Relationship of plasma lipids to renal function and length of time on maintenance hemodialysis.

Significant hypertriglyceridemia, the most common lipid abnormality in renal failure, first occurs when the creatinine clearance falls to 50 ml/min. The prevalence of hypertriglyceridemia continues to rise as creatinine clearance falls further with the highest rate developing at a creatinine clearance less than 10 ml/min. Hypertriglyceridemia is correlated with plasma glucagon levels but not growth hormone or insulin. Plasma cholesterol values remain normal in the face of deteriorating renal function and show no correlation with any of the hormones measured. Although all three hormones became elevated as renal function diminished, none were directly correlated with glomerular filtration rate. There was a distinct decrease in the prevalence of hyperlipidemia after 5 years of maintenance hemodialysis therapy. Plasma growth hormone and glucagon through an effect on plasma triglyceride and plasma insulin by effecting plasma cholesterol may play a role in this decline of hyperlipidemia with duration of hemodialysis.


Effect of acetate administration on blood lipids.

An infusion of 180 mEq sodium acetate was given to nine dialysis patients and eight normal volunteers simulating the transfer of acetate that occurs during 30 min of rapid hemodialysis. While serum acetate concentrations had almost normalized 15 min after the end of infusion, there was no increase in serum cholesterol and triglyceride concentrations. In this short-term study, acetate does not appear to be a major contributing factor for the hyperlipidemia of dialysis patients.


Comparison of acetate-1-14C metabolism in uremic and nonuremic dogs.

Acetate-1-14C was infused into six anephric uremic and six anephric nonuremic dogs during a 4-hr hemodialysis against a standard acetate containing (39.5 mM) dialysis solution. Arterial acetate (nonradioactive) levels achieved a steady state by the end of dialysis indicating that the maximum rate of acetate metabolism had not been exceeded. The mean arterial acetate level at the end of dialysis was 2.6 mM in both groups of dogs. Acetate disappearance after the cessation of dialysis followed first order kinetics with a mean half-life of 3.8 +/- 0.5 min in the uremic and 3.7 +/- 0.5 min in the nonuremic dogs. Most of the infused acetate-1-14C was metabolized to 14CO2 within 8 hr after dialysis. An average of 84 and 71% of the infused acetate-1-14C was metabolized to 14CO2 in the uremic and nonuremic dogs, respectively. Small but significant amounts of radioactivity were incorporated into lipids of plasma and other tissues. Incorporation of radioactivity into total lipids of liver, omental fat, and sciatic nerve was significantly greater in the uremic as compared to the nonuremic dogs. Incorporation of radioactivity into total lipids of heart, aorta, and plasma was the same in both groups of dogs.


Reduction in hyperlipidemia in hemodialysis patients treated with charcoal and oxidized starch (oxystarch).

A combination of two oral sorbents, oxystarch 35 g/day plus activated charcoal 35 g/day, was administered to four patients undergoing maintenance hemodialysis during thrice weekly and once weekly treatments. Patients tolerated oxystarch and charcoal without complaint during the 4-week period of thrice weekly hemodialyses. All four patients became clinically uremic when hemodialyses were reduced to once weekly and only two patients were able to continue through the end of this 4-week period. Mean serum cholesterol concentration diminished significantly from 200 mg/dl during control periods to 140 mg/dl after each 4-week trial of sorbents (P less than 0.02). Hypertriglyceridemia (range 181 to 543 mg/dl) was corrected in three of four patients with triglyceride values falling to less than 150 mg/dl during ingestion of sorbents (P less than 0.05). Activated charcoal, which is inert as an intestinal nitrogen binding sorbent, may lower serum lipids by direct intragut binding of lipids and bile acids. The potential use of oral charcoal in long-term therapy to reduce hyperlipidemia and prevent vascular accidents due to atherosclerosis requires additional study.


Effect of vitamin D on growth in experimental uremia.

Acceleration of growth of uremic children after administration of vitamin D has been demonstrated by various authors. This has been attributed to healing of skeletal lesions. Clinical observations suggest that vitamin D has also an effect on food intake perhaps associated with improvement of vitality. This could be confirmed in an experimental study in which uremic rats (subtotal nephrectomy) with and without vitamin D supplementation were compared with sham-operated pair-fed control rats with and without vitamin D supplementation. In uremic animals supplemented with vitamin D, weight gain and growth were significantly greater than in uremic animals on the control diet. Both with and without vitamin D supplements, weight gain and growth rate were greater in sham-operated pair-fed control than in the corresponding uremic animals. Histological abnormalities in the growth zone of uremic rats were markedly reduced by vitamin D. Since food intake was greater in vitamin D-treated uremic animals than in nonvitamin D-treated uremic animals, the increase in growth rate under vitamin D cannot be attributed exclusively to the skeletal effects of vitamin D. This study demonstrates important extraskeletal actions of vitamin D which may be associated with or causally related to the improvement of growth.


Plasma pyridoxal-5'-phosphate levels and clinical correlations in chronic hemodialysis patients.

Plasma pyridoxal-5'-phosphate (PLP) was measured by a specific method in 45 stable, chronic hemodialysis patients and 13 normal adults. Despite oral pyridoxine supplements (1 to 5 mg/day) a majority (64%) of patients had low levels. The difference between normals (8.5 +/- 3.7 ng/ml) and dialysis patients (3.6 +/- 3.6 ng/ml) was significant at P less than 0.01. Plasma PLP appeared to decrease with increasing duration of time on dialysis therapy. In vivo clearance studies as well as pre- and postdialysis plasma levels indicated that PLP was not removed by the dialyzer. Mean plasma PLP levels were normal in patients with stable motor nerve conduction velocity and a low transfusion requirement and low in those with decreasing motor nerve conduction velocity or a high transfusion requirement but the difference between the means in each group was not statistically significant. High oral doses of pyridoxine (100 to 200 mg/day) but not low doses (1 to 5 mg/day) restored PLP levels to normal in a majority of patients after 2 weeks.


Zinc and the sodium pump in uremia.

A defect in sodium transport is known to exist in the leucocytes of uremic patients. Recent work has shown changes in cation flux rates associated with alterations of extracellular zinc concentration. As plasma zinc is known to be low in uremia, the possibility that this might be the cause of the defect in membrane transport was investigated. Plasma zinc was shown to be lower in uremic patients than in normal controls but this was not matched by alterations in leucocyte zinc content. Leucocytes from normal subjects and from patients with uremia have similar increases in the sodium efflux rate constant when exposed to elevated extracellular zinc concentrations. However, the abnormality in leucocyte sodium transport in uremia was not completely corrected by elevation of the extracellular zinc, when compared with normal cells in the same zinc concentrations. Although extracellular zinc is a factor that must be controlled in studies of cellular membrane transport, a low plasma zinc is not the explanation for the defect of sodium transport seen in uremia.


Hypogeusia and zinc depletion in chronic dialysis patients.

Dialysis patients generally have a poor appetite, do not enjoy eating, and complain of food, particularly protein, as being disagreeable. Twenty dialysis patients with the above symptoms were tested for taste acuity, serum zinc (Zn), Zn concentrations in hair samples (intracellular Zn), and daily caloric intake. A double-blind, cross-over study was instituted using a Zn supplement and a placebo. After supplementation with Zn, taste acuity markedly improved in 95% of patients and Zn concentrations in hair increased in 85% of patients. The patients' appetites were improved; the average caloric intake increased by 675 kcal/day, and intolerance to protein diminished. In addition 10 normal control subjects were studied pre- and post-Zn supplementation for fasting blood glucose, serum Zn levels, and hair Zn concentration. Side effects were noted, and these usually correlated with elevated serum Zn levels and were minimized or disappeared with decrease in dosage or cessation of therapy.


Amino acid content of erythrocytes in uremia.

The amino acid content of plasma and erythrocytes in patients with severe renal failure (serum creatinine less than 8 mg/100 ml) treated with selective low-protein diets, in patients on regular hemodialysis, and in a control group of healthy subjects were studied. Most amino acids in erythrocytes of the patients showed the same changes as in plasma with the exception of histidine, serine, and alanine. In spite of low histidine plasma levels, the erythrocytes level is increased as compared with healthy controls. In uremic patients the plasma serine was constantly reduced whereas the serine content of the erythrocytes did not differ from healthy controls. Alanine concentrations in the erythrocytes of uremic patients were increased in spite of normal alanine plasma levels. This finding may be due to the increased glycolytic ratio of red cells from uremic subjects delivering more pyruvate for transmination to alanine. In the control group the cysteine content of erythrocytes was decreased with a gradient between plasma and erythrocytes of 3.5:1. The same gradient could be observed in uremic patients in spite of the elevation in their plasma cysteine levels by a factor of 2.7 compared with controls. The low cysteine levels in erythrocytes may be due to loss of cysteine for glutathione synthesis in red cells. High glutathione levels in the erythrocytes of uremic patients support this hypothesis.


Dietary fiber sources for human studies.

Some precautions in choosing fiber materials for feeding studies are listed. A food grade wheat bran of defined composition is described.


Dietary fiber: analysis and food sources.

The sources of dietary fiber are reviewed and the chemistry of the various components discussed in relation to their possible physiological properties and their analytical measurement in foods and the diet as a whole. Complete fractionation of all the polysaccharide species would be a time-consuming exercise; nevertheless some characterization of dietary fiber seems essential to an understanding of any physiological role. The composition of the dietary fiber in a range of foodstuffs is presented, and the relative contributions of the major food groups to the intake of total dietary fiber is outlined.


Cellulose digesting bacteria from human feces.

Anaerobic, gram-negative, nonsporing rod-shaped bacteria that digest wet-ballmilled filter paper have been isolated in numbers of over 10(8) per gram wet weight of feces, about 0.3% of total viable bacteria, from feces of two humans. Significant numbers of cellulolytic bacteria were not detected in four other humans. One of the strains is a Bacteroides sp., which only slowly digests cellulose and produces succinate, acetate, and H2 in carbohydrate fermentation.


Fecal flora in different populations, with special reference to diet.

