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The relationship of hookworm infection, anaemia and iron status in a Papua New Guinea highland population and the response to treatment with iron and mebendazole.

In 345 apparently healthy Papua New Guinea male subjects, predominantly highlanders, 89% of whom were infected with hookworm (Necator americanus), there was a statistically significant inverse correlation of hookworm egg count with haemoglobin and serum ferritin level, but no significant correlation with serum albumin, folate or B12 values. A sub-group of 128 was chosen for a six-month study on the effect of treatment with the anthelmintic mebendazole and/or parenteral iron on haemoglobin and serum ferritin levels. Mebendazole-treated subjects remained worm-free and the hookworm egg counts of the controls decreased during the study period. Parenteral iron treatment had the expected effect of raising haemoglobin to a normal level. There was a statistically significant improvement in haemoglobin level in all treated groups but not in the control. Serum ferritin levels decreased significantly in all groups, but more in the control than in the treated groups, although treatment groups were not significantly different. Although probable inadequate uptake of iron by the subjects and blood donation by some subjects was apparently more detrimental to iron status than hookworm infection, the results of this study support the view that hookworm infection in this country contributes to lowered haemoglobin levels and iron status.

Anemia, Hypochromic↗

Red cell folate in elderly patients with myelodysplastic syndrome.

During a 7-month period a prospective study of 71 anaemic patients (29 males and 42 females) over the age of 50 was undertaken in order to identify patients with myelodysplastic syndrome (MDS). The mean values of mean corpuscular volume (MCV), serum ferritin, folate, vitamin B12 and red cell folate (RCF) of patients grouped according to the diagnosis were compared to those observed in age-matched blood donors. Forty-four of the 71 elderly patients showed macrocytic anaemia: 21 of them had gastric disease and the remaining 23 MDS. Two further patients with MDS showed microcytic anaemia. The 25 patients diagnosed with MDS were subclassified according to the FAB nomenclature: 9 had a refractory anaemia with excess of blasts and 16 refractory anaemia. The mean values of MCV, serum folate, ferritin, vitamin B12 and RCF were statistically different between patients with macrocytic anaemia due to gastric disease and patients with MDS. Among patients with MDS, the RCF level pathologically high was inversely correlated to the haemoglobin level (r=-0.39; p<0.05). Thus the RCF and serum folate may represent useful parameters for the diagnosis of MDS in elderly anaemic patients.

Aged↗

Intakes of nutrients and nutritional status in coeliac patients.

BACKGROUND: The intake of nutrients and the nutritional status of untreated coeliac patients and coeliac patients in remission were investigated at Kuopio University Hospital. METHODS: Forty untreated and 52 coeliac patients in remission were admitted to the study. The control group included 77 persons. Four-day food records, anthropometric measurements, and blood biochemistry were examined to obtain nutrient intake and nutritional status. RESULTS: Concentrations of serum ferritin, vitamin B12, and erythrocyte folate were lower in patients with untreated coeliac disease than in those in remission. Altogether, 15-38% of the untreated patients but only 0-20% of the patients in remission had levels of haemoglobin, serum ferritin, iron, vitamin B12, or erythrocyte folate below the reference values. No difference in anthropometric measurements was found between the two groups of coeliac patients. CONCLUSIONS: Except for some subclinical abnormal values in biochemical analyses in 20-38% of coeliac patients, nutritional status was quite normal in both groups of coeliac patients.

Adult↗

Evaluation of patients with progressive intellectual deterioration.

Sixty consecutive patients with progressive intellectual deterioration were evaluated by a specific protocol. Eighteen (30%) were found to have an underlying disease potentially reversible by medical or surgical therapy. Sixteen patients had a specific diagnosable but untreatable disease as a cause of dementia. The laboratory and radiologic tests of the protocol that uncovered treatable illnesses were the radioisotope brain scan (two cases of bilateral subdural hematoma), the pneumoencephalogram (seven patients with normal-pressure hydrocephalus), thyroid function screen, and liver function studies (one case each). Unrewarding tests included serum barbiturate, bromide, vitamin B12, and folate levels.

Aged↗

Racial variation in fasting and random homocysteine levels.

