RESUMEN
BACKGROUND: The role of vitamin A in early primary biliary cirrhosis (PBC) remains uncertain. METHODS: We assessed dark adaptation and assayed vitamin-A-related compounds in 10 patients with early PBC and a group of age- and sex-matched controls. RESULTS: In patients compared with controls: (i) mean final light threshold value was 11.8% greater (p < 0.004), (ii) time taken to see the first light stimulus was longer (2.8 +/- 0.6 vs 1.4 +/- 0.2 min, mean +/- SEM; p < 0.03) and (iii) sensitivity to light stimuli was impaired after 6 min in the dark (p < 0.03). Three patients had an abnormal final light threshold despite receiving regular vitamin A; two had a low serum vitamin A. Raised serum bilirubin and increased age were the most important determinants of impaired dark adaptation. CONCLUSIONS: Patients with early PBC have modestly impaired dark adaptation, despite standard vitamin A supplementation, although these changes may not have a significant effect on visual function. Vitamin A supplementation should be recommended for older patients with jaundice, but its effect should be carefully monitored.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Antihipertensivos/farmacología , Hipertensión Ocular/tratamiento farmacológico , Mecánica Respiratoria/efectos de los fármacos , Timolol/farmacología , Administración Oral , Administración Tópica , Anciano , Anciano de 80 o más Años , Broncoconstricción/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Persona de Mediana Edad , Ápice del Flujo Espiratorio/efectos de los fármacos , Capacidad Vital/efectos de los fármacosRESUMEN
A substantial minority of patients with coeliac disease (estimated at anything between 7 and 30%) fail to respond to treatment with a gluten-free diet. Non-responsiveness may be primary, that is when the patient fails to respond to treatment following initial diagnosis, or secondary, when a patient who has previously had a documented response to gluten exclusion becomes non-responsive to therapy. The commonest cause of non-responsiveness is continued gluten ingestion, either voluntary or inadvertent. Other causes to be considered include intolerances to dietary constituents other than gluten (e.g. milk, soya), pancreatic insufficiency, enteropathy-associated T-cell lymphoma and ulcerative jejunitis. There is some evidence that ulcerative jejunitis is, in fact, a manifestation of lymphoma. The most important steps in the management of the non-responsive coeliac patient are (a) to determine whether the patient is indeed coeliac, (b) to exclude lymphoma and (c) to establish the cause of the non-responsiveness. In those coeliac patients with no demonstrable cause for non-responsiveness, a variety of therapeutic stratagems (mostly based on small, uncontrolled studies) have been described; these include elimination diets, dietary supplementation with zinc and copper, and pharmacological therapy in the form of steroids, azathioprine and cyclosporin. In a minority of non-responsive patients, the clinical course is characterized by a rapid decline, and total parenteral nutrition is required. None of the therapies described above has been subjected to rigorous controlled studies. The precise mechanisms of non-responsiveness in coeliac patients need to be unravelled before rational therapeutic approaches can be established.
Asunto(s)
Enfermedad Celíaca/tratamiento farmacológico , Cobre/uso terapéutico , Zinc/uso terapéutico , Azatioprina/administración & dosificación , Azatioprina/uso terapéutico , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/etiología , Ensayos Clínicos como Asunto , Cobre/administración & dosificación , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Dieta , Alimentos Fortificados , Glútenes/metabolismo , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Nutrición Parenteral Total , Esteroides/uso terapéutico , Zinc/administración & dosificaciónRESUMEN
Factor XIII (XIII), an enzyme found in plasma (present as a pro-enzyme), platelets and monocytes, is essential for normal haemostasis. It may also have a role to play in the processes of wound healing and tissue repair. Inherited XIII deficiency results in a life-long, severe bleeding diathesis which, if untreated, carries a very high risk of death in early life from intracranial bleeding. XIII is a zymogen requiring thrombin and calcium for activation. In plasma, XIII has two subunits: the 'a' subunit, which is the active enzyme, and the 'b' subunit which is a carrier protein. Activated XIII modifies the structure of clot by covalently crosslinking fibrin through an epsilon (gamma-glutamyl)lysine link. It also crosslinks other proteins, including fibronectin and alpha-2-plasmin inhibitor (alpha-2PI), into the clot through the same link. Clot modified by XIII is physically stronger, relatively more resistant to fibrinolysis and may be a more suitable medium for the ingrowth of fibroblasts. Inheritance of factor XIII is autosomal recessive. The majority of patients with the inherited defect show no XIII activity and absence of 'a' subunit protein in plasma, platelets and monocytes. At the molecular level, the defect is not a major gene rearrangement or deletion, but most likely a single point mutation which may be different in each family. Because of the severity of the bleeding diathesis, prophylaxis is desirable and has been shown to be very effective as the in vivo half-life of plasma XIII is long, and low plasma levels are sufficient for haemostasis. Acquired inhibitors have been reported in only two cases with inherited XIII deficiency. Acquired XIII deficiency has been described in a variety of diseases and bleeding has been controlled by therapy with large doses of XIII in such conditions as Henoch-Schönlein purpura, various forms of colitis, erosive gastritis and some forms of leukaemia. Large dose XIII therapy has also been used in an endeavour to promote wound healing after surgery and bone union in non-healing fractures. The use of XIII in these conditions remains controversial. Very rarely a bleeding diathesis results from the development of a specific inhibitor to XIII arising de novo, often as a complication in the course of a disease or in association with long-term drug therapy. The bleeding diathesis in these patients is difficult to treat.
