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Biomedical subjects

J Pavia

Publications and source records attributed to J Pavia.

At least 19 recordsLinked to original sources
PubMed2003

Dynamic model of the left ventricle for use in simulation of myocardial perfusion SPECT and gated SPECT.

Simulation is a useful tool in cardiac SPECT to assess quantification algorithms. However, simple equation-based models are limited in their ability to simulate realistic heart motion and perfusion. We present a numerical dynamic model of the left ventricle, which allows us to simulate normal and anomalous cardiac cycles, as well as perfusion defects. Bicubic splines were fitted to a number of control points to represent endocardial and epicardial surfaces of the left ventricle. A transformation from each point on the surface to a template of activity was made to represent the myocardial perfusion. Geometry-based and patient-based simulations were performed to illustrate this model. Geometry-based simulations modeled (1) a normal patient, (2) a well-perfused patient with abnormal regional function, (3) an ischaemic patient with abnormal regional function, and (4) a patient study including tracer kinetics. Patient-based simulation consisted of a left ventricle including a realistic shape and motion obtained from a magnetic resonance study. We conclude that this model has the potential to study the influence of several physical parameters and the left ventricle contraction in myocardial perfusion SPECT and gated-SPECT studies.

Algorithms↗
PubMed2003

Tetrofosmin as predictors of tumour response.

Non-invasive imaging methods in the evaluation of chemotherapy response in malignant tumours are currently being explored. Standard Nuclear Medicine procedures seem to offer the clinician a promising tool in the management of those oncologic patients, who might benefit from chemotherapy. Early studies focused on the relationship between radionuclides used in tumour diagnosis and factors associated with multidrug resistance (MDR). The tumour expression of P-glycoprotein (Pgp) and multidrug resistance-related protein-1 expression (MRP) have been suggested as important factors in the failure of chemotherapy. Most studies found an association between Pgp levels and (99m)Tc-sestamibi ((99m)Tc-MIBI) or (99m)Tc-Tetrofosmin uptake ((99m)Tc-TF). Currently investigations in nuclear medicine oncology are focusing on the potential role of radionuclide imaging in the assessment of chemotherapy. Recent papers discuss the usefulness of radionuclides as (99m)Tc-MIBI and (99m)Tc-TF as non-invasive procedures to predict and to monitor therapy response in patients affected by malignant tumours treatable using chemotherapy. This chapter will review the latest development in (99m)Tc-TF, giving an overview of recent investigations carried out using this radiotracer in therapy oncology, with emphasis on its potential role as predictor of tumour response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Quantified 99mTc-MIBI scintigraphy for predicting chemotherapy response in breast cancer patients: factors that influence the level of 99m Tc-MIBI uptake.

The aim of this study was to establish whether tumour uptake of 99mTc-MIBI can predict response to chemotherapy in patients with breast carcinoma. Forty women suffering from breast carcinoma confirmed by tumour biopsy were studied prospectively. Fifteen patients subsequently underwent surgery and 25 were candidates for neoadjuvant chemotherapy. Breast scintigraphy was performed and planar and tomographic views (single photon emission computed tomography (SPECT)) were obtained after injection of 740 MBq of 99mTc-MIBI. The tumoural uptake was quantified by computer analysis. P-glycoprotein was evaluated by immunohistochemistry only in operable patients. The response to chemotherapy was evaluated at 3 months upon completion of treatment. The results of this study showed no relationship between 99mTc-MIBI uptake and the histological type or tumour size. There was an inverse correlation with the degree of tumour differentiation (P<0.05). 99mTc-MIBI uptake in negative P-glycoprotein lesions (2.36+/-1.72) was higher than in positive P-glycoprotein lesions (1.53+/-1.29), although the difference was not statistically significant. Lesions which responded to chemotherapy (16) showed higher 99mTc-MIBI uptake (7.70+/-5.20) than non-responding lesions (nine) (2.21+/-1.0) (P<0.001). In conclusion, there is a correlation between 99mTc-MIBI uptake in breast cancer and response to chemotherapy. Furthermore, 99mTc-MIBI uptake may be influenced by other factors such as the degree of tumour differentiation or tumour P-glycoprotein levels.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours.

