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A high-performance liquid chromatography method is described for the determination of digoxin and its metabolites digoxigenin, digoxigenin monodigitoxoside, digoxigenin bis-digitoxoside and dihydrodigoxin (20S and 20R) excreted in urine and feces. The urine sample or fecal supernatant is extracted with methylene chloride in the presence of digitoxigenin or digitoxin as internal standard. Pre-column derivatization is achieved using 1-naphthoyl chloride with subsequent separation of the derivatized compounds on either a normal- or reversed-phase system with fluorescence detection. Recoveries for digoxin and all metabolites from fecal samples were in the range 60-74%, which is comparable to that previously determined for urine samples. Standard curve data revealed linearity over a wide range of concentrations. Coefficients of variation for the analysis were less than 10% for all compounds over a range of 5-125 ng per ml urine and 10-250 ng per 200 mg feces. Peaks for digoxin and metabolites in urine and feces were obtained when human excreta were analyzed.

We reviewed colonoscopic biopsies of the lower gastrointestinal tract performed during a two-year period. Those representing neoplasia were excluded. Formalin-fixed paraffin-embedded biopsy specimens from 53 patients were studied by in situ DNA hybridization for cytomegalovirus (CMV) using commercially available biotinylated DNA probes detected by an avidin-biotin peroxidase technique. Nine of the patients were severely immunocompromised: four had acquired immunodeficiency syndrome, three had ulcerative colitis and were receiving high-dose steroid therapy, one was a bone marrow transplant recipient, and one had idiopathic pulmonary fibrosis and was receiving therapy with prednisone and cyclophosphamide. Four of these had evidence of CMV infection by routine histology and DNA hybridization. Three additional immunocompromised patients had evidence of CMV infection by DNA hybridization alone. Forty-four patients had inflammatory conditions or ulcerations of the lower gastrointestinal tract. Six of these had evidence of CMV by DNA hybridization alone. Histologically normal as well as enlarged and cytomegalic cells were probe positive, and the cells were sparse to numerous in number. They were found in the epithelium and/or lamina propria. This technique was demonstrated to be applicable to routinely processed colonic biopsy specimens.

One hundred fifty-four survivors of out-of-hospital ventricular fibrillation (VF) with coronary artery disease underwent radionuclide ventriculography an average of 4.2 months after VF. All patients were studied at rest, and 91 of these patients were also studied during supine bicycle exercise. Clinical histories and 24-hour ambulatory electrocardiograms were also assessed, and patients were followed for an average of 3.1 years after ventriculography. The mean left ventricular (LV) ejection fraction (EF) at rest was 40 +/- 16%; in 34% of patients, it was 30% or less; in 37%, 31 to 50%; and in 29%, more than 50%. Regional LV wall motion was normal in 18%. The most severe segmental abnormality was hypokinesia in 22%, akinesia in 45% and dyskinesia in 14%. Wall motion abnormalities were usually located at the apex. During exercise, only 3% of patients (3 of 91) had a normal increase in EF of more than 5%, and the mean EF decreased from 42 to 38%. New exercise-induced wall motion abnormalities occurred in 30%. During the follow-up period, 54 patients died (35%): 48 from cardiac causes and 42 from unexpected and sudden causes. Predictors of death included EF at rest, presence of akinesia or dyskinesia on the ventriculogram at rest, the number of abnormal LV segments, history of congestive heart failure, history of acute myocardial infarction, absence of acute myocardial infarction at the time of VF and the presence of ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied 7 patients with eosinophilic gastroenteritis presenting with obstruction of the gastrointestinal tract. Five had required surgical treatment for relief of obstructive symptoms or because of diagnostic uncertainty. Immunological studies, including serum immunoglobulins, serum complement, lymphocyte quantitation, and lymphocyte response to nonspecific mitogens revealed no striking abnormalities. None was clinically allergic or food sensitive, and serum IgE was normal in all. A review of the literature since 1970 suggests that the obstructive form of eosinophilic gastroenteritis accounts for about half of the reported cases. Allergy, especially hypersensitivity to food, is not required for the diagnosis.

