Long-term results and complications of the syringopleural shunting for treatment of syringomyelia: a clinical study.

BACKGROUND: The use of drains in the treatment of syringomyelia has a simple and immediate appeal. Syringopleural shunting in syringomyelia has produced good short-term results, but limited information is available on long-term effects. We analyzed the complications and long-term outcomes after syringopleural shunting for syringomyelia. CLINICAL MATERIAL AND METHODS: Fourthy-four patients with large-sized syringomyelia underwent syringopleural shunting because of spinal cord compression between 1992 and 2010 in our clinic. Thirty-two patients had Chiari malformation type I (Group B), and 12 patients were associated with primary parenchymal cavitations (Group A). Their ages ranged from 14 to 71 years. Both craniovertebral decompression and syringopleural shunting were performed on 21 patients, whereas only syringopleural shunting was performed on another 21 patients. RESULTS: The follow-up period ranged from 1 year to 17 years (mean: 9.1 years). There was no operative mortality. Early postoperative MRI revealed that syringes of 43 patients had collapsed. There were 9 (20.5%) minor complications in 9 patients, including temporary neurological deficits (6), respiratory distress (2) and headache (1). Seven (15.9%) serious complications [permanent neurological deficit (1), shunt migration (2), shunt misplacement (1), spinal instability (1), tethering (1), CSF over drainage (1)] were seen in five patients. Four of them were treated with a secondary operation. Three patients (3/9; 33.3%) who were treated by syringopleural shunt alone (Group B2) required craniovertebral decompression, although the shunt was functional. During long-term follow-up, three patients stabilized, five patients (11.3%) developed a worse neurological condition, and two of these patients died 10 and 7 years after surgery. Of all patients, 88.6% showed significant clinical improvement. CONCLUSIONS: Although there were complications and failures, syringopleural shunting produced satisfactory results at long-term follow-up.

Comparison of bone mineral density in the jaws of patients with and without chronic periodontitis.

OBJECTIVES: Although several studies have addressed the relationship between systemic bone mineral status and the severity of periodontitis, there is little knowledge of the relationship between periodontal disease and locally detected bone mineral density. The aim of this study was to compare the mandibular bone mineral density of patients with chronic periodontitis with that of periodontally healthy subjects. METHODS: 48 systemically healthy subjects were included in the study and underwent a periodontal examination to determine their status. 24 subjects were periodontally healthy and the other 24 had moderate or severe chronic periodontitis. The mandibular bone mineral density of the subjects was determined by dual energy X-ray absorptiometry. The region of interest on the body of the mandible was independently determined on the dual energy absorptiometry radiographs, and a computer calculated the bone mineral density of these regions. RESULTS: The mandibular bone mineral density of the subjects with periodontitis was significantly lower than that of the periodontally healthy subjects (p < 0.01). There were significant negative correlations between the mandibular bone mineral density values and parameters related to the amount of periodontal destruction. CONCLUSIONS: Low bone mineral density in the jaw may be associated with chronic periodontitis.

Thyroid cancer in toxic and non-toxic multinodular goiter.

BACKGROUND: Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG) than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. AIM: To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. SETTINGS AND DESIGN: Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. MATERIALS AND METHODS: We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. STATISTICAL ANALYSIS USED: Significance of the various parameters was calculated by using ANOVA test. RESULTS: The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. CONCLUSIONS: The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

Ambulatory monitoring of blood pressure (AMBP) in patients with primary hyperparathyroidism.

