abortion, and ectopic pregnancy were distributed across the 12-month period. RESULTS: Total pregnancy showed a seasonal rhythm of occurrence, with peak values in March. The rate of ectopic pregnancy showed a rhythm with 2 peaks, in June and December. Nadirs were coincident with the peak and nadir of total conceptions and also with the equinoxes. Spontaneous abortions tended to show a rhythm the inverse of that of ectopic pregnancy. CONCLUSIONS: These data show an influence of the seasons on the rate of ectopic pregnancy, which may have implications for both the understanding of ectopic pregnancy's causative mechanisms and its prevention.

Abortion, Spontaneous↗

PubMed1999

Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism.

OBJECTIVE: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. PATIENT(S): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). INTERVENTION(S): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. MAIN OUTCOME MEASURE(S): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. RESULT(S): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. CONCLUSION(S): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.

Adult↗

PubMed1999

Biometrical threshold of biparietal diameter for certain fetal sex assignment by ultrasound.

OBJECTIVES: The aim of this study was to establish the biometric threshold of biparietal diameter (BPD), assumed to be an independent variable of gestational age, at which 100% accuracy in the assessment of fetal sex by ultrasonography is achievable. METHODS: Transvaginal and/or transabdominal sonography was used for detecting the 'sagittal sign' as a marker of fetal sex in 385 fetuses with BPD between 18 and 29 mm. The results of ultrasound examination were compared with sex at birth or with karyotype obtained from amniotic fluid cells or chorionic villus sampling. RESULTS: Fetal sex assignment was feasible in 337 of 385 cases (87.5%). Of the 312 fetuses with known fetal sex outcome, 164 were males and 148 were females. An accuracy rate of 100% was achieved when a BPD of > or = 23 mm was obtained. CONCLUSION: This study provides important information about the earliest stage of fetal development, expressed in terms of BPD, at which a diagnosis of fetal sex can be made with 100% accuracy.

Biometry↗

PubMed1999

Diurnal variation of semen quality in human males.

The possibility of a diurnal variation in semen quality was tested in 54 human males attending our infertility clinic. Of the enrolled subjects, 24 were normozoospermic and 30 were suffering from oligo- and/or asthenozoospermia. Seminal fluid was collected by masturbation twice by each subject, once in the morning (7:00-7:30 a.m.) and once in the afternoon (5:00-5:30 p.m.). Abstinence from sexual intercourse for 3-4 days before each of the two collections was requested. Semen parameters were evaluated independently by two biologists before and after pellet swim-up. Beside similar macroscopic parameters, specimens collected in the afternoon showed a higher number (P < 0.01) and concentration (P < 0.01) of spermatozoa. Also, immediately (P < 0.05), and at 1 h (P < 0.02) and 2 h (P < 0.01) after pellet swim-up, the number of spermatozoa with progressive linear motility was higher in the afternoon than in the morning. These data are the first documenting a diurnal rhythm in sperm quality which may contribute to the reported variability in semen parameters, and may prove useful for spontaneous and assisted conceptions.

Adult↗

PubMed1999

Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism.

Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women.

Adult↗

PubMed1999

Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women.

The effect of a 2-mo treatment with transdermal estradiol (50 microgram/day) versus placebo on 24 h of blood pressure rhythm was investigated in 18 normotensive healthy postmenopausal women. Whereas daytime blood pressure was not modified, nighttime blood pressure was reduced by estradiol. Estradiol magnified the nocturnal decrement of systolic (14.3 +/- 7.2 vs. 9.8 +/- 6.7 mmHg, P = 0. 0033), diastolic (11.6 +/- 5.0 vs. 7.5 +/- 7.3 mmHg, P = 0.028), and mean (10.8 +/- 5.6 vs. 7.2 +/- 4.5 mmHg, P = 0.011) blood pressure. As a consequence, the 24-h rhythm of mean blood pressure was restored in 50% of the subjects (P = 0.045) in whom it was absent and was amplified in the remaining 50% of the subjects. Body mass index was an independent determinant of blood pressure values being directly related to the amplitude of the 24-h mean blood pressure rhythm (r2 = 0.38; P = 0.0067). In normotensive postmenopausal women, physiological doses of estradiol amplify the nocturnal decline of blood pressure.

Blood Pressure↗