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Biomedical subjects

Ignasi Carrió

Publications and source records attributed to Ignasi Carrió.

At least 19 recordsLinked to original sources

Targeting neuronal dysfunction and receptor imaging.

The sympathetic nervous system has great influence on cardiovascular physiology, and the importance of cardiac innervation abnormalities in the physiopathology of various cardiac diseases has been emphasized. Cardiac neurotransmission imaging with single-photon emission computed tomography (SPECT) allows in vivo assessment of the myocardial nervous system. At present, the most commonly used SPECT tracer to assess cardiac neurotransmission is metaiodobenzylguanidine labelled with iodine-123 ((123)I-MIBG). In patients with heart transplantation, ischemic heart disease, dysautonomias and drug-induced cardiotoxicity, assessment of neuronal function can help characterise the disease and improve the prognostic stratification. Cardiac (123)I-MIBG scintigraphy allows autonomic neuropathy to be detected in the early stages of diabetes mellitus. In patients with heart failure, the assessment of cardiac sympathetic activity has important prognostic implications. Future directions in cardiac sympathetic neurotransmission include the development of new tracers, targeting of second-messenger molecules and early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention of heart failure.

3-Iodobenzylguanidine↗

Dopamine D2 receptor occupancy by risperidone: implications for the timing and magnitude of clinical response.

The objective of the study is to investigate whether dopamine D2 receptor occupancy by risperidone and plasma levels over time can account for therapeutic efficacy and the latency period to response. Thirty-eight examinations with (123)I-IBZM single photon emission computed tomography were performed on 22 patients with schizophrenia, at diagnosis, 48 h after starting risperidone treatment and at a stable dose. Risperidone plasma levels were determined and psychopathologic evaluations (Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale) were carried out. No differences in the striatal/occipital (S/O) ratio or plasma levels were found between examinations at the 48-h time point and when a stable dose level had been established, so these parameters could not account for the latency period required for clinical response. D2 receptor occupancy at 48 h correlated positively with clinical improvement after 2 weeks of treatment. Therefore, if these results are confirmed, D2 receptor occupancy at the beginning of treatment with risperidone may be a predictor of subsequent clinical response.

Adolescent↗

Increased frontal and paralimbic activation following ayahuasca, the pan-Amazonian inebriant.

RATIONALE: Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase inhibitors that render DMT orally active. Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention, with individuals reporting altered somatic perceptions and intense emotional modifications, frequently accompanied by visual imagery. Despite recent advances in the study of ayahuasca pharmacology, the neural correlates of acute ayahuasca intoxication remain largely unknown. OBJECTIVES: To investigate the effects of ayahuasca administration on regional cerebral blood flow. METHODS: Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double-blind clinical trial. Regional cerebral blood flow was measured 100-110 min after drug administration by means of single photon emission tomography (SPECT). RESULTS: Ayahuasca administration led to significant activation of frontal and paralimbic brain regions. Increased blood perfusion was observed bilaterally in the anterior insula, with greater intensity in the right hemisphere, and in the anterior cingulate/frontomedial cortex of the right hemisphere, areas previously implicated in somatic awareness, subjective feeling states, and emotional arousal. Additional increases were observed in the left amygdala/parahippocampal gyrus, a structure also involved in emotional arousal. CONCLUSIONS: The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes.

Adult↗

Value of radionuclide studies in cardiac transplantation.

Effective noninvasive evaluation of acute and chronic allograft rejection remains an important challenge in patients with cardiac transplantation. Radionuclide studies have demonstrated utility because of their ease of use, giving relevant information about the pathophysiology of the transplanted heart, along with valuable diagnostic and prognostic indicators. This article focuses on reviewing the pathophysiological changes of the transplanted heart and implications for radionuclide studies.

Graft Rejection↗

Striatal D2 receptor binding as a marker of prognosis and outcome in untreated first-episode psychosis.

In a preliminary 123I-IBZM SPECT study in first-episode psychosis, a relationship between striatal dopaminergic D2 receptor (D2R) binding and premorbid adjustment was suggested. These results were replicated in the present study (n = 18), and D2R binding at diagnosis predicted a high probability for schizophrenia outcome by 2-year follow-up. The present findings contribute to the evidence of abnormal D2R binding in schizophrenia and suggest that SPECT might be useful for outcome prediction in first-episode psychosis.

Adult↗

Striatal dopaminergic D2 receptor occupancy and clinical efficacy in psychosis exacerbation: a 123I-IBZM study with ziprasidone and haloperidol.