The purpose of our study was to evaluate the behaviour of blood pressure (BP) by ambulatory monitoring of blood pressure (AMBP) in 53 patients with primary hyperparathyroidism (PHPT) compared to 100 essential hypertensive (EH) and 31 healthy subjects (HS). The correlations between calcium-phosphorus metabolism and haemodynamic parameters in all groups are included in the study. AMBP was performed using the oscillometric technique (Space-Labs, 90207, Redmond, WA, USA) and the following AMBP parameters were evaluated: average day time systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) (when awake), average night time SBP, DBP and HR (when asleep) and average 24-h-SBP, DBP and HR. The definition of 'dipper' or 'non-dipper' subjects was established if night time SBP and DBP fall was >10% and <10%, respectively. In total, 25 PHPT patients (47.2%) were hypertensive (HT-PHPT) and 28 PHPT (52.8%) were normotensive (NT-PHPT). Mean 24-h-SBP and DBP obtained by AMBP was higher in HT-PHPT (P < 0.05) and EH (P < 0.05) than in NT-PHPT and HS. The multiple linear regression has shown that in PHPT-HT patients ionized calcium is an independent factor for the rise of 24-h-DBP values (r: 0.497; P < 0.05) and daytime DBP values (r: 0.497; P < 0.05). In 56% of HT-PHPT patients there is an absence of physiological BP nocturnal fall ('non-dipper'), which is statistically significant (P < 0.05) compared with 'non-dipper' EH patients (30%). In conclusion, in our study the prevalence of hypertension in PHPT was 47%. AMBP revealed that the 'non-dipping 'pattern was much higher in HT-PHPT patients in respect to EH patients.

Plasma adrenomedullin concentrations in patients with renovascular or malignant hypertension.

AIM: The aim of the present study was to investigate the behaviour of plasma adrenomedullin (AM), a hypotensive peptide, in patients with malignant (MHT) and renovascular hypertension (RVH), 2 pathologic conditions in which renin-angiotensin system (RAS) is activated and to compare them with those in essential hypertensive patients (EHT) and normotensive subjects (NS). METHODS: Three groups of hypertensive patients have been studied: group 1 (4 patients with MHT), group 2 (10 patients with RVH), group 3 (24 patients with EHT) and 21 patients NS were enrolled as controls. In all patients, 10 ml vein blood samples were collected and AM was measured with specific radioimmunoassay. RESULTS: As expected, the plasma renin activity (PRA) levels in the RVH and MHT patients were significantly higher (p<0.0001) respect to NS and EHT. The mean plasma AM (+/-SD) concentrations in EHT (22.5+/-9.1 pg/ml) and RVH (46.8+/-19.4 pg/ml) were significantly (p<0.0001) higher than those in NS (13.7+/-6.1 pg/ml). The plasma AM concentrations were further elevated in MHT patients (107+/-12.3 pg/ml) and were significantly higher (p<0.0001) than those in EHT and RVH patients. In the MHT patients the elevated plasma AM levels, similarly to blood pressure and PRA values, declined after antihypertensive treatment (36.8+/-5.7 pg/ml; p<0.01). CONCLUSION: In conclusion, the findings demonstrated that the plasma AM concentrations were increased in proportion to the severity of arterial hypertension. RAS was activated in patients with MHT and RVH suggesting that activation of this system may contribute to increased in the plasma levels of AM.

Adrenomedullin and endocrine disorders.

Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

Plasma levels of endothelin-1 increase in patients with sarcoidosis and fall after disease remission.

BACKGROUND: Sarcoidosis is a chronic systemic disease, characterized by an imbalance of immunity processes and the presence of granuloma. Endothelin-1, a new vasoactive and bronchoconstrictive peptide, is a powerful mitogen for smooth muscle cells and fibroblasts and plays a role in the inflammation state. We postulate that endothelin-1 has a role in sarcoidosis. METHODS: We studied the behaviour of circulating levels of endothelin-1 in 20 patients with sarcoidosis and its correlation with some biochemical parameters of activity disease, such as erythrocyte sedimentation rate (ESR) and serum angiotensin-converting enzyme (SACE). We measured serum levels of ESR, SACE, calcium and plasma endothelin-1 levels in all patients at the beginning of the study and one again in 9 patients with clinical-biochemical remission of disease after steroid treatment. RESULTS: In patients with sarcoidosis, circulating levels of endothelin-1, SACE and ESR were significantly higher (p<0.001) than those of healthy subjects. Moreover, in patients with pulmonary involvement, there was a significant statistical difference (p<0.001) between endothelin-1 levels and radiological stage compared to normal subjects. In the 9 patients with remission of disease, both endothelin-1 levels and parameters of activity disease normalized. CONCLUSIONS: Our results seem to suggest that the increase of plasma endothelin-1 levels in active sarcoidosis can represent an expression of the endothelial dysfunction and reflect the picture of cellular activation.

