Impact of sarcopenia in SARS-CoV-2 patients during two different epidemic waves.

BACKGROUND: Sarcopenia was reported to be associated with poor clinical outcome, higher incidence of community-acquired pneumonia, increased risk of infections and reduced survival in different clinical settings. The aim of our work is to evaluate the prognostic role of sarcopenia in patients with the 2019 novel coronavirus disease (COVID-19). MATERIALS AND METHODS: 272 COVID-19 patients admitted to the University Hospital of Modena (Italy) from February 2020 to January 2021 were retrospectively studied. All included patients underwent a chest computed tomography (CT) scan to assess pneumonia during their hospitalization and showed a positive SARS-CoV-2 molecular test. Sarcopenia was defined by skeletal muscle area (SMA) evaluation at the 12th thoracic vertebra (T12). Clinical, laboratory data and adverse clinical outcome (admission to Intensive Care Unit and death) were collected for all patients. RESULTS: Prevalence of sarcopenia was high (41.5%) but significantly different in each pandemic wave (57.9% vs 21.6% p < 0.0000). At the multivariate analysis, sarcopenia during the first wave (Hazard Ratio 2.29, 95% confidence intervals 1.17 to 4.49 p = 0.0162) was the only independent prognostic factor for adverse clinical outcome. There were no significant differences in comorbidities and COVID19 severity in terms of pulmonary involvement at lung CT comparing during the first and second wave. Mixed pattern with peripheral and central involvement was found to be dominant in both groups. CONCLUSION: We highlight the prognostic impact of sarcopenia in COVID-19 patients hospitalized during the first wave. T12 SMA could represent a potential tool to identify sarcopenic patients in particular settings. Further studies are needed to better understand the association between sarcopenia and COVID-19.

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Basilar Dependence on a Persistent Hypoglossal Artery Visualized at CT Angiography. A Case Report.

The persistent hypoglossal artery is a rare perseverance of an embryonic vessel connecting the anterior and posterior circulations and is generally considered an incidental finding. This report describes a patient with a basilar dependence on a persistent hypoglossal artery visualized at CT angiography. The pertinent findings and clinical implications of this anomalous vessel are discussed.

Occasional finding of a dural arteriovenous fistula in a newborn with orbital lymphangioma. A case report.

Dural arteriovenous fistulas (DAVF) are vascular malformations rarely occurring in the paediatric population (1,2,3). Prompt diagnosis and treatment are mandatory to prevent life-threatening complications including congestive heart failure and severe brain injury (1,2). We describe the case of a female newborn with an orbital lymphangioma treated for a posterior fossa DAVF. We emphasize the role of MR imaging as a useful non-invasive tool in the diagnosis of these malformations and in the evaluation of associated brain parenchymal lesions.

Refractures in cemented vertebrae after percutaneous vertebroplasty and pain relief after a second procedure: a retrospective analysis.

Refractures of cemented vertebrae occasionally occur after vertebroplasty. It is unclear whether such fractures are procedure-related or part of the natural course of osteoporosis and neoplasy. Our aim was to identify why there is an increased risk of subsequent fracture in cemented vertebrae. We retrospectively analyzed the incidence and possible causative mechanism of refracture in patients who had received vertebroplasty for multiple levels of vertebral compression fracture and the reduction of pain after a subsequent vertebroplasty procedure. A total of 356 patients were evaluated with follow-up from June 2003 to September 2008. We identified 59 refractured patients (54 osteoporotic and four neoplastic). Refractures of cemented vertebrae after vertebroplasty occurred in 59 patients (16%: 98% osteoporotic and 2% neoplastic). Refractures occurred in 8% at the same level as the first vetebroplasty, 31% at an inferior level, 19% at a superior level, 41% at superior and inferior levels and 1% at superior and same levels. Pain was significantly reduced after retreatment in 45 patients (76%) with a moderate reduction in 14 patients (24 %). In conclusion, significant anterior vertebral height restoration increases the risk of subsequent fracture in cemented vertebrae.

