Vitamin A relative dose response test: validation by intravenous injection in children with liver disease.

The relative dose response (RDR) test has been proposed as a tool for estimation of total body stores of vitamin A. In this study we have validated a variation of this test in children with or without liver disease. Administration of vitamin A was done by intravenous injection of 1000 micrograms of retinyl palmitate. We conclude that the RDR test by intravenous injection performed after 5 h is a reliable and sensitive indicator of vitamin A status. Values found were greater than 20% when liver vitamin A concentration is less than 20 micrograms/g liver and less than 10% when liver vitamin A concentration is greater than 20 micrograms/g liver. We also conclude that the RDR test can be applied to evaluate the efficiency of vitamin A therapy and we confirm that plasma retinol levels should not be used to screen vitamin A status.

Impression cytology detects subclinical vitamin A deficiency.

The vitamin A status of 16 children with normal eyes and liver disease was evaluated by plasma retinol concentration and by liver vitamin A concentration or iv relative-dose-response test. Conjunctival impression cytology was performed on each child. All children with normal vitamin A status had normal conjunctival impression cytology. All children with abnormal vitamin A status had abnormal conjunctival impression cytology despite their seemingly normal clinical ocular examination. These results suggest that impression cytology can identify individuals with physiologically significant, preclinical vitamin A deficiency.

Short- and long-term vitamin A treatment in children with cholestasis.

Newborns have limited reserve supplies of vitamin A. Infants with chronic cholestasis are in a precarious nutritional state because of their limited ability to build these stores even though the vitamin is present in their diet. In this study, we investigated liver concentrations of vitamin A in 30 children with extrahepatic biliary atresia. We demonstrate that correction of the deficiency occurs after intramuscular administration of a water-miscible solution of retinyl palmitate (100,000 IU, or 30 mg retinol equivalent). Furthermore, we evaluated the effect of vitamin A injections on liver and blood concentrations in nine children with chronic cholestasis over a 1-y period. We conclude this treatment is efficient and is well tolerated.

The influence of schistosomiasis on the serum concentrations of retinol and retinol binding protein of a rural population in Liberia.

121 persons from rural areas of central Liberia were examined for possible interactions between helminthic infections and the retinol (vitamin A) and retinol binding protein (= RBP) status. About 2/3 of this mainly adult population had retinol and RBP serum concentrations less than or equal to 400 micrograms/l and less than or equal to 40 micrograms/ml, respectively. Only one person had a serum retinol concentration less than 100 micrograms/l which is critical for the appearance of xerophthalmia. The retinol and RBP concentrations showed a linear, positive correlation. 19 parasitologically helminth free individuals had mean serum retinol and RBP concentrations of 414 micrograms/l and 43 micrograms/ml, respectively, while the corresponding values of 20 individuals with schistosomiasis as the only helminthic infection were 339 micrograms/l and 35 micrograms/ml. 65 other persons with mixed intestinal and/or tissue helminthiases, and 9 persons with pure Onchocerca volvulus infection exhibited intermediate mean concentrations. 32 persons without serological evidence of helminthic infections had higher serum concentrations of retinol and RBP than 32 individuals in whose sera at least one raised antibody titer was found in the enzyme-linked immunosorbent assay with 3 different helminthic test antigens. In addition to age, sex and pregnancy schistosomiasis might be a further risk factor of latent retinol and RBP deficiency among adults and teenagers living in a schistosomiasis endemic area.

A longitudinal study on relations of retinol with parasitic infections and the immune response in children of Kikwawila village, Tanzania.

From 1982 to 1984 170 children of Kikwawila village (Kilombero district, Tanzania) were followed for nutritional (anthropometric measures, hematocrit, serum retinol, prealbumin, and zinc concentrations), parasitological (malaria parasitemia, urinary schistosomiasis, intestinal parasites) and immunological characteristics. Between 2.9% and 12.4% had serum retinol levels less than 100 micrograms/l which indicate deficiency. Retinol concentrations were correlated with age, hematocrits, prealbumin levels and mid upperarm circumferences. The latter correlation may be useful in nutritional surveys and primary health care programs for the identification of populations at risk of retinol deficiency. No association was found between average retinol levels and the presence of parasites, with the exception of malaria. Retinol levels were inversely correlated with malaria parasitemia in 1982, and directly correlated with antibody titers to synthetic sporozoite peptide in 1984. Since retinol, malaria parasitemia, and antisporozoite antibodies increased with age, confounding by age could not be excluded. Six months after administration of ornidazole in a single oral dose of 10 mg/kg, a significant effect on the prevalence of Giardia lamblia was found. Following treatment, average retinol levels were increased in persons with confirmed G. lamblia infections, but not in uninfected or untreated controls.

