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Biomedical subjects

D Le Guludec

Publications and source records attributed to D Le Guludec.

At least 37 records · Page 2Linked to original sources

Cell irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences.

Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings. Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.

Humans↗

Activity and diffusion of LY333328 in experimental endocarditis due to vancomycin-resistant Enterococcus faecalis.

The activity of LY333328 against Enterococcus faecalis JH2-2, which is susceptible to glycopeptides, and against its transconjugants E. faecalis BM4281 and BM4316, with VanB and VanA phenotypes, respectively, was investigated. LY333328 was active in vitro against the three strains, for which MICs were 2 microg/ml on agar and 0.25 microg/ml in broth. LY333328 was bactericidal in broth against E. faecalis JH2-2 and BM4281 at a concentration of 8 microg/ml and against BM4316 at a concentration of 30 microg/ml. The protein binding of LY333328 to rabbit serum was >99%, and the bactericidal activity of LY333328 in broth was reduced when it was tested in the presence of 90% rabbit serum. Autoradiographic studies performed in rabbits with enterococcal endocarditis showed that 14[C]LY333328 was distributed heterogeneously throughout cardiac vegetations. In rabbits with aortic endocarditis, a regimen of 20 mg of LY333328 per kg of body weight administered intramuscularly twice a day for 5 days after a loading dose of 40 mg/kg was active against the three strains in vivo (P < 0.01), whereas vancomycin was not active against the VanB-type strain and teicoplanin was not active against the VanA-type strain. We conclude that the activity of LY333328 is not significantly modified by acquired resistance to glycopeptides in E. faecalis either in vitro or in experimental endocarditis.

Animals↗

111Indium antimyosin antibody imaging of primary myocardial involvement in systemic diseases.

OBJECTIVE: The diagnosis of primary myocardial involvement in systemic diseases is clinically relevant but difficult in the absence of specific criteria. Whatever the underlying disease, myocytes degeneration is observed during the active phase of myocardial damage. The aim of this study was to assess the diagnostic value of scintigraphic imaging with 111Indium antimyosin antibody (AM), a specific marker of the damaged myocyte, for ongoing myocardial damage related to systemic diseases. METHODS: 40 patients with histologically confirmed systemic diseases were studied. They were classified into two groups according to the presence (group 1, n = 30), or the absence (group 2, n = 10) of clinical, electrocardiographic (ECG) or echocardiographic signs suggestive of myocardial involvement. Planar and tomographic acquisitions were obtained 48 hours after injection of AM (90 MBq). Rest 201thallium (T1) scintigraphy was also performed to assess myocardial perfusion and scarring. Clinical, ECG, and echocardiographic +/- scintigraphic evaluations were repeated during follow up (17 +/- 19 months) in 36 of 40 patients. RESULTS: In group 1, 13 of 30 patients (43%) showed diffuse significant AM uptake throughout the left ventricle (LV), and no or mild T1 abnormality. Two of these were asymptomatic, four had normal ECG, and two had no clinical or echographic LV dysfunction. All patients in group 2 had negative AMA scintigraphy and normal T1 scintigraphy. During follow up of 12 AM positive patients, cardiac status improved after immunosuppressive treatment was intensified in nine cases, worsened in two cases, and remained stable in one. During follow up of 24 AM negative patients, cardiac status remained stable in 23 cases despite treatment not being increased in 20, including two patients with sequellary myocardial involvement. The last patient developed mild LV dysfunction after 36 months. CONCLUSION: AM scintigraphy allows detection of active myocardial damage related to systemic diseases, with increased specificity compared with conventional methods, and increased sensitivity in some cases. Further studies are needed to assess the potential value of AM scintigraphy as a therapeutic guide.

Adult↗

Spontaneous late improvement of myocardial viability in the chronic infarct zone is possible, depending on persistent TIMI 3 flow and a low grade stenosis of the infarct artery.

