The analysis of factors influencing the success of diagnosing salpingemphraxis by x-ray hysterosalpingography.

OBJECTIVE: The factors influencing the diagnosing of salpingemphraxis by X-ray hysterosalpingography (HSG) are identified and summarized, to provide a reference for improving the precision of the diagnosis procedure. PATIENTS AND METHODS: In order to analyze the collected data, the methods of stratified sampling and retrospective analysis were adopted. Two county-level medical units, two medical units in prefecture-level cities and two provincial medical units in our province were chosen. Patients were selected from a group of women diagnosed with infertility and probable salpingemphraxis who were admitted to a hospital for further studies between February 2010 and January 2015. From those, 3 individual cases were selected in each month summing up to a total of 1,080 cases. Surgical processes and results were analyzed to identify the determining factors that lead to a precise diagnosis. RESULTS: The success rate of the surgical procedures had nothing to do with the trauma level of hospitals, instead it is positively correlated with the period of sampling (p < 0.05). The precision of surgeries correlates with the age group of the patients, the selection time bracket of samples, the types of contrast agents used, the location of the salpinx, whether anticholinergic agents are used before operations, the depth of catheter with double-cavity saccule, and the procedures for injecting contrast agents (p < 0.05). On the other hand, the precision of the surgeries has nothing to do with the level of hospitals, the types of X-ray machines used or the types of salpingemphraxis. Through multi-factor regression analysis, it can be seen that the selection time period of samples, the location of the salpinx, whether anticholinergic agents are used before operations, the depth of catheter with double-cavity saccule and the procedures for injecting contrast agents are independent risk factors that determine the precision of the procedure (p < 0.05). CONCLUSIONS: Clinical factors that seem to influence the precision of HSG are proposed based on analysis of a large sample in a small area using a stratified sampling method.

Prospective, randomized, single-blind, sham treatment-controlled study of the safety and efficacy of an electromagnetic field device for the treatment of chronic low back pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of therapeutic electromagnetic fields (TEMF) on chronic low back pain. Secondary objectives included the investigation of the effects of TEMF on psychometric measures. SETTING: Pain Research center in an Urban Academic Rehabilitation Facility. DESIGN: Prospective, randomized, single-blind, placebo (sham) treatment-controlled design in which participants were evaluated over a 6-week period. A total of 40 subjects were randomly assigned: 20 subjects to 15 milliTESLA (mT) treatment using a prototype electromagnetic field device and 20 to sham treatment. INTERVENTIONS: After a 2-week baseline period, eligible individuals were randomized to one of the treatment groups (sham or 15 mT) for six 30-minute treatments over 2 weeks, then a 2-week follow-up period. OUTCOME MEASURES: The primary outcome measure was the self-report of pain severity using a 100 mm visual analog scale collected using a twice daily McGill Pain Questionnaire-Short Form. Several secondary measures were assessed. RESULTS: Both groups (15 mT and sham) improved over time (P < 0.05). Although groups were similar during the treatment period, treated subjects (TEMF of 15 mT) improved significantly over sham treatment during the 2-week follow-up period (20.5% reduction in pain; F(1,34) = 10.62, P = 0.003). There were no reported serious adverse events. CONCLUSIONS: This study demonstrates that TEMF may be an effective and safe modality for the treatment of chronic low back pain disorders. More studies are needed to test this hypothesis.

Multisystemic, eosinophilic, epitheliotropic disease with intestinal lymphosarcoma in a horse.

Multisystemic, eosinophilic, epitheliotropic disease and intestinal lymphosarcoma were diagnosed in a Paso Fino mare that presented with anorexia and weight loss. The stomach, ileum, cecum, colon, pancreas, and lungs were infiltrated by large numbers of eosinophils forming prominent eosinophilic granulomas, as well as lymphocytes and plasma cells. Two jejunal masses composed of solid sheets of neoplastic lymphocytes were present. In contrast to the regions of inflammation, the infiltrates in these masses did not contain plasma cells, eosinophils, and eosinophilic granulomas. Immunohistochemically, the neoplastic lymphocytes expressed CD3 but not CD20 or kappa and lambda light chains, supporting a diagnosis of T-cell lymphosarcoma. Concurrent diagnoses of hypereosinophilic syndrome and lymphosarcoma in this horse and several humans suggest that the multisystemic eosinophilic and lymphoplasmacytic infiltrates were caused by the clonal proliferation of T-lymphocytes that secreted interleukin-5 triggering differentiation and activation of eosinophils.