The effect of furosemide on secretin-stimulated pancreatic secretion was examined in 12 normal subjects using a perfusion method to quantitate pancreatic output. During continuous secretin infusion (0.9 U per kg per hr), secretory volume rose to a steady state level of 32.5 +/- 10.2 ml per min. When a bolus injection of furosemide (20 mg) was given during continuous secretin infusion, mean secretory volume increased further to a maximum value of 110 +/- 14.7 ml per min. Similarly, the outputs of bicarbonate, sodium, and chloride increased significantly after furosemide, compared to values obtained with secretin infusion alone. Total bilirubin output fell after furosemide, suggesting that the effect of furosemide on secretory volume and electrolyte output was not due to a stimulatory effect on bile flow. Furosemide also had no effect on duodenal water transport. These observations demonstrate that furosemide stimulates pancreatic secretion of water and electrolytes, possibly via inhibition of pancreatic ductal absorption of sodium.

To determine whether intracoronary streptokinase improves late regional wall motion or reduces left ventricular aneurysm or thrombus formation in patients with acute myocardial infarction, two-dimensional echocardiography was performed at 8 +/- 3 weeks after infarction in 83 patients randomized to streptokinase (n = 45) or standard therapy (n = 38) in the Western Washington Intracoronary Streptokinase Trial. Among the patients treated with streptokinase, the average time to treatment was 4.7 +/- 2.5 hours after the onset of chest pain, and 67% had successful reperfusion. Regional wall motion was assessed in nine left ventricular segments on a scale of 1 to 4 (normal, hypokinetic, akinetic and dyskinetic). Left ventricular thrombus formation was interpreted as positive, equivocal or negative. All patients received anticoagulant therapy in the hospital and 52 received such therapy after hospital discharge. The mean (+/- SD) global (1.5 +/- 0.4 in both groups) and regional wall motion scores in the streptokinase-treated and control groups were not significantly different. The prevalence of aneurysm was 16% in both groups. Left ventricular thrombus was identified in only five patients (positive identification in four, and equivocal in one), all in the streptokinase-treated group (p = NS). There were also no differences between streptokinase and control treatment in any of the echocardiographic variables in subgroups of patients with anterior infarction, inferior infarction, no prior infarction or reperfusion with streptokinase. It is concluded that intracoronary streptokinase given relatively late in the course of acute myocardial infarction does not result in improved global or regional wall motion or a reduction in left ventricular thrombus or aneurysm formation in survivors studied 2 months after myocardial infarction.

The intracoronary injection of radionuclide-labeled macroaggregated albumin particles has been shown to be safe and to provide excellent myocardial imaging. When performed in the resting state, it is more sensitive than either the ECG or ventriculogram in identifying areas of scarring and fibrosis due to previous myocardial infarction. Combined with contrast induced coronary hyperemia, intracoronary MAA particles are useful in identifying stenoses of moderate severity that do not alter resting coronary blood flow. Particle studies are likely more sensitive than the rest-exercise 210T1 myocardial scan in identifying patients with significant coronary artery disease. Resting perfusion abnormalities are more closely related to improved or unimproved left ventricular function after surgery than are the ECG or resting left ventriculogram. While the long-range clinical utility of the particle technique is uncertain, its most useful application currently is identification of significant stenoses undetected by 201T1 and of questionable significance by arteriography.

A case of adult idiopathic hypertropic pyloric stenosis whose radiographic study was repeatedly normal is presented. Only a functional test of gastric emptying disclosed the degree of outlet obstruction present. Vagotomy and pyloroplasty resulted in prolonged relief of obstructive symptoms and a return of the saline load test to normal. The saline load test may be of value when gastroduodenal x-rays or endoscopy do not reveal the cause or extent of gastric outlet obstruction.

