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The management of giant and large pituitary adenomas with wide intracranial extension or infrasellar involvement of nasal and paranasal cavities is a big challenge for neurosurgeons and the best surgical approach indications are still controversial. Endoscopic extended endonasal approaches have been proposed as a new surgical technique for the treatment of such selected pituitary adenomas. Surgical series coming from many centers all around the world are flourishing and results in terms of outcomes and complications seem encouraging. This technique could be considered a valid alternative to the transcranial route for the management of giant and large pituitary adenomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Dissecting aneurysms of the cerebral arteries are uncommon vascular malformations. Neurosurgical treatment remains critical in the management of patients with such vascular pathologies., Case Presentation: A 20-year-old Caucasian woman presented with a sudden onset of severe headache and loss of consciousness. Computed tomography revealed diffuse subarachnoid hemorrhage, while a computed tomography disclosed a dissecting aneurysm of the precommunicating segment of the right anterior cerebral artery. Cerebral carotid angiography confirmed the presence of the dissecting aneurysm. Due to the peculiar anatomic configuration, endovascular treatment was excluded and surgery was selected. As the left circulation perfused both postcommunicating segments of the anterior cerebral artery and the distal right precommunicating segment was hypoplastic, direct clipping of the right precommunicating segment, close to its origin from the internal carotid artery, was carried out. She recovered after surgery and a late angiography showed the correct positioning of the clip, with regular perfusion of both right and left postcommunicating segments., Conclusions: The management of dissecting aneurysms of the cerebral arteries is still controversial. With this report we highlight a possible neurosurgical option among therapeutic strategies for these uncommon vascular lesions.

Objective: A survey-based study was designed to assess opinions related to transsphenoidal endoscopy, to evaluate the current global attitudes of neurosurgeons regarding the use of this procedure, and to solicit basic data from key institutions worldwide, with the advantage that large series of cases become available for analysis., Methods: A web-based multi-item questionnaire was distributed to the surgical departments of 393 neurosurgical centers by means of an invitation e-mail. The questionnaire was composed of 2 sections: section 1 focused on the surgical technique for pituitary adenomas (standard technique), and section 2 concentrated on surgery for skull base tumors (extended technique). Each section was composed of 2 parts: multiple choice questions and free textual responses., Results: From a total of 393 neurosurgical centers, from 23 countries, that received the questionnaire, 87 of them (22%) submitted complete or incomplete responses. The surgical procedure, in 60 cases had been performed by a neurosurgeon, in 53 cases by a neurosurgeon and an otolaryngologist, and in 4 cases by an otolaryngologist only. The endoscope (2- and 3-dimensional) was used in 85.2% of transsphenoidal procedures versus the microscope in 14.8% of cases. The endonasal route was used for approach in 93.2% versus the sublabial route in 6.8% of cases. Computer-guided navigation was used by survey population in 71 cases, micro-Doppler in 51 cases, and Cavitron Ultrasonic Surgical Aspirator in 43 cases. Several hundreds of extrasellar tumors were operated using the extended technique., Conclusions: Transsphenoidal endoscopy for pituitary and anterior skull base tumors has become established as a routine method of dealing with a variety of lesions. The level of interest in the neurosurgical surgery community is reflected by the geometric expansion of contributions to the literature on endoscopic surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: To define from a series of surgically treated suprasellar, anterior clinoid, and sphenoid wing meningiomas, an unequivocal criterion for performing optic canal deroofing in patients with basal meningiomas with deteriorated vision., Methods: One hundred-fifty consecutive patients with suprasellar and parasellar meningiomas (44 tuberculum sellae, 46 clinoidal, and 60 spheno-orbital) who underwent surgery between 1988 and 2008 are retrospectively analyzed. The rate of preoperative visual deficit, the incidence of optic canal involvement, the related surgical management, and its influence on visual outcome are reviewed in all tumor localizations., Results: All 44 patients with tuberculum sellae meningiomas had variable preoperative visual impairment. All were operated on by transcranial approach. Unroofing of the optic canal was performed in the two cases with intracanalar tumor extension. Postoperatively, the visual function improved in 27 patients (61.4 %) and was unchanged in 17 (25 %). Among 46 patients with clinoidal meningiomas, visual dysfunction was found in 30 (65.2 %). The first 32 patients were operated on by classical pterional approach, with selective opening of the optic canal in six cases (group A), whereas all the last 14 underwent routine anterior clinoidectomy and opening of the optic canal (group B). The visual function improved postoperatively in 17 among 30 patients (56.7 %), with a significantly higher rate in group B cases (80 % versus 45 %). Among 60 patients with spheno-orbital meningiomas, 36 (60 %) had visual dysfunction and 43 (71.6 %) involvement of the optic canal. The visual function improved in 18 cases (50 %), was unchanged in 13 (36 %), and worsened in 5 (14 %). Lateral tumors had the lowest rate of optic canal involvement and a 100 % rate of visual improvement; on the other hand, all orbital apex and diffuse tumors had concentric invasion of the optic canal with a 18.6 % rate of visual worsening., Conclusions: UOC seems to be a safe procedure not associated with immediate postoperative impairment of the vision. We recommend routine deroofing of the optic canal coupled with extradural anterior clinoidectomy in all clinoidal meningiomas in order to obtain early and complete exposure of both intradural and extradural segments of the optic nerve. For tuberculum sellae meningiomas, we advise to open the optic canal only in cases with intracanalar tumor extension. Finally, for spheno-orbital meningiomas, we recommend UOC through a cranio-orbital approach in almost all cases, except for lateral meningiomas, where the involvement of the lateral wall of the optic canal is rare and may be successfully managed through a lateral orbitotomy without craniotomy.

