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Biomedical subjects

R Sara

Publications and source records attributed to R Sara.

16 recordsLinked to original sources

A human ImmunoChip cDNA microarray provides a comprehensive tool to study immune responses.

DNA microarray technology has developed rapidly in recent years and has become an essential tool, providing novel approaches to biomedical research. In this paper, we describe a self-designed ImmunoChip cDNA array for immunological research. With a comprehensive selection of genes of interest, we can focus on key signalling pathways and molecular mechanisms at relatively low cost compared to commercial platforms which are usually targeted at global screening of gene expression. To validate the efficiency of the ImmunoChip, we studied T helper cell polarization to functionally distinct subsets (Th1 and Th2). We also developed a tool for quality control of cDNA microarrays that assesses the technical quality of an ImmunoChip. The information produced with the quality control tool is shown to be valuable for extracting correct information from cDNA microarrays. Gene expression measurements with ImmunoChip are in agreement with the results obtained using oligonucleotide microarrays and with published quantitative RT-PCR data. The ImmunoChip provides reliable measurements and gives new insights into various aspects of human immune responses.

DNA, Complementary↗

[Diagnostic modalities in patients affected by differentiated thyroid carcinoma with high thyroglobulin levels and total body Iodium-131 negative: PET/CT use after recTSH].

In the follow-up of differentiated thyroid carcinoma (DTC), after total thyroidectomy and Iodine-131 therapy, thyroglobulin (Tg) levels and Iodine-131 total body have particular importance. The Tg level becomes a specific and very sensitive marker of DTC recurrence: it is usually evaluated after eradication of thyroid residual tissue (by thyroidectomy and radiometabolic therapy), in presence of high level of TSH (>35 microU/ml) obtained with the suspension of therapy or after rec-TSH administration and in absence of anti-Tg antibodies. Usually, to solve diagnostic problems in patients with negative total body Iodine-131 and high levels of thyroglobulin, we consider one or more of the following investigations, on the basis of prognostic factors: radiological examinations (neck US, skeletal X-ray, CT chest and abdomen, MRI) and scintigraphy (bone scintigraphy, Tc-MIBI or Tl-201 scintigraphy, octreoscan, PET/CT). The use of PET is well known in patients in whom carcinoma metastases are strongly suspected and who are unable of concentrating Iodine-131. In order to increase the PET sensitivity, scintigraphy is performed with high TSH levels obtained through a rec-TSH injection on the 1st and 2nd day, PET/CT scan and blood withdrawal (for Tg level evaluation) on the 3rd day. Considering the hypothesis of a recurrence with lesion size below the resolution power of the diagnostic equipment (5 mm), if PET/CT results are negative, the patients are strictly followed-up and Tg is monitored every 4-6 months. An alternative hypothesis might be not to consider the negative-PET patients as sick persons, but to attribute high Tg levels to illegitimate transcription of mRNA for Tg by the non-thyroid cells or to ectopic thyroid tissue (e.g. intrathymus). Positive PET/CT patients are evaluated for a possible surgical removal of the lesions or alternative appropriate therapies.

Antineoplastic Agents, Hormonal↗

Resting echocardiography and quantitative dipyridamole technetium-99m sestamibi tomography in the identification of cardiac allograft vasculopathy and the prediction of long-term prognosis after heart transplantation.

AIMS: To evaluate the accuracy of echocardiography in conjunction with quantitative high-dose dipyridamole technetium-99m sestamibi tomography (SPECT) in detecting coronary allograft vasculopathy. METHODS AND RESULTS: Seventy-eight consecutive heart transplant recipients underwent echocardiography while at rest and high-dose dipyridamole SPECT within 48 h of a yearly angiogram. Resting wall motion abnormalities were considered significant if present in two or more segments. SPECT was considered abnormal in the presence of reversible/fixed defects. The coronary angiogram was normal in 53, showed non-significant coronary allograft vasculopathy in 13 and significant (> or = 50% stenosis) coronary allograft vasculopathy in 12 cases. Resting wall motion abnormalities were observed in nine cases and perfusion defects in 20. Echocardiography and SPECT were concordant in 59 cases (five positive and 54 negative); in these, accuracy was 100% for significant coronary allograft vasculopathy and 83% for any coronary allograft vasculopathy. Over 6.5+/-2 years, 17 patients suffered coronary allograft vasculopathy-related events, including death in six and retransplantation in three. Resting wall motion abnormalities, SPECT perfusion defects and angiographic coronary allograft vasculopathy were significant predictors of cardiac events. CONCLUSION: Normal resting wall motion at echocardiography coupled to normal stress myocardial perfusion, rules out the presence of significant coronary allograft vasculopathy in many heart transplant recipients. Conversely, resting wall motion abnormalities and perfusion defects strongly predict cardiac events. Therefore, a strategy which reserves angiography for patients with resting wall motion abnormalities and/or perfusion defects may be safe and cost-effective.

