Resumos
Estudo comparativo dos efeitos hematológicos e neurológicos com o emprêgo do extrato hepático, do ácido fólico e da vitamina B12 em 15 casos de anemia perniciosa com sinais de lesão neurológica, não submetidos anteriormente a tratamento, ou apresentando recidiva hêmato-neurológica após o abandono de tratamentos prévios. Foi estudada a evolução da hematimetria, da taxa de hemoglobina, da sensibilidade vibratória e da sintomatologia neurológica em geral. Os resultados foram submetidos a tratamento estatístico. Os autores chegam às seguintes conclusões: 1. Os resultados hematológicos, embora nítidos em todos os casos, evidenciam superioridade do extrato hepático e ácido fólico em relação à vitamina B12; aquêles mostraram-se eqüivalentes. 2. Houve nítida correlação entre a evolução da hematimetria e da taxa de hemoglobina. 3. Os resultados neurológicos, embora favoráveis nos três grupos, denotaram diferenças que, apesar de estatìsticamente não significantes, evidenciaram a superioridade da vitamina B12 sôbre o ácido fólico e o extrato hepático. 4. Não houve correlação estatística entre as evoluções da palestesia e da hematimetria, evidenciando-se acentuada discordância no comportamento das síndromes hematológica e neurológica. 5. O ácido fólico, em média, revelou-se inferior à vitamina B12 no tocante aos efeitos neurológicos, mas ligeiramente superior ao extrato hepático. 6. As melhoras neurológicas foram mais nítidas em relação aos sintomas do que aos sinais. 7. A vitamina B12 e o ácido fólico determinaram acentuada melhora da síndrome piramidal, ao passo que o extrato hepático quase não atuou; em relação à síndrome periférica, a vitamina B12 e o extrato hepático determinaram melhora nítida, enquanto o ácido fólico pouco efeito denotou; os três medicamentos revelaram efeitos semelhantes no que tange à síndrome funicular dorsal. 8. Dentre as manifestações neurológicas, melhoras mais evidentes foram observadas em relação à síndrome psíquica, ao déficit piramidai. à hipotonia e às desordens da artrestesia. Os sinais piramidais de libertação, a depressão dos reflexos tendíneos e particularmente os distúrbios da sensibilidade táctil mostraram-se mais rebeldes ao tratamento.
Three groups of 5 cases of pernicious anemia with signs of subacute combined degeneration of the spinal cord were treated with vitamin B12, folic acid and liver extract. Nine patients had not been submitted to other therapies; six patients had some treatment 7 to 48 months before (table 2) but were in hematoneurological relapse. The three drugs were administered twice a week, each treatment lasting for a month, so that 10 injections of each drug were made. In group 1 vitamin B12 was given in the total dosis of 100 y; in group 2 folic acid was administered in the total dosis of 500 mgm; group 3 received liver extract at the total dosis of 10 ml (150-200 USP anti-anemic unities). No associated treatment was instituted; the diet contained 70 to 80 gm of proteins by day. Red cell counts were made by usual methods; hemoglobin contents of the blood were determined by means of an alcaline solution of oxyhemoglobin, with spectrophotometric reading; the hematologic evolution (tables 3 and 4 and graphics 1, 2 and 3) was followed up by examinations made twice a week (in each case an average of 10 examinations was made). Neurologic evolution was studied by examination of the vibration sense every ten days and by complete neurologic examination before and after the treatment (tables 5 and 6). The results were submitted to statistical analysis. The homogeneity (Snedecor) of the initial values was proved. It was calculated the linear regression relating time and the average values of red cell count, hemoglobin content and pallesthesia of each group. The regression coefficients of the evolution of the red cell count and hemoglobin content proved to be statistically significant and were compared; the differences were also significant, showing the superiority of liver extract and folic acid over vitamin B12. The correlation between red cell count and hemoglobin content was positive. The regression coefficients of the evolution of pallesthesia were not significant, as well as the differences between the neurologic scores (table 6) before and after treat- ment in the three groups. However, neurologic results showed the superiority of vitamin B12 over folic acid and liver extract according to the values of the regression coefficients (table 5). No correlation between the evolutions of pallesthesia and of the red cell count was found. Disagreement between hematologic and neurologic results of the drugs was evidenced. Folic acid was less effective than vitamin B12 but it was slightly better than liver extract in relation to the neurologic evolution. Neurologic subjective symptoms improved in higher degree than objective signs. Vitamin B12 and folic acid evidenced better results in relation to the pyramidal syndrome; liver extract and vitamin B12 were more effective in the improvement of the peripheral syndrome; similar effects on dorsal funicular syndrome were evidenced by the three drugs (table 7). Among the neuropsychiatrie manifestations the most impressive results were observed on the psychical syndrome, muscular weakness, hypotonus and position sense disorders; signs of pyramidal release, depression of deep reflexes and particularly superficial sense disorders were the most resistant signs (table 8), irrespective of the kind of treatment.
