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Biomedical subjects

R Carmel

Publications and source records attributed to R Carmel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hormone replacement therapy and cobalamin status in elderly women.

Serum cobalamin concentrations are frequently low in the elderly but the cause is often not apparent. Because oral contraceptives have been associated with low cobalamin concentrations in young women, we compared hormone use with cobalamin status in elderly women to determine whether it could account for their unexplained low cobalamin concentrations. Thirty-eight of the 111 women had abnormal cobalamin status (defined by low cobalamin, elevated methylmalonic acid, and/or elevated homocysteine concentrations) and 73 had normal status. There was no difference in hormone use between the two groups: 7 (18.4%) of the 38 cobalamin-deficient subjects used estrogens compared with 20 (27.4%) of the 73 control subjects. No differences in hormone use were apparent either when analysis was confined to abnormal serum cobalamin concentrations alone. Similarly, the 27 women taking hormones and the 84 women not taking hormones did not have significantly different serum cobalamin or serum total homocysteine concentrations. Indeed, hormone users had slightly, though not significantly, higher cobalamin concentrations and lower homocysteine concentrations than nonusers; furthermore, hormone users also had significantly lower serum methylmalonic acid concentrations. Thus, neither cobalamin concentrations nor cobalamin metabolic status were significantly worse in elderly women taking estrogen than in those not taking it (and, if anything, may have been slightly better). Hormone use does not appear to be a significant contributor to the low cobalamin concentrations or the mild metabolic evidence of cobalamin deficiency so often seen in the elderly.

Aged↗
PubMed1996

Neutrophil nuclear segmentation in mild cobalamin deficiency: relation to metabolic tests of cobalamin status and observations on ethnic differences in neutrophil segmentation.

Neutrophil hypersegmentation is considered the most sensitive peripheral blood cell marker of cobalamin deficiency. However, its diagnostic value in the mild deficiency states that accompany most low cobalamin levels and its relation to metabolic test of cobalamin status are unknown. The authors compared neutrophil lobe averages and percent neutrophils with 5 or more lobes (%5+ lobes) in 169 subjects with their mean corpuscular volume (MCV) and serum cobalamin, methylmalonic acid (MMA), homocysteine, and folate levels and, in 65 cases, with the deoxyuridine suppression test (dUST). Only 9 subjects had hypersegmentation by lobe average and 20 subjects by %5+ lobes. They were not more often cobalamin-deficient than subjects without hypersegmentation. Moreover, only one of 34 subjects with dUST results diagnostic for cobalamin deficiency had neutrophil hypersegmentation. Both indices of neutrophil segmentation in the 169 subjects correlated significantly with homocysteine levels. They also showed weak inverse correlation with cobalamin levels, but did not correlate with MMA, folate, or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondeficient controls, and only marginally improved the %5+ lobes. A surprising, incidental observation was that blacks had significantly greater neutrophil segmentation by both criteria than did whites and others. This difference was unrelated to cobalamin or folate status. Our results indicate that dUST abnormalities precede all morphologic changes of deficiency, including hypersegmentation. Although a tendency exists for neutrophil segmentation to increase very slightly as some serum values, especially homocysteine, start to worsen in mild cobalamin deficiency, the metabolic changes precede overt hypersegmentation. Neutrophil nuclear segmentation is insufficiently sensitive in relation to metabolic evidence of deficiency to be used as a clinical tool in the diagnosis of mild cobalamin deficiency.

Asian People↗
PubMed1996

Spouses of demented patients with low cobalamin levels: a new risk group for cobalamin deficiency.

Low serum cobalamin levels are common in conditions such as dementia and often represent mild deficiency. We surveyed serum cobalamin levels prospectively in spouses and blood relatives of demented patients to determine if any familial predisposition exists for the low levels. Cobalamin status in most of the relatives found to have low levels was assessed further by means of blood counts, metabolic tests, neurologic evaluation, absorption studies and response to cobalamin therapy. Serum cobalamin levels in 36 spouses correlated with those of the 36 demented patients related to them (r = 0.46, p = 0.004). A significant association was not seen in 34 blood relatives of 34 demented patients (r = 0.27). Most importantly, 67% of the spouses of demented patients with low serum cobalamin had low values themselves, compared with only 3% of the spouses of patients with normal levels (p = 0.001). Detailed study of 4 of the 5 spouses (and 3 blood relatives) with low cobalamin levels showed no anemia in any case. Nevertheless, 4 of the subjects had metabolic evidence of deficiency and one had electrophysiological abnormalities; all these defects improved with cobalamin therapy. These observations identify a hitherto unsuspected group of people at high risk for cobalamin deficiency and suggest that spouses of demented patients with low cobalamin levels should also have their cobalamin levels measured. The increased frequency of low serum cobalamin levels in spouses of demented patients with low levels represents in most cases a true, mild cobalamin deficiency that responds to treatment.