Adolescent↗

Technetium-99m hexamethylpropylene amine oxime leucocyte scintigraphy in the differential diagnosis of cerebral abscesses.

The diagnosis of brain abscess is often difficult, as the clinical symptoms are not specific. Computed tomography (CT) and magnetic resonance imaging (MRI) are highly sensitive, but different cerebral lesions, especially neoplasms, can have the same ring-like contrast enhancement. Brain abscess is a severe illness requiring rapid diagnosis to choose the most appropriate therapy. Technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled leucocyte scintigraphy is commonly used to detect an inflammatory process. The aim of this study was to present the results obtained with leucocyte scintigraphy in 65 patients with intracranial mass lesions and clinical findings compatible to or suggestive of brain abscess. The final diagnosis, based on surgery, clinical findings and stereotatic puncture, was brain abscess in 17 patients, primary brain neoplasm in 22, brain metastasis in 16, lymphoma in 2, cysticercosis in 2, hematoma in 2 and cerebral infarction in 4. 99mTc-HMPAO leucocyte scintigraphy was positive in all abscess cases. The scan was negative in the rest of the patients examined, with the exception of one lesion, which was finally diagnosed as a tumour (1 false-positive). All patients who did not have false-negative scans were treated with steroids. The sensitivity, specificity and diagnostic accuracy of leucocyte scintigraphy was 100%, 97.8% and 98.4%, respectively. In conclusion, in our experience, leucocyte scintigraphy is a valuable aid in the differential diagnosis between abscess and neoplasm.

Adolescent↗

Preoperative assessment of cardiac risk in noncardiac major vascular surgery.

We evaluated whether a preoperative clinical algorithm allows an adequate stratification in cardiac risk and the predictive value of dipyridamole thallium-201 scintigraphy and rest echocardiography for postoperative adverse cardiac outcomes. Three hundred twenty patients undergoing 338 vascular surgery procedures were prospectively stratified into low, intermediate, and high risk. The low- and intermediate-risk patients underwent surgery without further diagnostic evaluation. In 7 high-risk patients the vascular procedure was canceled (1 died of myocardial infarction at 6-month follow-up), 9 underwent presurgical myocardial revascularization (1 died of myocardial infarction), and 49 underwent vascular surgery with perioperative intensive care treatment. Hospital mortality was 3.8%. Cardiac mortality and morbidity were 1.5% and 10.4%, respectively. We observed a significant difference in "hard" (death, myocardial infarction, pulmonary edema, major arrhythmias) and "soft" (myocardial ischemia, minor arrhythmias) events between groups, p <0.001. Previous pulmonary edema was a predictive variable of cardiac outcomes (multiple logistic regression analysis). Ninety-nine of 220 intermediate-risk patients randomly underwent dipyridamole thallium-201 scintigraphy: 37 had redistribution, 10 persistent, and 52 no defects; 7 of 13 soft and hard cardiac events occurred in patients without redistribution defects. Sensitivity, specificity, and positive and negative predictive values of redistribution defects for postoperative adverse outcomes were 38%, 63%, 14%, 87%, respectively. This algorithm may provide a safe and cost-effective approach (average cost saving per patient $1,500) to cardiac risk stratification. These results suggest that routine use of dipyridamole thallium-201 scintigraphy for screening of intermediate-risk patients may not be warranted.

Adult↗

Dipyridamole thallium-201 imaging very early after uncomplicated acute myocardial infarction in patients treated with thrombolytic therapy.

The aim of this study was to assess the safety and prognostic value of dipyridamole 201T1 imaging very early after acute myocardial infarction in patients treated with thrombolytic therapy. Fifty-two consecutive patients with an uncomplicated clinical course underwent quantitative planar dipyridamole 201T1 imaging 2 5 days after acute myocardial infarction. The patients were followed for 14 +/- 7 months after discharge. No major complications occurred during the test. Of the 30 patients with redistribution, five (16.6%) developed in-hospital unstable angina as against none of the 22 patients without redistribution. During follow-up, a total of live late cardiac events were observed: two deaths and two cases of unstable angina in the group with reversible defects and one reinfarction in the group with fixed defects. The 1-year actuarial probability of being free of cardiac events was, respectively, 66 +/- 10% and 94 +/- 5% in the patients with and without redistribution (P < 0.01). In conclusion, in patients treated with thrombolysis, dipyridamole-201T1 imaging very early after uncomplicated acute myocardial infarction is a feasible and safe test. Patients with fixed defects appear to be at low risk and may be candidates for early discharge; the presence of redistribution identifies a subgroup of patients who may benefit from further careful clinical evaluation.

