Cases Of Pernicious Anemia Research Articles

A Case of Pernicious Anemia with Advanced Spinal Cord Lesions Treated Favorably.

A Case of Pernicious Anemia with Advanced Spinal Cord Lesions Treated Favorably.

Lactate dehydrogenase in the diagnosis and assessment of response to treatment of megaloblastic anaemia.

Gross elevation of the serum lactate dehydrogenase (S.L.D.) in megaloblastic anaemia was first reported by Hess and Gehm (1955) who found values from 5 to 21 times the upper limit of normal in 16 cases of pernicious anaemia. They also noted an inverse correlation between the serum enzyme activity and the peripheral red blood cell count. The rise in the S.L.D. has since been confirmed by Lührs and Negelein (1955), Cintrön‐Rivera, Acosta‐Martienzo and Diaz‐Rivera (1956), Zimmerman, West and Heller (1958), Heller, West and Zimmerman (1959), Gordin and Enari (1959), Levitan, Wasserman and Wróblewski (1959), Amelung (1960), Grönvail (1961), Elliott and Wilkinson (1963) and Goldfarb and Papp (1963), but there are conflicting reports concerning the relation between the degree of S.L.D. elevation and the severity of the anaemia.While Gordin and Enari (1959) reported that the S.L.D. activity correlated inversely with the serum vitamin B12 level, but not with either the blood haemoglobin concentration or the peripheral red cell count, in patients with pernicious anaemia or Diphyllobothrium latum infections, Levitan et al. (1959) found S.L.D. elevations in Addisonian anaemia only and not in megaloblastosis due to other causes. However, Amelung (1960) and Grönvall (1961) have suggested that the occurrence of extremely high S.L.D. activities might be diagnostic of megaloblastosis, and Fleming and Elliott (1964) have recently reported high levels of S.L.D. and of serum 2‐hydroxybutyrate dehydrogenase (S.H.B.D.) in folic acid‐deficient Nigerian patients with macrocytic anaemia of pregnancy. Similar elevation of the S.H.B.D. in pernicious anaemia had previously been reported by Elliott and Wilkinson (1963) who also observed a rise in the S.H.B.D./S.L.D. ratio during specific therapy.The present investigation was carried out to assess the reliability of S.L.D. and S.H.B.D. determinations in the diagnosis of megaloblastic anaemia and as indicators of the response to treatment. The enzyme levels have also been compared with the results of haematological investigations.

Chromosomal Aberrations in Pernicious Anemia: Study of Three Cases before and after Therapy

Abstract Numerical and morphologic chromosomal aberrations were demonstrated in three cases of pernicious anemia in relapse. The morphological abnormalities including chromatid breaks, gaps and "giant" chromosomes were reduced in remission following vitamin B12 therapy. The numerical changes consisted of aneuploidy (45 and 44 chromosomes) with the most common finding encountered (6 to 100 per cent of the cells) being monosomy involving the G 21 chromosome. This was present, not only in the marrow cells, but also in other tissues, e.g., peripheral blood and possibly skin fibroblasts, thus suggesting a more generalized disorder. The numerical anomalies persisted in remission. It is postulated that the structural anomalies, namely chromatid breaks, gaps, acentric fragments and "giant" chromosomes are related to vitamin B12 deficiency and are correctable. The cause of the aneuploidy, since it was not correctable by treatment, is not clear. Since the patients were not studied before the disease had ensued, a congenital or acquired predisposition to megaloblastosis on the basis of G 21 monosomy cannot be excluded. The origin and significance of the extra chromatin material translocated onto the short arms of G 21 chromosomes in cases 1 and 3 remains unexplained.

ORAL TREATMENT OF PERNICIOUS ANAEMIA.

