Search PubMed⌕ Search

Biomedical subjects

J B Watkins

Publications and source records attributed to J B Watkins.

At least 109 records · Page 6Linked to original sources
PubMed1981

Fecal 13C analysis for the detection and quantitation of intestinal malabsorption. Limits of detection and application to disorders of intestinal cholylglycine metabolism.

The use of 14CO2 breath tests and fecal analyses for the detection and quantitation of intestinal malabsorption has been extensively documented in adult subjects. The use of stable isotopes has extended the range of breath test applications to include pediatric and obstetric subjects. Here we report a fecal 13C analysis that can be used in conjunction with 13CO2 breath tests. Twenty-four-hour fecal samples were collected before and after the administration of a labeled substrate. The samples were homogenized and combusted to CO2, and the 13C abundance was determined by high-precision, differential isotope ratio mass spectrometry. The isotopic variation between successive 24 hr fecal samples was 0.6 0/00 (0.0006 atom percent). This variation limited the sensitivity of the fecal analysis to 13 mumol of 13C label per mold of fecal carbon. Simultaneous cholyglycine 13CO2 breath tests and fecal assays were performed in five children. One child with bacterial overgrowth had an abnormal breath test and a normal fecal test. Of three children with ileal dysfunction, only one had an abnormal breath test, whereas the fecal test was abnormal in all three, Both the breath test and fecal test were abnormal for a child who had undergone an ileal resection. Both tests were normal for a child with ulcerative colitis.

Adolescent↗
PubMed1980

13C abundances of nutrients and the effect of variations in 13C isotopic abundances of test meals formulated for 13CO2 breath tests.

Unlike 14CO2 breath tests, 13CO2 breath tests are performed in the presence of a large background of naturally occurring isotope. Because the exact abundance of 13CO2 in breath can be changed by variations in diet, a study of the 13C abundance of dietary constituents and their effects on breath 13CO2 has been undertaken. Dietary constituents have been combusted to CO2 and the relative abundance of 13C analyzed by mass spectrometry. Breath CO2 was collected and isotopically analyzed after the ingestion of several dietary constituents and test meals. The 13CO2 abundance of breath CO2 was shown to change in response to the 13C abundance of the substrate being oxidized. Conversely, a test meal that closely approximates the 13C abundance of fasting breath CO2 from North Americans was shown not to alter the 13CO2 abundance in breath. Investigation of the breath 13CO2 response to individual 13C-labeled dietary constituents demonstrated that amino acids produced the earliest 13CO2 response followed in order by medium chain triglycerides, carbohydrates, and long chain triglycerides. Because of the variation in 13C abundances in nature, the 13C abundance of any unlabeled substrate ingested during a 13CO2 breath test must be considered in order to eliminate artifacts that may reduce the sensitivity of the breath test or produce erroneous results. Methods for correcting breath tests for changes in background 13CO2 abundance are also discussed.

Adult↗
PubMed1980

The effect of insulin and of anti-insulin serum on handling of sodium by the isolated, perfused kidney of the streptozotocin-diabetic rat.

We studied the effects of insulin and of anti-insulin serum (AIS) on sodium excretion in isolated diabetic and normal, fed, rat kidneys perfused at a constant pressure of 100 mm Hg with Krebs-Ringer bicarbonate buffer containing 7.5% bovine serum albumin and 5 mM glucose and gassed with 95% O2 and 5% CO2. The addition of insulin produced antinatriuresis in kidneys from diabetic rats but not in those from normal rats. Moreover, before the addition of insulin, the baseline rate of sodium excretion was greater in the diabetic rat kidney than in the normal rat kidney, while no differences in glomerular filtration rate (GFR) were observed. The addition of AIS (enough to bind 1.4 mU of insulin per milliliter of perfusate) produced a brisk natriuresis in kidneys from normal rats, and this natriuresis could be reversed by the addition of saturating amounts of insulin. By contrast, the addition of normal guinea pig serum to the perfusate of normal kidneys or AIS to the perfusate of diabetic kidneys was unassociated with natriuresis. We conclude that (a) insulin promoted antinatriuresis in diabetic but not in normal rat kidneys, (b) AIS promoted natriuresis in normal kidneys, and (c) this natriuresis was a specific effect of AIS and was reversed by the addition of insulin. Our data support the view that insulin-induced antinatriuresis depends on endogenous levels of circulating insulin and on the availability of insulin-binding sites in the kidney.

Animals↗
PubMed1980

Liver in the cerebro-hepato-renal syndrome: defective bile acid synthesis and abnormal mitochondria.

