Classical pterional compared to the extended skull base approach for the removal of clinoidal meningiomas.

We reviewed a series of 46 consecutive, surgically treated patients with clinoidal meningioma to compare the classical pterional approach (32 patients) to an extended approach including extradural clinoidectomy and removal of the optic canal roof (14 patients). The tumor size and Al-Mefty type, the extension into the optic canal, the time to identification of the optic nerve and internal carotid artery, and the visual outcome were evaluated. Complete tumor resection was obtained in 81% of patients with the classic pterional approach compared to 93% of patients using an extended approach. The extended skull base approach should be used routinely in clinoidal meningiomas >2.5 cm in size, in ones of Al-Mefty type III, and in all patients with tumor extension into the optic canal.

Spinal meningiomas: age-related features.

OBJECTIVES: Spinal meningiomas mainly occur in old patients, with a remarkable female prevalence. This study investigates the different features between younger and older patients in an adult population (>18 years). MATERIALS AND METHODS: A surgical series of 120 adult patients operated on for spinal meningiomas at the Neurosurgical Clinic of the "Federico II" University of Naples is reviewed. In this series 117 patients with a sporadic spinal meningioma were divided in two groups: group I including 30 patients (25.6%) younger than 50 years of age, group II including 87 patients (74.4%) older than 50 years. 3 patients had a spinal meningioma and neurofibromatosis. Several parameters, including sex, predisposing factors, tumor location and growth, histology, recurrences, proliferation index Ki-67 LI, and outcome, are considered and compared in the two age groups. RESULTS: Group I showed an incidence of high cervical spine (C1-C4) meningiomas higher than group II (23.3% vs 3.4%, p=0.026) and lower rate of thoracic tumors (60% vs 82.7%, p=0.04). No significant differences of histological type and Ki-67 LI were found. Group I had 2 cases of atypical meningiomas (6.6% vs 0%, ns). Recurrences occurred in 6.6% of group I and 2.6% of group II, with no significance. In recurrent meningiomas values of Ki-67 LI were significantly higher than values in not recurrent meningiomas (p=0.0001), whereas no difference of estrogen and progesterone receptor expression was noted. CONCLUSIONS: Younger adult patients with spinal meningiomas show not rare occurrence of NF (9%) and significantly higher incidence of high cervical and lower incidence of thoracic localizations with respect to the older patients. On the other hand, there are not significant differences of histology, Ki-67 LI and recurrence rate, excepting for a slight difference for atypical meningiomas.

Coronary vasoreactivity is not altered in young people with type 1 diabetes.

BACKGROUND AND AIM: Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. METHODS AND RESULTS: Twenty-five type 1 diabetic patients without microvascular complications (DC-), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC-, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16 m/s), DC- (0.69±0.18 m/s), and DC+ (0.66±0.11 m/s). Mean CFR ratio was similar in C (3.33±0.66), DC- (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA(1c), duration of diabetes, and complications. CONCLUSION: Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.

Extended endoscopic endonasal approach to the midline skull base: the evolving role of transsphenoidal surgery.

The evolution of the endoscopic endonasal transsphenoidal technique, which was initially reserved only for sellar lesions through the sphenoid sinus cavity, has lead in the last decades to a progressive possibility to access the skull base from the nose. This route allows midline access and visibility to the suprasellar, retrosellar and parasellar space while obviating brain retraction, and makes possible to treat transsphenoidally a variety of relatively small midline skull base and parasellar lesions traditionally approached transcranially. We report our current knowledge of the endoscopic anatomy of the midline skull base as seen from the endonasal perspective, in order to describe the surgical path and structures whose knowledge is useful during the operation. Besides, we describe the step-by-step surgical technique to access the different compartments, the "dangerous landmarks" to avoid in order to minimize the risks of complications and how to manage them, and our paradigm and techniques for dural and bony reconstruction. Furthermore, we report a brief description of the useful instruments and tools for the extended endoscopic approaches. Between January 2004 and April 2006 we performed 33 extended endonasal approaches for lesions arising from or involving the sellar region and the surrounding areas. The most representative pathologies of this series were the ten cranioparvngiomas, the six giant adenomas and the five meningiomas; we also used this procedure in three cases of chordomas, three of Rathke's cleft cysts and three of meningo-encephaloceles, one case of optic nerve glioma, one olfactory groove neuroendocrine tumor and one case of fibro-osseous dysplasia. Tumor removal, as assessed by post-operative MRI, revealed complete removal of the lesion in 2/6 pituitary adenomas, 7/10 craniopharyngiomas, 4/5 meningiomas, 3/3 Rathke's cleft cyst, 3/3 meningo-encephalocele. Surgical complications have been observed in 3 patients, two with a craniopharyngioma, one with a clival meningioma and one with a recurrent giant pituitary macroadenoma involving the entire left cavernous sinus, who developed a CSF leak and a second operation was necessary in order to review the cranial base reconstruction and seal the leak. One of them developed a bacterial meningitis, which resolved after a cycle of intravenous antibiotic therapy with no permanent neurological deficits. One patient with an intra-suprasellar non-functioning adenoma presented with a generalized epileptic seizure a few hours after the surgical procedure, due to the intraoperative massive CSF loss and consequent presence of intracranial air. We registered one surgical mortality. In three cases of craniopharyngioma and in one case of meningioma a new permanent diabetes insipidus was observed. One patient developed a sphenoid sinus mycosis, cured with antimycotic therapy. Epistaxis and airway difficulties were never observed. It is difficult todav to define the boundaries and the future limits of the extended approaches because the work is still in progress. Such extended endoscopic approaches, although at a first glance might be considered something that everyone can do, require an advanced and specialized training.

