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Biomedical subjects

R Carmel

Publications and source records attributed to R Carmel.

At least 19 recordsLinked to original sources
PubMed1992

Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race.

Anti-parietal cell antibody has been reported in nearly all patients with pernicious anaemia in past studies, in contrast with anti-intrinsic factor (IF) antibody which occurs in only 50-70% of such patients. However, observations in the more diverse patient population at our hospital suggest that these prevalences, originally described in predominantly elderly, white patients of European origin, no longer apply. Anti-IF antibody was found in 70% of the 324 patients, with blacks (84%) and Latin Americans (69%) having a significantly higher prevalence than whites (55%). In contrast, only 55% of the 266 patients tested had anti-parietal cell antibody. It was noteworthy that this low rate was similar in all racial groups. However, patients lacking anti-parietal cell antibody were significantly younger than those who had the antibody (54.8 +/- 17.8 vs 59.6 +/- 16.2 years, P = 0.022). Overall, a striking 30% of all patients had anti-IF antibody but not anti-parietal cell antibody, while only 13% had the latter antibody without having anti-IF antibody. This pattern was particularly striking among black patients. An interesting incidental observation was that gastrin levels were not associated with antibody status, but were significantly higher not only among women than among men but also among white and black patients than among Latin-American patients. The findings show that anti-parietal cell antibody is not found nearly as often in pernicious anaemia as has been reported in the past, and thus has no value as a diagnostic tool in pernicious anaemia. They also suggest clues to different expressions of pernicious anaemia or of its immunologic response, particularly among younger patients with the disease.

Adolescent↗
PubMed1992

Serum transferrin receptor in the megaloblastic anemia of cobalamin deficiency.

In order to further study the relation between transferrin receptor and erythropoiesis we examined serum receptor levels in megaloblastic anemia, which is the classic example of ineffective erythropoiesis. We studied 33 patients with unequivocal cobalamin deficiency, only 22 of whom were anemic. High serum transferrin receptor levels were found in 12 patients, all of whom were anemic and had high lactate dehydrogenase (LDH) levels; in contrast, only 10 of the 21 patients with normal receptor levels were anemic. Receptor correlated most strongly with LDH (r = 0.573, p < 0.001) and, inversely, with hemoglobin values (r = -0.560, p < 0.001); it also correlated with ferritin and total bilirubin levels, but not with cobalamin, MCV or erythropoietin. No association was found with the hemolytic component of megaloblastic anemia, represented indirectly by haptoglobin levels. Changes induced by cobalamin therapy were also examined in 13 patients. Transferrin receptors rose in all 6 patients who initially had high levels and in 2 of 3 patients who had borderline levels, but not in the 4 patients with initially normal levels. The receptor levels began to rise within 1-3 days, peaked at about 2 weeks and returned to normal at about the 5th wk. The findings indicate that serum transferrin receptor levels reflect the severity of the megaloblastic anemia. The elevated receptor levels rise further with cobalamin therapy, however, as effective erythropoiesis replaces ineffective erythropoiesis, and these persist until the increased erythropoiesis returns to normal.

Anemia, Megaloblastic↗
PubMed1992

Erythropoietin levels in cobalamin deficiency: comparison of anemic and non-anemic, subtly deficient patients.

The major stimulus for erythropoietin secretion is the circulating hemoglobin level, but other poorly understood factors appear to influence the erythropoietin level as well. Therefore, the effect of cobalamin deficiency was studied in patients who were not anemic, even though many of them had macrocytosis or metabolic deficiency of the bone marrow cells. All 15 cobalamin-deficient patients without anemia had normal erythropoietin levels, including the 4 patients with macrocytosis and 3 in whom metabolic cobalamin deficiency of the marrow cells was documented with the deoxyuridine suppression test. Moreover, among 21 cobalamin-deficient patients with anemia, the 4 least anemic patients also had normal erythropoietin levels. The other 17 anemic patients had elevated erythropoietin levels. Erythropoietin levels correlated with the severity of the anemia (r = 0.423, p less than 0.05). However, wide individual variations were observed; 4 patients with hemoglobin levels of 37-43 g/l had erythropoietin levels ranging from 69 to 3300 units/l, for example. These observations support the hypothesis that the hemoglobin level is the major, but not the sole factor that determines erythropoietin levels. As long as it does not produce anemia, however, cobalamin deficiency does not raise erythropoietin levels even when it induces metabolic deficiency of the bone marrow and macrocytosis.