Adult↗

Morphological bases for thallium-201 uptake in cardiac imaging and correlates with myocardial blood flow distribution.

To determine the morphological bases of thallium-201 myocardial distribution in chronic cardiac dysfunction and their relation to myocardial blood flow, myocardial slices from ten excised hearts of five chronic ischaemic heart disease patients and five idiopathic dilated cardiomyopathy patients, were imaged on a gamma camera to quantitate the uptake of thallium-201, injected 4 h before surgery, and myocardial blood flow from distribution of technetium-99m-labelled human albumin microspheres injected during surgery. Tracer distribution was correlated with histologically assessed myocardial fibrosis and myocytolysis. Thallium-201 uptake was inversely related to fibrosis (r = -0.73, in ischaemic heart disease, r = -0.65 in idiopathic dilated cardiomyopathy). In ischaemic heart disease, myocardial blood flow was related neither to thallium-201 uptake (r = 0.41) nor to the extent of fibrosis (r = -0.48). In this group, segments with normal or mildly reduced thallium-201 uptake showed significantly lower fibrosis than those with moderate or severe uptake defects (5 +/- 7% and 7 +/- 11% vs 33 +/- 14% and 42 +/- 12%, respectively, P < 0.0001. In a clinical model of chronic ischaemic dysfunction, despite severely depressed myocardial blood flow, extensive areas of myocardium devoid of significant structural impairment are present. Thallium-201 uptake effectively discriminates regions with preserved viability from those with relevant myocardial damage.

Adult↗

Assessment of myocardial viability after thallium-201 reinjection or rest-redistribution imaging: a multicenter study. The Italian Group of Nuclear Cardiology.

UNLABELLED: To establish the real nature of 201Tl defects in the assessment of myocardial viability (e.g., fixed versus reversible), 201Tl reinjection was evaluated in a multicenter trial involving 402 consecutive patients with ischemic heart disease and exercise 201Tl defects. METHODS: Twelve hospitals, using the same type of gamma camera and computer software, adopted one of the two most widely used reinjection protocols. In 230 patients (Group A), reinjection was performed immediately after stress-redistribution planar imaging; in 172 patients (Group B), reinjection was performed on a separate day and followed by rest-redistribution imaging. The images were interpreted by three blinded observers in a core laboratory on a five-point qualitative scale; the reproducibility in visual scoring was excellent. RESULTS: Groups A and B had a similar prevalence of myocardial segments with abnormal uptake at stress (39%, 40%), as well as with reversible (16%, 17%), partially reversible (21%, 19%) and irreversible (63%, 64%) defects at redistribution. After reinjection, 201Tl uptake improved in 27% and 36% of both partially reversible and irreversible defects in Groups A and B. No differences were found when comparing early and delayed reinjection imaging in Group B. CONCLUSION: This study confirms the validity of 201Tl reinjection in a large, unselected population, but the discordance with stress/redistribution is less than has been previously reported for both 201Tl reinjection protocols, the prevalence of improved segments after reinjection was higher with the separate day approach.

Exercise Test↗

DNA analysis in Finnish patients with hereditary neuropathy with liability to pressure palsies (HNPP).

Hereditary neuropathy with liability to pressure palsies (HNPP) is a dominantly inherited disorder that presents as recurrent mononeuropathies precipitated by apparently trivial traumas. The presence of a deletion in 17p11.2 was analysed in 13 Finnish families with HNPP. The deletion was found in all patients who were neurologically and neurophysiologically confirmed to have HNPP. In the problematic cases the detection of the gene defect is the method of choice in the diagnosis of HNPP. Analysis of DNA can also be used to detect clinically unaffected family members.

Chromosome Deletion↗

A multicenter trial on interobserver and intraobserver reproducibility of segmental scoring of thallium-201 planar myocardial imaging before and after reinjection. Italian Group of Nuclear Cardiology.