Adult↗
PubMed1995

Malabsorption of food cobalamin.

Food-cobalamin malabsorption is marked by the inability to release cobalamin from food, which therefore cannot be taken up by intrinsic factor for absorption. The defect is not detectable by classical clinical tests like the Schilling test which are all based on the absorption of free, crystalline cobalamin. Tests of food-cobalamin absorption have been devised, the most popular ones using cobalamin bound to eggs or to chicken serum. The disparity between the abnormal results of these tests and the normal results with the Schilling test defines the disorder of food-cobalamin malabsorption. Release of cobalamin from food requires acid and pepsin, and most food-cobalamin malabsorptive states can be traced to gastric defects. However, other mechanisms may also play a role. The malabsorption is limited to food cobalamin and any free cobalamin, presumably including recycled biliary cobalamin, will be absorbed normally, which may explain its frequently insidious nature. The effect on cobalamin status covers a broad spectrum. At one extreme, some individuals, perhaps in the earliest stages, have normal cobalamin status, while at the other extreme may be found deficiency every bit as severe as in the most florid case of pernicious anaemia. Most often, however, the deficiency is mild, frequently marked by only a low serum cobalamin level, mild evidence of metabolic insufficiency and, sometimes, minimal clinical sequelae. Moreover, in some cases the gastric defect progresses and intrinsic factor secretion is affected, thus transforming into classical pernicious anaemia; this is not inevitable, however, and probably occurs in only a minority of patients. The course of food-cobalamin malabsorption is therefore a varied one. Nevertheless, it may be the most common cause of subtle or mild cobalamin deficiency and it is also sometimes associated with severe deficiency. Its identification and treatment need to be considered more widely in the clinical setting.

Animals↗
PubMed1995

The frequently low cobalamin levels in dementia usually signify treatable metabolic, neurologic and electrophysiologic abnormalities.

Cobalamin levels are frequently low in patients with dementia, but it is unclear if they represent definable deficiency and what the mechanisms are. Therefore, patients being evaluated for dementia who had low cobalamin levels but no obvious evidence of deficiency were studied hematologically, neurologically and with metabolic tests and were re-evaluated after cobalamin treatment. Abnormalities suggestive of or diagnostic for deficiency were documented in most of the 16 demented and nondemented patients. Metabolic results: 50% of patients tested had abnormal deoxyuridine suppression and 44% had increased serum methylmalonic acid and/or homocysteine levels; these test results correlated with each other. Neurologic results: 73% of patients had clinical abnormalities, primarily mild neuropathies, not attributable to other causes, 75% had electroencephalographic abnormalities, 77% had abnormal visual evoked potentials and 33% had abnormal somatosensory potentials. Metabolic and neurologic dysfunction were present together or absent together in all but 2 cases. Cobalamin therapy improved 50-100% of the various types of abnormalities, although it did not improve cognitive function in the 13 demented patients. Food-cobalamin malabsorption was found in 60% of the patients. Despite the absence of megaloblastic anemia and rarity of traditional malabsorption of free cobalamin, low cobalamin levels in demented patients frequently represent mild cobalamin deficiency and are often associated with food-cobalamin malabsorption. Perhaps most importantly, this is accompanied not only by metabolic changes but by evidence of mild neurologic dysfunction. Their frequent reversibility by cobalamin confirms that these defects indeed arise from cobalamin deficiency. Although the long-standing dementia does not improve, treating such patients with cobalamin has other concrete benefits.

Aged↗
PubMed1994

In vitro studies of gastric juice in patients with food-cobalamin malabsorption.

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric Juice↗
PubMed1994

Helicobacter pylori infection and food-cobalamin malabsorption.