Anemia↗
PubMed1992

Reversal by cobalamin therapy of minimal defects in the deoxyuridine suppression test in patients without anemia: further evidence for a subtle metabolic cobalamin deficiency.

Subtle cobalamin deficiency states, where low serum cobalamin levels are not accompanied by megaloblastic anemia or malabsorption of free cobalamin, often display metabolic evidence of cellular depletion as shown by the deoxyuridine suppression test. However, the suppression test abnormalities are usually mild and are sometimes atypical; moreover, their response to cobalamin therapy has never been documented. Four patients with this subtle defect, at least three of whom had food-cobalamin malabsorption, were therefore tested before and after cobalamin treatment. Each patient had low serum cobalamin levels but did not have megaloblastic anemia, and all but one had normal serum levels of methylmalonic acid and total homocysteine. Two patients had mildly but typically cobalamin-deficient deoxyuridine suppression test results (baseline values 15.7% and 12.8%; normal less than 8.5%). The other two patients had normal or borderline baseline values (5.4% and 8.9%) that became abnormal on incubation with methyl tetrahydrofolate (16.1% and 12.3%), a pattern previously noted in subtle acquired and hereditary cobalamin deficiencies. After 6 months of cobalamin therapy, the deoxyuridine suppression test abnormalities reversed in all four patients. These findings show that the mild deoxyuridine suppression test stigmata of subtle cobalamin deficiency respond to therapy and thus represent true metabolic deficiency; the unusual abnormality induced in vitro by added methyl tetrahydrofolate responds as well, indicating that it, too, represents metabolic cobalamin deficiency. The findings provide further proof that subtle cobalamin deficiency often exists even when megaloblastic anemia and malabsorption of free cobalamin are lacking, and that the deoxyuridine suppression test can be a reliable tool for its identification.

Aged↗
PubMed1991

Helicobacter pylori infection in pernicious anemia: a prospective controlled study.

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Anemia, Pernicious↗
PubMed1990

Human umbilical vein endothelial cells secrete transcobalamin II.

Transcobalamin II (TC II) is essential for cellular uptake of cobalamin. However, the origin of this transport protein is controversial and many organ sources have been suggested. We studied human umbilical vein endothelial cells cultured in vitro. The cells contained TC II (2.3 pmol/10(8) cells) and released progressively increasing amounts of the protein into the surrounding medium during the 3-day incubation period. This release exceeded the starting intracellular content of TC II. In contrast, endothelial cells did not contain or elaborate R binder, the other major circulating binding protein for cobalamin, Cycloheximide inhibited the elaboration of TC II, suggesting that the endothelial cells synthesize the protein. Thrombin, which stimulates tissue plasminogen activator release, did not enhance TC II release, and neither did endotoxin or mellitin. However, thrombin did appear to partially protect TC II release from inhibition by cycloheximide. Among other cells studied, human fibroblasts also released TC II into the incubation medium, while K562 human leukemia cells, ARH-77 and HS Sultan human plasma cell lines, and Raji strain lymphoblasts did not. The data suggest that endothelial cells are an important source of the metabolically crucial TC II.

Cycloheximide↗
PubMed1990

Neurologic and evoked potential abnormalities in subtle cobalamin deficiency states, including deficiency without anemia and with normal absorption of free cobalamin.

The meaning of a low serum cobalamin level when the classic findings of pernicious anemia are lacking is undergoing reevaluation. We therefore studied the neurologic status of 11 patients who had low cobalamin levels without definite hematologic evidence of deficiency. Neurologic evaluation included pattern-shift visual and median and posterior tibial nerve somatosensory evoked potentials. None of the patients had megaloblastic changes in the blood or bone marrow, although 7 of the 11 had subtle cellular cobalamin disturbances demonstrated by an abnormal deoxyuridine suppression test result. Seven patients had normal Schilling test results and 2 had borderline results; however, 2 of the 5 patients tested further had food-cobalamin malabsorption, while a third had prepernicious anemia. The patients displayed a variety of neurologic problems, including dementia, depression, myelopathy, neuropathy, and seizure disorder; 1 patient was neurologically normal by clinical criteria. Evoked potential abnormalities were demonstrable in 8 of the 9 patients with subtle cobalamin deficiency, and in at least 5 cases the disturbance was central. In contrast, both patients whose low serum cobalamin levels were found on evaluation to be spurious had normal evoked potentials. Evoked potential abnormalities improved in the one patient retested after cobalamin therapy. These findings demonstrate that neurologic deficits occur not only in classic cobalamin deficiency but also in subtle or atypical cobalamin deficiency states in which anemia is absent and Schilling test results are normal. Electrophysiologic evidence of neurologic impairment is often present, even in patients without obvious clinical neurologic abnormalities.

