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Biomedical subjects

J Morais

Publications and source records attributed to J Morais.

At least 37 records · Page 2Linked to original sources

Evaluation of gastric emptying function in clinical practice.

In this retrospective analysis, we compared different methods to evaluate gastric emptying function, aiming to improve the sensitivity and the clinical availability of our diagnostic testing. In the first study, we compared, in 72 patients clinically suspected of gastroparesis, the emptying of a meal containing two solid nutrients with different disintegration rates: 111In-labeled scrambled eggs and 99Tc-labeled liver cubes. Gastric emptying of 111In-labeled egg was delayed in 12 of our patients and the evacuation of the 99Tc-labeled liver was prolonged in 19 patients. The choice of the nutrient was not important for the identification of diabetic gastroparesis (43% vs 57%; NS), but it was determinant in the case of patients suspected of idiopathic gastroparesis (12% were positive with the egg and 25% with the liver; P < 0.05). In the second study, we compared two different diagnostic methods in 46 patients: a simple radiological detection of the gastric emptying of radiopaque pellets, and the scintigraphic emptying of a solid meal containing 99Tc-labeled liver cubes. Both tests correlated perfectly in 78% of our patients. In 15% of the population (six of these seven patients were diabetics suspected of gastroparesis) the scintigraphic method was normal, while the evacuation of radiopaque pellets was delayed. For clinical purposes, we therefore propose: (1) the scintigraphic method should use liver rather than egg as a radiolabeled tracer in order to improve the sensitivity of the test for detection of gastroparesis; and (2) the radiological detection of radiopaque markers is a reliable and convenient method for the detection of gastroparesis in clinical practice. It is possibly more sensitive than scintigraphy.

Adult↗

Methodological validation and clinical usefulness of carbon-14-urea breath test for documentation of presence and eradication of Helicobacter pylori infection.

UNLABELLED: A simple [14C]urea breath test (C-14-UBT) was validated with aims of determining accuracy in documenting both the presence and proof of eradication of Helicobacter pylori infection. METHODS: Fifty-six dyspeptic patients had endoscopy with biopsies and C-14-UBT. Eleven biopsy-proven H. pylori-negative patients allowed C-14-UBT normal value determination. Forty-three patients with recurrent peptic ulcer disease and biopsy-proven H. pylori infection were included in an antimicrobial eradication protocol. Endoscopy with biopsies and C-14-UBT were done again 8 wk after initiation of treatment in 35 patients. For C-14-UBT, 185 kBq (5 microCi) of [14C]urea was swallowed. Breath samples obtained up to 20 min were counted to calculate AS20, [(% 14CO2 dose excreted/mmol of CO2) x kg] at 20 min. Combined histologic and microbiologic analyses of antral biopsies were used as a gold standard. RESULTS: The positivity value was set as AS20 > 0.33% (mean + 3 s.d. of AS20 in H. pylori-negative patients). Diagnosis of H. pylori infection was correct with C-14-UBT in 55/56 patients (44 true-positive, 11 true-negative and 1 false-negative; sensitivity = 98%; specificity = 100%). As a proof of eradication, C-14-UBT correctly classified 33/35 patients (5 true-positive, 28 true-negative and 2 false-positive; sensitivity = 100%; specificity = 93%). The C-14-UBT global performance yielded sensitivity, specificity and accuracy of 98%, 95% and 97%, respectively. A significant correlation (r = 0.84) was found between AS20 and the number of H. pylori colonies on culture. CONCLUSION: This C-14-UBT is highly accurate both for diagnosis and proof of eradication of H. pylori infection and reflects the antral bacterial load. It is simple, fast and inexpensive, and it is therefore suitable for clinical practice.

Breath Tests↗

Preliminary crystallographic analysis and further characterization of a dodecaheme cytochrome c from Desulfovibrio desulfuricans ATCC 27774.

