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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Vitamin neurotoxicity. 146 88

The paper reports on the efficacy and side effects of high-dose vitamin A, administered as adjuvant treatment for resected stage I lung cancer in a randomized clinical trial. After a median follow-up of 28 months, 283 patients were evaluable: 138 allocated to treatment with retinol palmitate (300,000 IU daily for at least 12 months) and 145 to standard observation. The clinical results available to date do well justify a continuation of the study. Skin dryness and desquamation were the most frequent symptoms, affecting 60% of all treated patients. Other symptoms such as dyspepsia, headache, nosebleeds and mild hair loss occurred in less than 10% of patients, and were self-terminating. Only in 4 patients (3%) was the treatment interrupted because of symptoms potentially related to vitamin A administration. As for laboratory tests, gamma-GT levels were abnormally elevated in 69% of treated patients vs. 39% of controls at 24 months (mean 149 vs. 58 IU/l; p less than 0.05). Serum triglyceride concentrations over 150 mg/dl were seen in 74% of treated patients vs. 43% of controls at 12 months (mean 283 vs. 179 mg/dl; p less than 0.05). There were no other laboratory signs of toxicity attributable to vitamin A. In our experience, high-dose retinoyl palmitate administration was a well-tolerated and safe treatment. The long-term impact on lipid metabolism still remains to be determined.
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PMID:Safety of high-dose vitamin A. Randomized trial on lung cancer chemoprevention. 167 95

Twenty-three patients with benign intracranial hypertension (BIH) were seen at the Royal Alexandra Hospital for Children, Sydney over an 18 year period to 1988. Age at presentation ranged from 6 months to 13 years and 5 months. The female to male ratio was 2.3:1. The aetiological factors (sometimes multiple) included: chronic middle ear infection, 30%; dural sinus thrombosis, 22%; head injury, 13%; Vitamin A overdosage, 4%; tetracycline exposure, 4%; and no apparent cause, 43%. Headache was the most common presenting symptom occurring in 91% of patients, followed by vomiting in 65% and blurred or double vision in 57%. Papilloedema occurred in 96% of patients, abducens palsy was noted in 48% and visual impairment in 45%. All patients improved clinically after treatment, one with lumbar puncture only. Of 17 patients treated with steroids, 10 patients recovered and seven patients went on to lumboperitoneal shunt. Two patients recovered with steroid and diuretic treatment. Of two patients initially treated with diuretics only, one recovered and one subsequently required a shunt. Only one patient was initially treated with a lumboperitoneal shunt. Three of the shunted patients had shunt block requiring revision. None had permanent visual loss or other significant sequelae. The visual prognosis of BIH in childhood is good. In view of the relatively high complication rate of steroids and shunting, a controlled comparison of steroid vs acetazolamide/diuretic therapy should be undertaken.
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PMID:Benign intracranial hypertension in childhood: a review of 23 patients. 156 75

The authors report two cases of pseudotumor cerebri in patients taking lithium for treatment of bipolar disorder. Pseudotumor cerebri is a poorly understood syndrome characterized by chronic headaches, bilateral papilledema, and increased intracranial pressure without localized neurologic signs or symptoms, intracranial mass, or hydrocephalus. Ventriculography, computed tomography, and nuclear magnetic resonance imaging reveal normal or small ventricles. Multiple etiologies may include Vitamin A toxicity, obesity, head trauma, hypothyroidism or hyperthyroidism, prolonged steroid therapy or its withdrawal, Addison's disease, Cushing's disease, pituitary insufficiency, and lithium therapy. Patients treated with lithium whose antidiuretic hormone-cyclic adenosine monophosphate mechanism is disturbed are most likely to develop pseudotumor cerebri via disregulation of sodium balance, thyroid-stimulating hormone production, and glucose metabolism. The authors recommend careful medical monitoring to avoid iatrogenic effects of lithium, including pseudotumor cerebri.
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PMID:Pseudotumor cerebri associated with lithium therapy in two patients. 203 32

Vitamin A deficiency is a serious problem throughout the developing world. An estimated 25-50 million children may well suffer the physiologic consequences of vitamin A deficiency; 5 million develop xerophthalmia, of whom 250,000 to 500,000 go blind every year; and untold numbers are at increased risk of diarrhea, respiratory disease, and death. Even mild vitamin A deficiency has been associated with a 14- to 10-fold increase in mortality, and controlled field trials have demonstrated vitamin A supplementation can reduce childhood death rates by 30%-70%. Three general intervention strategies exist for improving vitamin A status of high-risk, rural, economically deprived populations. These include nutrition education leading to increased dietary intake; vitamin A fortification of centrally processed, widely consumed dietary items; and periodic administration of large doses of vitamin A. At present, the latter is far and away the most widely employed intervention activity, because of its immediate impact, and because it can be implemented through the existing (and specialized) health care infrastructure. Vitamin A is a fat-soluble vitamin stored in the liver, so that a large dose of 200,000 IU (100,000 IU for children under 1 year of age) every 6 months reduces mortality, stimulates growth, and prevents xerophthalmia and nutritional blindness. Recent data suggest more frequent administration, every 3 to 4 months, may be desirable. Side effects have been minimal, with mild nausea, vomiting, and headaches in less than 1% to 4% of recipients. Care should be taken, however, that doses above 10,000 IU not be administered to women during the first trimester of pregnancy because of potential teratogenic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Large dose vitamin A to control vitamin A deficiency. 250 5