Absorption↗
PubMed1990

Subtle and atypical cobalamin deficiency states.

Evidence for cobalamin (vitamin B12) deficiency usually involves some combination of low serum cobalamin levels, clinical abnormalities (classically, megaloblastic anemia and neurologic defects), metabolic abnormalities, and response to therapy. However, cobalamin deficiency may often display few of the expected clinical findings. Identification of the underlying cause is also important in the diagnosis of deficiency, and its value may be particularly great when the expression of deficiency is subtle. The cause of cobalamin deficiency is usually malabsorptive, but may sometimes be limited to malabsorption of food cobalamin while free cobalamin is absorbed normally. Nongastroenterologic entities may sometimes also be found. All of these considerations allow the proposal of four patterns of cobalamin deficiency. The first type is classical deficiency; typical megaloblastic anemia with or without neurologic dysfunction occurs because of classical cobalamin malabsorption such as lack of intrinsic factor (pernicious anemia). The second type consists of classical cobalamin malabsorption in which the cobalamin deficiency is expressed subtly rather than in classical fashion. There is no megaloblastic anemia and sometimes the only evidence of deficiency may be metabolic. In the third type, cobalamin deficiency is expressed classically but is attributable to a subtle or atypical cause, such as food-cobalamin malabsorption. In the fourth type, deficiency is both expressed subtly and arises from subtle or atypical causes. Such presentations require further investigation but are a challenging expansion of our understanding and recognition of cobalamin deficiency.

Diagnosis, Differential↗
PubMed1990

Transfer of cobalamin from the cobalamin-binding protein of egg yolk to R binder of human saliva and gastric juice.

Patients may fail to absorb cobalamin (vitamin B12) bound to food even when they have adequate intrinsic factor to absorb free cobalamin normally. We studied cobalamin transfer from egg yolk cobalamin-binding protein to human saliva and gastric juice as a model of this important first step in cobalamin assimilation. The cobalamin-binding protein of egg yolk eluted with human R binder on Sephadex gel chromatography and bound cobalamin with a comparable affinity, but it did not cross-react with R binder immunologically. Transfer of cobalamin from egg yolk to saliva or gastric juice R binder did not occur at neutral pH. Slight transfer (8%-12% of the 57Co-cobalamin bound to egg yolk) occurred when the saliva was acidified to pH 1.5. This minor transfer by acid was not inhibited by pepstatin A, a pepsin inhibitor. Acidification caused variable transfer to gastric juice R binder (12%-40%) that appeared to be partially due to residual gastric pepsin activity. Adding 1200 U of pepsin per milliliter enhanced cobalamin transfer to saliva or gastric juice R binders (39%-58% transfer). At no time was cobalamin transferred directly to intrinsic factor; R binder-deficient gastric juice failed to accept cobalamin from egg yolk. The transfer of cobalamin from egg yolk to human R binder requires both an acid pH and pepsin activity. While as little as 30 U of pepsin added per milliliter of saliva promoted transfer of cobalamin, the requirement for an acid pH was very strict. Virtually no transfer occurred when pH exceeded 2.0, regardless of the amount of pepsin present. Acid provided an optimal pH for pepsin activity and, to a lesser extent, affected transfer by a mechanism unrelated to pepsin. Our data suggest that compromised pepsin secretion and, probably even more importantly, compromised acid secretion interfere with transfer of food cobalamin to R binder.

Anemia, Pernicious↗
PubMed1990

Autoimmune cytopenias in pernicious anemia: a report of four cases and review of the literature.

Pernicious anemia appears to be autoimmune in origin and is associated with immune disorders of several organ systems. We report 4 patients with pernicious anemia and immune cytopenias, an association that may sometimes pose diagnostic problems unless specifically considered. Pernicious anemia coexisted with or was closely followed by idiopathic thrombocytopenic purpura in 3 patients and by autoimmune hemolytic anemia in a 4th patient. In addition to cobalamin therapy, all patients required corticosteroids (2 also received danazol), while 1 also required splenectomy. All 4 patients were women. The 3 patients with idiopathic thrombocytopenic purpura were also blood group O and were iron-deficient. Autoimmune cytopenias may occur in patients with treated or untreated pernicious anemia and require specific therapy.

Adult↗
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↗