[High circulating levels of adrenomedullin and endothelin-1 in obesity associated with arterial hypertension]. / Elevati livelli circolanti di adrenomedullina e di endotelina-1 nell'obesità associata ad ipertensione arteriosa.

BACKGROUND: The aim of the study was to investigate the behavior of two endothelial vasoactive peptides, adrenomedullin (vasodilator) and endothelin-1 (vasoconstrictor), in human obesity with and without arterial hypertension. METHODS: The study was carried out on 30 obese subjects (body mass index > 27 kg/m2) divided into two groups: 15 normotensive obese patients (10 males, 5 females, mean age 42 +/- 12 years) and 15 hypertensive obese patients (9 males, 6 females, mean age 42 +/- 13 years). The control group consisted of 21 normal subjects (12 males, 9 females, mean age 38 +/- 12 years) and of 16 patients with essential hypertension (10 males, 6 females, mean age 41 +/- 12 years) but without organ damage. All studied subjects were taking a normocaloric (20-22 kcal/kg/day), normosodic (120-140 mEq/day) and normopotassic (50-60 mEq/day) diet. Between 8.00 and 9.00 a.m., a venous blood sample was taken for the determination (radioimmunoassay) of plasma adrenomedullin and endothelin-1 concentrations. RESULTS: Plasma adrenomedullin levels in normal subjects (13.7 +/- 6.1 pg/ml) were similar to those in normotensive obese patients (14.8 +/- 7.2 pg/ml), whereas in hypertensive obese patients (22.5 +/- 9.1 pg/ml) and in those with essential hypertension (22.7 +/- 8.2 pg/ml) levels were significantly higher (ANOVA = 0.000, p < 0.05) than those of normal subjects and of normotensive obese patients. Moreover, endothelin-1 plasma concentrations were found to be significantly higher (ANOVA = 0.000, p < 0.05) in hypertensive obese patients (10.3 +/- 2.7 pg/ml) compared to normal subjects (6.5 +/- 2.4 pg/ml), normotensive obese patients (8.3 +/- 1.5 pg/ml) and to those with essential hypertension (8.5 +/- 2.9 pg/ml). In patients with essential hypertension, a positive correlation (r = 0.493, p < 0.05) was found between adrenomedullin and endothelin-1 plasma levels. CONCLUSIONS: These results revealed that in human obesity associated with arterial hypertension there is an increased production of plasma adrenomedullin and endothelin-1 that, with their opposite vasoactive properties (vasodilation/vasoconstriction), can contribute to this pathological association.

Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma.

BACKGROUND: The hypotensive peptide adrenomedullin was first isolated in extracts of human pheochromocytoma. There is, however, no information available on the behaviour of circulating adrenomedullin or on the correlation with catecholamines in patients with pheochromocytoma. OBJECTIVES: 1) to investigate whether plasma adrenomedullin levels were changed in 10 patients with pheochromocytoma when compared to 21 healthy subjects and 16 patients with essential hypertension; 2) to determine whether or not adrenomedullin has a counter-regulatory role in catecholamine excess in pheochromocytoma or is responsible for hemodynamic modifications before and after tumour resection; 3) to determine tissue distribution of iradrenomedullin in the pheochromocytoma. METHODS: Plasma adrenomedullin and catecholamine levels were measured in all patients with pheochromocytoma before and four weeks after tumour removal. In the four patients undergoing resection of tumours, plasma levels of adrenomedullin were measured at different time-points during surgery. RESULTS: The mean plasma adrenomedullin concentrations ( SD) in patients with pheochromocytoma (37.9 +/- 6pg/ml) were significantly higher (p<0.0001) than those in normal subjects (13.7 +/- 6.1 pg/mI) and patients with essential hypertension (22.5 +/- 9.lpg/ml). Adrenomedullin levels correlated with plasma noradrenaline (r = 0.516, p = 0.0124). In all patients with pheochromocytoma, plasma adrenomedullin concentrations decreased after removal of tumours (from 37.9 +/- 6 to 10.9 +/- 4.6 pg/ml; p < 0.0001). In the four patients studied during surgery, baseline plasma adrenomedullin and noradrenaline levels were markedly elevated, and increased significantly with tumour manipulation, decreasing 24 hours after operation. Adrenal medulla cells surrounding the pheochromocytoma site stained for ir-adrenomedullin, whereas only isolated cells of pheochromocytoma stained for the peptide. CONCLUSIONS: This study demonstrates that circulating adrenomedullin is increased in pheochromocytoma, and is also correlated with plasma noradrenaline levels. Adrenomedullin may represent an additional biochemical parameter for clinical monitoring of patients with pheochromocytoma.