Dodecaheme cytochrome c has been purified from Desulfovibrio (D.) desulfuricans ATCC 27774 cells grown under both nitrate and sulfate-respiring conditions. Therefore, it is likely to play a role in the electron-transfer system of both respiratory chains. Its molecular mass (37768 kDa) was determined by electrospray mass spectrometry. Its first 39 amino acids were sequenced and a motif was found between amino acids 32 and 37 that seems to exist in all the cytochromes of the c(3) type from sulfate-reducing bacteria sequenced at present. The midpoint redox potentials of this cytochrome were estimated to be -68, -120, -248 and -310 mV. Electron paramagnetic resonance spectroscopy of the oxidized cytochrome shows several low-spin components with a g(max) spreading from 3.254 to 2.983. Two crystalline forms were obtained by vapour diffusion from a solution containing 2% PEG 6000 and 0.25-0.75 M acetate buffer pH = 5.5. Both crystals belong to monoclinic space groups: one is P2(1), with a = 61.00, b = 106.19, c = 82.05 A, beta = 103.61 degrees, and the other is C2 with a = 152.17, b = 98.45, c = 89.24 A, beta = 119.18 degrees. Density measurements of the P2(1) crystals suggest that there are two independent molecules in the asymmetric unit. Self-rotation function calculations indicate, in both crystal forms, the presence of a non-crystallographic axis perpendicular to the crystallographic twofold axis. This result and the calculated values for the volume per unit molecular weight of the C2 crystals suggest the presence of two or four molecules in the asymmetric unit.

Journal Article↗

Cytochrome c3 from Desulfovibrio gigas: crystal structure at 1.8 A resolution and evidence for a specific calcium-binding site.

Crystals of the tetraheme cytochrome c3 from sulfate-reducing bacteria Desulfovibrio gigas (Dg) (MW 13 kDa, 111 residues, four heme groups) were obtained and X-ray diffraction data collected to 1.8 A resolution. The structure was solved by the method of molecular replacement and the resulting model refined to a conventional R-factor of 14.9%. The three-dimensional structure shows many similarities to other known crystal structures of tetraheme c3 cytochromes, but it also shows some remarkable differences. In particular, the location of the aromatic residues around the heme groups, which may play a fundamental role in the electron transfer processes of the molecule, are well conserved in the cases of hemes I, III, and IV. However, heme II has an aromatic environment that is completely different to that found in other related cytochromes c3. Another unusual feature is the presence of a Ca2+ ion coordinated by oxygen atoms supplied by the protein within a loop near the N-terminus. It is speculated that this loop may be stabilized by the presence of this Ca2+ ion, may contribute to heme-redox perturbation, and might even be involved in the specificity of recognition with its redox partner.

Amino Acid Sequence↗

Left ventricular function after late thrombolysis with alteplase in myocardial infarction.

OBJECTIVE: Late thrombolytic treatment (after 6 hours from pain onset) for acute myocardial infarction has been shown to improve survival in a cohort of patients. The mechanisms underlying such benefit have been debated and a controversy exists about the influence of late thrombolysis over left ventricular function as one potential mechanism. The present study intended to clarify the effects of late thrombolysis with alteplase on left ventricular function parameters. DESIGN: Prospective, multicenter, randomised, double-blind study. Ancillary study to LATE trial. PATIENTS: We studied 103 patients, 81.6% men, randomly allocated to alteplase (100 mg over 3 hours) or placebo 6 to 24 hours after onset of myocardial infarction. METHODS: Left ventricular function parameters by radionuclide ventriculography were evaluated at 1 and 6 months after myocardial infarction. RESULTS: At 1 month, left ventricular ejection fraction was 48.86% on alteplase and 43.19% in placebo group (p = 0.028), with greater benefits for septal and apical regions. At 6 months no significant differences were found. CONCLUSIONS: Those data suggest that late thrombolysis with alteplase improves left ventricular function 1 month after myocardial infarction although the difference did not persist at 6 months. Improvement of left ventricular function shall, therefore, be considered as one of the possible mechanisms underlying the benefit of late thrombolysis.

Double-Blind Method↗

Structure of the tetraheme cytochrome from Desulfovibrio desulfuricans ATCC 27774: X-ray diffraction and electron paramagnetic resonance studies.