Fluorescence imaging of reactive oxygen metabolites generated in single macrophage cells (NR8383) upon phagocytosis of natural zeolite (erionite) fibers.

In this paper we address the phenomenon of reactive oxygen metabolite generation subsequent to phagocytosis of mineral fibers by macrophages. Natural erionite fibers were chosen because of their established toxicity. Macrophages (cell line NR8383) were loaded with the dye 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate and exposed to erionite particles by centrifuging cells and fibers together to effect adherence. Reactive oxygen metabolite generation was examined by monitoring the fluorescence of oxidized dye formed via the reaction with oxygen species produced during phagocytosis. Individual cells were repeatedly scanned for up to 2 hr to monitor the evolution of this fluorescence. It was found that erionite-exposed cells had a mean total fluorescence of three times that of controls during the first 35 min, declining to two times that of controls at 35-60 min and about the same level as that of controls at 60-80 min. Ultrastructural studies of similarly treated aliquots of cells showed marked variation in size and numbers of the phagocytized particles. This study demonstrates that intracellular oxidation can be monitored on a single cell basis over a period of time. Quantitative studies are in progress to establish the relationship between the phagocytized particulate load and the extent of fluorescence.

Multifocal polyostotic aneurysmal bone cysts in a llama.

A 3.3-year-old 125-kg castrated male llama was evaluated because of acute non-weight-bearing lameness on the left hind limb. Physical examination revealed crepitus in the midportion of the femur. On radiographs, a comminuted middiaphyseal fracture was seen. There was also a region of bone lysis with cortical thinning and expansion in the distal metaphysis and epiphysis of the left femur. Multiple small circular lesions were observed in the proximal metaphysis of the left femur, and the proximal portion of the left tibia appeared irregular. The owner elected to pursue treatment, and the fracture was repaired with 2 compression plates. Multiple bone biopsy specimens were obtained and submitted for bacterial culture and histologic examination. Cultures yielded neither bacteria nor fungi. Histologic examination revealed fibrous connective tissue, normal appearing cortical bone, and an absence of medullary structures. The llama was maintained in a hind-limb sling for 14 days after surgery, at which time follow-up radiography revealed a comminuted fracture of the proximal portion of the femur. The llama was euthanatized, and multifocal polyostotic aneurysmal bone cysts were found in the proximal and distal metaphyses of the left femur and tibia. Cysts were lined by fibroblasts or endothelial-like cells.

In vitro interaction of zeolite fibers with individual cells (macrophages NR8383): measurement of intracellular oxidative burst.

Inhalation of fibrous minerals such as asbestos and erionite can cause various lung diseases, including cancer. The mechanism by which these fibers induce disease is an area of active research. Interaction of fibers with lung macrophages leads to release of many substances. Among these, reactive oxygen metabolites (which include hydrogen peroxide, superoxide, and possibly hydroxyl radicals) are proposed to cause cellular damage. In this paper, we report a method for observing intracellular hydrogen peroxide release as rat lung-derived macrophages (NR-8383) phagocytize erionite fibers. This is possible by observing the fluorescence of 2',7'-dichlorofluorescein-the intracellular, oxidized form of 5 (and 6)-carboxy-2', 7'-dichlorodihydrofluorescin formed in the presence of newly released hydrogen peroxide. We are able to image the fluorescence within a single cell, thereby allowing us to get information on the spatial distribution of the metabolites.

Cisapride for gastroesophageal reflux disease: a placebo-controlled, double-blind study.

