Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging.

PURPOSE: [123I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [123I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks. PROCEDURES: One hundred forty-three subjects [84 with Parkinson's disease (PD) and 59 control individuals (CG)] underwent DATSCAN® imaging. The [123I]FP-CIT binding was evaluated by multivariate SBM approach, as well as by a whole-brain voxel-wise univariate (statistical parametric mapping, SPM) approach. RESULTS: As compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [123I]FP-CIT binding reduction in PD group), SBM identified six sources of non-artefactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of [123I]FP-CIT binding) significantly different between PD and CG. Notably, even if not significantly different between PD and CG, the remaining three non-artefactual sources were characterized by a predominant frontal, brainstem, and occipito-temporal involvement. CONCLUSION: The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in [123I]FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal than extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

Robot assisted laparoscopic excision of a paraganglioma: new therapeutic approach

The Paraganglioma is the most common extra-adrenal pheochromocytoma arising from neural crest (1) (It will better to write: The paraganglioma is an extra-adrenal pheocromocytoma arising from the neural crest. 10% of pheocromocytomas are extra-adrenal and can arise form chromaffin tissue derived from primitive neuroectoderm). Minimally invasive techniques allow surgeons to perform the procedure without wide exposure and mobilization of intra abdominal organs. To our knowledge we present the third case of robotic excision of a retroperitoneal paraganglioma (2,3).

[Biomarkers of prostate cancer. A review]. / Biomarker della neoplasia prostatica. Una review.

Prostate cancer has the highest tumour incidence in the male population and represents 9.2% of cancer-related deaths. The most commonly used screening technique up to the present has been serum measurement of PSA which has led to a marked increase in the number of prostate cancer cases diagnosed every year. Nevertheless PSA in the early diagnosis of prostate cancer has many limitations. It can lead to a very high number of unnecessary biopsies in patients with benign prostate hyperplasia and, in addition, may also lead to an overdiagnosis and overtreatment of clinically insignificant neoplasias. Moreover many neoplasias are already present with PSA within normal limits. It is clear, therefore, that new biomarkers for the diagnosis and follow-up of prostate cancer have to be developed. We present a review of the literature in which we have analysed the most promising biomarkers in terms of sensitivity and diagnostic specificity for prostate cancer and which are currently under study, analysing recent developments and future prospects.

Presacral myelolipoma. A case report.

Presacral myelolipoma is a rare benign tumour composed of fat and haemopoietic tissue. Ultrasound, computed tomography and magnetic resonance imaging are of help to achieve the diagnosis, but pathologic confirmation is mandatory. The Authors report an asymptomatic case whose diagnosis has been achieved by means of CT scan-guided percutaneous needle biopsy. Unnecessary surgical treatment was avoided in this case. Clinical approach and role of surgery are discussed.

Platelet amyloid precursor protein forms in AD: a peripheral diagnostic tool and a pharmacological target.

Alzheimer Disease (AD) is characterized by the progressive deposition of beta-amyloid in the parenchyma and cerebral microvasculature. The beta-amyloid peptide derives from the metabolism of a larger precursor, Amyloid Precursor Protein (APP). This protein is present in central nervous system, but it is also expressed in peripheral tissues such as circulating cells. An alteration of the APP forms pattern in platelets has been recently reported in AD patients when compared to platelets both of control subjects or non AD patients (NADD). The accuracy of the assay to identify AD is high and decreased levels are found throughout the course of AD with a significant association with severity of symptoms. Moreover, a recent study has demonstrated that AD patients on donepezil (5 mg daily) for 4 weeks displayed two-fold increase in their APPr baseline levels up to normal range. Thus, platelet APP ratio (APPr) holds the potential to be a clinical marker, which might be of helpful and adjunctive value in the diagnosis of AD and in tracking the course of illness, also in the early stages when pharmacological treatment has the greatest potential of being effective.

Long-term CAPD patients are volume expanded and display more severe left ventricular hypertrophy than haemodialysis patients.