Patients with head and neck cancers can develop salivary hypofunction after radiotherapy. The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment, although its usefulness is being discussed. The aim of this study was: (1) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours; and (2) to study the usefulness of pilocarpine as a salivary gland protector during radiotherapy. We prospectively studied 49 patients (mean age 61 years, range 29-87 years) with head and neck cancer in need of radiotherapy. Patients were divided into two groups consecutively: group P (26 patients) received 5 mg of pilocarpine three times per day starting the day before radiation therapy, and group NP (23 patients) received radiotherapy without pilocarpine and were used as the control group. Salivary gland scintigraphy and a visual analogue scale (VAS) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment. The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion (P < 0.001). There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group. Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups (P < 0.001). However, a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary glands at 12 months. No differences were found comparing the VAS results in both groups. Strikingly, VAS data did not correlate with salivary gland dysfunction observed by means of scintigraphy. In conclusion, salivary scintigraphy is a useful technique to evaluate objectively the salivary gland function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine. However, despite better results on the salivary uptake at 12 months, pilocarpine did not significantly improve salivary gland function.

Adult↗
PubMed1999

Experiences in setting up the first centralized radiopharmacy in Spain.

The centralized radiopharmacy set up in Spain by the Cetir Medical Group allows optimal use of radiopharmaceuticals and complies with laws (Directive 89/343/EEC and Royal Decree 479/1993/Spain) governing their use. More than 220,000 individual patient doses have been supplied since the unit was established in November 1995. In this paper, we describe the infrastructure of the centralized radiopharmacy, including the operations and procedures involved, and how we believe we have achieved our original objectives.

Drug Storage↗
PubMed1997

Effect of S-adenosyl methionine on muscarinic receptors in young rats.

In the present study we have investigated the effect of a chronic administration of S-Adenosyl Methionine (SAM) on muscarinic receptor subtypes in young rat forebrain, cerebellum, heart and lacrimal gland. Saturation binding experiments were performed using 3H-N-methylscopolamine (3H-NMS) to label the total population of muscarinic receptors in plasma membranes from forebrain, cerebellum, heart and lacrimal gland. 3H-Pirenzepine (3H-Pz) was used to label the M1 subtype in plasma membranes from forebrain. The results obtained in cerebellum, heart and lacrimal gland show no changes in the affinity (Kd) nor in the number of receptors (Bmax) of the treated versus control groups. Saturation experiments in forebrain show an increase in the number of receptors of the treated versus control groups when using 3H-NMS (Bmax 2117 +/- 63 versus 1643 +/- 104 fmol/mg protein) without changes in the affinity. Saturation experiments with 3H-Pz, show an increase in the number of M1 receptors in the treated group with no changes in the affinity (Bmax 421 +/- 16 versus 225 +/- 19 fmol/mg protein). From our results, we conclude that SAM increase the number of receptors in forebrain and this increase is mainly due to changes in the number of M1 receptor subtypes.

Animals↗
PubMed1997

Estimation of 99Tcm-MAG3 clearance using a single blood sample obtained over a continuous time interval.

Simplified methods based on a single blood sample have been proposed to estimate the clearance of 131I-hippuran (HIP) and 99Tcm-mercaptoacetyltriglycine (MAG). The blood sample is usually drawn at that time which yields a minimum error between the estimated clearance and that obtained by the standard nine-sample method. In this paper, we establish the regression equations to obtain the HIP and MAG clearances using one sample withdrawn during a fixed time interval. As HIP has long been the agent of choice, we have also established regression equations to estimate the clearance of HIP using one sample after MAG administration. Our results suggest that it is possible to obtain plasma samples 30-50 min post-injection which result in an error of the estimate only slightly higher than the minimum.

Adult↗
PubMed1997

The role of the aspartate-arginine-tyrosine triad in the m1 muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signaling.