Homocysteine (Hcy) levels have been shown to be a predeterminant of thrombotic diseases. We measured the Hcy levels of 50 blacks and 50 whites equally divided by gender to determine if there is a significant racial difference in either fasting or random Hcy levels. Dietary, medication, smoking, alcohol, past medical, educational, and occupational histories were obtained, and the body mass index calculated. Total serum fasting and random Hcy levels, B12, folate, BUN, creatinine, and lipid profiles were drawn from each participant. Analysis of the results showed that white males have the highest fasting Hcy levels, 10.5 microM/l, whereas random Hcy levels were not significantly different. Correlation between fasting and random Hcy levels was poor (R = 0.61). B12 levels in black subjects were significantly higher, 490.8 pg/ml, compared to whites, 382.8 pg/ml, P = 0.001, but contributed little to total Hcy levels (R(2) = 0.08). Folic acid levels, all within normal range, were not significantly different between the two racial groups and also did not appear to greatly affect Hcy levels (R(2) = 0.06). Our study demonstrates that, despite the genetic diversity of these two racial groups in the U.S., white males in this age group have higher fasting Hcy levels than black males, and white males, but not black males, have higher fasting homocysteine levels than females. This discrepancy in Hcy levels may reflect methylene-tetrahydrofolate reductase (MTHFR) enzyme polymorphisms, known to be higher in whites, rather than socioeconomic influences.

Black People↗

Deoxyuridine suppression: biochemical basis and diagnostic applications.

The deoxyuridine (dU) suppression test evolved out of investigations into the biochemical basis of the megaloblastic changes seen in vitamin B12 and folate deficiency. Although the abnormality in dU suppression which occurs in vitamin B12- or folate-deficient states is assumed to reflect impaired methylation of deoxyuridylate, there is still no direct demonstration that this is so. Furthermore, there is evidence that reactions other than the methylation of deoxyuridylate are involved in the phenomenon of dU suppression. Nevertheless, in clinical practice abnormal dU suppression serves as a sensitive index of the presence of megaloblastosis due to vitamin B12 or folate deficiency. dU suppression is also abnormal in a number of conditions other than vitamin B12 or folate deficiency, but its overall specificity in detecting tissue dysfunction due to these two deficiency states is considerably higher than that of the serum vitamin B12 or red cell folate levels. Consequently, the test enables us simply and rapidly to define those patients in whom macrocytosis is unrelated to a deficiency of vitamin B12 or folate. For these reasons, the dU suppression test has been adopted by several laboratories across the world for investigating patients with (a) possible vitamin B12 or folate deficiency, (b) macrocytosis, and (c) megaloblastic erythropoiesis. Since the dU suppression test is abnormal in transcobalamin II deficiency and in some congenital disorders of vitamin B12 and folate metabolism, it is very useful in the investigation of obscure anaemias in infancy and childhood. In addition, it has contributed to our understanding of the mechanisms underlying the myelotoxicity of certain drugs, and particularly of nitrous oxide.

Deoxyuridine↗

Marginal maternal vitamin B12 status increases the risk of offspring with spina bifida.

OBJECTIVE: The purpose of this study was to investigate B vitamins and homocysteine as risk factor for offspring with spina bifida. STUDY DESIGN: Blood samples from 45 mothers and their children with spina bifida and from 83 control mothers and their children were obtained to determine the levels of serum and red blood cell folate, serum vitamin B(12), whole blood vitamin B(6), and total plasma homocysteine. RESULTS: In the case mothers, the vitamin B(12) concentration was 21% lower (95% CI, 8%-33%) compared with control mothers. Unlike folate, vitamin B(6,) and homocysteine, a vitamin B(12) concentration of <or=185 pmol/L was associated with a 3.5-fold (95% CI, 1.3- 8.9) spina bifida risk. In children, no differences in folate, vitamin B(6), vitamin B(12), and homocysteine concentrations were observed after adjustment for the child's age. CONCLUSION: A marginal maternal vitamin B(12) status increases the risk of an offspring with spina bifida.

Case-Control Studies↗

Alcohol consumption and plasma homocysteine.