Aim: Acute Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency, most commonly found in chronic alcoholics. It is not so easy to suspect acute WE when the clinical picture does not include all the typical symptoms and alcohol abuse is not reported. Three rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients are reported., Cases Presentation: Two patients developed the disease following prolonged intravenous feeding, the third was carrying a gastric lymphoma. None of them presented with the classic clinical triad of WE (ophtalmoplegia/nystagmus, ataxia and consciousness disturbance), showing just one or two of the typical symptoms. Brain Magnetic Resonance Imaging (MRI) represented the key tool to suspect and define WE diagnosis, showing a picture characterized by bilaterally altered signal of the thalamic pulvinar, mesencephalic cup, mammillary bodies, periaqueductal grey matter and floor of fourth ventricle. All patients dramatically improved within 48 h after administration of thiamine., Conclusion: We emphasize that WE should be suspected in all patients showing typical MRI features presenting with at least one of the clinical triad of WE., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In diabetes mellitus, structural and functional alterations of the heart can be already present at the time of first diagnosis. However, how early these alterations may occur has never been fully clarified. The present study aimed at investigating cardiac functional abnormalities in uncomplicated hypertensive or normotensive patients with a recent diagnosis of diabetes mellitus. We studied 40 diabetics (24 normotensives and 16 hypertensives) by means of routine echocardiography plus pulse tissue Doppler analysis. Data were compared with those obtained in healthy age- and sex-matched controls. Left ventricular remodelling was more evident in hypertensive diabetics than in normotensive diabetics vs controls. Diastolic function was altered in diabetic patients only when detected by pulse tissue Doppler analysis and not by conventional transmitral Doppler evaluation. Normotensive patients with type 2 diabetes with little or no evidence at standard echocardiography of alterations in cardiac structure and function, already displayed an alteration in diastolic function when the evaluation was based on the tissue Doppler approach. Patients with type 2 diabetes combined to hypertension showed more evident functional cardiac alterations at echocardiography. These findings support the conclusion that cardiac abnormalities are very early phenomena in type 2 diabetes.

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to report our experience and illustrate our technique in the use of fibrin glue in the treatment of post-operatory cerebrospinal fluid (CSF) leaks and collections following different neurosurgical procedures., Methods: In a 3-year period, 40 subjects underwent endoscopic endonasal approach for different sellar and skull base lesions (three tuberculum sellae meningiomas, six craniopharyngiomas, three Rathke's cleft cysts and 28 pituitary macroadenomas), in which an intraoperative CSF leakage was evident. In such subjects, the fibrin glue was used as a first step of the final phase of the procedure-i.e. the reconstruction of the skull base defect-followed by the other materials employed. Furthermore, ten other patients, who had undergone transsphenoidal (four cases), spinal (two cases), posterior fossa (three cases) and transcortical intraventricular tumour removal (one case) neurosurgical procedures and developed CSF leaks or collections, were conservatively treated by single or repeated in situ injections of "modified" fibrin glue under local anaesthesia according to different described techniques. In total, 50 patients constitute the clinical material of the present study., Technique: In the cases where the fibrin glue was used during the reconstruction phase of the procedure (40 cases), the glue was injected inside the tumour cavity to fill the dead space left by the removal of the lesion. In case of post-operative CSF leak or CSF fluid collection (ten cases), after discarding 50-80% of the thrombin solution to obtain prevalence of the product's adhesive properties, fibrin glue was injected directly in the path of the CSF leak or into the collection cavity after aspiration of the collection's content. This was performed with the provided application system or through lumbar or Tuohy needles. Applications were repeated every 48 h until the disappearance of the leak. In all the treated cases, the disappearance of CSF leaks or collections was obtained with a number of applications ranging from one to five. Successful results are stable with a follow-up ranging from 6 months to 3 years., Conclusions: In our experience, the injection of fibrin glue has proved to be effective in filling or sealing post-operative "dead spaces" and treating minor or initial CSF leaks resulting from procedures of transsphenoidal, cranial and spinal surgery, adding another possibility in the management of many of these dreadful complications.

Purpose: Our aim was to analyze the effects of 3-month antihypertensive therapy by nebivolol, a beta-blocking agent with nitric oxide-mediated vasodilatory properties, on coronary flow reserve (CFR) and left ventricular filling pressure (LVFP) in uncomplicated arterial hypertension., Methods: Twenty newly diagnosed, never treated, uncomplicated hypertensive patients (14 male and six female patients, mean age = 49 years), I-II WHO grade, underwent single-blind nebivolol treatment. At baseline and at 3-month follow-up, patients underwent Doppler echocardiography including pulsed Tissue Doppler of septal mitral annulus: the ratio between transmitral E velocity and myocardial early diastolic velocity (E/Em ratio) was calculated as an index of LVFP degree. Transthoracic Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was also determined., Results: After 3-month nebivolol therapy, rate-pressure product decreased (P < 0.0001). No significant change of left ventricular mass index, relative wall thickness and midwall shortening was detected. Left ventricular end-diastolic diameter and stroke volume were both marginally increased. Nebivolol increased Em (P < 0.0001), reduced E/Em ratio (from 9.0 +/- 1.6 to 8.2 +/- 1.1, P < 0.0001) and enhanced CFR (from 2.07 +/- 0.2 to 2.20 +/- 0.2, P = 0.003), because of increased hyperemic coronary flow velocity (P < 0.001). CFR increase remained significant (P < 0.001) after normalizing resting and dipyridamole coronary velocities for the respective rate-pressure product. The increase of normalized CFR induced by nebivolol was related with E/Em ratio decrease (r = -0.65, P < 0.002)., Conclusion: Nebivolol improves LVFP as well as CFR in uncomplicated hypertension. The association between changes of CFR and those of LVFP indicates a possible common denominator between improvement of coronary microvascular function and myocardial stimulation of nitric oxide release induced by the drug.