Although potent antimicrobial agents may effect rapid and significant changes in fecal microflora, changes in diet or dietary supplements usually produce modest changes by comparison. It may be, however, that even such minor changes may result in significant changes in metabolic activity, particularly in terms of production of possible carcinogens or cocarcinogens. It is clear that significant changes may occur in metabolic activity without major qualitative or quantitative changes in the fecal microflora. Other research that might help explain the epidemiological observations of the association between diet and colon cancer would be studies of the flora at different levels of the gastrointestinal tract (particularly the cecum and small bowel), studies of the mucosa-associated flora at different levels, and long-term dietary studies.


Dietary fibers: their definition and nutritional properties.

Fiber is a variable material with respect to its nutritional qualities depending upon its composition and physical properties. Biological properties possessed by one type of fiber might not be shared by another type. Separate methods are required to describe quantity, composition, and quality of fiber in foods. Fibers can be generally classified into three groups: vegetable fibers, which are highly fermentable with low indigestible residue; brans, which are less fermentable; and chemically purified fibers such as wood cellulose, which are relatively unfermentable. A class of soluble substances including pectins and gums may not be true fibers, but are considered part of the dietary fiber complex because of the similar effects they can elicit in the diet. A major need is the replacement of the crude fiber method, the present official method, which is seriously defective. Since crude fiber values are erratic and poorly related to the true fiber value of food, a second major need is the reanalysis of all foodstuffs by appropriate methods and the replacement of standard tables of food composition. Accomplishment of these purposes will require more support and promotion than is presently being received.


Fecal flora of volunteers on controlled diets.

Ten volunteers completed a 4-month diet series consisting of a control diet, a meatless diet, a high-beef diet, and the same control diet, each lasting 1 month. Fat and fiber contents were essentially the same in all four diets, but protein content was doubled during the high-beef diet. High-beef protein consumption had little effect on the composition of the intestinal flora of the volunteers. There were no significant differences detween the high-beef and meatless diets in total numbers of anaerobic, facultative, or aerobic organisms isolated, nor were there major differences in the counts of the individual genera and species of bacteria encountered. The data indicate that animal protein consumption has little effect on the fecal bacterial profile in humans. The possible influence of animal fat consumption on the metabolic activities of intestinal bacteria is discussed.


Bacterial ecology in the small intestine.

A modified intubation method allowed collection of samples of human small intestinal contents with no contamination from other intestinal sites and with no exposure to air. Use of the method has disclosed strains resembling Haemophilus as among the most abundant bacteria in the small intestine of some subjects. Stimulation by bile and rapid growth under conditions simulating the natural habitat suggest that it is well adapted to upper intestinal conditions.


Degradation of polysaccharides by intestinal bacterial enzymes.

Polysaccharides with structures resembling components of dietary fiber were fermented by a number of species of anaerobic bacteria from the human colon. Some strains also fermented glycoprotein mucins. The strains that fermented the widest range of polysaccharide substrates were in the two genera Bacteroides and Bifidobacterium. Polysaccharide degrading enzymes from several Bacteroides species have been studied, and in most cases the enzyme activities were cell bound rather than extracellular. In all cases, the polysaccharide degrading enzymes were inducible rather than constitutive. Thus the metabolic activity of the flora could be altered considerably by the amount and type of fiber in the diet, even though the composition of the flora itself remained unchanged. The products of enzyme action included monosaccharides and oligosaccharides of varying chain lengths.


Factors involved in colonization of the gut epithelial surface.

Some indigenous microbes form climax communities on gastrointestinal epithelial surfaces during succession in animals of many types. Most communities form in mucous layers on the surfaces, where some microbes in the communities may utilize the mucin as a source of carbon and energy. The mucous gel may also serve physically to stabilize the community. Some microbial types that colonize early during succession may serve, perhaps synergistically with dietary components, to lower the oxygen tension and oxidation-reduction potential so that oxygen-intolerant anaerobes can colonize the epithelial surfaces. Microbes in the communities may adhere to the epithelial surface; the mechanisms by which they adhere may depend upon a variety of factors, including the type of epithelium and the rate of flow of lumenal contents in the areas. Dietary fiber may influence the composition of these communities by providing nutrients for the microbes or altering their environmental conditions including peristaltic rate, mucous concentration and composition, and oxygen tension and oxidation-reduction potential.


Stability of human fecal flora.

Recent experimental studies show that neither increased dietary fiber nor its absence alters the numbers and major groups of fecal bacteria. Although the total number of bacteria per gram of feces remains constant, the daily fecal mass doubles with added dietary fiber and is halved in its absence. Thus, the total output of fecal bacteria is related to dietary fiber.


Fiber and the development of gastrointestinal function.

Dietary lipid represents a major calorie source for the developing infant, yet dietary lipid absorption is relatively inefficient by adult standard. Recent studies are presented, indicating that the developmentally related improvement in lipid absorption observed in the preterm and fullterm infant relate to the maintenance of an intact intraluminal phase and completion of the enterohepatic circulation for bile salts. Critical issues including the absorption of nonpolar vitamins, iron, and the type of dietary lipid are discussed. The possible influence of the introduction of dietary fiber to the food of the developing infant is examined, and areas for future investigation are discussed.


Dietary fiber, bowel habits, and colonic function.

Bowel habits have different characteristics, and frequency, amount, and consistency of stools should be recorded in any study, including those on the effects of dietary fiber. Several studies suggest that addition of fiber to the diet reduces long and prolongs short transit time and increases water content of the stool. Conflicting data are difficult to reconcile, and mechanisms remain unknown.


Physiological implications of microbial digestion in the large intestine of mammals: relation to dietary factors.

The rate of digesta marker passage through the large intestine of the dog, pig, and pony correlated with the relative length and degree of sacculation of the colon. Volatile fatty acids (VFA), the end products of microbial digestion of all forms of carbohydrate, were the major anions present in large intestinal contents of all three species. Total VFA concentration was little affected by the feeding of high-versus low-fiber diets. VFA were rapidly transported across colonic mucosa of all three species. Results of comparative studies indicate that production and absorption of VFA are important to the nutrition of some mammals and to the normal secretory and absorptive functions of the large intestine of most mammals.


Effect of dietary fiber on intestinal gas production and small bowel transit time in man.

The influence of dietary fiber on intestinal gas production and on small bowel transit time was studied in eight healthy subjects using breath H2 excretion as an indicator of colonic gas production. Hydrogen excretion following ingestion of bran was substantially less than that following ingestion of lactulose, a nonabsorbable fermentable sugar. Likewise, human fecal homogenates produced only about 10% as much H2 and CO2 during incubation with bran as with glucose or lactulose. Thus, the polysaccharides in bran appear to be relatively poor substrate for colonic bacterial gas production, and reported gas-related symptoms after bran ingestion may be due to some other mechanism. The small bowel transit time of bran was greater than that of lactulose; however, addition of bran to lactulose did not slow lactulose transit.


Influence of dietary fiber on trace element balance.

Five adult male volunteers were fed a diet containing (as percent of calories) 16% protein, 40% fat, and 44% carbohydrate, a diet similar to that consumed by many American males. Twenty-six grams of soft white wheat bran or corn bran were added to the daily bread, and the effects on zinc, iron, and copper balance were assessed during the last 12 days of each 30-day study period. The soft white wheat bran appeared to decrease retention of zinc in four subjects but not significantly so. Iron retention was similar in all three treatments. Copper balance was improved by addition of soft white wheat bran and to a lesser degree by corn bran. An apparent copper requirement of 1.28 mg/day for the volunteers was calculated by regression analysis.


Modification of stool content by increased bran intake.

Six healthy subjects, four males and two females, were studied for 8 weeks with daily dietary history, 72-hr weekly stool collections, and analysis of stool specimens for fecal weight, water, pH, and total aerobic and anaerobic qualitative and quantitative bacteria. Subjects were studied first for a 3-week control period, followed by 3 weeks of 5.4 g of crude fiber supplementation daily (Kellogg's "All Bran"), and then by a 2-week control period. Analysis of diets revealed that the mean intake of crude fiber rose to at least 10 g/day, and stool volume increased significantly during the high-fiber intake. The stools remained at the same pH, and the same percentages of water and solids were present durin- control and high-fiber-intake periods. Bacteriological analysis revealed no significant differences in qualitative or quantitative counts; however, the ratio of anaerobic to aerobic organisms appeared to increase.


Coronary heart disease mortality among Seventh-Day Adventists with differing dietary habits: a preliminary report.

Seventh-Day Adventists (SDAs) are a conservative religious denomination who abstain from tobacco and alcohol; approximately one-half follow a lacto-ovo-vegetarian diet. In this 6-year prospective study of 24,044 California SDAs age 35 and over, coronary heart disease (CHD) mortality rates for ages 35 to 64 and 65+ are 28% and 50% respectively, of the rates for the same age groups of the total California population. This reduced risk of CHD mortality among SDAs is partially due to abstinence from smoking; however, at least half the low risk among SDAs is likely attributable to other characteristics of the SDA lifestyle. The risk of fatal CHD among nonvegetarian SDA males, ages 35 to 64, is three times greater than vegetarian SDA males of comparable age (P less than 0.01), suggesting that the SDA diet may account for a large share of their low risk. This differential was much smaller for older SDA males and SDA females. Although the differential in risk of fatal CHD for male nonvegetarians versus vegetarians may be partially accounted for by other CHD risk factors, which are more frequent among nonvegetarians, a significant differential persists after adjustment for each of six other CHD risk factors.


Bile acid metabolism and fiber.

Studies in experimental animals and in humans have shown a definite interaction of dietary fiber with bile acid metabolism. In experimental animals, some types of fiber have been shown to increase bile acid excretion as well as increase pool size and turnover of bile acids. In man, increases in bile acid excretion have been observed but not consistently. Alternations in excretion and biliary bile acid levels indicate an influence of dietary fiber in bile acid metabolism. In vitro experiments have attempted to determine the nature of the fiber-bile acid interaction. Some types of fiber and some components of fiber have been shown to bind bile acids and bile salts in appreciable quantities. The capacity for various types of fiber to bind bile acids or bile salts is quite variable, and a high capacity seems to correspond with a hypocholesteremic effect. A great deal of research is still needed for elucidation of these interactions of fiber and bile acid metabolism and the resultant beneficial effects on cholesterol metabolism and the disease-related abnormalities in cholesterol metabolism.