Estudo comparativo dos efeitos hematológicos e neurológicos do extrato hepático, ácido fólico e vitamina B12 no tratamento da anemia perniciosa de Addison-Biermer
Comparative study of the hematologic and neurologic effects of liver extract, folic acid and vitamin B12 in the treatment of pernicious anemia
Horacio M. CanelasI; Michel Abu JamraII
IAssistente de Clínica Neurológica da Fac. Med. da Univ. de São Paulo
IILivre docente de Clínica Médica da Fac. Med. da Univ. de São Paulo
RESUMO E CONCLUSÕES
Estudo comparativo dos efeitos hematológicos e neurológicos com o emprêgo do extrato hepático, do ácido fólico e da vitamina B12 em 15 casos de anemia perniciosa com sinais de lesão neurológica, não submetidos anteriormente a tratamento, ou apresentando recidiva hêmato-neurológica após o abandono de tratamentos prévios. Foi estudada a evolução da hematimetria, da taxa de hemoglobina, da sensibilidade vibratória e da sintomatologia neurológica em geral. Os resultados foram submetidos a tratamento estatístico. Os autores chegam às seguintes conclusões:
1. Os resultados hematológicos, embora nítidos em todos os casos, evidenciam superioridade do extrato hepático e ácido fólico em relação à vitamina B12; aquêles mostraram-se eqüivalentes.
2. Houve nítida correlação entre a evolução da hematimetria e da taxa de hemoglobina.
3. Os resultados neurológicos, embora favoráveis nos três grupos, denotaram diferenças que, apesar de estatìsticamente não significantes, evidenciaram a superioridade da vitamina B12 sôbre o ácido fólico e o extrato hepático.
4. Não houve correlação estatística entre as evoluções da palestesia e da hematimetria, evidenciando-se acentuada discordância no comportamento das síndromes hematológica e neurológica.
5. O ácido fólico, em média, revelou-se inferior à vitamina B12 no tocante aos efeitos neurológicos, mas ligeiramente superior ao extrato hepático.
6. As melhoras neurológicas foram mais nítidas em relação aos sintomas do que aos sinais.
7. A vitamina B12 e o ácido fólico determinaram acentuada melhora da síndrome piramidal, ao passo que o extrato hepático quase não atuou; em relação à síndrome periférica, a vitamina B12 e o extrato hepático determinaram melhora nítida, enquanto o ácido fólico pouco efeito denotou; os três medicamentos revelaram efeitos semelhantes no que tange à síndrome funicular dorsal.
8. Dentre as manifestações neurológicas, melhoras mais evidentes foram observadas em relação à síndrome psíquica, ao déficit piramidai. à hipotonia e às desordens da artrestesia. Os sinais piramidais de libertação, a depressão dos reflexos tendíneos e particularmente os distúrbios da sensibilidade táctil mostraram-se mais rebeldes ao tratamento.
SUMMARY AND CONCLUSIONS
Three groups of 5 cases of pernicious anemia with signs of subacute combined degeneration of the spinal cord were treated with vitamin B12, folic acid and liver extract. Nine patients had not been submitted to other therapies; six patients had some treatment 7 to 48 months before (table 2) but were in hematoneurological relapse. The three drugs were administered twice a week, each treatment lasting for a month, so that 10 injections of each drug were made. In group 1 vitamin B12 was given in the total dosis of 100 y; in group 2 folic acid was administered in the total dosis of 500 mgm; group 3 received liver extract at the total dosis of 10 ml (150-200 USP anti-anemic unities). No associated treatment was instituted; the diet contained 70 to 80 gm of proteins by day. Red cell counts were made by usual methods; hemoglobin contents of the blood were determined by means of an alcaline solution of oxyhemoglobin, with spectrophotometric reading; the hematologic evolution (tables 3 and 4 and graphics 1, 2 and 3) was followed up by examinations made twice a week (in each case an average of 10 examinations was made). Neurologic evolution was studied by examination of the vibration sense every ten days and by complete neurologic examination before and after the treatment (tables 5 and 6). The results were submitted to statistical analysis.