Intraduodenal amino acids are known to stimulate the release of gastric inhibitory polypeptide and cholecystokinin. In order to separate and quantitate gastric inhibitory polypeptide secretion selectively, 12 normal subjects received an intraduodenal perfusion of a mixed amino acid solution (158 mM) containing either methionine, phenylalanine, tryptophan, and valine (perfusate 1), or an amino acid solution containing arginine, histidine, isoleucine, leucine, lysine, and threonine (perfusate 2). Serum concentrations of gastric inhibitory polypeptide and insulin were significantly greater in the group receiving perfusate 2 (P less than 0.001). In contrast, after administration of amino acid perfusate 1, there was only a slight increase in serum gastric inhibitory polypeptide concentration and insulin secretion increased only slightly. Mean trypsin and bilirubin outputs in the group receiving perfusate 1 were nearly 3 times greater than the outputs of the group receiving the other amino acid mixture. This study expands the importance of intraduodenal amino acid mixtures in stimulating secretion of gastric inhibitory polypeptide and insulin and quantitatively separates gastric inhibitory polypeptide release from release of hormones that stimulate pancreatic enzyme secretion, such as cholecystokinin.

An emission computed tomography system (SPECT), which uses a single large-field-of-view gamma camera, was evaluated for its ability to measure the relative distribution of myocardial blood flow and to assess the effect of attenuation, scatter, and cardiac motion on the tomographic images. Normalized regional myocardial counts from the SPECT images of the living dogs correlated closely with those from the anatomic slices and the samples counted at necropsy except for an over-estimate of tracer in the perfusion defect (SPECT) 57.7 compared to tissue count 32.1; p less than 0.05. The differences were less for the other imaging conditions. Heart and thorax motion, attenuation, and scatter contributed less than 25% to the over-estimate of defect counts. We conclude that the SPECT system accurately reflects regional distribution of myocardial blood flow except for overestimation of flow in regions of perfusion defects. Small perfusion defects might therefore be missed, but no artifactual defects are created.

The biliary excretion of 3H-digoxin in rats prepared for bile sampling with minimal interruption of the enterohepatic circulation was compared with that in rats with complete interruption after intraduodenal or intravenous administration. Following dosage by either route, significantly more radioactivity was recovered from animals with nearly intact enterohepatic circulation. The method described allows direct measurement of this cycle in unanesthetized animals without the consequences of bile depletion.

Although caffeine is known to stimulate small intestinal water secretion in man, no available studies have examined the effect of coffee on small intestinal fluid transport. We have studied the effect of both coffee and caffeine on jejunal sodium and water transport by the triple lumen intestinal perfusion technique. Both caffeine and coffee solutions had equivalent caffeine concentrations, approximating the caffeine concentration in one cup of coffee. Control and coffee perfusion resulted in net absorption of 0.9 +/- 0.2 and 1.1 +/- 0.3 ml per min per 30 cm, respectively, whereas caffeine perfusion resulted in net water secretion of 2.4 +/- 0.4 ml per min per 30 cm (P less than 0.02). Net sodium absorption was observed with control and coffee solutions with a mean absorption of 190 +/- 32 and 184 +/- 40 muEq per min per 30 cm, respectively. Net sodium secretion of 334 +/- 25 muEq er min per 30 cm was observed during caffeine perfusion (P less than 0.02). We conclude that coffee perfusion has no significant effect on sodium and water transport in the jejunum in spite of the marked secretory effects of caffeine solutions. The results of this study yield further support to the suggestion that the effects of caffeine may not be similar to the effects of caffeine-containing compounds such as coffee.

To determine the site of endogenous release of gastric inhibitory polypeptide (GIP), glucose perfusions (556 mmoles per liter) of duodenum, proximal jejunum, midjejunum, and ileum were performed in human volunteers using an occluding balloon perfusion technique. Preperfusion GIP concentrations were below assay sensitivity (125 pg per ml) in all subjects. After glucose perfusion, maximal serum GIP concentrations for the four groups were: duodenum, 1383 +/- 152 pg per ml; proximal jejunum, 904 +/- 87 pg per ml; midjejunum, 545 +/- 91 pg per ml, and ileum 305 +/- 38 pg per ml. Integrated GIP secretion was significantly greater with duodenal perfusion (111 +/- 21 ng-min ml-1) d proximal jejunal perfusion (69 +/- 5 ng-min ml-1), as compared to either midjejunal (47 +/- 7 ng-min ml-1) or ileal (25 +/- 6 ng-min ml-1) perfusions. Peak serum insulin concentrations and integrated insulin secretion were also significantly greater with perfusion of the duodenum or proximal jejunum. Serum glucose concentrations, integrated serum glucose, and glucose absorption were similar for the four areas perfused. The results of this study indicate that the proximal small intestine is the primary site of endogenous GIP release in man, but that smaller quantities are also released by the distal small bowel.