Context: Although coronary flow reserve (CFR) is reduced in patients with subclinical hypothyroidism (SHypo), the endothelial response of coronary vasomotion has never been explored in this clinical setting., Objective: To investigate the endothelial response of coronary flow in young and middle-aged patients with SHypo, without associated cardiovascular risk factors compared with healthy control subjects., Patients and Methods: The study population consisted of 20 women (mean age 38.4+12.1 years) with newly diagnosed, untreated and persistent SHypo due to Hashimoto's thyroiditis. A total of 15 volunteers served as controls. Age, gender, body surface area, glucose, insulin levels, heart rate, systolic, diastolic, and mean blood pressure were similar in patients and controls. Body mass index was significantly higher in SHypo patients. Total cholesterol and low-density lipoprotein cholesterol, despite not significant, tended to be higher, and high-density lipoprotein cholesterol to be lower in SHypo. Coronary blood flow velocities were recorded in patients at rest and after the cold pressor test (CPT), a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities., Results: Coronary diastolic peak velocities at rest did not differ between the two groups but were significantly lower after CPT in patients with SHypo, thereby resulting in a lower CFR. The difference remained significant after adjusting resting and CPT velocities for the respective mean blood pressures. TSH was inversely correlated with CFR in the pooled population., Conclusion: Patients with SHypo without associated cardiovascular risk factors have a coronary endothelial dysfunction that appears in response to a physiological stimulus (the CPT).

Background: Myocardial mechanical efficiency can be measured as the ratio between systolic work and energy consumption. We evaluated the relation between myocardial mechanical efficiency and left ventricular (LV) mass in untreated hypertensive patients., Methods: Myocardial work was estimated in 256 normotensive (35 +/- 12 years) and 306 hypertensive patients (47 +/- 10 years) with normal ejection fraction, as stroke work in gram-meters (stroke work = BPs x SV x 0.0144, where BPs is systolic blood pressure, SV is echocardiographic stroke volume). Myocardial O2 consumption was estimated as the product of heart rate (HR) x BPs (eMVO2). Myocardial mechanical efficiency was estimated as the ratio of stroke work/eMVO2, which can be simplified and expressed as ml/s., Results: LV mass was greater in hypertensive than in normotensive patients (46 +/- 13 vs. 38 +/- 11 g/m2.7, P < 0.0001), but myocardial mechanical efficiency was identical (85 +/- 23 vs. 86 +/- 26 ml/s). Relations between myocardial mechanical efficiency and LV mass were close (both P < 0.0001), but more scattered among hypertensive patients because of 56 patients exhibiting low myocardial mechanical efficiency relative to the magnitude of LV mass. At comparable age and body size, these patients had higher HR, BPs, and pulse pressure than those with normal myocardial mechanical efficiency (all P < 0.001). After adjusting for age and sex, hypertensive patients with low myocardial mechanical efficiency showed greater relative wall thickness and lower ejection fraction and midwall shortening than those with normal myocardial mechanical efficiency (all P < 0.001). Low myocardial mechanical efficiency was also associated with inappropriately high LV mass (P < 0.0001)., Conclusion: In some hypertensive patients the left ventricle works inefficiently with a high energy wasting, at the same level of LV mass as hypertensive patients with normal myocardial mechanical efficiency. Those patients feature a high cardiovascular risk phenotype, with concentric LV geometry, systolic dysfunction, and indirect signs of more severe vascular impairment.

Background: It has been recognized that "cross-talk" occurs between coronary flow and left ventricular (LV) function. This study tested the hypothesis that impairment of coronary flow reserve (CFR) in arterial hypertension is associated with LV systolic and diastolic dysfunction, independent of abnormalities in LV geometry., Methods: We studied 59 newly diagnosed, never-treated hypertensive patients, using transthoracic Doppler echocardiography including pulsed Tissue Doppler of mitral annulus and CFR on left anterior descending artery (low-dose dipyridamole). The study population was divided into two groups on the basis of age-normalized relative wall thickness (RWTn): 36 patients with normal LV geometry (RWTn < or = 0.41) and 23 patients with LV concentric geometry (RWTn > 0.41)., Results: Patients with LV concentric geometry (RWTn > 0.41) had significantly lower values of midwall shortening (but not of endocardial shortening), longer isovolumic relaxation time (IVRT), lower Tissue Doppler-derived early diastolic velocity (Em), higher ratio of transmitral E velocity to Em, and lower CFR as compared to patients with normal LV geometry (RWTn < or = 0.41). In the whole population, a lower CFR was significantly associated with lower values of midwall shortening and Em, longer IVRT, and higher E/Em ratio. After controlling for heart rate, mean blood pressure, and RWTn, only the relation of CFR with IVRT, Em, and E/Em ratio remained significant., Conclusions: Reduced midwall mechanics is associated with lower CFR, a relationship that depends on LV concentric geometry. A reduced CFR is associated with both impaired relaxation and increased filling pressure, a relation that is independent of LV geometry and pressure load.