Vitamin nutrition in patients on continuous ambulatory peritoneal dialysis (CAPD).

In 10 patients who had been on CAPD for 8.75 months, blood levels of the vitamins A, E, B-complex and C were measured and a precise diet history using food weighing for 3 days was obtained. Plasma vitamin A was elevated in all; since retinol binding protein (RPB) was elevated even more, the ratio of retinol to RBP was low. Vitamin E levels were also high. The vitamins B1, B2 and B6 were measured using erythrocyte enzyme activities. Vitamin B1 was low or borderline in 5, vitamin B6 was decreased in 3 and erythrocyte pyridoxal phosphate in 8 patients. Folic acid was low or borderline in 6 patients, whereas the vitamins B2 and B12 were normal in all. Vitamin C was diminished in 4 patients, and in dialyzate 60% of plasma concentrations were found. The intakes of the vitamins B1, B6 and B12 were below the recommended range. After supplementation of water soluble vitamins for 7 weeks the vitamins A and E remained elevated and B1 remained low, B6 and C had normalized in all and folic acid was markedly elevated. In CAPD decreased blood concentrations of some water soluble vitamins are found due to insufficient dietary intake and loss into dialyzate. Tentative recommendations are given for the replacement of the vitamins B1, B6, folic acid and C.

Influence of vitamin A deficiency on the excretion of uromucoid and other substances in the urine of rats.

Male Fü-albino rats were weaned at the age of four weeks and maintained on a vitamin A-deficient diet. When they were 14-18 and 21-26 weeks old, the concentration of uromucoid, calcium and other substances possibly important for the pathogenesis of urinary calculi were determined. Reduced uromucoid excretion with hypercalciuria and reduced phosphate levels were observed. Subsequent examination of the kidneys did not demonstrate the presence of nephrocalcinosis or lithiasis. The relation between vitamin A, the synthesis of uromucoid and AMPS and calcium metabolism in the renal tubules is discussed.

Reduced vitamin A tolerance in a hyperlipidaemia patient with rapid destructive and hyperostotic osteoarthritis of the hip.

A 59-year-old patient suffering from hyperlipidaemia developed a chronic vitamin A intoxication syndrome after ingestion of 30000 IE retinol/daily over a period of six years. Functional disability of the right hip was caused by radiologically documented hyperostosis of the acetabular circumference. Finally, a prosthesis had to be implanted because of rapid destructive osteoarthritis of the right hip. Implications of vitamin A for rheumatological management are discussed.

The biochemical and physiological role of vitamins A and E and their interactions.

The therapeutic applications of vitamin A and vitamin E are reviewed, with special references to their role in the retinal functions, epithelial differentiation and maintainance, deficiency due to liver diseases and malabsorption, antioxidant activity, membrane protection, and antiatherogenic function. The interference between the two vitamins and their synergism is discussed on the basis of the protective role of tocopherol on retinol. From experimental studies on chicken, a mathematical model linking the optimal plasma value of the two vitamins is obtained.

Tolerance and effects of high doses of ascorbic acid. Dosis facit venenum.

The few literature references suggesting adverse effects of high doses of ascorbic acid are outnumbered by a large number of clinical studies in which no adverse effects have been observed. Up to 5 g ascorbic acid daily may be administered safely even over a long term. Favourable effects of even higher doses in man may justify therapeutic trials in the range of 15 g daily which in our trials have proven safe during treatment of up to 2 years. Nevertheless, trials in the high dosage range mentioned should always be closely supervised by a physician, being aware that exceptional behaviour can occur at any time, as exception proves the rule.

Vitamins in "malattie evolutive".

