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Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos II. Avaliação do líqüido cefalorraqueano

High-dose intravenous penicillin G in the treatment of neurosyphilis: a study of 62 patients. II. Cerebrospinal fluid evaluation

Resumos

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhões de UI. por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento foi de 30 meses. Antes do tratamento, 41 pacientes apresentavam pleocitose ao exame do LCR. Seis meses e doze ou mais meses depois, foi constatada pleocitose em 4 (9,8%) e em 3 pacientes (7,3%), respectivamente. A proteinorraquia e os títulos das reações de Wassermann do soro e do LCR reduziram-se lentamente depois do tratamento. O teor de globulinas gama do LCR e os índices de imunoprodução local do sistema LCR ainda encontravam-se elevados depois do primeiro ano após tratamento. Os resultados da penicilinoterapia intravenosa em altas doses constatados neste estudo não diferiram daqueles obtidos com penicilinoterapia intramuscular em baixas doses registrados na literatura.


Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Forty-one patients had pleocytosis in the CSF before treatment. Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively. The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment. The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature.


Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos II. Avaliação do líqüido cefalorraqueano

High-dose intravenous penicillin G in the treatment of neurosyphilis: a study of 62 patients. II. Cerebrospinal fluid evaluation

Ricardo NitriniI; A. Spina-FrançaII

IProfessor Assistente - Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

IIProfessor Titular - Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

RESUMO

Sessenta e dois casos de neurossífilis sintomática foram tratados com penicilina G, na dose diária de 20 ou 24 milhões de UI. por via intravenosa, durante 15 a 30 dias. O tempo médio de acompanhamento foi de 30 meses. Antes do tratamento, 41 pacientes apresentavam pleocitose ao exame do LCR. Seis meses e doze ou mais meses depois, foi constatada pleocitose em 4 (9,8%) e em 3 pacientes (7,3%), respectivamente. A proteinorraquia e os títulos das reações de Wassermann do soro e do LCR reduziram-se lentamente depois do tratamento. O teor de globulinas gama do LCR e os índices de imunoprodução local do sistema LCR ainda encontravam-se elevados depois do primeiro ano após tratamento. Os resultados da penicilinoterapia intravenosa em altas doses constatados neste estudo não diferiram daqueles obtidos com penicilinoterapia intramuscular em baixas doses registrados na literatura.

SUMMARY

Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Forty-one patients had pleocytosis in the CSF before treatment. Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively. The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment. The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature.

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REFERENCIAS

1. ADAMS, R.D. & VICTOR, M. - Principles of Neurology. Mc-Graw-Hill, New York, 1977, pg. 618.

2. BAYNE, L.L.; SCHMIDLEY, J.W. & GOODIN, D.S. - Acute syphilitic meningitis: its occur ence after clinical and serological cure of secondary syphilis with penicillin G. Arch Neurol. 43:137, 1986.

3. BOS, J.D; HAMERLINCK, F. & CORMANE, R.H. - T lymphoid cells in primary syphilis: quantitative studies. Brit. J. vener. Dis. 56:74, 1980.

4. BURNS, R.E. - Spontaneous reversion of FTA-ABS reactions. J. Amer. med. Assoc. 2S 1:617, 1975.

5. CALLAWAY, J.L.; FLOWER Jr., A.H.; HIRSCHMANN, V.R. & OLANSKY, S. - A fou-year study of penicillin treatment of syphilis of the central nervous system. S h. med. J. 43:412, 1950.

6. CHU, A.B., SEVER, J.L.; MADDEN, D.L.; LEON, M.; IIVANAINEN, M.; WALLEN, N.; BROOKS, B.R.; LEE, Y.J. & HOUFF, S. - Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases. Ann. Neurol. 13:434, 1983.

7. COLLART, P.; BOREL, L.J. & DUREL, P. - Significance of spiral organisms found after treatment in late human and experimental syphilis. Brit. J. vener. Dis. 40:81, 1964.