BACKGROUND: Whether hypertension and left ventricular hypertrophy (LVH) are more prevalent in CAPD than in haemodialysis (HD) patients is still under discussion. METHODS: To examine this problem we compared a group of 51 CAPD patients, with a group of 201 HD patients. The evaluation included the measurement of atrial natriuretic peptide (atrial natriuretic factor (ANF)), taken as indicator of volume status, and echocardiographic measurements. RESULTS: CAPD patients were older, had been treated for a shorter time, and had lower serum albumin and phosphate than HD patients. Plasma ANF was higher (P<0.01) in CAPD (median 33.8 pmol/l (interquartile range 18.2-63.0)) than in HD patients (22.7 pmol/l (14.9-38.7)). Similarly, the left atrial volume was substantially higher (P<0.0001) in CAPD patients (49+/-22 ml) than in HD patients (37+/-17 ml), while the left ventricular end-diastolic diameter was similar in the two groups (CAPD 51+/-7 mm; HD 50+/-7 mm). Furthermore, left ventricular hypertrophy was more severe (P<0.0001) in CAPD (157+/-37 g/m(2)) than in HD patients (133+/-39 g/m(2)). The proportion of CAPD patients requiring antihypertensive drugs was markedly higher than that of HD patients (65 vs 38% P<0.001). Multivariate modelling showed that volume expansion and pressure load as well as serum albumin were independent predictors of left ventricular mass. CONCLUSIONS: Left ventricular hypertrophy is more severe in long-term CAPD patients than in HD patients. This finding is associated with evidence of more pronounced volume expansion, hypertension, and hypoalbuminaemia. Volume and pressure load along with factors associated with hypoalbuminaemia may aggravate LVH in uraemic patients on CAPD.

Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment.

BACKGROUND: Amyloid precursor protein (APP) forms with apparent molecular weights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets. OBJECTIVE: To investigate whether acetylcholinesterase (AChE) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD. PATIENTS AND METHODS: From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical evaluation including the Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline and after 30 days. During this interval, 20 of 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjected to Western blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher-molecular-weight APP form (130 kd) and the lower forms (106 and 110 kd) was measured. RESULTS: All patients taking donepezil completed the 30 days of treatment without adverse effects. The platelet APP forms ratio at baseline did not differ between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant difference was found at follow-up (mean +/- SD optical density ratio: untreated AD, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improvement in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P =.09). CONCLUSIONS: Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD, suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell.

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations.

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD.

BACKGROUND: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. OBJECTIVE: To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD. METHODS: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. RESULTS: Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). CONCLUSION: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

Presenilin 2 mutation does not influence expression and concentration of APP forms in human platelets.

BACKGROUND: The pattern of platelet amyloid precursor protein (APP) forms is altered in sporadic Alzheimer's disease patients, compared with both control subjects and non-Alzheimer's disease-demented patients. The aims of this study were to evaluate in platelets of symptomatic and presymptomatic patients carrying the mutation Met239Val in presenilin 2 (PS2) whether: i) PS2 and presenilin 3 (PS1) were expressed in platelets; ii) an altered expression of different APP isoforms mRNAs could be related to the presence of the mutation; and iii) an abnormal pattern of APP forms was associated to the mutation. MATERIALS AND METHODS: Reverse transcriptionpolymerase chain reaction (RT-PCR) of APP isoforms, PS1 and PS2 was performed on RNA extracted from platelets of three PS2 Met239Val mutated subjects, seven sporadic Alzheimer's patients and nine control subjects. The pattern of platelet APP forms at protein level was evaluated in the same population of subjects by means of Western blots analysis with specific antibody. RESULTS: We found that PS1 and PS2 were expressed correctly in human platelets. When the relative amount of expression of mRNA coding for APP 771/ 751-695 was measured, a similar ratio of expression was found in PS2-mutated subjects, compared with both sporadic Alzheimer's patients and to control subjects. Furthermore, when APP forms were evaluated in platelet homogenates by means of Western blots analysis with appropriate antibody, no difference was found in the pattern of APP forms in presence of PS2 mutation in platelets, compared with control subjects. CONCLUSIONS: These results indicated that PS2 was expressed in human platelets and that PS2 mutation did not affect APP forms pattern, thus, suggesting that in this peripheral cell the pathological effect of PS2 mutation might occur upstream of the amyloid cascade.

Prediction of left ventricular geometry by clinic, pre-dialysis and 24-h ambulatory BP monitoring in hemodialysis patients: CREED investigators.