OBJECTIVES: To evaluate the safety and efficacy of cisapride in patients with gastroesophageal reflux disease. METHODS: Patients (N = 177) were randomized to double-blind treatment with cisapride (10 or 20 mg q.i.d.) or placebo for 12 wk. Efficacy was determined by pre- and poststudy endoscopies, symptom assessments by patient and physician, and Maalox consumption. Safety evaluations included vital signs, electrocardiograms, clinical laboratory tests, and reports of adverse events. RESULTS: Cisapride 10 mg significantly reduced daytime and nighttime heartburn at 4 wk compared with placebo. Cisapride 20 mg reduced both daytime and nighttime heartburn at 4, 8, and 12 wk, compared with placebo, and was also significantly superior to the 10-mg dose at 12 wk. The percent of patients with endoscopic healing was significantly higher with cisapride 20 mg than with placebo [healing: 51 vs 36% (p < or = 0.044)]. Maalox usage declined significantly with cisapride 20 mg compared with placebo. No clinically significant changes in safety variables occurred with cisapride. The most frequently reported adverse events in the cisapride group were diarrhea, headache, and sinusitis. CONCLUSIONS: Cisapride 10 and 20 mg q.i.d. were safe and well tolerated in a population of patients with mild-to-moderate gastroesophageal reflux disease. Both symptoms and endoscopic grade improved after 12 wk of treatment with cisapride 20 mg q.i.d.

Comparative effects of calcitriol and parathyroid hormone on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented diet.

Under normal circumstances, the body barriers effectively limit the entry and retention of dietary aluminum. However, both parathyroid hormone (PTH) and calcitriol (physiologically active hormonal form of vitamin D3) have been reported to produce elevation of serum aluminum in animals fed an aluminum-supplemented ration. To compare the effects of calcitriol with those of PTH with reference to their putative effect to enhance aluminum absorption, an experiment was designed wherein the serum levels of both PTH and calcitriol would be changing markedly during a short time-frame. To condition the rabbits used for this comparison, they were fed a vitamin D-free diet, which caused the level of calcitriol and its precursors to decline rapidly. The calcitriol deficit together with the ensuing lack of calcium absorption resulted in a state of secondary hyperparathyroidism. Vitamin D-depletion was shown to be complete by the high level of serum PTH and a low (unmeasurable) level of serum calcitriol. To enable comparison of PTH with calcitriol, exogenous calcitriol infusion (60 IU/day) was started by osmotic pump simultaneously with the beginning of an aluminum (aluminum lactate) supplemented diet. Aliquots were collected for both serum PTH and serum calcitriol at intervals during the 7 day study. A rising serum aluminum level was highly correlated with the rising serum calcitriol level in the rabbits (r = 0.903, p = 0.036) during the first 4 days of the infusion. The mean serum aluminum levels rose nearly 13 parts per billion (ppb) in the 7 day period. Declining serum PTH (due to feedback mechanisms of calcitriol suppressing PTH synthesis) showed a negative correlation of serum aluminum and serum PTH (r = -0.959, p = < 0.01) during the first 4 days of infusion. Control rabbits (vitamin-D depleted) fed aluminum-supplemented rations have shown only a minimal transient rise in serum aluminum level which returned to the pre-test level by the end of the week. To test for any effect of PTH on serum aluminum in the absence of calcitriol, five rabbits were implanted with osmotic pumps infusing PTH (mean 6.0 U/hr) and started on an aluminum supplemented diet. These rabbits, having previously been depleted of vitamin D were already in a state of nutritional secondary hyperparathyroidism as shown by their elevated pretest PTH levels. During the 7 day infusion, the serum aluminum rose only a mean of approximately 1 part per billion (ppb).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of calcitriol infusions on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented ration.

