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Biomedical subjects

R F Labbe

Publications and source records attributed to R F Labbe.

At least 19 recordsLinked to original sources

Quantitative study of the variability of hepatic iron concentrations.

BACKGROUND: The hepatic iron concentration (HIC) is widely used in clinical practice and in research; however, data on the variability of HIC among biopsy sites are limited. One aim of the present study was to determine the variability of HIC within both healthy and cirrhotic livers. METHODS: Using colorimetric methods, we determined HIC in multiple large (microtome) and small (biopsy-sized) paraffin-embedded samples in 11 resected livers with end-stage cirrhosis. HIC was also measured in multiple fresh samples taken within 5 mm of each other ("local" samples) and taken at sites 3-5 cm apart ("remote" samples) from six livers with end-stage cirrhosis and two healthy autopsy livers. RESULTS: The within-organ SD of HIC was 13-1553 microg/g (CV, 3.6-55%) for microtome samples and 60-2851 microg/g (CV, 15-73%) for biopsy-sized samples. High variability of HIC was associated with mild to moderate iron overload, because the HIC SD increased with increasing mean HIC (P <0.002). Livers with mean HIC >1000 microg/g exhibited significant biological variability in HIC between sites separated by 3-5 cm (remote sites; P <0.05). The SD was larger for biopsy-sized samples than for microtome samples (P = 0.02). CONCLUSION: Ideally, multiple hepatic sites would be sampled to obtain a representative mean HIC.

Biopsy↗

Environmental chemical exposures and disturbances of heme synthesis.

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.

Environmental Exposure↗

Ascorbic acid determination with an automated enzymatic procedure.

Given the widespread interest in antioxidant nutrients, we have developed a new procedure that will permit the automated determination of plasma ascorbic acid (AA) concentration with a Roche Fara centrifugal analyzer. After the deproteinization of plasma with metaphosphoric acid, AA is oxidized to dehydroascorbic acid by AA oxidase. The product is coupled to o-phenylenediamine to produce a chromophore for which the absorbance is measured at 340 nm. The procedure allows much faster throughput than conventional HPLC methods while yielding results that correlate well and provide improved precision. Linearity extends beyond the reference range of 26.1-84.6 micromol/L, and severe hemolysis is the only interference identified.

Adult↗

Delayed bottle weaning and iron deficiency in southeast Asian toddlers.

We undertook this study to determine if culturally influenced feeding practices are associated with iron deficiency in infants and toddlers from low-income families. We obtained a dietary survey, illness history, hematocrit, and zinc protoporphyrin-to-heme ratio (ZPP/H) from 35 Southeast Asian children and 73 children of other ethnicities between ages 5 and 30 months. We confirmed iron deficiency by serum ferritin measurement in children with ZPP/H > 80 mmol/mol or evaluated them after a 3-month iron treatment. Sixty percent of the Southeast Asian children had elevated ZPP/H ratios, compared with 14% of children of other ethnicities. Follow-up studies confirmed iron deficiency in 12 of 21 Southeast Asian children with elevated ZPP/H; 75% (eight) of those with confirmed iron deficiency were 24 to 30 months of age. We found that toddler feeding practices differ between Southeast Asians and other ethnic groups. All 17 Southeast Asian toddlers were still bottle fed at their second birthday, compared with 10 of 21 same-age children of other ethnicities. Persistence of bottle feeding after 2 years of age was highly associated with elevation of ZPP/H in Southeast Asian children but not in other children. Clinicians need to be aware of this problem and carefully monitor iron status in children not weaned from the baby bottle by age 2 years. Changes in education practices and policies are needed to prevent iron deficiency from the overintake of cow's milk that results from prolonged bottle feedings in this ethnic group.

Asia, Southeastern↗

Elevated zinc protoporphyrin associated with thalassemia trait and hemoglobin E.