Desmin-free cardiomyocytes and myocardial dysfunction in end stage heart failure.

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end-stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end-stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non-cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real-time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin-positive myocytes (P<0.01) in ICM hearts compared to controls. At real-time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin-free cardiomyocytes and ejection fraction (EF) (r=-0.834; P<0.02) on echocardiogram. A negative relationship (r=-0.688) was also found between desmin-negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end-stage heart failure of ischaemic origin, shows a decreased number in desmin-positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.

Large sphenocavernous meningiomas: is there still a role for the intradural approach via the pterional-transsylvian route?

BACKGROUND: Large-sized sphenocavernous meningiomas represent a surgical challenge. Although the role of skull base techniques with combined extra- and intradural steps has been recently emphasized, pure intradural resection tactics via the pterional route constitute the traditional microsurgical approach for resection of such tumours. METHOD: We report the application of the pterional-transsylvian approach in 13 patients with sphenocavernous meningiomas. This series is unique because it includes only patients with tumours exceeding 5 cm in their greatest dimension. FINDINGS: A gross total resection was accomplished in 10 patients (77%). Eight patients had a good outcome, one had a persistent mild hemiparesis, and one died. No recurrences occurred in this group. Three patients (23%) had subtotal resections owing to invasion of the cavernous sinus in one instance and encasement of the middle cerebral artery in the others. Two had a good outcome and one died. In these patients minimal asymptomatic tumour progression was seen 3 and 6 years after surgery. The overall surgical outcome was good in 10 patients (77%), fair in one, and death in two. INTERPRETATION: In our experience, large sphenocavernous meningiomas may be operated on adopting pure intradural resection tactics via the pterional-transsylvian route with rates of gross total removal and surgical complications related to brain retraction or vascular manipulation comparable to those of extensive skull base approaches. The traditional intradural pterional transsylvian approach continues to have a place in the treatment of these lesions.

Right ventricular diastolic dysfunction in arterial systemic hypertension: analysis by pulsed tissue Doppler.

AIMS: This study analyses right ventricular longitudinal function in arterial systemic hypertension by pulsed tissue Doppler. METHODS AND RESULTS: Thirty normotensives and 30 hypertensives, free of cardiac drugs, underwent standard Doppler echocardiography and pulsed tissue Doppler of right ventricular lateral tricuspid annulus and left ventricular lateral mitral annulus. By tissue Doppler, systolic and diastolic measurements were obtained. Hypertensives had higher left ventricular mass and impaired Doppler diastolic indexes, without changes of global systolic function. Tissue Doppler showed reduction of right ventricular E/A ratio and prolongation of relaxation time in comparison with controls (both P<0.00001). In the overall population, the length of tissue Doppler derived right ventricular relaxation time was positively related to right ventricular anterior wall thickness while right ventricular E/A ratio was positively related to E/A ratio of left ventricular mitral annulus (both P<0.00001). These relations remained significant even after adjusting for clinical and echocardiographic confounders by separate multivariate models. CONCLUSIONS: Arterial systemic hypertension is associated to right ventricular longitudinal diastolic dysfunction. This dysfunction involves the prolongation of active relaxation, which is independently associated with the degree of right ventricular hypertrophy and the impairment of passive wall properties, which is mainly due to ventricular interaction occurring under left ventricular pressure overload conditions.