OBJECTIVE: In the chronic phase of myocardial infarction, the relation between myocardial recovery and infarct related artery status remains unclear. The spontaneous changes in rest-redistribution thallium defect size were prospectively studied over six months in 52 patients with chronic Q wave myocardial infarction. DESIGN: Changes in rest thallium defect size, thallium uptake in the infarct area, and radionuclide left ventricular ejection fraction were compared to the quantitative coronary angiogram data. Two groups of patients were considered: patients with a percentage of stenosis below 100% (group 1, n = 31); and patients with an occluded artery (group 2, n = 21). RESULTS: In the overall population, the mean (SD) defect size decreased from 28.2 (17.2)% to 24.9 (19.3)% of the whole myocardium (p = 0.01), while, in this area, the thallium uptake increased from 62.9 (13.7)% to 66. 9 (15.6)% (p < 0.001). At the time of inclusion, the defect size, thallium uptake, and ejection fraction were similar in both groups. In group 1 patients only, the reduction in defect size correlated with the improvement in ejection fraction (r = 0.41, p = 0.02) and was related to the percentage of coronary artery stenosis. TIMI 3 patients reduced the defect size while other patients increased this defect (-5.1 (7.0)% v +11.0 (14.4)%, p < 0.001). In contrast, no significant relations were found in group 2 patients. CONCLUSION: Late spontaneous recovery in thallium defect can occur in patients with a patent infarct related artery, depending on the TIMI flow grade and a low grade stenosis of the infarct related artery, and is associated with functional improvement.

Aged↗

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer.

BACKGROUND: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results. METHODS: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.2 years) presenting with signs, symptoms, or preliminary diagnostic results suggestive of this disease. Cystoscopy was the standard of detection. RESULTS: In the 100 patients found to have bladder cancer, the overall sensitivities of the BTA TRAK assay (at a previously determined decision threshold of 14 kilounits/L) and cytology were 66% (66 of 100) and 33% (33 of 100), respectively (P <0.001). The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grades I and II and for stage Ta and T1 tumors. In contrast, the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69% (83 of 120) and that of cytology was 99% (119 of 120; P <0.001). The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer (76%; n = 89) than in patients with these conditions. When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone, increases in overall sensitivity and equivalent specificity were observed. CONCLUSION: Because of its relatively high sensitivity, the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer.

Adult↗

201Tl and 99mTc-MIBI gated SPECT in patients with large perfusion defects and left ventricular dysfunction: comparison with equilibrium radionuclide angiography.

UNLABELLED: Left ventricular ejection fraction (LVEF) is a major prognostic factor in coronary artery disease and may be computed by 99mTc-methoxyisobutyl isonitrile (MIBI) gated SPECT. However, 201Tl remains widely used for assessing myocardial perfusion and viability. Therefore, we evaluated the feasibility and accuracy of both 99mTc-MIBI and 201Tl gated SPECT in assessing LVEF in patients with myocardial infarction, large perfusion defects and left ventricular (LV) dysfunction. METHODS: Fifty consecutive patients (43 men, 7 women; mean age 61 +/- 17 y) with a history of myocardial infarction (anterior, 26; inferior, 18; lateral, 6) were studied. All patients underwent equilibnum radionuclide angiography (ERNA) and rest myocardial gated SPECT, either 1 h after the injection of 1110 MBq 99mTc-MIBI (n = 19, group 1) or 4 h after the injection of 185-203 MBq 201Tl (n = 31, group 2) using a 90 degrees dual-head camera. After filtered backprojection (Butterworth filter: order 5, cutoff 0.25 99mTc or 0.20 201Tl), LVEF was calculated from reconstructed gated SPECT with a previously validated semiautomatic commercially available software quantitative gated SPECT (QGS). Perfusion defects were expressed as a percentage of the whole myocardium planimetered by bull's-eye polar map of composite nongated SPECT. RESULTS: Gated SPECT image quality was considered suitable for LVEF measurement in all patients. Mean perfusion defects were 36% +/- 18% (group 1), 33% +/- 17% (group 2), 34% +/- 17% (group 1 + group 2). LVEF was underestimated using gated SPECT compared with ERNA (34% +/- 12% and 39% +/- 12%, respectively; P = 0.0001). Correlations were high (group 1, r= 0.88; group 2, r = 0.76; group 1 + group 2, r = 0.82), and Bland-Altman plots showed a fair agreement between gated SPECT and ERNA. The difference between the two methods did not vary as LVEF, perfusion defect size or seventy increased or when the mitral valve plane was involved in the defect. CONCLUSION: LVEF measurement is feasible using myocardial gated SPECT with the QGS method in patients with large perfusion defects and LV dysfunction. However, both 201Tl and 99mTc-MIBI gated SPECT similarly and significantly underestimated LVEF in patients with LV dysfunction and large perfusion defects.