Vitamins are playing an increasingly important role in "malattie evolutive", both in the newer sense meaning diseases connected with general development and in the original sense of progressive diseases. Examples of the preventive use of vitamins in certain development phases are the prophylactic administration of vitamin E in premature and new-born babies as protection against retrolental fibroplasia, vitamin K against haemorrhage and vitamin D against bone deformation. Deficient ossification in osteogenesis imperfecta can be prevented by high doses of vitamin C. Recently, greater medical interest has centred around the preventive use of high vitamin dosage in "malattie evolutive" in the original sense. Here, the main interest has been in vitamins E and C which, as recent investigations show, are capable of retarding or preventing deleterious cardiovascular or oncological diseases.

[Blood coagulation in man during a 3-week daily rg L(+)-ASCORBIC ACID ADMINISTRATION]. / Die Blutgerinnung beim Menschen während einer dreiwöchigen Einnahme von 4 gL(+)-Ascorbinsäure pro Tag

A daily dose of 4 g L (+) ascorbic acid administered for 3 weeks showed no significant influence on coagulation of venous blood, as determined by thromboelastography. The investigation was carried out on 11 healthy men aged from 25 to 45 with no history of abnormal blood clotting. The mean values of 7 different coagulation parameters are given, the differences in these parameters in individual subjects (before and after administration of ascorbic acid) being checked for significance by means of the Wilcoxon test for pair differences. The values found are comparable with those in the literature.

Dexpanthenol (Ro 01-4709) in the treatment of constipation.

Functional constipation is not a life-threatening disease, but as a chronic state it worries the patient and causes him discomfort and often leads him to self-medication with potentially dangerous drugs. Ro 01-4709 contains as active substance dexpanthenol, which is the alcohol of pantothenic acid, a vitamin of the B-complex. In the cells, dexpanthenol is readily oxidized to pantothenic acid, which stimulates peristalsis when administered in therapeutically effective doses. Ro 01-4709 has already proven its efficacy in the prevention and treatment of adynamic ileus. Recently, several open and two double-blind studies have been carried out, investigating the efficacy of oral Ro 01-4709 in the treatment of chronic functional constipation. The two double-blind studies showed Ro 01-4709 to be superior to placebo in all parameters measured. The studies with an open design also demonstrated a favourable effect of Ro 01-4709 in the treatment of chronic functional constipation. Owing to its physiological action-which is in a favourable contrast to that of normal laxatives. Ro 01-4709 can be recommended for the treatment of functional constipation in pregnant women, children and the elderly.

Water soluble vitamins in chronic hemodialysis patients and need for supplementation.

Forty-three patients on chronic hemodialysis who before the present study had only received a low-dose supplement of folic and ascorbic acid were studied prospectively for one year. After baseline values were obtained in month one, increasing doses of postdialysis vitamin supplements were prescribed for the vitamins which were found to be insufficient in order to determine the minimal amount of oral postdialysis supplement necessary to normalize vitamin levels. According to our results no systematic supplement was indicated for biotin, riboflavin or vitamin B12. For folic acid and vitamin C, supplementation with lower doses than those prescribed in many dialysis units allowed optimal vitamin levels in the majority of patients; 2 to 3 mg/week (300 to 400 micrograms/day) of folic acid and of 1000 to 1500 mg/week (150 to 200 mg/day) of vitamin C was considered sufficient. A severe pyridoxine deficiency was present in most (> 80%) unsupplemented patients, either as judged by pyridoxal-5-phosphate determinations in plasma or determination of specific enzyme activation in erythrocytes (EGOTo and alpha-EGOT); a postdialysis supplement of at least 100 to 150 mg/week of pyridoxine hydrochloride (> 15 to 20 mg/day) corrects this deficiency. The activity of the thiamine-dependent enzyme transketolase in erythrocytes (ETKo) was insufficient in 35% and marginal in 21% of the patients, while whole blood thiamine determined simultaneously in 10 of the ETKo-deficient patients was within the normal range. These results suggest that in uremia insufficient transketolase activity may be related to inhibition of the enzymatic system rather than to true vitamin deficiency. On a long-term basis a supplement of 200 to 300 mg/week of thiamine hydrochloride (30 to 45 mg/day) restored ETKo to satisfactory levels in most patients; whether this supplement is to be recommended warrants further studies.