IT will not surprise many workers in the B12 field to read that Dr. Heinivaara and Dr. Palva have obtained a remission over a period of 50 days in one case of pernicious anaemia, which was receiving a daily dosage of 60 µg of crystalline B12 (see above). Indeed, in our original work1 we chose this dosage because we knew that, being in the sub-optimal range, it should be sufficient to prevent deterioration during the period of test, and thus be ethically justifiable. To draw firm deductions about the significance of glutamic acid additives, however, from a comparison between the blood responses in two selected cases is too ingenuous. The important finding, of course, during this initial period of treatment on sub-optimal dosage is not the haematological response as assessed by haemoglobin (Hb) or packed cell volume (P.C.V.) readings over 50 days (which vary greatly from patient to patient), but the reticulocyte response, obtained from the same patient, on one form of therapy compared with that on another. This test—the double reticulocyte response test—is not our test as Heinivaara and Palva infer. It was originally described in 1935 by Minot and Castle2, and is still regarded as the most reliable short-term method for the comparison of the therapeutic effect of two haematinics of unknown potency3.

ADDISON'S DISEASE AND ADDISONIAN ANEMIA; A CASE REPORT.

Pernicious anemia has been associated with a number of other diseases, but there are few case reports documenting adrenal cortical insufficiency and pernicious anemia occurring in the same patient. Concurrently found with 370 cases of pernicious anemia were asthma, bronchitis, pneumonia, hypertension, thyroid disease, diabetes, tuberculosis, gastric carcinoma, polycythemia, and leukemia.1However, no mention was made of associated adrenal cortical insufficiency. Wintrobe has stated that the simultaneous occurrence of the two diseases is of historical interest.2The purpose of this report is to describe a patient with adrenal cortical insufficiency who subsequently developed pernicious anemia (with a brief review of the literature) and to review the possible etiologic relationship between the two diseases. Report of Case A 48-year-old white male was admitted to the Hospital of St. Raphael on July 1, 1957, with increasing weakness and pigmentation of approximately eight years' duration. The pigmentation was first noted on

Pernicious anemia in a young girlassociated with idiopathic hypoparathyroidism, familial Addison's disease, and moniliasis

A girl with familial Addison's disease, idiopathic hypoparathyroidism, and moniliasis developed pernicious anemia at the age of 10 years. Investigations of her gastrointestinal tract including peroral biopsy were performed. Because of the possible immunologic relationship of pernicious anemia and the endocrinopathies, antibody tests against human gastric mucosa and parietal cells were done and found to be negative. Five cases of pernicious anemia associated with one or the other of these endocrinopathies have been previously reported. At the present time the exact relationship between her hematologic and endocrinologic diseases has not been clarified. A girl with familial Addison's disease, idiopathic hypoparathyroidism, and moniliasis developed pernicious anemia at the age of 10 years. Investigations of her gastrointestinal tract including peroral biopsy were performed. Because of the possible immunologic relationship of pernicious anemia and the endocrinopathies, antibody tests against human gastric mucosa and parietal cells were done and found to be negative. Five cases of pernicious anemia associated with one or the other of these endocrinopathies have been previously reported. At the present time the exact relationship between her hematologic and endocrinologic diseases has not been clarified.

Pernicious Anemia and Polycythemia Vera in One Patient

The evolution of one myeloproliferative disorder into another is not unusual.^1,2Thus, polycythemia vera, myeloid metaplasia, and myelocytic leukemia may follow, or imperceptibly merge into, one another. Pernicious anemia may also be followed by myelocytic leukemia, and the incidence of myelocytic leukemia in the relatives of patients with pernicious anemia has been reported to be higher than it is in the general population.³On the other hand, myeloid metaplasia or polycythemia vera occurring in proved cases of pernicious anemia is distinctly uncommon. The present report concerns a patient who developed polycythemia vera following therapy for pernicious anemia, relapsed into pernicious anemia 6 years after the onset of polycythemia vera, and again became polycythemic after 9 months of vitamin B₁₂therapy. <h3>Report of Case</h3> A 62-year-old white woman who was first seen at the Mayo Clinic in January, 1960, complained of severe fatigue, loss of appetite, and a loss