Background: The intensive physical activity is often associated with cardiac changes., Objectives: (i) To evaluate the IGF-I system and myocardial structure and function by standard Doppler echocardiography and Tissue Doppler in athletes and sedentary controls; and (ii) to determine any relationship between IGF-I system and echocardiographic parameters., Methods: Nineteen male top-level rowers and 19 age-matched healthy sedentary male controls underwent blood determination of fasting serum IGF-I, IGFBP-3 and acid-labile subunit levels and standard Doppler echocardiography combined with pulsed Tissue Doppler of posterior septal wall, left ventricular (LV) lateral mitral annulus and right ventricular (RV) tricuspid annulus. Myocardial presystolic (PS(m)), systolic (S(m)), the ratio of early diastolic (E(m)) to atrial (A(m)) velocities as well as myocardial time intervals were calculated., Results: Rowers had higher serum IGF-I levels (P = 0.04), higher biventricular cavity dimensions and wall thicknesses compared to controls. They also had better LV and RV myocardial function than controls. In the rowers, IGF-I was associated with LV ejection fraction (r = 0.50, P = 0.03), RV PS(m) velocity (r = 0.55, P = 0.01) and with RV myocardial precontraction time (r = -0.57, P = 0.01). These associations remained significant after adjusting for age and heart rate., Conclusions: Top-level athletes showed higher IGF-I levels and a better myocardial performance than controls, particularly for the RV systolic activity. The independent correlations between IGF-I and systolic parameters of the left (ejection fraction) and right (PS(m) velocity and precontraction time) ventricles may possibly indicate a role of IGF-I system in the modulation of myocardial inotropism in athletes. Further studies are needed to confirm this hypothesis.

Introduction: Interest in using the extended endonasal transsphenoidal approach for management of suprasellar lesions, with either a microscopic or endoscopic technique, has increased in recent years. The most relevant benefit is that this median approach permits the exposure and removal of suprasellar lesions without the need for brain retraction., Materials and Methods: Fifteen human cadaver heads were dissected to evaluate the surgical key steps and the advantages and limitations of the extended endoscopic endonasal transplanum sphenoidale approach. We compared this with the transcranial microsurgical view of the suprasellar area as explored using the bilateral subfrontal microsurgical approach, and with the anatomy of the same region as obtained through the endoscopic endonasal route., Results: Some anatomic conditions can prevent or hinder use of the extended endonasal approach. These include a low level of sphenoid sinus pneumatization, a small sella size with small distance between the internal carotid arteries, a wide intercavernous sinus, and a thick tuberculum sellae. Compared with the subfrontal transcranial approach, the endoscopic endonasal approach offers advantages to visualizing the subchiasmatic, retrosellar, and third ventricle areas., Conclusion: The endoscopic endonasal transplanum sphenoidale technique is a straight, median approach to the midline areas around the sella that provides a multiangled, close-up view of all relevant neurovascular structures. Although a lack of adequate instrumentation makes it impossible to manage all structures that are visible with the endoscope, in selected cases, the extended endoscopic endonasal approach can be considered part of the armamentarium for surgical treatment of the suprasellar area.

Cardiovascular (CV) risk factors, primarily arterial hypertension, modify the structural and functional features of the myocardium and the blood vessels, a process known as CV remodeling. Cardiac remodeling refers to changes in left ventricular (LV) geometry, such as concentric LV geometry and LV hypertrophy (LVH), an independent hallmark of CV risk. Vascular remodeling consists of structural changes of the arterial walls, such as increased intima-media thickness, arterial stiffening, and deteriorating endothelial function. CV remodeling is to a large extent a result of compensatory mechanisms, and its pathophysiology is partially mediated by the activation of the renin-angiotensin-aldosterone system and its primary effector peptide angiotensin II, which together play a key role in the progression of CV disease. Angiotensin-converting enzyme (ACE) inhibitors, a class of drugs used in the treatment of arterial hypertension, appear to be effective in controlling or even reversing CV remodeling, independently of simple blood pressure reduction. Evidence shows that ACE inhibitors counteract CV remodeling by reducing LV mass and regressing LVH, attenuating vascular atherosclerosis and improving vascular compliance. ACE inhibitors possessing a sulfhydryl moiety appear to have additional benefits in increasing nitric-oxide release and improving vascular endothelial function.

Objectives: Dural replacement materials and other measures can provide an effective barrier between the subarachnoid compartment and the extradural space when a watertight closure of the patient's own dura is not possible., Patients and Methods: We evaluated the efficacy and safety of a novel collagen-derived dural substitute on a series of 208 patients undergoing a variety of neurosurgical procedures., Results: No patients experienced any local or systemic complications nor toxicity related to the dural patch. No patients experienced post-operative CSF fistula except for one. Post-operative MRIs showed signs of moderate inflammatory response in only one patient, who did not present any post-operative clinical symptom nor neurological deficits. Three patients underwent reoperation for bone flap repositioning after decompressive craniectomy: in these cases, the dural substitute appeared to have promoted a satisfactory dural regeneration, as confirmed by the histological studies. Furthermore, in such cases no or minimal adherences with the other tissues and the brain cortex was observed., Conclusions: The new collagen-only biomatrix is a safe and effective dural substitute for routine neurosurgical procedures. The absence of local and systemic toxicity or complications, and the scarce promotion of adherences and inflammation, make this material appealing for its use as dural substitute even in cases when a needed re-operation is anticipated.

Objective: A watertight and meticulous dural closure is an essential step after intradural neurosurgical procedures. When such a task cannot be performed, dural replacement materials and other adjunctive measures can provide an effective barrier between the subarachnoid compartment and the extradural space., Methods: We present our experience with a novel collagen-derived dural substitute in a series of 114 patients undergoing a variety of neurosurgical procedures. The patients were clinically or neuroradiologically observed, for immediate and delayed local or systemic complications related to the implant. In three patients who underwent reoperation after decompressive duraplasty and craniectomy for bone flap repositioning, we performed biopsy of the dural implant for histopathological studies., Results: None of the patients experienced local or systemic complications or toxicity related to the dural patch. None of the patients experienced a postoperative cerebrospinal fluid fistula, except one patient who underwent an endoscopic endonasal transsphenoidal marsupialization of a large intrasuprasellar arachnoid cyst; the fistula required reoperation for cerebrospinal fluid fistula repair and intravenous antibiotic therapy for bacterial meningitis. Postoperative magnetic resonance imaging scans showed signs of severe inflammatory response in only one patient who did not present any postoperative clinical symptom or neurological deficits. Three patients underwent reoperation for bone flap repositioning after decompressive craniectomy; in all patients, the dural substitute appeared to have promoted satisfactory dural regeneration, as confirmed by the histological studies. Furthermore, in such patients, no or minimal adherence with the other tissues and the brain cortex was observed., Conclusion: This study demonstrates that the new collagen-only biomatrix is a safe and effective dural substitute for routine neurosurgical procedures. The absence of local and systemic toxicity or complications and the scarce promotion of adherences and inflammation make this material appealing for its use as a dural substitute, even in cases in which the necessity of reoperation is foreseen.