OBJECTIVE: The aim of this study was to compare striatal dopaminergic D2 receptor occupancy (D2 RO) induced by ziprasidone and haloperidol and its relationship with clinical response and extrapyramidal side effects (EPS) in patients with acute psychosis exacerbation. METHOD: Twenty patients hospitalized with an acute psychosis exacerbation were randomised in a single-blind study to receive either ziprasidone (80-120 mg/day) or haloperidol (5-20 mg/day) for more than 2 weeks. When stable doses were achieved, data on 123I-IBZM single-photon emission computed tomography (SPECT), as well as data on clinical efficacy (positive and negative symptoms scale [PANSS]) and EPS (Simpson Angus scale [SAS]), were compared between the two groups of patients. Clinical response was defined as a percentage of change of >30% in PANSS. Striatal D2 RO and clinical data were also compared between responders and nonresponders on each treatment group. RESULTS: All patients on haloperidol and four patients on ziprasidone showed EPS. Mean D2 RO was significantly higher in the haloperidol (74.7+/-3.5) than in the ziprasidone (60.2+/-14.4) group (Mann Whitney U-test [M-W U-test] 8.50; p=0.002). Five patients were responders, and five were nonresponders on each group of treatment. Haloperidol responders and nonresponders did not differ in D2 RO, duration of treatment, doses or EPS. Ziprasidone responders were on higher doses than nonresponders and showed higher D2 RO although below 74%. A positive correlation of ziprasidone D2 RO was found with dose (r Spearman 0.87; p=0.001) and with SAS scores (r Spearman 0.88; p=0.001). CONCLUSIONS: Ziprasidone induces lower D2 RO and EPS than haloperidol, which is consistent with an atypical antipsychotic profile. A direct relationship of ziprasidone D2 RO with dose, clinical efficacy and EPS has been found in this study. These data suggest that high ziprasidone doses might be more beneficial in patients with psychosis exacerbation and claim for caution regarding EPS appearance with such high dosages.

Adult↗

Left ventricular end-diastolic volume is decreased at maximal exercise in athletes with marked repolarisation abnormalities: a continuous radionuclide monitoring study.

PURPOSE: Although marked repolarisation abnormalities (MRAs) are considered innocuous in trained athletes, their functional significance awaits clarification. The aim of this study was to further evaluate the pathophysiological implications of such MRAs. METHODS: We compared left ventricular (LV) functional response to exhausting exercise in 39 male athletes with (n=22) or without (n=17) MRAs and with no structural cardiac abnormalities, by means of a portable radionuclide monitoring system (Vest, Capintec, Inc., Ramsey, NJ). MRAs were defined by the presence of negative T waves > or =2 mm in three or more rest ECG leads. The Vest data were averaged for 30 s and analysed at baseline and at different heart rate (HR) values (50%, 75%, 85%, 95% and 100% of peak HR), as well as at 2, 5 and 10 min of recovery. RESULTS: There were no significant differences in the effect of exhausting exercise between athletes with and athletes without MRAs. However, there was a significant difference in the trend in end-diastolic volume (EDV) during exercise depending upon the group of athletes considered (p=0.05). EDV differed significantly between the two groups of athletes at peak HR (p=0.031). EDV in athletes with MRAs was lower than that in athletes without MRAs (102%+/-7% vs 107%+/-8%, p=0.034). CONCLUSION: EDV is decreased at peak HR in athletes with MRAs. Such high HR values are infrequently achieved or maintained during sporting activities; therefore, in the absence of structural heart disease, MRAs should not preclude physical training and competitive availability.

Adult↗

Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake.

PURPOSE: Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. METHODS: Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second 123I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. RESULTS: After amitriptyline administration, there was a decrease in regional MIBG uptake in 10+/-4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. CONCLUSION: A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging.

3-Iodobenzylguanidine↗

99mTc-depreotide scintigraphy of bone lesions in patients with lung cancer.

PURPOSE: Scintigraphy with 99mTc-depreotide, a somatostatin analogue-technetium ligand, has been used for evaluation of various malignant neoplasms, including lung cancer. The diagnosis of bone metastases in patients with lung cancer is not always definitive with current imaging methods. Visualisation of somatostatin receptors (SSTRs) in bone lesions, when the primary tumour exhibits such receptors, could be helpful in characterising them as metastatic. The aim of this study was to assess the value of 99mTc-depreotide in differentiating between benign and malignant bone lesions in patients with lung cancer. METHODS: The study population comprised 20 patients (17 males and three females, mean age 63 years) with proven lung cancer in whom bone lesions had been detected by conventional imaging methods. All patients underwent 99mTc-hydroxydiethylene diphosphonate and 99mTc-depreotide scintigraphy within 2 weeks. Bone lesions were classified as benign or malignant on the basis of clinical, imaging and/or histological criteria. RESULTS: 99mTc-depreotide uptake in the primary tumour was seen in 19 of the 20 patients. Conventional imaging methods detected 55 bone lesions, 31 of which were classified as malignant. Twenty-eight (90%) of these lesions showed 99mTc-depreotide uptake, suggesting bone metastases, while three did not. Twenty-four bone lesions were classified as benign by conventional imaging methods, and none of them showed 99mTc-depreotide uptake. In addition, 99mTc-depreotide demonstrated extra-osseous lesions in six patients. CONCLUSION: In patients with lung cancer and bone lesions, 99mTc-depreotide scintigraphy uptake in the bone lesions supports the diagnosis of malignancy, in particular if the primary lung tumour also exhibits SSTRs. Furthermore, whole-body 99mTc-depreotide scintigraphy may disclose extra-osseous disease.

