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R Carmel

Publications and source records attributed to R Carmel.

At least 109 records · Page 6Linked to original sources
PubMed1981

Cobalamin binding and uptake in vitro in the human central nervous system.

Little information exists about the CNS transport of cobalamin. Therefore we undertook to characterize the cobalamin-binding proteins of CSF and to examine uptake of the vitamin by homogenates of CNS tissue. CSF from 24 patients had a mean unsaturated cobalamin-binding capacity of 335 +/- 282 pg/ml. The vast majority of this was TC II (302 +/- 276 pg/ml). The remainder consisted of R binder and a binder eluting with the void volume on Sephadex G-200 gel chromatography. CSF TC II was identical to serum TC II immunologically, functionally, in molecular size, and in electrophoretic mobility, but the levels of the two did not correlate. CSF TC II levels may correlate best with CSF protein levels and tended to be higher in abnormal fluids. Unlike serum TC II, CSF TC II tended to adhere to glass surfaces; uncorrected, this may be a source of artifact in studying various fluids. CSF contains little cobalamin, but most of the endogenous cobalamin was carried by TC II instead of by R binder. Thus CSF appears to have a much higher total TC II: R binder ratio than does plasma. TC II enhanced 57CoB12 uptake by neonatal and adult human brain homogenate and by mouse brain homogenate. The primary phase of TC II-57CoB12 uptake in vitro by human brain cortex homogenate occurred mostly within 30 min and was maximal at 22 degrees C. Uptake was specific, but apo-and holo-TC II appeared to have equal affinity for the receptors. Spinal cord homogenate took up less TC II-57CoB12 per wet weight of tissue than did brain homogenate. R binders did not enhance cobalamin uptake; in fact, they inhibited it. We conclude that uptake of cobalamin by CNS tissue is dependent on TC II and that TC II may be even more prominent in cobalamin transport in the CSF than it is in plasma.

Animals↗
PubMed1980

The Schilling test.

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Anemia, Pernicious↗
PubMed1979

Anemia. Textbook vs practice.

Anemia, particularly if mild, is ignored frequently. We conducted a questionnaire survey of 252 physicians and medical students to verify this impression and to explore the reasons for it. A cumulative 40% to 57% depending on the hypothetical patients' circumstances) of respondents chose to investigate anemia only at hemoglobin levels too low for the accepted criteria in female patients; a striking 78% to 89% did so in male patients. Only 54% and 30% knew the correct textbook definition of anemia for women and men, respectively. More importantly, 35% to 60% demonstrated criteria for choosing to investigate anemia were lower than even their own perception of the textbook definition. Little difference existed among the various physician subgroups in their responses. The discrepancy between what physicians do and what they are taught appears to arise from several factors, of which lack of knowledge is only one.

Adult↗
PubMed1979

Leukocyte hexose monophosphate shunt activity during phagocytosis in vitamin B12 and folic acid deficiencies.

Little information exists about leukocytic function in megaloblastic anemia. A report of abnormal hexose monophosphate shunt and phagocytic activity only in vitamin B12 deficiency and not in folate deficiency prompted us to examine latex-stimulated hexose monophosphate shunt activity in the two conditions. Only two of our five patients with pernicious anemia demonstrated defective activation, while one of the two folate-deficient patients also had this defect. These findings clearly indicate that hexose monophosphate shunt activity is neither consistently impaired in vitamin B12 deficiency nor consistently unaffected in folate deficiency.

Anemia, Megaloblastic↗
PubMed1979

Macrocytosis, mild anemia, and delay in the diagnosis of pernicious anemia.

Various factors led to delays of several months to several years in the diagnosis of pernicious anemia in 11 patients, occasionally with serious consequences. These cases illustrate that earlier diagnosis is possible with closer attention to abnormal results of common tests. Macrocytosis, detected by high mean corpuscular volume, often preceded anemia but was not investigated, especially when anemia was only slight. Several cases demonstrated that vitamin B12 deficiency may initially produce only a mild macrocytic anemia, which is maintained for a long period before a rapid worsening supervenes; the reason for the latter acceleration of anemia is unknown. Most serious was the evidence that mild anemias are often ignored. Stricter attention to the established limits of normal hemoglobin values is required. These aspects of physician performance have implication for the recognition of all anemias.

Aged↗
PubMed1978

Racial patterns in pernicious anemia. Early age at onset and increased frequency of intrinsic-factor antibody in black women.

Pernicious anemia affects primarily elderly northern Europeans, but may affect others more often than previously thought. Therefore, we analyzed the data from 156 documented cases: there were 73 patients of "European" origin, 52 black patients and 31 Latin-American patients. The mean age (+/- 1 S.D.) at presentation among black women, 53 +/- 16 years, was lower than that of all the others (P less than 0.001 in most comparisons), and seven of the 33 black women were less than 40 years old. In addition, 23 of the 24 black women tested had circulating antibody to intrinsic factor. A similar though less striking antibody prevalence (85 per cent) and age pattern (60 +/- 13 years) in Latin-American women did not reach statistical significance. No other group exceeded the usual 55 to 70 per cent prevalence of antibody. These finding suggest a different form of or a different response to the disease in black women and perhaps in Latin-American women.

Adult↗
PubMed1978

Vitamin B12-binding proteins in serum and plasma in various disorders. Effect of anticoagulants.