Percutaneous sclerotherapy for lymphangioma and soft-tissue venous malformation located in the maxillofacial region in children and young adults.

To demonstrate that percutaneous sclerotherapy for lymphangioma using a new fibrosing agent (OK-432) and for soft-tissue venous malformation with alcoholization can improve management of these congenital vascular abnormalities. Between February 2003 and November 2005 five patients with lymphangioma, ranging in age from 23 months to 18 years (mean age = 9 years) and four patients with soft-tissue venous malformation, raging in age from 25 months to 18 years (mean age = 11 years) underwent percutaneous sclerotherapy. Ultrasound Computed tomography and/or Magnetic Resonance imaging were performed beforehand to evaluate the anatomic boundaries of the malformation. General anesthesia is mandatory for children under three years. Direct puncture of the mass with a 23-gauge venous infusion set (butterfly) was performed by means of palpation alone or with ultrasonographic guidance using OK-432 PICIBANIL (0.1-0.2 mg dilute in 10 ml normal saline) for lymphangioma and alcohol in venous malformation. The volume of sclerosing solution varied from 0.2 to 15 ml per injection course. Processing time was less than 20 minutes. Swelling of lesion, pain, local inflammatory reactions and mild fever (37.5°-39°) in lymphangioma, were constant findings after sclerotherapy. Satisfactory results (when the regression was estimated to be more than 50% of the initial volume; negative in inspection, but positive in palpation and imaging study) were obtained in four patients with head and neck lymphangioma. One patient was completely cured with an excellent (when there was a complete regression of malformations; negative in inspection, palpation and imaging study) result. All patients with soft-tissue venous malformation were satisfied with the results. In conclusion, in consideration of its low cost, rare complications and good results, we strongly recommend percutaneous sclerotherapy in the treatment of head and neck lymphangioma and soft-tissue venous malformation in children.

Weight gain in women with breast cancer treated with adjuvant cyclophosphomide, methotrexate and 5-fluorouracil. Analysis of resting energy expenditure and body composition.

BACKGROUND: Weight gain is a common side effect observed in women undergoing adjuvant chemotherapy for breast cancer. Among possible causes a direct effect of chemotherapy on metabolism has been proposed. Body composition variations after adjuvant chemotherapy suggest the occurrence of sarcopenic obesity, possibly due to ovarian failure. We investigated acute and chronic effects of adjuvant chemotherapy on body weight, resting energy expenditure (REE) and plasma catecholamines in a group of menopausal women. PATIENTS AND METHODS: Thirty menopausal women with stage I-II breast cancer were recruited for the study. We measured REE and respiratory quotient (RQ) and body composition at the beginning and after 3 and 6 months of adjuvant cyclophosphomide, methotrexate, and 5-fluorouracil (CMF). REE, RQ, and plasma catecholamines were assessed before and after each chemotherapy session. At each session food intake was also assessed in all patients, by a food diary. Seven patients out of the group of 30 were also evaluated after a placebo infusion (saline). RESULTS: A significant weight gain was observed in all women (70.5 +/- 3 v.s. 67.7 +/- 3 kg, p < 0.001), with increase in both fat-free mass (FFM) (45.2 +/- 1.5 v.s. 43.6 +/- 1.3 kg, p < 0.001) and fat-mass (FM) (25.3 +/- 1.7 v.s. 24.1 +/- 1.8 kg, p < 0.005). A decrease in REE and RQ was observed both during CMF and placebo infusion (p < 0.05). During acute CMF and placebo infusion a reduction of plasma levels of noradrenaline was observed at the first and last session. REE increased progressively during the study period. CONCLUSIONS: CMF therapy apparently has no effect on REE either acutely or during a 6-month-period; the increased REE observed in the long-term is likely due to the concomitant increase in FFM. The lack of evidence of sarcopenic obesity, at variance with previous literature, is likely due to different patient selection.

Loco-regional thrombolysis in the treatment of cerebral venous and sinus thrombosis: report of two cases.

