[Interindividual-variability of the analysis of regional myocardial wall function after myocardial infarction and revascularization]. / Interindividuelle-Variabilität der regionalen myokardialen Wandfunktionsanalyse nach Herzinfarkt und Revaskularisierung.

PURPOSE: The gold standard for diagnosis myocardial viability is the functional recovery after revascularization. Aim of the study was to compare (1) qualitative analysis and (2) quantitative wall thickening by cine MRI and (3) circumferential shortening by tagged MRI the analysis of regional wall function of an infarcted area before and after revascularization. MATERIAL AND METHODS: Ten patients (age 60 +/- 11 years) with infarct-associated regional left ventricular wall motion abnormalities were examined by cine and tagged MRI on average two weeks after the myocardial infarction and re-examined three months after revascularization. Eight healthy volunteers served as a control for tagged MRI. Interobserver-variabilities of two observers were calculated using the kappa-statistics for grading of wall motion abnormalities as well as for detection of functional recovery by qualitative analysis, measurement of wall thickening of cine MRI, and measurement of circumferential shortening by tagged MRI, respectively. RESULTS: Grading of wall motion abnormalities revealed interobserver-variabilities of the study and control group of kappa = 0.8 and kappa = 0.84, kappa = 0.02 and kappa = 0.5, and kappa = 0.1 and kappa = 0.17 for qualitative analysis, wall thickening analysis and measurement of circumferential shortening, respectively. The interobserver-variability for the definition of wall motion recovery was kappa = 0.8 for all three methods. CONCLUSION: Qualitative analysis of wall motion abnormalities has the lowest interobserver-variability for the grading of wall motion abnormalities. The interobserver-variabilities of qualitative and quantitative analysis are comparable for the diagnosis of regional wall motion recovery. Thus, qualitative analysis of cine MRI can be used for grading regional wall motion in clinical studies.

Time course of contrast enhancement patterns after Gd-BOPTA in correlation to myocardial infarction and viability: a feasibility study.

Our objective was to analyze contrast enhancement patterns (CEP) and their time course after myocardial infarction (MI) following injection of Gd-BOPTA in correlation with recovery of regional function. Seven patients with subacute MI (18 +/- nine days) were examined before, as well as three and six (n = six) months after, revascularization of the infarct-related artery. Regional wall motion abnormalities were assessed by cine-MRI, and repetitive images of one representative slice were acquired up to 45 minutes after 0.05 mmol/kg Gd-BOPTA using a T1-w TSE-sequence. Two patients showed mid-wall/subendocardial, one patient subendocardial enhancement of MI associated with mechanical improvement after revascularization. Three patients without improvement revealed a mid-wall hypoenhanced zone within the first five minutes after injection, which was unchanged at follow-up. One patient with partial functional improvement showed transmural enhancement and a mid-wall hypoenhanced zone in adjacent areas. With this feasibility study, we concluded that mid-wall and/or subendocardial enhancement after Gd-BOPTA was associated with viable myocardium, whereas detection of microvascular obstruction correlating with scar formation is suggested by mid-wall hypoenhancement within the first five minutes after injection.

Assessment of myocardial infarction in humans with (23)Na MR imaging: comparison with cine MR imaging and delayed contrast enhancement.

PURPOSE: To demonstrate the feasibility of sodium 23 ((23)Na) magnetic resonance (MR) imaging for assessment of subacute and chronic myocardial infarction and compare with cine, late enhancement, and T2-weighted imaging. MATERIALS AND METHODS: Thirty patients underwent MR imaging 8 days +/- 4 (subacute, n = 15) or more than 6 months (chronic, n = 15) after myocardial infarction by using a (23)Na surface coil with a double angulated electrocardiogram-triggered three-dimensional gradient-echo sequence at 1.5 T. In addition, cine, inversion-recovery gradient-echo, and, in the subacute group, T2-weighted images (n = 9) were obtained. Myocardial infarction mass was depicted as elevated signal intensity or wall motion abnormalities and expressed as a percentage of total left ventricular mass for all modalities. Correlations were tested with correlation coefficients. RESULTS: All patients after subacute infarction and 12 of 15 patients with chronic infarction had an area of elevated (23)Na signal intensity that significantly correlated with wall motion abnormalities (subacute; r = 0.96, P <.001, and chronic; r = 0.9, P <.001); three patients had no wall motion abnormalities or elevated (23)Na signal intensity. Only 10 patients in the subacute and nine in the chronic group revealed late enhancement; significant correlation with (23)Na MR imaging occurred only in subacute group (r = 0.68, P <.05). Myocardial edema in subacute infarction correlated (r = 0.71, P <.05) with areas of elevated (23)Na signal intensity but was extensively larger. CONCLUSION: (23)Na MR imaging demonstrates dysfunctional myocardium caused by subacute and chronic myocardial infarction.