STUDIES ON THE ABSORPTION OF VITAMIN B12

For the purpose of investigating whether or not Co60-B12 absorption tests are successfully applicable to Japanese subjects, the intestinal absorption of orally administered Co60-B12 was studied for the first time on the Japanese patients suffering from hematologic disorders including Addisonian pernicious anemia as well as the normals. At the same time, in view of the fact that pernicious anemia is rare in Japan, an attempt was made to study the difference in B12 metabolism between the Japanese and the European or the American pernicious anemia patients. As the methods for measuring intestinal absorption of B12, fecal or urinary excretion tests and hepatic uptake method were used in this study. Prior to this study, some fundamental investigations were made on these methods. The results obtained are as follows:1. In Japanese normals, fecal excretion was 29.0±9.0% of the radioactivity of the oral Co60-B12 on the average, urinary excretion 17.4±6.8%, and hepatic uptake 8.74±2.93%, showing a good agreement with those in the foreign normals.2. The measurement of hepatic uptake presented the evidence that absorbed B12 was preferentially taken up by the liver in the Japanese as well. It was also found that 0.2 or 0.5μg of Co60-B12 should be given as a test dose in urinary excretion test, since percentage urinary radioactivity was significantly decreased when the oral dose was raised above 1.0μg.3. In hematologic disorders such as leukemia, aplastic anemia, iron deficiency anemia, hemolytic anemia, lupus erythematosus, or anemia due to the lodging of tape worm, there could be observed no significant defect in B12 absorption.4. However, in three cases of pernicious anemia in relapse or in remission, B12 absorption was exceedingly abolished without exception, unless hog intrinsic factor concentrate was added. This fact indicates that the pathogenesis of pernicious anemia of the Japanese patients was quite identical with the patients of other countries.5. In addition, a diagnostic availability of B12 absorption tests for the differentiation of pernicious anemia from other resembling megaloblastic anemias was also referred to.Thus, the author was led to the general conclusion that B12 absorption test was also well applicable to Japanese subjects and that the mechanism of pernicious anemia was identical with each other, irrespective of the patients' nationality, no matter how low the incidence of pernicious anemia may be.

Histopathology of the stomach in pernicious anaemia and jejunum in steatorrhoea.

The post-mortem finding of gastric atrophy in pernicious anaemia, first recorded in 1870 by Fenwick, has been confirmed in a number of further autopsies reviewed by Faber (1935), Magnus and Ungley (1938) and Schindler (1947). The main changes in the stomach (Magnus, 1958) are diffuse atrophy of the mucosa of fundus and body but not of pyloric antrum and atrophy of the muscle coats of the body of stomach. In some cases there is total loss of body chief and parietal mucosal glandular cells without inflammatory change: gastric atrophy. In others, there are occasional scattered surviving specialised cells and quite well marked interstitial infiltration with lymphocytes and plasma cells: atrophic gastritis. The introduction of a flexible gastric biopsy tube by Wood, Doig, Motteram and Hughes in 1949 has led to histological studies of the gastric mucosa in a total of hundreds of living cases of pernicious anaemia and has allowed comparison with other clinical conditions (Doig and Wood, 1950, Badenoch and Richards, 1953, Palmer, 1954; Siuarla, 1954; Joske, Finckh and Wood, 1955; Markson and Davidson, 1956; Shiner and Doniach, 1957; Wynn Williams, Coghill and Edwards, 1958). The mucosa is strikingly thinned as a result of loss of gastric glands (Figs. 1a and 1b). The surviving glands form discrete rounded collections separated by fine connective tissue which is infiltrated to varying degrees with lymphocytes, macrophages, plasma cells and eosinophils (Fig. 1b).

Relationship between red cell and plasma volume during recovery from pernicious anemia.

Introduction The disparity between the subjective improvement, the reticulocytosis, and the increase in hematocrit early in the course of treatment of pernicious anemia has been observed but is incompletely understood. 1,8 In view of the prompt clinical improvement and early reticulocytosis it seems probable that the lag in hematocrit response does not indicate delayed hematologic improvement but more likely indicates a proportionate increase in plasma volume during the initial response of the red cell volume, and so the hematocrit is little affected. Despite studies by many workers on blood volume in pernicious anemia, no characteristic abnormal pattern in this disease has been established. Consequently, no suitable explanation for the lag in rise of the hematocrit has been obtained. Review of Literature Smith, 2 in 1900, studied seven cases of pernicious anemia and, using a carbon monoxide absorption and dilution method, found the blood volume to be normal or even elevated.

Pernicious anemia, 1822-1929.