Hyphae of many fungi drive electric currents through themselves. In Achlya bisexualis the current is carried by protons which enter the apical region by symport with amino acids and are expelled distally. The proton current may play a role in the spatial localization of apical growth.

A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.

We have measured the biliary excretion of 3H-digoxin in normal subjects by intestinal perfusion methods which impose minimal interruption of the enterohepatic circulation. In contrast to data obtained in patients with liver disease and postoperative patients with biliary fistulas, our data show that about 30% of an intravenous dose of 3H-digoxin reaches the digestive tract in 24 hr. Most of the excreted radioactivity is chloroform-soluble and presumably reabsorbably and most of this fraction is probably biologically active drug. The results suggest that (1) consideration of hepatobiliary function may be relevant in observations regarding digoxin pharmacokinetics and that this route may be exploited in trials of therapy designed to shorten the duration of digoxin intoxication.

Visual analysis of the severity of coronary stenosis is limited by observer variability. However, more complex techniques of proved accuracy are tedious and costly. Therefore, a new digital electronic caliper (DEC) was evaluated as a potentially more accurate, rapid and less costly alternative for measuring stenosis severity. Stenosis minimum diameter (Dmin) and percent diameter reduction (% S) were measured from the screen of the cine projector using a DEC. These measurements were compared with visual estimates (VIS) by 4 experienced angiographers and with measurements made by a computer-assisted method (QCA) of proved accuracy. In routine cineangiograms from 7 patients, 10 lesions were significant (greater than 50% S) and 8 were mild (less than 50% S). Variability, the standard deviation of multiple estimates of Dmin and % S, averaged 0.09 mm and 3.1% for QCA; 0.18 mm and 5.9% for DEC; and 0.26 mm and 7.4% for VIS. Compared with QCA, the visual determination of % S significantly underestimates (-5%; p less than 0.02) mild and overestimates (+11%; p less than 0.002) significant stenosis. VIS underestimates Dmin in significant lesions by 20% (p less than 0.04). In contrast, the mean error for DEC measurement of Dmin and % S was not significantly different from 0 in either lesion group. For the entire group of lesions, and particularly in significant lesions, the mean error for measurement of these 2 indexes of disease was significantly less with DEC than with VIS. Thus, variability and error with DEC are acceptably low for clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four depressed patients with heart disease were treated for four weeks in a double-blind trial of imipramine, doxepin, or placebo to assess the effects of tricyclic antidepressants on ventricular function and rhythm. The tricyclic antidepressants had no effect on left ventricular ejection fraction at rest or during maximal exercise, as measured by radionuclide ventriculograms obtained before and after treatment. Premature ventricular contractions were reduced by imipramine but were not consistently changed by doxepin or placebo. Treatment with imipramine and doxepin, but not placebo, was associated with significant improvement (P less than 0.001) in standard ratings of depression. Our findings underscore the need for a reappraisal of the cardiovascular risks of tricyclic antidepressants and suggest that in the absence of severe impairment of myocardial performance, depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or hemodynamic function.

Neuronal function depends crucially on the spatial segregation of specific membrane proteins, particularly the segregation associated with sites of synaptic contact. Understanding the factors governing this localization of proteins is a major goal of cellular neurobiology. A conspicuous example of synaptic specialization is the almost exclusive localization of vertebrate skeletal muscle acetylcholine (ACh) receptors to the subsynaptic membrane of the neuromuscular junction (for example, refs 1,2). The localization of other membrane proteins in skeletal muscle has been much less studied, but a knowledge of their distribution is crucial for understanding the factors governing regional specialization. We have explored the distribution in muscle of the voltage-gated Na channel responsible for the action potential using the loose patch-clamp technique, and have measured Na currents in 5-10 micron-diameter membrane patches as a function of distance from the end plate region of snake and rat muscle fibres. Here we report that the Na current density immediately adjacent to the endplate is 5-10-fold higher than at regions away from the endplate. The increased Na current density falls off rapidly with distance, reaching the background level 100-200 micron from the endplate. Although one might expect ACh receptors to be concentrated near the region of ACh release, such a concentration for Na channels, which propagate the impulse throughout the length of the cell, is surprising and suggests that factors similar to those responsible for concentrating ACh receptors at the endplate also operate to concentrate Na channels.