Objective: Tuberculum sellae meningiomas represent 5 to 10% of all intracranial meningiomas. Such lesions are classically removed through a variety of well-standardized transcranial approaches. The extended endonasal transsphenoidal route, under either microscopic or endoscopic visualization, has only recently been proposed as a viable surgical technique for the management of such tumors., Material and Methods: A total of 51 consecutive patients with tuberculum sellae meningiomas were treated at our institution during a 21-year period. Forty-four patients had transcranial surgery, and the last seven were treated via the extended endoscopic transsphenoidal approach. We also compared our data with those reported in the pertinent literature related to the surgical, ophthalmological, and endocrinological outcome., Results: The significant difference among the transcranial and transsphenoidal series, both in our experience and in the reviewed literature, did not allow us to draw statistically significant results but rather a reporting of the outcomes. In the transcranial group, 86.4% had a gross total removal of the lesion, whereas the percentage was 83.3% in the transsphenoidal group. Concerning the visual outcome, we experienced postoperative improvement in 61.4% of the transcranial patients and a worsening of 13.6%, whereas improvement was reported in 71.4% of the patients in the transsphenoidal group; in the last group, we did not observe any postoperative worsening. The main drawback of the transsphenoidal approach still remains the difficulty in reconstructing the cranial base dural and bone defects, which expose patients to a greater risk of postoperative cerebrospinal fluid leakage (28.6% in our series) and related complications., Conclusion: When treating a patient with a diagnosis of tuberculum sellae meningioma, a neurosurgeon should know that, aside from the classical transcranial approach, the possibility of an extended transsphenoidal approach exists. Although it is still not a standardized procedure, in carefully selected cases (i.e., small midline lesions, without major vessel encasement, or parasellar extension) and in experienced hands, it could be considered a viable alternative, especially in overcoming the reconstruction-related problems.

Pituitary surgery is a continuous evolving speciality of the neurosurgeons' armamentarium, which requires precise anatomical knowledge, technical skills and integrated appreciation of the pituitary pathophysiology. What we consider "pure" endoscopic transsphenoidal surgery is a procedure performed through the nose and the sphenoid bone, with the endoscope alone throughout the whole approach to visualize the surgical target area and without the use of any transsphenoidal retractor. It offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Concerning results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease and complication rate, they are, at least, similar to those reported in the major microsurgical series, but patient compliance is by far better. Furthermore transsphenoidal endoscopy brings advantages to the patient (less nasal traumatism, no nasal packing, less post-op pain and usually quick recovery), to the surgeon (wider and closer view of the surgical target area, increase of the scientific activity as from the peer-reviewed literature on the topic in the last 10 years, smoothing of interdisciplinary cooperation), to the institution (shorter post-op hospital stay, increase of the case load). Besides, further progress and technological advance are expected from the close cooperation between different technologies and industries. Continuing works in such field of "minimalism" will offer further possibilities to provide the surgeon with even more effectiveness and safety, and, on the other hand, the patient with improvement of results.

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.

Object: The extended transnasal approach, a recent surgical advancements for the ventral skull base, allows excellent midline access to and visibility of the anterior cranial fossa, which was previously thought to be approachable only via a transcranial route. The extended transnasal approach allows early decompression of the optic canals, obviates the need for brain retraction, and reduces neurovascular manipulation., Methods: Between 2004 and 2007, 11 consecutive patients underwent transnasal resection of anterior cranial fossa meningiomas--4 olfactory groove (OGM) and 7 tuberculum sellae (TSM) meningiomas. Age at surgery, sex, symptoms, and imaging studies were reviewed. Tumor size and tumor extension were estimated, and the anteroposterior, vertical, and horizontal diameters were measred on MR images. Medical records, surgical complications, and outcomes of the patients were collected., Results: A gross-total removal of the lesion was achieved in 10 patients (91%), and in 1 patient with a TSM only a near-total (> 90%) resection was possible. Four patients with preoperative visual function defect had a complete recovery, whereas 3 patients experienced a transient worsening of vision, fully recovered within few days. In 3 patients (2 with TSMs and 1 with an OGM), a postoperative CSF leak occurred, requiring a endoscopic surgery for skull base defect repair. Another patient (a case involving a TSM) developed transient diabetes insipidus. The operative time ranged from 6 to 10 hours in the OGM group and from 4.5 to 9 hours in the TSM group. The mean duration of the hospital stay was 13.5 and 10 days in the OGM and TSM groups, respectively. Six patients (3 with OGMs and 3 with TSMs) required a blood transfusion. Surgery-related death occurred in 1 patient with TSM, in whom the tumor was successfully removed., Conclusions: The technique offers a minimally invasive route to the midline anterior skull base, allowing the surgeon to avoid using brain retraction and reducing manipulation of the large vessels and optic apparatus; hastens postoperative recovery; and improves patient compliance. Further assessment and refinement are required, particularly because of the potential risk of CSF leakage. Other studies and longer follow-up periods are necessary to ascertain the benefits of the technique.