Three dosages of calcitriol (10, 30 and 60 IU/day) were given to rabbits by subcutaneously implanted osmotic pumps. The purpose was to compare the dosages with regard to their putative effect in elevating serum aluminum levels by mechanisms such as enhancing intestinal absorption, diminishing renal excretion, or others. To establish uniform levels of endogenous calcitriol and its precursors, all rabbits had been depleted of vitamin D. The depletion was demonstrated by their serum calcidiol and calcitriol levels declining to unmeasurable levels, following the regimen of a vitamin D-free diet. The 8 rabbits were then placed on an aluminum-supplemented (aluminum lactate) ration. The amount of feed (and aluminum) consumed was determined at daily intervals. Serum aluminum levels were determined at intervals during the 7 days on this regimen. In a second test, the same 8 rabbits received the same regimen but in addition were infused with 10, 30 or 60 IU calcitriol per day. It was found that the aluminum-fed rabbits receiving 60 IU/day and 30 IU/day calcitriol infusions showed statistically significantly elevated serum aluminum levels as compared to their levels without calcitriol (p = 0.0208 and p = 0.434, respectively). Rabbits receiving pumps delivering 10 IU/day while receiving the aluminum-supplemented ration showed no rise in serum aluminum with time or treatment during the 7 day study. Likewise rabbits receiving aluminum-supplemented rations without calcitriol showed only an early minimal rise in mean serum aluminum which returned to the pre-test level by the end of a week in spite of continued consumption of aluminum-supplemented rations.

Multivariate time series projections of parameterized age-specific fertility rates.

PIP: 1 solution to the dimensionality problem raised by projection of individual age-specific fertility rates is the use of parametric curves to approximate the annual age-specific rates and a multivariate time series model to forecast the curve parameters. Such a method reduces the number of time series to be modeled for women 14-45 years of age from 32 to 40 (the number of curve parameters). In addition, the curves force even longterm fertility projections to exhibit the same smooth distribution across age as historical data. The data base used to illustrate this approach was age-specific fertility rates for US white women in 1921-84. An important advantage of this model is that it permits investigation of the interactions among the total fertility rate, the mean age of childbearing, and the standard deviation of age at childbearing. In the analysis of this particular data base, the contemporaneous relationship between the mean and standard deviation of age at childbearing was the only significant relationship. The addition of bias forecasts to the forecast gamma curve improves forecast accuracy, especially 1-2 years ahead. The most recent US Census Bureau projections have combined a time series model with longterm projections based on demographic judgment. These official projections yielded a slightly higher ultimate mean age and slightly lower standard deviation than those resulting from the model described in this paper.^ieng

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

Serum calcitriol and parathyroid hormone levels following prolonged infusion of calcitriol in vitamin D replete and depleted rabbits.

The objectives of this study are (1) to determine if serum calcitriol levels resulting from calcitriol infusion by subcutaneously implanted osmotic pumps are in proportion to dose, (2) to determine if such serum levels remain steady during the "pump-life" and (3) to determine if these increased calcitriol levels have an effect on serum parathyroid hormone (PTH) levels. A general objective of the study is to define a model whereby agents (calcitriol, and parathyroid hormone) suspected of enhancing absorption of metals other than calcium from the gastrointestinal tract could be evaluated individually by the levels of these hormones present in serum at a series of intervals during calcitriol infusion by osmotic pump. Calcitriol was infused into rabbits by subcutaneously implanted osmotic pumps at 3 different dosages (30, 60, and 100 IU/day) for 7 days and one dose (60 IU/day) for a 28 day period. The serum calcitriol levels initially rose markedly in all experimental rabbits in proportion to infused dosage and peaked at 3 days. The quantitative relationship between infused calcitriol and serum calcitriol at 3-5 days showed a correlation coefficient of 0.977 (P less than 0.005) for rabbits receiving the 7 day pumps with the 3 different dosages. There was subsequent decline of serum calcitriol which continued for the remainder of the pump-life, suggesting acceleration of degradation mechanisms. There was a sharp reduction in serum parathyroid hormone (PTH) levels 3-5 days after starting the calcitriol infusion, which was interpreted to result from direct suppression of PTH synthesis by calcitriol and/or the feedback effect of enhanced intestinal calcium absorption. Rabbits which had been depleted of vitamin D prior to implantation of the 28 day osmotic pumps showed a similar pattern of serum calcitriol and PTH. Multiple analyses within a single rabbit showed a reciprocal relationship between the serum calcitriol and PTH during the 28 days. There was a statistically significant negative correlation between these parameters (r = 0.635, P less than 0.05). The data indicate that despite a constant rate of infusion of calcitriol by osmotic pump, the levels of serum calcitriol and parathyroid hormone do not remain constant, but rather undergo marked changes. These findings demonstrate the necessity of monitoring blood levels, even in studies in which animals receive a constant infusion of calcitriol.