(31)P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans.

OBJECTIVE: Experimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemic insult on energy metabolism of intact septal myocardium was analyzed using 31P-Magnetic resonance spectroscopy (MRS). PATIENTS AND METHODS: In eight patients with wall motion abnormalities in the anterior wall 31P-spectra were obtained from non-infarcted adjacent septal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29+/-8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MRI was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group. RESULTS: According to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28+/-0.10 and 1.14+/-0.09 vs. 1.45+/-0.29). No recovery of regional function was detected in 4/8 patients with-therefore-non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77+/-0.17 and 0.49+/-0.23; P<0.05). DISCUSSION: These preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.

Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P-MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P-MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P-MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented.

[(23)sodium MRI for infarct imaging of the human heart]. / 23Natrium-MRT zur Infarktdarstellung am menschlichen Herzen.

PURPOSE: Sodium is elevated in acute/subacute myocardial infarction due to three distinct mechanisms: Breakdown of ion homeostasis with accumulation of intracellular sodium, extracellular edema formation and, during scar formation, increase of extracellular vs. intracellular space as cardiomyocytes are replaced by connective tissue. 23Na MRI has previously been shown to have the potential to demonstrate myocardial infarction in an animal model. Aim of this study was, therefore, to demonstrate myocardial infarction with the use of 23Na-MRI in patients. MATERIAL AND METHODS: 10 patients were examined 14 +/- 7 days after first myocardial infarction using a 23Na surface coil at 1.5 T. Double angulated short axis images of the entire heart were imaged using an ECG-triggered 3d-FLASH-sequence (FOV, 450 mm; matrix, 64 x 128; spatial resolution, 3.5 x 7 mm2; slice thickness, 16 mm; 32 acquisitions). Areas of elevated sodium signal intensity were correlated with infarct-related wall motion abnormalities imaged by Cine MRI in breathhold-technique. RESULTS: All patients showed an area of elevated sodium signal intensity that correlated well with the clinically determined localization of myocardial infarction as well as with regional wall motion abnormalities detected by Cine MRI. CONCLUSIONS: Elevated 23Na MR image signal intensity demonstrates subacute myocardial infarction in patients.

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age-matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two-dimensional cine fast low-angle shot sequence was used for the evaluation of absolute values and indices related to 1 m(2) body surface area for function, mass, and LV wall thickening. Fourteen age-matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end-systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year.

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans.

The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ ATP) ratio of volunteers (SD 1.72+/-0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47+/-0.38 (non-significant vs volunteers; p>0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92+/-0.73 vs 6.68+/-0.80; patients vs volunteers; p<0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Analysis of first-pass and delayed contrast-enhancement patterns of dysfunctional myocardium on MR imaging: use in the prediction of myocardial viability.

OBJECTIVE: The purpose of the study was to analyze first-pass and delayed contrast-enhancement patterns of dysfunctional myocardial regions on MR imaging after injection of gadopentetate dimeglumine to predict myocardial viability in patients with coronary artery disease. SUBJECTS AND METHODS: Twelve patients with wall motion abnormalities and related coronary artery disease revealed by conventional coronary angiography underwent MR imaging at 1.5-T before and 3 months after revascularization therapy. Short-axis images were acquired using a cine gradient-echo sequence. Each slice was divided into eight segments. Overall, 73 segments with impaired contractility were imaged during the first-pass and 14 +/- 2 min after injection of 0.05-mmol/kg gadopentetate dimeglumine at a flow of 3 ml/sec using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as the criterion of viability. RESULTS: At study entry, 26 dysfunctional segments showed delayed hyperenhancement compared with the adjacent functional segments within the same slice, and 47 did not reveal hyperenhancement. After revascularization, 25 (96%) of the 26 hyperenhanced segments did not recover function, whereas 39 (83%) of the 47 segments without hyperenhancement showed mechanical improvement. Segment-related sensitivity and specificity for the correlation of lack of delayed hyperenhancement with myocardial viability were 39 (98%) of 40 and 25 (76%) of 33, respectively. Hypoenhancement during first-pass did not serve as a reliable criterion of viability. CONCLUSION: Evidence of delayed hyperenhancement of dysfunctional myocardium may be used to predict lack of mechanical improvement or nonviability, whereas the lack of hyperenhancement can be correlated with improvement of regional contractility or viability after revascularization.

[Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy]. / Untersuchungen des kardialen Energiestoffwechsels bei Herzvitien mit der 31P-MR-Spektroskopie.

PURPOSE: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. PATIENTS AND METHODS: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. RESULTS: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p = 0.0002) reduced to 0.80 +/- 0.25 in patients compared to 1.65 +/- 0.21 in volunteers. 3 months after SVR, LV mass had significantly (p = 0.04) decreased from 238 +/- 33 g to 206 +/- 47 g. At the same time a significant (p = 0.04) increase of the PCr-ATP ratio from 0.80 +/- 0.25 to 1.28 +/- 0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. CONCLUSIONS: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

[The quantification of energy-rich phosphates in healthy and damaged heart muscle by SLOOP 31P-MR spectroscopy. Spatial localization with optimal pointspread function]. / Quantifizierung energiereicher Phosphate im gesunden und geschädigten Herzmuskel mittels SLOOP 31P-MR-Spektroskopie.

PURPOSE: A quantitative 31P-MR-spectroscopic technique was used to assess the energy metabolism in healthy and diseased myocardium. METHODS: 31P spectra were acquired on a 1.5 T scanner using a 3D-chemical shift imaging technique. Based on the anatomical information provided by 1H images, SLOOP (Spatial Localization with Optimal Pointspread Function) allows to obtain spectra from defined compartments. With SLOOP a free voxel shape with adaption to anatomic structures, e.g. the myocardium, is possible. Absolute values for phosphocreatine (PCr) and adenosine triphosphate (ATP) were determined using an external standard. RESULTS: 31P-spectra showed only minimal contamination by surrounding tissue. The standard deviation for the determined values of healthy volunteers was low. Compared to healthy volunteers, reduced PCr and ATP concentrations were seen for dilative cardiomyopathies and coronary artery disease and unchanged concentrations were observed for hypertensive heart disease. CONCLUSION: 31P-MR spectroscopy with SLOOP allows a non-invasive, quantitative analysis of cardiac energy metabolism.

[CINE-MRT for the study of the effects of regional left ventricular wall motion disorders on global heart function after a myocardial infarct and revascularization]. / CINE-MRT zur Untersuchung der Auswirkungen regionaler linksventrikulärer Wandbewegungsstörungen auf die globale Herzfunktion nach Herzinfarkt und Revaskularisierung.

PURPOSE: To determine changes in global cardiac function and mass caused by infarct-associated regional wall motion abnormalities and to compare the changes after revascularization in patients with and without improvement of regional contractility. MATERIALS AND METHODS: 21 patients with regional left ventricular wall motion abnormalities and associated coronary artery stenoses requiring revascularization were examined with a Cine FLASH-2D sequence 26 +/- 12 days after their first myocardial infarction and re-examined three months after revascularization. Regional contractility and volumes and masses of both ventricles were determined. RESULTS: After revascularization, regional wall motion improvement led to decreased left ventricular volumes and improved ejection fractions, whereas patients with persisting wall motion defects showed unchanged left ventricular functional parameters. Comparing both groups of patients, the patients with improvement of regional contractility revealed lower end-systolic volumes and higher ejection fractions at follow-up. Cardiac masses and right ventricular parameters were not different, patients with a depressed right ventricular ejection fraction showed improvement at follow-up. DISCUSSION: After myocardial infarction, revascularization of the infarct-related coronary artery leads to an improvement of left ventricular function only if there is also an improvement of regional contractility. An effect on right ventricular function was not observed three months after the first small- or middle-sized myocardial infarction.

Cardiac high-energy phosphate metabolism in patients with aortic valve disease assessed by 31P-magnetic resonance spectroscopy.

