Carotid atherosclerosis and ischemic stroke in young patients.

BACKGROUND: Epidemiological studies indicate a high prevalence of carotid atherosclerosis in elderly patients with ischemic stroke. The aim of this study was to investigate the presence of early carotid atherosclerotic lesions in young subjects with ischemic stroke, in the absence of the common atherosclerotic risk factors. METHODS: We studied 98 young patients with first ischemic stroke (54 males and 44 females; mean age 41.2 years; range 32-50) and 96 healthy controls. All subjects underwent ultrasonographic scanning of the carotid arteries according to a standardized protocol. RESULTS: The carotid intima-media thickness was significantly increased in the patient group (p<0.001) compared with controls. In addition, the prevalence of carotid atherosclerotic plaques was greater in the patients than in the controls (p<0.001). In particular, we detected 18 non-occlusive carotid plaques and 16 thrombotic occlusions. In 8 patients, the lesions were bilateral. The echographic pattern of the plaques was hard in 8 cases, soft in 5 cases, and mixed in the remaining 5 cases. CONCLUSIONS: We detected an increased wall thickness of the carotid arteries and an increased prevalence of carotid atherosclerotic lesions and carotid thrombotic occlusions in young patients with ischemic stroke, with a relative low incidence of cardiovascular risk factors. This finding suggests that arterial intima-media thickness per se is an important determinant of vascular disease in young patients. The data also provide indirect support for the potential role of genetic factors in the genesis of atherosclerosis in young patients.

Myocardial ischemia caused by an hydatid cyst of the interventricular septum successfully treated with albendazole.

We report the case of a 33-year-old patient with clinical history of echinococcosis admitted to our Hospital for the appearance of chest pain and electrocardiographic findings of anterior ischemia. The cardiac enzymogram was in the normal range, the chest roentgengram did not show any pathological findings, but two-dimensional echocardiography revealed the presence of a small circular area in the interventricular septum. Transesophageal echocardiography and cardiac nuclear magnetic resonance confirmed the presence of a small hydatid cyst in the middle ventricular septum; in addition, a myocardial scintigraphy revealed an apical stress defect with late reperfusion. Besides cardiologic therapy, the patient was treated with albendazole, an antiparasitic drug, 400 mg bid, for cycles of 28 days with 14 day withdrawal. After two cycles of albendazole therapy, two-dimensional echocardiography showed the absence of the round cystic mass of the interventricular septum previously described. In conclusion, in the case described, long-term therapy with albendazole determined the complete recovery from the illness with the simultaneous disappearance of the cyst and of clinical and electrocardiographic findings of myocardial ischemia.

Cardiovascular effects of short-term growth hormone hypersecretion.

Many studies have shown that acromegaly has relevant effects on cardiovascular system, but few data are available regarding the effects of short-term acromegaly on heart morphology and function. These data would help to clarify the natural history of acromegalic disease and could provide new insight into the mechanisms of GH action on the human heart. Therefore, we studied by Doppler echocardiography a group of 10 young subjects strictly selected as having short-term (<5 yr) uncomplicated acromegaly. The results of this study have shown that shortterm acromegaly is characterized by significantly increased left ventricular mass (P<0.005), with normal relative wall thickness, associated with Doppler indices of diastolic function in the normal range. Furthermore, stroke index and cardiac index were significantly enhanced in the patient group (P<0.01 and P<0.001, respectively), whereas systemic vascular resistance was significantly reduced (P<0.001). In conclusion, our study shows that short-term acromegaly significantly affects the heart, but, at variance with long-term disease, it is characterized by increased left ventricular mass, with eccentric remodeling and normal diastolic function. Moreover, short-term acromegaly induces a high cardiac output state with reduction of systemic vascular resistance.

Pulmonary hypertension associated with liver cirrhosis: an echocardiographic study.