Because of recent developments in the study of vitamin B12-binding proteins, the levels of the three serum binders were compared in serum and plasma samples from subjects with various disorders. The results allow the following conclusions: (1) As previously reported, transcobalamin (TC) III and to a lesser extent TC I are artifactually elevated in serum. The appear to be released in vitro during the clotting process, presumably from granulocytes. (2) Blood cells of patients with polycythemia vera release exceedingly large amounts of TC I and TC III in vitro. (3) The above findings support, but do not prove, at least a partial granulocytic source of TC I. Nevertheless, factors other than granulocytes influence TC I levels, as disorders characterized by increased TC I (most prominently chronic myelogenous leukemia but also several cases of cancer) manifest relatively little cellular release of TC I in vitro. (4) Despite the serum artifact, the serum abnormalities described in various conditions were seen in plasma also, even though the actual values of themselves were lower in plasma. The chief exception was TC III, which was elevated in plasma only in polycythemia vera (and in a few cases of leukocytosis). (5) EDTA-NaF anticoagulant is not suitable, as it causes plasma dilution, thus explaining previous reports of TC II level differences between serum and plasma. EDTA is therefore a preferable anticoagulant for vitamin B12-binding protein studies, although it too may not be ideal.

Anticoagulants↗
PubMed1978

Effects of antineoplastic drugs on Lactobacillus casei and radioisotopic assays for serum folate.

Microbiologic assay, usually employing Lactobacillus casei, remains the standard assay for serum folate to date. Among its disadvantages have been falsely low results in patients receiving bacteriostatic agents such as antibiotics. This study examined whether commonly used antineoplastic drugs had similar effect. Methotrexate and 5-fluorouracil depressed microbiologic serum folate levels. No effect was found for adriamycin, bleomycin, BCNU, cyclophosphamide, cytosine arabinoside, vincristine, vinblastine, mechlorethamine, mithramycin, hydroxyurea, and hydrocortisone. None of the drugs affected radioassay except methotrexate, which produced falsely high folate results. Thus, it appears that L. casei assay for folate becomes unreliable in patients receiving 5-fluorouracil and radioisotopic assay becomes unreliable in those receiving methotrexate.

Antineoplastic Agents↗
PubMed1978

Artifactual radioassay results due to serum contamination by intravenous radioisotope administration. Falsely low serum vitamin B12 and folic acid results.

Radioisotopic contamination by recent radioisotope administration (either 99mtechnetium or 67gallium) to the patient for scanning purposes was found in 28 sera submitted for vitamin B12 or folic acid assay, or both, during the year prior to this study. In half the cases serum radioactivity was so great as to be readily identifiable during the assay. In the rest, however, the radioactivity would not have been detected had serum supernatant blanks not been routinely incorporated in the assay procedure. Many radioassay kits make no provision for such supernatant control blanks. Were it not for these blanks, five patients would have been falsely identified as vitamin B12-deficient and three others as possible deficient in the present series. Two of the five radioactive sera assayed for folate would also have given misleading results in the borderline-low range. The clinician should avoid ordering tests requiring radioassay when the patient has been given radioisotopes, and those performing radioassays must institute appropriate maneuvers to detect any such contamination.

False Positive Reactions↗
PubMed1978

Nutritional vitamin-B12 deficiency. Possible contributory role of subtle vitamin-B12 malabsorption.

Dietary deficiency of vitamin B-12 has been reported, yet most people ingesting vitamin-B12-deficient diets even for many years appear to achieve a balance that does not lead to overt signs and symptoms of deficiency. I present the case of a vegan of 25 years' duration who developed severe neurologic abnormalities due to vitamin-B12 deficiency. His diet provided 1.2 microgram of vitamin B12 daily at most. Despite normal Schilling test findings, he absorbed subnormal amounts of vitamin B12 given with ovalbumin. This poor absorption appeared to be related to his gastritis, achlorhydria, and subnormal intrinsic-factor secretion. Probably, vitamin-B12 deficiency in this patient resulted from both dietary restriction and the subtle malabsorption, neither of which would have sufficed alone to produce the clinical problem. Possibly such malabsorption may also be present in many of those vegans developing overt vitamin-B12 deficiency in whom Schilling test findings have been normal.

Diet, Vegetarian↗
PubMed1978

Comparison of radioassay and microbiological assay for serum folate, with clinical assessment of discrepant results.

Folate assays by use of radiolabeled folate provide obvious practical advantages over the standard microbiological assay, but remain incompletely tested. We therefore compared results for 415 sera with a kit involving 3H-labeled folate and the Lactobacillus casei microbiological method. We examined the patients' data when there were discrepancies between the two methods. Although the correlation overall was satisfactory, results were discrepant in 25% of cases. In 74% of the latter, the radioassay result appeared to be the correct one, primarily because L. casei results were suppressed by antibiotics being taken by the patient. The radioassay occasionally gave falsely high values for patients with liver disease and falsely low ones for patients who had received isotopes for scanning purposes. Several assay kits that make use of 125I- or 75Se-labeled folate were also tested. Although these results correlated with the results of 3H-labeled folate assay, various problems appeared, including the possible need for serum-supernate control tubes in one kit. Answers to these and other questions and careful clinical correlation of results are needed for any folate radioassays before their adoption for routine clinical use.

Biological Assay↗
PubMed1978

The laboratory diagnosis of megaloblastic anemias.

The diagnostic approach to megaloblastic anemia involves four usually sequential steps. The first step, recognition of megaloblastosis, requires attention to altered blood cell size and morphology. These changes may sometimes be subtle or masked. The cornerstone of the second step, identification of the specific vitamin deficiency, is assay of serum vitamin B(12) and folic acid levels, although they may occasionally be misleading. The third step, identification of the specific disease entity responsible for the vitamin deficiency, generally revolves around tests of absorption and gastric function. The fourth step, reevaluation after replacement therapy, is often not thought of as a diagnostic step but carries important diagnostic implications and is sometimes the only way in which coexisting abnormalities can be unmasked and identified.

Anemia, Macrocytic↗