Endothelin-1 circulating levels increase in patients with orthotopic heart transplantation and in chronic therapy with cyclosporine.

BACKGROUND: The aim of the study was to investigate the behaviour of plasma levels of endothelin-1 (ET-1), an endothelial peptide with vasoconstrictive and proliferative actions, in patients with cardiac transplantation and in chronic treatment with cyclosporine A, some of whom became hypertensive after cardiac transplantation. METHODS: We studied: 1) 18 consecutive patients (15 M, 3F; mean age 53 +/- 7 yrs) who underwent cardiac transplantation about six months ago at least (range 6-108 months); 2) 15 patients with essential arterial hypertension (10 M, 5 F; mean age 42 +/- 15 yrs) without organ damage; 3) 21 normal subjects (15 M, 6 F; mean age 31 +/- 12 yrs). Plasma levels of ET-1 (RIA), haemodynamic and functional renal parameters were determined in all groups and plasma levels of cyclosporine were measured in patients with cardiac transplantation. RESULTS: ET-1 was higher in patients with cardiac transplantation than in the other two groups (p < 0.05); instead there was no difference between patients with essential arterial hypertension and controls (p>0.05). A statistical difference was found between circulating ET-1 in hypertensive transplanted patients. In heart transplanted patients a positive and significative correlation was found between plasma levels of ET-1 and systolic (r=0.525; p<0.037) blood pressure.

Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma.

It has been demonstrated that adrenomedullin, a newly discovered peptide with structural similarity to calcitonin gene-related peptide (CGRP), is expressed in pituitary gland and affects basal and corticotropin (ACTH)-releasing factor (CRF)-stimulated ACTH release in animals, thus suggesting its potential role in regulating the hypothalamus-pituitary-adrenal axis. To evaluate whether ACTH and cortisol levels affect adrenomedullin production in humans, we studied 14 patients with Cushing's syndrome due to pituitary adenoma and 8 patients with Cushing's syndrome due to adrenal tumor, with measurement of circulating adrenomedullin by a specific radioimmunoassay (RIA). Adrenomedullin concentrations were significantly higher in patients with pituitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) and patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surgical treatment, plasma adrenomedullin decreased significantly. In one patient with Cushing's syndrome due to pituitary adenoma who underwent simultaneous sampling of the inferior petrosal venous sinuses, the adrenomedullin concentration was significantly higher in plasma collected from the side with the adenoma and increased after CRF administration (delta increase, 42.6%), according to ACTH levels. Our findings indicate that circulating adrenomedullin is increased in Cushing's disease, and the pituitary gland may represent the site of the elevated production of adrenomedullin in this condition.

Plasma levels of endothelin-1 in patients with Crohn's disease and ulcerative colitis.

AIM: The purpose of this study was to investigate the behavior of circulating endothelin-1, a vasoconstrictor and mitogenic peptide, in patients with inflammatory bowel disease. PATIENTS: We investigated plasma endothelin-1 levels in 29 patients with Crohn's disease, 13 with ulcerative colitis and 26 healthy subjects as controls. METHODS: Erythrocyte sedimentation and C-reactive protein were also measured in all patients. Plasma endothelin-1 was measured by specific radioimmunoassay and expressed as pg/ml. RESULTS: Both Crohn's disease and ulcerative colitis patients showed a significant increase in plasma endothelin-1 concentration (22.3 +/- 8.2 pg/ml and 11.2 +/- 2.7 pg/ml, respectively) when compared to healthy subjects (6.2 +/- 1.5 pg/ml). Moreover, plasma endothelin-1 levels were significantly higher in Crohn's disease patients than those in ulcerative colitis patients (22.3 +/- 8.2 pg/ml vs 11.2 +/- 2.7 pg/ml; p < 0.001, respectively). A weak correlation (r = 0.645; p < 0.013) between erythrocyte sedimentation and endothelin-1 levels was observed in Crohn's disease patients. Age, sex, clinical activity of the disease, duration of history, anatomical localization of disease and therapy had no influence on plasma endothelin-1 levels. CONCLUSION: Our results show that plasma endothelin-1 levels increase in chronic inflammatory bowel disease and mainly in Crohn's disease. This observation leads us on to believe that endothelin-1 has a important role in inflammatory bowel disease.

