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Biomedical subjects

C Pieroni

Publications and source records attributed to C Pieroni.

15 recordsLinked to original sources

Implementation of myocardial perfusion imaging in the early triage of patients with suspected acute coronary syndromes.

The risk of overlooking an underlying acute coronary syndrome remains an important challenge in patients complaining of chest pain but who have a non-diagnostic ECG (CP). Indeed, myocardial scintigraphy associated with exercise testing (exercise SPET) represents a valuable tool for excluding coronary artery disease (CAD) especially in patients with CP and delayed presentation to the emergency department. We sought to implement diagnoses of CAD in the early triage of CP patients by exercise gated SPET and compare diagnoses with outcomes. A total of 306 consecutive patients presenting with CP were found to be free of CAD at first line work-up including clinical evaluation, markers of myocardial injury and echocardiogram. These patients were studied initially with exercise SPET, and those with perfusion defects underwent angiography, while those with normal scans were discharged and followed up. Patients with positive scans (34%, n=105) had documented coronary stenoses in 43% (n=45); patients with negative scans (66%, n=201) had evidence of non-fatal coronary events at 6 months in 1.5% (n=3). When imaging was analysed with gating by the presence of transmural perfusion defects associated with wall motion abnormalities (n=86), only one patient, among 19 excluded, was recognized as having coronary stenosis by angiography (SPET vs gated SPET: negative predictive value 98.5% and 98%, respectively, P=NS; diagnostic accuracy 79% and 85%, respectively; P< or =0.03). Therefore, implementation of myocardial perfusion imaging in the early triage of patients with suspected acute coronary syndromes was effectively obtained by early exercise gated SPET, especially in patients with transmural myocardial perfusion defects associated with wall motion abnormalities.

Acute Disease↗

Chest pain unit management of patients at low and not low-risk for coronary artery disease in the emergency department. A 5-year experience in the Florence area.

In this study, we screened a total of 6723 consecutive patients with chest pain and ECG non-diagnostic for acute myocardial infarction (AMI) on presentation to the emergency department (ED). The aim of the study was to avoid missed AMI, improve safe early discharge and reduce inappropriate coronary care unit (CCU) admission. Chest pain patients were triaged using a clinical chest pain score and managed in a chest pain unit (CPU). Patients with a low clinical chest pain score were considered at very 'low-risk' for cardiovascular events and discharged from the ED; patients with a high chest pain score were submitted to CPU management. Observation and titration of serum markers of myocardial injury were obtained up to 6 hours. Rest or stress myocardial scintigraphy (SPECT) was performed in patients > 40 years or with > or = 2 major coronary risk factors. Exercise Tolerance Test (ETT) or Stress-Echocardiogram (stress-Echo) were performed in younger patients or with < 2 coronary risk factor, or unable to exercise, respectively We discharged directly from the ED the majority of patients (4454; 66%): in this group there was only a 0.2% final diagnosis of coronary artery disease (CAD) at follow-up. The remaining 34% of patients, with non-diagnostic or normal ECG, were managed in the CPU. In this group, 1487 patients (representing 22% of the overall study group) were found positive for CAD, two-thirds because of delayed ECG or serum markers of myocardial injury, and one-third by Echo, SPECT or ETT. In conclusion, CPU based management allowed 22% early detection of myocardial ischaemia and 78% early discharge from the ED avoiding inappropriate CCU admission and optimizing the use of urgent angiography.

Aged↗

Early detection of myocardial ischaemia in the emergency department by rest or exercise (99m)Tc tracer myocardial SPET in patients with chest pain and non-diagnostic ECG.

Chest pain (CP) represents a frequent reason for presentation at the emergency department (ED). A large proportion of patients have non-diagnostic ECG on presentation, and in many cases several hours have elapsed since onset of symptoms. Acute rest myocardial scintigraphy (rest SPET) has been shown to have a relevant role in the detection of patients at risk for coronary events, but its sensitivity and negative predictive value are optimal only within the first 3 h following onset of symptoms. In those with delayed presentation, exercise SPET alone, as a screening approach, appears more promising, but its feasibility and diagnostic role in the ED are still unresolved. A total of 231 consecutive patients with a recent-onset (<24 h) first episode of CP had a negative first-line work-up including ECG, troponins, creatine kinase-MB and echocardiography. These patients were considered at low risk for short-term coronary events. Patients were studied with rest SPET if they presented <3 h after onset of CP and exercise SPET if they presented after > or =3 h. The end-points of the study were detection of significant coronary artery disease (CAD) by angiography and major coronary events or cardiac death at 6 months. Eighty patients (35%) underwent rest SPET, while 151 (65%) underwent exercise SPET. Two of the 159 patients with negative SPET had evidence of critical CAD at 6-month follow-up (one patient in the rest SPET group and one in the exercise SPET group; P=NS). Of the 72 patients (31%) with a positive scan, 34 (15%) had documented CAD (16 patients in the rest SPET group and 18 in the exercise SPET group; P=NS). Sensitivity, specificity, accuracy and predictive value were not statistically different between the two groups. In conclusion, the accuracy of exercise SPET in patients with CP and delayed presentation to the ED is comparable to that of validated rest SPET in patients with early presentation. Owing to the high negative predictive value (99%), exercise SPET is especially valuable as a screening tool for the exclusion of CAD in low-risk patients and implementation of early discharge.