More than a century elapsed between the first description of a case of pernicious anemia, by Combe, of Edinburgh, in 1822, and the investigations of Castle and his colleagues, which mark the beginning of our present understanding of the disease. This paper gives an account of the work carried out during that period in defining and investigating the condition. Clinical Observations A paper 1 entitled History of a Case of Anaemia, read by Combe, on May 1, 1822, contains the first authentic description of a case of pernicious anemia. The patient was a corn merchant's servant, aged 47 years, who had always enjoyed perfect health. When Combe was first consulted he was immediately struck by the man's peculiar appearance. His face, lips and the whole extent of the surface, were of a deadly pale color . . . his motions and speech were languid; he complained much of weakness.

Pernicious anemia masked by a multivitamin preparation.

IN patients suffering from unrecognized pernicious anemia, the correct diagnosis may be obscured by use of a multivitamin preparation. Conley and Krevans1 first emphasized this danger in 1951. They presented 14 new cases of pernicious anemia with "crippling neurologic disease in the absence of an appreciable degree of anemia."2 To re-emphasize the serious danger of folic acid in multivitamins, the following case is reported.Case ReportA 57-year-old Negro was admitted to the hospital with the tentative diagnosis of multiple sclerosis. Over a 4-year period he had noted progressive hoarseness, poor memory, paresthesias, ankle edema, palpitation, dyspnea, weakness and impotence. . . .

Report of a Case of Pernicious Anemia Under Treatment for 31 Years

Report of a Case of Pernicious Anemia Under Treatment for 31 Years

Sub-acute combined degeneration: the incidence in a series of 110 cases of pernicious anaemia.

Sub-acute combined degeneration: the incidence in a series of 110 cases of pernicious anaemia.

A fatal case of pernicious anaemia associated with chloramphenicol treatment.

A fatal case of pernicious anaemia associated with chloramphenicol treatment.

THE PYRUVIC PHOSPHOFERASE OF ERYTHROCYTES: II. ACTIVITY IN ANEMIC AND TUMOR-BEARING ANIMALS AND IN HUMAN BLOOD DISORDERS

Pyruvic phosphoferase (PPFase) activity of the erythrocytes (RBC) was determined in rabbits and rats made anemic by acetylphenylhydrazine injection or by bleeding, in rats bearing the Walker 256 carcinoma, and in human patients suffering from anemia, including several cases of pernicious anemia. An elevation of the PPFase activity was found to accompany the appearance of new RBC in the circulation, but the enzyme level was not always related to the proportion of reticulocytes or the mean RBC volume. Administration of vitamin B12 to a previously untreated case of pernicious anemia resulted in a marked increase in the PPFase activity during regeneration of RBC. The highest PPFase activity was found in a patient with nutritional microcytic anemia. It is concluded that a high PPFase activity is associated with immature RBC; but as there are several types of immature RBC a separation would be necessary before enzyme activity could be correlated with the stage of cell development. Sodium and potassium concentrations in the RBC of the various animals and patients exhibited no consistent relationship with the PPFase activity; hence it seemed unlikely that the cation concentration influenced the level of enzyme activity.

THE PYRUVIC PHOSPHOFERASE OF ERYTHROCYTES: II. ACTIVITY IN ANEMIC AND TUMOR-BEARING ANIMALS AND IN HUMAN BLOOD DISORDERS

Pyruvic phosphoferase (PPFase) activity of the erythrocytes (RBC) was determined in rabbits and rats made anemic by acetylphenylhydrazine injection or by bleeding, in rats bearing the Walker 256 carcinoma, and in human patients suffering from anemia, including several cases of pernicious anemia. An elevation of the PPFase activity was found to accompany the appearance of new RBC in the circulation, but the enzyme level was not always related to the proportion of reticulocytes or the mean RBC volume. Administration of vitamin B12 to a previously untreated case of pernicious anemia resulted in a marked increase in the PPFase activity during regeneration of RBC. The highest PPFase activity was found in a patient with nutritional microcytic anemia. It is concluded that a high PPFase activity is associated with immature RBC; but as there are several types of immature RBC a separation would be necessary before enzyme activity could be correlated with the stage of cell development. Sodium and potassium concentrations in the RBC of the various animals and patients exhibited no consistent relationship with the PPFase activity; hence it seemed unlikely that the cation concentration influenced the level of enzyme activity.

