Evaluation of regional myocardial systolic and diastolic function using ECG-gated Sestamibi scintigraphy Preliminary results in patients with and without coronary artery disease

Sestamibi allows ECG-gated acquisition and similarly to radionuclide angiography a time-activity curve from a defined myocardial region can be derived and analysed. Diastolic (peak relaxation velocity) and systolic (per cent thickening) functional parameters from Sestamibi ECG-gated acquisition were obtained; this data were compared in 10 patients with radionuclide angiographic data (peak filling rate and ejection fraction, respectively). A high correlation was found between peak relaxation velocity and peak filling rate (r = 0.792), while no significant correlation was found between thickening and ejection fraction (r=0.577). Sestamibi parameters were calculated in 15 patients with known or suspected coronary artery disease and compared with those obtained in 10 normal subjects. In regions supplied by stenotic vessels the average values of peak relaxation velocity and thickening were significantly lower than those obtained in control subjects in the corresponding vascular territory. The average regional values of the diastolic parameter were significantly lower than the corresponding normal range also in regions with preserved systolic function, i.e. with thickening values within 1SD from the mean value of normals.In conclusion, from the ECG-gated acquisition of Sestamibi regional diastolic and systolic functional parameter may be derived; this completes the spectrum of information that can be obtained by a single injection of tracer.Abbreviations EDc end-diastolic counts - EDV end-diastolic volume - EF% ejection fraction - ESc end-systolic counts - ESV end-systolic volume - PFR peak filling rate - PRV peak relaxation velocity - TH% percent thickening     

Minimally invasive treatment of synchronous colorectal tumours

In patients with colorectal cancers synchronous neoplastic lesions are an increasingly frequent finding at preoperative staging; 3% of the cases are other cancers while 33-35% of the synchronous lesions are villous adenomas. The treatment of most colorectal adenomas can be performed by endoscopic poplypectomy. In 5% of cases there are synchronous colorectal lesions also requiring surgical treatment. From January 1995 to June 2007 we treated 5 patients with rectal lesions by transanal endoscopic microsurgery (TEM) together with a laparoscopic colectomy for the presence of synchronous lesions at the "Clinica Chirurgica Generale e d'Urgenza" of the University of Perugia,. Surgical timing involved performing a sequential exeresis characterised by a cancer resection, followed by resection of the voluminous adenoma: TEM for rectal cancer followed by a laparoscopic right hemicolectomy with an extracorporeal anastomosis for a voluminous villous adenoma (1 patient) and laparoscopic right hemicolectomy with an extracorporeal anastomosis for cancer followed by TEM for a voluminous villous adenoma (2 patients). One patient with left colon cancer associated with a voluminous villous rectal adenoma first underwent TEM for the rectal adenoma and then a left laparoscopic hemicolectomy with an extracorporeal anastomosis in order to ease the transit of the circular mechanical stapler. Another patient with rectal and right colon adenomas first underwent TEM for a voluminous rectal sessile adenoma and later a right hemicolectomy. The use of this minimally invasive approach allowed rectum preservation and less invasive surgery.     

Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis

Sympathoadrenergic mechanisms may play a role in multiple sclerosis (MS). We examined catecholamine (CA) levels and production and tyrosine hydroxylase (TH) expression in peripheral blood mononuclear cells (PBMCs) from MS patients, and the correlation between CA production and apoptosis in PBMCs. PBMCs from MS patients had increased norepinephrine (NE) levels. However, phytohaemagglutinin (PHA)-stimulated PBMCs from MS patients with active disease synthesized less dopamine (DA) than cells from both healthy controls and patients with inactive disease. PBMCs from patients with inactive disease showed lower expression of TH. Pharmacological inhibition of TH in cultured PBMCs stimulated with PHA reduced the percentage of apoptotic cells. Since a failure of activation-induced apoptosis in immune cells may be involved in MS, it is suggested that altered CA production by PBMCs may be implicated in such dysregulation.     

Myocardial metabolic and receptor imaging in idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) is a distinct disease of the myocardium, of unknown etiology. The disease can occur acutely, or evolve in a subacute fashion. IDC is often associated with a substantial impairment of ventricular function, which may recover over time. Although spontaneous recovery of LV function occurs in 20%-45% of newly diagnosed patients, the majority of patients do not do well. IDC has an average 5-year mortality of 20%. Abnormalities of energetics, perfusion, and adrenergic control of the myocardium are markers of the status of LV dysfunction. As the heart fails, changes occur in the production and catabolism of high-energy substrates, the efficiency of mitochondrial oxidative processes, the distribution of resting perfusion and coronary vasodilating capacity and the adrenergic receptor density and function. This article reviews the information provided by metabolic and receptor imaging in patients with IDC, and the role the data may play in patient management.     

Cardiac phantom measurement validating the methodology for a cardiac multi-centre trial with positron emission tomography

In an ongoing international multi-centre trial, positron emission tomography (PET) is being used to evaluate the effect of a new P-selectin antagonist on the infarct size in patients with acute myocardial infarction, treated with thrombolysis. Although it is possible to correct for site-dependent factors, it is desirable to reduce these factors to a minimum. Therefore, acquisition and reconstruction protocols have been defined that can be closely followed by all participating centres. The resulting reconstructed images are transferred to the core centre for central processing with semi-automatic software. This paper reports on the multi-centre phantom experiment that was carried out to assess the inter-centre reproducibility of defect size determination with this protocol. Also, the spatial resolution of the short axis slices was examined. In addition, the analysis procedure was applied to normal PET studies to evaluate the specificity of perfusion defect detection. The transmural cold defect in the phantom occupied 14.8% of the left ventricular area. The automated analysis was applied to the phantom measurements from the 14 participating PET cameras. It yielded an accurate estimate of 15.1% with a standard deviation of 0.6%, indicating excellent reproducibility. The spatial resolution in the short axis slices was similar for all PET systems: 9.6+/-0.8 mm. The same procedure produced a defect size of zero in the studies of normal volunteers. This study indicates that cardiac studies from multiple PET systems can be pooled for statistical analysis.     