An Asp-Arg-Tyr triad occurs in a majority of rhodopsin-like G protein-coupled receptors. The fully conserved Arg is critical for G protein activation, but the function of the flanking residues is not well understood. We expressed in COS-7 cells m1 muscarinic receptors that were mutated at Asp122 and Tyr124. Most mutations at either position strongly attenuated or prevented the expression of binding sites for the antagonist [3H]N-methylscopolamine. However, sites that were expressed displayed unaltered affinity for the antagonist. Receptor protein, visualized with a carboxyl-terminally directed antibody, was reduced but never completely abolished. The effects of these mutations were partially reversed by the deletion of 129 amino acids from the third intracellular loop of the receptor. In several cases, comparison of immunocytochemistry with binding measurements suggested the presence of substantial amounts of inactive, presumably misfolded, receptor protein. Some of the variants that bound [3H]N-methylscopolamine underwent small changes in their affinities for acetylcholine. All retained nearly normal abilities to mediate an acetylcholine-induced phosphoinositide response. We propose that Asp122 and Tyr124 make intramolecular contacts whose integrity is important for efficient receptor folding but that they do not participate directly in signaling. The role of these residues is completely distinct from that of Arg123, whose mutation abolishes signaling without diminishing receptor expression.

Acetylcholine↗
PubMed1996

Regional cerebral blood flow pattern in normal young and aged volunteers: a 99mTc-HMPAO SPET study.

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (99m-Tc-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers - 40 young (mean age 29. 5+/-6.3 years) and 28 aged (mean age 71.2+/-4.3 years) - were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (-1. 01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.

Adult↗
PubMed1996

Angiotensin II receptor in human placental syncytiotrophoblast plasma membranes.

Previous studies have reported the presence of high-affinity angiotensin II (Ang II) binding sites in human placental tissue, but it has not been determined whether these are located in brush border (BBM) or basolateral plasma (BPM) membranes of the syncytiotrophoblast. Our findings provide no evidence for Ang II receptors in BBM, yet they reveal a single class of binding sites in BPM preparations (Kd of 4.08+/-0.61 nM and B(max) of 2368.7+/-658.2 fmol/mg protein). Pharmacological characterization also revealed that this receptor was an AT1 receptor subtype. Moreover, isoelectric focusing analysis demonstrated a predominant Ang II-receptor complex migrating to pl 7.0, and two minor receptors at pl 7.2 and 6.5. These data suggest a physiological role of the renin-angiotensin system on syncytiotrophoblast BPM in regulating placental function.

Angiotensin II↗
PubMed1996

Salbutamol reduces pulmonary neutrophil sequestration of platelet-activating factor in humans.

To investigate whether salbutamol inhibits platelet-activating factor (PAF)-induced neutrophil sequestration in the lungs, we studied eight nonatopic, nonsmoking, healthy subjects (six men; aged 27.0 +/- 1.5 (SE) yr) with PAF-induced bronchial response. Prior to PAF challenge (24 micrograms), they inhaled either salbutamol (300 micrograms) or placebo in a randomized, double-blind, crossover manner two weeks apart. Respiratory system resistance (Rrs), arterial blood gases, and neutrophil counts were measured 4, 8, 12 and 30 min after PAF. Neutrophil kinetics in the lungs were assessed by tracking autologous 99mTc-erythrocytes and 111in-neutrophils. Compared with salbutamol, arterial blood neutrophil counts fell (p < 0.04) maximally at 4 min after PAF, followed by a mild rebound neutrophilia, whereas Rrs increased (p < 0.01) and Pao2 decreased (p < 0.05) at 4 min only. The intrapulmonary activity of 111in-neutrophils after pretreatment with placebo was higher compared with salbutamol (1.98 +/- 0.15 versus 1.33 +/- 0.23 cps/mCi/pixel) (p < 0.01) although both their initial sequestration (first-pass) and subsequent washout were not significantly different. Inhaled salbutamol blocks pulmonary neutrophil sequestration and lung function abnormalities following PAF challenge in humans.

Administration, Inhalation↗
PubMed1995

Characterization of the rat m3 muscarinic acetylcholine receptor produced in insect cells infected with recombinant baculovirus.