A few reports show that consumption of spirits and of wine correlate with elevated plasma total homocysteine (tHcy), which is associated with the risk of cardiovascular disease. We analyzed the relation between tHcy and current daily ethanol consumption cross-sectionally in middle-aged Japanese men (n = 974, age 51-59 years). Plasma tHcy was positively associated with consumption of whiskey but not with consumption of shochu (Japanese spirits), sake, beer, or wine. Odds ratios of an increase in daily intake of 30 ml ethanol (approximately 1 standard deviation) for hyperhomocysteinemia (>14.0 micromol/l) were 2.58 (95% confidence interval, 1.29-5.14) for whiskey, 1.08 (0.78-1.50) for shochu, 0.99 (0.59-1.66) for sake, 0.98 (0.58-1.63) for beer, and 1.70 (0.31-9.50) for wine in a multivariate logistic regression analysis adjusted for the daily number of cigarettes smoked, physical activity, vegetable consumption, and serum creatinine levels. After inclusion of plasma folate and vitamin B12 in the multivariate analysis model, the association between whiskey ethanol consumption and hyperhomocysteinemia remained significant with odds ratio of 2.79 (1.36-5.72). These results suggest that whiskey consumption correlates with hyperhomocysteinemia independently of plasma folate or vitamin B12 or lifestyle factors in the population studied.

Alcohol Drinking↗

Dietary management of obesity: evaluation of the time-energy displacement diet in terms of its efficacy and nutritional adequacy for long-term weight control.

1. An unsupplemented 4200 kJ (1000 kcal) diet emphasizing large quantities of relatively unrefined complex carbohydrates was evaluated among sixty obese adults for its effectiveness and nutritional adequacy in a long-term weight-control programme. Patients were followed individually as outpatients by a physician and dietician-an average of thirteen visits over 26 weeks. Assessment of health indices included anthropometric measurements, blood pressure, lipid levels and assays for seven vitamins, beta-carotene and iron. 2. Weight loss averaged 8.2 kg or 24% of excess weight during the 6 months of active treatment. Over an average of 17 months of post-treatment follow-up, 44% of patients continued to lose weight and 92% remained below pretreatment levels. 3. Average skinfold thickness fell 7 mm (P less than 0.001) whereas muscle mass was maintained (arm muscle circumference + 10 mm, not significant; creatinine-height index + 3% of standard (Bistrian et al. 1975; not significant). Systolic and diastolic blood pressure fell 7 and 5 mmHg respectively (P less than 0.01). Total serum cholesterol and triglycerides fell 200 and 660 mg/1 respectively (P less than 0.01), while high-density-lipoprotein-cholesterol remained statistically unchanged. Mean serum levels of retinol, beta-carotene, folate, vitamin B12, ascorbic acid, Fe and transferrin saturation, and activity coefficients for thiamin, riboflavin and pyridoxine were within normal limits after periods of treatment ranging from 5 to 84 weeks. 4. An earlier age of onset of obesity tended to be associated with greater weight loss during treatment and lesser weight rebound during follow-up. 5. The results indicate that the experimental diet, without supplementation, was nutritionally adequate as well as effective for long-term weight control.

Adult↗

Leukocyte migration inhibition factor production in marasmic infants.

Production of leukocyte migration inhibition factor was measured in vitro with purified protein derivative and phytohemagglutinin in 14 marasmic infants 6 to 18 months of age. Twenty-seven well-nourished infants served as controls. All the children had received BCG vaccine in the neonatal period. Tuberculin reaction was positive in four of 14 of the marasmic infants and 13 of 27 of the controls. When leukocyte migration inhibition factor was induced with purified protein derivative, the four tuberculin positive malnourished subjects had a mean migration inhibition index of 55.7% which was significantly higher than the mean migration inhibition index of 38.2% in the tuberculin positive controls. In the tuberculin negative subjects the mean migration inhibition index was 24.7 and 16.6% in the marasmic and control groups, respectively. The difference was not statistically significant. Phytohemagglutinin-induced migration inhibition was comparable in malnourished and control infants. There was no correlation between leukocyte migration inhibition factor production and biochemical indices of iron nutrition, erythrocyte or serum folate, vitamin A, carotene, or serum zinc levels in either group. It is suggested the capacity of lymphocytes to produce leukocyte migration inhibition factor is unchanged in marasmus.

Blood Proteins↗

Effect of nitrous oxide on folate and vitamin B12 metabolism in patients.