Circulating levels of adrenomedullin in patients with Addison's disease before and after corticosteroid treatment.

BACKGROUND AND OBJECTIVE: A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure. DESIGN: Plasma AM levels were measured in patients with proven Addison's disease using a specific radioimmunoassay and compared to those in healthy normotensive subjects. PATIENTS: Eighteen patients with Addison's disease (10 men and eight women; ages 21 to 72 years) and 21 healthy control subjects (13 men and eight women; ages 20 to 71 years) were enrolled in the study. All patients were studied under basal conditions and 10 were reassessed following corticosteroid treatment. RESULTS: All patients with Addison's disease showed increased levels of AM compared to the control group. Mean plasma AM levels were correspondingly higher in patients with Addison's disease than in normal subjects (102.1 +/- 33.4 (SD) ng/l versus 13.7 +/- 6.1 ng/l; P < 0.0001). In 10 patients studied after corticosteroid treatment, plasma AM levels were significantly reduced (P < 0.0001: 110.3 +/- 35.8 ng/l versus 32.4 +/- 10.3 ng/l) after 2 weeks of treatment. A weak correlation (r = 0.458; P = 0.048) was observed between systolic blood pressure and plasma AM concentrations in all patients with Addison's disease. CONCLUSIONS: These results indicate a consistent but reversible increase of adrenomedullin in patients with Addison's disease.

Adrenomedullin levels are high in primary aldosteronism due to adenoma and decline after surgical cure.

The aim of the study was to evaluate the possible changes in plasma adrenomedullin (AM) levels in patients with primary aldosteronism before and after surgical resection. The study included 13 patients affected by aldosterone-producing adenoma (9 women, 4 men; mean age 36.2+/-14.2 years) and 20 healthy control subjects (7 women, 13 M; mean age 31.8+/-12.4 years). Unilateral adrenalectomy was performed in all patients and adrenal mass consisted of a benign adrenal cortical adenoma. The mean plasma AM concentrations in patients with primary aldosteronism (36.2+/-19.3 pg/ml) were significantly (p < 0.0001) higher than those of normal subjects (13.2+/-6.2 pg/ml). In these patients the plasma AM levels significantly (p < 0.0001) reduced after surgical removal of the tumours (14.9+/-7.6 pg/ml). In all patients with aldosterone-producing adenoma, tumour diameter correlated with the plasma AM concentrations (r=0.631; p < 0.021). In conclusion, the present investigation shows that in primary aldosteronism due to adrenal adenoma plasma AM levels are higher at the moment of diagnosis and decline after successful adrenal operation.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7 +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/- 3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

[Behavior of plasma levels of endothelin 1 and noradrenaline in patients with stable angina during the cold pressor test]. / Il comportamento dei livelli plasmatici di endotelina-1 e di noradrenalina nei pazienti con angina stabile in corso di cold pressor test.

The aim of this study was to evaluate the behaviour of plasma endothelin-1 (ET-1) and norepinephrine (NE) levels in patients with stable angina during a sympathetic stimulation test as the cold pressor test. We enrolled in the study 29 subjects: 14 patients with stable angina (all men, mean age 58.3 +/- 7.3 years) and 15 healthy subjects (all men, mean age 54 +/- 5 years). All patients with stable angina had a stenosis of the coronary arteries (at least 70% of the stenosis in one of the coronary arteries) confirmed by angiography. Before (-15 min; 0 min) during (+2 min) and after the cold pressor test (+5 min, +10 min, +20 min, +30 min) were measured the blood pressure and the heart rate. At the same time were collected venous samples for the ET-1 and NE determination. ET-1 levels increased only in the patients with stable angina (ET-1: O' = 9.8 +/- 3.7 pg/ml; +2' = 11.1 +/- 4.5 pg/ml; +10' = 14.8 +/- 7.1 pg/ml; +20' = 11.6 +/- 5.1 pg/ml; p < 0.05 vs 0', +2'; +20'). The NE levels increased in both groups (NE stable angina: 0' = 105 +/- 31 pg/ml; +2' = 206 +/- 127 pg/ml; +5' = 223 +/- 135 pg/ml; p < .05 vs +2', +5'); (NE healthy subjects 0' = 85 +/- 10 pg/ml; +2' 165 +/- 49 pg/ml; p < 0.05 vs + 2'). In conclusion, our study showed that cold pressor test is a stimulus for the sympathetic system in both groups. The increased levels of ET-1 detected only in the patients with stable angina suggest that this peptide can take part to the pathogenesis of the coronary artery disease.