Two entities of considerable recent interest, Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody to H. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT < 1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0-1.99%) and 42% of 59 subjects with normal absorption (EYCAT > or = 2.0%) (chi 2 = 9.52, P < 0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03 +/- 1.83% vs 3.11 +/- 2.13%, t = 2.913, P = 0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence of H. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced by H. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.

Adult↗
PubMed1994

Megaloblastic anemias.

Data continue to emerge that the low cobalamin levels often seen in the elderly and in various other settings represent a subtle cobalamin deficiency state. Even though such individuals do not have megaloblastic anemia and absorb free cobalamin normally, metabolic tests frequently document insufficiency of cobalamin that reverses after treatment with cobalamin. In many cases, malabsorption limited to food cobalamin seems responsible for the mild deficiency state. A major development related to folate has been the conclusive documentation that folate supplementation halves the risk of having a baby with neural-tube defect. The explanation for this phenomenon and the possible long-term side effects of regular folate supplementation remain to be determined. Another issue with public health implications is the association of mild homocysteinemia with premature cardiovascular disease and evidence that the homocysteinemia responds to vitamin supplementation. Important advances are being made with molecular biologic techniques in unraveling the structure of key transport proteins for cobalamin and folates.

Aging↗
PubMed1993

Transfusion practice in medical patients.

OBJECTIVE: Blood transfusion raises serious issues of safety and economics. We therefore examined blood usage and its characteristics in medical inpatients, given the relative scarcity of existing data. DESIGN: During a 1-year period, transfusion episodes on two medical services were reviewed by five specialists for justifiability on the basis of generally agreed on guidelines. SETTING: The study was conducted at two institutions, a municipal teaching hospital where house staff deliver care and a community hospital where patients are under the direct care of private physicians. PATIENTS: Four hundred thirty-eight randomly selected transfusion episodes on the medical services of the two institutions were reviewed. MAIN OUTCOME MEASURES: The prevalence of unjustifiable transfusions based only on the information available to the managing physician at the time of transfusion. RESULTS: Eighteen percent of the 438 randomly selected transfusion episodes were viewed as not justifiable by at least four of five reviewers; another 17% were classified as equivocal because two or three reviewers judged them to be not justifiable. The most striking observation was the greater prevalence of nonjustifiable transfusion episodes at the community hospital (26% vs 16% at the teaching institution; P = .0121). Other observations included a tendency for physicians to prescribe transfusions by the numbers (at least 11% of nonjustifiable transfusions) and to overtransfuse. The routineness with which transfusion was viewed by managing physicians was also identifiable by the absence of written transfusion notes in 39% of all episodes reviewed, which incidentally raises questions about the adequacy of the medical chart's documentary functions today. CONCLUSIONS: The rate of nonjustifiable or equivocal transfusion on medical services may be as high as 35%. Reliance on numbers rather than clinical status seems to be a major problem. Education is obviously a critical issue and should also target private practitioners, who seemed to perform less well than physicians in training. Transfusion guidelines that use specific hematocrit values also need to be reexamined.

Blood Transfusion↗
PubMed1993

Metabolic evidence of cobalamin deficiency in bone marrow cells harvested for transplantation from donors given nitrous oxide.

Nitrous oxide inactivates cobalamin, but clinically apparent sequelae ensue in nondeficient individuals only when exposure is prolonged. The gas is widely used in anesthesia, therefore, and is commonly given to donors during harvesting of their bone marrow cells for transplantation. The present study shows that nitrous oxide administered for only 75-120 minutes induced mild but unequivocal DNA synthetic abnormalities attributable to cobalamin deficiency in the harvested marrow cells of 4 out of 5 donors; the deoxyuridine suppression test in these 4 patients showed abnormal results more than 4 standard deviations above the reference mean. Metabolic evidence of cobalamin deficiency in cryopreserved cells diminished only slightly when they were thawed and retested 1 day later, but was no longer detectable in cells thawed and tested on the 3rd day. In contrast, cells harvested under nitrous oxide-free anesthesia in 4 subjects showed no evidence of cobalamin deficiency in the deoxyuridine suppression test. These results demonstrate that even relatively brief exposure to nitrous oxide induces cobalamin deficiency in harvested bone marrow cells, and that the cells remain metabolically impaired for more than 24 hours. Although clinical sequelae are not apparent at this time, the several potential implications of our findings indicate that the use of nitrous oxide in bone marrow transplantation needs to be evaluated further.

Anesthesia↗
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↗