The homogeneity (Snedecor) of the initial values was proved. It was calculated the linear regression relating time and the average values of red cell count, hemoglobin content and pallesthesia of each group. The regression coefficients of the evolution of the red cell count and hemoglobin content proved to be statistically significant and were compared; the differences were also significant, showing the superiority of liver extract and folic acid over vitamin B12. The correlation between red cell count and hemoglobin content was positive. The regression coefficients of the evolution of pallesthesia were not significant, as well as the differences between the neurologic scores (table 6) before and after treat- ment in the three groups. However, neurologic results showed the superiority of vitamin B12 over folic acid and liver extract according to the values of the regression coefficients (table 5). No correlation between the evolutions of pallesthesia and of the red cell count was found. Disagreement between hematologic and neurologic results of the drugs was evidenced.
Folic acid was less effective than vitamin B12 but it was slightly better than liver extract in relation to the neurologic evolution. Neurologic subjective symptoms improved in higher degree than objective signs. Vitamin B12 and folic acid evidenced better results in relation to the pyramidal syndrome; liver extract and vitamin B12 were more effective in the improvement of the peripheral syndrome; similar effects on dorsal funicular syndrome were evidenced by the three drugs (table 7). Among the neuropsychiatrie manifestations the most impressive results were observed on the psychical syndrome, muscular weakness, hypotonus and position sense disorders; signs of pyramidal release, depression of deep reflexes and particularly superficial sense disorders were the most resistant signs (table 8), irrespective of the kind of treatment.
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BIBLIOGRAFIA
1. Spies, T. D., López, G. G., Milanés, F., Aramburu, T. e Toca, R. L. - Association between gastric achlorydria and subacute combined degeneration of the spinal cord. Postgrad. Med., 4:89-95 (agôsto) 1948. Cit. por Israëls e Wilkinsons3.
2. Ross, J. F., Beldin, H. W. e Paegel, B. L. - Development and progression of subacute combined degeneration of the spinal cord in patients with pernicious anemia treated with synthetic pteroylglutamic (folic) acid. Blood, 3: 68-90, 1948.
3. Israëls, W. C. G. e Wilkinson, J. F. - Risk of neurological complication in pernicious anemia treated with folic acid. Brit. M. J., 2:1072-1075 (17 novembro) 1949.
4. Fuld, H. - Effect of vitamin B12 on neuropathy in pernicious anemia treated with folic acid. Brit. M. J., 2:147-148 (15 julho) 1950.
5. Schwartz, S. O., Kaplan, S. R. e Armstrong, B. E. - The long-term evaluation of folic acid in the treatment of pernicious anemia. J. Lab. a. Clin. Med., 35:894-898 (junho) 1950.
6. Chodos, R. B. e Ross, .1. F. - The effect of combined folic acid and liver extract therapy. Blood, 6:1213-1233 (dezembro) 1951.
7. Spanipinato, V. - Mielosi funicolare da acido folico nel Mus musculus albinus (nota preventiva). Arch. Ital. Anat. e Istol. Patol., 25:23-28, 1952. Referencia in Excerpta Médica (secção VIII), 6:115 (fevereiro) 1953.
8. a) Polia-koff, H., Sternbach, A., Walker, W. H., Kascht, R. L. e Meyer, L. M. -- Administration of folic acid to patients without anemia. Proc. Soe. Exper. Biol. a. Med., 72:392-393 (novembro) 1949. b) Harvey, E. A., Koward, I. e Murphy, W. P. - Absence of toxic effect of folic acid on the central nervous systeni of persons without pernicious anemia. New England J. Med., 242:446-447 (23 março) 1950. c) Weissberg, J., McGavack, T. H., Vogel, M. e Kenigsberg, S. - The effect of folic acid on the central nervous system of normal subjects and subjects with anemia other than pernicious anemia. Blood, 5:148-154 (fevereiro) 1951.