Endoscopic fenestration of symptomatic septum pellucidum cysts: three case reports with discussion on the approaches and technique.

OBJECTIVES: We describe three patients with symptomatic septum pellucidum cysts treated by endoscopic fenestration and discuss the different endoscopic approaches to these cysts. CLINICAL PRESENTATION: The patients are an 8-year-old boy, a 7-year-old boy and a 21-year-old woman; this last also had a right frontal cavernous angioma and a pituitary microadenoma. All patients presented with headache, associated with vomiting in two and behavioral changes in one. In all cases magnetic resonance showed a septum pellucidum cyst. INTERVENTION: Two patients were operated upon by posterior approach through a right occipital burr hole and underwent fenestration from the right occipital horn to the cyst, with a second fenestration from the cyst to the left lateral ventricle in one. Another patient underwent microsurgical removal of a right frontal cavernoma and endoscopic cyst fenestration with both lateral ventricles through a right frontal craniotomy. Postoperatively, headache and vomiting resolved in all cases and behaviour changes improved in one. CONCLUSIONS: Endoscopic fenestration is the treatment of choice for septum pellucidum cysts, where it results in immediate relief of the mass effect of the cyst and in the remission of the associated symptoms. We suggest a posterior approach through a right occipital burr hole. It allows one to easily cannulate the occipital horn, which is usually larger than the frontal one, thus avoiding the risk of damaging the vascular and neural structures surrounding the foramen of Monro. Besides, the endoscopic trajectory is in our opinion more direct. The two-window technique, with fenestration of the cyst into both lateral ventricles, improves the chances of long-term patency.

Independent association of plasma leptin levels and left ventricular isovolumic relaxation in uncomplicated hypertension.

BACKGROUND: On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension. METHODS: Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively). RESULTS: The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant. CONCLUSIONS: Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.

Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood.

BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.

Impact of myocardial diastolic dysfunction on coronary flow reserve in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: The aim of the study was to assess the possible association, in hypertensive patients, between left ventricular myocardial diastolic dysfunction and coronary flow reserve (CFR) in relation to the presence of left ventricular hypertrophy (LVH). METHODS: Twenty-eight untreated hypertensives (22 males, 6 females, mean age 53.1 years), free of coronary artery disease, were enrolled in the study. Standard Doppler echocardiography, color Doppler tissue imaging of the posterior septum during dobutamine stress and second harmonic Doppler of the distal left anterior descending coronary vessel, at baseline and after maximal hyperemia induced by dipyridamole, were performed. CFR was estimated as the ratio between hyperemic and baseline diastolic velocities. Hypertensives were divided into two groups according to the left ventricular mass index: 15 without LVH (left ventricular mass index < 51 g/m2.7) and 13 with LVH (left ventricular mass index > 51 g/m2.7). The two groups were comparable for sex prevalence, age, body mass index, baseline heart rate and blood pressure. RESULTS: Color Doppler tissue imaging did not show any significant difference of both the baseline and high-dobutamine septal systolic peak velocities between the two groups. The ratio between myocardial early and atrial peak velocities (Em/Am ratio) was lower in patients with LVH, either at baseline (p < 0.01) or at high-dose dobutamine (p < 0.0001). Also, CFR was lower in the presence of LVH (p < 0.01). After adjusting for age, body mass index, left ventricular mass index, diastolic blood pressure and high-dose dobutamine heart rate by a multiple linear regression analysis, the high-dose dobutamine Em/Am ratio was an independent contributor of CFR in the overall hypertensive population (beta = 0.65, p < 0.0001) (cumulative r2 = 0.38, p < 0.0001). CONCLUSIONS: The combined use of second harmonic Doppler and color Doppler tissue imaging identifies, in arterial hypertension, an association between myocardial diastolic properties and CFR, independent of the presence of LVH. In hypertensive patients free of coronary artery stenosis, left ventricular myocardial diastolic dysfunction may be a determinant in the impairment of the coronary microvessel vasodilation capacity or a marker of silent ischemia involving the microvascular circulation.

Inverse association between free insulin-like growth factor-1 and isovolumic relaxation in arterial systemic hypertension.