Aged↗

Octreoscan SPET evaluation in the diagnosis of pancreas neuroendocrine tumors.

The study describes the results of Octreoscan SPET (OCTSPET) qualitative and semi-quantitative evaluation in 38 patients with suspected pancreatic neuroendocrine tumors. SPET studies were acquired at 4 and 24 hours after the injection of 111-220 MBq of 111-In-pentetreotide (Octreoscan). Qualitative and semi-quantitative evaluations were performed. The semi-quantitative approach was based on the time course of Tumor/Non Tumor ratios (TNTinc) from 4 and 24 hours. The OCTSPET results were true positive in 18 of 19 patients (10 gastrinoma, 5 insulinoma, 1 neuroendocrine tumor, 1 glucagonoma and 1 carcinoid) and false negative in one insulinoma. Besides, 20 of 38 patients (52%) had clinical plans modified after OCTSPET; OCTSPET was the only positive diagnostic test in 14 of 19 patients (73%) and guided the surgery decision in 14 of 25 patients (56%). In conclusion, these data indicate that Octreoscan represents an excellent tool for the diagnosis of pancreatic neuroendocrine tumors.

Adult↗

Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. A case report.

BACKGROUND: Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis usually presents after menarche with progressive abdominal pain during menses secondary to hematocolpos. We describe a case with the unique presentation of rectal pain and constipation. CASE: A 13-year-old girl presented to the emergency department complaining of lower abdominal and rectal pain and constipation of two weeks' duration. Pelvic ultrasound, physical examination and laparoscopic findings established a diagnosis of hematometracolpos secondary to uterus didelphys with unilateral imperforate hemivagina. An incision in the vaginal septum allowed drainage of the hematocolpos, providing relief of the patient's symptoms. CONCLUSION: Uterus didelphys with unilateral imperforate hemivagina and ipsilateral renal agenesis may present with apparent gastrointestinal symptoms. With increased awareness of this problem, timely diagnosis may be achieved.

Adolescent↗

Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer's disease.

Cyclooxygenase-2 (COX-2), a key enzyme in prostanoid biosynthesis, may represent an important therapeutic target in Alzheimer's disease (AD). In the present study, we explored the regulation of COX-2 in the hippocampal formation in sporadic AD. Using semiquantitative immunocytochemical techniques, we found that in AD cases (vs. age-matched controls) neurons of the CA1-CA4 subdivisions of the hippocampal pyramidal layer showed elevation of COX-2 signal; COX-2 levels correlated with amyloid plaque density. In contrast, the level of COX-2 immunostaining in the dentate gyrus granule neurons was not elevated in AD. No expression of COX-2 in cells with glial morphology was found in any case examined. In parallel, in vitro studies found that neurons derived from transgenic mice with neuronal overexpression of COX-2 are more susceptible to beta-amyloid (Abeta) toxicity, with potentiation of redox impairment. The results indicate elevated expression of neuronal COX-2 in subregions of the hippocampal formation in AD and that such elevation may potentiate Abeta-mediated oxidative stress.

Adult↗

Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily.

The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC beta-sheet and includes residues on the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds alpha4 integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1.

Amino Acid Sequence↗

Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased beta-amyloidogenesis.

The early endosome is the first vacuolar compartment along the endocytic pathway. It is the site of internalization and initial processing of amyloid precursor protein (APP) and apolipoprotein E (ApoE), two proteins of etiological importance in Alzheimer's disease, and a putative site of beta-amyloid peptide (Abeta) formation. Here, we identify early endosomes in human pyramidal neurons, using specific compartmental markers and morphometry, and show that in Alzheimer's disease individual endosomes display up to 32-fold larger volumes than the normal average. Endosomal enlargement contributed to an average 2.5-fold larger total endosomal volume per neuron, implying a marked increase in endocytic activity. Endosomal alterations were evident in most pyramidal neurons in Alzheimer brain, detectable at early stages of the disease but absent in several other neurodegenerative disorders examined. In addition, mature and proenzyme forms of the proteases cathepsin B and cathepsin D, a candidate APP secretase, were identified in most early endosomes in Alzheimer brains but were detectable in only a minor proportion of endosomes in normal brain. Expression of the cation-dependent 46 kDa mannose 6-phosphate receptor was elevated in pyramidal neurons of Alzheimer brains, which could be a possible basis for the altered cathepsin trafficking pattern. Enhanced endocytic activity, coupled with increased trafficking to endosomes of proteases, which may have the ability under pathological conditions to generate Abeta, constitutes a potential mechanism by which beta-amyloidogenesis may become accelerated in sporadic AD and also be subject to influences by ApoE.

