Giovanni Ciuffetti

Plasma profiles of adrenocorticotropic hormone, cortisol, growth hormone and prolactin in patients with untreated Parkinson's disease

SummaryPlasma profiles of prolactin, growth hormone, adrenocorticotropic hormone (ACTH) and cortisol were evaluated in a group of untreated patients with idiopathic Parkinsons disease and a group of healthy age-matched controls. Plasma integrated concentrations of all hormones except prolactin were significantly lower in the patients as compared with the controls; however, prolactin nocturnal peak concentration was significantly elevated in the patients; nocturnal growth hormone levels were significantly reduced in the Parkinson group; ACTH and cortisol plasma concentrations were also consistently lower during most of the day in the patients with Parkinsons disease. These data confirm the presence of a hypothalamic disturbance in patients with idopathic Parkinsons disease, which can affect pituitary function.

WHOLE-BLOOD FILTERABILITY IN SUDDEN DEAFNESS

Sixteen patients with sudden deafness (SD), diagnosed on the basis of a battery of audiometric tests, but with no other medical or surgical pathology requiring drug treatment, underwent monitoring of their hemorheological profiles to see whether disturbances in the microcirculation could be linked to SD. Plasma viscosity, the filterabilities, (using a low‐shear positive pressure system) through 5‐μm‐diam‐eter pore Nuclepore filters, of whole blood and red and unfractionated white cells were monitored in 16 SD patients and 32 controls matched for age, sex and socioeconomic status. Whole blood filterability and the filterability of the red blood cells were significantly impaired in the SD patients, which suggests that alterations in the microcirculation are linked, in some way, to sudden deafness.

Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease : results of a double-blind placebo-controlled study

SummaryThe effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study. Leucocyte-derived free radical generation (by the superoxide dismutase-inhibitable reduction of ferricytochrome), the release of reactive oxygen metabolites (as plasma oxidant activity), unfractionated leucocyte and erythrocyte filterability rates (using a constant-flow positive-pressure system), plasma viscosity, and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease, before and after treatment. Transcutaneous oxygen pressure (PtcO2) during treadmill exercise to stress leg circulation was also measured.Leucocyte-derived free radicals were generated during peripheral ischaemia. Pentoxifylline inhibited their generation, blocked the release of reactive oxygen metabolites, and reduced impairment of the filterability rate of unfractionated leucocytes.The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure, indicating that ischaemic damage had been contained.

Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia

High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol [LDL-c] 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.

Blood cell rheology in acute cerebral infarction.

Recently it has been hypothesized that leukocyte rheology could be a relevant variable of the microcirculation during cerebral ischemia. However, relatively few studies have been carried out on the rheologic behavior of leukocytes in vascular diseases. This study aimed at quantifying the filterability through Nuclepore filters (mean pore diameter 5 microns) of both leukocyte subpopulations and red blood cells in patients with acute stroke compared with age-matched healthy controls. Leukocytes were separated by density into polymorphonuclear and mononuclear cells. Filterability of the red blood cells and polymorphonuclear and mononuclear subpopulations in buffer was measured using a constant-flow and low-positive pressure system. We used one-way analysis of variance, signed rank sum, and simple and multiple regression tests for statistical analysis. Twenty consecutive male patients with acute ischemic infarction were compared with 20 age-matched healthy subjects. Mononuclear cell filterability was impaired in acute stroke (7.26 +/- 2.00) compared with the controls (5.55 +/- 1.23) (p less than 0.01). Polymorphonuclear cell filterability was less, but still significantly (p less than 0.05), impaired in acute infarction (5.75 +/- 0.87 vs. 4.19 +/- 0.43). The results show that leukocyte and, especially, mononuclear cell filterability is impaired in acute infarction, while no differences exist in red blood cell filterability.

Renal dysfunction predicts long‐term mortality in patients with lower extremity arterial disease

Abstract.  Pasqualini L, Schillaci G, Pirro M, Vaudo G, Siepi D, Innocente S, Ciuffetti G, Mannarino E (University of Perugia, Perugia, Italy). Renal dysfunction predicts long‐term mortality in patients with lower extremity arterial disease. J Intern Med 2007; 262: 668–6.

Predictors of overall and cardiovascular mortality in peripheral arterial disease