Background: Coronary flow reserve (CFR) may be reduced even in the absence of coronary artery disease. We investigated the determinants of CFR impairment in Type 2 diabetes mellitus (DM2) and in arterial hypertension (HTN) without epicardial coronary artery stenosis., Methods: Twenty-eight patients with DM2 and 27 with HTN, both with normal coronary angiography, and 18 healthy controls underwent transthoracic echocardiography, including Doppler recording of the distal left anterior descending artery, at rest as well as after high-dose dipyridamole. Coronary flow reserve was calculated as the hyperemic to resting coronary diastolic peak velocities ratio., Results: The three groups were comparable for sex, age, and heart rate. Systolic and mean blood pressures were higher in DM2 and HTN patients than in control subjects. Diabetic and hypertensive patients had a higher left-ventricular mass index (LVMi) and relative wall thickness, impaired diastolic indexes, and lower CFR compared with control subjects (P = .02 and P = .03, respectively) because of lower hyperemic coronary velocity (P = .005 and P = .004, respectively). After a multilinear regression analysis (using age, sex, HTN status, DM2 status, smoking, total cholesterol/HDL-cholesterol ratio, and LVMi as potential determinants), the LVMi increase was the main predictor of the reduction of CFR, adjusted for mean BP (P < .0001), in the pooled population, with a minor contribution of age (P = .03), HTN status (P = .02), and DM2 status (P = .03)., Conclusions: In Type 2 DM and HTN without epicardial coronary stenosis, an impairment of CFR is demonstrable. This is partly explained by an increased left-ventricular mass, able to condition the hyperemic stimulation of myocardial blood flow.

Objective: In the last 10 years, experience with endoscopic transsphenoidal surgery for the treatment of sellar and perisellar lesions has highlighted advantages brought about by the endoscope for less-invasive procedures. Focusing on these advantages, there is increasing interest in endoscope use for treatment of lesions located in other regions such as the cerebellopontine angle (CPA). Epidermoid tumors, especially those located on the CPA, resulting from their avascular and noninfiltrative nature, appear particularly suited to being treated using an endoscopic approach., Clinical Presentation: A 37-year-old man with a 2-year history of left trigeminal neuralgia responded poorly to medical therapy. Magnetic resonance imaging scans revealed a left CPA lesion compatible with an epidermoid tumor, and he was admitted for surgical treatment., Technique: We report a patient who underwent freehand dynamic endoscopic resection of an epidermoid tumor of the CPA. This technique requires two surgeons to work in close cooperation: the "navigator," who holds the endoscope and makes fine position adjustments, and the "pilot," who uses both hands to perform the procedure itself under dynamic endoscopic view., Conclusion: The patient's postoperative course was uneventful. The trigeminal neuralgia completely resolved, and postoperative control magnetic resonance imaging scans demonstrated no residual lesion. The benefits of endoscopic treatment for CPA lesions, with special emphasis on the dynamic aspect of this new technique, are discussed.

Objective: Suprasellar craniopharyngiomas have been classically removed using a variety of transcranial approaches. Historically, the transsphenoidal route was reserved for intrasellar-infradiaphragmatic, and preferably cystic, lesions. With the advent of the endoscope in transsphenoidal surgery, its obvious advantages combined with neurosurgeons' increasing interest in extended transsphenoidal approaches made suprasellar and even intraventricular craniopharyngiomas accessible for removal via such a low route., Patients and Methods: Between January of 2004 and April of 2006, six men and four women (mean age, 57.2 yr; range, 26-70 yr) underwent surgery for craniopharyngioma, including two intrasuprasellar, one suprasellar, six suprasellar-intraventricular, and one that was purely intraventricular. Three patients had undergone a previous transcranial surgery via the pterional approach, whereas one patient had undergone a transsphenoidal microsurgical approach. The surgical method consisted of an extended endoscopic transsphenoidal approach with removal of the upper half of the sella, the tuberculum sellae, and the posterior part of the planum sphenoidale, using a "three-four hands" technique., Results: Total craniopharyngioma removal was achieved for seven patients, subtotal removal was possible for two patients, and one patient had a partial removal. Two patients developed a postoperative cerebrospinal fluid leak that required a successful endoscopic revision of the cranial base reconstruction. One patient died 5 weeks later because of hypothalamic dysfunction. All patients with visual field and/or visual acuity defect improved except one patient, in which we observed a slight worsening of visual acuity in one eye. Preoperative pituitary dysfunction did not improve in any patient. In three patients, we observed the new occurrence of permanent diabetes insipidus. One patient developed a sphenoid sinus mycosis, which was treated with antimycotic therapy. We did not observe carotid injury, epistaxis from the sphenopalatine artery, or airway difficulties., Conclusion: For selected patients, the extended endoscopic endonasal approach for removal of suprasellar craniopharyngioma seems to provide a valid alternative to transcranial approaches.

Object: The extended transsphenoidal approach to the suprasellar region has the advantages of minimal invasiveness and brain manipulation in the surgical treatment of small to medium lesions. At the same time, however, it carries a higher risk of postoperative cerebrospinal fluid (CSF) leakage and related complications than those for the standard transsphenoidal approach. Effective reconstruction of large skull base defects is a major concern in such extended approaches and remains challenging., Methods: Between January 2004 and April 2006, 21 patients affected by different suprasellar lesions underwent the extended endoscopic endonasal transtuberculum-transplanum approach. Three different techniques were used for the skull base reconstructions. In all cases, dehydrated human pericardium (Tutoplast) for dural reconstruction and a copolymer of L-lactic acid and glycolic acid (LactoSorb) as a bone substitute were used. Collagen sponges, fibrin glue, and an inflated Foley balloon catheter were also used to fill the sphenoid sinus cavity., Results: Two cases of postoperative CSF leaks (9.5%) and one case of mycotic sinusitis (4.8%) occurred following the intradural (inlay) and intraextradural (inlay-overlay) graft positioning. No cases of postoperative CSF leakage occurred in cases in which the extradural-only reconstruction procedure was applied. No meningitis or other complications related to the closure were noticed., Conclusions: The rate of postoperative CSF leakage after an extended approach to the suprasellar area is higher compared with that following standard pituitary surgery. Reconstruction after craniopharyngioma surgery exposes patients to an increased risk of postoperative CSF leaks. The extradural (overlay) technique was found to be the most effective in assuring a watertight closure.