Exposure to nitrous oxide (N2O) markedly enhances excretion of formic acid and formiminoglutamic acid (FIGLU) in the urine of rats, suggesting a disruption in the normal pathways of folic acid metabolism secondary to an N2O-induced inactivation of methionine synthase. We tested whether surgical patients (23 having total hip replacements and 26 having resection of acoustic neuromas) exposed to isoflurane alone or combined with N2O responded similarly. We found no increase in urinary formic acid and FIGLU in patients exposed to N2O for hip replacement, but a small, transient increase in the FIGLU-to-creatinine ratio in those undergoing resection of acoustic neuromas (mean duration of anesthesia = 9.3 h). This increase peaked at the end of anesthetic exposure and returned toward control levels by the first day after anesthesia and surgery. Low preoperative levels of red blood cell folate and low-normal levels of serum vitamin B12 did not predict an increase in formic acid or FIGLU in response to N2O. Although an occasional patient may prove highly susceptible to and develop signs of severe vitamin B12 and folic acid deficiency after exposure to N2O, our findings suggest that this is a rare event.

Adult↗

Biodistribution of radiolabeled adenosylcobalamin in patients diagnosed with various malignancies.

OBJECTIVE: To study the biodistribution of a vitamin B12 analog, indium In 111-labeled diethylenetriaminepentaacetate adenosylcobalamin (In 111 DAC), in patients recently diagnosed as having primary or recurrent malignancy. PATIENTS AND METHODS: Thirty patients (14 women and 16 men) with radiographically or clinically diagnosed breast, lung, colon, sarcomatous, thyroid, or central nervous system malignancies were studied prior to definitive surgery or biopsy. A maximum of 650 microCi (2.2 microg) of In 111 DAC was administered intravenously. Vitamin B12 and folate levels were determined prior to injection. Serum clearance and urinary and stool excretion of the tracer were measured. Images were routinely obtained at 0.5, 3 to 5, and 20 to 24 hours after injection. Biodistribution of In 111 DAC was determined by computer analysis of regions of interest. RESULTS: Serum T1/2 clearance was 7 minutes. Average urinary and stool excretion of the injected dose over 24 hours was 26.1% and 0.4%, respectively. The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands. The average tumor uptake of the injected dose was 2% at 30 minutes and 1.5% at 24 hours. High-grade primary and metastatic breast, lung, colon, thyroid, and sarcomatous malignancies were all imaged at 3 to 5 hours after injection. Central nervous system tumors and advanced metastatic prostate cancer were best identified at 24 hours. Mammographically occult, palpable, and nonpalpable breast cancers were delineated by In 111 DAC. Low-grade malignancies as well as early skeletal metastatic disease were not effectively imaged by the vitamin B12 tracer. Patients with elevated baseline vitamin B12 or those concurrently taking corticosteroids appeared to have optimal visualization of their malignancies. CONCLUSION: Vitamin B12 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.

Adult↗

[Maternal oligo-elements and fetal malformations].

Serum levels of zinc, copper, manganese, magnesium, folates and vitamin B12 and A, were titrated in the early stage of pregnancy in women who delivered children presenting malformations. These levels were compared with those of control patients who delivered normal children. There were 65 malformations. The most frequent were cardiac, musculo-skeletal, urogenital and chromosomal malformations. Only 2 cases of spina bifida were studied. The oligo-elements and vitamin levels are not different in both groups of women: those who carry malformed fetuses and those carrying normal fetuses. These results are compared with those from the literature.

Congenital Abnormalities↗

Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia.

This paper describes the progress of two previously reported brothers with familial glucocorticoid deficiency, achalasia of the cardia, and alacrima. In their early 'teens both boys developed polyneuropathy with sensory, motor and autonomic components, Parkinsonism, and signs of both dorsal column and pyramidal tract damage. The older boy also showed signs of dementia. Red cell folate levels were markedly reduced but plasma and CSF folate were normal. Serum B12 and erythrocyte concentrations were at or below the lower limit of normal CSF levels of homovanillic acid and 5-hydroxyindole acetic acid (the major metabolites of dopamine and serotonin in brain) were low, indicating impaired turnover of the two amines within the nervous system. Positron emission photometry scans in the older boy showed low binding of c-methyl-spiperone and reduced uptake of 18-F-L-fluorodopa in the striatum, confirming the impairment in dopamine metabolism and suggesting both reduced synthesis and reduced receptor density. Treatment with L-dopa up to 800 mg/day (along with carbidopa 200 mg/day) corrected the low CSF homovanillic acid levels and produced some improvement in the Parkinsonism but no other obvious clinical benefit. Empirical treatment with hydroxycobalamin (1000 micrograms three times a week) and folinic acid (15 mg/day) was without clinical effect. The cause of the neurological disorder, low red-cell folate concentrations, and amine disturbance remains unknown, as does the pathogenesis of the adrenocortical failure.