Aged↗

Occult thyrotoxicosis in patients with chronic and paroxysmal isolated atrial fibrillation.

Thyroid function tests, including thyrotropin releasing hormone administration (TRH), were performed in 40 consecutive patients with isolated atrial fibrillation (IAF) (i.e., without any other evidence of cardiac disease). The arrhythmia was chronic in 5 and paroxysmal in 35 patients. Thyrotoxicosis could not be diagnosed either clinically or by abnormal serum levels of T4, T3, T3 BC, and thyroid stimulating hormone (TSH). Thyroid stimulating hormone response to TRH, which was normal in 35 patients, was absent in 5 (12.5%) who were considered to have occult thyrotoxicosis. One had chronic and the other 4 had paroxysmal IAF. The arrhythmia did not recur after antithyroid treatment in these four patients who were in sinus rhythm after a mean follow-up period of 21 months. Full exploration of the thyroid function therefore seems useful not only in patients with chronic IAF, but also in those affected by the paroxysmal form.

Adult↗

Binding of low-molecular-weight heparin to aortic endothelium in rabbits.

The ability of a low-molecular-weight heparin to bind in vivo to the aortic endothelium in rabbits, compared with that of unfractionated extractive sodium heparin (UHEP), was investigated. For this purpose a low-molecular-weight heparin (LMWHEP) fraction (CY 216 A, 4,000-5,000 daltons) and an extractive UHEP (average 17,000 daltons) were labeled with 99m Tc and injected (0.2, 0.6, and 1.2 mg/kg) intravenously in groups of 6 rabbits. The binding to endothelium was then measured by counting the radioactivity of samples of abdominal aorta. Both heparins bound to endothelium with a fast, saturable, and reversible binding. No significant difference in the total bound radioactivity was found between the two heparins, suggesting that the investigated LMWHEP retains the ability to bind to the endothelium, contributing to its athrombogenic properties.

Animals↗

Nitrate tolerance in patients with effort angina.

BACKGROUND: In some patients with chronic stable angina the beneficial effects of nitrates may result not only from a reduction in venous return, but also from their action on coronary circulation. In these patients, rate-pressure product at ischemia (RPPI) increases to > 2500 bpm x mmHg after sublingual nitrates (SLN). The relative susceptibility of the venous system and the coronary circulation to the development of nitrate tolerance and the effects of two different drug schedules on the development of tolerance were investigated in patients with these characteristics. METHODS: Five patients were treated with isosorbide-5-mononitrate (IS5MN) 20 bid (8.00 am and 3.00 pm) for 1 week (Group 1) and 5 patients with IS5MN 40 bid (8.00 am and 8.00 pm) for 1 week (Group 2). Tolerance was identified as the decreased effect of SLN; the effects of nitrates were evaluated in relation to: reduction in left ventricle area (delta LVA), which had been measured using equilibrium radionuclide ventriculograms in LAO 45 degrees; this area was considered as an index of the venous return effects; increase in RPPI (delta RPPI), which had been assessed by ergometric test; RPPI was considered an index of coronary flow reserve. Measurements of LVA and RPPI were made in wash-out at the start of the study (delta LVA 1 and delta RPPI 1) and after 1 week of treatment (delta LVA 2 and delta RPPI 2). The mean values of the differences were then evaluated and compared using Student's "t" test. RESULTS AND CONCLUSIONS: In Group 1 patients delta LVA 2 and delta RPPI 2 showed values which were similar to delta LVA 1 and delta RPPI 1 (mean value delta LVA 2 47 vs mean delta LVA 1 48.2 pixels, p = ns; mean value delta RPPI 2 5264 vs mean delta RPPI 1 5536 bpm x mmHg, p = ns). These results suggest that Group 1 patients did not develop tolerance either at the coronary or at the venous level. In Group 2 patients, delta LVA 2 was significantly lower than delta LVA 1 (mean delta LVA 2 18.4 vs mean delta LVA 1 54 pixels, p < 0.01). This finding indicated tolerance to nitrates at the venous level. On the other hand, in all Group 2 patients, values of delta RPPI 2, though lower than delta RPPI 1 (mean delta RPPI 2 3095 vs mean delta RPPI 1 6083 bpm x mmHg, p < 0.01) were still higher than 2500 bpm x mmHg, indicating that the effect of nitrates at the coronary level was preserved. These data suggest that in patients treated with high doses of nitrates, the effect of these drugs at the coronary level is still present when tolerance has already developed at the venous level.

Angina Pectoris↗