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Biomedical subjects

C H Halsted

Publications and source records attributed to C H Halsted.

At least 91 records · Page 5Linked to original sources

Jejunal perfusion of simple and conjugated folates in tropical sprue.

Absorption of labeled simple 3',5',9'-(3)H pteroylmonoglutamate, ([(3)H]PG-1) and conjugated pteroyl-mu[(14)C]glutamyl-gamma-hexaglutamate, ([(14)C]PG-7) folates was assessed in six patients with tropical sprue, before and after 6 mo of treatment, utilizing jejunal perfusion and urinary recovery techniques. Degradation products of [(14)C]PG-7 which were produced during perfusion were identified by DEAE-cellulose column chromatography. Jejunal mucosal activities of folate conjugase, lactase, sucrase, and maltase were measured in every patient. Malabsorption of both [(3)H]PG-1 and [(14)C]PG-7 was found in every untreated patient, with significant improvement after therapy. The urinary excretion of (3)H and (14)C paralleled the luminal disappearance of both isotopes. The chromatographic patterns of intraluminal degradation products of [(14)C]PG-7 obtained during perfusion did not differ from those previously found in normal subjects and were similar in studies performed before and after treatment. The activity of folate conjugase was increased in the mucosa of the untreated patients when compared to the post-treatment levels while the activities of mucosal lactase, sucrase, and maltase were originally low and increased significantly after therapy. These observations suggest that folate conjugase originates at a different mucosal locus than the brush border disaccharidases, and are consistent with previous evidence that folate conjugase is an intracellular enzyme. The present studies have demonstrated unequivocal malabsorption of both simple and conjugated folates in tropical sprue. In tropical sprue, folate malabsorption is the reflection of impaired folate transport and not of impaired hydrolysis.

Journal Article↗

Association of inflammatory bowel disease and large vascular lesions.

A case of inflammatory bowel disease with associated multiple large vessel vascular lesions similar to that seen in Takayasu's arteritis is described in a 15-year-old female. It is suggested that this type of vascular lesion may represent another rare systemic manifestation of inflammatory bowel disease.

Adolescent↗

Jejunal perfusion of simple and conjugated folates in man.

The technique of human jejunal perfusion was used to study the process of digestion and absorption of conjugated folates in five healthy volunteers. The test solution of isotonic saline contained equimolar concentrations of purified [3H]pteroylmonoglutamate ([3H]PG-1) and of [14C]pteroylheptaglutamate ([14C]PG-7) which was labeled on the first glutamyl unit. Calculations were made of the luminal disappearance of each labeled folate, and degradation products of [14C]PG-7 were identified in luminal contents obtained 15 and 30 cm from the infusion site. The percentage of disappearance of [3H]PG-1 was 74.7% and of [14C]PG-7 was 52.6% (P less than 0.001)9 Column chromatography of intestinal aspirates demonstrated a spectrum of 14C-labeled folates corresponding to chain lengths from [14C]PG-1 to [14C]PG-7, with distal accumulation of derived [14C]PG-1. Intraluminal hydrolysis of [14C]PG-7 was excluded by finding the compound unchanged after in vitro incubation with intestinal juice obtained by saline perfusion or siphonage. These data indicate that there are separate rates for the luminal disappearance of PG-1 and PG-7, and show that the digestion of PG-7 requires its contact with the intestinal mucosa. The evidence suggests that progressive mucosal hydrolysis is integral to the process of PG-7 absorption in man.

Carbon Radioisotopes↗

Effect of cycloheximide on intestinal secretion induced by hypertonic glucose.

Since intestinal fluid production in experimental cholera can be limited by cycloheximide, an inhibitor of protein synthesis, the same agent was used to determine whether there are similar mechanisms for fluid production in response to an osmotic gradient. Intestinal fluid production was measured by perfusion of paired rabbit jejunal loops (10 cm) in vivo, in controls, and in animals receiving 20 mg/kg intravenous cycloheximide one hour before perfusion. In each animal one loop was perfused with isotonic Ringer's lactate and the other with a hypertonic glucose-Ringer's lactate solution, 563 mOsm/litre. In control animals mean fluid production in the hypertonic loop was seven times that in the isotonic loop. Cycloheximide decreased the fluid response to the hypertonic stimulus by one half (p < 0.001). In a separate measurement of bidirectional sodium fluxes, using sodium(22), it was shown that the decreased net sodium movement into the lumen observed after cycloheximide was the result of decreased flux from blood to lumen. The major histological alteration after cycloheximide was on the crypt epithelial cells with sparing of villus crests. Glucose absorption was unaffected. These data parallel the observed effect of cycloheximide on cholera exotoxin induced secretion, suggesting that a process requiring continued protein synthesis is also necessary for the intestinal fluid response to an osmotic gradient.

Animals↗