Dietary fiber and cholesterol metabolism in rabbits and rats.

Rabbits fed semipurified diets have elevated plasma cholesterol levels, and they oxidize [26-14C]cholesterol to expired 14CO2 more slowly than rabbits on a natural ingredient diet. Addition of several different types of fibrous material to a semipurified diet failed to prevent the hypercholesterolemic response. Rats on semipurified diets also oxidized [26-14C]cholesterol more slowly and tended to have somewhat higher plasma cholesterol levels than rats on commercial feed. Cholesterol oxidation was not stimulated by addition of fibrous materials to the semipurified diet, but rats fed a semipurified diet containing raw potato starch oxidized cholesterol at a rate comparable to that of rats on commercial diet. Raw potato starch was poorly digested by the rats. Cooked potato starch was well digested and failed to stimulate the rate of oxidation of cholesterol. A semipurified diet containing raw potato starch did not produce a hypercholesterolemic response in rabbits, even though the raw starch was well digested.


Dietary fiber and lymphatic absorption of cholesterol in the rat.

The indirect effects of short-term (3-day) feeding of several types of dietary fiber and nonnutritive materials on the subsequent absorption of cholesterol has been investigated in thoracic duct cannulated rats. Absorption was studied at timed intervals over 24 hr after duodenal introduction of a tracer dose of cholesterol at least 20 hr after the last feeding. In animals fed for 3 days with diets containing cholestryamine, bran, or cellulose, cholesterol absorption was significantly less than in control animals maintained on rat chow. Rats fed for 3 days with an alfalfa-containing diet showed large variations in cholesterol absorption that were not significantly different from controls. However, after 5 weeks, rats on the alfalfa diet showed a marked reduction in lymphatic absorption of the tracer sterol. These indirect effects of cholestryamine and fibers on cholesterol absorption were not attributable to a common mechanism; i.e., differences in transit times that were not significant, or dirrect binding of bile acids and cholesterol by the test materials.


Diet and cell growth modulation by ammonia.

Fiber is not digested by endogenous enzymes but is fermented by microbes principally in the large intestine. With fermentable energy available, microbes synthesize protein by using ammonia released by their enzymes from urea and other nitrogenous substances in ingesta and intestinal secretions. Fibber fermentation also yields fatty acids that lower the concentration of free ammonia by lowering pH. Fiber increases bulk and water of intestinal contents, shortens transit time, and decreases the concentration of toxic substances in contact with the intestinal mucosa. These processes decrease duration and intensity of exposure of the intestinal mucosa to free ammonia, the form of nitrogen that is most toxic and most readily absorbed by cells. At concentrations found in the lower bowel on usual Western diets, ammonia destroys cells, alters nucleic acid synthesis, increases intestinal mucosal cell mass, increases virus infections, favors growth of cancerous cells over noncancerous cells in tissue culture, and increases virus infections. Ammonia in the bowel increases as protein intake increases. The attributes of ammonia and the epidemiological evidence comparing populations that maintain low intakes of unrefined carbohydrate with those that consume high intakes of protein, fat, and refined carbohydrates implicate ammonia in carcinogenesis and other disease processes.


Metabolism of biliary steroids by human fecal flora.

Biliary excreted steroid hormones are metabolized by the intestinal flora. The metabolic pathways of deoxycorticosterone and progesterone, including the bacterial species involved, have been established. The pathways for other biliary steroids are unknown. Information on the biological activities of the metabolites is lacking, but methods for their investigation are now available. Evidence suggests that the formation of the metabolites is influenced by dietary habits, and that, in some cases, it may be controlled by suppression of the responsible bacteria.


Colon cancer in a low-risk population.

Data are presented on colon mortality in Utah. For the years 1950 to 1969, the state population had 34% fewer deaths from colon cancer than the average United States population. Colon cancer incidence was also studied for the years 1966 to 1970, both for the state and for a large subgroup (Mormons) who abstain from tobacco and alcohol for religious reasons; the colon cancer incidence of Mormons was 37% below the United States average, and that of non-Mormons was 18% below the United States average. A preliminary dietary survey found little difference in meat, fat, and fiber consumption between the population of Utah and that of the United States as a whole.


Interaction of dietary fiber with other dietary components: a possible factor in certain cancer etiologies.

Dietary fiber is a highly interacting dietary component and is made up of a wide variety of enzyme-indigestible polymers: cellulose, pectins, gums, mucilages, lignin, and water-insoluble hemicelluloses. The study of the effect of dietary fiber on prevention of cancer, specifically of colonic cancer, cannot be carried on without considering that: 1) various types of dietary fiber have different metabolic effect; 2) other components of the diet (e.g., amount of fat) may influence the way dietary fiber affects the colonic environment; 3) the overall effect of dietary fiber may be the sum of effects on fecal bulk, colonic microflora pattern and metabolites, dilution of carcinogens, colonic pH, transit time, alteration of nutrient absorption, and postprandial hormonal function. It is unlikely that dietary fiber can be studied in isolation in experimental diets unless great care is taken to consider all interactions with other dietary components.


Fecal hydroxysteroid dehydrogenase activities in vegetarian Seventh-Day Adventists, control subjects, and bowel cancer patients.

Cell-free extracts were prepared from mixed fecal anaerobic bacteria grown from stools of 14 vegetarian Seventh-Day Adventists, 16 omnivorous control subjects, and eight patients recently diagnosed with cancer of the large bowel. Preparations were assayed for NAD- and NADP-dependent 3alpha-, 7alpha- and 12alpha-hydroxysteroid dehydrogenases with bile salts and androsterone as substrates (eight substrate-cofactor combinations were tested). A significant intergroup difference was observed in the amounts of NAD- and NADP-dependent 7alpha-hydroxysteroid dehydrogenase produced: bowel cancer patients exceeded controls, and controls exceeded Seventh-Day Adventists. Other enzyme activity comparisons were not significant. The pH values of the stools were significantly higher in cancer patients compared to Seventh-Day Adventists; values were 7.03 +/- 0.60 and 6.46 +/- 0.58 respectively. The pH value for controls was 6.66 +/- 0.62. A plot of pH value versus NADP-dependent 7alpha-hydroxysteroid dehydrogenase tended to separate the cancer patients from the other groups. Comparative data suggest that much of the 3alpha-hydroxysteroid dehydrogenase active against bile salt is also active against androsterone.


Diet, transit time, stool weight, and colon cancer in two Scandinavian populations.

In samples of adult men from two Scandinavian populations with 4-fold differences in colon cancer incidence, a comparison was made of estimated food records over 4 days, defecation habits, mouth-to-anus transit time, and stool weight. The "high incidence" group consumed more white wheat breads and total meat and beer, but less potatoes and milk than the "low incidence" group. Defecation habits were similar. Transit time and stool weight had few significant correlations with diet and defecation habits, but stool weights were higher in the low incidence group. The results are consistent with a possible protective role of dietary fiber, unrelated to transit time.


Characterization of 7-alpha-dehydroxylase in Clostridium leptum.

7-alpha-Dehydroxylation of primary bile acids was demonstrated radiochromatographically in whole cells of Clostridium leptum but was not observed in intestinal Bacteroides species. Activity of 7-alpha-Dehydroxylase was detected within a pH range of 5 to 9 and was 8-fold higher in specific activity in cell cultures in the presence of 0.1 mM sodium cholate than in its absence. 7-alpha-Dehydroxylase activity in whole cells was markedly inhibitied by 2,4-dinitrophenol, carbonyl-cyanide-m-chlorophenylhydrazine, and dicyclohexylcarbodiimide. A hypothesis concerning the dietary regulation of 7-alpha-dehydroxylating intestinal anaerobic bacteria is presented.


The relationship between bowel cancer and fiber content in the diet.

Colon cancer, very rare in rural South African blacks, is also rare in urban dwellers despite considerable rise in prosperity. The disease has scarcely increased during the last quarter of a century. The same situation applies to appendicitis. Endeavors to characterize different black populations in transition (including subjects who have had appendicitis) are being made respecting 1) diet, especially dietary fiber intake; 2) bowel physiology (e.g., transit time); 3) concentrations of fecal bile acids and other metabolites; and 4) the activity of certain fecal enzymes.


Distention of the small intestine, satiety, and the control of food intake.

The studies reported here investigated the role that filling of the small intestine plays in the control of ingestion. Adding mannitol, a nonabsorbable carbohydrate, to a palatable solution reduced meal size in rats in proportion to its concentration. Intake is suppressed for the duration of time that the small intestine remains full. If dietary fiber, which sequesters water and swells, fills the small intestine sufficiently, it may act to suppress meal size and prolong the length of intermeal intervals.


Energy density of food, gastric emptying, and obesity.

Certain receptors in the duodenal mucosa respond to the osomotic effects of the digestion products of dietary carbohydrates and proteins with a resultant slowing of gastric emptying. Other receptors respond to the soaps formed during the digestion of fats. The relative effectiveness of these two sets of receptors is such that foods with equal energy produce equal slowing of gastric emptying. Thus the rate of delivery of energy to the duodenum, and hence to the blood, can be regulated without the energy having been directly measured. The results in the literature that we have examined are consistent with this duodenal system playing some part in the regulation of food intake.


Caloric compensatory responses to diets containing either nonabsorbable carbohydrate or lipid by obese and lean Zucker rats.

