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Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 199 records · Page 11Linked to original sources

The prevalence of vitamin K deficiency in chronic gastrointestinal disorders.

Vitamin K deficiency results in the appearance of abnormal prothrombin, deficient in gamma-carboxyglutamic acid, in the blood. The presence of abnormal prothrombin can be eliminated or lowered by the administration of vitamin K. Since the abnormal prothrombin antigen assay is approximately 1000-fold more sensitive than the prothrombin time for the diagnosis of vitamin K deficiency, this assay was used to evaluate patients with intestinal abnormalities. Vitamin K deficiency was found in 18 of 58 patients (31%) with chronic gastrointestinal disease and/or resection. All patients with vitamin K deficiency had either Crohn's disease involving the ileum or ulcerative colitis treated with sulfasalazine or antibiotics. Abnormal prothrombin levels returned toward normal in patients treated with vitamin K but not in patients who were not treated with vitamin K. The mean plasma vitamin E level in patients with vitamin K deficiency was significantly lower than in vitamin-K sufficient patients (p less than 0.01). We conclude that certain chronic forms of gastrointestinal disorders are associated with vitamin K deficiency.

Adolescent↗

Folic acid uptake characteristics of a human colon carcinoma cell line, Caco-2. A newly-described cellular model for small intestinal epithelium.

To investigate a newly described model for differentiated small intestinal function, folic acid uptake characteristics were examined in the human colon carcinoma cell line, Caco-2. Monolayers of this cell line spontaneously exhibit structural and functional differentiation patterns characteristic of mature enterocytes, with the appearance of brush border microvilli and high activity levels of the enzymes associated with the brush border. Our results concur with other models of folic acid uptake that emphasize the importance of intraluminal factors on micronutrient absorption. Folate uptake declined rapidly between pH 5.8 and 7.5, and was dependent on the initial folate concentration in the media. A dual uptake process is suggested, with a high rate of uptake at folate concentrations below 20 nmol/ml and linear uptake characteristics at higher concentrations.

Cell Line↗

Impairment of taste and olfaction in patients with cirrhosis: the role of vitamin A.

Taste and olfaction sensory modalities and the response to vitamin A replenishment were studied in 37 vitamin A deficient patients (determined by low serum levels and abnormal dark adaptation) with stable alcoholic cirrhosis. Among this group of patients, 11 also had low serum zinc levels which ranged from 45 to 63 micrograms/dl. Initial taste and olfaction mean detection thresholds for all test substances were significantly higher (less sensitive) in all patients as compared to 21 sex-matched healthy subjects of the same age range (P less than 0.05). Twenty-seven patients including the 11 patients with low serum zinc were treated with oral vitamin A (10 000 micrograms/d) for 4 weeks. Among the vitamin a deficient patients there was significant improvement following vitamin A treatment in the mean detection and mean recognition thresholds for bitter and salty taste (P less than 0.01) and for pyridine olfaction (P less than 0.05) regardless of zinc status. Improvement in taste and olfaction correlated with a reversal of serum vitamin A levels and dark adaptation toward normal. The mechanism whereby vitamin A affects specific taste and smell (ie salty and bitter taste; pyridine smell) modalities is at present unknown.

Adult↗

Effect of the administration of zinc sulfate on hypogonadism and impotence in patients with chronic stable hepatic cirrhosis.

Zinc sulfate was administered in a double-blind manner for 6-8 months to cirrhotic outpatients with impotence and/or hypogonadism. Seven placebo and six zinc-treated patients showed mild symptomatic improvement; however, there was no significant clinical difference between the two groups. Serum zinc levels rose significantly in the zinc-treated group but urinary gonadotropin and serum testosterone levels did not change in either group. Zinc sulfate does not appear to be an effective treatment for sexual dysfunction associated with alcohol-induced hepatic cirrhosis.

Adult↗

Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion.