Two infants with the cerebro-hepato-renal syndrome (Zellweger's disease) exhibited cholestasis and progressive liver damage. Because abnormalities of mitochondrial structure and function have been reported in this condition, we examined the bile acids for evidence of defects in the mitochondrial phase of bile acid synthesis, namely, oxidation of the cholesterol side chain to form C-24 bile acids. The presence of increased amounts of the C-27 bile acid intermediates (trihydroxycoprostanic acid, varanic acid, and dihydroxycoprostanic acid) were noted and identified by gas-liquid chromatography-mass spectrosocopy confirming that a defect in the mitochondrial pathways for bile acid side chain cleavage is involved in this entity. The clinical course, liver histopathology, and hepatocyte ultrastructural abnormalities suggest that these bile acids may reflect an underlying mitochondrial dysfunction in this disease and possibly may contribute to the progressive hepatic lobular fibrosis observed in these patients.

Abnormalities, Multiple↗
PubMed1979

Solution properties of sulfated monohydroxy bile salts. Relative insolubility of the disodium salt of glycolithocholate sulfate.

Physical-chemical properties of the major sulfated monohydroxy bile salts of man are described. In general, the sulfates are significantly more water-soluble than the non-sulfated species as a result of lower critical micellar temperatures, high aqueous monomeric solubilities and critical micellar concentrations. Nevertheless, at 37 degrees C the disodium salt of glycolithocholate sulfate, the major monohydroxy bile salt of man is not more soluble than its non-sulfated form. Since aqueous solubility correlates inversely with the cholestatic potential of bile salts, our results suggest that this sulfate may be potentially hepatoxic. Micellar solubility of phosphatidylcholine and cholesterol by the majority of non-sulfated and sulfated monohydroxy bile salts is slight. Nonetheless, phosphatidylcholine is very well solubilized by taurolithocholate sulfate but cholesterol solubility is not increased appreciably. Cholesterol saturation in model bile systems of taurochenodeoxycholate and phosphatidylcholine is impaired by the addition of sulfated lithocholate conjugates but with physiological bile salt compositions this reduction is not significant.

Bile Acids and Salts↗
PubMed1979

Recurrent abdominal pain of childhood due to lactose intolerance.

The role of lactose malabsorption was studied prospectively in 80 schoolchildren with recurrent abdominal pain. Malabsorption was documented in 40 per cent (16 of 59 whites, 12 of 16 blacks and four of five Hispanic children) on the basis of elevated levels of hydrogen in their breath. Those with lactose malabsorption, however, were not clinically distinguishable on the basis of past milk ingestion (P greater than 0.05), weekly pain frequency (median, five vs. six times), presence of diarrhea (40 vs. 27 per cent) or symptom response to lactose load. In children with malabsorption who completed a six-week diet trial, 70 per cent reported increased frequency of pain (P less than 0.002) when placed on their usual lactose-containing diet. Lactose malabsorption has a substantial role in the symptoms of children with recurrent abdominal pain, and it should be considered before performing invasive procedures or assuming a psychogenic origin.

Abdomen↗
PubMed1979

Laboratory measures of copper metabolism in the differentiation of chronic active hepatitis and Wilson disease in children.

The accuracy of the serum ceruloplasmin level in distinguishing chronic active hepatitis from Wilson disease was compared to the 24-hour urinary copper excretion and hepatic copper content in 20 untreated patients with chronic active hepatitis and 25 with Wilson disease. Serum ceruloplasmin levels were decreased in five patients (25%) with chronic active hepatitis and were normal in seven patients (28%) with Wilson disease at the time of diagnosis. The 24-hour urinary copper excretion failed to provide accurate discrimination between the two groups, being elevated in all patients with Wilson disease and in five of eight patients with chronic active hepatitis studied. All patients with Wilson disease had hepatic copper levels greater than 400 microgram/gm dry weight, whereas patients with chronic active hepatitis had levels less than 300 microgram/gm dry weight. The discriminatory value of hepatic copper concentration makes this the most reliable test for differentiating chronic active hepatitis and Wilson disease in children and adolescents. The serum ceruloplasmin level may not be significantly accurate for definitive diagnosis in this age group.

Adolescent↗
PubMed1979

Mesenteric vascular occlusion and varices complicating midgut malrotation.

Long-standing complete obstruction of the superior mesenteric artery and vein and recurrent gastrointestinal bleeding from varices within the bowel were encountered in a child as a complication of midgut malrotation and volvulus. This condition is unusual, but should be considered in cases of gastrointestinal bleeding, or when small bowel biopsy is contemplated for the evaluation of diarrhea or malabsorption in cases of malrotation.

Child, Preschool↗
PubMed1979

Enhanced colonic carcinogenesis with azoxymethane in rats after pancreaticobiliary diversion to mid small bowel.