8. COLLART, P. & POITEVIN, M. - Persistance des tréponèmes pâles après traitment au cours de la syphilis expérimentale et humaine. Ann. Med. Int. 126:223, 1975.

9. COLLART, P. & POITEVIN, M. - Is penicillin always infallible in syphilis? J. clin. Neuro-ophthal. 2:77, 1982.

10. COLLART, P. & POITEVIN, M. - La syphilis. I: Actualités physio-biologiques Sem. Hop. Paris 57:857, 1981.

11. COLLART, P. & POITEVIN, M. - La syphilis: actualités physio-biologiques. II: Processus évolutif de l'infection syphilitique expérimentale et humaine. Sem. Hôp. Paris 57:989, 1981.

12. COLLART, P. & POITEVIN, M. - La syphilis: actualités physio-biologiques. IV: Le problème de la penicillinothérapie. Sem. Hôp. Paris 57:1161, 1981.

13. CONFERENCE on therapy: treatment of neurosyphilis. Amer. J. Med. 9:373, 1950.

14. CURTIS, A.C.; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis: III. Evaluation after three, years of treatment with penicillin alone and with a combination of penicillin and malaria. Amer. J. Syph. 33:527, 1949.

15. CURTIS, A.C.; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis: IV. Post-treatment evaluation four to five years following penicillin and penicillin plus malaria. Amer. J. Syph. 34:554, 1950.

16. DATTNER, B. - Penicillin failures in neurosyphilis. Amer. J. Syph. 33:571, 1949.

17. DATTNER, B. ; THOMAS, E.W. & WEXLER, G. - The Management of Neurosyphilis. Grune & Stratton, New York, 1944.

18. DATTNER, B. ; THOMAS, E.W. & MELLO, L. de - Criteria for the management of neurosyphilis. Amer. J. Med. 10:463, 1951.

19. FAGGI, L.; CITTERIO, A.; FRIGO, G.M.; PERUCCA, E. LECCHINI, S. & GIANETTI, A. - Penicillin CSF levels following intravenous therapy in syphilitic patients. Ital. J. neurol. Sci. 4:423, 1983.

20. GAGER, W.E.; ISRAEL, C.W. & SMITH, J.L. - Presence of spirochaetes in paresis despite penicillin therapy. Brit. J. vener. Dis. 44:227, 1968.

21. GANTI, S.R. ; COHEN, M. ; SANE, P. & HILAL, S.K. - Computed tomography of cerebral syphilis. J. comp. assist. Tomogr. 5:345, 1981.

22. GILES, A.J.H. - Tabes dorsalis progressing to general paresis after 20 years despite routine penicillin therapy. Brit. J. vener. Dis. 56:368, 1980.

23. GJESTLAND, T. - The Os'o study of untreated syphilis. Acta derm-venereol. (Stockholm) 35 (suppl. 34) :1, 1955.

24. GODT, P.; STOEPPLER, L.; WISCHER, U. & SCHROEDER, H.H. - The value of computed tomography in cerebral syphilis. Neuroradiology 18:197, 1979.

25. HAHN, R.D. - Some remarks on management of neurosyphilis. J. chron. Dis. 13:1. 1961.

26. HOLLAND, B.A.; PERRET, L.V. & MILLS, CM. - Meningovascular syphilis: CT and MR findings. Radiology 158:439, 1986.

27. HOOSHMAND, H.; ESCOBAR, M.R. & KOPF, S.W. - Neurosyphilis: a study of 241 patients. J. Amer. med. Assoc. 219:726, 1972.

28. JAFFE, H.W. & KABINS, S.A. - Examination of cerebrospinal fluid in patients with syphilis. Rev. infect. Dis. 4 (suppl.) :5842, 1982.

29. JENSEN, J.R. & FROM, E. - Alterations in T-lymphocytes and T-lymphocyte subpopulation in patients with syphilis. Brit. J. vener. Dis. 58:18, 1982.