Left ventricular angiography frequently produces one or more premature atrial or ventricular contractions which may make quantitative volume analysis unreliable. Three hundred left ventricular power injections were analyzed and found to produce premature ventricular contractions (PVC's) in 28 per cent of injections and PAC's in 6 per cent. Forty-four per cent of injections starting near the end of the T wave were associated with PVC's, whereas those starting near the end of diastole during the P wave produced PVC's in only 11 per cent. Injections through a Gensini catheter were associated with PVC's in 24 per cent compared to 37 per cent when a pigtail catheter was used (p less than 0.05). The introduction of an 0.6 second delay in the development of peak injection pressures and ECG triggering to start the injection in the last half of the cardiac cycle did not alter the incidence of PVC's. The use of timed diastolic injections with pressure rate-rise delay is of little value in reducing injection induced arrhythmias.

Thirty-six patients with prior myocardial infarction, and 14 patients without, had myocardial imaging at rest using both seven-pinhole emission tomography and planar imaging with thallium-201. The sensitivity and specificity of the two approaches for the detection of prior myocardial infarction were compared. Qualitatively, planar imaging yielded sensitivities of 69% (25 of 36) and 80% (29 of 36) with Polaroid and video display formats, respectively. A semiquantitative analysis gave a sensitivity of 75% (27 of 36). Specificities for these three planar approaches were, respectively, 100% (14 of 14), 93% (13 of 14), and 71% (10 of 14) for the Polaroid, video, and semiquantitative analyses. Seven-pinhole tomography had a sensitivity of 83% (30 of 36) by qualitative or visual inspection and 86% (31 of 36) by semiquantitative analysis. Specificities by these two techniques were 71% (10 of 14) and 57% (8 of 14). There were no statistically significant differences in either sensitivity or specificity between the planar and tomographic approaches. Repeat seven-pinhole images were identical in 95% (46 of 48) of patients, showing that reproducibility was satisfactory. We conclude that the seven-pinhole tomographic approach has no advantage over standard planar imaging in the detection of prior myocardial infarction.

The 2-nitroimidazole fluoromisonidazole is metabolically trapped in viable hypoxic cells in inverse proportion to PO2. This attribute suggests that [18F]fluoromisonidazole may be useful for imaging hypoxic tissue using positron emission tomography. To examine this potential, we studied the pharmacokinetics and biodistribution of [3H]fluoromisonidazole in six open chest dogs. In two normal dogs, plasma and urine samples were collected over a 4-hr period following i.v. injection of the drug. In four animals, regional myocardial ischemia was produced 2 hr prior to drug injection by occlusion of the circumflex coronary artery and maintained during the 4-hr sampling period. In all animals, postmortem samples of myocardium and other organs were obtained and tissue, plasma, and urine tritium activity were determined by liquid scintillation counting. In areas of reduced flow, [3H]fluoromisonidazole accumulated in myocardium in inverse proportion to myocardial blood flow measured by microspheres, indicating enhanced binding in hypoxic tissues. Maximum tissue concentrations in ischemic myocardium were two- to three-fold greater than in normal myocardium and plasma. Plasma clearance data indicate the drug is rapidly distributed into the total-body water, clears from the body with a half-life of 275 +/- 50 min, and undergoes minimal metabolism by 4 hr. We conclude [18F]fluoromisonidazole may be a suitable agent for radionuclide imaging of hypoxic myocardium.

Three cases of esophageal intramural pseudodiverticulosis (EIP) are described and the literature reviewed. We conclude that EIP is an inflammatory disease of unknown etiology characterized by dilatation of the esophageal submucosal glandular elements. The classic radiographic picture which is that of collar-button-shaped outpouchings projecting in a perpendicular fashion from the luminal surface is mainly related to dilatation in the glandular ductal system. It is usually diagnosed in the sixth and seventh decades, but all ages may be affected. Dysphagia is a very common but not universal symptom of the disease process. Approximately one third of these patients have diabetes mellitus. Strictures of the esophagus are frequently seen, and varying degrees of esophagitis may be manifest endoscopically. Esophageal motility disturbances are common and may be severe. Candida infestation with and without tissue invasion has been seen in a number of patients and should be searched for in all cases of EIP.