9. Klinia, R. e W'engraf, G. - Vergleichende Beobachtungen zur Wirkung der Folsàure und Lebertherapie bei perniziöser Anamie und funikuláren Myelose. Wien. med. W'chnschr., 100:210-213 (25 março) 1950. Cit. por Ventra, D. e D'Aniello, L.: La vitamina B12 in neurologia. Acta Neurol., 8:118-133 ( janeiro-fevereiro) 1953.
10. Jamra, M. A., Canelas, H. M. e Bittencourt, J. M. T. - O ácido fólico no tratamento da síndrome nervosa da anemia perniciosa. Estudo do comportamento da sensibilidade vibratória. Arq. Neuro-Psiquiat., 6:301-333 (dezembro) 1948.
11. a) Needles, W. - Neurologic complication of pernicious anemia. Arch. Neurol, a. Psychiat., 26:346-358 (agôsto) 1931. b) Grinker, R. R. e Kandel, E. - Pernicious anemia. Results of treatment of the neurologic complications. Arch. Int. Med., 54:851-871 (dezembro) 1934. c) Goldhammer, S. M., Bethell, F. H., Isaacs, R. e Sturgis, C. C. - The occurrence and treatment of neurologie changes in pernicious anemia. J.A.M.A., 103:1663-1667 (4 dezembro) 1934. d) Hyland, H. H. e Farquharson, R. F. - Subacute combined degeneration of the spinal cord in pernicious anemia. Results of treatment in seventy-four consecutive cases with certain clinical observations. Arch. Neurol, a. Psychiat., 36: 1166-1205 (dezembro) 1936. e) Björkenheim, G. - Neurological changes in pernicious tapeworm anemia. Acta Med. Scandinav., suplemento 260, 1951. f) Slepian, A. e Vaughan, S. L. - Nervous system manifestations in pernicious anemia. New York State J. Med., 51:1524-1526 (15 junho) 1951.
12. Ungley, C. C. - Subacute combined degeneration of the cord. Brain, 72:382-427 (setembro) 1949.
13. Girdwood, R. H. e Carmichael, K. M. - The content of haemopoietic factors in liver extracts. Relationship to clinical response. Brit. M. J., 2:1357-1361 (16 dezembro) 1950.
14. Alexander, L. - New concept of critical steps in course of chronic debilitating neurologic disease in evaluation of therapeutic response. Arch. Neurol, a. Psychiat., 66:253-271 (setembro) 1951.
15. Snedecor, G. W. - Métodos de Estadística. Su aplicación a experimentos en Agricultura y Biología. Trad, da 4ª ed. americana por A. E. Marino. Acme Agency, Buenos Aires, 1948.
Trabalho da Clínica Neurológica da Fac. Med. da Univ. de São Paulo (Serviço do Prof. Adherbal Tolosa) e do Laboratório Central do Hospital das Clínicas (Chefe: Dr. O. Germek), Secção de Hematologia, da 1ª Clínica Médica da Fac. de Med. da Univ. de São Paulo (Serviço do Prof. A. B. de Ulhoa Cintra).
Nota dos autores - Êste trabalho representa uma síntese do original laureado com o Prêmio "Enjoints Vampré" de 1952, distribuído pela Associação Paulista de Medicina.
Clínica Neurológica - Hospital das Clínicas - São Paulo.
- 1. Spies, T. D., López, G. G., Milanés, F., Aramburu, T. e Toca, R. L. - Association between gastric achlorydria and subacute combined degeneration of the spinal cord. Postgrad. Med., 4:89-95 (agôsto) 1948. Cit. por Israëls e Wilkinsons3
- 2. Ross, J. F., Beldin, H. W. e Paegel, B. L. - Development and progression of subacute combined degeneration of the spinal cord in patients with pernicious anemia treated with synthetic pteroylglutamic (folic) acid. Blood, 3: 68-90, 1948.
- 3. Israëls, W. C. G. e Wilkinson, J. F. - Risk of neurological complication in pernicious anemia treated with folic acid. Brit. M. J., 2:1072-1075 (17 novembro) 1949.
- 4. Fuld, H. - Effect of vitamin B12 on neuropathy in pernicious anemia treated with folic acid. Brit. M. J., 2:147-148 (15 julho) 1950.
