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Lymphocyte cultures from homozygotes for the beta-thalassaemia gene were found to contain chromosomal gaps, breaks, and rearrangements more often than those from controls. Culture time seemed to have a determinant effect on the results. The possible influence of folic acid deficiency is discussed.
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We assayed serum folate levels of 60 patients with chronic fatigue syndrome (CFS) and found that 50% had values below 3.0 micrograms/l. Some patients with CFS are deficient in folic acid.
Consideration of environmental influences on human reproduction must include an investigation of the socioeconomic factors that play an important role in embryo-fetal development. Nutritional factors are of prime importance, and modern methods of food production and supply have led to new hazards for pregnant women. For example, pregnant women have been advised in a number of European countries not to eat liver due to the very high concentration (frequently exceeding 100,000 IU per 100 g) of vitamin A. The clear demonstration that periconceptional vitamin supplementation can dramatically reduce the recurrence rate of neural tube defects suggests that folic acid deficiency may be common even in otherwise well-nourished women. Modern methods of food production manufacture and sale have increased the risks of Salmonella and Listeria infections in pregnancy. The dangers of social drug use, especially alcohol and tobacco, are discussed. The types of adverse effect that can result from chemical exposure during the different stages of pregnancy is reviewed with a discussion of some of the problems of epidemiological studies in attempting to identify toxic chemicals. The extent of the ignorance concerning the reproductive toxicity of industrial and environmental chemicals is emphasized by the fact that data are available on only a small percentage of even the high-production volume (1000 tons/year) chemicals. The evidence of reproductive toxicity from exposure to lead, methyl mercury, polychlorinated biphenyls, polychlorinated dibenzofurans, and hexachlorobenzene are briefly reviewed. Some areas of research needs are discussed with emphasis on nutrition, food production, preparation, and storage and the new problems that may be introduced by genetic manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)
During the past 10 to 20 years it has become increasingly clear that a certain number of drugs may lead to increased vitamin requirements. However, it is unusual for symptomatic avitaminosis to develop, and then only when circumstances are present which in themselves increase the risk of vitamin deficiency. Therapeutic doses of drugs will interfere with the vitamin status only to a restricted degree, provided they are administered for brief periods and to patients receiving a normal supply of vitamins. Most cases of vitamin deficiency have in fact been described in connection with drugs usually taken for a longer period of time by patients who were already in negative vitamin balance as a result of disease or marginal supply of the necessary vitamins. This review describes some of the more important articles covering this topic.
A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient.
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Folate, vitamin B12, and iron are the subjects of active biochemical and molecular research so that further understanding of their metabolism in health and in a wide variety of Inherited and acquired diseases can be achieved. The roles of folate and vitamin B12 in cardiovascular and neurologic diseases and in neural tube defects (NTDs) will be further explored in the next decade. The effects of prophylactic therapy and of food fortification with the vitamins on these diseases remain to be established. Iron deficiency is a public health problem in all countries and prevention or treatment, particularly in children in developing countries, are major goals. The increased recent understanding of iron metabolism and absorption may clarify the etiology of diseases of iron metabolism and of dietary iron overload. Improved iron chelation therapy for transfusion-dependent patients with refractory anemias will continue to be actively researched over the next decades.
Clinical investigation of the small bowel at The Mount Sinai Hospital began with David Adlersberg's arrival in 1931. His research interests were in bile acids, cholesterol, carotene, and vitamin A. In 1952, he was given a Nutrition Laboratory and later, a Nutrition Clinic. His vitamin A tolerance test and interest in malabsorption led him to a comprehensive study of sprue, the separation of the tropical and non-tropical forms, and their different etiologies and treatments. Adlersberg's work was complemented by (a) Marshak and Wolf's radiologic examination of the small bowel (especially in sprue and other malabsorption disorders); (b) Gerson s perfusion experiments; and (c) Friedman, Waye and Wolf's motility studies. Lieber and his colleagues explored the deleterious effects of alcohol on the function and structure of the small intestine. Gerson explored the nutrition of patients with Crohn's disease of the small intestine, especially after extensive resection or bypass leading to ascorbic and folic acid deficiencies and hypergastrinemia.