Several trials have suggested that insulin-like growth factor-1 (IGF-1) may have a pathophysiological role in the development of arterial essential hypertension. To verify the possible association of IGF-1 with left ventricular morphological and functional echocardiographic parameters in hypertension, we studied 40 male patients with newly diagnosed hypertension and 15 normotensive control subjects. Doppler echocardiography was performed and circulating free IGF-1 levels were determined in all subjects. Circulating free IGF-1 levels were higher in hypertensives than in control subjects (P<0.01). A significant inverse correlation was observed between free IGF-1 and isovolumic relaxation time in the overall population (r=-0.37, P<0.01) and in hypertensives (r=-0.57, P<0.0001), whereas this relation disappears in normotensives. These results were confirmed by multivariate analysis. The present study confirms that arterial essential hypertension represents a clinical condition associated with an increased synthesis of IGF-1. The observation of an inverse, independent association between free IGF-1 and isovolumic relaxation time suggests 2 alternative hypotheses: a possible beneficial effect of IGF-1 to diastolic relaxation or a resistance to IGF-1 in hypertension.

Immunohistochemical TRF1 expression in human primary intracranial tumors.

BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling telomere shortening by inhibiting telomerase activity: down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. PATIENTS AND METHODS: To determine the TRF1 expression by immunohistochemistry (IHC) in human brain tumors, a cohort of 20 consecutive flash-frozen surgical specimens (14 meningiomas and 6 anaplastic astrocytomas (AA)) were collected. RESULTS: Variable levels of TRF1 expression in 12 out of the 14 (87.5%) meningioma samples were observed. By contrast, no expression of TRF1 in tissue samples from AA (p = 0.008) was detected. Positive TRF1 cells were usually more differentiated (less atypical features) and Ki67 negative (inverse statistical association, chi2 = p < 0.001). CONCLUSION: We demonstrated, for the first time, that routine IHC techniques are capable of identifying TRF1 expression in intracranial tumors, which is heterogeneously expressed in meningiomas, but absent in AA. Although these preliminary observations need confirmation from larger studies, the TRF1 status in intracranial tumors might become of prognostic value.

Easy sellar reconstruction in endoscopic endonasal transsphenoidal surgery with polyester-silicone dural substitute and fibrin glue: technical note.

OBJECTIVE: To describe a simple method of sellar reconstruction after endoscopic endonasal transsphenoidal surgery that will allow rapid watertight closure of the sellar floor. METHODS: A bent sheet of a polyester-silicone dural substitute, fashioned for this purpose with scissors, is introduced into the sella after removal of the lesion. Because of the consistency of the sheet, it opens spontaneously and becomes stuck. Autologous fat tissue or gelatin foam is positioned thereafter, followed by another layer of the dural substitute; a film of fibrin glue completes the sealing. RESULTS: Fifteen patients underwent this method and no postoperative cerebrospinal leak or other complication was experienced. CONCLUSION: This easy method of sellar reconstruction represents an effective and fast possibility to perform the final step of the endoscopic transsphenoidal procedure, which otherwise may cause maneuverability problems in the limited space of one nostril.

Association of left ventricular hypertrophy and aortic dilation in patients with acute thoracic aortic dissection.

This study was designed to evaluate the impact of left ventricular mass on aortic diameters in patients who presented with acute thoracic aortic dissection where aortic dilation is common. Retrospective review of transthoracic and transesophageal echocardiograms was conducted for 63 patients treated for acute thoracic aortic dissection and for 16 normal subjects who were comparable for gender prevalence, age, heart rate, and blood pressure. The diameter of the aortic root was measured by transthoracic echocardiography. Diameters of the ascending aorta, and of the aorta at locations of 25, 30, and 35 cm from the dental arch were measured by transesophageal echocardiography. The findings indicated that all aortic diameters were significantly larger in patients with aortic dissection. Patients with aortic dissection also presented with greater left ventricular mass indices (p<0.00001) than normal subjects. Fractional shortening and left atrial diameter measurements obtained in patients with aortic dissection were similar to those obtained in the control group. Overall, the left ventricular mass index exhibited univariate relationships with aortic root diameter (r=0.27, p<0.02) and aortic diameters at 25 cm (r=0.51, p<0.00001), 30 cm (r=0.58, p<0.00001), and 35 cm (r=0.55, p<0.00001) distal to the arch but not with the diameter of the ascending aorta. After adjusting for gender, body mass index, history of hypertension and aortic dissection extent (Stanford types) by separate multivariate models, the authors found that the left ventricular mass index was independently associated with aortic diameters at 25 cm (beta=0.32, p<0.001), 30 cm (beta=0.38, p<0.0001), and 35 cm (beta=0.34, p < 0.0005) distal to the arch. They conclude that left ventricular mass is independently associated with aortic arch and descending aorta diameters in patients with acute thoracic aortic dissection. Left ventricular hypertrophy may be considered a risk factor for aortic enlargement and subsequent dissection.