Although intravenous (i.v.) heparin is widely used as the first line treatment for cerebral venous and sinus thrombosis (CVST), the most appropriate therapy for this disease is still controversial. We report 2 cases of CVST who were successfully treated by means of loco-regional thrombolysis with urokinase. In the first case we chose this treatment instead of i.v. heparin because clinical conditions of the patient appeared critical for life on hospital admission; in the second case loco-regional thrombolysis was performed because a full-dose heparin treatment over 8 days failed to improve the clinical picture of the patient. In the literature, there are no established criteria for the use of loco-regional thrombolysis in CVST. On the basis of our own experience and few previous reports on the matter, we suggest that loco-regional thrombolysis should be considered an appropriate treatment for CVST when patients are at life risk, when an involvement of deep cerebral veins is present or when, after full heparinization, patients are doing poorly clinically.

Resting metabolic rate, fat-free mass and catecholamine excretion during weight loss in female obese patients.

The reduction in resting metabolic rate (RMR) during weight loss exceeds that accounted for by changes in body composition by 15%, suggesting that factors other than fat-free mass (FFM) explain the metabolic adaptation during food restriction in obesity. Our study aimed to establish if changes in the sympathoadrenal system activity, as inferred from an integrated measure such as 24 h urinary excretion of catecholamines, may play a role in the RMR adaptation observed during dietary restriction in obese patients. Ninety-three obese female subjects consumed a low-energy diet (LED) (2930 kJ/d (700 kcal/d)) for a 3-week period. At the beginning and at the end of the study, 24 h urinary excretion of catecholamines, FFM and RMR were measured. The LED induced a significant reduction in body weight (-3.3 (SEM 0.4) kg; P < 0.01), FFM (-1.9 (SEM 0.7) kg; P < 0.01) and in the fat mass (-1.2 (SEM 0.5) kg; P < 0.01). Noradrenalin excretion (24 h) decreased during the LED from 264 (SEM 26) during a weight-maintenance period to 171 (SEM 19) nmol/24 h after consumption of the LED for 3 weeks (P < 0.001); mean 24 h adrenalin excretion did not change during the LED (22 (SEM 3) during the weight-maintenance period v. 21 (SEM 3) nmol/24 h after consumption of the LED for 3 weeks; NS). The LED induced a significant decrease in RMR (7300 (SEM 218) v. 6831 (SEM 138) kJ/24 h; P < 0.001). The only independent variable that significantly explained variations in RMR both before and after consumption of the LED for 3 weeks, was FFM (r2 0.79 and r2 0.80 respectively). Urinary noradrenalin excretion explained a further 4% of the variability in RMR, but only before the diet, so that a role of sympathoadrenal system on RMR seems to be present in obese patients in basal conditions but not at the end of the LED.

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.

Metabolic effects of fluoxetine in obese menopausal women.

Our objective was to assess thermogenic action of fluoxetine (FL) in obese menopausal women, evaluating the effect of FL administration on resting energy expenditure (REE) and on glucose-induced thermogenesis both after acute administration (40 mg in single dose the evening before measurements) and after a 12- week period of diet treatment plus FL (60 mg per day) or placebo. It was a double-blind, placebo-controlled design both in acute and in chronic study. The subjects were 32 obese, otherwise healthy, menopausal women. The patients were assigned randomly to three groups, one performing an acute study protocol, in which resting and glucose-induced thermogenesis was measured after FL and placebo administration, performed in randomised order. The other two groups underwent dietary plus pharmacological treatment (FL or placebo, PL). Resting and glucose-induced thermogenesis was measured at baseline and after 12 weeks of treatment. The results showed that acute FL administration caused an increase in resting energy expenditure (PL: 5.35+/-0.18 vs FL: 5.53+/-0.24 KJ/min, p<0.05). A significant decrease of REE was observed in the PL group after 12 weeks (p<0.03), while a slight, but not significant, decrease was observed in the FL group (p=NS). FL did not affect thermic response to oral glucose neither after acute nor chronic administration (p=NS for all groups studied). The conclusion was that our data give support to thermogenic actions of FL after acute administration, suggesting also that chronic FL treatment may restrain to some degree the metabolic adaptation expected during weight loss in obese subjects. At variance with what observed with other drugs, such as dexfenfluramine, an increased thermic effect of oral glucose does not seem to be involved in the thermogenetic action of FL.

alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.