Circulating endothelin-1 in non-insulin-dependent diabetic patients with retinopathy.

Endothelin-1 (ET-1), a novel 21-amino acid vasoconstrictive peptide secreted by endothelial cells, has been thought to play a role in various forms of vascular disease. Diabetes mellitus is well known for its association with microvascular damage. To investigate whether ET-1 levels may be related to microangiopathy in diabetes mellitus, plasma ET-1 levels were measured in two groups of diabetic patients: A) 47 patients with non-insulin dependent diabetes mellitus (NIDDM) and retinopathy (28 M, 19 F; mean age 60.7+/-8.5 yrs) but without nephropathy (microalbuminuria < 30 mg/day) and hypertension (SBP < 140, DBP < 90 mmHg); group A was divided in three subgroups based on the severity of retinopathy: a) 16 with background retinopathy; b) 21 with pre-proliferative retinopathy; c) 10 with proliferative retinopathy. B) 8 patients with insulin-dependent diabetes mellitus (IDDM) recently diagnosed (6 M, 2 F; 16.4+/-3.8 yrs) without complications. C) 28 healthy subjects (HS) (16 M, 12 F; 47.8+/-11.8 yrs) as controls. In the NIDDM group the ET-1 concentration was significantly higher (17.3+/-2.4 pg/ml) than both in the HS (8+/-4.7 pg/ml) and IDDM patients (10.2+/-3.7 pg/ml) (p < 0.0001). In the subgroups with retinopathy the ET-1 levels were a) 15.1+/-4.3 pg/ml; b) 22.2+/-6.8 pg/ml and c) 16.6+/-5.1 pg/ml. These values were significantly elevated as compared to HS (p<0.001; p < 0.0001; p < 0.002, respectively), being the highest levels of ET-1 observed in the NIDDM patients with pre-proliferative retinopathy. In conclusion our study revealed that the ET-1 concentrations are elevated in NIDDM patients with retinopathy especially in those patients with pre-proliferative retinopathy.

High plasma levels of endothelin-1 in untreated Addison's disease.

The aim of this study has been to investigate the plasma endothelin-1 (ET-1) levels in adult patients with proven Addison's disease (AD). Plasma ET-1 levels were measured in 29 subjects (17 males and 12 females, aged between 20 and 54 years): 15 of them were patients with AD and 14 were sex- and age-matched normal subjects, used as a control group. All patients with AD have been studied under basal conditions and nine of them also after 2 weeks on oral corticosteroid therapy (individual cortisol dosage ranging from 25 to 37.5 mg/day and 0.1 mg/day 9 alpha-fluorohydrocortisone). Extracted plasma ET-1 was determined by a specific radioimmunoassay using rabbit endothelin antisera. Mean ET-1 values in the patients with AD were three times higher than in normal subjects (21.09 +/- 4.38 pg/ml vs 6.72 +/- 1.74 pg/ml; p < 0.0001). Plasma ET-1 levels assayed in the patients with AD after 2 weeks of corticosteroid therapy were significantly decreased (14.47 +/- 3.7 pg/ml vs 22.8 +/- 5.2 pg/ml; -37%; p < 0.001) compared to values in untreated patients. However, the plasma ET-1 values obtained following corticosteroid therapy were still significantly higher (p < 0.001) than those detected in the control subjects. These results clearly indicate that patients with untreated AD have increased circulating ET-1 levels that may be reduced by short-term corticosteroid therapy.