OBJECTIVE: Arterial hypertension is an established risk factor for left ventricular hypertrophy (LVH) in the uremic population. However, whether 24-h monitoring is a better predictor of LVH than clinic blood pressure and routine pre-dialysis measurements in these patients is still undefined. METHODS: This problem was studied in 64 nondiabetic hemodialysis patients without heart failure. The echocardiographic study as well as the clinic and 24-h ambulatory blood pressure (BP) measurements were performed during the day off-dialysis. Pre-dialysis arterial pressure was calculated as the average value of the 12 routine recordings taken during the month preceding the study. RESULTS: In multivariate models, including also sex, body mass index, hematocrit and serum cholesterol, pre-dialysis systolic, diastolic and pulse pressures were the only independent BP determinants of heart geometry. Twenty-four hour ambulatory BP monitoring (ABPM) did add significant (but weak) information to the prediction of left ventricular internal dimension, i.e. it increased by 9% (P = 0.01) the variance already explained by pre-dialysis diastolic BP and other significant covariates. However, 24-h ABPM did not add any significant and independent explanatory information to the corresponding pre-dialysis measurements for the posterior wall and interventricular septum measurements, and for left ventricular mass (-0.6 to +3.9%; average +1.1%). CONCLUSIONS: In dialysis patients, pre-dialysis BP is at least as strong a predictor of left ventricular mass as 24-h ambulatory monitoring. Thus, the average of 12 routine pre-dialysis measurements may be used to predict heart geometry in dialysis patients without any loss of information in comparison with 24-h ambulatory monitoring.

[Longitudinal echocardiographic study of HIV positive patients]. / Studio ecocardiografico longitudinale in pazienti HIV positivi.

BACKGROUND: From May 1992 to June 1996 the authors have studied a group of 39 subjects with positive anti-HIV, with echo 2D color Doppler examination, to evaluate with semi-annual controls, the wide variety of cardiac complications in the various phases of clinical evolution of the illness. METHODS: At the moment of recruiting, all the subjects with HIV infection were asymptomatic A1 (HIV + As). The patients whose average age was 29 +/- 5, were composed of 60% drug addicts, 17% homosexuals, 8% haemophiliacs and for the 15% heterosexual. RESULTS: The most frequent cardiac complications are represented by hypokinesia of the left ventricle (h-aLV) and by pericardial effusion (PE); more rarely of endocardial vegetations (EV), dilatation of the left ventricle (dLV) and tricuspid insufficiency (TI). The entity of damage and the number of cases observed, are correlated with the grade of clinical severity of the illness. CONCLUSIONS: In accordance with the literature data, cardiac pathologies, particularly in the first phases of the illness, are asymptomatic or paucisymptomatic, making the clinical-instrumental observation of the patient useful also in cardiology.

Evaluation of left ventricular diastolic function by pulmonary venous and mitral flow velocity patterns in endurance veteran athletes.

More and more older people exercise endurance training. Physical activity regularly exercised has been proven to exert beneficial effects on the cardiovascular system. The aim of the present study was to investigate left ventricular diastolic function by analysis of the pulmonary venous flow velocity pattern (PVFVP) in conjunction with the mitral flow velocity pattern (MFVP) in endurance veteran athletes. The study was performed in 15 trained veteran athletes (mean age 60 +/- 10) and 15 sedentary older subjects (mean age 61 +/- 7). Between the two groups there were no differences of age, body surface area and blood pressure. All subjects were without evidence of cardiovascular diseases. They underwent transthoracal pulsed Doppler echocardiography and the following parameters were measured: early (E) and late (A) peak diastolic filling velocities from mitral flow and E/A ratio; peak forward flow velocities during systole (S) and diastole (D) and peak reverse flow velocity at atrial contraction (Ar) from right upper pulmonary vein. The peak early diastolic filling and E/A ratio resulted significantly increased in the veteran athletes compared with the older sedentary subjects (E 80.0 +/- 13.6 and 62.2 +/- 8.2, respectively, p < 0.01; E/A 1.20 +/- 0.1 and 0.90 +/- 0.1, respectively, p < 0.001), whereas there were no significant differences m the PVFVP between the two groups. Heart rate at rest was significantly lower in the veteran athletes compared with sedentary older subjects (58.3 +/- 8 and 72.8 +/- 7.6, respectively, p < 0.001). These data demonstrate an improvement of left ventricle diastolic function in endurance veteran athletes (E/A ratio > 1 ) in comparison with sedentary older subjects (E/A ratio > 1). Analysis of PVFVP suggests that the left atrial contribution to left ventricular filling increases with aging without any significant differences between the two groups. Therefore, left atrial function, i.e., the main determinant of PVFVP is not likely influenced by training. In conclusion, physical activity was found to attenuate alterations in the cardiovascular system that occur in advanced age by an improvement of left ventricular diastolic filling. These changes at rest may be due to a decreased sympathetic tone, as well as to an improvement of intrinsic properties of myocardium of the endurance veteran athletes.

