Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.

BACKGROUND: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). METHODS: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. RESULTS: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. CONCLUSION: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

Measurement of blood pressure using the auscultatory and oscillometric methods in the same cuff deflation: validation and field trial of the A&D TM2421 monitor.

We have evaluated under laboratory validation conditions and in an extensive field trial the behaviour of an ambulatory monitoring device that is capable of recording both by the Korotkoff-sound and oscillometric methods in a single cuff deflation (TM2421: A&D Co, Tokyo, Japan). The effects of subject age and blood pressure (BP) level on the accuracy and field reliability of the two methods implemented in the device have been determined. In the validation phase, automatic BP measurements were compared with readings by two trained observers in 96 subjects, and the results compared with the AAMI criteria for automatic BP monitors. In the field trial phase, the performances of Korotkoff-sound and oscillometric methods over a 24-h period of ambulatory BP monitoring were compared in 515 subjects, with analysis of the agreement between the two methods in patients where both provided satisfactory recordings. In the validation phase, the Korotkoff-sound method gave satisfactory results for both systolic and diastolic BP, but the oscillometric technique narrowly failed to meet the AAMI criteria for the measurement of either systolic or diastolic BP. In the field trial, the K-sound method failed to record BP accurately in 12% of subjects whereas the oscillometric method was successful in all of these. Where both methods provided technically adequate records, agreement between mean values for each method was close. In 18% of patients, the availability of the oscillometric measurement as a 'back-up' method for the K-sound method significantly improved the number of available measurements in the monitoring period, which should result in improved accuracy and reproducibility of the ambulatory mean values.

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension are normalized after treatment with doxazosin but not propranolol.

OBJECTIVE: Marked alterations have been demonstrated to occur in the platelet alpha2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with alpha-adrenergic blocker doxazosin or beta-adrenergic blocker propranolol can affect the affinity and the density of platelet alpha2-adrenoceptors in such patients. SUBJECTS AND METHODS: In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (B(max)) of platelet alpha2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. RESULTS: Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and B(max) values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and B(max) returned to normotensive values. CONCLUSIONS: In previously untreated, essential hypertensive patients platelet alpha2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the alpha-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet alpha2-adrenoceptors whereas the treatment with the beta-adrenergic blocker propranolol does not alter the Kd and B(max) values.

Platelet alpha2-adrenoceptor alterations in patients with essential hypertension.

AIMS: The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives. METHODS: The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured. RESULTS: Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM). CONCLUSIONS: Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.

Effect of residual endogenous insulin secretion on the abnormal oxytocin response to hypoglycaemia in insulin-dependent diabetics.

OBJECTIVES: Arginine-vasopressin (AVP) and oxytocin (OT) secretions are abnormally stimulated by hypoglycaemia in patients with IDDM. Since previous studies showed that AVP secretion is influenced by the persistence of residual endogenous insulin secretion, we wondered whether this factor also regulates OT secretion. DESIGN: Case-control study: the OT response to insulin-induced hypoglycaemia was measured in normal and diabetic patients with or without residual endogenous insulin secretion. SUBJECTS: Ten normal male subjects, 10 C-peptide positive (CpP) and 11 C-peptide negative (CpN) male diabetic patients. PRELIMINARY STUDIES: plasma C-peptide levels were measured after intravenous administration of 1 mg glucagon. Insulin tolerance test (ITT): diabetics were studied after optimization of their metabolic status by 3 days of treatment with constant subcutaneous insulin infusion. CpP and CpN diabetics and normal controls were tested with an intravenous administration of 0.15 IU per kg body weight insulin. Blood samples for OT assay were taken just before the rapid injection of insulin (time 0) and at time 15, 30, 45 and 60 min. RESULTS: The basal concentrations of OT were similar in all groups. Insulin induced a similar hypoglycaemic nadir in all groups at 30 min, even though diabetic groups showed a delayed recovery in blood glucose levels. The glycaemic pattern was similar in all diabetic patients. Hypoglycaemia-induced OT rise was significantly higher in the two diabetic groups than in the normal group. However, CpN patients showed significantly higher OT increments than CpP subjects. CONCLUSIONS: These data indicate that a residual endogenous insulin secretion exerts a partial protective action against the hypothalamic-pituitary disorder affecting the OT secretory system in IDDM.

Arginine vasopressin and oxytocin responses to angiotensin II are mediated by AT1 receptor subtype in normal men.