Asunto(s)
Deficiencia del Factor XIII , Secuencia de Aminoácidos , Activación Enzimática , Factor XIII/química , Factor XIII/genética , Factor XIII/fisiología , Deficiencia del Factor XIII/diagnóstico , Deficiencia del Factor XIII/genética , Deficiencia del Factor XIII/terapia , Fibrina/metabolismo , Trastornos Hemorrágicos/etiología , Hemostasis , Humanos , Datos de Secuencia Molecular , Conformación Proteica , Cicatrización de HeridasRESUMEN
The immune status of 29 patients with Crohn's disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohn's disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.
RESUMEN
We tested the hypothesis that super-efficient starch absorption, by reducing the supply of carbohydrate to the colon, may be associated with and possibly promote colonic neoplasia. By means of breath hydrogen measurements following a potato meal and comparison with the hydrogen response to lactulose, the amount of starch escaping small bowel absorption was measured in 10 patients who had a colonic adenoma removed endoscopically and in 10 controls. The subjects' consumption of starch and fiber was assessed. Percentage unabsorbed starch was approximately half as much in the patients (5.3%) compared with the controls (10.9%, P less than 0.05). Consumption of starch and dietary fiber, and mouth-to-cecum transit times were not significantly different. Unabsorbed starch was calculated to contribute to 6.0 g/day colonic carbohydrate in the patients and 10.9 g/day in the controls (P less than 0.05). This study confirms that unabsorbed starch provides an important quantity of colonic carbohydrate and suggests that super-efficient starch absorption, by reducing this provision, may promote colonic neoplasia.
Asunto(s)
Pólipos del Colon/metabolismo , Carbohidratos de la Dieta/metabolismo , Absorción Intestinal , Almidón/metabolismo , Pruebas Respiratorias , Fibras de la Dieta/administración & dosificación , Femenino , Tránsito Gastrointestinal , Humanos , Hidrógeno/análisis , Lactulosa/metabolismo , Masculino , Persona de Mediana Edad , Factores de Riesgo , Solanum tuberosumRESUMEN
Seventeen patients on constant doses of pancreatic enzymes were randomised to receive either cimetidine or placebo for either of two successive six month periods. Nutritional state and maldigestion were assessed at the beginning and end of each period. Reductions in mean values of faecal fat, nitrogen, wet weight, and bile salts of approximately 30% were found on cimetidine therapy. Results showed considerable variation and only the fall in faecal fat was statistically significant. No benefit was demonstrated for height, weight, skinfold thickness, albumin, vitamin A, bone age or Crispin-Norman score.
Asunto(s)
Cimetidina/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Pancreatina/uso terapéutico , Adolescente , Adulto , Ácidos y Sales Biliares/metabolismo , Niño , Preescolar , Ensayos Clínicos como Asunto , Método Doble Ciego , Quimioterapia Combinada , Heces/análisis , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Fenómenos Fisiológicos de la Nutrición , Vitaminas/metabolismoRESUMEN
The vitamin status (vitamins A, E, C, Carotene, B1, B2 and B6) of 18 patients receiving maintenance haemodialysis was assessed. All patients were receiving vitamin B1, B2 and B6 supplements and the effect of stopping these supplements on subsequent vitamin status was further studied. Apart from vitamin A, which was significantly increased in all patients, the mean level of all other vitamins was similar to the control group. Despite these normal group means, individual patients could be identified with low or marginally low vitamin C and B2 levels. When the vitamin B complex supplements were stopped, vitamin B2 and B6 remained normal over the subsequent six months maintenance haemodialysis but there was deterioration in vitamin B2 status. Leucocyte vitamin C levels responded well to oral supplements of 400 mg vitamin C per day. This study suggests that vitamin C and B2 supplements are necessary in patients receiving maintenance haemodialysis, other vitamin supplements being unnecessary.
Asunto(s)
Avitaminosis/epidemiología , Diálisis Renal , Femenino , Humanos , Masculino , Vitaminas/administración & dosificación , Vitaminas/sangreRESUMEN
The water-soluble (B1, B2, B6, C, folic acid) and fat-soluble vitamin (A, carotene, E, and D) status of 36 patients with cystic fibrosis was assessed and compared with a control group of 21 age-matched normal children. Twenty-seven of the patients were receiving vitamin supplements (except folic acid and vitamin E) at the time of investigation. Vitamin B1, B2, and B6 status was adequate in all patients, and there was little evidence of folic acid deficiency. Vitamin C stores might not have been adequate in some of these patients, despite daily supplements with 50 mg of the vitamin. Steatorrhoea, often severe, was present in most of them. Serum carotene and vitamin E concentrations were low in over 90% of patients and were related to the severity of steatorrhoea. Vitamin A was low in over 40% of the patients despite daily vitamin supplements of 4000 IU and correlated with the serum retinol-binding protein level. Serum 25-OH cholecalciferol was low in some patients whether or not they were receiving a daily supplement of 400 IU vitamin D. In a short-term supplementation trial with water-miscible preparations of vitamin A and E in 14 patients, the serum levels of both vitamins responded well to 2 weeks of treatment with 50 mg vitamin E and 4000 IU vitamin A. Except for serum vitamin A, which was lowest in patients with the poorest clinical grading, the other vitamins were not influenced by the clinical grade of the patients.