Comparative demographic effects of Canadian-U.S. immigration flows.

"A joint study by Statistics Canada and the U.S. Bureau of the Census examines special tabulations of U.S. residents born in Canada from the 1980 census of the United States and compares them with matching tabulations of Canadian residents born in the United States from the 1981 census of Canada. As might be expected, the two populations are remarkably similar and the preponderance of the migration flow is from Canada to the United States. The comparative social and economic characteristics of the two migrant stocks show the effects of increasing legal restrictions on migration between the two countries in the last two decades. The characteristics of the migrant flows have changed from large, unregulated population movements responding to economic motivations similar to internal migration flows to a much smaller, highly controlled movement more typical of long-distance international migration flows." This is a revised version of a paper originally presented at the 1987 Annual Meeting of the Population Association of America.

Antiulcer agents. 3. Structure-activity-toxicity relationships of substituted imidazo[1,2-a]pyridines and a related imidazo[1,2-a]pyrazine.

Investigation of the interrelationship between structure, antiulcer activity, and toxicology screening data derived from a series of compounds selected from structure-activity studies directed toward identifying a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1), has identified 3-(cyanomethyl)-2,7-dimethyl-8-(phenylmethoxy)imidazo[1,2 -a]pyridine (5), 3-amino-2-methyl-8-(2-phenylethyl)imidazo[1,2-a]pyridine (6), and 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine (7). These analogues exhibit a combination of antisecretory and cytoprotective activity in animal models, while eliminating the adverse effects of the prototype 1. One of these, 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyrazine, Sch 32651 (7), has a profile meeting all criteria.

Bioavailability of three oral dosage forms of cisapride, a gastrointestinal stimulant agent.

Relative bioavailability of the investigational gastrointestinal stimulant agent cisapride after oral administration was determined in healthy men. Treatments administered were (A) two 5-mg tablets; (B) one 10-mg tablet; (C) 10 mL of a 1-mg/mL suspension; and (D) 10 mL of a 1-mg/mL aqueous reference solution. The study had a randomized four-way, crossover design; drug administration was followed by a standard breakfast. Plasma cisapride concentrations in blood samples drawn over 48 hours were measured by high-performance liquid chromatography. Individual and mean values for bioavailability parameters were subjected to analysis of variance followed by multiple comparison testing. Time to maximum concentration was shortest after administration of the solution. There was a significant difference in mean peak plasma concentrations between treatment A (48.8 +/- 12.8 ng/mL) and treatment D (41.6 +/- 10.6 ng/mL), with treatment A producing a 17.3% higher peak concentration. No significant differences between treatments were found for area under the plasma concentration-time curve. The overall mean elimination half-life was 7.01 hours. The results of the study indicate that the tablet and suspension dosage forms of cisapride are bioequivalent to the reference solution.

A survey of Census Bureau population projection methods.

"Population projections methods of the U.S. Census Bureau draw upon several different traditions of forecasting: demographic accounting, judgmental, time series, deterministic, and explanatory. This paper reviews each of the forecasting traditions in population projections, describes the U.S. Census Bureau's current methods for national and state population projections, and proposes new hybrid approaches such as demographic-time series methods for national fertility projections and economic-demographic methods for state migration projections. Throughout the article, possible parallels with forecasting in other disciplines are noted."

The Canada-United States joint immigration study: issues in data comparability.