30. KAMPMEIER, R.H.; SWEENEY, A.; QUINN, R.W. ; LEFKOWITZ, L.B.; DUPONT, W.D. - A survey of 251 patients with acute syphilis treated in the collaborative study of 1943-1950. Sex. transm. Dis. 8:266, 1981.

31. LINK, H. & TIBBL1NG, G. - Principles of albumin and IgG analyses in neurological disorders: II. Relation of the concentration of the proteins in serum and cerebrospinal fluid. Scand. J. clin. lab. Invest. 37:391, 1°77.

32. LIVRAMENTO, J.A. - Contribuição de reações de imunofluorescência no liqüido cefalorraqueano ao estudo da neurocisticercose. Tese. São Paulo, 1980.

33. LIVRAMENTO, J.A. - Síndrome do líquido cefalorraqueano na neurocisticercose: estudo crítico sobre a evolução da imunidade humoral. Tese. São Paulo, 1986.

34. LÖWHAGEN, G.B. ; ANDERSSON, M.; GLOMSTRAND, C. & ROTJPE, C. - Central nervous system involvement in early syphilis: I. Intrathecal immunoglobulin production. Acta derm-venereol. (Stockholm) 63:409, 1983.

35. LÖWHAGEN, G.B.; ROSENHALL, U.; ANDERSSON, M.; BLOMSTRAND, C.; LINDHOLM, L. & ROUPE, G. - Central nervous system involvement in early syphilis: II. Correlation between auditory brainstem responses (ABR) and cerebrospinal fluid abnormalities. Acta derm-venereol. (Stockholm) 63:530, 1983.

36. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano. II: Técnica. Arq. Neuro-Psiquiat. (São Paulo) 41:132, 1983.

37. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano. IIII: Valores normais. Arq. Neuro-Psiquiat. (São Paulo) 41:137, 1983.

38. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano normal. I: Principais registros da literatura. Arq. Neuro-Psiquiat. (São Paulo) 41:119, 1983.

39. MERRITT, H.H. ; ADAMS, R.D. & SOLOMON, H.C. - Neurosyphilis. Oxford Univ. Press, New York, 1946.

40. MICHEL, D.; BLANC, A.; LAURENT, B.; FOYATIER, N. & PORTFAIX, M. - Étude biologique, psychométrique et tomodensimétrique de la neurosyphilis traitée. Rev. neurol. (Paris) 139:737, 1983.

41. MOHR, J.A.; GRIFFITHS, W.; JACKSON, R.; SAADAH, H.; BIRD, P. & RIDDLE, J. - Neurosyphilis and penicillin levels in cerebrospinal fluid. J. Amer, med. Assoc. 236:2208, 1976.

42. MÜLLER, F. & MOSKOPHIDIS, M. - Estimation of the local production of antibodies to Treponema pallidum in the central nervous system of patients with neurosyphilis. Brit. J. vener. Dis. 59:80, 1983.

43. NICHOLS JR., F.T. & HEYMAN, A. - Penicillin therapy in asymptomatic neurosyphilis: a comparison of the, effects of amorphous penicillin in oil and wax, and crystalline penicillin G. Amer. J. Syph. 33:561, 1949.

44. NITRINI, R. (a) Neurossífilis: análise de alguns aspectos clínicos e laboratoriais. Tese, São Paulo, 1981. (b) Neurossífilis: penicilinoterapia intravenosa em altas doses. Tese. São Paulo, 1986.

45. NITRINI, R. & SPINA-FRANÇA, A. - Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos. I. Avaliação clínica. Arq. Neuro-Psiquiat. (São Paulo). 45:99, 1987.

46. OSELKA, G.; LEVI, G.C.; LOPES, H.V.; MENDONÇA, J.S.; BALDY, J.L.S.; TRABULSI, L.R. & AMATO NETO, V. - Antibióticos na Prática Médica. Gremed, São Paulo, 1978.