Electrocardiography↗

Detection of bone metastases in patients with endocrine gastroenteropancreatic tumors: bone scintigraphy compared with somatostatin receptor scintigraphy.

UNLABELLED: Scintigraphy with somatostatin analogs is a sensitive method for the staging and therapeutic management of patients with endocrine gastroenteropancreatic (GEP) tumors. The aim of this study was to compare prospectively somatostatin receptor scintigraphy (SRS) using 111n-pentetreotide with bone scintigraphy using 99mTc-hydroxymethylene diphosphonate for the detection of bone metastases. METHODS: One-hundred-forty-five patients with proven endocrine GEP tumors were investigated. Patients were classified according to the presence of bone metastases as indicated by CT, MRI or histologic data. Group I included 19 patients with confirmed bone metastases, and group II included 126 patients without bone metastases. RESULTS: In group I, SRS was positive in all 19 patients with bone metastases, and bone scintigraphy was positive in 17 patients. Bone metastases were found to occur predominantly in patients with liver metastases. In group 11, 5 patients had recent bone surgery for fracture or arthritis. SRS showed bone uptake in 4 of these patients, and bone scanning showed abnormal uptake in 5. In 7 of the remaining 121 group II patients, SRS was negative and bone scanning showed abnormal bone uptake suggesting bone metastases. The detection of bone metastases was of major prognostic value, because 42% of group 1 patients died during a 2-y follow-up. CONCLUSION: In patients with GEP tumors, the accuracy of SRS appears to be similar to that of bone scintigraphy for the detection of bone metastases.

Adult↗

Comparison of cellular and conventional dosimetry in assessing self-dose and cross-dose delivered to the cell nucleus by electron emissions of 99mTC, 123I, 111In, 67Ga and 201T1.

The radionuclides used in nuclear medicine imaging emit numerous mono-energetic electrons responsible for dose heterogeneity at the cellular level. S(self) the self-dose per unit cumulated activity (which results from the radionuclide located in the target cell), and S(cross) the cross-dose per unit cumulated activity (which comes from the surrounding cells) delivered to a target cell nucleus by electron emissions of technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201 were computed at the cellular level. An unbounded close-packed hexagonal cell arrangement was assumed, with the same amount of radioactivity per cell. Various cell sizes and subcellular distributions of radioactivity (nucleus, cytoplasm and cell membrane) were simulated. The results were compared with those obtained using conventional dosimetry. S(self) and S(cross) values depended closely on cell dimensions. While the self-dose depended on the tracer distribution, the latter affected the cross dose by less than 5%. When the tracer was on the cell membrane, the self-dose was particularly low compared to the cross-dose, as the self-dose to cross-dose ratio was always less than 11%. In the case of cytoplasmic or cell membrane distribution of radioactivity, conventional electron dosimetry slightly overestimated the dose absorbed by the target cell nucleus (by 1.08-to 1.7-fold). In contrast, conventional dosimetry strongly underestimated the absorbed dose (1.1- to 75-fold) when the radioactivity was located in the nucleus. The discrepancies between conventional and cellular dosimetry call for calculations at the cellular level for a better understanding of the biological effects of radionuclides used in diagnostic imaging.

Algorithms↗

Diagnostic accuracy and prognostic value of combined dipyridamole-exercise thallium imaging in hemodialysis patients.

BACKGROUND: Non-invasive detection of coronary artery disease in dialysis patients, a major cause of mortality, often remains difficult. The aim of the study was to test the diagnostic and prognostic accuracies of combined dipyridamole-exercise thallium imaging in dialysis patients. METHODS: Dipyridamole-exercise thallium imaging and coronary angiography were both performed prospectively in 60 asymptomatic hemodialysis patients who were followed up, long term, by recording any major coronary event. RESULTS: Coronary angiography was abnormal in 13 patients (21%), and there was abnormal thallium uptake in 17 patients. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of thallium to detect a coronary artery disease were 92, 89, 71, 98 and 90%, respectively. After a median follow-up of 2.8 years, 12 patients experienced at least one major coronary event (4 cardiac deaths, 5 myocardial infarctions and 3 revascularizations). Eight of the 17 patients with abnormal thallium uptake (47%) suffered a coronary event, compared to only 4 of the 43 patients (9%) with a normal thallium uptake (P < 0.001). The positive prognostic predictive value of thallium imaging was 47% and its negative predictive value was 91%. The probability of survival free of coronary events was significantly higher in patients with normal thallium uptake than in those with abnormal thallium uptake (crude risk ratio 7.6; P < 0.001) even after adjustment for several risk factors for cardiovascular disease (adjusted risk ratio 9.2; P < 0.005). CONCLUSION: In dialysis patients, combined dipyridamole-exercise thallium imaging is an accurate method for detecting coronary stenosis and for predicting future coronary events.