Conflicting results about the prevalence of pulmonary hypertension, ranging from 0.25% to 20%, in liver patients with portal hypertension, have previously been reported. The aim of this study was to evaluate pulmonary arterial pressure in a consecutive series of cirrhotic patients, using a noninvasive method. A complete clinical, laboratory, ultrasonographic, and endoscopic evaluation were performed in 83 consecutive liver patients assessed according to Child's classification and Pugh's score and according to evidence of ultrasonographic and/or endoscopic signs of portal hypertension. A complete echocardiographic evaluation was also performed and pulmonary arterial systolic pressure (PASP) was estimated by measuring tricuspidal regurgitation, using the modified Bernoulli equation. These same evaluations were performed by the same observers in a group of 60 healthy volunteers. The results showed a surprisingly high prevalence (about 20%) of pulmonary hypertension. Patients with more severe liver damage and portal hypertension showed a high prevalence for pulmonary hypertension. A progression in the frequency of portopulmonary hypertension (PPH) was found in Child's classification A to C, and in patients without to patients with evidence of portal hypertension. However, increased PASP was detected in some patients belonging to Child's class A, without evidence of portal hypertension. In conclusion, the echocardiographic examination (a noninvasive technique), appears suitable for detecting pulmonary hypertension in patients with compensated liver cirrhosis, and can elucidate some aspects of the clinical course of the so-called PPH syndrome.

[Carotid atherosclerosis and thrombotic stroke. Diagnostic and therapeutic perspectives]. / Aterosclerosi carotidea ed ictus aterotrombotico. Attuali prospettive diagnostiche e terapeutiche.

Carotid atherosclerotic lesions can be studied with color-Doppler ultrasonography vascular systems. Ultrasonography of the carotid plaques at major risk for the development of cerebrovascular ischemic events showed the following characteristics: irregular surface, degree of stenosis > 70%, intimal hemorrhage and ulceration. The plaques with these ultrasonography patterns have to be considered for surgical approach (TEA). The other patients with carotid atherosclerotic lesions will be initially treated with diet and changes of life style to obtain the correction of cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes). Furthermore, medical therapy with antithrombotic agents will be instituted which, used with good results also in acute cerebral stroke, proved to be effective in the reduction of vascular events in patients with extracranial atherosclerotic plaques. However, it has not been clarified if the positive effect of antiaggregation therapy in carotid atherosclerosis is due to the inhibition of the progression and plaque growth or if other hemorheological factors are involved.

Long-term safety and efficacy of picotamide, a dual-action antithromboxane agent, in diabetic patients with carotid atherosclerosis: a 6-year follow-up study.

In a controlled, randomized, 6-year trial the safety and efficacy of picotamide, a dual-action antithromboxane agent, were assessed in 50 patients with type 2 diabetes mellitus at increased risk of thrombotic vascular events. The patients were randomized to two groups of equal size and received 900 mg picotamide daily or placebo. After phase I (double-blind; years 1 - 2), patients receiving placebo were treated, if necessary, with antiplatelet drugs (aspirin, ticlopidine) while members of the other group continued to receive 600 mg picotamide daily. In the course of the study 21 vascular events occurred: 16 in the group receiving placebo (fatal myocardial infarction, n = 7; non-fatal stroke, n = 3) and five in the group receiving drug (fatal myocardial infarction, n = 2) (P < 0.005; Fisher's exact test). One patient (placebo group) died of malignant disease. During the initial double-blind phase a total of nine vascular events was observed (six and three in the groups receiving placebo and drug, respectively). Picotamide treatment was well tolerated and no major side-effects were observed during the study periods.

Increased arterial intima-media thickness in childhood-onset growth hormone deficiency.

Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/- 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/- 0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

Antiaggregatory effects of picotamide in long-term treatment: a 2-year, double-blind placebo-controlled trial.

The ex vivo antiaggregatory activity of picotamide, a dual antithromboxane agent, was assessed to find whether it was maintained in long-term treatment. In a double-blind, placebo-controlled 2-year study, 50 type 2 diabetic patients (35 men and 15 women; mean age 66 +/- 5 years) were enrolled and randomly given picotamide, 300 mg t.i.d. or the corresponding placebo. Platelet aggregation studies were performed at baseline and after 1, 3, 6, 12, 18 and 24 months. Compliance to the treatment was assessed by pill count at each visit. Forty-nine patients concluded the study. Starting from month 1, compared with placebo, picotamide-treated patients showed a significant inhibition of agonist-induced (ADP, arachidonic acid and collagen) platelet aggregation (-41%). The antiaggregatory effect was maintained throughout the study. At month 24, in the picotamide group, platelet aggregation was significantly lower compared with placebo (-30%). After 24 months of treatment, 20 out of 23 (86%) picotamide-treated patients showed a significant inhibition of platelet aggregation, whereas the remaining three patients had a normal platelet response. During the study, 12 patients suffered from thrombotic events of death: nine in the placebo group and three in the picotamide group, respectively. It was concluded that picotamide maintains its antiaggregatory effect, in long-term treatment, in more than 85% of patients.