UNLABELLED: Inter- and intraobserver reproducibility (R) of segmental 201Tl scores after stress (ST), redistribution (RD) and reinjection (RI) planar imaging were evaluated. METHODS: Images were examined from 396 patients with suspected coronary artery disease, demonstrated by means of post-ST imaging of at least one perfusion defect. To eliminate external sources of variability, the same gamma camera, acquisition protocol and computer software were used in this multicenter study. Thallium-201 images of the anterior, left anterior oblique and left lateral projections were obtained immediately, 4 hr after exercise and 30 min after the injection of additional 201Tl either on the same day or on a different day. The left ventricle was divided into 15 segments and evaluated by three independent observers, blinded to clinical data, according to a five-point scale. RESULTS: The R score for ST, RD and RI images, expressed as an intraclass correlation coefficient, was 0.76, 0.74 and 0.72, respectively. After averaging multiple observer scores, R increased to 0.91, 0.90 and 0.89, respectively. Individual observer measurement of the R score was 0.48, 0.51 and 0.32 for ST-RD, ST-RI and RD-RI image pairs, respectively, and multiple observer scores showed R increases to 0.74, 0.76 and 0.58. CONCLUSION: This qualitative scale reliably assesses the severity of 201Tl perfusion defects, particularly when multiple-observer scores are averaged. Individual observer change scores should be taken with great caution, especially in studies involving the visual evaluation of RD-RI image changes.

Coronary Disease↗

Comparison of conformations of cyclosporin A and macrolide FK506 fragments: localization of putative binding sites with phosphatase calcineurin.

The three-dimensional structures of two immunosuppressants, cyclosporin A and macrolide FK506, were compared. The sites N-methylglycine3-N-methylleucine4 and valine5-N-methylleucine6 of cyclosporin A were found to be similar to each other (the root-mean-square value was 0.29 A for six reference points of the main chain) and also to the site C17-C22 of FK506 (the root-mean-square values were 0.33 A and 0.13 A, respectively). We suggest these fragments of cyclosporin A and FK506 make a major contribution to the interaction of the immunosuppressants with the phosphatase calcineurin.

Amino Acid Sequence↗

In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([123I]SDZ 204-090).

The recent availability of a Tyr3-substituted octreotide (SDZ 204-090) for radioiodination has allowed somatostatin (SRIH) receptor binding to be studied in vivo, and receptor-positive tumors of different origins to be visualized with a gamma-camera. This prompted us to investigate whether this compound could be used for external imaging of functionless pituitary adenomas displaying SRIH receptors. Eight patients with functionless pituitary adenomas, three patients with acromegaly, and three with macroprolactinoma were injected iv with 123I-labeled Tyr3-octreotide and then scanned with a gamma-camera. Positive scans were obtained in the three acromegalics and in two of the eight patients with functionless pituitary tumors. The patients with macroprolactinoma had negative scans. The diagnosis of functionless pituitary adenomas was confirmed by light and electron microscopic examination as well as immunocytochemical studies. In vitro binding of [125I]Tyr11-SRIH to cell membranes was evaluated in four functionless and three GH-secreting adenomas removed from seven of the patients. All of the GH-secreting as well as one of the four functionless adenomas had high affinity SRIH-binding sites, without differences in number or affinity, whereas SRIH-binding sites were not detected in the others. Positive scans were observed only in patients bearing tumors with high affinity SRIH-binding sites. In conclusion, [123I]Tyr3-octreotide appears to be a promising tool for singling out, in vivo, patients with functionless pituitary tumors displaying SRIH receptors who might potentially benefit from octreotide treatment.

Adenoma↗

The 99mTc-HMPAO leukocyte scan: an alternative to radiology and endoscopy in evaluating the extent and the activity of inflammatory bowel disease.

Seventy-eight patients, 47 with Crohn's disease and 31 with ulcerative colitis, were studied using 99mTc-HMPAO-labelled leukocytes, in order to assess the reliability of the scan in evaluating the location and activity of the disease. The granulocyte integrity was assessed by evaluating the lung wash-out and the early liver and spleen uptake using a 20 minute initial dynamic study. The results of the leukocyte scan revealed a high correlation with radiological and endoscopic findings in the diagnosis of the inflamed bowel segments. The disease activity correlated well with uptake in the bowel, graded from 0 to 3. The leukocyte scan exactly documented the activity in the 9 cases of Crohn's disease located in the ileum and in 5 cases in which the endoscopic exploration was hampered by scarring. Four fistulae were correctly visualized. Moreover, the change in activity after therapy in 6 patients was documented. This technique provides images of excellent quality, superior to those obtainable with indium-111.

Adult↗