Adult↗

Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment.

PURPOSE: Patients with malignant hematologic disorders undergoing bone marrow transplantation (BMT) may develop renal insufficiency. A study was undertaken to assess prospectively the subclinical renal function changes with radioisotopic methods in patients undergoing BMT for hematologic malignancies. METHODS AND MATERIALS: We studied 71 patients with normal renal function undergoing BMT for various hematologic malignancies, mostly leukemias. Conditioning included chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total-body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was limited to 10 Gy using partial transmission blocks fabricated after renal opacification with nonionic, hypo-osmolar contrast medium. The glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined radioisotopically before conditioning and at 4, 12, and 18 months, using (51)Cr ethylene-diamine-tetra-acetic acid and (131)I ortho-iodo-hippurate, respectively. Renal insufficiency was defined as a decrease of >/=30% in GFR or ERPF compared with the baseline values. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed. RESULTS: At 4 (early) and 12-18 (late) months, a >/=30% GFR drop was observed in 54% and 49% of patients and a >/=30% ERPF drop in 44% and 34% of patients, respectively. After stepwise logistic analysis, a GFR reduction at 4 months correlated significantly with age (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop at 4 months was independently related with the days of amphotericin use and days of prostaglandin E(1) use (prophylaxis against hepatic venoocclusive disease). A GFR and ERPF reduction at 12-18 months correlated with days of amphotericin use and days of prostaglandin E(1) use, respectively. CONCLUSION: Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was observed; patients whose kidneys received 10 Gy through the use of partial shielding blocks had significantly greater renal dysfunction at 4 months. The administration of potentially nephrotoxic contrast agents used in radiotherapy treatment planning may be responsible for the latter observation. Prostaglandin E(1) use correlated with a significant reduction in ERPF at both 4 and 12-18 months.

Adolescent↗

Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected for renal size.

BACKGROUND: Decreased relative 99mTc dimercaptosuccinic acid (99mTc-DMSA) uptake can be a consequence of abnormal kidney size, associated with normal or impaired function. When there is a small kidney, relative 99mTc-DMSA uptake is decreased, and it is sometimes difficult to distinguish a small, normal kidney from a hypofunctioning kidney. Here, relative renal function was studied by quantifying the relative 99mTc-DMSA uptake corrected for renal size (RCU). METHODS: Five hundred and fifty-five consecutive patients (184 adults) aged 1 month to 82 years (mean, 14.8 years) underwent a 99mTc-DMSA study for various renal diseases. Results were compared with the relative 99mTc-DMSA uptake without size correction (RUU). Visual evaluation of images was also performed. RESULTS: In 288 patients (52%) the relative 99mTc-DMSA uptake was normal, either uncorrected or corrected, for renal size; in 184 (33%) it was abnormal by both quantification methods; and in 83 (15%) it was abnormal only by one method. Two hundred and fifty-seven patients (46%) presented with decreased RUU in one kidney, associated with a small kidney in 73 patients (13%). RCU was normal in all of these 73 patients (100%, P<0.0001). The sensitivity and specificity of RCU for evaluating renal function in relation to small renal size and with respect to RUU were 72% and 97%, with positive and negative predictive values of 95% and 80%, and an accuracy of 85%. Visual analysis of the 73 studies with decreased RUU and normal RCU showed a small, normal kidney on 55 occasions (75%), cortical scars in eight (11%), and impaired bilateral function in 10 (14%). Visual analysis of 10 studies with normal RUU and decreased RCU showed dilated pyelocalyceal system in seven occasions (70%) and normal kidneys in three (P<0.0001). CONCLUSION: It is concluded that relative 99mTc-DMSA uptake corrected for renal size is a more accurate method for assessing individual renal function. When there is a small kidney, relative 99mTc-DMSA uptake corrected for renal size can distinguish between a normal and a hypofunctioning kidney.