OBJECTIVE: Increased zinc protoporphyrin/heme (ZPP/H) ratio has been used in pediatrics to screen for iron deficiency and lead poisoning. This study was conducted to determine whether common hereditary hemoglobin disorders (alpha- and beta-thalassemia traits, hemoglobin E) found in U.S. minority groups are associated with an increase in the ZPP/H ratio in an iron-sufficient population. METHODS: The database was compiled from hemoglobinopathy screens performed between 1987 and 1993 at a regional referral laboratory in Washington State. ZPP/H ratio and hemoglobin type were obtained for 326 subjects between the ages of 15 and 49 years of age who were iron sufficient (serum ferritin levels > or = 50 micrograms/L). RESULTS: The mean ZPP/H ratio was significantly higher (p < 0.01) for subjects with beta-thalassemia trait (87 +/- 32 micromol/mol), (alpha-thalassemia trait (73 +/- 37 micromol/mol), and hemoglobin E disorders (73 +/- 24 micromol/mol) than for subjects with normal hemoglobin values (60 +/- 8 micromol/mol). Fifty-one percent of subjects with beta-thalassemia trait, 22% with hemoglobin E, and 20% with alpha-thalassemia trait had elevated ZPP/H ratios (> 80 micromol/mol), compared with only 1.5% with normal hemoglobin values. CONCLUSIONS: The ZPP/H ratio is elevated in common hereditary hemoglobin disorders that mimic the microcytic anemia of iron deficiency, even in individuals without associated nutritional iron deficiency. For children who are treated for presumed iron deficiency, failure of the ZPP/H ratio to return to normal after adequate iron treatment, especially if microcytosis persists, indicates that a hereditary hemoglobin disorder may be present.

Adolescent↗

Laser photobioactivation mechanisms: in vitro studies using ascorbic acid uptake and hydroxyproline formation as biochemical markers of irradiation response.

Clinical investigations of laser photobioactivation, or biostimulation, might be differently designed and more fruitful if knowledge of basic biochemical mechanisms were better understood. In this investigation, biochemical events identified as responses to 904 nm irradiation included increased ascorbic acid uptake by fibroblasts. These cells also showed increased hydroxyproline formation, and this was increased several-fold by the addition of proline to the medium. Maximum biochemical responses were observed at a pulse frequency of 67 Hz and a pulse width of 150 nsec with an energy density of approximately 7 mJ/cm2 per exposure. Elements in the mitochondrial cytochrome system are proposed as the radiation absorbing chromophore(s). Hypothetically, the energy generated is linked to ascorbic acid uptake, which in turn stimulates collagen synthesis.

Ascorbic Acid↗

Ascorbic acid status: biochemical and clinical considerations.

Ascorbic acid (AA) plus dehydroascorbic acid (DHAA) was stable in whole blood in unopened vacutainer tubes. Oxidation of DHAA in plasma was irreversible and rapid at 25 degrees C but not at 4 degrees C. The half-life of AA + DHAA in total parenteral nutrition solutions was greater than 24 h. Conditions are described for dithiothreitol reduction of DHAA followed by assay of total AA, with DHAA being determined by difference. DHAA accounted for less than 5% of the total plasma AA + DHAA in both healthy and diabetic subjects. Infection and postpartum-induced stresses resulted in no significant change in the AA content of polymorphonuclear leukocytes (PMN) per unit of blood but AA content per cell was decreased. When glucose concentration was increased, the Km for AA uptake by PMNs doubled. These chemical and physiological factors combined with the rapid movement of the vitamin between plasma and cells suggest that a reliable indicator of AA status remains to be identified.

Ascorbic Acid↗

Serum levels of selenium and retinol and the subsequent risk of cancer.

A nested case-control study was conducted to assess the relation between serum levels of selenium and retinol and the subsequent risk of cancer. During the years 1972-1984, in northwest Washington State, 156 cases of cancer were identified among members of two employee cohorts from whom specimens had been previously obtained and stored. Two hundred eighty-seven controls were selected from these cohorts and matched to cases on the basis of employer, age, sex, race, and date of blood draw. Selenium and retinol levels were measured by neutron activation and high pressure liquid chromatography, respectively. Information on known cancer risk factors was collected by telephone interviews of subjects and next of kin. Levels of selenium and retinol were unassociated with the incidence of cancer of all sites combined, both overall and within subgroups defined by age, sex, levels of the other micronutrient, time between blood draw and diagnosis, smoking status, and family history of cancer. These findings suggest that neither serum levels of selenium nor those of retinol have an appreciable effect on the risk of cancer.