BACKGROUND: The purpose of this work was to determine the clinical and hemodynamic correlates of alterations in cardiac high-energy phosphate metabolism in patients with aortic stenosis and with aortic incompetence. METHODS: Fourteen volunteers, 13 patients with aortic stenosis, and 9 patients with aortic incompetence were included. Patients underwent echocardiography and left and right heart catheterization. 31P-MR spectra from the anterior myocardium were obtained with a 1.5 Tesla clinical MR system. RESULTS: Aortic stenosis and aortic incompetence patients had similar New York Heart Association (NYHA) classes (2.77 +/- 0.12 vs 2.44 +/- 0.18), ejection fractions (normal), left ventricular (LV) end-diastolic pressures, and LV wall thickness. In volunteers, phosphocreatine/adenosine triphosphate (ATP) ratios were 2.02 +/- 0.11. For all patients, phosphocreatine/ATP was significantly reduced (1.64 +/- 0.09; *p = 0.011 vs volunteers). Phosphocreatine/ATP decreased to 1.55 +/- 0.12 (*p = 0.008) in aortic stenosis, while in aortic incompetence, phosphocreatine/ATP only showed a trend for a reduction (1.77 +/- 0.12; p = 0.148). For all patients, phosphocreatine/ATP decreased significantly only with NYHA class III (1.51 +/- 0.09; *p = 0.001), but not with NYHA classes I and II (phosphocreatine/ATP 1.86 +/- 0.18). In aortic stenosis, phosphocreatine/ATP ratios decreased (1.13 +/- 0.03; *p = 0.019) only when LV end-diastolic pressures were > 15 mm Hg or when LV diastolic wall stress was > 20 kdyne cm-2 (1.13 +/- 0.03; *p = 0.024). CONCLUSIONS: For a similar clinical degree of heart failure in human myocardium, volume overload hypertrophy does not, but pressure overload does, induce significant impairment of cardiac high-energy phosphate metabolism. In aortic valve disease, alterations of high-energy phosphate metabolism are related to the degree of heart failure.

Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.

BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Pattern of 24 hour intragastric acidity in active duodenal ulcer disease and in healthy controls.

Twenty four hour intragastric acidity was measured by continuous recording using intragastric combined glass electrodes in 46 duodenal ulcer patients within 48 hours of endoscopic confirmation of active ulceration. Acidity during predefined time periods was compared with that measured in 40 healthy controls without gastrointestinal disease: it was significantly higher in duodenal ulcer patients at all times, but 25% of ulcer patients had median 24 hour acidity within the interquartile range of the normal group. During the evening (18,00 to 22,00 h) ulcer patients had considerable acidity with a median of 39.8 (63.1-31.6) mmol/l (interquartile range) compared with 5.6 (22.3-0.4) mmol/l of controls. It is suggested that antisecretory treatment be directed to decrease this period of unbuffered acidity, as well as during the night, which is presently considered of prime importance.

Early evening ranitidine administration promotes faster duodenal ulcer healing.

In a prospective double-blind clinical trial, 141 patients with endoscopically diagnosed duodenal ulcer were randomly assigned to treatment with ranitidine 300 mg, taken either at 6 PM or at 10 PM. After 2 wk of treatment, 52 of 70 patients (74%) in the 6 PM treatment group had healed, compared with 32 of 64 patients (50%) taking ranitidine at 10 PM (p less than 0.01). After 4 wk, the cumulative healing rates were 100% and 94%, respectively, for the 6 PM and 10 PM treatment regimens. These results suggest that ranitidine, taken as a single daily 300-mg dose at 6 PM after dinner, provides more rapid duodenal ulcer healing than the same dose of the drug taken at 10 PM.

Day-to-day variation of 24-hour intragastric acidity.

Twenty-four-hour intragastric acidity was measured continuously using an intragastric electrode in 13 normal volunteers studied four times. Subjects were studied twice in the hospital and twice as outpatients. The dietary conditions were strictly controlled and the replicate studies were compared to assess the variability of such recordings of acidity. The accuracy of the technique was assessed, and a detection limit for differences was calculated for commonly used time periods. Over 24 h, during the night, during the day, and during the evening the technique is able to detect consistent changes of pH of greater than 0.1 units. During separate 5-min periods the limits of detection were considerably greater. This study demonstrates the variability of 24-h intragastric acidity and confirms that continuous monitoring is able to detect important changes of acidity under both hospitalized and ambulant conditions.

Single dose treatment with H2 receptor antagonists: is bedtime administration too late?

Using ambulatory ph-metry, intragastric acidity was measured over three separate 24 hour periods in each of 12 healthy volunteers receiving either (a) placebo (1800 h and 2200 h), (b) 300 mg ranitidine (1800 h) and placebo (2200 h), or (c) placebo (1800 h) and 300 mg ranitidine (2200 h). Ranitidine was significantly more effective in decreasing 24 h median intragastric acidity when the drug was administered at 1800 h rather than at 2200 h. Median pH (and interquartile range) was 1.45 (1.4-1.7) on placebo, 2.55 (2.05-3.2) on ranitidine given at 2200 h and 3.35 (2.5-3.85) on ranitidine given at 1800 h (p less than 0.004). The total duration of highly acidic electrode readings (pH less than 1.5) over a 24 h period was reduced significantly by administering the H2-receptor antagonist at 1800 h compared with the later administration. It is suggested that treatment of duodenal ulcers by single administration of ranitidine in the early evening should be evaluated by clinical trial.