BACKGROUND: Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN: In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls. RESULTS: During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS: This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.

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.

Baseline and stimulated catecholamine secretion in normotensive patients with active acromegaly: acute effects of continuous octreotide infusion.

OBJECTIVE: Alterations in catecholamine plasma levels may contribute to the cardiovascular complications of acromegaly. Since few data are available on the catecholamine secretory dynamics in active acromegaly and no evidence exists on catecholamine variations during GH decrease, we studied acromegalic patients before and during octreotide administration. METHODS: We evaluated the catecholamine responses to upright posture and a cold pressure test (CPT) in 11 acromegalic (A) patients before and during continuous administration of octreotide (500 microgram/24h by s.c. pump) compared with 11 normal (N) subjects. RESULTS: All the acromegalic patients showed left ventricular cardiac hypertrophy. The cardiovascular responses to upright posture were similar between normal subjects and acromegalics both before and during octreotide treatment. The basal levels of norepinephrine (NE) were significantly higher in A patients compared with N subjects (423+/-45 vs 264+/-32pg/ml, P<0. 05) and decreased during therapy (291+/-32pg/ml; P<0.01). The increase in plasma NE during upright posture was significantly lower in A than in N subjects (P<0.01), but was restored to normal during octreotide treatment. CPT increased systolic and diastolic blood pressure, pulse rate and NE plasma levels in N (P<0.05) but not in A subjects both before and during octreotide treatment. CONCLUSIONS: Our data demonstrate the presence of increased basal NE levels in acromegalic patients with a defective sympathetic response to stimuli. Short-term octreotide infusion is able to induce a reduction in the basal levels of NE and a normalization of the catecholamine response to posture.

Adrenomedullary response to caffeine in prepubertal and pubertal obese subjects.

OBJECTIVE: To investigate whether blunted adrenomedullary responsiveness to stimuli is a primary feature of human obesity in childhood and adolescence DESIGN: Comparison of plasma catecholamine response to caffeine in obese and lean subjects before and after puberty onset. SUBJECTS: Twelve lean prepubertal subjects (six males and six females), 15 prepubertal obese subjects (seven males and eight females), 12 pubertal lean subjects (six males and six females) and 24 pubertal obese subjects (12 males and 12 females) MEASUREMENTS: Plasma levels of Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol and testosterone were used to validate Tanner score. Systolic and diastolic blood pressure, pulse rate and plasma catecholamines before and after caffeine administration (4 mg/kg of ideal body weight). RESULTS: Caffeine administration significantly stimulated adrenaline release in all subjects studied. The incremental area of adrenaline response to caffeine, analysed by multiple comparison test, was lower in pubertal obese subjects with respect to other groups. CONCLUSIONS: At variance with what is observed in adulthood obesity, prepubertal obese subjects show an intact adrenomedullary response to caffeine.

Acute infusion of naloxone, an opioid receptor antagonist, does not modify serum leptin concentrations in amenorrheic and healthy women.

OBJECTIVE: To determine whether the opioidergic system is involved in the modulation of leptin secretion in healthy and amenorrheic subjects. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, University of Modena, Modena, Italy. PATIENT(S): Healthy subjects (n = 8) and patients with hypothalamic amenorrhea (n = 17) or hyperandrogenism (n = 7) and low body mass index (BMI). INTERVENTION(S): Acute infusion of naloxone (4-mg bolus) and blood sampling 15 minutes before infusion; at time of infusion; and 15, 30, 45, 60, 75, 90, and 120 minutes after infusion. MAIN OUTCOME MEASURE(S): Plasma leptin, LH, FSH, E2, and cortisol concentrations. RESULT(S): Plasma leptin concentrations were lower (P <.01) in both hypothalamic and hyperandrogenic amenorrheic subjects than in healthy controls. In all groups of subjects, no significant changes in leptin levels were observed after infusion of naloxone. A significant correlation was found between leptin concentrations and BMI when all subjects were considered together (P <.05) but was not found in the single groups. CONCLUSION(S): The present data do not support the hypothesis that opioidergic receptors are involved acutely in the modulation of leptin release in healthy and amenorrheic women.