Adult↗

Quantitative autoradiography using a radioimager based on a multiwire proportional chamber.

Determination of the biodistribution of radiopharmaceuticals is an important issue for the evaluation of their performance in diagnosis and therapy. In this study, we evaluated a digital radioimager (RI) based on a multiwire proportional chamber for quantitative autoradiography (AR). The RI allows direct detection of electronic emissions of gamma emitters. Its qualitative and quantitative performances were tested on 99mTc and (111)In labelled sections and compared with conventional film AR. Linearity of count rate versus activity was verified over a 104 range of activity. As compared with film AR, a substantial improvement of the detection limit was obtained even for acquisition periods up to 20 times less than film exposure times. We provided the basis for quantitative analysis with tissue equivalent paste standards: the 99mTc and (111)In RI counting efficiencies were respectively 1.19% and 2.35%. We illustrated the respective values of RI and film AR in two rat studies: 99mTc-DMSA in kidney and dual-isotope 99mTc-MIBI and (111)In-antimyosin in heart. Calculated activity concentrations on sections of rat organs confirmed good correlation to gamma counting (deviation less than 12%). We suggest RI as a convenient technique for fast localization of single or dual-isotope tracers and determination of activity distribution.

Animals↗

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.

Administration, Oral↗

Left ventricular-arterial system coupling at peak exercise in dilated nonischemic cardiomyopathy.

We assessed the ventricular-arterial coupling at peak exercise in 20 patients with dilated cardiomyopathy (ejection fraction, 27+/-12%) and 7 normal subjects by radionuclide ventriculography during exercise, coupled with respiratory gas analysis. The end-systolic pressure-volume ratio, taken as an index of contractility, and the effective arterial elastance were calculated at rest and at peak exercise. The end-systolic pressure/volume ratio increased from 3.7+/-2.7 to 6.9+/-4.0 mm Hg/mL at peak exercise in the normal subjects, but did not change significantly (from 0.9+/-0.5 to 1.0+/-0.6 mm Hg/mL) in the patients. Arterial elastance did not change significantly in the patients (+17+/-32%, not significant [NS] vs rest) or in the normal subjects (+22+/-28%, NS vs rest). The change in ejection fraction during exercise correlated both with the end-systolic pressure/volume ratio and with effective arterial elastance changes (r=0.60 and 0.68, respectively). We conclude that ventricular arterial coupling is further altered at peak exercise in these patients because of the lack of increase in contractility and not of altered effective arterial elastance response.

Adult↗

[Diagnostic strategy in acute myocarditis].

Myocarditis is a focalised or diffuse disease of the myocardium. The principal causal agents are viruses in Europe and North America and a parasite in South America (Chagas' disease). The prevalence of acute myocarditis is variable, related to the periodic cycle of viral epidemics. The diagnosis is difficult to establish because the clinical presentation is variable, ranging from asymptomatic forms to rapidly fatal acute congestive heart failure. The diagnostic tools suffer from lack of sensitivity or specificity. Endomyocardial biopsy, despite its low sensitivity, remains the reference investigation as it provides histological proof of the myocarditis. Myocardial scintigraphy with antimyosin antibodies has the advantage of very good sensitivity but with less specificity. The authors discuss the critical indications and limitations of each investigation.

Biopsy↗

Increased myocardial muscarinic receptor density in idiopathic dilated cardiomyopathy: an in vivo PET study.

BACKGROUND: Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased Gi-binding protein, attenuated parasympathetic tone, and increased modulation of beta-adrenergic inotropic left ventricular stimulation by parasympathetic agonists. Despite these abnormalities, changes in the density or affinity of ventricular muscarinic receptors have not been demonstrated in patients. METHODS AND RESULTS: The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, in 20 patients with congestive heart failure due to idiopathic dilated cardiomyopathy (mean left ventricular ejection fraction, 22+/-9%) and compared with values in 12 normal subjects. The mean receptor concentration was significantly higher in patients than in control subjects (B'max, 34.5+/-8.9 versus 25+/-7.7 pmol/mL, P<.005), with no changes in affinity constants. The change in heart rate after injection of 0.6 mg of cold MQNB was lower in patients than in control subjects (34+/-20% versus 55+/-36%, P<.05), and receptor density correlated negatively with maximal heart rate in the patients (r=.45, P<.05). CONCLUSIONS: Congestive heart failure is associated with an upregulation of myocardial muscarinic receptors. This may be an adaptive mechanism to beta-agonist stimulation and should increase the number of potential targets for pharmacological intervention.