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.

[Neoadjuvant combined hormonal therapy and radiotherapy with external beam irradiation in prostatic carcinoma]. / Ormonoterapia neoadiuvante-concomitante e radioterapia con fasci esterni nel carcinoma prostatico.

From January, 1991, to December, 1995, forty-two patients with prostatic cancer (T2-T4: 40 patients) were treated with a luteinizing hormone-releasing hormone (LHRH) analog (2 administrations before and 3 during irradiation), Flutamide (1 month) and external beam radiation therapy (45 Gy to the whole pelvis and a 20 Gy boost). All patients completed the protocol and the LHRH analog was continued for 1-6 months in 5 patients with partial response at the end of radiotherapy. The incidence of acute toxicity was low according to the Radiation Therapy Oncology Group and European Organization for Research and Treatment in Cancer score (grades 1-2; 19% hematologic, 36% intestinal and 38% urological toxicity). At a median follow-up of 21 months (range: 1-60 months), one patient had local disease progression and lung metastases and two had bone metastases; the three relapsing patients were given the LHRH analog and exhibited partial response to rectal examination (1 case) and to bone scan (2 cases). Pain disappeared completely in both the patients with bone metastases. Overall 3-year survival and disease-free survival rates were 97% and 79%, respectively. Disease-free survival was significantly related to cT (at 3 years: cT2: 100%; cT3: 81.2%; log rank test: 0.0081). Late toxicity was observed in two patients: rectal bleeding in one case and chronic diarrhea in the other. The combined protocol used in this study was feasible and well tolerated. Our results seem to confirm the promising preliminary results of Radiation Therapy Oncology Group 8610 study.

Is respiratory sinus arrhythmia a good index of cardiac vagal tone in exercise?

To assess the relative roles of neural and nonneural mechanisms in respiratory sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21 +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan camsylate (3-5 mg/min i.v.). GB was confirmed by the abolition of the reflex bradycardia in response to intravenous phenylephrine and of the blood pressure rise with the cold pressor test. RSA was calculated from the power of the spectral component of the R-R interval variability centered at the breathing frequency. GB decreased but did not abolish RSA. At rest, this nonneural component of RSA was negligible, accounting for < 1% of the control RSA. During GB, exercise did not affect RSA significantly. However, because control RSA was decreased by exercise, the proportion of nonneural RSA increased by 32% (range from 17 to 75%). These results indicate that as the vagal tone decreases with exercise, an increasing proportion of RSA is due to nonneural mechanisms.

Trough:peak ratio of nifedipine gastrointestinal therapeutic system and nifedipine retard in essential hypertensive patients: an Italian multicentre study.

OBJECTIVE: To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy. METHODS: According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout. RESULTS: Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations. CONCLUSIONS: Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.

Inhibition by somatostatin of the growth hormone, but not corticotropin response to angiotensin II in normal men.

The effect of an i.v. infusion of somatostatin (SRIH) (4.1 micrograms/min/180 min) on angiotensin II (ANG II infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg/min; each dose for 20 min)-stimulated growth hormone (GH) and corticotropin (ACTH) release was studied in 7 normal men. In addition, 7 additional normal subjects were tested with ANG II alone (as described above), GH-RH (0.1 microgram/kg body weight as an i.v. bolus) alone or the combination of GH-RH and ANG II. The ACTH response to ANG II was not modified by SRIH infusion; in contrast, the GH response to ANG II was significantly reduced by the concomitant treatment with SRIH. On the other hand, the administration of GH-RH together with ANG II produced peak GH levels comparable to the sum of the individual responses to ANG II and GH-RH, given alone. These findings provide evidence that the stimulatory effect of ANG II on GH, but not ACTH secretion, is under the inhibitory control of somatostatin, suggesting an interaction between ANG II and SRIH in regulation of GH secretion.

Influence of residual C-peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin-dependent diabetes.

Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin-induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin-dependent diabetic men and 10 age- and weight-matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15 IU kg-1). The diabetic patients were subdivided into C-peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic beta cell activity) (group I) and C-peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of substance P on basal and thyrotropin-releasing hormone-stimulated thyrotropin release in humans.