The effect of ethanol on the kinetics of folic acid urinary excretion was studied in five chronic alcoholic patients who were maintained in a folate replete state. For 17 days, 95% ethanol was administered orally at 2-h intervals (X9). The folate pool(s) were labeled with the tritium labeled pteroyl glutamic acid at the start of the period of ethanol ingestion and at the start of a control abstinent period. The 24-h urine volume did not change with consumption of ethanol. Total urinary folate excretion was significantly greater by 20 to 40% in four of five patients during the ethanol administration period (p less than 0.05). The fall-off in urinary radioactivity corrected for total folate excretion (dpm/microgram Lactobacillus casei folate) was resolved into a biexponential decay with two distinct slopes. Ethanol caused the slope of the second component to flatten significantly with mean t1/2 of 63.7 days on ethanol versus 9.6 days off (p less than 0.05). These kinetic results are consistent with the known interference by ethanol of folate utilization in a functional tissue pool.

Adult↗

Zinc and the special senses.

There is evidence that zinc is important for maintenance of the special senses: vision, taste, and smell. Rod function is impaired in zinc deficiency due partly to its role in vitamin A metabolism. However, optic nerve function may also be affected by zinc status. Microophthalmia, anophthalmia, and optic nerve abnormalities have all been found in the offspring of female rats fed zinc-deficient diets. Zinc deficiency clearly decreases taste acuity in both animals and humans. However, other nutritional and non-nutritional conditions also produce hypogeusia. There is limited evidence that zinc deficiency impairs olfactory acuity in humans. New approaches to the assessment of taste and smell abnormalities may provide reliable and reproducible associations between zinc deficiency and taste and smell defects.

Animals↗

Protein-energy malnutrition and liver dysfunction limit the usefulness of the relative dose response (RDR) test for predicting vitamin A deficiency.

The relative dose response (RDR) test was examined for its value in predicting vitamin A nutriture among chronically ill patients with protein-energy malnutrition and among patients with varying degrees of liver dysfunction. The RDR test was elevated (ie greater than 14 per cent) and, thus, predictive of vitamin A deficiency in only 4 out of 9 patients with combined vitamin A deficiency and protein-energy malnutrition. Among 27 patients with liver dysfunction who had vitamin A determinations performed on liver biopsy material, there was no correlation found between the RDR response and the hepatic vitamin A level. Of 12 patients with low hepatic vitamin A levels (less than 100 micrograms/g wet weight), the RDR test was normal in 9 (75 per cent). Inability of the RDR test to predict vitamin A nutriture in patients with protein-energy malnutrition and in patients with liver dysfunction may, in part, be due to inadequate synthesis or release of retinol-binding protein.

Aged↗

Application of a rapid dark adaptation test in children.

The rapid dark adaptation test (after Thornton) has been shown to correlate with classical dark adaptation test results and vitamin A nutriture in adults. Using this test, 27 children in Guatemala (aged 5-12 years) and 18 children in Baltimore (aged 4 and 5 years) were studied. Plasma for vitamin A and zinc analysis was obtained from the Guatemalan children and dietary histories were obtained from the parents of the Baltimore children. All but two children (ages 4 and 5) were able to complete the study. For the Guatemalan group, the mean time to complete the test was 144 s, and for the Baltimore group, 171 s. Rapid dark adaptation test performance was significantly correlated to the dietary intake of vitamin A by a logarithmic model, p less than 0.05. The rapid dark adaptation test appears to be acceptable for use in childhood populations and could complement biochemical determination of vitamin A and/or zinc in clinical settings, field surveys, and research.

Adolescent↗

Deficiency of fat-soluble vitamins in treated patients with pancreatic insufficiency.

Deficiency of fat-soluble vitamins (A,D,E, and K) was evaluated in 15 patients with exocrine pancreatic insufficiency secondary to chronic alcoholic pancreatitis. Mild to moderate steatorrhea was present in all patients despite oral pancreatic enzyme therapy for 27 +/- 4 months (mean +/- SE). Deficiency of a single fat-soluble vitamin was seen in six patients and deficiency of two fat-soluble vitamins was seen in two patients. One patient was deficient in three fat-soluble vitamins. Deficiency of vitamins A and E was most frequent. Treatment with specific vitamin supplements resulted in correction of these vitamin deficiencies. These data suggest that deficiency of a single or multiple fat-soluble vitamins is frequent even in treated patients with pancreatic insufficiency.

Adult↗

The effect of ethanol feeding on zinc balance and tissue zinc levels in rats maintained on zinc-deficient diets.