The three-dimensional X-ray structure of cytochrome c3 from a sulfate reducing bacterium, Desulfovibrio desulfuricans ATCC 27774 (107 residues, 4 heme groups), has been determined by the method of molecular replacement [Frazão et al. (1994) Acta Crystallogr. D50, 233-236] and refined at 1.75 A to an R-factor of 17.8%. When compared with the homologous proteins isolated from Desulfovibrio gigas, Desulfovibrio vulgaris Hildenborough, Desulfovibrio vulgaris Miyazaki F, and Desulfomicrobium baculatus, the general outlines of the structure are essentialy kept [heme-heme distances, heme-heme angles, His-His (axial heme ligands) dihedral angles, and the geometry of the conserved aromatic residues]. The three-dimensional structure of D. desulfuricans ATCC 27774 cytochrome c3Dd was modeled on the basis of the crystal structures available and amino acid sequence comparisons within this homologous family of multiheme cytochromes [Palma et al. (1994) Biochemistry 33, 6394-6407]. This model is compared with the refined crystal structure now reported, in order to discuss the validity of structure prediction methods and critically evaluate the steps used to predict protein structures by homology modeling. The four heme midpoint redox potentials were determined by using deconvoluted electron paramagnetic resonance (EPR) redox titrations. Structural criteria (electrostatic potentials, heme ligand orientation, EPR g values, heme exposure, data from protein-protein interaction studies) are invoked to assign the redox potentials corresponding to each specific heme in the three-dimensional structure.

Crystallography, X-Ray↗

Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine.

BACKGROUND: Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylic acid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. MATERIALS: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-153 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. RESULTS: The Pentasa tablet appeared completely dissolved in the stomach by 117 +/- 18 min. Samarium oxide was first detected in the small intestine 60 +/- 5 min after its ingestion; it reached the colon after 280 +/- 13 min and it was completely absent from the small intestine at 360 +/- 26 min. Plasma concentrations of 5-ASA started to rise after 67 +/- 7 min and were maximal at 222 +/- 25 min. CONCLUSION: In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect.

Adult↗

Gastric emptying of solid food in edentulous patients.

Whether mastication of food by teeth is a physiological contributor in the process of nutrient digestion remains a debatable issue. In this study we sought to determine whether mastication could influence the gastric emptying of solid food. In 8 edentulous patients, we measured the gastric emptying of a test meal ingested with or without their dental prostheses. Clinical dental evaluation and Helkimo chewing test were first performed to verify that the mastication deficiency was adequately corrected by the dental prostheses. A mixed meal containing ten cubes (1.5 cm) of beef liver labeled with 99mTc and mixed in a chicken stew was ingested by the subjects and followed by gamma camera external scintigraphy. The gastric emptying rate of the 99mTc-labeled liver was similar whether the meal was ingested with the denture properly inserted, allowing normal mastication of the liver cubes, or whether the food was swallowed unmasticated in the absence of functional prostheses (Tlag = 60 +/- 5 vs. 58 +/- 11 min, p = NS; T1/2 = 73 +/- 21 vs. 55 +/- 10 min, p = NS; Tlag+T1/2 = 133 +/- 19 vs. 114 +/- 17 min, p = NS). These results show that gastric trituration and emptying of solid food was not facilitated by prior mastication.

Dentures↗

Myocardial viability. Open artery theory.

Left ventricular ejection fraction at rest is the most powerful predictor of death in survived patients after acute myocardial infarction (AMI). Areas of poor contractility after AMI are not always related to necrosis. Stunned and hibernating myocardium are areas of potentially reversible damage which can improve spontaneously or after intervention to re-establish coronary blood flow. Several techniques has been investigated to study myocardial viability. Positron emission tomography (PET) is the gold standard for that purpose. However PET scan is a very expensive technique not available in a lot of countries. Myocardial perfusion scintigraphy and stress echocardiography are the most attractive alternative strategies. With these techniques is possible to predict the outcome and to properly select such patients which can improve with revascularization. A close relationship between open coronary artery and left ventricular (LV) function after AMI is a very well addressed topic in some published trials. However, the most significant benefits are obtained when artery patency is achieved in few hours, with a strong flow and the patency is sustained. We can summarize the benefits of an open artery: time dependent benefits (the traditional sequence of events after early reperfusion with infarct size reduction and left ventricular function improvement) and time independent benefits (thrombolysis may improve healing of infarction; may prevent the infarct expansion; may perfuse areas of hibernating segments; may increase electrical stability; may improve collateral blood flow). The role of collateral blood flow after AMI and its influence on LV function preservation is an important topic poorly elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

Collateral Circulation↗

Crystallization and preliminary X-ray diffraction analysis of tetra-heme cytochrome c3 from sulfate- and nitrate-reducing Desulfovibrio desulfuricans ATCC 27774.

