The significance of folate deficiency in alcoholic and nutritional neuropathies: analysis of a case.

OBJECTIVE: To elucidate the significance of folate deficiency in alcoholic and nutritional neuropathies. METHODS: We preformed a comprehensive clinical screening of a patient with chronic alcoholism who manifested neuropathy, macrocytic anemia, liver dysfunction, and folate deficiency. RESULTS: A 33-y-old woman with chronic alcoholism presented with acutely progressive glove- and stocking-type sensorimotor polyneuropathy. Although an episode of neuropathy preceded the current episode by 2 y, its cause was never determined. The findings of nerve conduction studies were indicative of axonal neuropathy. Laboratory findings revealed macrocytic anemia and liver dysfunction. Her serum level of folate was reduced, whereas thiamine, riboflavin, and cobalamin levels were within normal range. The neuropathy and anemia showed gradual recovery after the initiation of folic acid supplementation. CONCLUSIONS: This case study indicates that folate deficiency should be monitored closely in patients with chronic alcoholism and associated malnutrition. Additionally, folate deficiency should be considered as a differential diagnosis of neuropathy.

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium.

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1-4 received CY (600mlkg(-1)b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150mgkg(-1)b.wt), Se (0.25mgkg(-1)b.wt), and Vit E (150mgkg(-1)b.wt)+Se (0.25mgkg(-1)b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1-3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.

BACKGROUND: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey. DESIGN: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine. RESULTS: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.

Bone marrow status of anaemic pregnant women on supplemental iron and folic acid in a Nigerian community.

The bone marrow status of 31 consecutive pregnant women who had been on supplemental oral iron and folic acid since early pregnancy at the University of Benin Teaching Hospital was assessed later in pregnancy to test the efficacy of oral iron and folic acid in preventing iron deficiency and/or megaloblastic anaemia in our community. Only those pregnant patients with haemoglobin genotype AA or AS took part in the study. Nobody was excluded except those with CC or SC. 96.77% (30 out of 31 patients) had iron deficiency with no stainable iron in the bone marrow. 35.4% (11 out of 31 patients) had megaloblastic changes in the bone marrow. 32.2% (10 out of 31 patients) had a combined iron deficiency and megaloblastic anaemia while only one out of 31 patients (3.23%) had megaloblastic anaemia without concurrent iron deficiency. 60.4% (20 out of 31 patients) had iron deficiency alone without concomitant megaloblastic changes in marrow. The bone marrow in all the patients were normal in other respects except with regards to iron-deficiency and/or megaloblastic status. The significance of this high incidence of iron-deficiency and/or megaloblastic anaemia in patients already on routine pre-natal drugs is discussed.

Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta.

Mice homozygous for mutant genes at the W locus have a marked macrocytic anemia that is fatal in some genotypes. The defect is believed to originate in the developmentally pluripotent hematopoietic stem cell population. Anemia is first grossly manifest on day 13 of gestation, when the liver is the chief hematopoietic organ. The known paucity of blood-forming foci in livers of homozygotes and the limited formation of their erythrocytes suggested that such fetuses-unlike normal ones-might have conditions favorable for in utero seeding of genetically normal hematopoietic tissue. If this were accomplished before day 13, the anemia might essentially be prevented, or at least substantially mitigated, and normalcy soon achieved by cell selection. This proved to be the case. Allogeneic normal fetal liver cells were microinjected into the blood vessels of the fetal placenta on day 11 of gestation. Of eight mutant homozygotes born from segregating matings, six (four W/W, two W(v)/W(v)) were successfully populated with donor cells. Strain-specific hemoglobin markers demonstrated replacement of the erythroid lineage with the normal type, the rate of substitution being more rapid in the W/W (ordinarily more anemic) recipients. Strain-specific isozyme differences revealed that white blood cells were also replaced. Thus, the initial selective pressure, hence the W-mutant phenotypic lesion, must have occurred at the pluripotent stem cell stage. The animals remained immunologically tolerant of the donor cells and no graft-versus-host reaction occurred. The early introduction of hematopoietic cells differing genetically from all the other tissues of the animal provides possibilities for tracing normal hematopoietic lineages in vivo, for analyzing cell and tissue interactions, such as those between lymphocytes and thymus, and for clarifying the etiology of other blood or immune insufficiencies or malignancies.