The m3 muscarinic acetylcholine receptor from rat heterologously produced in insect cells after infection with a recombinant baculovirus has an apparent molecular mass of approximately 75 kDa. Polyclonal antibodies raised against a carboxy-terminal nonapeptide that is unique to the m3 subtype can detect the receptors produced in the insect cells by Western blot and can also immunoprecipitate solubilized receptor. Immunofluorescence microscopy as well as electron microscopy revealed that the receptor was located intracellularly, visualized as a ring around the nucleus of the infected insect cells. Solubilization of the receptor was accomplished with digitonin which was added in increments (over 10 min) to a final concentration of 0.8% (mass/vol). The solubilized receptor is unstable when the ligand-binding site is not protected by a ligand. Here the low-affinity ligand propylbenzilylcholine (approximately 10 nM) has demonstrable protective ability during solubilization, but the usefulness of this ligand is limited by a very slow off rate. From the behaviour of the solubilized receptor during DEAE-Sephacel chromatography and lectin-affinity chromatography it can be deduced that the receptor produced in insect cells is heterogeneously glycosylated in the producing insect cells.

Affinity Labels↗
PubMed1994

Three-dimensional realignment of activation brain single-photon emission tomographic studies.

Two methods for 3D realignment of activation brain single-photon emission tomographic (SPET) studies are analyzed. The first is based on principal axes transformation (PAT). The second uses the results of the first method as initial values to start a least-squares iterative process (LS) to search for the maximum value of the correlation function. Both methods were tested with simulated and real studies. The results of the PAT method showed a maximum translation error of 0.3 +/- 0.1 pixels and a rotational error of 1.2 +/- 0.7 degrees in a total of 100 runs. For the LS method these errors were 0.2 +/- 0.1 and 0.6 +/- 0.3. The realignment for 34 real studies was assessed by three expert observers. The alignment was found to be satisfactory in all cases for the LS method, and in 18 cases (53%) for the PAT method. From the results we conclude that a combination of both methods allows the accurate realignment of SPET neuroactivation studies.

Algorithms↗
PubMed1994

Estimate of relative function and transit time in renographic studies.

Renal transit time and relative renal function are the most commonly used parameters in the study of renal function. In clinical practice the determination of these two parameters is carried out either using the renal retention function or directly from the renogram. This study seeks to compare the values for the transit time and the relative function, as calculated from the renogram and from the renal retention function, in renographic studies using 131I-OIH and 99mTc-MAG3. For both tracers it was found that the estimated renal transit time from the renogram (OIH: 289 +/- 118 s, MAG3: 297 +/- 110 s) generated values that were higher than those obtained from the renal retention function (OIH: 245 +/- 85 s, MAG3: 274 +/- 97 s), with significant differences between the two estimates (p < 0.001). As regards the relative function, there were no significant differences between the estimates obtained from the renogram (58.5 +/- 8.3%) and the renal retention function (59.5 +/- 9.3%) in the case of OIH. For MAG3 the estimate obtained from the renogram (58.3 +/- 6.3%) and from the renal retention function (59.9 +/- 7.1%) were significantly different (p < 0.025).

Humans↗
PubMed1993

Evaluation of myocardial perfusion defects by means of "bull's eye" images.

The purpose of this study was to evaluate the usefulness of so-called "bull's eye" imaging as a simplified display of tomographic slices in the detection of coronary artery disease (CAD). A total of 64 patients were studied at stress and at rest, by single photon emission computed tomography (SPECT), either with thallium-201 (201Tl) or with technetium-99m methoxy-isobutyl-isonitril (Tc-MIBI). The myocardial perfusion defects detected by bull's eye image alone and in combination with visual analysis of tomographic images were evaluated in all cases, taking coronary arteriographic results as a gold standard. The overall sensitivity and specificity for detection of CAD were as follows: bull's eye imaging, 100% and 70.8%; tomographic imaging (SPECT), 90% and 91.6%. The results of bull's eye imaging and SPECT interpreted together were 96.6% and 83.3%. The regional sensitivity and specificity of bull's eye for individual coronary arteries were: right coronary artery (RCA), 100% and 73.7%; left anterior descending (LAD), 100% and 87.2%; left circumflex (LCx), 100% and 97.3%. For SPECT they were: RCA, 93.7% and 89.5%; LAD, 86.6% and 92.3%; LCx, 73.3% and 97.4%. For bull's eye with SPECT they were: RCA, 94.4% and 86.1%; LAD, 87.5% and 92.1%; LCx, 82.3% and 97.2%. We conclude that the bull's eye image display allows an easier and more objective assessment of myocardial perfusion defects and shows higher sensitivity. However, it has a relatively low specificity which can cause an overestimation of perfusion defects. Thus, visual analysis of bull's eye imaging is a useful diagnostic tool but must be evaluated in conjunction with tomographic imaging.