Survival and Prognostic Factors of Cirrhotic Patients with Ascites: A Study of 134 Outpatients

Ascites is a complication of chronic liver disease that is associated with decreased survival. The purpose of the present study was to identify some prognostic factors easily obtainable by the clinician in a large group of cirrhotic patients with ascites, possibly useful for first screening of outpatients as candidates for liver transplantation. We studied 134 ambulatory patients with cirrhosis who came to our outpatient clinic between July 1983 and March 1989 because of an episode of ascites. These patients were then followed up for an average period of 31 ± 23 months and survival was determined. Thirty-one variables determined at the time of inclusion were analyzed with a Cox proportional hazards model to identify predictors of mortality. Cumulative mortality as of June 30, 1991, was 59%. Factors independently correlated with death were: refractory ascites (relative risk, 4.78), low albumin levels (3.77), high Child-Pugh score (3.31), encephalopathy (2.71), high bilirubin levels (2.03), high γ-glutamyl-transferase levels (1.87), and old age (1.57). The results show that 1 ) the occurrence of refractory ascites has a prognostic value superior to those of other variables, and 2 ) simple clinical and biochemical parameters, most of them components of the Child-Pugh score, are useful for a first screening of ascitic cirrhotic patients as candidates for liver transplantation.     

Effect of muscarinic receptor blockade on canine gastric tone and compliance in vivo.

Muscarinic pathways are involved in maintaining gastric tone during fasting and atropine is known to decrease gastric tone via blockade of a tonic vagal cholinergic input. Our aim was to assess the role of different muscarinic receptors in modulating canine gastric tone and compliance in vivo by using "selective" muscarinic receptor antagonists (telenzepine, AF-DX 116 and 4-DAMP for M1, M2, and M3 receptors, respectively) and the non-selective muscarinic receptor antagonist atropine. In four fasting, conscious dogs, we characterized the pressure-volume relationship in the proximal stomach by using a barostat. Drug effects were investigated by studying pressure-volume relationships before and 15 min after intravenous administration telenzepine, AF-DX 116, 4-DAMP or atropine. Pressure-volume curves were fitted by non-linear regression analysis. Before drug administration, the curve that best fitted the pressure-volume relationship was exponential. Atropine (100 microg kg-1) immediately decreased baseline gastric tone, i.e. relaxed the stomach (Deltavolume at 2 mmHg=236+/-15 ml; P<0.05), and significantly (P<0.01) shifted the pressure-volume curve to the left. Telenzepine, at the lowest dose (3 microg kg-1), shifted the pressure-volume curve to the right (P<0.01). AF-DX 116 at the lower dose (422 microg kg-1) had no effect on baseline gastric tone or the gastric pressure-volume curve, whereas the higher dose (2532 microg kg-1) significantly shifted the pressure-volume curve to the left (P<0.01), but did not increase baseline gastric volume. Finally, 4-DAMP (13.5, 45, 135 microg kg-1) immediately decreased baseline gastric tone (Deltavolume at 2 mmHg=97+/-29 ml, 110+/-35 ml and 155+/-21 ml, respectively) and significantly shifted the pressure-volume curve to the left (P<0.01). We conclude that muscarinic pathways are involved in modulating canine gastric tone and compliance during fasting: M3 receptors seem to play a key role in excitatory pathways, whereas the shift of pressure-volume curve to the right observed with the lowest dose of telenzepine is consistent with the existence of M1 receptors on inhibitory pathways.     

Extension of myocardial necrosis differently affects MIBG retention in heart failure caused by ischaemic heart disease or by dilated cardiomyopathy

Purpose This study aims to investigate the relationship between cardiac sympathetic nervous function (CSNF) and myocardial perfusion/function in patients with heart failure (HF) due to dilated cardiomyopathy (DCM) or ischaemic heart disease (CAD).Methods Twenty patients (10 DCM, 10 CAD, 17 males, age 69±5 years) with NYHA class IIIb HF were studied. CSNF was evaluated by early/delayed ¹²³I-metaiodobenzylguanidine (MIBG) uptake and regional washout (WO). Myocardial perfusion and function were evaluated by ^99mTc-tetrofosmin gated single-photon emission tomography (G-SPECT) using a 20-segment model for 400 segments. In each segment, regional MIBG WO was computed as (count density in early images–count density in delayed images/count density in early images)×100.Results DCM and CAD showed similar summed rest perfusion score (6.7±5 vs 9.5±5, p=NS) and mean ejection fraction values (29±7% vs 30±9%, p=NS). By contrast, the summed thickening score was higher in DCM than in CAD patients (26±7 vs 17±6, p<0.05). QGS analysis identified akinesis/dyskinesis in 129/137 (94%) severely hypoperfused segments which were considered as damaged. According to the underlying aetiology of HF, marked differences in regional MIBG WO were observed. In fact, within the CAD group, regional MIBG WO was lower in reference than in damaged segments (38±21% vs 46±19%, p<0.05). By contrast, in DCM patients, regional MIBG WO was faster in reference than in damaged segments (49±18% vs 41±30%, p<0.05). When the two groups were directly compared, regional MIBG WO from damaged areas was similar irrespective of the underlying disease, while it was faster in DCM than in CAD patients from reference segments.Conclusion These data confirm the hypothesis that the presence of myocardial necrosis in HF due to CAD and the consequent loss of neuronal endings cause alterations in regional MIBG WO different from those observed in DCM.