Metabolic Interrelations between Gastric Intrinsic Hematopoietic Factor and Vitamin B12: II. Further Assays of Vitamin B12 in Blood and Urine of Patients with Pernicious Anemia and Following Total Gastrectomy by Means of Escherichia coli mutant and Euglena gracilis Technics

Abstract The concentration of vitamin B12 in blood serum and its excretion in the urine were assayed by the E. coli mutant technic in two patients after total gastrectomy and by use of the more sensitive Euglena gracilis method in four cases of pernicious anemia in relapse and 1 case of well controlled nutritional macrocytic anemia. Following parenteral administration of 100 µg. vitamin B12 intramuscularly to two patients with total gastrectomy, much higher blood levels were observed within the first few hours than those reported by others under similar circumstances in normals. Following oral administration of vitamin B12 together with a potent intrinsic factor concentrate from hog stomach, a rise in blood levels of vitamin B12 was observed in patients with pernicious anemia. The normal serum levels of vitamin B12 could not be maintained, however, for the entire duration of the oral treatment, in spite of the apparent hematologic and clinical remission. The urinary output of vitamin B12 was in all instances less than 0.5 per cent of the total dose of vitamin B12 ingested during the experimental period, in spite of an optimal or suboptimal hematopoietic response obtained. A similar situation existed in patients with total gastrectomy, as well as in the patient with controlled macrocytic nutritional anemia, when vitamin B12 was ingested alone or with intrinsic factor concentrate. The intensity of the obtained hematopoietic response in patients with pernicious anemia indicates the absorption of much larger amounts of vitamin B12 from the intestine than is indicated by the total urinary output of vitamin B12; therefore the anchorage and retention of a large part of vitamin B12 in the storage depots of the body after its absorption from the intestine must occur. A sharp increase in the urinary output of vitamin B12 was observed during or immediately following the hematopoietic response in all patients with pernicious anemia treated orally with vitamin B12 and intrinsic factor concentrate, i.e., coincident with or immediately following the reticulocyte peak in blood. Similar observation was reported by the authors in the previous series of investigations. Of many possible interpretations of this finding, the most plausible appears to be the metabolic release of free vitamin B12 from its complex binding in the body during hyperactivity of the hematopoietic organs and its escape through the kidneys.

The electroencephalogram in pernicious anaemia and subacute combined degeneration of the cord

Eighty cases of pernicious anaemia in relapse, of which 24 had subacute combined degeneration of the cord (one with optic atrophy), 41 mild neurological involvement and 15 none, have been studied by means of the EEG. Seven cases showed mild organic reactions and in all of these the pre-treatment record was abnormal. The pre-treatment record was also abnormal in 60 per cent of the remaining patients who showed no significant mental abnormality. In some cases abnormality was severe (delta activity, generalised, paroxysmal or focal), in some slight (slight or moderate excess of theta activity), but the degree of abnormality bore no relationship to the severity of the anaemia, the age of the patient or the degree of neurological involvement. Ten cases of anaemia of miscellaneous type were also studied before treatment; although in 3 of these the haemoglobin level was less than 40 per cent, only in one case did the EEG show a significant abnormality and this patient had severe hypertension and atherosclerosis. Seventy-six of the cases of pernicious anaemia were re-examined after treatment with vitamin B 12. In 14 of the 29 cases which gave normal records before treatment there was a significant increase in mean frequency of the alpha rhythm and diminution in overall amplitude. Forty-two of the remaining 47 cases in which the initial record was abnormal s showed a satisfactory clinical response to treatment and in 31 (74 per cent) the EEG returned to normal, so that 60 of the 76 cases (79 per cent) eventually gave normal records. Improvement in the record began as a rule 7–10 days after the beginning of treatment and was often complete within a month, although some cases showed further improvement after intervals varying from 3–16 months. In the other 11 cases (26 per cent) who responded, persisting abnormalities consisted of a slight excess of generalised theta activity, a finding which in some could possibly be accounted for by age or constitution. Another 50 cases of pernicious anaemia (including 37 with subacute combined degeneration of the cord, 8 with mild neurological involvement and one with optic atrophy) were first studied after treatment had been in progress for between 3 months and 8 years (average 18 months). Excluding 5 cases showing epileptic discharges, 38 (84 per cent) of the other 45 patients had normal records; the remaining 7 cases (16 per cent) were restudied and in all EEG showed further improvement 5 months to 3 years after the beginning of treatment. The final total of normal records was 42 (93 per cent). Eight (6 per cent) of the 130 cases of pernicious anaemia studied gave records showing epileptic discharges (usually temporal spikes or sharp waves) and of these 4 (3 per cent) gave a personal or family history of fits or faints. It is suggested that the EEG changes in pernicious anaemia are due not to the anaemia but to a specific defect in cerebral metabolism, presumably related to the deficiency state responsible for the anaemia. Though not as sensitive as studies of cerebral metabolism by the blood flow method, the EEG is a useful tool in the investigation of these cases and reveals that maximum improvement may be delayed for up to 3 years after treatment has begun. The possible relationship of the EEG changes to alterations in glucose and pyruvate metabolism is discussed.