Adolescent↗

Non-invasive in vivo imaging of myocardial apoptosis and necrosis.

Myocardial necrosis plays an important role in the pathogenesis of various cardiovascular disorders and can result from different myocardial insults. Its non-invasive identification and localisation therefore may help in the diagnosis of these disorders, as well as in prognosis and assessment of treatment response. Apoptosis, or programmed cell death, is important in the spectrum of myocardial damage since it is gradually becoming more apparent that cell death may begin as apoptosis and not as necrosis. First attempts to directly visualise the area of myocardial necrosis were based on recognition of myocardial infarction with "hot spot imaging agents" in patients with chest pain. Since then, the study of myocardial necrosis with gamma imaging agents has gone beyond the detection of myocardial infarction, and attempts have been made to diagnose other cardiovascular disorders associated with cardiac cell death such as heart transplant rejection, myocarditis, cardiotoxicity and cardiomyopathies. Traditionally, two hot spot imaging agents have been used for the detection of myocardial necrosis, (99m)Tc-pyrophosphate and (111)In-antimyosin. In addition, preliminary studies have demonstrated promising results with (99m)Tc-glucarate. Recently, (99m)Tc-annexin V has been successfully used for non-invasive gamma imaging of apoptosis after acute myocardial infarction, acute myocardial ischaemia, acute cardiac allograft rejection and malignant intracardiac tumours. This review article focusses on the characteristics of these different myocardial necrotic and apoptotic markers and compares their role in the assessment of myocardial damage.

Annexin A5↗

Coronary endothelial dysfunction and myocardial cell damage in chronic stable idiopathic dilated cardiomyopathy.

UNLABELLED: Impairment of endothelium-dependent vasodilatation in response to acetylcholine reflects an abnormal endothelial function. Labelled indium-111 monoclonal antimyosin antibodies enable detection of myocardial cell damage. We analysed whether endothelial dysfunction correlates with myocardial antimyosin uptake in a selected group of patients with idiopathic dilated cardiomyopathy. METHODS: Twenty-two consecutive patients with chronic stable idiopathic dilated cardiomyopathy (18 males and four females) were included. The duration of heart failure symptoms was 46+/-34 months. At inclusion, the functional class of New York Heart Association was 2.1+/-0.7. Endothelial function was evaluated using intracoronary graded concentrations of acetylcholine. Vasomotor responses of the left anterior descending coronary artery were measured by quantitative coronary analysis. Myocardial uptake of antimyosin antibodies was quantified by means of a heart-to-lung ratio (HLR). RESULTS: Eighteen patients showed endothelial dysfunction (82%) and the remaining four patients showed a normal endothelial function. There were no statistically significant differences between patients with and without endothelial dysfunction in relation to clinical, echocardiographic and hemodynamic parameters. In addition, these variables did not correlate with the magnitude of the vasomotor response to acetylcholine. Eighteen patients (82%) showed abnormal antimyosin uptake; 15 of them (83%) showed endothelial dysfunction. The global mean HLR of antimyosin uptake was 1.73+/-0.24. The coronary vasomotor response to acetylcholine correlated with the intensity of uptake of antimyosin antibodies (r=-0.45, P<0.04). CONCLUSIONS: Coronary endothelial dysfunction and myocardial antimyosin uptake was found in a high percentage of patients with chronic stable idiopathic dilated cardiomyopathy. The abnormal vasomotor response seems to be related to the degree of myocardial damage.

Antibodies, Monoclonal↗

Use of electrical impedance tomography (EIT) for the assessment of unilateral pulmonary function.

We describe a fully automatable quantification process for the assessment of unilateral pulmonary function (UPF) by means of EIT and propose a measurement protocol for its clinical implementation. Measurements were performed at the fourth and sixth intercostal levels on a first group of ten healthy subjects (5M, 5F, ages 26-48 years) to define the proper protocol by evaluating the most common postures and ventilation modes. Several off-line processing tools were also evaluated, including the use of digital filters to extract the respiratory components from EIT time series. Comparative measures were then carried out on a second group consisting of five preoperatory patients with lung cancer (4M, IF, ages 25-77 years) scheduled for radionuclide scanning. Results show that measurements were best performed with the subject sitting down, holding his arms up and breathing spontaneously. As regards data processing, it is best to extract Fourier respiratory components. The mean of the healthy subject group leads to a left-right division of lung ventilation consistent with literature values (47% left lung, 53% right lung). The comparative study indicates a good correlation (r = 0.96) between the two techniques, with a mean difference of (-0.4+/-5.4)%, suggesting that the elimination of cardiac components from the thoracic transimpedance signal leads to a better estimation of UPF.

Adult↗