Inverse correlation of TRF1 expression and cell proliferation in human primary intracranial tumors.

BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling cellular proliferative potential. TRF1 is involved in a negative feedback mechanism that allows telomere shortening by inhibiting the activity of telomerase. Down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. The goal of the present study was to determine whether routine immunohistochemical (IHC) techniques can characterize TRF1 expression in different human brain tumor specimens and whether it correlates with other indices of brain tumor's proliferative potential. METHODS: A cohort of 20 flash-frozen surgical specimens [14 meningiomas and 6 anaplastic astrocytomas (AA)] were evaluated for TRF1 expression. Results of parallel investigations of tumor's proliferative indices as assessed by Ki67 labeling index (LI) determinations were cross-correlated with TRF1 expression results and histotype. RESULTS: We demonstrated variable levels of TRF1 expression in 12 out of 14 (87.5%) meningioma samples. By contrast, we detected no expression of TRF1 in tissue samples from AA (p=0.008). The Ki67 LI was higher in AA than in meningioma samples (15.21+/-9.34 vs 26.6+/-13.89, p=0.044). Statistical analysis revealed a significant inverse correlation between TRF1 expression, histotype, and LI (c2=14.1; p=0.0008). CONCLUSIONS: We demonstrated for the first time that routine IHC techniques are capable to identifying TRF1 expression in intracranial tumors. The results suggest that TRF1 is heterogeneously expressed in meningiomas, and absent in AA. The TRF1 status in intracranial tumors might be of prognostic value and possibly represent a potential application for biologically targeted therapeutic strategies.

Plasma leptin concentration, insulin sensitivity, and 24-hour ambulatory blood pressure and left ventricular geometry.

Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality. Hemodynamic factors, such as 24-h blood pressure (BP) values, are responsible for left ventricular hypertrophy in hypertensives. On the other hand, some metabolic factors have also been suggested to affect LV mass and geometry. In particular, plasma leptin concentrations have been found associated to LV myocardial growth. Because chronic leptin infusion stimulates sympathetic nervous system activity and increases BP levels, the role of 24-h BP values on leptin-related changes in myocardial wall geometry cannot be ruled out. Thus, the aim of our study was to evaluate whether the relationship between plasma leptin levels and LV wall thickness is mediated by 24-h BP values in hypertensive male patients. Thirty-six newly diagnosed hypertensive patients underwent Doppler echocardiographic examination, 24-h ambulatory BP recording, and metabolic (euglycemic hyperinsulinemic glucose clamp and fasting plasma leptin levels) measurements. Left ventricular mass correlated positively only with ambulatory diastolic BP (DBP) values, whereas the indices of myocardial wall growth such as interventricular septum thickness and sum of wall thickness (ie, septal + posterior wall thickness) correlated either with 24 h, daytime, or nighttime DBP, as well as with fasting plasma glucose, fasting plasma leptin, and insulin action after adjustment for age, body mass index (BMI), and waist/hip ratio (WHR). In contrast, plasma leptin concentration did not correlate with clinical and ambulatory BP values. A multiple linear regression analysis allowed to investigate the independent role of main anthropometric and cardiovascular covariates on the sum of wall thickness variability. A model that includes age, BMI, WHR, fasting plasma leptin concentration, plasma Na+ concentration, insulin action, and nighttime DBP explained 68% of the sum of wall thickness variability. In such a model, plasma leptin concentration (P < .001), insulin action (P < .029), and nighttime DBP (P < .002) were significantly and independently associated with myocardial wall thickness. In conclusion, our study demonstrates that in hypertensive men fasting plasma leptin levels are determinant of myocardial wall thickness independently of 24-h BP values.

Right ventricular myocardial diastolic dysfunction in different kinds of cardiac hypertrophy: analysis by pulsed Doppler tissue imaging.