PIP: The Canada-US immigration project is an attempt to assess carefully the flows, trends, and characteristics of immigrants between the 2 countries. The primary focus for data is the census information derived from the 1980 US and 1981 Canadian censuses. Some observations of the comparison follow. 1) US-born immigrants tend to migrate later. 2) Immigrants have an older age structure than the total population. 3) The sex ratio pattern is similar with older migrants having lower ratios. 4) Immigration of elderly/retired is not a common pattern. 5) Changes in regional destinations is a basic feature of immigration flows. The destination of US immigrants shifted over time from northern states to southern states. Destinations of Canadian immigrants shifted over time from Quebec and prairie provinces to Ontario and British Columbia. 6) A higher proportion of US immigrants ever married and were widowed; higher proportions of Canadian immigrants divorced, and lower proportions separated. These aspects reflect age structure. 7) US immigrants' fertility is similar to the US population in general; Canadian immigrants' fertility is similar to the Canadian population in general. 8) US immigrants born in Canada have a considerably higher attainment. 9) Males aged 16-64 among US immigrants born in Canada have a consistently higher labor force participation rate. 10) Professional specialty occupations increase in importance in the 1975-1980 period in both countries. 11) Incomes of recent immigrants who were full-time, year-round workers from Canada or the US were well above the incomes of the native populations of either country. Comparability had to be examined in light of the variations built into the 2 censuses. Some of these issues are: 1) differences in sampling and collection methods, 2) differences in under/over-enumeration, 3) misreporting of country of birth, 4) differences in questions used, 5) different editing and imputation procedures applied, 6) variations in residence rules, and 7) the exclusion or inclusion of certain groups in the national census counts.^ieng

Migration and the phases of population redistribution.

PIP: This paper describes a framework for major historical settlement patterns, the major stages of population redistribution that accompany such migration, and the other forms of migration that occur within a given settlement pattern. Using a top-down approach has the advantage of tying together a number of diverse types and patterns of migration from differing historical periods and geographic areas. This broad macro level framework is one in which the level of social and economic interaction increases with economic development. With increasing economic development comes the need for greater interaction through the exchange of goods and the establishment of commercial and administrative functions for society. Explanation of the changing trends in population redistribution requires a detailed look at the phases of population redistribution: 1) initial urbanization, 2) frontier expansion, 3) traditional urbanization, 4) overurbanization, 5) suburbanization, and 6) metropolitan and nonmetropolitan turnaround. Less massive migration movements occur within a given settlement pattern as adjustments are made in the population distribution to reflect the relative economic fortunes of competing subunits of the society. In addition, migration may occur with little or no population redistribution because the net migration cancels out a differential in natural increase between subunits, or because the gross in-migration and out-migration cancel out and produce close to zero net migration. Lastly, research on the current migration turnaround from metropolitan to nonmetropolitan areas, emphasizing the change in social interactions from face to face contact to a society in which a large portion of interactions can be performed at a distance, is suggested.^ieng

Gastric antisecretory and cytoprotective activities of SCH 28080.

SCH 28080 (2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile) is a novel antiulcer agent which has both antisecretory and cytoprotective activities. The antisecretory ED50 values in the pylorus-ligated rat were 3.7 mg/kg p.o. and 2.8 mg/kg i.p., being 7 and 10 times more potent than cimetidine, respectively. In dogs, SCH 28080 was effective in inhibiting acid secretion stimulated by histamine (ED50 of 0.09 mg/kg i.v. and 4.4 mg/kg p.o.), dimaprit, pentagastrin, insulin and feeding. The cytoprotective activity of SCH 28080 was demonstrated by inhibition of ethanol-induced gastric lesions in a dose-dependent manner in rats (ED50:3.0 mg/kg p.o.). SCH 28080 was active in similar dose ranges (1-10 mg/kg) by both p.o. and i.v. routes of administration. This gastric cytoprotective activity was not affected by indomethacin pretreatment. Furthermore, the gastric potential difference was effectively sustained by SCH 28080 (3, 10 and 30 mg/kg p.o.) after intragastric ethanol. SCH 28080 (1-30 mg/kg p.o.) also inhibited gastric ulcers provoked by aspirin, aspirin + acid, indomethacin and stress (cold-restraint) in rats. The data support the concept that it is possible to have combined antisecretory and cytoprotectant actions in a single molecule which is not a prostaglandin.