During studies that showed the presence of fetal antigens on the surface of human malignant melanoma tumor cells, polyvalent antisera specific for human fetal tissues of varying ages were developed. These reagents demonstrated varying patterns of expression of fetal antigens at different ages in various tissues of the human fetus. The possibility that nonneoplastic adult cells showing either maturation arrest or excessive proliferation also might express fetal antigens led to studies of human bone marrow. Although normal bone marrow cells expressed low levels of fetal antigens, large amounts were seen on bone marrow cells of patients with anemias due to iron, B12, or folic acid deficiencies, as well as on those with leukemia. Moreover, normal adult tissues adapted to long-term culture also expressed fetal antigens. After 3 weeks in organ culture adult human skin showed morphological changes similar to those seen in fetal periderm and strongly expressed fetal antigens. In addition, lymphoblasts in long-term cultured human lymphoid cell lines established from normal donors also carried surface fetal antigens. These latter antigens were shared with neoplastic B-cells (chronic lymphocytic leukemia) but not with T-cells. Their expression varied with the cell cycle. The reexpression of fetal antigens on malignant cells is thought to signal a basic derangement in the control of differentiation which is considered to be peculiar to neoplasia. However, these studies indicate that normal adult cells also may reexpress fetal antigens under circumstances unrelated to neoplasia but associated with either maturation arrest or rapid and excessive proliferation.
Depression of one or more parameters of cellular and/or humoral immune responses was found in 60% of general hospital patients treated with phenytoin and 47% of patients treated with carbamazepine. Phenytoin-treated patients failed to manifest delayed hypersensitivity (DHS) reactions to common antigens, and to make antibody to Salmonella typhi and tetanus toxoid. Serum levels of IgA and IgM, DNA synthesis in circulating leucocytes, and phytohaemagglutinin (PHA) induced deoxyribonucleic acid synthesis were also low. Depression of IgA, DHS reactivity and antibody responsiveness to S. typhi were shown to develop after the commencement of phenytoin therapy in a study of eleven patients. The presence of immunological defects was independent of the dosage of drug, its serum concentration, the duration of therapy and the sex of the subject. Studies in vitro provided evidence that immunosuppression was the result of a direct effect of phenytoin on the metabolism of lymphoid cells. Carbamazepine was shown to have a similar but less potent direct effect. Pharmacological concentrations of phenytoin caused a significant depression of DNA synthesis in PHA-stimulated and non-stimulated blood cell cultures in vitro. High concentrations in addition caused depression of cell counts, lymphocyte blastogenesis, ribonucleic acid and protein synthesis. Phenytoin was not cytocidal at concentrations of up to 125 mug/ml. Depression of DNA synthesis by phenytoin was maximal when phenytoin was added within 4-8 hr of the addition of PHA. PHA-induced DNA synthesis was not significantly affected by pre-incubation with phenytoin. In vivo, the presence of immunological defects was not related to phenytoin-induced folic acid deficiency. High concentrations of carbamazepine, but not phenobarbitone or diazepam caused a significant depression of PHA-stimulated DNA synthesis in blood cell cultures. The data show that immunosuppression is a common side-effect of phenytoin therapy, and that lymphoma is rare. They suggest that in the presence of phenytoin-induced immunosuppression another factor, or factors are required to induce the formation of lymphoma.
Oral cancer represents 2-4% of all diagnosed cancers, showing an annual increase of 5,000 new cases. Unfortunately, due to delays in diagnosis the 5-year survival rate is only 25%. For this reason, any measures to restrict the consumption of tobacco and alcohol and that will help preserve oral health and maintain a balanced diet will lead to benefits in terms of a reduction in the occurrence of this pathology. There are many articles that warn us of the implications of smoking, of oral infections from Candida or papillomavirus, of the consequences of iron or folic acid deficiencies, all elements considered to favour the development of oral cancer. On the other hand, less well known are dietary aspects, the study of which called our attention. In this article we summarize some of the more relevant knowledge on carcinogenesis and the phases in which certain groups of foods and nutrients act as preventive factors.