Effects of picotamide, an antithromboxane agent, on carotid atherosclerotic evolution. A two-year, double-blind, placebo-controlled study in diabetic patients.

BACKGROUND AND PURPOSE: We assessed the effects of long-term treatment with picotamide, an antiplatelet agent with dual antithromboxane activity, on the evolution of early asymptomatic carotid atherosclerotic lesions in diabetic patients. METHODS: In a double-blind, placebo-controlled, 2-year study, 50 type II normotensive diabetic patients (35 men; mean age, 66 +/- 5 years) with asymptomatic mild or moderate nonstenotic (< 50%) carotid atherosclerotic lesions and negative history of cerebrovascular ischemic events were enrolled and randomly given picotamide (300 mg TID) or the corresponding placebo. A high-resolution, real-time B-scan echographic assessment of carotid arteries was performed at baseline and after 1, 3, 6, 12, 18, and 24 months of double-blind treatment. Prevalence and evolutionary trends of carotid atherosclerotic lesions (number per patient and mean stenosis expressed as percent) were considered as efficacy primary end points. RESULTS: At baseline, mean +/- SD numbers of carotid atherosclerotic lesions per patient were 2.7 +/- 1.8 and 2.2 +/- 1.2 in the picotamide and placebo groups, respectively. Mean +/- SD percent stenosis was 25.3 +/- 7% in the picotamide group and 27.3 +/- 6% in the placebo group. Forty-nine patients completed the study. At month 24, the placebo group (n = 24) showed a significant progression in number of carotid atherosclerotic lesions (3.04 +/- 1.8; P < .02 versus baseline) and in mean percent stenosis (35 +/- 17%; 95% confidence interval, 33% to 37%; P < .01 versus baseline). In the picotamide group (n = 25), mean number of carotid atherosclerotic lesions (2.7 +/- 1.6) and percent stenosis (26 +/- 9%; 95% confidence interval, 24.8% to 27.2%) remained unchanged. At month 24, compared with randomized placebo, lesion numbers (P < .03) and percent stenosis (P < .01) in the picotamide group were significantly lower. During the study, 12 patients experienced major or minor ischemic vascular events (9 in the placebo group and 3 in the picotamide group; P = .07). CONCLUSIONS: In diabetic patients compared with patients receiving placebo, long-term treatment with picotamide can slow the evolution of early carotid atherosclerotic lesions, inhibiting progression of plaque number and growth.

Platelet aggregability in patients with a VVI pacemaker.

Several studies have suggested an increased incidence of thromboembolic events in patients with VVI pacemaker (VVI patients); furthermore, other authors have demonstrated that a treatment with anticoagulants or antiplatelet drugs may be effective in reducing thromboembolic events, thus suggesting an increased formation of platelet thrombi in these patients. In this respect, platelet aggregability was investigated in ten VVI patients and ten age- and sex-matched subjects. beta-thromboglobulin (beta-Tg) and platelet factor 4 (PF4) plasma levels were determined as well as platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid. Plasma beta-Tg levels were increased in the patient group (86 +/- 24 vs 24 +/- 13 ng/mL; P < 0.001) in presence of normal PF4 values (14 +/- 11 vs 13 +/- 6 ng/mL; NS). Aggregation curves showed abnormal values of maximal amplitude, slope, and lag time. In particular, maximal amplitude was significantly higher in VVI patients as compared with controls (ADP P < 0.01, collagen P < 0.001, adrenaline P < 0.01, arachidonic acid P < 0.05). These findings strongly suggest an increase of platelet activity in VVI patients.

Steady state pharmacokinetics of idebenone in patients with moderate hepatic impairment.

The kinetics of idebenone (45 mg twice daily p.o.) in 6 Caucasian chronic hepatopathic patients without portal hypertension were studied. The pharmacokinetic parameters were evaluated both for single (day 1) and multiple (day 10) administrations. These 6 patients showed a first order bi-compartimental kinetic curve for idebenone and for its metabolites, superimposable on the curves obtained from healthy volunteers. The C(max) parameters, tmax and bioavailability confirm the absence of accumulation. On day 12, 48 h after the last administration (performed on day 10), there was no evidence of residual drug. One of these patients was being treated with diuretics (chlorthalidone) and with perfusion fluids, including 5% glucose, and no interference was shown between the two drugs. There is no evidence of any particular side effect or alteration of the haematochemical parameters that could be thought to be drug related. This study confirms that idebenone at the dose of 90 mg/day p.o. administered to hepatopathic patients does not cause accumulation or toxicity.