Crystals of the tetra-heme cytochrome c(3) (M(r) = 13 kDa, 107 residues, four heme groups) from sulfate- and nitrate-reducing Desulfovibrio desulfuricans ATCC 27774 have been obtained and crystallographically characterized. They belong to space group P6(1)22 with cell dimensions a = b = 61.84 (4) and c = 109.7 (2) A, and Z = 12. Intensity data were initially collected on a FAST system with a rotating-anode X-ray source leading to a total of 22 592 observations, from which only 4930 were unique, in the resolution range 20.0-2.4 A with an R(merge)(I) of 7.0%. Higher resolution data were measured on a FAST system at station 9.6 of the SRS (Daresbury, England), leading to 19 328 intensities, of which 11 179 were unique, in the resolution range 20.0-1.75 A and an R(merge)(I) of 5.5%. Cross-rotation and translation functions were performed with ALMN and TFSGEN programs from the CCP4 suite. The packing of the molecules in the unit cell was checked with TOM/FRODO. Rigid-body refinement of the model and subsequent refinement using molecular dynamics were performed with X-PLOR, leading to a current R factor of 25.9%, for data up to 2.3 A.

Journal Article↗

Visual separability: a study on unschooled adults.

It has been suggested in previous studies that unschooled adults present serious difficulties at performing tasks which, like part verification, dimensional filtering, or orientation judgments, require them to pay attention to a specific aspect of the stimulus structure. In the present study we examined the performance of unschooled adults by using a task which does not explicitly require the subjects to attend selectively to a specific component of the stimuli. Separability either of parts or of dimensions as well as line-orientation registration were estimated by the occurrence of illusory conjunctions. Whatever the properties involved in the illusions, these occurred in unschooled adults, at about the same rate as in age-matched schooled controls. The two sets of contrasting findings suggest that a critical variable is whether or not the subjects' attentional control is required. The relevance of the present findings as regards the level of processing responsible for illusory conjunctions is discussed.

Aged↗

[Hemodynamic effects of propafenone in dogs anesthesized with halothane or isoflurane].

OBJECTIVE: Several studies suggest that anaesthetic drugs influence the haemodynamic effects of the antiarrhythmic drugs. The aim of this study was to compare the haemodynamic effects of a standard dose of propafenone (1.5 mg/kg) on dogs anaesthetized with halothane or with isoflurane. DESIGN: Randomized laboratory animal study. MATERIAL AND METHODS: Six dogs were anaesthetized with 1% of halothane-Group I, and six dogs with an equianaesthetic dosage of isoflurane (1.5%)-Group II. Dogs breathed in spontaneous ventilation. Haemodynamic monitoring was performed with a femural arterial catheter and a flow-directed pulmonary artery catheter and cardiac output was measured by thermodilution. After a haemodynamic assessment considered as initial a bolus of 1.5 mg/kg of propafenone was given during a period of 30 seconds and similar assessments were made 5, 15, 30 and 60 minutes after. RESULTS: Before propafenone, heart rate was significantly higher in Group II-isoflurane (p < 0.05). After propafenone we found: In both Groups, a decrease in the cardiac output (p < 0.05) with the mean arterial pressure maintained; in Group I (halothane) a decrease in the stroke volume (p < 0.05) which was not found in Group II (p = ns); In Group II (isoflurane) a decrease in heart rate (p < 0.05) not found in Group I (p = ns). All the changes were higher at the 5th minute values. 30th minute and 60th minute values were not significantly different from initial values. CONCLUSION: In dogs anaesthetized with halothane 1.2 MAC a reduction in the stroke volume, resulting in a cardiac output decrease, was observed, suggesting that propafenone increases the negative inotropic action of halothane. In dogs anaesthetized with isoflurane 1.2 MAC the decrease in cardiac output was similar to the decrease in heart rate, and therefore no reduction in the stroke volume was observed. The decrease in the heart rate found in this group but not in the halothane group was probably related with the beta-blocker action of the propafenone. Looking to the systemic vascular resistances, our study suggested that propafenone didn't have any vasodilator effect during halogenated anaesthesia.