Folic acid supplementation in low birth weight infants.

Low birth weight infants (246) entered a trial to folic acid supplementation from 3 weeks to 12 months of age. The folic acid group had significantly higher mean hemoglobin levels at 6 and 9 months of age but the differences were only about 0.5 gm/dl, there was no significant difference in hematocrit, and in both groups of infants the mean hemoglobin levels were higher than those of normal birth weight infants. The differences in hemoglobin, although statistically significant, are of uncertain clinical significance. Median red cell folate levels remained within the normal adult range in both groups of infants. A minority of infants in the untreated group had low red cell folate levels but this was usually temporary, corrected by dietary folate, and not associated with low hemoglobin. Weight gain was not affected by folic acid supplementation. The infants in this trial were fed with a milk preparation containing 3.5 microgram/100 ml of folic acid which is a similar concentration to that of human milk and we recommend that the folate content of milks fed to low birth weight infants should not fall below this level. We do not have sufficient grounds to recommend routine folic acid supplements for all low birth weight infants throughout the first year of life but there is a possibility that their folate intake may sometimes be suboptimal.

A prophylactic trial of iron and folic acid supplements in pregnant Burmese women.

Hemoglobin (Hb) concentration, serum iron level, iron binding capacity and blood folate (Lactobacillus casei) activity were determined in 310 unselected pregnant Burmese women. Hb concentration was less than 11 g/dl in 72% of the women; the serum iron level was less than 50 mug/dl in 33%; serum folate activity was less than 3ng/ml in 13%; and red cell folate activity was less than 100 ng/ml in 17% of the women. Ninety-six of the women in our study were randomly divided into four groups, treated from the 22nd to the 25th week of pregnancy until full term with either ferrous sulfate containing 60 mg elemental iron twice daily, 5 mg folic acid twice daily, a combination of both, or a placebo only. At full term, Hb concentration fell in the groups given placebo or folic acid. On the other hand, in the groups given iron alone or iron plus folic acid there was an increase in Hb of 0.4 and 0.7 g/dl, respectively (intergroup difference not statistically significant). Serum iron and blood folate levels fell in the groups not receiving the appropriate hematinic. In spite of deficient serum and red cell folate levels in 30 and 40%, respectively, of the group on iron alone, the mean Hb concentration increased at full term and none of the women had a Hb concentration lower than 10 g/dl. Blood folate levels were lower in the iron-supplemented group than in the placebo group, indicating that iron deficiency does not aggravate the folate nutritional status.

[Macrocytic animia due to the combination trimethoprim-sulfamethoxazole]. / Anémie macrocytaire due a l'association triméthoprime-sulfaméthoxazole

The authors report a case of macrocytic anemia due to folate deficiency occurring suddenly after the administration of trimethoprime-sulfamethoxazole and completely cured by folic acid. This type of complication occurs particularly often in patients who already have a relative folate deficiency. In our case only moderate alcoholism was found. Thus individual predisposition due to enzyme abnormality must be considered. Prophylactic administration of folic acid in patients receiving this drug association is thus advisable.

Megaloblastic anaemia of pregnancy: a clinical and laboratory study with particular reference to the total and labile serum folate levels.

It has been shown that the incidence of megaloblastic anaemia in a group of 463 randomly selected pregnant women receiving iron was 12 times as high as in a control group of 235 pregnant women receiving iron and folic acid. The incidence of all types of anaemia in the women receiving iron alone was more than three times the incidence in those having iron and folic acid. Some women who were not anaemic or who had normoblastic anaemia had serum folate levels in the same range as the women with megaloblastic anaemia, but none of the women with megaloblastic anaemia had high serum folate levels. The labile fraction of the serum folate was no more reliable than the total serum folate as a diagnostic criterion of megaloblastic erythropoiesis in the individual case. The blood group distribution in the women with megaloblastic anaemia was the same as in the general population. Babies born to mothers with megaloblastic anaemia tended to be smaller than the rest, although there was no difference in the placental weights. The significance of these findings is discussed.