Asunto(s)
Fibrosis Quística/sangre , Vitaminas/sangre , Adolescente , Ácido Ascórbico/sangre , Niño , Preescolar , Fibrosis Quística/tratamiento farmacológico , Femenino , Ácido Fólico/sangre , Humanos , Lactante , Masculino , Riboflavina/sangre , Vitamina A/sangre , Complejo Vitamínico B/sangre , Vitamina D/sangre , Vitamina E/sangreRESUMEN
1. The effect of pectin on the structure and function of the rat small intestine was compared with that of a standard pellet diet and of a fibre-free basal diet. 2. The length and wet weight of the small bowel was significantly greater inpect in-fed rats than in either pellet- or basal-diet-fed rats. 3. Histological measurements of longitudinal sections from the small bowel showed a significantly greater crypt depth and muscle layer thickness in the mid-jejunum and ileum of the pectin fed rats. Villous height showed less variation. 4. The specific activity of alkaline phosphatase (EC 3.1.3.1) and leucyl-beta-naphthylamidase (EC 3.4.11.1) in mucosal scrapings was significantly lower in the upper jejunum of pectin-fed rats compared with either of the other dietary groups. The differences were not so marked in mid-jejunum or ileum. 5. Glucose absorption measured in vivo from jejunal and ileal loops was similar in all three dietary groups. 6. With two minor exceptions there were no significant differences in any of these measurements between the pellet- and basal-diet-fed rats. 7. These findings could be explained by increased epithelial cell turnover caused by pectin. The possible mechanisms of this are discussed. 8. The effect of pectin on the human small bowel requires study before it can be widely prescribed in man.
Asunto(s)
Intestino Delgado/anatomía & histología , Pectinas/farmacología , Fosfatasa Alcalina/metabolismo , Animales , ADN/metabolismo , Fibras de la Dieta/farmacología , Femenino , Glucosa/metabolismo , Mucosa Intestinal/anatomía & histología , Mucosa Intestinal/metabolismo , Intestino Delgado/efectos de los fármacos , Intestino Delgado/fisiología , Leucil Aminopeptidasa/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Proteínas/metabolismo , RatasRESUMEN
1. The absorption of an oral dose of paracetamol was measured in rats given either a basal fibre-free diet, or the basal diet with either pectin or bran added. 2. Urinary excretion of the oral dose was significantly greater during the first 8 h in the pectin-fed rats compared with those on basal diet, though cumulative excretion after 72 h was the same. 3. Free paracetamol levels in the plasma were significantly higher in the pectin-fed rats compared with those on basal diet at 30, 60, 90 and 120 min after the oral dose. 4. The plasma half-life of intravenously-injected paracetamol was shorter in the pectin-fed rats than in those on basal diet alone, but the antipyrine half-lives were not significantly different. 5. Pectin feeding had no effect on either the apparent volume of distribution of paracetamol and antipyrine, or on the rate of gastric empyting. 6. Perfusion of the whole length of the small bowel showed a significantly greater capacity for paracetamol absorption in the pectin-fed rats. 7. Bran had no effect on paracetamol absorption. 8. It was concluded that dietary fibre intake affects drug absorption and that the effect varies with the type of fibre. Unexpectedly pectin accelerates rather than retards absorption of paracetamol, though the mechansim of this effect is unknown.
Asunto(s)
Acetaminofén/metabolismo , Celulosa , Fibras de la Dieta , Absorción Intestinal , Pectinas/farmacología , Animales , Antipirina/metabolismo , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Semivida , Absorción Intestinal/efectos de los fármacos , Ratas , Factores de Tiempo , TriticumRESUMEN
The effect of dietary selenium (Se) and vitamin E supplementation on tissue reduced glutathione (GSH) and glutathione peroxidase activity has been studied in the rat. Increasing Se intake by 0.4 ppm gave significantly higher enzyme levels in all tissues studied, an effect not influenced by vitamin E intake. Further increasing Se to 4 ppm gave higher enzyme levels in red blood cells only, while in liver there was a significant decrease in enzyme activity probably reflecting Se hepatotoxicity. In the absence of Se supplements increasing dietary vitamin E to 100 mg/kg diet significantly increased enzyme activity but this effect was modified by simultaneous Se supplementation. Se intake had no effect on GSH levels. Rats on a high vitamin E intake 500 mg/kg had a significantly higher tissue GSH level. Dietary Se had a sparing effect on vitamin E, rats supplemented with Se having significantly raised plasma vitamin E levels. These results confirm the role of selenium in glutathione peroxidase and also show that vitamin E influences the activity of the enzyme.