The effects on food intake and body weight in lean and obese Zucker rats were evaluated following substitution in the diet with either 1) poorly absorbable lipid (hydrogenated soybean oil) for corn oil, or 2) nonabsorbable carbohydrate (fiber) for glucose. Lean Zucker rats compensated for the reduced caloric availability of the high-fiber and hydrogenated oil diets by increasing food consumption. In contrast, obese rats did not respond significantly to these dietary alterations and failed to attain caloric balance during the 16-day study. These differences in caloric compensatory responses were reflected in body weight gains. There were no differences in the amount of weight gained by lean rats fed either the high-or low-fiber diets because of compensatory hyperphagia in the high-fiber group. Lean rats fed the hydrogented oil diets gained less weight than controls fed corn oil diets, even in the presence of compensatory hyperphagia, because of the enhanced fecal excretion of water and metabolites caused by the poorly absorbed fat diet. As a result of a delayed and incomplete response to reduced caloric availability, obese rats fed the high-fiber and hydrogenated oil diets gained significantly less weight than the obese rats fed low-fiber and corn oil diets.


The effects of specified chemical meals on food intake.

Rats received intragastric infusions of various specified chemical meals and were subsequently tested for a reduction in food intake. A second experiment, using a novel technique, tested for conditioned aversion to the meal infusions. The nonnutritive substances, kaolin clay and emulsified fluorocarbon, had no significant effect on food intake. Infusions of 1 M glucose and 1 M sorbitol reduced feeding behavior, but the 1 M sorbitol infusion also produced a conditioned aversion to flavored pellets paired with the sorbitol infusion, showing that the reduced feeding could have been caused by discomfort. Infusion of a high-fat meal consisting of emulsified triolein mixed with small amounts of sugar and protein or the rat's normal liquid diet, Nutrament, also reduced food intake, and both infusions failed to produce a conditioned aversion. The use of specified meals to understand the chemical basis of satiety requires a sensitive behavioral test to establish that the meal does not cause discomfort or other nonspecific effects.


Studies in man of partially absorbed dietary fats.

A saturated long-chain triglyceride (SLCT) has been prepared by esterification with glycerol of the saturated long-chain fatty acid fraction of coconut oil, isolated by molecular distillation of the hydrolyzed oil. The resultant SLCT is comprised principally of stearate (89%) and palmitate (11%). The intestinal absorption of SLCT in man was compared with that of corn oil or a 1:1 mixture of SLCT and corn oil. Each fat or the mixture was incorporated in isocaloric amounts into a complete formula diet deriving 30% of its caloric content from fat, 55% from carbohydrate (dextrose), and 15% from protein (casein). The formula diets were administered in sequential feeding periods as the sole source of food. The results indicate that SLCT was poorly absorbed (31 to 39%) compared with virtually complete absorption of corn oil (98%). Fat absorption was improved when the dietary fat was an equal mixture of SLCT and corn oil. The poor absorption of SLCT was ascribed to its high melting point and related to impaired emulsification and micellar solubilization in the small intestine.


Dietary fiber, plasma insulin, and obesity.

The relationship between obesity, insulin resistance, and hyperinsulinemia is briefly reviewed. The possibility is considered that excess insulin secretion is the cause rather than the result of insulin resistance and obesity. Glucose administration is one of the most frequently studied of those factors known to stimulate insulin secretion. Much less well documented is the fact that meals of equal protein, fat, and carbohydrate content may cause different responses of plasma glucose and insulin. An experiment is reported in which the effects of a high-carbohydrate, high-fiber meal administered to seven healthy young adults were compared with the effects of a meal equally high in carbohydrate but composed largely of glucose in liquid formula form. The high-fiber meal caused an insulin rise less than half that caused by the liquid formula meal although the plasma glucose response to the two meals was not significantly different. The hypothesis is proposed that a high-carbohydrate, fiber-depleted diet, high in simple sugars, by repeatedly stimulating an excessive insulin response, may lead to insulin resistance and obesity in susceptible individuals and may play a role in the common occurrence of obesity in industrialized societies.


The development of the concept of dietary fiber in human nutrition.

Fundamental studies of the laxative action of wheat bran were undertaken in the United States in the early decades of the 20th century. Walker in South Africa extended these studies among African blacks and later suggested that cereal fiber protected them against certain metabolic disorders. Trowell in Uganda elaborated this concept with regard to the rarity of common noninfective diseases of the colon. Another stream of inquiry stemmed from the hypothesis of Cleave who postulated that the presence of refined sugar, and to a lesser extent white flour, caused many metabolic diseases, while the loss of fiber caused certain colonic disorders. Meanwhile Burkitt had collected massive evidence of the rarity of appendicitis and many venous disorders in rural Africa and parts of Asia. In 1972 Trowell proposed a new physiological definition of fiber in terms of the residue of plant foods that resisted digestion by alimentary enzymes of man. Southgate has proposed chemical methods to analyze the components of dietary fiber: cellulose, hemicellulose, and lignin.


Fiber in the gastrointestinal tract.

It has long been recognized that fruit, vegetables, and cereal fiber alter bowel function. The right colon can be regarded as a fermenter and an absorbing organ, and the left colon is for continence. A rationale for the use of fiber based on physical chemical properties is discussed. On this basis, the use of coarse wheat bran, apples, oranges, and carrots is recommended to treat diverticular disease, spastic colon, and constipation.


Some current concepts in intestinal bacteriology.

Quantitative studies of the fecal flora of populations at different risk of colon cancer indicate that the relative proportions of some particular species of bacteria rather than of different genera of bacteria may be correlated with colon cancer incidence. Since the metabolic activity of different species in each genus varies widely, a shift in proportions of species could cause a major change in total metabolic activity in the individual. In samples taken from various areas of the intestinal tract and in scrapings from the intestinal wall, the composition of the flora remained relatively constant from the ascending colon to the rectum. Therefore, the bacteria in feces do reflect the flora of the large colon. The composition of the flora was not significantly affected by drastic changes in diet, but statistically significant shifts in the proportions of some species were noted in individuals under conditions of anger or fear stress. Although diet may not change the flora the individual maintains, the bacteria present may convert the different substrates provided by a high-fat diet as opposed to a high-fiber diet into metabolites that are potentially carcinogenic. The conversion of dietary components to carcinogenic compounds, identification of the bacteria capable of effecting such conversions, and the conditions favoring the proliferation of such bacteria will be investigated in greater detail.


Dietary fiber and obesity.

It has been suggested that sufficient fiber in the diet will tend to prevent excessive food intake and depot fat accumulation by decreasing the caloric density of the diet, stowing rate of food ingestion, increasing the effort involved in eating, promoting intestinal satiety, and interfering slightly with efficiency of energy absorption. The increase in the prevalence of obesity in Western countries since 1900 has taken place concurrently with marked changes in the nature of the diet. Per capita intake of dietary fiber associated with starchy foods has greatly decreased, but intake of fiber associated with fruits and green vegetables has increased. Thus, although the type of fiber in the diet has changed, the total quantity may not have diminished considerably. Studies of the effect of caloric dilution with cellulose and other metabolically inert bulking agents have disclosed little or no inhibitory effect on the spontaneous energy intake of nonobese laboratory animals and human subjects. Nevertheless, there is evidence that obese rats and humans may defend their excess weight against nutritive dilution with less tenacity than their nonobese counterparts. The hypothesis that dietary fiber can protect against obesity therefore deserves further testing since an increase in the fiber content of the diet may tend to prevent overeating and excessive weight gain even if it does not reduce spontaneous energy intake in nonobese organisms.


Diabetes mellitus and dietary fiber of starchy foods.

The rarity of diabetes mellitus in rural Africans and the increased incidence in urban Africans suggested that high-fiber, high-carbohydrate diets might protect against diabetes. Conversely it has been suggested that low-fiber starchy food is a diabetogenic factor in susceptible human phenotypes. Many years ago experimental studies demonstrated that carbohydrate tolerance was increased in healthy adults if they ate high-carbohydrate diets but was decreased if they ate high-fat diets. From 1940 in England and Wales, diabetes death rates reported only those who died directly from diabetes mellitus; all cardiovascular complication deaths were excluded. Standardized diabetes mellitus death rates in England and Wales fell from 1941 until 1954 to 1957 by 55% in men and 54% in women. These years coincided with the production of high-fiber National flour. These data suggested the dietary fiber hypothesis of the etiology of diabetes mellitus, namely that fiber-depleted starchy foods were diabetogenic and conversely that high-fiber starchy foods were protective. Recent experimental studies of diabetic hyperglycemic men have shown that high-fiber, high-carbohydrate diets cause remission of diabetes mellitus in many men who had been treated previously by oral agents of moderate doses of insulin, but not those who had previously received large amounts of insulin.


Colonic-rectal cancer: fiber and other dietary factors.

The prevalence of colonic-rectal cancer is generally directly related to the fat content and inversely related to the fiber content of diet. In the few exceptions to this generalization, tumor prevalence is more closely related to fiber than to fat. Hypotheses have been postulated to explain the possible ways in which dietary fiber may protect against colonic-rectal cancer and to account for the close relationships between the geographical distribution of these tumors and that of certain other diseases.


Plant cell wall fractionation and structural analysis.

The structure of the major plant polysaccharides contributing to dietary fiber, their organization within the plant cell wall, and the problems associated with their analysis are briefly reviewed. Alkaline, acidic, and detergent fractionation methods are described and considered in relation to their specificity. The analysis of pectin, often ignored as a component of dietary fiber, is examined in detail. The solubility of pectins from a number of common plant foods was determined, indicating that a considerable portion of pectin polyuronide is lost to many of the commonly used analytical procedures.


Physical and biological properties of structural and other nondigestible carbohydrates.

Selected characteristics of dietary fiber and associated nondigestible polysaccharides are discussed. These properties, which could alter gastrointestinal function, include particle size, solubility and viscosity, and interactions with small organic compounds, cations, salts, and proteins. The relationship between structure and the physiochemical properties is indicated.


Complex carbohydrate breakdown in the human colon.

Concentrations of water-soluble high- and low-molecular-weight carbohydrates were determined in the intestinal contents of four human subjects who had died accidentally. In all four subjects, concentrations of high-molecular-weight carbohydrate were lower throughout the colon than in the ileum. In some subjects, similar but less dramatic differences were also found with low-molecular-weight carbohydrate. Components of both high- and low-molecular-weight peaks included neutral sugars such as rhamnose, galactose, mannose, xylose, and arabinose, which are found in many plant polysaccharides. Components characteristic of mucins (fucose, hexosamines, and sialic acids) were also detected. These results indicate that dietary fiber and mucin are degraded in the human colon.