Adult↗

Comparison of left ventricular responses to the six-minute walk test, stair climbing, and maximal upright bicycle exercise in patients with congestive heart failure due to idiopathic dilated cardiomyopathy.

Submaximal exercise tests have been advocated to assess exercise capacity in chronic heart failure, but hemodynamic responses have not been characterized. To determine left ventricular (LV) responses during submaximal exercise, the LV ejection fraction (EF) and volumes were evaluated by using an ambulatory radionuclide detector in 13 patients with idiopathic dilated cardiomyopathy during upright maximal graded bicycle exercise, stair climbing and a 6-minute walk test. The 3 tests elicited different responses in volumes and, to a lesser degree, in LVEF. The maximal bicycle exercise led to a decrease in LVEF from 22 +/- 9% to 17 +/- 8% (p <0.05), with marked increases in both end-diastolic volume (EDV) (+15 +/- 10%, p <0.001) and end-systolic volume (ESV) (+23 +/- 18%, p <0.001). Stair climbing tended to reduce LVEF (from 24 +/- 11% to 21 +/- 10%, p = 0.05), with a lesser increase in volumes, which was more marked for ESV (+8 +/- 9%, p <0.01) than for EDV (+4 +/- 4%, p <0.01). The 6-minute walk test did not significantly change LVEF (23 +/- 10% vs 22 +/- 10%), but increased both EDV (+10 +/- 6%, p <0.001) and ESV (+8 +/- 8%, p <0.01) moderately and proportionally. Exercise capacity indexes (peak oxygen consumption, maximal bicycle work rate, stair climbing time, and the distance covered during the 6-minute walk test) correlated significantly with one another. There was no correlation between submaximal exercise tolerance indexes and resting or exercise LVEF. This study shows that (1) LVEF changes are inadequate to report on LV volume changes during exercise; (2) the 3 tests induce different LV volume changes; (3) the 6-minute walk test induces significant changes in LV volumes but no change in LVEF.

Adult↗

Multivariate analysis of pathophysiological factors in reflux oesophagitis.

BACKGROUND: Reflux oesophagitis is considered a multifactorial disease, but the respective roles of the main factors involved in its pathophysiology have not been clearly established. AIMS: To attempt to assign these roles by means of a multivariate logistic regression analysis of the main parameters associated with reflux oesophagitis. PATIENTS: Eighty seven patients with gastro-oesophageal reflux disease were studied: 41 without oesophagitis and 46 with reflux oesophagitis grade 1 to 3. METHODS: (1) Monovariate comparison of patients' characteristics and of parameters derived from in hospital 24 hour oesophageal pH monitoring, oesophageal manometry, double isotope gastric emptying studies, and basal and pentagastrin stimulated gastric acid and pepsin output determinations, between patients with and without oesophagitis. (2) Multivariate logistic regression analysis including the parameters significant in the monovariate analysis. RESULTS: Among the 16 significant parameters from monovariate analysis, three significant independent parameters were identified by multivariate logistic regression analysis: number of refluxes lasting more than five minutes, reflecting oesophageal acid clearance (p = 0.002); basal lower oesophageal sphincter pressure (p = 0.008); and peak acid output (p = 0.012). These three parameters were not correlated with each other. The multivariate model was highly discriminant (correct classification of 81.3% of the cases (95% confidence intervals 0.723, 0.903). Risk for oesophagitis increased as a function of the tercile threshold values of the three parameters. Odds ratios of the three parameters for oesophagitis risk were similar, regardless of whether they were calculated when the patients were compared as a function of oesophagitis grade or the presence or absence of oesophagitis. CONCLUSIONS: This multivariate approach adds evidence that impaired oesophageal acid clearance and hypotonic lower oesophageal sphincter are the two major independent pathophysiological factors of oesophagitis, but also showed that the acid secretion level is an independent pathophysiological factor.

Adult↗