Steady-state pharmacokinetics of idebenone in patients with moderate renal impairment.

Idebenone (45 mg twice daily) was administered to 7 patients with moderate renal impairment (creatinine clearance 21-40 ml/min) for 10 days. Standard pharmacokinetic parameters were computed on day 1 (single administration) and on day 10. On day 1 the mean of the maximum plasma concentration values (C(max)) was 364 ng/ml (standard deviation (S.D.) 100); time to C(max) (t(max)) was in the range of 1-2 h for 6 patients and 12 h for the remaining patient: the mean was 3 h (S.D. 3.99); the mean area under the plasma concentration vs. time curve (AUC) was 3005 ng h/ml (S.D. 1152). On day 10 the mean C(max) was 531 ng/ml (S.D. 355.3), the mean t(max) was 0.07 h (S.D. 0.19), the mean AUC was 3167 ng/ml (S.D. 2944) and the mean elimination half-life (t(1/2)) was 4.9 h (S.D. 1.1). Idebenone metabolites (QS-4, QS-6 and QS-10) showed a kinetic profile similar to the parent compound, with pharmacokinetic parameters comparable to idebenone for QS-4 and lower than idebenone for QS-6 and QS-10. Idebenone was metabolized and easily excreted and no accumulation was observed for the compound and its metabolites. No significant modification of the biohumoral indexes and vital signs and no adverse reactions were observed.

Evaluation of the clinical efficacy of idebenone in patients affected by chronic cerebrovascular disorders.

This study evaluated the efficacy and tolerability of idebenone, a new neuroactive drug, in 33 patients aged from 50 to 80 years. They were affected by chronic cerebrovascular disease (CCVD) and their last cerebrovascular accident had taken place at least 3 months prior to enrollment. All these subjects presented a score within the range of the following psychometric scales: Hamilton Scale for Depression <24; Hachinski Dementia Score >/=18 and < 25; Mini Mental State >/=16 and

[Diabetes and atherosclerosis: a follow-up echographic study of atherosclerotic carotid lesions]. / Diabete ed aterosclerosi: studio ecografico evolutivo delle lesioni aterosclerotiche carotidee.

A two years follow up on 105 diabetic patients and 50 normal subjects was carried out by high resolution real time echotomography, aiming to evaluate the prevalence and the evolutionary trends of carotid atherosclerotic plaques. The prevalence of atherosclerotic lesions was higher in diabetic patients than in normal subjects, and the most part of them showed an "intermediate" echographic pattern, minimal stenosis and regular surface. The results of the two years follow up indicate that the "soft" and the "hard" plaque types were those showing a more significant progression toward to the "mixed" type. "Hard" and "mixed" plaques, particularly those showing irregular surface, resulted most associated with higher degree of vessel stenosis. Four diabetic patients experienced three minor and one major ischemic events during the follow up; however all the patients had shown plaques with "intermediate" pattern, regular surface, and no signs of vessel stenosis progression. Further studies, performed for longer period of time with a higher number of patients are needed to evaluate the evolutionary trends of carotid plaques in diabetic patients and their relationship with clinical ischemic events.

POEMS syndrome: an Italian case with diagnostic and therapeutic implications.

A young Italian patient with a multisystem disorder and a solitary osteosclerotic bone lesion is described. His clinicopathological situation involved sensory-motor polyneuropathy, organomegaly, endocrine dysfunction, skin alterations, edema of the lower limbs and generalized lymphadenopathy. These features were consistent with the diagnosis of POEMS syndrome, reported primarily in Japanese patients. M components were not found in this patient's serum or urine. Bone marrow biopsy showed only a slight plasma cell infiltrate; histological study of the sural nerve evidenced a mixture of both axonal degeneration and segmental demyelinization. Lymph node biopsy revealed peculiar pathological changes resembling those of type II Castleman-like disease. A wide bone defect with osteosclerotic margins and trabeculation was evidenced in the right ilium. The relationship of these findings to plasma cell dyscrasias is discussed. After prednisone and local radiotherapy failed, the patient was treated with human recombinant interferon for 18 months. After three months of therapy he has experienced remarkable improvement of his neurological symptoms and almost complete recovery of organomegaly and lymphadenopathy. These improvements have continued to the present.