Acute estradiol and progesterone administration reduced cardiovascular and catecholamine responses to mental stress in menopausal women.

Steroid hormones are involved in the regulation of sympathoadrenal activity. Since the effect of sex steroids on the cardiovascular system and catecholamine secretion could also be exerted through an acute, nongenomic mechanism, we have studied the response to mental stress (color word test, CWT) in a group of 15 menopausal women during estrogen (100 microg of estradiol by patch), progesterone (100 mg i.m.) or placebo administration. Systolic blood pressure (SBP) increased during CWT in the three sessions (F = 11.0, p < 0.001) but the area under the curve of SBP was higher during placebo (2,855 +/- 131 mm Hg x min) than during estradiol (2,585 +/- 139 mm Hg x min) and progesterone (2,553 +/- 179 mm Hg x min, p < 0.05 for both). Plasma epinephrine increased during CWT in the three sessions (F = 31.1, p < 0.001) and the plasma epinephrine response to mental stress was higher during placebo than during estradiol administration (F = 4.3, p < 0.01). The area under the curve of epinephrine was 10,342 +/- 1,348 pmol/min x 1 during placebo and 7,280 +/- 818 pmol/min x 1 during estradiol (p < 0.03). The plasma glycerol levels at the end of CWT were higher during placebo (0.26 +/- 0.04 nmol/l) than during estradiol (0.19 +/- 0.03 mmol/l) and progesterone (0.17 +/- 0.04 mmol/l) administration (p < 0.05 for both). No significant differences were found in the responses of diastolic blood pressure, heart rate, norepinephrine and cortisol to mental stress during placebo and estradiol or progesterone administration. This study demonstrates that acute steroid administration is able to modify the cardiovascular and catecholamine response to mental stress in menopausal women.

Alpha-2 adrenergic activity in perimenopausal women.

Lipid alterations and increased blood pressure may occur during perimenopause. No data are available in perimenopausal women on the alpha-2 adrenergic activity which affects norepinephrine secretion. We studied cardiovascular and catecholamine responses to clonidine (300 mg per os) in a group of 15 perimenopausal women (PeriMW) and in a control group of 13 premenopausal women (PreMW). Nine of the perimenopausal women were also studied after 4-month percutaneous estrogen replacement therapy (PeriMWE). Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma norepinephrine (NE) and epinephrine (E) were evaluated before and at 120 min, 130 min, 140 min after clonidine administration. Basal values of SBP, DBP and HR were not different (F = 0.7, p = NS; F = 0.2, p = NS and F = 0.1, p = NS respectively) between PeriMW both before and after therapy and PreMW. Resting levels of E were similar in PreMW and in PeriMW before and during estrogen therapy (F = 0.8, p = NS); PeriMW showed higher basal NE levels both before and during estrogen therapy than PreMW (F = 12; p < 0.001). Clonidine administration decreased SBP, DBP and NE levels in PreMW, in PeriMW and in PeriMWE without any difference between the groups (F = 1.2, p = NS; F = 0.5, p = NS and F = 1.3, P = NS respectively). HR decreased significantly after clonidine in PreMW (F = 5.4, p < 0.03) but not in PeriMW before (F = 1.0, p = NS) and during estrogen therapy (F = 0.5, p = NS). Clonidine did not affect plasma E in the three groups studied (F = 2.8, p = NS; F = 2.2, P = NS and F = 0.1, p = NS). The present study demonstrates that increased basal plasma NE levels are present in PeriMW. The cardiovascular and catecholamine response to clonidine in PeriMW both before and during estrogen therapy are similar to those observed in PreMW, suggesting a normal inhibitory alpha-2 receptor pathway.

Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects.

OBJECTIVE: To further investigate the role, if any, of acetylcholine and the parasympathetic nervous system in modulating beta-cell secretion in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min) alone and preceded by pyridostigmine (PD, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasions, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index (BMI): 34.2 +/- 2.1 kg/m2, waist to hip ratio (WHR): 0.83 +/- 0.01, aged 39.0 +/- 5.3y) and six normal women (NS, BMI: 22.7 +/- 1.9 kg/m2, WHR: 0.74 +/- 0.01, aged 37.1 +/- 4.8y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measured in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina using high performance liquid chromatography with electrochemical detection. Pulse rate (PR), systolic (SBP) and diastolic blood pressure (DBP) were also measured every 15 min during the tests by an automated cuff device. RESULTS: OGTT raised glucose concentrations in OB and NS (incremental area: 420 +/- 44 vs 288 +/- 70 mmol/l. 2 h, respectively) without significant differences between groups (F = 0.6, P = ns). On the other hand, OB showed an insulin response to OGTT higher than NS (10,120 +/- 1074 vs 6692 +/- 1962 microU ml-1 2 h, respectively P < 0.01). After OGTT alone NA concentrations increased to the same extent in NS (peak vs basal: 1.40 +/- 0.16 vs 1.07 +/- 0.10 nmol/l, P < 0.05) and in OB (peak vs basal: 1.50 +/- 0.14 vs 1.04 +/- 0.18 nmol/l P < 0.05). Both in NS and in OB, PD administration failed to modify basal glucose and insulin (P = ns for both) as well as basal NA concentrations. In NS, the combined administration of PD and OGTT did not modify glucose and insulin responses compared to OGTT alone 335 +/- 65.4 mmol/l. 2h and 6348 +/- 1348 microU ml-1 2h, respectively) while in OB, PD significantly increased the insulin response to OGTT (14640 +/- 3030 microU ml-1 2h, P < 0.03), while the glucose response was not significantly different from OGTT alone (478 +/- 45 mmol/l. 2h). PD administration did not modify the NA response to OGTT, in NS or OB (P = ns). In both groups, pyridostigmine administration did not affect systolic or diastolic blood pressures, but decreased pulse rate to the same extent in NS (74 +/- 2 vs 66 +/- 2 beats/min, P < 0.05) and in OB (72 +/- 1 vs 67 +/- 2 beats/min, P < 0.05). CONCLUSIONS: Our present data indicate that in man, as in animals, acetylcholine has a stimulatory influence on insulin secretion.

Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy.

Perimenopause and menopause may be associated with an increased risk of cardiovascular disease, so we have investigated the cardiovascular and catecholamine response to caffeine in perimenopausal women compared to young cycling premenopausal subjects. Caffeine (250 mg per os) was administered to nine perimenopausal women and nine premenopausal women. The perimenopausal women repeated the test after 4 months of percutaneous estrogen replacement therapy. Systolic and diastolic blood pressure, pulse rate, plasma norepinephrine, epinephrine, glucose, insulin and free fatty acids were determined at 0, 15, 30, 45, 60, 90 and 120 min after caffeine administration. No differences were found in the basal values of systolic blood pressure, diastolic blood pressure, pulse rate, norepinephrine, epinephrine, insulin, glucose and free fatty acids between perimenopausal women, both before and after therapy, and premenopausal women. Caffeine induced a higher increase of systolic (F = 4.9; p < 0.05) and diastolic blood pressure (F = 4.7; p < 0.05) in perimenopausal women before and during estrogen therapy as compared with premenopausal women. Pulse rate increased significantly only in perimenopausal women before therapy (F = 6.5; p < 0.03). These data show that perimenopause either before or during short-term estrogen therapy is associated with enhanced cardiovascular reactivity to caffeine. This phenomenon is not due to increased adrenergic and metabolic responses.