- 5. Schwartz, S. O., Kaplan, S. R. e Armstrong, B. E. - The long-term evaluation of folic acid in the treatment of pernicious anemia. J. Lab. a. Clin. Med., 35:894-898 (junho) 1950.
- 6. Chodos, R. B. e Ross, .1. F. - The effect of combined folic acid and liver extract therapy. Blood, 6:1213-1233 (dezembro) 1951.
- 7. Spanipinato, V. - Mielosi funicolare da acido folico nel Mus musculus albinus (nota preventiva). Arch. Ital. Anat. e Istol. Patol., 25:23-28, 1952. Referencia in Excerpta Médica (secção VIII), 6:115 (fevereiro) 1953.
- 8. a) Polia-koff, H., Sternbach, A., Walker, W. H., Kascht, R. L. e Meyer, L. M. -- Administration of folic acid to patients without anemia. Proc. Soe. Exper. Biol. a. Med., 72:392-393 (novembro) 1949.
- b) Harvey, E. A., Koward, I. e Murphy, W. P. - Absence of toxic effect of folic acid on the central nervous systeni of persons without pernicious anemia. New England J. Med., 242:446-447 (23 março) 1950.
- c) Weissberg, J., McGavack, T. H., Vogel, M. e Kenigsberg, S. - The effect of folic acid on the central nervous system of normal subjects and subjects with anemia other than pernicious anemia. Blood, 5:148-154 (fevereiro) 1951.
- 9. Klinia, R. e W'engraf, G. - Vergleichende Beobachtungen zur Wirkung der Folsàure und Lebertherapie bei perniziöser Anamie und funikuláren Myelose. Wien. med. W'chnschr., 100:210-213 (25 março) 1950. Cit. por Ventra, D. e D'Aniello, L.: La vitamina B12 in neurologia. Acta Neurol., 8:118-133 ( janeiro-fevereiro) 1953.
- 10. Jamra, M. A., Canelas, H. M. e Bittencourt, J. M. T. - O ácido fólico no tratamento da síndrome nervosa da anemia perniciosa. Estudo do comportamento da sensibilidade vibratória. Arq. Neuro-Psiquiat., 6:301-333 (dezembro) 1948.
- 11. a) Needles, W. - Neurologic complication of pernicious anemia. Arch. Neurol, a. Psychiat., 26:346-358 (agôsto) 1931.
- b) Grinker, R. R. e Kandel, E. - Pernicious anemia. Results of treatment of the neurologic complications. Arch. Int. Med., 54:851-871 (dezembro) 1934.
- c) Goldhammer, S. M., Bethell, F. H., Isaacs, R. e Sturgis, C. C. - The occurrence and treatment of neurologie changes in pernicious anemia. J.A.M.A., 103:1663-1667 (4 dezembro) 1934.
- d) Hyland, H. H. e Farquharson, R. F. - Subacute combined degeneration of the spinal cord in pernicious anemia. Results of treatment in seventy-four consecutive cases with certain clinical observations. Arch. Neurol, a. Psychiat., 36: 1166-1205 (dezembro) 1936.
- e) Björkenheim, G. - Neurological changes in pernicious tapeworm anemia. Acta Med. Scandinav., suplemento 260, 1951.
- f) Slepian, A. e Vaughan, S. L. - Nervous system manifestations in pernicious anemia. New York State J. Med., 51:1524-1526 (15 junho) 1951.
- 12. Ungley, C. C. - Subacute combined degeneration of the cord. Brain, 72:382-427 (setembro) 1949.
- 13. Girdwood, R. H. e Carmichael, K. M. - The content of haemopoietic factors in liver extracts. Relationship to clinical response. Brit. M. J., 2:1357-1361 (16 dezembro) 1950.
- 14. Alexander, L. - New concept of critical steps in course of chronic debilitating neurologic disease in evaluation of therapeutic response. Arch. Neurol, a. Psychiat., 66:253-271 (setembro) 1951.
- 15. Snedecor, G. W. - Métodos de Estadística. Su aplicación a experimentos en Agricultura y Biología. Trad, da 4ª ed. americana por A. E. Marino. Acme Agency, Buenos Aires, 1948.
Datas de Publicação
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Publicação nesta coleção
16 Abr 2014 -
Data do Fascículo
Set 1953