Blood Preservation↗

Agreement between laboratory tests and self-reports of alcohol, tobacco, caffeine, marijuana and other drug use in post-partum women.

The agreement between self-reported consumption of several drugs and laboratory tests used to detect their use is examined. Post-partum women (N = 108) enrolled in a research study participated in a detailed interview covering alcohol and caffeine ingestion, tobacco smoking and use of marijuana and other psychoactive drugs. They also kept a 4-day record of their use of these substances. Blood and urine samples were taken and a physical exam done at the close of the record period. Laboratory tests to detect use of alcohol, tobacco, caffeine, marijuana and other drugs were carried out and the results compared to self-reported drug use in the interview and the record. The degree of agreement depended on the drug taken, the test used and the pattern of drug use in the sample. Sporadic or infrequent consumption related poorly to laboratory tests, especially those that were designed as screening tools. Regular consumption could be identified with greater accuracy. However, the group associations evident between self-reports of drug use and laboratory results were not sufficient to guarantee that subjects were correctly classified. Error in both self-report and the decision made from laboratory values must be taken into account in determining the confidence that should be placed in the data and the conclusions drawn from it.

Adult↗

Supplement use: vitamin intakes and biochemical indexes in 40- to 108-month-old children.

Intakes and related biochemical indexes of ascorbic acid, thiamin, riboflavin, pyridoxine, vitamin B-12, and folic acid were examined for adequacy in 30 normal children aged 40 to 108 months. Comparisons were made between intake and biochemical index values of children who reported regular use of vitamin supplements and those who reported none. Three-day food records provided nutrient intake data; blood samples, drawn following an overnight fast, were analyzed for biochemical indexes. Student's t-test and the Pearson r were used for comparisons. Mean intakes of most nutrients differed significantly between the supplemented and nonsupplemented groups only when supplements were considered. Mean biochemical indexes differed significantly for riboflavin (p less than .005). Correlations between intakes and respective biochemical indexes were significant for riboflavin (p less than .01) and vitamin B-12 (p less than .01) in the supplemented group and for folate with RBC folate (p less than .005) in the nonsupplemented group. No deficiencies in either group were evident from biochemical indexes; improvement in indexes with supplement use was interpreted as being only relative and not suggestive that such use is beneficial.

Anthropometry↗

Alcohol use and iron status in pregnant women.

Iron status, assessed by ferritin (ng/ml), transferrin saturation (%), and hemoglobin (g/100 ml), was examined in a sample of 1398 women from blood samples drawn at their first prenatal visit and in 712 of these women later at their 32-week prenatal visit. Self-reported alcohol use (average ounces of absolute alcohol consumed per day around the time of conception) was not systematically related to iron status. Furthermore, the proportion of iron-depleted or anemic women did not vary according to different levels of alcohol use. An exception is noted in a small group of nine very heavy drinkers, reporting eight or more drinks per day, who, at 32 weeks gestation, had a higher proportion of iron depletion but not anemia. It was concluded that at least in a sample of primarily middle class women receiving good prenatal care, iron depletion and/or anemia probably do not explain the alcohol-related adverse pregnancy outcomes that have been reported previously. Nevertheless, results from several very heavy drinkers suggest that the iron status of pregnant alcoholic women should be investigated further.

Adolescent↗

Erythrocyte transketolase activity and sudden infant death.

Postmortem heart blood aspirates from 24 consecutive sudden infant deaths and 23 consecutive infant deaths from other causes yielded evidence of erythrocyte transketolase activity (ETKA) in every instance. ETKA measurements from cadaver specimens have not been previously reported. ETKA values did not correlate with the interval from death to sampling or with age at death. Activity coefficients from postmortem material corresponded closely to those from previous studies on living subjects which suggests that the method of Bayoumi and Rosalki yields valid measurements at least for 77 h postmortem. Statistical comparisons of the sudden infant deaths with non-sudden infant deaths revealed no significant differences. This investigation failed to disclose evidence in favor of the hypothesis, advanced by Read, that unsuspected thiamin deficiency may explain some cases of the sudden infant death syndrome.

Erythrocytes↗