We have studied tissue zinc levels and zinc balance in isocalorically pair-fed weanling rats on ZD liquid diets (0.9 microgram of zinc per milliliter of diet). Tissues were analyzed for zinc levels at weekly intervals while the animals were on the diets. The experimental animals were fed a ZDE diet, whereas sucrose was isocalorically substituted for alcohol in the pair-fed controls. After 1 week on ethanol feeding, the zinc content (microgram/gm wet weight) of the testes of the ethanol-fed rats was significantly lower than of the controls (p less than 0.001). After 2 weeks of ethanol, ethanol-fed animals also showed significantly lower zinc content in liver, hair, spleen, and kidneys (p less than 0.02) than their pair-fed controls. The zinc levels of the experimental animals in all tissues after 3 and 4 weeks of ethanol feeding were significantly lower (p less than 0.001) than that of the pair-fed controls with the exception of bone. Urinary and fecal zinc excretions of the ethanol-fed rats were significantly higher than that of the controls. Cumulative mean +/- S.D. fecal zinc excretions (microgram/28 days) were 1557 +/- 160 among the ethanol-fed animals vs. 730 +/- 150 among controls, p less than 0.01. Ethanol resulted in a mean negative zinc balance of 520 micrograms over 28 days, whereas controls showed a positive cumulative zinc balance of 300 micrograms. Thus ethanol ingestion resulted in negative zinc balance and decreased zinc concentrations of most tissues as compared to pair-fed controls.

Alcoholism↗

Evaluation of the relative dose response test for vitamin A nutriture in cirrhotics.

The rise in serum vitamin A 5 h after a 450 microgram oral dose of the vitamin (retinyl palmitate) was used to assess vitamin A nutriture in patients with alcoholic cirrhosis. The test was carried out on 21 hospitalized male patients and 12 normal age and sex-matched control subjects. The relative dose response (RDR), expressed as percentage, was calculated as A5 - A0/A5 X 100 where A0 = the fasting serum retinol level and A5 = the serum retinol 5 h postdosing. Vitamin A-deficient patients (those with serum retinol levels less than 30 microgram/dl and an abnormal dark adaptation test or RDR greater than or equal to 14%) were treated with 4 wk of oral vitamin A (10,000 microgram/day), then repeat RDR and dark adaptation tests were carried out. Among eight cirrhotics with abnormal dark adaptation, the mean +/- SEM RDR was 21 +/- 9 versus 3 +/- 3% in patients with normal dark adaptation (p less than 0.01). RDR tests of patients with normal dark adaptation did not differ from those of 12 normal age and sex-matched control subjects (normal RDR response 0 to 14%). Among patients found to be vitamin A-deficient, treatment with vitamin A resulted in the mean +/- SEM RDR declining from 21 +/- 9 to 5 +/- 2%. However, this fall failed to reach statistical significance (p = 0.06). The RDR test appears to be useful as a predictor of vitamin A deficiency, even among patients with far advanced hepatic disease.

Dark Adaptation↗

The interrelationship of thyroid hormones with vitamin A and zinc nutritional status in patients with chronic hepatic and gastrointestinal disorders.

To define the role of vitamin A, retinol binding protein, and zinc deficiency in producing the thyroid hormone abnormalities found in chronic illness, we studied 62 clinically stable patients with hepatic and gastrointestinal disorders. Serum triiodothyronine (T3) and free T3 index (FT3I) were depressed compared to controls (p less than 0.05) in the patients. Retinol binding protein and prealbumin levels correlated with both T3 and FT3I (p less than 0.01), whereas vitamin A levels did not. Vitamin A therapy in patients with documented vitamin A deficiency produced an increase in T3, thyroxine (T4), FT3I, FT4I, and free T3 by dialysis, with a concomitant increase in retinol binding protein and no alteration in prealbumin concentrations. Zinc-deficient patients had significantly depressed T3 and FT3I (p less than 0.001) and increased prolactin levels (p less than 0.01). Zinc supplementation failed to return any of these parameters to normal. Vitamin A therapy in normals produced a transient decrease in T3 and T4 after 1 wk of therapy, but after a further 2 wk, thyroid function returned to normal. Our data suggest a causal relationship between the pathogenesis of deranged vitamin A-retinol binding protein metabolism and the low T3 syndrome either by interfering with T4 entry into tissues or by directly affecting the enzymatic conversion of T4 to T3.

Chronic Disease↗