Effects of the treatment with matrix on elderly people with chronic articular degeneration.

Clinical trials have been conducted to evaluate the effectiveness of Matrix in osteoarthritis, mainly as regards the advantages offered by its physiological mechanism of action. The experiment, lasting 6 months, was performed on two hundred patients in four different Hospital Departments and one University Center. The results showed a considerable improvement both in pain and in mobility. No relevant side effects were found; only 3% of patients, with oral administration, noticed slight nausea and found it necessary to interrupt treatment.

[Restrictive cardiomyopathy in eosinophilic leukemia: echocardiographic and nuclear magnetic resonance aspects]. / Miocardiopatia restrittiva in corso di leucemia eosinofila: aspetti ecocardiografici e di risonanza magnetica nucleare.

This paper reports a case of endomyocardial disease due to hypereosinophilic syndrome. Two-dimensional echocardiography showed prevalent right ventricular involvement, with obliteration of the apex due to an echogenic mass progressively filling the whole ventricular cavity. RMN accurately defined the presence and the characteristics of the infiltrative mass in the right ventricular chamber. A different intensity of spin-echo imaging sequence was used to differentiate between thrombotic and infiltrative leukemic images. It is concluded that prevalent right ventricular involvement during eosinophilic endomyocardiopathy is a relatively rare disease which can be detected and evaluated by the use of echocardiography and RMN studies.

Regression of left ventricular hypertrophy and systolic function in hypertensive patients during long-term treatment with ketanserin.

It is now generally accepted that antihypertensive therapy can induce regression of left ventricular hypertrophy (LVH) in hypertensive subjects. However, the influence of LVH reversal on both the systolic and diastolic functions, and particularly the ability of the heart to meet sudden overloads caused by exercise and/or recurrence of hypertension, remain unanswered questions. The long-term effects of ketanserin, a selective serotonin S2-receptor antagonist with additional alpha 1-adrenergic blocking properties, on LVH and systolic function were studied in 13 untreated subjects (age range 35-55 years) with mild-to-moderate essential hypertension, echocardiographic evidence of LVH, and normal ejection fraction. Blood pressure values and echocardiographic measurements of dimensions, wall thicknesses, and indices of LV mass were determined before and after 3, 6, and 12 months treatment; ejection fractions at rest and during exercise were evaluated by equilibrium multigated radionuclide angiocardiography at baseline and after 12 months of therapy. Mean arterial pressure was significantly reduced from the first month of treatment (p less than 0.001) and remained well controlled up to the end of the trial. Both posterior and septum wall thicknesses decreased after 3 months of therapy and remained stable throughout the whole study period. LV mass index decreased from a mean +/- SD of 187.7 +/- 47.6 g/m2 to a mean of 157.81 +/- 31.63 g/m2 (p less than 0.01) at the third month, reaching greater decreases after 6 months (156.05 +/- 31.00 g/m2) and after 12 months (153.21 +/- 28.80 g/m2) of treatment. A significant correlation was found between LV mass and posterior wall thickness at the different observation times in the study. Finally, the regression of LVH at the end of therapy was not associated with impairment of systolic function, as assessed by measurements of ejection fraction at rest and during exercise.

Clinical efficacy of picotamide in long-term treatment of intermittent claudication.

The clinical efficacy of picotamide was investigated in a randomized, double-blind, placebo-controlled study in patients with peripheral occlusive arterial disease of the lower limbs at functional stage II of the Fontaine classification. Forty patients with a history of claudication for at least six months were admitted to the study and were given either 3 x 300 mg tablets of picotamide (20 subjects) or three identical placebo tablets (20 subjects) for six months. The two groups of patients were similar in regard to clinical features and potential risk factors. At the end of treatment painfree walking distance and systolic ankle-arm pressure ratio improved more in the picotamide than in the placebo group (p = 0.05). Systolic ankle pressure curves, determined before and after the six-month treatment, showed a positive trend to a higher postexercise ankle pressure and a faster return to the preexercise levels in the picotamide group; however, the difference was not statistically significant. Laboratory monitoring revealed a slight prolongation of bleeding time, a significant decrease in arachidonic acid-induced platelet aggregation, and an enhanced fibrinolysis with absence of interference with hemostasis in the picotamide group. One patient in the placebo group developed a major cardiovascular event (angina pectoris) during the study. These results indicate that picotamide is an effective drug that may modify the natural course of intermittent claudication and associated vascular problems.