Adolescent↗

The relationship between micronuclei in human lymphocytes and selected micronutrients in vegetarians and non-vegetarians.

A vegetarian diet results in higher intake of vitamins and micronutrients, which - although providing antioxidant defence - may lead to deficiency in other micronutrients involved in DNA metabolism and stability (such as vitamins belonging to the B group). The principal difference among various vegetarian diets is the extent to which animal products are avoided. We have performed a pilot study to determine the relationship between the micronucleus frequency in lymphocytes and diet, and we compared the levels of Vitamins C and E, beta-carotene, B(12), folic acid, homocysteine and total antioxidant capacity in healthy vegetarians and non-vegetarians. The vegetarian group, consisting of 24 volunteers (13 women and 11 men), were matched for age and sex with 24 volunteers (12 women and 12 men) with a traditional dietary habit. Among the vegetarians were 13 lacto-ovo-vegetarians with average duration of vegetarian diet 10.8 years (ranging from 5 to 26 years) and 11 lacto-vegetarians with average duration of vegetarian diet 8.2 years (ranging from 3 to 15 years). Homocysteine, Vitamins C and E and beta-carotene levels in plasma were assayed by HPLC, and serum folate and Vitamin B(12) were determined with Elecsys Immunoassay tests. The total antioxidant capacity of plasma was estimated by measuring the ferric-reducing activity in a spectrophotometric assay. Micronuclei were measured in cytokinesis-blocked lymphocytes. Vegetarians had significantly higher levels of Vitamin C and beta-carotene (but not Vitamin E) in plasma compared with non-vegetarians (P<0.001). There were no significant differences in serum levels of folic acid and Vitamin B(12) between the monitored groups. Levels of folic acid in vegetarians correlated with length of vegetarianism (r=0.62, P=0.001, N=24). Vegetarians had elevated levels of homocysteine compared with non-vegetarians (P=0.007), as did vegetarian women compared with non-vegetarian women (P=0.031). We did not find any differences in total antioxidant capacity or in micronucleus frequency between the groups. Micronuclei correlated with age (r=0.62, P<0.001, N=48), women having higher frequencies than men. Multifactorial regression analysis showed significant effects of age, sex and total antioxidant capacity on micronucleus frequency (N=48, P<0.001).

Adult↗

Optic neuropathy in a patient with vitamin B12 deficiency: a case report.

A 19-year-old man presented with blurring of vision for 2 weeks. He also complained of anorexia with weight loss during the past 4 months. Eight years ago, his small bowel from midportion of the jejunum, ileum, ascending colon and transverse colon were resected because of gangrene. He gave no history of exposure to tobacco, alcohol or other toxins. The bone marrow aspiration showed hypocellular with panhypoplasia. Serum vitamin B12 level was low while serum and red cell folate were within normal limits. His visual acuity was 5/200 in both eyes with centrocecal scotomas in both eyes. Other neurologic and ophthalmic examinations were found to be normal. The patient was given intramuscular injections of 1,000 micrograms of cyanocobalamin. Four months later, his visual acuity improved, serum vitamin B12 level and the bone marrow returned to be normal. This is a frank case of optic neuropathy in a patient with vitamin B12 deficiency due to a massive small bowel resection.

Adult↗

The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia.

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

The influence of serum vitamin B12 and folate status on cognitive functioning in very old age.

This study examined the relationship between low levels of serum vitamin B12 and folic acid (FA) and cognitive functioning in very old age. The four subsamples of non-demented persons aged 75-96 years - normal B12/normal FA; low B12/normal FA; normal B12/low FA; and low B12/low FA, were matched for age and education. A battery of cognitive tests was administered including Clock Tests, Block Design, Trail Making Tests (TMT), Digit Span, and tests of verbal fluency. Subjects with low levels of vitamins showed deficits in Block Design, TMT-B, Digit Span Backward, and letter fluency, but not in the remaining tests. In general, the effects of FA exceeded those of B12. This pattern of results was interpreted to mean that elderly persons with low vitamin levels have difficulty when fast and accurate processing of novel information is required, but are quite efficient in utilizing pre-existing knowledge structures.

Aged↗