Clinically apparent pancreatic disease due to sarcoidosis has not been described in typical sarcoid patients. A few cases have been described at exploratory laparotomy and pancreatic involvement in autopsied cases is more common than generally appreciated. We report a patient not previously known to have sarcoidosis whose presentation with pruritus, eosinophilia and cholestatic serum chemistry suggested a reaction to phenothiazines. The correct diagnosis was made during surgery for an asymptomatic gallstone. No other evidence of pancreatic disease has become apparent during follow-ups of two years.

Secretion of tritium-labeled digoxin was studied in rats using noneverted gut sacs, in ligated and perfused intestinal preparations in bile duct ligated rats, and by measuring 4 day fecal excretion of total radioactivity in bile duct ligated rats. Serosal to mucosal transfer was proportional to substrate concentration in vitro. In ligated intestinal loops radioactivity was concentrated in the lumen relative to serum. In perfused intestinal preparations the fraction of dose increased with time and was similar over a 100-fold range of doses. Bile duct ligated rats excreted 13.4 +/- 5.8 (S.D.) % of parenterally administered label in 4 day stool collections. Bile duct ligated rats treated with p.o. activated charcoal excreted significantly more radioactivity (33.4 +/- 7.9%). The results suggest that net nonbiliary intestinal secretion of digoxin and metabolites can be augmented by intraluminal binding. A role for this phenomenon in accounting for some effects of diseases and drug interactions is suggested.

The diagnostic value of determining total conjugated serum bile acid (SBA) concentrations was evaluated in fasting dogs with spontaneous liver disease. Conjugated primary SBA values were determined by radioimmunoassay in 12 healthy dogs, 64 dogs with hepatobiliary disease, and 9 dogs with intestinal disorders unassociated with clinical or biochemical evidence of liver disease. Reference values for SBA concentrations ranged from 0 to 5 mumol/L and were not significantly different from those determined in dogs with intestinal disease (P less than 0.05). Mean SBA concentrations determined in dogs with portosystemic shunts, glucocorticoid-induced hepatopathy, hepatic neoplasia, hepatitis, cholestasis, and cirrhosis were significantly greater than reference values (P less than 0.05). The mean SBA concentration in dogs with glucocorticoid-induced hepatopathy was significantly (P less than 0.05) lower than that in all other clinical groups of dogs with liver disease, except in dogs with cholestasis. Although these 2 groups were statistically indistinguishable, dogs with glucocorticoid-induced hepatopathy generally had lower SBA values (2 to 37 mumol/L) than did the group with cholestasis (2 to 562 mumol/L). The SBA concentrations in fasting dogs were weakly correlated with histologic evidence of hepatic damage, as determined by a total biopsy score (r = 0.28, P less than 0.02). Because total SBA concentrations were increased in 89% of all dogs with hepatobiliary disease, the determination of SBA appears to be a sensitive test of hepatic dysfunction.

Seven-pinhole emission tomography has been studied under conditions that simulate clinical myocardial imaging with thallium-201, and is compared with planar imaging with a heart phantom. The seven-pinhole technique produces reconstructed images that offer a tomographic presentation of the object but do not quantitatively represent true cross sections of the object's activity distribution. Tomography produces significantly greater image contrast than planar imaging, even when maximal background subtraction is used to enhance the planar images. Two quantitative limitations of seven-pinhole tomography are noted for a simulated 24-g, 1.5-cm-thick complete transmural infarct: (a) the defect's activity concentration is not accurately reconstructed, and (b) it propagates longitudinally into some reconstructed planes that do not contain it. The imaging limitations of seven-pinhole tomography under the conditions studied are shown to be consistent on several camera/computer/software configurations.