S rates in patients with intermittent claudication and in patients with critical leg ischemia (CLI) have never been compared directly in a western population, and no report has yet determined the prognostic significance of the 2 clinical presentations of peripheral arterial disease (PAD) in long-term followup. Most observational studies have examined patients with critical and noncritical leg ischemia separately, or have reported the prognostic value of the ankle-brachial blood pressure index. We conducted a study to determine whether CLI is an independent risk factor for all-cause and cardiovascular mortality, paying attention to the confounding effect of other prognostic factors, including traditional cardiovascular risk factors and concomitant cardiac and cerebrovascular disease. • • • We studied 297 consecutive Caucasian patients with symptomatic PAD who were referred to the outpatient clinic of the Internal Medicine, Angiology and Arteriosclerosis Unit at the University of Perugia, Italy, between 1988 and 1999. Two hundred thirteen patients had intermittent claudication, defined as lower extremity pain induced by walking or equivalent muscular activity that was promptly relieved by rest. Eighty-four patients were affected by chronic CLI, defined as persistently recurring pain at rest for 2 weeks (12 patients) or foot ulceration and gangrene (72 patients). All subjects had an ankle-brachial index of 0.9. Patients with neoplasms or concomitant severe, life-threatening disease were excluded from the study. Patients were interviewed and examined by a physician, who recorded the patients’ demographic and clinical characteristics. Smoking habits were assessed by questionnaire. A history of cardiovascular disease (previous myocardial infarction, angina, heart failure, stroke, or transient ischemic attack) and a history of peripheral revascularization procedures (coronary artery bypass graft, percutaneous transluminal angioplasty) or major amputations (at or above the ankle) were recorded. Arterial hypertension was defined as systolic blood pressure 160 mm Hg and/or diastolic blood pressure 95 mm Hg, or use of antihypertensive treatment. Glucose, cholesterol, and triglyceride concentrations were determined by a fasting blood sample. Diabetes mellitus was defined as fasting serum glucose levels 7.8 mmol/L (140 mg/dl) or current treatment with insulin or oral hypoglycemic agents. All patients underwent a noninvasive vascular evaluation of the lower limbs by Duplex scanning. A standard 12-lead electrocardiographic examination and a Duplex scan of common and internal carotid arteries were also performed and coded independently by 2 observers. The following electrocardiographic abnormalities were recorded: previous myocardial infarction, ischemia, left ventricular hypertrophy, and atrial fibrillation. Carotid artery disease was defined as 50% diameter stenosis. Clinical visits were planned every 6 months for patients with CLI, and every year for patients with claudication. Contacts with family physicians and telephone interviews were undertaken to determine vital status in those patients who ignored follow-up. All subjects were advised to discontinue smoking, and regular physical exercise was recommended for patients with claudication. The best treatment aimed at correcting other risk factors was based on appropriate lifestyle measures and pharmacologic therapy. Eightythree percent of patients received antiplatelet agents, and 5% received oral anticoagulants, with no significant differences between patients with CLI and patients with intermittent claudication. Using the International Classification of Diseases, 9th Revision, Clinical Modification, deaths due to cardiovascular disease were assigned a code from 400 to 444. Reported deaths were confirmed by death certificates; relevant hospital record forms and other available original source documents were reviewed in conference by the investigators. Follow-up for mortality was completed for all patients. Nonfatal cardiovascular events included myocardial infarction and stroke. Myocardial infarction was diagnosed on the basis of 2 of 3 criteria (typical chest pain, electrocardiographic QRS changes, and transient elevation of myocardial enzymes). Stroke was diagnosed on the basis of rapid onset of localizing and persistent neurologic deficit in the absence of any other disease process explaining the symptoms. Progression of peripheral ischemia was defined by the onset of CLI in patients with intermittent claudication at baseline, or by the need for major amputations or revascularization procedures. Parametric data are reported as mean SD. Standard descriptive and comparative analyses were undertaken. The death rate is presented as the number of deaths per 100 patient-years based on the ratio of the number of deaths observed to the total number of patient-years of exposure up to death or censor. For From the Unit of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. Dr. Pasqualini’s address is: Internal Medicine, Angiology and Arteriosclerosis, University of Perugia, via Brunamonti, 06122 Perugia, Italy. E-mail: lpasqua@unipg.it. Manuscript received April 16, 2001; revised manuscript received and accepted June 11, 2001.

Prognostic impact of low‐shear whole blood viscosity in hypertensive men

Background  The role of blood viscosity as a marker for discriminating cardiovascular risk in essential hypertension remains uncertain. The aim of this study was to assess whether whole blood viscosity (WBV) could be useful in assessing cardiovascular risk in men with a first diagnosis of hypertension.

Efficacy of Low-Molecular-Weight Heparin in the Management of Intermittent Claudication

Treating chronic arterial occlu sive disease with heparin is contro versial because of the risks associated with long-term anticoagulant ther apy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa fac tor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both ve nous and acute arterial thromboem bolism. Therefore, 44 patients with inter mittent claudication were recruited to a randomized, double-blind, con trolled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain- free walking time by 25 %) but also significantly modified the hemor rheologic pattern (by reducing fibrin ogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an anti thrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen ac tivity without markedly modifying activated partial thromboplastin time ( + 20 %). No LMW heparin- treated patient hemorrhaged or re ported other noteworthy side effects. These results suggest LMW hepa rin might be a useful drug in the long- term treatment of chronic arterial occlusive disease of the limbs.

Effect of Oral Administration of Sulodexide on Fibrinolysis and Plasma Viscosity: A Pilot Study

SummaryThe purpose of this pilot study was to examine the effects of a new enteric-coated formulation of sulodexide, a glycosaminoglycan extracted from mammalian intestine, on blood, plasma and serum viscosity, and fibrinolysis in patients with plasma hyperviscosity. Six outpatients with plasma viscosity exceeding 1.40cP were administered oral sulodexide 100mg once daily for 7 days. On days 1 and 7 whole blood and plasma viscosity were measured before administration of sulodexide and 2, 4 and 8 hours after drug administration; at the same time functional and antigenic PAI (plasminogen activator inhibitor) and functional and antigenic tPA (tissue plasminogen activator) were evaluated to investigate the fibrinolytic balance of patients.The results demonstrated a marked reduction in plasma viscosity, which was observed 2 to 4 hours after the first dose of sulodexide and was even more marked on the seventh day, while whole blood and serum viscosities dropped only slightly after 7 days of sulodexide treatment. Sulodexide also induced a marked decrease in functional and antigenic PAI, and an increase in functional tPA, while no changes were observed in antigenic tPA.