The nutritional status of 121 psychiatric patients over the age of 60 years was examined on admission in a general psychiatric hospital. Before admission all patients were living independently. They were admitted directly from their homes. We found that the older psychiatric patient is evidently at risk for malnutrition. A quarter of the males had, according to the Quetelet's index, a low weight. Half of the males and one third of the females had a thiamin-deficiency, whereas half of all patients showed a deficiency of folic acid. Furthermore, in half of the males and one tenth of the females anaemia was diagnosed. Widowers and to a lesser extent also patients with an organic brain disease or psychotic disturbance ran a greater risk of malnutrition in comparison to their fellow patients. A relation between behaviour, measured by the Nosie (Nursing Observation Scale for Inpatient Evaluation) and the nutritional status was not found.
BACKGROUND: Although folic acid deficiency is known to be one of the factors in the development of spina bifida and other neural tube defects (NTD) the exact pathophysiology still remains unclear. Progesterone is an endogenous hormone which increases significantly during pregnancy. AIMS: We aimed to study the possible negative effects of high dose progesterone on neural tube development in early chick embryos. In order to test our hypothesis, early chick embryos were exposed to physiological saline, normal and high doses of progesterone. SETTINGS AND DESIGN: 160 fertile, specific pathogen free white leghorn eggs (Gallus gallus), all at stage eight of development were divided into four equal groups. MATERIALS AND METHODS: The first group was incubated without any operation. The second group was injected with physiological saline. The third and fourth groups were injected with two and twenty times more than physiologic doses of progesterone respectively. After 48 hours of incubation, all embryos were analyzed for the presence of NTDs under light microscopy. STATISTICAL ANALYSIS USED: None. RESULTS: At 48 hours of incubation, 84% (135/160) of the embryos passed characteristics of Stage 12 development and were included to the study. None of the eggs in the first three groups showed NTDs, whereas 81.8% (27/33) of the eggs in the fourth group showed NTDs. CONCLUSIONS: Our study showed that progesterone at levels twenty times more than its physiologic level might cause NTDs. Further studies are needed to explain the mechanisms of this teratogenic effect.
Anemia is a frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A systematic review of the literature shows that the overall prevalence of anemia ranges from 8.8% to 73.7% but differs whether in a setting of Crohn's disease or ulcerative colitis. A disabling complication of IBD, anemia worsens the patient's general condition and quality of life, and increases hospitalization rates. Different factors, including vitamin B12 and folic acid deficiency, bone marrow suppression secondary to drug therapy, autoimmune hemolytic anemia and the coexistence of myelodysplastic syndromes are involved in the pathogenesis of anemia in IBD. The main types of anemia in IBD are iron deficiency anemia and anemia accompanying chronic diseases. Correct diagnostic definition of anemia is a fundamental step in guiding the choice of therapeutic options, since the co-presence of different pathogenetic factors may sometimes require a more complex treatment plan. A review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on evidence from recent studies is the focus of this article.
Pap smear examinations of 139 infertile women taken between June 19, 1983 and December 26, 1983 were studied at the Cytological Room, Department of Obstetrics & Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University. The range of age was 17 to 44 years, the mean age being 28.2 +/- 4.9 years. The percentage of cytological findings were: 84.9 normal women, 10.1 hormonal abnormality (of those with non-normal hormone, 7.2 of the total had a mild degree of abnormality), 5.0 no hormonal evaluation, 1.4 few abnormal cells and 0.7 folic acid deficiency.
The increase in volume of human erythrocytes during chronic alcoholic intoxication and its decrease after alcoholic deprivation was studied with a multichannel analyzer. When fractions of the population of red cells were separated by differential centrifugation the macrocytosis was found to be uniformly distributed. The presence of macrocytes was not related to changes of plasma osmolality or hyperhydration of red cells. A central origin was evoked, however, the role of the folic acid deficiency could not explain the macrocytosis, the mechanism of which remains to be elucidated.