BACKGROUND: Right ventricular (RV) chamber involvement has been demonstrated in hypertrophic cardiomyopathy (HCM) as well as in hypertensive left ventricular hypertrophy (LVH) but little is known about RV myocardial dysfunction occurring in these two pathologies. The aim of this study was to compare Doppler tissue imaging (DTI) of the right ventricle in HCM and LVH in relation to DTI of the left ventricle and Doppler standard of the RV and left ventricular (LV) inflow. METHODS: Thirty controls, 20 hypertensives with LVH, and 23 patients with HCM involving the interventricular septum underwent Doppler echocardiography and pulsed DTI of the LV lateral mitral annulus and the RV lateral tricuspid annulus. RESULTS: Patients with HCM had a higher blood pressure, septal thickness and LV mass in comparison with the other two groups. The RV wall thickness did not differ between HCM and LVH. The fractional shortening, but not the tricuspid annular plane excursion, was higher in HCM. After adjusting for the mean blood pressure, the Doppler-derived global LV and RV diastolic functions were more impaired in HCM than in LVH. Also the majority of DTI LV and RV diastolic measurements were altered more in HCM. At the RV tricuspid annulus, myocardial diastolic indexes were impaired in HCM and LVH in comparison with controls but the deceleration and relaxation times distinguished also HCM and LVH, being much longer in HCM (p < 0.0001). In the overall population, the RV myocardial relaxation time was positively related to the septal wall thickness and the RV wall thickness, even after adjusting for age, heart rate, diastolic blood pressure, fractional shortening and DTI mitral relaxation time. CONCLUSIONS: The impairment of RV myocardial relaxation is much more evident in HCM than in LVH, its degree being independently associated with the extent of both the septal and RV wall thickness. Pulsed DTI may be useful to distinguish the extent of RV myocardial dysfunction in different types of cardiac hypertrophy.

Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans.

AIM: To investigate in vivo the intermediate cytoskeletal filaments desmin and vimentin in myocardial tissues from patients with dilated cardiomyopathy, and to determine whether alterations in these proteins are associated with impaired contractility. METHODS: Endomyocardial biopsies were performed in 12 patients with dilated cardiomyopathy and in 12 controls (six women with breast cancer before anthracycline chemotherapy and six male donors for heart transplantation). Biopsy specimens were analysed by light microscopy and immunochemistry (desmin, vimentin). Myocyte contractile protein function was evaluated by the actin-myosin in vitro motility assay. Left ventricular ejection fraction was assessed by echocardiography and radionuclide ventriculography. RESULTS: Patients with dilated cardiomyopathy had a greater cardiomyocyte diameter than controls (p < 0.01). The increase in cell size was associated with a reduction in contractile function, as assessed by actin-myosin motility (r = -0.643; p < 0.01). Quantitative immunochemistry showed increased desmin and vimentin contents (p < 0.01), and the desmin distribution was disturbed in cardiomyopathy. There was a linear relation between desmin distribution and actin-myosin sliding in vitro (r = 0.853; p < 0.01) and an inverse correlation between desmin content and ejection fraction (r = -0.773; p < 0.02). Negative correlations were also found between myocardial vimentin content and the actin-myosin sliding rate (r = -0.74; p < 0.02) and left ventricular ejection fraction (r = -0.68; p < 0.01). CONCLUSIONS: Compared with normal individuals, the myocardial tissue of patients with dilated cardiomyopathy shows alterations of cytoskeletal intermediate filament distribution and content associated with reduced myocyte contraction.

[Venous thromboembolism. Introduction]. / Introduzione al tromboembolismo venoso.

The main aim of the treatment of deep venous thrombosis (DVT) is to prevent the onset of the main complications: embolism (acute) and post-phlebothrombotic syndrome-PPS--(late complication). If not treated, during the acute phase DVT presents extension and/or embolism in 60% of cases and pulmonary embolism is potentially fatal in 5-10%. PPS is the most frequent complication (up to 70% of cases). The treatment of acute DVT has been based for over thirty years on heparin and oral anticoagulants: thrombolytic agents and low molecular weight (LMWH) heparins have been introduced more recently. Anticoagulants treatment is continued for 3-6 months (or longer in the event of recidivation or thrombophilia). LMWH have proved more effective and easier to manage than non-fractioned heparin. The association of thrombolytic and heparin presents no advantages compared to the use of heparin alone. It is currently reserved for cases of venous gangrene and acute massive pulmonary embolism. The possibility of surgical embolectomy or the use of catheters should only be considered in treatment is ineffective or contraindicated. The aim of this paper is to analyse the treatment of DVT and the diagnostic, clinical, laboratory and instrumental procedures used, and to describe the most up-to-date indications for its diagnosis and treatment.