Introduction: Interest in using the extended endonasal transsphenoidal approach for management of suprasellar lesions, with either a microscopic or endoscopic technique, has increased in recent years. The most relevant benefit is that this median approach permits the exposure and removal of suprasellar lesions without the need for brain retraction., Materials and Methods: Fifteen human cadaver heads were dissected to evaluate the surgical key steps and the advantages and limitations of the extended endoscopic endonasal transplanum sphenoidale approach. We compared this with the transcranial microsurgical view of the suprasellar area as explored using the bilateral subfrontal microsurgical approach, and with the anatomy of the same region as obtained through the endoscopic endonasal route., Results: Some anatomic conditions can prevent or hinder use of the extended endonasal approach. These include a low level of sphenoid sinus pneumatization, a small sella size with small distance between the internal carotid arteries, a wide intercavernous sinus, and a thick tuberculum sellae. Compared with the subfrontal transcranial approach, the endoscopic endonasal approach offers advantages to visualizing the subchiasmatic, retrosellar, and third ventricle areas., Conclusion: The endoscopic endonasal transplanum sphenoidale technique is a straight, median approach to the midline areas around the sella that provides a multiangled, close-up view of all relevant neurovascular structures. Although a lack of adequate instrumentation makes it impossible to manage all structures that are visible with the endoscope, in selected cases, the extended endoscopic endonasal approach can be considered part of the armamentarium for surgical treatment of the suprasellar area.

Background: Myotonic dystrophy is associated with arrhythmias and risk of sudden death but also with symptoms of heart failure. Our study aimed to identify early biventricular dysfunction in asymptomatic patients with myotonic dystrophy by tissue Doppler., Methods: Thirty-six patients with myotonic dystrophy (M/F=20/16, mean age=36.4 years), asymptomatic for heart failure, and 36 age- and sex-matched healthy controls underwent Doppler echocardiography and pulsed tissue Doppler of lateral mitral annulus and of tricuspid annulus., Results: The two groups had similar body mass index, blood pressure, heart rate, cardiac mass and endocardial shortening. Standard Doppler showed significantly lower transmitral early (E) diastolic peak velocity, longer transmitral deceleration and isovolumic relaxation times and higher tricuspid inflow atrial peak velocity in myotonic dystrophy than in controls. Tissue Doppler of mitral annulus showed lower myocardial systolic velocity (p<0.02), lower early diastolic velocity (E(m)) (p<0.05) and atrial velocity (A(m)) (p<0.005), but no difference of E(m)/A(m) ratio. At tricuspid annulus, E(m) and E(m)/A(m) ratio were lower (p<0.02 and p<0.005, respectively). The ratio between tricuspid inflow E velocity and E(m), index of the degree of right ventricular filling pressure, was higher (p<0.001) than in controls. Tissue Doppler derived left ventricular and right ventricular measurements were all associated with the disease condition, independent of age and heart rate., Conclusions: Tissue Doppler identifies subclinical biventricular involvement in myotonic dystrophy. Early left ventricular myocardial systolic and diastolic changes are evident. Right ventricular dysfunction, involving myocardial relaxation and right ventricular filling pressure, might be the arrhythmogenic substratum of these patients.

Background: Left ventricular (LV) concentric geometry and hypertrophy, depressed wall mechanics, and abnormal diastolic properties have been described in the diabetic heart. However, the cardiac response to dynamic exercise in diabetic patients remains controversial. The present study assessed strain rate (SR) imaging during dobutamine stress, to investigate inotropic response in patients with type 2 diabetes mellitus and without coronary artery disease., Methods: Twenty-four diabetics and 16 controls, both free of coronary artery disease, underwent Doppler echocardiography at rest and during dobutamine stress. Tissue Doppler systolic (S(m)) and early diastolic (E(m)) velocities, SR, and strain of middle posterior septum were measured at rest, low-dose, and high-dose dobutamine., Results: Diabetics had higher LV mass and relative wall thickness, lower midwall shortening, and transmitral pattern of abnormal LV relaxation. At rest, E(m) was significantly lower but S(m), SR, and strain were similar between the two groups. At low-dose and high-dose dobutamine, without difference of S(m), SR and strain were significantly lower in diabetics. At every level of dobutamine, strain increased with increasing heart rate (HR) in either group (both P < .0001), but the slope of the overall relation between HR and strain was lower in diabetics (b = -0.08) than in controls (b = -0.14) (P < .01)., Conclusions: In type 2 diabetes SR imaging allows detection of reduced longitudinal mechanics during dobutamine stress. The blunted slope of the relation between HR and regional strain suggests the impairment of the myocardial force-frequency relation, indicating altered contractile reserve in uncomplicated diabetes.