Adult↗
PubMed1993

Relations among intragastric pressure, postcibal perception, and gastric emptying.

Our aims were to investigate, first, the relationship between gastric tone (measured with a barostat) and gastric emptying (measured by radioscintigraphy with and without barostat) and, second, to determine the effect of a symptomatic intragastric pressure increment on gastric emptying. In 16 healthy subjects we quantified simultaneously gastric tone, emptying, and perception at two different intragastric pressure levels: 2 mmHg (low pressure) or 8 mmHg above intra-abdominal pressure (high pressure). At the low intragastric pressure level, ingestion of the meal induced an additional expansion in intragastric volume of 285 +/- 50 ml (P < 0.001), which reflected a gastric accommodative relaxation. At the high pressure level, intragastric volume expanded further, but neither low nor high pressure levels had significant effects on solid emptying. Interestingly, low and high pressure levels produced a similar, modest but significant, acceleration of liquid emptying (17 +/- 5 and 17 +/- 4%, respectively). However, although the low pressure was largely unperceived (score 1.0 +/- 0.5; NS), the high pressure level produced significant symptomatic perception (score 2.5 +/- 0.9; P < 0.05 vs. low pressure). We conclude that 1) gastric accommodation to a meal prevents volume-dependent wall tension increments and 2) the stomach adapts to increments in postcibal intragastric pressure by a limited acceleration of liquid emptying, but wall stress triggers a symptomatic alert mechanism.

Adult↗
PubMed1992

Muscarinic receptor subtypes in human and rat colon smooth muscle.

Muscarinic receptor subtypes in human and rat colon smooth muscle homogenates were characterized with [3H]N-methylscopolamine ([3H]NMS) by ligand binding studies. [3H]NMS saturation experiments show the existence of a homogeneous population of non-interacting binding sites with similar affinity (KD values of 1.38 +/- 0.20 nM in human colon smooth muscle and 1.48 +/- 0.47 nM in rat colon smooth muscle) and with Hill slopes close to unity in both samples of tissue. However, a significant (P less than 0.01) increase in muscarinic receptor density (Bmax) is found in human colon (29.9 +/- 2.9 fmol/mg protein) compared with rat colon (17.2 +/- 1.5 fmol/mg protein). Inhibition of [3H]NMS binding by non-labelled compounds shows the following order in human colon: atropine greater than AF-DX 116 greater than pirenzepine. Whereas in rat colon the rank order obtained is atropine greater than pirenzepine greater than AF-DX 116. Atropine and pirenzepine bind to a homogeneous population of binding sites, although pirenzepine shows higher affinity to bind to the sites present in rat colon (Ki = 1.08 +/- 0.08 microM) than those in human colon (Ki = 1.74 +/- 0.02 microM) (P less than 0.05). Similarly, IC50 values obtained in AF-DX 116 competition experiments were significantly different (P less than 0.01) in human colon (IC50 = 1.69 +/- 0.37 microM) than in rat colon (IC50 = 3.78 +/- 0.75 microM). Unlike atropine and pirenzepine, the inhibition of [3H]NMS binding by AF-DX 116 did not yield a simple mass-action binding curve (nH less than 1, P less than 0.01) suggesting the presence of more than one subtype of muscarinic receptor in both species. Computer analysis of these curves with a two binding site model suggests the presence of two populations of receptor. The apparent Ki1 value for the high affinity binding site is 0.49 +/- 0.07 microM for human colon smooth muscle and 0.33 +/- 0.05 microM for rat colon smooth muscle. The apparent Ki2 for the low affinity binding site is 8.01 +/- 1.0 microM for human samples and 6.07 +/- 1.1 microM for rat samples. These values are close enough to suggest that the first subtype of muscarinic receptor may be considered cardiac (M2) and the second subtype glandular (M3). The relative densities of the receptor subtypes are significantly different for both species. Human colon samples show the major densities of subtype M2, 22.62 +/- 1.11 fmol/mg protein, this represents 75.66 +/- 3.73% of the total receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