Anesthesia↗

[Isonitrile (sestamibi) as a valid alternative to thallium 201 for myocardial perfusion studies].

OBJECTIVE: SestaMIBI is a new technetium labeled radiopharmaceutical agent approved for myocardial perfusion studies. In the present work the authors analyzed the accuracy of this agent on the study of ischemic heart disease. CONCEPTION: The present paper was made considering the results of four previous studies around defined goals performed by the same research group. SETTING: Cardiology and Nuclear Medicine departments in a general hospital. RESULTS: Planar studies: global sensitivity for the diagnosis of ischemic heart disease was 100% and specificity of 67%. Tomocintigraphic studies and segmentary analysis of IHD: the accuracy for stenosis involving the left anterior descending artery was of 80%, 91% for the right coronary artery and 67.2% for left circumflex artery. Planar studies versus tomocintigraphy--SPECT (comparative study in the same population): global sensitivity of 86% for planar method and 97% for "SPECT". In patients with single vessel disease the results are also better with "SPECT" (75% vs 94%). In this series the presence of rest perfusion defects is frequent. In 75% was possible to correlate them with a significant lesion over the related coronary artery. The positive predictive value of this finding is of 92% for the lesions on the left coronary artery, 100% for left cincumflex and 59% for the right coronary artery. CONCLUSIONS: 1. The SestaMIBI is an excellent radiopharmaceutical agent for myocardial perfusion studies. 2. The accuracy of this agent for diagnosis of ischemic heart disease is quite good with a high sensitivity and specificity values. This conclusion is also valid for those patients with single vessel disease. 3. Scintigraphic studies performed with planar acquisition provide good quality images. Nevertheless tomoscintigraphy (SPECT) is more accurate namely in patients with single vessel disease. 4. In the present state of the art and regarding our results we can conclude that is too early for considering SestaMIBI like and agent for viability studies.

Coronary Disease↗

Structure analysis of cytochrome c3 from Desulfovibrio vulgaris Hildenborough at 1.9 A resolution.

The three-dimensional X-ray structure of cytochrome c3 from sulfate-reducing bacteria Desulfovibrio vulgaris Hildenborough (DvH) (M(r) 13 kDa, 107 residues, 4 heme groups) has been determined at 1.9 A resolution, by the method of molecular replacement, using the homologous part of the refined structure of cytochrome c3 from D. vulgaris Miyazaki F (DvMF). Crystals of c3 DvH were obtained with space group P61, a = 77.0 A, c = 77.2 A, Z = 12, corresponding to two independent molecules in the asymmetric unit. The structure was refined to an R-factor of 19.6%. The structures of the two molecules are analyzed, compared with each other and also with that of c3 DvMF. The main-chain atoms are, for the three structures, generally within 1.0 A. The intramolecular heme edge to edge distances and interplanar angles indicate two groups of values. Shorter distances are associated with near-normal angles, while longer distances with acute angles. Moreover, two of the four hemes, II and IV, are close to only one other heme, while the remaining two hemes, I and III, have two close neighbors each. The two histidine residues that co-ordinate the heme irons on the fifth and sixth positions are nearly parallel, except in the case of heme II. The only substitution from DvMF which is inside the molecule, A68V, occurs in the vicinity of that same heme. However, the non-paralellism between the two flanking histidine residues was also observed in DvMF. Heme II has a conserved higher exposure to solvent and one of the lowest redox potentials in the fully oxidized forms of the two cytochromes. A comparison between data obtained by spectroscopic techniques, nuclear magnetic resonance and electron paramagnetic resonance, and the structural results presented here, indicates two types of interactions, between hemes I and II and between hemes III and IV.

Amino Acid Sequence↗

Ga-67 imaging in primary and secondary psoas abscess.

Primary and secondary psoas abscesses are uncommon and frequently misdiagnosed. Two cases of pyogenic psoas abscess are presented to illustrate the usefulness of Ga-67 scintigraphy in determining the presence and the extent of the infectious process.

Adolescent↗