The lignin fraction of plant cell walls.

Methods are discussed for determining lignin in plant cell walls. The increase in apparent lignin content that may occur as a result of artifacts produced during food preparation is also discussed. The phenolic components, including lignin, of cell walls separated from 12 vegetable, fruit, and cereal foods are determined. Wheat bran, on a fresh weight basis, had a high cell wall content (48.6%) compared with the vegetables and fruit whose contents ranged from 1.0 to 6.0%. Wheat bran and spinach cell walls had the highest lignin contents (11.4 and 4.4%, respectively) and the lowest degradabilities (35.8 and 39.6%, respectively) as determined by a cellulase technique. Cell walls of spinach, beetroot, sweet corn, pineapple, and wheat bran contained the phenolic acids (ferulic, p-coumaric, and diferulic) bound to polysaccharide components. Cell walls of cabbage, Brussels sprout, celery, cauliflower, green bean, carrot, and pea contained only traces of these acids.


Mineral components of plant cell walls.

Plant cell walls that are secondarily thickened contain silicon and metal cations. The silicon occurs predominantly as silica (SiO2.nH2O) deposited in intimate association with the organic components of the walls and, according to recent evidence, as an integral constituent of polyuronides. Relatively large amounts of deposited (i.e., solid) silica are found in rice and other cereals and in grasses. When ingested by ruminant animals, practically all the solid silica may be recovered in the feces. However, microscopic particles of silica from plants are, to a small extent, absorbed as such through the gastrointestinal wall in both man and ruminant animals. It has now been shown that silicon is essential for animals, and that it is a constituent of certain mucopolysaccharides, thereby contribution to the architecture of connective tissues. The acidic silanol group of solid silica in plant cell walls may be involved in binding metal cations, but carboxyl and phenolic hydroxyl groups of the organic components of the walls are probably mainly responsible. Binding of metal cations by these components of plant cell walls, and possibly by silica, is likely to reduce availability of the cations for intestinal absorption.


Fiber content and structure in foods.

Crude fiber analysis does not accurately reflect the amount of dietary fiber in food materials, nor does it give a constant fraction of dietary fiber when used to compare sources in the diet. More accurate methods of estimating dietary fiber are compared. The neutral detergent method of Van Soest, modified for use with foods, was especially useful in measuring the insoluble fraction of dietary fiber. It not only provided a simple, quick method of analysis but also was useful in isolating dietary fiber for further experimentation. Water-holding capacity studies, trace mineral binding studies, and bile acid binding studies were run on the insoluble dietary fiber without interference from digestible food constituents.


Nutritional implications of dietary fiber.

When dietary fiber intakes are increased by supplementing diets with bran and whole wheat products, then fecal fat, nitrogen, energy, and mineral excretion rise. These changes suggest that fiber may be altering normal digestive and absorptive function. Recent studies have confirmed this and have also shown that fiber of different composition and from contrasting sources produces different physiological effects. The gel-forming polysaccharides such as guar gum and pectin alter the pattern of glucose absorption and are hypocholesterolemic; fiber from cereals is not hypocholesterolemic but exerts a pronounced effect on the large gut. Dietary fiber is largely digested in the colon by the microflora and so influences colonic function, fecal weight, and composition. The significance of the changes in fat, nitrogen, and energy output remains to be evaluated, but the impairment of mineral absorption--particularly of calcium, zinc, and iron--by fiber gives cause for concern. Fiber must now be considered with other dietary constituents in all nutritional studies.


Artifactual radioassay results due to serum contamination by intravenous radioisotope administration. Falsely low serum vitamin B12 and folic acid results.

Radioisotopic contamination by recent radioisotope administration (either 99mtechnetium or 67gallium) to the patient for scanning purposes was found in 28 sera submitted for vitamin B12 or folic acid assay, or both, during the year prior to this study. In half the cases serum radioactivity was so great as to be readily identifiable during the assay. In the rest, however, the radioactivity would not have been detected had serum supernatant blanks not been routinely incorporated in the assay procedure. Many radioassay kits make no provision for such supernatant control blanks. Were it not for these blanks, five patients would have been falsely identified as vitamin B12-deficient and three others as possible deficient in the present series. Two of the five radioactive sera assayed for folate would also have given misleading results in the borderline-low range. The clinician should avoid ordering tests requiring radioassay when the patient has been given radioisotopes, and those performing radioassays must institute appropriate maneuvers to detect any such contamination.


Hemangiopericytoma of the meninges. Mayo Clinic experience.

A study of 26 hemangiopericytomas of the meninges revealed that the histologic appearance--including ultrastructural features--was similar to that of hemangiopericytomas of soft tissues. Both sexes were affected, and occurrence was most frequent in the adult years, with no symptoms specific for the lesions. The lesions were characterized by an aggressive course, with recurrence in 80% of the patients, and metastases in 23%; thus, the importance of recognizing the lesion pathologically is emphasized.


Distributed laboratory computing. Integration of a laboratory computer into a hospital information system.

The University of Iowa Hospitals and Clinics, a large teaching hospital and tertiary care referral center, has implemented a vendor-supplied laboratory computer package operating on a dedicated minicomputer. A high-speed communications link allows the laboratory computer to share patient administrative, census, and test result data with the central hospital information system on an interactive basis. Operational characteristics of the system are discussed, and special attention is given to the critical problems and advantages of interfacing two computers.


Evaluation of a computer-directed pneumatic-tube system for pneumatic transport of blood specimens.

The results of sending specimens through a computerized pneumatic airtransport system and manually delivering specimens were compared for 15 chemical tests and six hematologic procedures. All specimens were collected from inpatients and outpatients into evacuated glass containers. The specimens traversed a maximum of 829 feet (253 meters) involving 16 bends and eight transfer units at 25 feet/second (7.6 meters/second). Only the activity of lactate dehydrogenase exceeded the precision of the test in pneumatically transported specimens. Ruptured erythrocytes in incompletely filled vacuum tubes were the likely source of the increased lactate dehydrogenase activity. Neither the serum sodium, potassium, chloride, carbon dioxide, total protein, albumin, calcium, glucose, creatinine, total bilirubin, alkaline phosphatase, aspartate transaminase, acid phosphatase, uric acid, leukocyte count, erythrocyte count, hemoglobin, hematocrit, nor the prothrombin time and partial thromboplastin time were affected by pneumatic transport. It is concluded that the pneumatic system tested provides a safe, efficient method of transporting the blood specimens tested.


Development and evaluation of a disposable device for performing simultaneous duplicate bleeding time determinations.

A disposable bleeding time device that provides two simultaneous standardized incisions is described. The mean bleeding time of 47 normal adults was 4.1 min with a 95% range of 2.2--7.0 min. The standard deviation of duplicate bleeding times was 0.7 min, and the day-to-day standard deviation for individuals was 0.9 min. In a double-blind crossover study of 20 normal adults, the mean bleeding time increased from 3.7 to 6.2 min after ingestion of 1 g aspirin. The device is extremely simple to use and is essentially painless. Physical trauma is minimal.


Accuracy of clinical laboratories studied by comparison with definitive methods.

Samples of lyophilized human serum were circulated to participants in the CAP Chemistry Survey program. The participants measured the concentrations in the samples of calcium, iron, lithium, magnesium, potassium, and sodium. Samples were also sent to the National Board of Standards (NBS), and the concentrations of these seven analytes were measured; definitive methods were used. The participant values and the NBS values were compared, providing a measure of the accuracy of the participating laboratories and of the individual methods used by the participants. There was, in general, close agreement between the NBS values and the participant values. A bias that varied with the concentration of the analyte was a common feature.


Statistical evaluation of CAP survey results for calcium, potassium, and blood urea nitrogen.

Throug the use of the statistical technic known as the linear model, a complete analysis has been made of data obtained in the Colleg of American Pathologists Survey of 1975 for calcium, potassium, and blood urea nitrogen (BUN). The analysis allows a separation of laboratories into core and non-core categories. It also allows for determination of the reproducibility of each analytic technic involved in this survey. For Ca and K, the results obtained by each analytic method were compared with the results obtained by the National Bureau of Standards through use of the definitive method. For BUN, the comparison was made with the average of values for all laboratories and all methods.


Evaluation of non-core laboratories.

The CAP Interlaboratory Survey data from the non-core laboratories identified by Paule and Mandel were examined. Some laboratories were designated non-core because they submitted one or more values that were widely discrepant and were caused by unit problems, decimal shifts, or reversal of the specimens. A second group of laboratories submitted a number of discrepant results that appeared to be caused by problems within the laboratories. A third group submitted results that appeared acceptable, and the exclusion and the effectiveness of the criteria differed for each of the three analytes. The findings suggest that examination of data from excluded laboratories can provide a valuable source of information to supplement the central data.


The 1977 College of American Pathologists Enzymology Survey. Principal findings.

A set of linearly related serum survey specimens was analyzed by more than 200 laboratories on four occasions in 1977 for the five enzymes lactate dehydrogenase, aspartate and alanine aminotransferases, creatine phosphokinase, and alkaline phosphatase. The survey technic, which employs specimens that are designed to have multiple informational redundancies for detecting discrepancies in the survey data, was found to be a feasible approach, as a variety of methodologic biases and analytic problems were readily detected. The specimens were shown to be stable,and the mean results obtained by a reference group of laboratories were quite reproducible. Consequently, changes observed in individual laboratories in successive surveys were attributable to intra-laboratory changes. The survey provides each participant with an objective evaluation of the linearity, precision, and calibration of his methods, in comparison with peer and reference laboratories, as well as information concerning the popularities of various methods, and the performances of various analytic systems. For each enzyme there are a few large peer groups and a large number of small peer groups. Differences among the laboratories within each peer group were due primarily to proportional biases that in some cases were clearly due to instrumental or reagent differences, rather than to methodologic differences.


Serum creatinine. A CAP survey.