Since biliary excretion of metabolites might determine the pattern of intestinal neoplasms induced by azoxymethane, the number and distribution of tumors were studied in rats after pancreaticobiliary diversion to the mid small bowel. Pancreaticobiliary diversion was performed either immediately before the first of 16 weekly injections of azoxymethane or 10 days after the last. Seven months after pancreaticobiliary diversion, persistent ileal hyperplasia was manifested by higher levels of mucosal RNA and DNA compared with controls (34--102%: P less than 0.001), while there was little residual adaptation in the colon. Qualitative and quantitative analysis of fecal bile acids 6--26 wk after pancreaticobiliary diversion showed few differences. Pancreaticobiliary diversion doubled the incidence of colonic tumors, whether operation preceded (P less than 0.005) or followed (P less than 0.02) the course of azoxymethane. Suture-line tumors were common in the small bowel, particularly in the transposed duodenal stump. Despite intense ileal hyperplasia as a consequence of pancreaticobiliary diversion, the ileum remained resistant to chemical carcinogenesis. The potentiation of colonic neoplasms by pancreaticobiliary diversion probably depends on the stimulation of colonic mucosal proliferation.

Adenocarcinoma↗
PubMed1978

Enhancement of bovine pancreatic ribonuclease activity by mercaptoethanol.

Incubation of ribonuclease with 0.1M mercaptoethanol at pH 8.5 can increase the enzyme's hydrolytic activity toward cytidine 2',3'-monophosphate (cyclic CMP) under standard assay conditions. Cation-exchange chromatography of the ribonuclease-thiol reaction mixture revealed seven fractions. The fraction with the highest activity had an approximate tenfold decrease in the apparent Michaelis constant for cyclic CMP with respect to native ribonuclease. The enhanced activity is a metastable property since this fraction reverts back to the control activity and chromatographic behavior of native ribonuclease on standing in solution at room temperature.

Animals↗
PubMed1978

Cholelithiasis and Wilson disease.

We have studied three children with Wilson disease who had clinical symptoms suggestive of cholecystitis as well as radiologic evidence of gallstones, subsequently proven at the time of laparotomy. The gallstones from the patients with Wilson disease had an appreciably higher content of cholesterol than gallstones from age-matched children with hemolytic disease. Since gallstones may be present for years before they produce clinical symptoms, young patients with Wilson disease should undergo routine investigation for the presence of stones; cholelithiasis should also be considered in the differential diagnosis of abdominal pain in such patients.

Child↗
PubMed1978

Sucrose malabsorption in children: noninvasive diagnosis by interval breath hydrogen determination.

To assess whether malabsorption of specific sugars is easily detected in a pediatric population by interval measurement of breath hydrogen excretion, hydrogen concentration was determined following administration of oral sucrose to six sucrose-intolerant children with congenital sucrase-isomaltase deficiency and in 16 sucrose-tolerant control subjects. Breath samples were collected by means of a newly devised nasal prong technique not requiring active patient cooperation and suitable for use in all age groups. Breath hydrogen concentrations obtained by samples collected by this method correlated highly (r = 0.94) with the previously validated modified Haldane-Priestley tube method for sampling alveolar air. Identification of sucrose-intolerant individuals was achieved on the basis of hydrogen excretion: peak values, expressed as parts per million above baseline (deltappm), equalled 114 +/- 63 (mean +/- SD) versus 2.4 +/- 3.6 deltappm in control subjects (P = 0.007). Best discrimination between the groups occurred at 90 minutes postingestion. The findings validate this simple method for collection of expired air and demonstrate that breath hydrogen determination permits the noninvasive detection of sucrose malabsorption in children.

Adolescent↗
PubMed1978

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.

Cellulose↗
PubMed1978

Determination of conjugated bile acids in human bile and duodenal fluid by reverse-phase high-performance liquid chromatography.

A simple mehtod using reverse-phase liquid chromatography is presented for resolution and quantitation of the major conjugated bile acids of man, including the glycine and taurine conjugates of the dihydroxy bile acids, chenodeoxycholic and deoxycholic acid. Using modern, high-performance chromatographic equipment, analysis time is less than 30 minutes. The quantitative range of the method, with detection by refractive index, is 0.05 to 0.1 mumol of bile acid and the limit of detection for an injection sample is 0.01 mumol. This provides a sensitivity sufficient for analysis of dilute duodenal and gallbladder bile with minimal sample preparation.

Bile↗
PubMed1978

Diagnostic dilemmas of Wilson's disease: diagnosis and treatment.

Wilson's disease, an autosomal recessive disorder of copper metabolism, may defy diagnosis in children. The classical triad of Kayser-Fleischer rings, neurologic dysfunction, and hypoceruloplasminemia may be absent. Patients may be seen initially with acute or chronic hepatitis, hemolytic anemia, or neurologic dysfunction. Guidelines are presented for diagnosis of Wilson's disease based on a review of 25 pediatric and adolescent patients. A high index of suspicion in necessary so that therapy with penicillamine may be begun before irreversible liver or neurologic damage occurs. The prognosis is excellent when diagnosis and treatment are established early.

Adolescent↗