To test the possible effects of intravenous administration of substance P (SP) on basal and thyrotropin-releasing hormone (TRH)-stimulated thyrotropin (TSH) release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 minutes) or after TRH (20 or 400 micrograms in an intravenous bolus) in 21 normal male subjects (aged 26 to 36 years) and in 18 normal women (aged 25 to 32 years). Women were studied during follicular (day 6 to 8) and luteal (day 21 to 23) phases of following regular menstrual cycles. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, significant increments in plasma cortisol levels were observed in men and women when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was administered. In contrast, in both men and women basal and TRH (20 or 400 mg)-induced TSH releases were not modified by SP at any tested amount. Results in the follicular and luteal phase were similar. These data suggest that in normal men and women plasma SP is not involved in the control of TSH release, at least not outside the blood-brain barrier.

Opioid modulation of the gamma-aminobutyric acid-controlled inhibition of exercise-stimulated growth hormone and prolactin secretion in normal men.

The possible involvement of endogenous opioids in the gamma-aminobutyric acid-controlled (GABAergic) inhibition of growth hormone (GH) and prolactin (PRL) during physical exercise was evaluated in normal men. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an iv bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. During exercise, plasma GH and PRL levels rose 5.5- and 1.9-fold, respectively. The administration of naloxone did not modify, whereas sodium valproate significantly reduced the plasma GH and PRL rise during exercise. In the presence of sodium valproate, GH and PRL levels rose 3- and 1.5-fold, respectively, in response to exercise. When naloxone was given together with sodium valproate, both GH and PRL responses to exercise were abolished completely. These data suggest the involvement of a GABAergic mechanism in the regulation of GH and PRL responses to physical exercise in men. Furthermore, the data argue against a role of naloxone-sensitive endogenous opioids in the control of these hormonal responses to exercise, whereas they suggest a modulation by opioids of the GABAergic inhibitory action.

Oxytocin response to challenging stimuli in elderly men.

The present study was carried out in order to establish possible alterations in oxytocin (OT) secretion with aging. Therefore, we evaluated the OT responses to insulin (0.15 U/kg)-induced hypoglycemia or to the administration of angiotensin II (i.v. infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg min; each dose for 20 min) or apomorphine (60 micrograms/kg s.c.) in male subjects aged 22-80 yr and divided into 3 groups by age (group I (n = 9): 22-38 yr; group II (n = 9): 41-60 yr; group III (n = 9): 63-80 yr). Basal OT concentrations were similar in all groups. The OT response during the insulin tolerance test and the administration of ANG II had similar patterns and magnitudes in all groups. The OT response to apomorphine was similar in the two younger groups, with plasma OT levels increased 118% vs. baseline. In contrast, apomorphine was unable to induce a significant OT rise in the oldest group. During apomorphine test plasma OT concentrations were significantly lower in group III than in groups I and II. For the first time in elderly human subjects, these data show normal responsiveness of the OT secretory system to releasing stimuli such as hypoglycemia and ANG II. These findings indicate that in aged men production of OT and capability of responding to challenging stimuli is unchanged. On the other hand, the reduced OT responsiveness to apomorphine in group III might be an expression of the general dopaminergic dysfunction affecting the aging brain.

Role of GABA and opioids in the regulation of the vasopressin response to physical exercise in normal men.

The present study was undertaken in order to establish the possible involvement of GABAergic and/or opioid pathways in the mechanism underlying the arginine-vasopressin (AVP) response to physical exercise. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3 min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an i.v. bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. Plasma AVP levels rose 4-fold during exercise. The administration of naloxone did not modify, whereas sodium valproate completely abolished the plasma AVP rise during exercise. When naloxone was given together with sodium valproate, AVP rose 3-fold in response to exercise. These data suggest the involvement of a GABAergic mechanism in regulation of the AVP response to physical exercise in men. Furthermore, the data argue against a role of naloxone sensitive endogenous opioids in the control of AVP during exercise, whereas they suggest a partial opioid mediation of the GABAergic inhibitory action.

Intravenously infused substance P is unable to change basal and TRH-stimulated PRL secretion in normal men.

In order to test the possible effects of an intravenous administration of substance P (SP) on basal and TRH-stimulated PRL release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 min) or after TRH (20 or 400 micrograms in an i.v. bolus) in 21 normal male subjects. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, a significant increase in plasma cortisol levels was observed when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was given. In contrast, basal and TRH (20 or 400 micrograms)-induced PRL release were not modified by SP at any tested amount. These data suggest that, in normal men, plasma SP is not involved in the control of PRL release at the anterior pituitary level.