The results of the 1976--1977 College of American Pathologists Survey of serum creatinine measurements performed by more than 5,000 laboratories are presented. The most widely used method employs the colorimetric measurement of the alkaline picrate-creatinine (Jaffe) reaction. In general, all manual and automated systems yielded comparable creatinine concentrations except the centrifugal analyzers, which manifested a consistently high bias. Interlaboratory variation was lowest for continuous-flow and the DuPont discrete systems. Lloyd's reagent resulted in a clinically insignificant reduction of creatinine concentration in lyophilized sera.


An interlaboratory comparison of serum total protein analyses.

An analysis of the 1976 CAP Comprehensive Chemistry Survey of total serum proteins is presented. More than 2,000 laboratories contributed data in this survey. Estimation of total serum protein concentration by the biuret reaction remains the most widely used technic, followed by refractometry. Precision and accuracy data for a number of analytic systems and methods are presented. Precisions for the entire group are nearly comparable. A negative bias for total protein concentration was shown by the SMAC.


The CAP Urine Chemistry Survey Program for 1977.

Eleven analytes were presented in the Urine Chemistry Survey Program during the year 1977. These included amylase, calcium, phosphorus, sodium, potassium, creatinine, osmolality, 17-ketosteroids, total protein, glucose, and urea nitrogen. More than 450 laboratories participated. Deficiencies in assay performance were found for amylase, 17-ketosteroids, and total protein. Sharp shifts in precision performance were seen in urea nitrogen analysis. Severe biases are apparent in glucose analysis using neocuproine and ferricyanide methods.


CAP Comprehensive Chemistry. Serum iron survey.

Approximately 1,600 participants replied to a special questionnaire about the serum iron determination used in their laboratories. The categories covered were (1) sample preparation, (2) system, (3) detection method, (4) reducing reagent, and (5) standards. Those using AutoAnalyzer methods uniformly had the highest reported values. The lowest values were reported by those using methods without protein removal. Whether this is a positive bias by the AutoAnalyzer group or a negative bias by methods without protein removal, or both, cannot be determined by this study. Hydroxylamine users reported lower results than others. No difference between the three commonly used chromogenic reagents, bathophenanthrolene sulfonate, tripyridyl-triazine, and ferrozine, could be demonstrated. Protein-based standards should be used when a method is found to be affected by protein. How to determine the assay value is an important problem yet to be solved.


Long-term stability of glucose in lyophilized quality control serum. A study utilizing data from the Quality Assurance Service (QAS) Program of the College of American Pathologists.

The long-term stability of glucose in 45 commercial pools of lyophilized quality control serum is evaluated. The pools have been used in conjunction with the Quality Assurance Service (QAS) of the College of American Pathologists by laboratories participating in Regional Quality Control Programs. Directional instability of glucose was detected by at least one analytic method in 69% of the pools studied. Two distinct and opposite directional trends in glucose concentration were found. Increasing concentration of analyte, averaging 4.7 mg/dl per year, were observed with manual and automated glucose oxidase methods and the automated neocuproine procedure in approximately one fourth of pool--method combinations. Decreasing concentrations of glucose, averaging 3.0 mg/dl per year, were found with automated ferricyanide and hexokinase methods and the manual orthotoluidine procedure in approximately one third of pool--method combinations. The results are best explained by postulating that in affected pools there is a gradual diminution of free and bound glucose and/or a shift of glucose from the protein-bound to the free state.


Reproducibility of mean values of duplicate specimens in the Basic Ligand Assay Survey.

Three paired samples were distributed at three--six-month intervals in the Basic Ligand Survey during 1976. The stabilities of mean values obtained by widely used commercial kit procedures and by all methods for eight analytes are reported. Significant improvements in accuracy and long-term precision were identified in assays for digoxin and thyroxine during 1976. However, a number of assays yielded unstable mean values that affected both within--laboratory maintenance of quality control and medical usefulness of the results.


Evaluation of tests for antibody to hepatitis B surface antigen (anti-HBs).

Participants in the American Association of Blood Banks--College of American Pathologists (AABB-CAP) HBsAg Survey Program primarily use a radioimmunoassay (RIA) method for detection of anti-HBs in samples found to be surface antigen-negative. Although this is a new procedure for most laboratories, survey results indicate excellent proficiency.


Factor VIII (antihemophilic factor) assay results in the 1976 College of American Pathologists Survey Program.

Data from the 1976 CAP Survey for the performance of Factor VII (antihemophilic factor) assays were analyzed. The results indicated an undesirable variation on both normal and abnormal specimens. Reagent-instrumentation systems and procedures were examined. The need for standardization of factor VIII assays is evident from the results of this study.


An interlaboratory comparison of analyses of clinical specimens.

A pilot study was conducted to identify some of the benefits and limitations of making interlaboratory comparisons of clinical assays. Sixteen laboratories that participated in a regional quality control program and used similar instrumentation each provided analyses of specimens from three male and three female healthy subjects, 25 male and 25 female clinical subjects, and several control specimens. Analysis of the data revealed that the derived normal ranges agreed well with those provided by the instrument manufacturer, and that for some analytes the laboratories produced comparable clinical assays. The control specimens were found to be indicators of the presence of analytic bias that affected the clinical assays, but they did not always correctly indicate the kind or magnitude of bias. Using pattern recognition technics, it was shown that a laboratory's clinical assays had characteristic distributions that were apparently related to the populations served, as well as to analytic precision. The results demonstrate that useful information may be gleaned from interlaboratory surveys of clinical assays.


An innovative method for the determination of normal values in hematology using peer group laboratories.

The author describes a proposed innovative method for the determination of normal values in hematology in which a large number of laboratories participating in the CAP proficiency testing program submit results of a previously performed, complete blood count. These data are compared with those derived from more formal studies of normal values. The advantages of this system, if validated, include its inexpensive simplicity and the possibility of determining normal values for relatively uncommon groups of patients such as neonates, infants, and small children.


Use of survey-validated reference materials (survey serum) to establish target values of quality control pools.

Specimens used in the College of American Pathologists Survey Programs are sometimes manufactured in excess of Survey needs, and these excess specimens are made available to Survey participants after a survey is completed. These survey-validated reference materials (SVRM's) are a valuable resource to the clinical laboratory field. SVRM's are continually renewed, have a range of analyte concentrations, have reliable target values assigned for more than 20 analytes, and for all methods that are in common use. The materials are useful for assigning appropriate target values to other serum materials used by laboratories, for investigating the accuracy of a laboratory's analytic procedures, and as trouble-shooting aids. The wide availability of SVRM's offers a new opportunity for improving the analytic reliability of quantitative clinical assays.


Proposed classification of clinical laboratory methods.

A Task Force appointed by the College of American Pathologists studied the key elements that may affect a laboratory result, including the types of reagents, manufacturers of detection equipment, blanking procedures, calibrators, diluting and dispensing devices, and sample preparation. A field trial was conducted using cholesterol assay as the pilot study. Participants completed a lengthy questionnaire that requested information regarding the key elements used in the cholesterol assay. This report presents the preliminary findings of the field trial. Examples are shown to illustrate how obtaining additional information about how the laboratory test was performed led to identification of subtle differences in test results.


Leukemic myelomatosis (plasma cell leukemia).

Six cases of leukemic myelomatosis (plasma cell leukemia), are reported. A spectrum of leukemic plasmacellular proliferation was observed in this group: in two cases the plasmacytic leukemia was a terminal event of multiple myeloma, in one of a chronic lymphocytic leukemia, and in the remaining three cases the peripheral blood plasmacytosis was a presenting manifestation of an acute immunocytic dyscrasia. The clinical features, frequencies of extraosseous plasmacytic infiltrations, hypercalcemia and Bence Jones proteinuria, and cytomorphologic difficulties in differentiating plasmacytic from chronic lymphocytic leukemia are discussed.


Diagnostic problems involved in detection of metastatic neoplasms by bone-marrow aspirate compared with needle biopsy. Am J Clin Pathol 70: 623--627, 1978. Comparison of a large series of bone marrow aspirations with simultaneously performed Jamshidi needle biopsies showed 75% correlation between the two procedures for detection of metastatic neoplasms. In cases where the two methods disagreed, false-negative aspirations resulting from perineoplastic desmoplasia was the usual reason for the discrepancy. Cytologic criteria for the evaluation of suspected neoplastic cells in aspirate preparations are discussed.


Platelet 5-hydroxytryptamine storage in the carcinoid syndrome.

The uptake and storage of 5-hydroxytryptamine by human platelets from normal donors and patients with the carcinoid syndrome are reported. When platelets were incubated in the presence of 3H-5-hydroxytryptamine (50 microM), an initial phase of rapid uptake was observed until 5-hydroxytryptamine levels of 1--2 microgram/10(9) cells were reached. Further accumulation occurred more slowly. Electron microscopic autoradiography of cells after 5-hydroxytryptamine uptake for 60 minutes revealed that in platelets from normal donors most of the label was localized in membranes (52%), alpha granules (27%), and cytoplasm (4%). Dense bodies were associated with 18% of the silver grains. Similar membrane (50%) and alpha-granule (27%) labeling was found with platelets from patients with carcinoid syndrome. However, more cytoplasmic labeling (10%) and less dense-body labeling (11%) were found with these cells. The results support a hypothesis of two or more sites for storage of 5-hydroxytryptamine in mammalian platelets and suggest that minimal exchange between cytoplasmic and dense-body amines occurs in carcinoid platelets.


The diagnostic significance of a prolonged erythrocytic glycerol lysis time (GLT50).

The predictive value of a prolonged glycerol lysis time (GLT50) was assessed by analysis of case records of 100 consecutive subjects with values greater than 73 seconds (normal = 26--73 seconds) reported by the clinical laboratory of The New York Hospital. There were 72 cases of hemoglobinopathy: 65 thalassemia trait, four sickle-thalassemia, and one each of Hb D-thalassemia, sickle-C disease, and sickle-cell anemia. Nine of the remaining subjects had iron-deficiency anemia, three had chronic renal disease, and seven had miscellaneous disorders. Four subjects were apparently normal, and in five cases there was insufficient information for a diagnosis. Of 78 patients who had both a prolonged GLT50 and microcytosis, 67 (86%) had thalassemia trait and seven (9%) had iron-deficiency anemia. In 74 patients with GLT50 greater than 100 seconds, thalassemia trait was found 16 times as often as uncomplicated iron-deficiency anemia. All 31 subjects with GLT50 greater than 180 seconds had hemoglobinopahy. A prolonged GLT50 strongly suggests thalassemia trait, especially when greater than 100 seconds or associated with microcytosis.