To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2). Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p less than 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 +/- 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 +/- 5, akinesia = 11 +/- 7 and dyskinesia = 18 +/- 5, all p less than 0.01 versus normal. Among regions with normal wall motion, only 3% had a perfusion defect score greater than or equal to 10. Conversely, among 68 regions with a large (greater than or equal to 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction. In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Forty-one patients with chest pain and suspected coronary artery disease underwent thallium-201 myocardial imaging, performed immediately following maximal treadmill exercise, also at "redistribution" 4--5 hr after exercise, and at rest 1 wk later. All had coronary angiography. All images in seven patients without coronary artery disease were normal. Twenty-seven of the 34 (79%) patients with coronary artery disease had new, exercise-induced image defects. The redistribution and rest images were identical in 15/27 (56%) patients (complete redistribution). In 10/27 (37%) patients with exercise-induced defects, some redistribution occurred but defect size on the redistribution image was larger than that on the rest images (incomplete redistribution). In 2/27 (7%) of patients with exercise-induced defects, redistribution was absent. The presence of prior myocardial infarction, regional abnormalities of left-ventricular contraction or the severity of coronary stenoses did not correlate with the presence or absence of redistribution. Overall image quality between the two studies was similar, although image collection times for the redistribution study were prolonged. We conclude that some redistribution (complete or incomplete) occurs in most patients with exercise-induced image defects. When both fixed and reversible perfusion defects are present, defect size was often larger in the redistribution image and may thus overestimate the extent of prior myocardial infarction.

We examined the effect of 150 ml of caffeinated instant coffee at two pHs, 4.5 and 7.0, on lower esophageal sphincter pressure in 20 normal volunteers and 16 patients with reflux esophagitis. When ingested alone coffee at pH 4.5 and 7.0 caused a decrease in basal sphincter pressure in normal volunteers from 19.4 +/- 1.5 to 13.7 +/- 1.0 mmHg (P ¿ 0.01) and from 18.7 +/- 1.5 to 16.0 +/- 0.8 mmHg (P < 0.05) respectively. When coffee at pH 4.5 was drunk with a mixed nutrient test meal, the resting sphincter pressure in normal subjects fell after 30-60 min with the nadir, 11.2 +/- 1.0 mmHg, being recorded at 60 min (P < 0.01). Coffee at pH 7.0 with the test meal resulted in a fall in pressure to 14.3 +/- 1.5 mmHg (P < 0.02) at 60 min. In patients with reflux esophagitis, coffee at pH 4.5 lowered lower esophageal sphincter pressure from 9.1 +/- 1.0 to 5.5 +/- 0.6 mmHg (P < 0.005); coffee at pH 7.0 decreased lower esophageal sphincter pressure from 8.5 +/- 1.1 to 6.9 +/- 0.7 mmHg (P < 0.05). In these patients, mean basal pressure, 9.2 +/- 0.8 mmHg, decreased to 5.2 +/- 0.7 mmHg (P < 0.001) 45 min after drinking coffee at pH 4.5 with the test meal. Coffee at the neutral pH caused a fall in pressure from 8.8 +/- 1.1 to 6.5 +/- 0.7 mmHg at 60 min after the test meal. Thus, coffee at either pH 4.5 or 7.0 caused a decrease in fasting and postcibal lower esophageal sphincter pressure in normal volunteers and patients with reflux esophagitis. The magnitude and the duration of the effect were greater after coffee at the lower pH. These data support the clinical belief that coffee may cause or aggravate heartburn by decreasing lower esophageal sphincter pressure.

Basal gastrin and acid secretion, and histamine- and food-stimulated acid secretion were examined before and after 6 weeks of regular antacid consumption by 20 normal volunteers, in order to test the hypothesis that regular use of antacids produces gastrin cell hyperplasia, altered gastrin inhibition by acid, and gastric hypersecretion. We found no differences in fasting serum gastrin, basal or maximal histamine-stimulated acid, or acid output in response to a protein meal after consumption of commercial antacids with or without calcium carbonate. The results suggest that normal subjects do not acquire functional hyperactivity of the gastrin mechanism after a period of regular antacid use.

The projections of the retina in Necturus maculosus were studied by injecting radioactive proline into one eye. Labeling was seen in both the contralateral and ipsilateral diencephalon and tectum. The contralateral fibers are divided into three major tracts: the marginal, axial, and basal. The ipsilateral fibers separate into a marginal and an axial optic tract. The contralateral and ipsilateral axial optic tracts have a similar distribution. The contralateral and ipsilateral marginal optic tracts projecting to the diencephalon also have a similar distribution. However, in the tectum the ipsilateral marginal optic tract ends in the anterior third while the contralateral extends almost the entire length of the tectum. The retinotectal ipsilateral projection ends in clumps as has been described in other vetebrates. A direct ipsilateral retinotectal projection has not been described in any other amphibian.