Background: Coronary flow reserve (CFR) may be reduced both in arterial hypertension and in hypercholesterolemia. The aim of the study was to assess an association between CFR and levels of plasma total cholesterol (TC) in untreated arterial hypertension., Methods: We studied 54 consecutive, untreated hypertensive outpatients free of coronary heart disease. Twenty of them had normal TC and 34 high TC (>/=200 mg/dL). Standard echocardiograms and transthoracic Doppler interrogation of the distal left anterior descending artery were obtained. Coronary diastolic peak velocities were measured both at rest and after low-dose dipyridamole. The CFR was calculated as dipyridamole/resting velocities ratio., Results: The two groups had similar age, body mass index, heart rate, and diastolic blood pressure (BP). Patients with high TC had higher systolic BP (P < .05), triglycerides (P < .02), LDL-cholesterol, and TC/HDL-cholesterol ratio (both P < .0001) than controls. Left ventricular (LV) mass index, relative wall thickness, and fractional shortening did not differ between the two groups. Coronary diastolic peak velocities were similar at rest but lower after dipyridamole in patients with high TC (P < .02). As a consequence, CFR was reduced (P < .002). In multiple linear regression analyses, adjusting for age, heart rate, systolic BP, smoking, and relative wall thickness, TC (beta = -0.338) or high LDL-cholesterol (beta = -0.301) (both P < .001) were predictors of lower CFR independently of the concomitant effect of potential confounders., Conclusions: In hypertensive patients free of coronary artery disease, the degree of impairment in coronary vasodilator capacity is independently associated with plasma cholesterol and LDL-cholesterol.

Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic) dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation.

Background: In remodelling ventricles, the progression of heart failure is associated with structural changes involving the extra-cellular matrix (ECM) and the cytoskeleton of cardiomyocytes, associated with fibrosis, cellular damage and death. The role of some cytokines and haematopoietic growth factors in the mechanism of both damage and regeneration of cardiac tissue during acute myocardial infarction has been demonstrated. Following heart damage, the development of scarred tissue was considered to be the only outcome, since myocytes were considered to be terminally differentiated cells. However, recent studies in animal models and adult human hearts have shown that myocytes can proliferate under the modulation of several factors., Aims: To assess Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) receptor expression in healthy and diseased human hearts, and to evaluate the possible role of GM-CSF and its receptor in the regeneration of cardiac tissue in chronic cardiomyopathy., Methods and Results: GM-CSFR expression in human cardiac tissue from explanted hearts of ten patients with end-stage heart failure and in cardiac biopsies from eight normal human hearts was studied by immunohistochemistry, and cellular and molecular biology assays. Our results demonstrated an increase in GM-CSFR in cardiomyocytes from end-stage heart failure tissues as compared to normal control tissues., Conclusions: We hypothesize that GM-CSF plays a role in apoptotic and/or ECM deposition processes as well as in cytoskeleton modification in the myocardium.

Objective: The aim of this study was to evaluate the incremental diagnostic role of tissue Doppler in primary cardiac amyloidosis (CA)., Methods: Eleven patients with CA at diagnosis and 11 healthy controls, matched for sex and age, underwent standard Doppler echocardiography and pulsed tissue Doppler of the left ventricular (LV) lateral annulus, in the apical four-chamber view. The ratio of early transmitral flow velocity to early diastolic mitral annular velocity (E/E(m) ratio) was derived as an index of LV filling pressure., Results: The two groups were comparable for body mass index, blood pressure, heart rate and standard Doppler diastolic measurements. Patients with CA had a significantly higher sum of wall thickness (SWT) and LV mass, a lower E(m) peak velocity (P < 0.002) and a higher E/E(m) ratio (P < 0.001) than controls. By dividing CA patients according to the transmitral E/A ratio, patients with an E/A ratio < 1 (abnormal relaxation) (n = 5) and patients with an E/A ratio > 1 (likely pseudonormal/restrictive pattern) (n = 6) did not show any difference in the E/E(m) ratio (14.5 + or - 7.1 vs. 15.1 + or - 6.4, P = NS). In the overall population, the E/E(m) ratio was related to SWT (r = 0.84, P < 0.0001) and LV mass index (r = 0.72, P < 0.0001). After adjusting for age and heart rate by separate multivariate models, SWT (beta = 0.78, P < 0.0001; cumulative r(2) = 0.63, SE = 3.38, P < 0.0001) and LV mass index (beta = 0.71, P < 0.0001; cumulative r(2) = 0.53, SE = 3.80, P < 0.002) were both independently associated with the E/E(m) ratio., Conclusions: Pulsed tissue Doppler is able to detect early myocardial diastolic impairment in CA. The E/E(m) ratio is very useful in diagnosing increased LV filling pressure, regardless of the transmitral pattern, and may, therefore, be helpful in the clinical management of these patients.

Object: The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors., Methods: Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor-b [TGFb], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFb expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFb, PDGF, and tenascin in more aggressive cavernomas., Conclusions: The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.

New ultrasound technology is mainly represented by tissue Doppler (TD), which allows the quantitative analysis of myocardial function and includes two modalies: pulsed-wave TD and color TD. Strain rate imaging (SRI) is an implementation of color TD. Pulsed-wave TD, performed and analyzed in real time, instantaneously measures myocardial velocities. Color TD, performed offline on digitally stored images, allows the quantification of mean myocardial velocities. The advantage of color TD compared with pulsed TD is the ability to simultaneously analyze multiple myocardial segments. The limit of both these methodologies consists of the myocardial velocity dependence by the base-apex myocardial gradient. SRI measures the rate and percentage of myocardial wall deformation. From digitally recorded color TD cine loops containing velocity data from the entire myocardium, SRI can be derived from regional Doppler velocity gradients. Strain rate is relatively load dependent, and, therefore, can be considered a strong index of myocardial contractility. Due to these favorable characteristics, SRI may potentially overcome the limitations of color TD, discriminating between active and merely passive wall motion. A novel technique is the implementation of 2D SRI, which is not angle dependent, and therefore potentially more feasible and reliable.