An evaluation of four automated coagulation instruments.

Four automated coagulation instruments were evaluated for performance of prothrombin time and activated partial thromboplastin time (APTT): the Dade Auto-Fi, General Diagnostics Dual Channel Coag-a-Mate, MLA Electra 600D, and Sherwood Lancer Coagulyzer. Statistical comparisons showed only minor differences among values determined with these instruments. Reproducibilities of duplicate prothrombin times and APTTs were equivalent on all machines except the Coag-a-Mate; the problem here was in the alignment of the two channels, and should be correctable. Differences exist in the costs, technician acceptance, computer interfacing, and normal values on these instruments. The MLA instrument has the lowest purchase price, followed by the Sherwood and then the General Diagnostics instruments. These three instruments have comparable costs for disposable supplies. The Dade has a substantially higher purchase price and higher costs of disposable supplies. The Sherwood and MLA had the best technician acceptance. All instruments except the Coag-a-Mate can be easily interfaced to a computer. The Dade instrument gave longer coagulation times than the other three instruments when General Diagnostics reagents were used.


Estrogen receptor assay of carcinomas of the breast by a simplified dextran--charcoal method.

Carcinomas of the breast from 352 women were assayed for binding of tritiated estradiol by tumor cytosol with dextran--charcoal adsorption, saturation analysis, and two-point Scatchard plots; the level of saturable binding defined a cytosol as positive or negative for estrogen receptor. Valid assays were obtained on specimens as small as 120 mg. Assays of replicate samples of a cytosol were more reproducible than assays of replicate samples of the tumor itself. Occasional disparity of results between a primary mammary carcinoma and its axillary metastases could be related to differences in tumor cellularity. Saturable binding consistent with the presence of estrogen receptor was found in 59% of 305 primary carcinomas and in 57% of 47 metastatic or recurrent carcinomas. There was a significant negative correlation between the patient's age and saturable estrogen binding in the tumor. Serum estradiol levels of less than 250 pg/ml appeared to have a negligible effect on estrogen receptor content. A small subgroup of high-binding carcinomas had high dissociation constants, but the significance of this observation is not clear.


Ristocetin precipitation test: a new simple test for detection of fibrin monomer and fibrin degradation products.

The ristocetin precipitation test was designed as a simplified test to detect fibrin monomers and fibrinogen/fibrin degradation products (FPD/fdp). The ristocetin precipitation test is positive in plasma samples containing either fibrin monomer (greater than 5--10 microgram/ml) or early fdp (greater than 50--100 microgram/ml). The ristocetin precipitation test is negative in plasma with fibrinogen concentrations to 1,000 mg/dl or fibrinogen degradation products FDP) and late fdp to 400 microgram/ml. The ristocetin precipitation test is positive in plasmas collected from rabbits after the infusion of thrombin (2.7 u/kg) or thrombin and streptokinase (10,000 u/kg); the test is negative in plasmas from animals treated with streptokinase or saline solution alone. The ristocetin precipitation test is negative in normal human plasmas and plasmas from patients who have primary firbinogenolysis, but positive in plasmas from patients with disseminated intravascular coagulation. These results suggest that the restocetin precipitation test can be a useful test for the detection of plasma fibrin monomers and early fdp.


Extraskeletal myxoid chondrosarcoma with "chordoid" features (chordoid sarcoma).

The light and electron microscopic features of a so-called chordoid sarcoma arising in the area of the gastrocolic ligament are described and illustrated. Despite the tumor's histologic resemblance to chordoma, the ultrastructural markers are those of chondroid rather than chordoid neoplasms. These are well-developed, vesciular granular endoplasmic reticulum, intracytoplasmic glycogen, lipid bodies, and a collagen-poor extracellular matrix with electron-dense granules, presumably representing chondroitin sulfate. Similar submicroscopic alterations have been observed in extraskeletal myxoid chondrosarcomas. Because of the distinctive morphologic appearance of this peculiar lesion, the term "myxoid chondrosarcoma with chordoid features" is suggested to reconcile histologic and ultrastructural features and histogenesis.


Myeloid metaplasia and osteolytic lesions.

The case of a patient with myelofibrosis and painful osteolytic lesions is described. Biopsy of the involved bone demonstrated myeloid proliferation. Foci of myeloid metaplasia may occasionally result in clinical disability, with bone pain and rarefaction. Myeloid metaplasia should be considered when these symptoms and signs occur in the setting of myelofibrosis. The role of radiation therapy as a palliative maneuver remains uncertain.


Bilateral ovarian endometriosis associated with carcinosarcoma of the right ovary and endometrioid carcinoma of the left ovary.

The case of a 44-year-old woman wih bilateral ovarian malignancies in association with endometriosis is presented. A carcinosarcoma was present in the right ovary, and a well-differentiated endometrioid carcinoma in the left ovary. This case is, to the authors' knowledge, unique.


Community perspectives on deviance: some factors in the definition of alcohol abuse.

This paper examines how alcohol abuse is ""defined'' by the social milieu within which it occurs, according to the three conceptual dimensions of (a) the perceived prospects for change, (b) perceived personal control, and (c) attributions concerning the causes of alcohol problems. Respondents from three socioeconomically different communities made similarity ratings between all possible pairings of 13 stimulus items (78 in all). These items reflected four types of drinker, and the three conceptual dimensions. Multidimensional scalings and an analysis of variance demonstrated substantial community differences, such that the lower socioeconomic status respondents had a more complex and more clearly articulated view of alcohol abuse than did the upper status respondents. Further, these communities differed in their perceptions of the internal or external origins of alcohol problems. Shared features of these communities' view of alcohol abuse included a basic normal vs. problem drinker distinction, as well as a distinction between alcoholics and ex-alcoholics according to the amount of personal control they were seen as having.


Efficacy of a group crisis-counseling program for men who accompany women seeking abortions.

This study investigated the effect of a group crisis-counseling session on the anxiety level and attitudes of males who accompanied women seeking legal abortions. Twenty-three companion males participated in one 2-hour counseling session. Each session was comprised of three to seven men. Twenty-three other men, who served as control subjects, remained in the waiting room of the abortion clinic and did not participate in a counseling session. All subjects completed the Spielberger State-Trait Anxiety Inventory (STAI) and four other attitudinal measures based on the semantic differential. These were filled out by all subjects when they first arrived at the clinic and again approximately 2 hours later. Results from both the STAI and the other attitudinal measures indicated that State anxiety (A-State) decreased and attitudes towards abortion concepts generally were more positive for men in the group which received crisis counseling.


Referral to a school mental health project: a screening note.

The screening efficiency of two measures of school-adjustment is considered by assessing the proportion of children referred to a school mental health program whose scores fall at or above the 85th centile on one or both measures. The study's findings demonstrate that 60-90% of referred children were identifiable by a screening cutoff score procedure. The implications for using a cutoff score approach in selecting children for the intervention are discussed.


Social activism and psychiatrists in community mental health centers.

A sample of psychiatrists (n = 72) working in 20 community mental health centers (CMHCs) representative of the organizational and catchment area characteristics of operating Centers were queried as part of a larger study (n = 595) of community mental health worker roles. It was found that psychiatrists were like other staff in perceived organizational expectations of social activism but were significantly lower in perceived personal/professional role activism and role discrepancy. Unlike other staff, psychiatrists' levels of activism and discrepancy were unaffected by personal characteristics or organizational and catchment area characteristics of the CMHCs. It was concluded that the psychiatrists' unwillingness to assume any but the most modest community activist stances may hinder the development of the CMHC movement.


Perspectives on the training experiences and the training needs of community psychologists.

The present study examined the attitudes and perspectives of Division 27 (Community Psychology) members toward training roles and issues. Surveys sent to Division members focused upon: (a) background and demographic data; (b) past and present academic and employment characteristics; (c) relevance of community psychology to present employment; (d) community psychology relevance as an area of training; and (e) roles and functions which are perceived as essential to community psychology. Results indicate that the membership perceives human service topics (social planning and community change) as more important than traditional direct service aspects. The significance of the emphasis on broader social system activities is discussed in relationship to the predominantly clinical academic background of Division members.


Goal Attainment Scaling: an effective treatment technique in short-term therapy.

The present study compares the outcome of short-term therapy for clients who established thearpy goals with their therapists and clients with whom no formalized goal setting occurred. When compared to control clients, clients receiving Goal Attainment Scaling (GAS) had significantly (a) more positive outcomes as measured by posttests of anxiety, self-esteem, and depression; (b) higher ratings of their own motivation to change; and (c) higher ratings of their own change as a result of therapy. Therapists perceived their GAS clients to have changed more as a result of therpy but not to have been more motivated to change than their control clients.


The effects of consultation style on consultee productivity.

This study examined the effectiveness of three different consultation styles adapted from Bindman's typology. Consultees were nurses on eight wards in a state hospital for the retarded, who were assigned to Expert, Resource, and Process consultation groups plus a no-treatment control. Data on the number of new programs independently initiated by consultees were collected during a 6-week base line, 12-week consultation, and 6-week follow-up period. Results showed a general increase in number of programs initiated during the second half of the consultation period, with trends established there continued through the follow-up. Degree of change was directly related to the style of consultation: the Expert role proved no better than the control condition; the Resource and Process roles generated significant consultee activity, with the Process model generating the most programs in both experimental and follow-up periods.


A method of evaluating the impact of services at a comprehensive community mental health center.

Efforts of one community mental health center to develop a system of program evaluation designed to meet criteria mandated by recent Federal legislation are described. This approach represents a comprehensive evaluation system with the capability of objectively assessing: (a) patterns of utilization of services, (b) satisfaction with services as well as the availability, accessibility, and acceptability of services, and (c) the quality of direct mental health services as measured by attainment of individualized treatment goals. A rationale for the development of this system as well as a description of the modifications and automatization of the procedure are included. Initial results are presented which pertain to 2,900 goals written for 1,250 clients receiving treatment within five of the Center's direct service elements.