Previous studies have demonstrated that considerable amounts of parenterally administered cardiac glycosides are excreted in the bile and reabsorbed across the intestinal mucosa in several species. It is currently believed that the more prolonged action of nonpolar digitalis glycosides is due to their retention and recycling in the enterohepatic circulation. This report describes studies carried out to evaluate the effects of pharmacologic interruption of this enterohepatic cycle with the intraluminal sequestering agent cholestyramine. Cholestyramine was found to bind substantial quantities of digitoxin-(3)H and digoxin-(3)H in vitro and this binding was only modestly inhibited by the presence of bile. Administration of cholestyramine to rats by intragastric catheter before the subcutaneous injection of the LD(100) dose of digitoxin (10 mg/kg) resulted in a 70% survival rate. Further, oral administration of cholestyramine to rats before the subcutaneous injection of digitoxin-(3)H resulted in accelerated fecal excretion of radioactivity and lower levels of digitoxin-(3)H and metabolites in brain tissue compared to controls. Similarly, pretreatment of guinea pigs with cholestyramine orally before the injection of digitoxin in dosages of 10.0 and 4.0 mg/kg resulted in a 25 and 70% survival rate respectively as compared to survival rates of 0 and 30% in control animals. Cholestyramine pretreatment of guinea pigs was also accompanied by lower levels of digitoxin-(3)H and metabolites in heart and liver 90 min after injection of digitoxin-(3)H. Cholestyramine therapy did not result in significant changes in serum potassium levels excluding the possibility that drug-induced hyperkalemia might have affected the cardiac uptake of digitoxin. The data obtained in this study indicate that cholestyramine treatment affords a significant degree of protection against lethal digitoxin intoxication in rats and guinea pigs. It is suggested that cholestyramine binds appreciable amounts of digitoxin in the intestinal lumen resulting in reduced reabsorption, increased fecal excretion, and lower tissue levels of glycoside in critical organs. The protective effects of cholestyramine appear to be mediated by interruption of the enterohepatic circulation of digitoxin.

Previous studies of digitalis glycoside metabolism and excretion have indicated that these compounds undergo a significant enterohepatic cycle in some species. It has been suggested that the existence of such a cycle in man contributes to the prolonged action of certain cardiac glycosides. Previous studies have demonstrated that cholestyramine binds digitoxin and digoxin in vitro and accelerates the metabolic disposition of digitoxin in rats and guinea pigs, presumably by interrupting the enterohepatic circulation. In order to assess the role of the enterohepatic circulation in the metabolism of digitalis glycosides in humans, maintenance doses of cholestyramine were administered to 7 of 15 normal human subjects beginning 8 hr after digitalization with 1.2 mg of digitoxin-(3)H. All subjects had frequent measurements of serum radioactivity, left ventricular ejection time (LVET), and electromechanical systole (QS(2)), the latter recorded as the interval from onset of Q wave to first major component of second heart sound. Measurement of the LVET and QS(2) intervals affords a sensitive index of the cardiac response to digitalis. In addition, chloroform extraction of serum was performed to separate unchanged digitoxin and active metabolites from cardioinactive metabolites of digitoxin. Cholestyramine treatment resulted in reduction in half-life to total serum radioactivity from 11.5 to 6.6 days, and in chloroform-extractable radioactivity from 6.0 to 4.5 days, as compared to controls. In addition, cholestyramine treatment was accompanied by more rapid return to base line values of digitoxin-induced changes in the LVET and QS(2) intervals. A significant positive correlation was found between QS(2) values and chloroform-extractable radioactivity, the latter reflecting unchanged digitoxin-H(3) (r=0.64; P=<0.01). The results indicate that administration of cholestyramine to digitalized human subjects accelerates the metabolic disposition of digitoxin and abbreviates the physiologic response to the glycoside. This effect is presumably mediated by interruption of the enterohepatic circulation of digitoxin by cholestyramine.