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study.

To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.

Luteinizing hormone response to an intravenous infusion of substance P in normal men.

The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1.0, or 1.5 pmol/kg-1/min-1 for 60 minutes, on gonadotropin secretion was evaluated in seven healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During the tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma testosterone concentrations were normal in all subjects and remained unmodified during all tests, regardless of the infused dose of SP. Plasma luteinizing hormone (LH) levels were not modified when either normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when larger amounts of SP were administered. In contrast, plasma follicle-stimulating hormone (FSH) concentrations did not change significantly during any test. These data demonstrate for the first time in normal men that the systemic infusion of SP stimulates LH release, without modifications of FSH secretion.

Inhibitory effect of dexamethasone on the oxytocin response to insulin-induced hypoglycemia in normal men.

Glucocorticoids are known to reduce both ACTH and arginine vasopressin responses to insulin-induced hypoglycemia in normal men. The present study was undertaken in order to establish whether glucocorticoids are capable of modifying the oxytocin (OT) response to hypoglycemia. For this purpose, 8 normal men (28-33 yr) were tested with insulin (0.15 IU/kg in an iv bolus) [insulin tolerance test (ITT)] with and without pretreatment with dexamethasone (2 or 4 mg in an iv bolus 10 min before insulin). Eight different subjects (29-35 yr) were tested with dexamethasone alone. The administration of dexamethasone (2 or 4 mg) alone changed neither ACTH nor OT concentrations in the plasma during the next hour. Insulin produced similar hypoglycemic responses, regardless of dexamethasone treatment. ACTH levels rose significantly in response to insulin-induced hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs baseline). Two and four mg dexamethasone produced similar significant reductions of the ACTH response to hypoglycemia (p less than 0.02 at 45 min, p less than 0.05 at 30 and 60 min vs ITT). In the ITT, OT levels rose significantly in response to hypoglycemia, with a mean peak response at 45 min (p less than 0.01 vs basal value). The pretreatment with 2 or 4 mg dexamethasone reduced in a similar manner the hypoglycemia-induced OT rise (p less than 0.05 at 30 and 45 min vs ITT). These findings show a partial inhibition by dexamethasone of the OT response to hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the safety and efficacy of the lisinopril + hydrochlorothiazide and captopril + hydrochlorothiazide combinations in the treatment of essential arterial hypertension]. / Valutazione della sicurezza e dell'efficacia delle associazioni lisinopril + idroclorotiazide e captopril + idroclorotiazide nel trattamento dell'ipertensione arteriosa essenziale.

The aim of this study was to assess the efficacy and tolerability of the combinations of lisinopril (LIS) 20 mg + hydrochlorothiazide (HCTZ) 12.5 mg and captopril (CAP) 50 mg + HCTZ 25 mg in moderately hypertensive patients not adequately controlled by LIS or CAP alone. The study was multicentre (11 centres), open, random and carried out in parallel groups. After two weeks' placebo run in patients were randomly assigned to LIS 10-20 mg/o.d. or CAP 25-50 mg/b.i.d. treatment for 6 weeks. After this, patients with supine diastolic blood pressure (SDBP) greater than 90 mmHg were treated with the combinations LIS 20 mg + HCTZ 12.5 mg/o.d. or CAP 50 mg + HCTZ 25 mg/o.d. for 4 weeks; this dose was doubled if DBP was found to be greater than 90 mmHg after 2 weeks' combined therapy. A total of 175 patients were enrolled (92 females and 83 males) of which 153 completed the study. The LIS + HCTZ association caused a significant reduction of DBP in comparison to the other combined treatment (88.1 +/- 0.7 vs 90.3 +/- 0.7; p = 0.026). The statistical analysis of mean SBP values showed no significant difference between the two groups (144.0 +/- 1.3 vs 146.8 +/- 1.3; p = 0.15). At the end of the study 79.5% of patients treated with LIS + HCTZ presented normal results (DBP less than or equal to 90 mmHg), whereas the percentage of similar results in the comparison group was 72%. The percentage of "responder" patients to therapy (DBP reduced by 10 mmHg or more in relation to basal values) was 96.3% in the LIS + HCTZ group and 86.7% in the CAP + HCTZ group. In the CAP + HCTZ group 0.6% of patients reported adverse reactions, while only 0.3% were observed in the LIS + HCTZ group.