Oral Treatment of Pernicious Anemia with Small Doses of Vitamin B12 Combined with Mucinous Materials Derived from the Hog Stomach

1. Twenty patients with pernicious anemia were treated under rigidly controlled conditions by administering small oral doses of vitamin B12 in combination with intrinsic factor containing mucinous materials processed from the hog stomach. This study was undertaken in view of our earlier observation concerning the relationship of one of the mucin fractions of the human stomach (glandular mucoprotein) to Castle’s intrinsic factor. The following sources of intrinsic factor from animal stomach were used: (a) commercial gastric mucin; (b) acetic acid extracts of hog pyloric mucosa; (c) mucinous materials precipitated by acetone or by saturation with ammonium sulfate from hydrochloric acid extracts of the hog pyloric mucosa; (d) mucous fractions obtained by further fractionation in the electroconvection apparatus of the above mucinous materials precipitated with ammonium sulfate; (e) an intrinsic factor concentrate from the hog stomach in combination with small doses of vitamin B12, processed under the trade name of Bifacton.2. Results obtained in this study indicate the feasibility of attaining complete clinical remission and suboptimal or optimal hematopoietic responses in patients with pernicious anemia in relapse when small daily doses (below 20 µg.) of vitamin B12 are given orally in combination with mucinous materials processed by various technics from the hog stomach and containing intrinsic factor. The provisions are that: (1) the doses of both vitamin B12 and intrinsic factor containing materials be adequate and optimal in regard to their mutual ratio; (2) the process involved in processing intrinsic factor containing materials not impair their activity and yield a product sufficiently concentrated.3. The hematopoietic responses and clinical remissions obtained in six cases of pernicious anemia with Bifacton (vitamin B12 with intrinsic factor concentrate) in different batches were uniform in our hands. The doses employed were marginal, in order to detect differences in potency, and although the reticulocyte responses were frequently suboptimal and protracted, the increases in red cells were roughly equivalent to those obtained with daily administration of approximately 1 unit of a standard oral antianemia preparation. Bifacton is supplied in strikingly smaller dosages than the standard liver or stomach oral preparations, and is fully active in a total daily oral dose of about 50 mg. of intrinsic factor concentrate with 15 µg. vitamin B12.4. Preliminary studies on two patients with pernicious anemia tend to indicate that the administration of massive single oral doses of Bifacton repeated at intervals of one week may imitate even more closely the results of parenteral treatment with injectable liver concentrates or vitamin B12 than does the administration of this concentrate in small daily doses. The single dose of Bifacton which was given once a week to one of these patients contained 150 µg. vitamin B12 with approximately 250 mg. of intrinsic factor concentrate. Five consecutive single doses administered at intervals of from seven to ten days induced a complete clinical and hematologic remission.5. The studies on two patients with pernicious anemia indicate that Bifacton is resistant to boiling and that it preserves its hematopoietic activity after being boiled in water for from thirty to forty-five minutes at 95 to 100° C. This suggests either that the intrinsic factor of the animal stomach becomes thermostable after the interaction in vitro with vitamin B12, or that the product of this binding is thermostable under conditions described.6. The data reported here indicate that various extraction and precipitation procedures may be applied to hog stomach tissue to obtain materials which will exhibit definite intrinsic factor activity in patients with pernicious anemia. Although at present some such extracts are active orally in such small doses as from 40 to 50 mg. per day, still further refinement appears to be possible.