Migrating electrical spike activity in the fasting human small intestine.

The purpose of the present investigation was to describe characteristics of migrating electrical phenomena in the human small intestine. A specially designed probe with several bipolar electrodes was placed in the upper small intestine of 5 normal, fasting volunteers for continuous registration of electrical spike potentials. A migrating myoelectric complex was observed resembling observations made previously in animal experiments. The active phase consisted of regular spike potentials propagating distally at a mean velocity of 12 cm/min, and a duration of about 5 min. In addition a "peristaltic rush" was observed consisting of spike potentials with a high amplitude, propagating distally at a mean velocity of 2 cm/sec and a duration of about 5 sec.


Somatostatin inhibits motilin-induced interdigestive contractile activity in the dog.

The interaction between motilin and somatostatin on gastrointestinal motor activity was studied in fasted, unanesthetized dogs. Contractions of the stomach, duodenum, jejunum, and ileum were recorded with extraluminal strain gage force transducers. Motilin initiated a pattern of contractile activity which closely resembled phase III of the interdigestive motor complex. Somatostatin delayed the onset of the motilin response and reduced motor activity in the stomach and the jejunum. During somatstatin infusion the motilin-induced contractile pattern did not migrate to the jejunum. The cycle of natural interdigestive motor complexes was also interrupted by somatostatin. Somatostatin alters natural and motilin-induced interdigestive migrating motor complexes of the canine gastrointestinal tract.


Esophageal prosthesis in cancer.

We describe the use of polyvinyl esophageal prosthetic tubes to treat 14 consecutive patients with malignant strictures and tracheoesophageal fistula from carcinoma of the esophagus. We found these prosthetic tubes easy to construct, simple to insert, and that their use improved the quality of remaining life in most patients by diminishing dysphagia and incessant coughing from pulmonary aspiration.


Small-intestinal mucosa in pseudoobstruction syndromes.

The purpose of this investigation was to determine the frequency and severity of small intestinal mucosal damage in pseudoobstruction syndromes. One hundred eighty-nine interpretable biopsies from 12 patients were blindly reviewed by two investigators. The underlying disorders were scleroderma in 7 and idiopathic intestinal pseudoobstruction in 5. All 12 had small-intestinal dilatation on small-bowel series. Eight of the 12 patients had biopsies characterized by moderate to severe mucosal damage; 3 of these had some biopsies which were flat. The damage did not correlate with: (1) types and numbers of organisms recovered from small intestinal aspirates; (2) duration of illness; (3) degree of dilatation of the proximal small bowel; (4) concentrations of deconjugated bile salts in small intestinal fluid; or (5) amount of fat absorbed in fat-balance studies. We conclude that mucosal damage is common in pseudoobstruction syndromes. The pathogenesis of the damage and its relationship to intraluminal bacteria remain undefined.


Oral cholecystography in chronic renal insufficiency.

Thirty-two patients with chronic renal insufficiency (CRI) had oral cholecystography. Eleven of 15 patients (73%) with moderately advanced renal impairment had diagnostically inadequate single-dose cholecystograms. In contrast, all 11 patients on chronic hemodialysis had diagnostically opacified gallbladders following a single dose of contrast. Six other patients had biliary disease, either calculi (5 patients) or neoplasia (1 patient). These data suggest that CRI diminishes the likelihood of diagnostic gallbladder opacification, even in the absence of gallbladder disease, and that if the metabolic consequences of CRI are controlled by dialysis, the chances of diagnostic opacification are significantly improved (P less than 0.005). As oral cholecystography may not only result in inadequate opacification, but also carry the potential of renal toxicity, abdominal ultrasound should prove a safer and possibly more effective alternative in such patients.


Percutaneous transperitoneal aspiration biopsy of pancreatic masses.

Percutaneous fine-needle aspiration biopsy of pancreatic masses was performed in 34 patients. Biopsies were performed with a 22 or 23-gage, spinal-type needle under fluoroscopic guidance. Correct results were obtained in 73% of the patients including 21 patients with pancreatic carcinoma. No complications occurred. The primary indication for aspiration biopsy was to document the presence of malignancy and avoid a diagnostic laparotomy in patients considered to be unresectable.


Proteins of ascitic fluid in constrictive pericarditis.

A patient with chronic calcific pericarditis, hepatic congestion, and fibrosis had massive ascites with a protein concentration of 5.1 g/100 ml. This fluid was in all likelihood largely derived from hepatic interstitial fluid. The ascites-serum concentration ratio for several protein species and molecular exclusion chromatography of these fluids suggested two processes may be involved in the transfer of protein from serum to ascites, namely bulk transfer of all species and molecular sieving.


Crohn's disease in Barrett's esophagus.

A patient with regional ileitis (Crohn's disease) developed a benign esophageal stricture. He had no history of heartburn or other symptoms of reflux esophagitis. The diagnosis of Crohn's disease was suspected but could not be proved preoperatively. The surgically resected esophagus showed the gross and microscopic features of Crohn's disease. Barrett's esophageal mucosa was also found in the resected esophagus. Postoperatively, the patient developed a fistula at the esophagogastrostomy site. Crohn's esophagitis has been reported in 15 patients but none had Barrett's esophagus. We believe our patient reported here is the first case with Crohn's disease and Barrett's esophagus.


Cardiovascular responses to upper gastrointestinal endoscopy.

Continuous Holter monitoring and serial blood pressure recordings were obtained during upper gastrointestinal endoscopy on 51 unselected patients, 18 with cardiovascular disease. Sedation with intravenous diazepam produced a small but significant fall (P is less than .001) in blood pressure, heart rate and rate-pressure product. During endoscopy, the blood pressure rose only to base line levels but the heart rate and rate-pressure product went significantly higher (P is less than .001). Nine subjects (fice with pre-existing cardiovascular disease, four normal) exhibited electrocardiographic changes, including supraventricular arrhythmias, ventricular ectopy and significant ST segment depression. None of the patients had bradycardia or significant vagal symptomatology. The difference in incidence of abnormalities between the normal patients (4/33) and those with cardiovascular disease (5/18) was not statistically significant (P = 0.3). Endoscopy can be safely performed even in patients with cardiovascular diseasebut attention to the reduction of cardiac stress would further increase its safety.


Adrenergic influences on the gallbladder emptying.

Dihydroergotamine (dhe) (or phentolamine), an alpha-adrenergic blocking agent, induced important changes on the CCK-stimulated gallbladder emptying of 70 volunteer subjects. Two cholecystograms were performed with 10-day intervals in each subject. The first cholecystogram showed gallbladder emptying provoked by a test meal (35 subjects or by 0.5 U. CCK Kg. injected intravenously (35 subjects). During the second cholecystogram 1 mg. of DHE was injected intramuscularly 45 minutes befor the cholecystokinetic stimulus. The drug counteracted the gallbladder emptying induced by both endogenous and exogenous CCK. The effect was more pronounced when DHE was administered prior to the test meal stimulus than before CCK administration. This difference could be explained by a delayed gastric emptying induced by the alpha-adrenergic blockade. Our results suggest that the lack of gallbladder emptying could be due to the relaxation of this organ, in addition to a duodenal spasticity induced by DHE (or phentolamine).


Rapid diagnosis of obstructive jaundice due to pancreatic abscess with pancreaticobiliary fistula.

A case of pancreatic abscess with pancreaticobiliary fistula manifesting as obstructive jaundice of occult etiology is presented. Diagnosis was made preoperatively by skinny needle percutaneous transhepatic cholangiography. In addition, a communication between the biliary tree and the pancreatic abscess cavity was demonstrated in the absence of previous biliary surgery or primary biliary tract disease. We feel this is the procedure of choice for emergency visualization of the biliary tree in a jaundiced patient where a surgically approachable lesion is suspected.


Pancreatic excretion test and barrier hypothesis in progression of chronic pancreatitis.

Simultaneous data of the pancreozymin-secretin test and the pancreatic excretion test with 5,5-dimethyl-2,4-oxazolidinedione DMO) were reported for 50 patients with chronic pancreatitis. The pancreozymin-secretin test was abnormal in 90% of the patients, while the pancreatic DMO excretion test showed abnormality in 100% of the patients. The dynamic process of pancreatic excretory dysfunction is discussed. Over 60% of patients with low to moderate grade chronic pancreatitis showed a discordant pattern of decreased DMO output with normal bicarbonate concentration or normal volume flow. Approximately 96% of patients with advanced grade chronic pancreatitis had a excretory pattern of decreased DMO output with low bicarbonate concentration and decreased volume flow. These findings may further develop a barrier hypothesis in chronic pancreatitis. In the early stage of chronic pancreatitis, when functional capacity of the duct is preserved fairly well, the extraductal barrier to the rapid DMO diffusion into the ducts (diffusion barrier) may be primarily responsible for impaired pancreatic DMO excretion. With progression of chronic pancreatitis, the intraductal barrier (outflow barrier) may become pronounced and precipitate pancreatic excretory dysfunction for DMO. The concept of pancreatic barriers may well serve to systematize major histologic alterations observed in chronic pancreatitis.


Inhibition of ethionine pancreatitis in the rabbit by DL-BETA-3 thienylalanine pretreatment.

Beta-3 thienylalanine, an inhibitor of zymogen formation, was studied in the experimental model of ethionine pancreatitis in the rabbit. Beta-3TA pretreated and nonpretreated rabbits were given ethionine for six days and controls were given chow only. Animals were killed and serum amylase values determined. Pancreatic tissue was studied by light and electron microscopy. Beta-3TA pretreated rabbits on ethionine showed normal amylase values, while those receiving only ethionine showed high values. Microscopic examination showed severe pancreatitis in the nonpretreated group but only mild vacuolization of cells in the Beta-3TA pretreated animals. Electron microscopy demonstrated integrity of rough endoplasmic reticulum in pretreated animals and severe distortion of cytoplasmic organelles in nonpretreated animals.