On the basis of epidemiologic and experimental evidence of an anticancer activity of vitamin A, a randomized clinical trial was activated in Milan with the aim of evaluating if retinol palmitate administration (per os, 300,000 I.U. daily) after complete resection of stage Ia non small-cell lung cancer could reduce the occurrence of cancer relapses (within 3 years) and/or the occurrence of new primary tumors (beyond 3 years). By September 1987, 181 patients had entered the trial: 87 in the treatment arm and 94 in the control arm. After a median follow-up of 14 months, the interim analysis was focused on the evaluation of toxicity, compliance, and early recurrences. Although the large majority of patients were affected by skin and mucous membrane desquamation and dryness during treatment, these symptoms were generally mild and well tolerated, and never induced the patient to stop the treatment. Other side effects like headache, hair loss, itching, or dyspepsia were detected at a much lower frequency. Only in 3 patients the treatment was interrupted, because of signs or symptoms potentially related to vitamin A administration. At the time of the analysis, a total of 42 (23%) patients had relapsed; 16 (18%) in the treated arm, and 26 (28%) in the control arm. The largest difference between treated patients and controls was observed for bone metastases (2 vs. 7) and brain metastases (3 vs. 6), and for squamous histology (6 vs. 11). Only 2 cases of new primary cancer were detected, both in the control arm. These results are promising both in terms of tolerance and efficacy of treatment, but given the short median follow-up they must be very cautiously interpreted. A longer follow-up is necessary to establish whether a significant proportion of early recurrences could be prevented, or only delayed, by vitamin A administration.
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PMID:Lung cancer chemoprevention with retinol palmitate. Preliminary data from a randomized trial on stage Ia non small-cell lung cancer. 285 45

Plasma retinol levels and toxicity were evaluated in thirteen metastatic breast cancer patients treated orally with high-dose (300,000 I.U./day) retinyl acetate in combination with oral tamoxifen. Following the first dose of the drug, there was a drop of plasma retinol concentrations followed by a recovery to the pre-treatment levels and by a further increase to reach a plateau six to eight hours after drug administration. During the first two months of treatment cumulative increase of plasma retinol was seen, and long-term systemic concentrations in the +50-60% range level were maintained by the treatment. The toxicity observed was acceptable and included gastrointestinal symptoms, skin toxicity and headache. These toxicities could be related to the long-term increase of retinol systemic concentrations. We concluded that the daily dose of 300,000 I.U. retinyl acetate can be administered to cancer patients over a period of several months, is well tolerated and yields a substantial increase of systemic retinol.
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PMID:Plasma retinol levels and side effects following high-dose retinyl acetate in breast cancer patients. 321 64

Thirteen subjects between the ages of 50 years and 70 years were administered a daily 25,000 IU dose of retinol for 9 months. Two subjects experienced mild skin dryness, headaches, and/or alopecia. There were no significant changes in serum chemistries. High performance liquid chromatography assays for plasma retinol revealed no evidence of drug accumulation; however, there was a significant increase in the plasma concentration-versus-time curve for retinyl palmitate concentrations between the first and subsequent sampling days (P = 0.009). The mean skin retinol and retinyl palmitate concentrations in 7 retinol-treated subjects (131.7 and 15.9 ng/g, respectively) were not significantly different from those observed in 13 age-matched controls (118.9 and 25.5 ng/gm, respectively).
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PMID:Pharmacokinetics and metabolism of retinol administered at a chemopreventive level to normal subjects. 322 46

A case of acute hypervitaminosis A complicating viral hepatitis is reported. Twenty days after presenting with hepatitis B, a 42-yr-old vegetarian developed acute hypervitaminosis A in the absence of recent, massive exposure to the vitamin. Findings included headache, confusion, skin desquamation, and hypercalcemia. Prior to developing hepatitis, he had ingested supplemental vitamin A without recognized ill effect. Liver and serum vitamin A without recognized ill effect. Liver and serum vitamin A levels were both elevated; the liver biopsy showed abundant, lipid-filled Ito cells and perisinusoidal fibrosis. This case demonstrates that patients with excessive hepatic stores of vitamin A may develop hypervitaminosis A during acute, intercurrent liver disease. Levels of retinol binding protein are reduced in hepatitis. This phenomenon may account for the findings in this case, since vitamin A is more toxic when not specifically bound to retinol binding protein. The size of the population at risk for this complication of hepatitis in unknown, but presumably it is growing with the widespread use of supplemental vitamin A.
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PMID:Hypervitaminosis A unmasked by acute viral hepatitis. 719 70

The case of a 69-year-old woman with a chronic vitamin A intoxication syndrome after self-administration of vitamin A is presented. The clinical picture included musculoskeletal disorders, headache and hepatomegaly. The diagnosis of chronic vitamin A intoxication was based on a history of excessive vitamin A ingestion, clinical chemistry and needle biopsy of the liver. Besides retinol and retinyl ester, the serum concentration of retinol-binding protein (RBP) should be determined. Whereas the serum retinol concentration in chronic vitamin A intoxication often does not correlate with toxicity, the ratio between retinol and RBP and the concentration of retinyl ester is more sensitive. Morphological alterations are associated with the cumulative dosage of ingested vitamin A, whereas the daily amount of vitamin A determines the latency until pathological changes occur. The hormone-like, retinoid-receptor mediated molecular mechanism of action seems to be responsible for the multisystemic manifestations in chronic vitamin A intoxication syndrome.
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PMID:[Chronic vitamin A poisoning with musculoskeletal symptoms and morphological changes of the liver: a case report]. 829 Sep 33


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