Importance of training in prevention of the decline of physical performance in elderly sedentary persons and veteran athletes.

Thirty-five male veteran athletes were studied between 55 and 79 years of age, having exercised track-and-field sports in the amateur class for at least 15 years without interruption. These athletes were divided into power and endurance groups. The subjects examined were compared to a male control group of 30 elderly, healthy persons aged between 51 and 77 years, leading a sedentary lifestyle. All the subjects were submitted to a standard protocol using BOSCO ERGOJUMP. These trials permitted us to evaluate in the laboratory the explosive power of the inferior limbs, maximal alactic and lactic capacities. The results obtained suggest interesting correlations between the unwinding of physical activity and a deterioration of explosive and anaerobic power, above all in subjects over 65 years of age. Therefore, a regular training program could attenuate the modifications and the age-associated decline.

Body composition and bone mineral density in competitive athletes in different sports.

Bone mineral density (BMD) of the vertebral spine, appendicular skeleton, and whole body was studied in male athletes who chronically trained by different forms of skeletal loading. Eighteen subjects performed weight-bearing activity (canoeists, n = 18), and 14 performed non-weight-bearing activity (cyclists, n = 14). Twenty-eight age-matched male students served as non-athletic controls. The canoeists had significantly higher spine, pelvic and total body BMD than cyclists and controls. No intergroup difference was observed in the BMD of arms and legs despite the fact that physical activity of canoeists and cyclists were characterized by forceful muscular contractions. It is concluded that weight-bearing activity is essential to obtain beneficial skeletal effects on total and regional bone mass in young subjects.

[An evaluation of the pulmonary venous flow pattern by transesophageal and transthoracic Doppler echocardiography in a normal subject]. / Valutazione del pattern di flusso venoso polmonare mediante ecocardiografia Doppler transesofagea e transtoracica nel soggetto normale.

Transesophageal echocardiographic studies have permitted a pulmonary venous flow velocity pattern to be identified which is comparable to that recorder using invasive methods. The pattern consists of 4 stages: an anterograde systolic flow with an early (S1) and late (S2) peak velocity, a diastolic anterograde flow (D) and a retrograde flow liked to atrial contraction (Ar). The aim of this study was to evaluate the pattern of pulmonary venous flow velocity using transesophageal and transthoracic colour Doppler echocardiography in normal subjects in an attempt to: 1) determine normal values derived from the pulmonary venous flow pattern which may contribute to future studies; 2) find correlations between the pattern of pulmonary venous flow and a number of physiological, hemodynamic and echocardiographic parameters which take account of the morphological variations of this flow pattern within a normal range; 3) demonstrate the possibility of being able to carry out study using transthoracic colour Doppler echocardiography. The study was carried out in 38 normal subjects aged between 15 and 76 years old (mean 45 +/- 15) who underwent transthoracic and transesophageal colour-Doppler echocardiography. The following parameters were measured: left atrium diameter, diameters and telediastolic and telesystolic volumes of the left ventricle, ejection fraction and systolic percentage shortening of the left ventricle, peak velocity of the mitral flow pattern and the pulmonary venous flow pattern. The results obtained show that: 1) the pattern of pulmonary venous flow alters with ageing causing the prevalence of systolic over diastolic peak velocity; 2) the pulmonary venous flow parameters which appear to be most significant in hemodynamic terms are the peak velocities of the early systolic flow and anterograde diastolic flow and the ratios S1/S2 and S2/D; 3) the echocardiographic parameters most closely correlated with the peak velocity of pulmonary venous flow are the dimensions of the left atrium, telediastolic and telesystolic ventricular volumes, and the pattern of transmitral flow; 4) heart rate does not appear to influence the pulmonary venous flow pattern significantly (at least within the range of 50-100 b/min), except for retrograde flow. Similar results were obtained using transesophageal and transthoracic Doppler echocardiography and therefore if future studies succeed in obtaining useful information, of not only speculative but also practical interest, from the evaluation of pulmonary venous flow, these can be obtained using a simple, widespread and completely non-invasive method such as transthoracic Doppler echocardiography.