47. OXELIUS, V.A.; RORSMAN, H.; LAURELL, A.B. - Immunoglobulins of cerebrospinal fluid in syphilis. Brit. J. vener. Dis. 45:121, 1969.

48. PEDERSEN N.S.; KAM-HANSEN, S.; LINK, H.; MAVRA, M. - Specificity of immunoglobulins synthesized within the central nervous system in neurosyphilis. Acta path, microbiol. scand. 90:97, 1982.

49. POLNIKORN, N.; WITOONPANICH, R.; VORACHIT, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis. Brit. J. vener. Dis. 56:363, 1980.

50. PRANGE, H.W.; MOSKOPHIDOS, M.; SCHIPPER, H.I. & MÜLLER, F. - Relationship between neurological features and intrathecal synthesis of IgG antibodies to Treponema pallidum in untreated and treated human neurosyphilis. J. Neurol. 230:241, 1983.

51. RICE, N.S.C.; DUNLOP, E.M.C.; JONES, B.R.; HARE, M.J.; KING, A.J.; RODIN, P.; MUSHIN, A. & WILKINSON, A.E. - Demonstration of treponeme-like forms in cases of treated and untreated late syphilis and of treated early syphilis. Brit. J. vener. Dis. 46:1, 1970.

52. ROSE, A.S. & SOLOMON, H.C. - Penicillin in the treatment of neurosyphilis. J. Amer. med. Assoc. 133:5, 1947.

53. SHORT, D.H.; KNOX, J.M. & GLICKSMAN, J. - Neurosyphilis, the search for adequate treatment: a review and report of a study using benzathine penicillin G. Arch. Derm. 93:87, 1966.

54. SIMON, R.P. - Neurosyphilis. Arch. Neurol. 42:606, 1985.

55. SMITH, J.L. & ISRAEL, C.S. - Recovery of spirochaetis in the monkey by passive transfer from human late sero-negative syphilis. Brit. J. vener. Dis. 44:109, 1968.

56. SPINA-FRANÇA, A. - Neurossifilis. In: A. Spina-França & H.M. Canelas (eds.): Cadernos de Clínica Neurológica. São Paulo, 1974, v. 1, pg. 94 (publicação interna).

57. TOURTELLOTTE, W.W.; STAUGAITIS, S.M.; WALSH, M.J.; SHAPSHAK, P.; BAUMHEFNER, R.W.; POTVIN, A.R. & SYNDULKO, K. - The basis of intra-blood-brain-barrier IgG synthesis. Ann. Neurol. 17:21, 1985.

58. TRAMONT, E.C. - Persistence of Treponema pallidum following penicillin G therapy. J. Amer. med. Assoc. 236:2206, 1976.

59. VARTDAL, F.; VANDIK, B.; MICHAELSEN, T.E.; LOE, K. & NORRBT, E. - Neurosyphilis: intrathecal synthesis of oligoclonal antibodies to Treponema pallidum. Ann. Neurol. 11:35, 1982.

60. WILLCOX, R.R. - Traitement de la syphilis. Bull. Org. mond. Santé 60:25, 1982.

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Clínica Neurológica, Hospital das Clínicas, FMUSP - Caixa Postal 3461 - 01000 - São Paulo. SP - Brasil.

  • 1. ADAMS, R.D. & VICTOR, M. - Principles of Neurology. Mc-Graw-Hill, New York, 1977, pg. 618.
  • 2. BAYNE, L.L.; SCHMIDLEY, J.W. & GOODIN, D.S. - Acute syphilitic meningitis: its occur ence after clinical and serological cure of secondary syphilis with penicillin G. Arch Neurol. 43:137, 1986.
  • 3. BOS, J.D; HAMERLINCK, F. & CORMANE, R.H. - T lymphoid cells in primary syphilis: quantitative studies. Brit. J. vener. Dis. 56:74, 1980.
  • 4. BURNS, R.E. - Spontaneous reversion of FTA-ABS reactions. J. Amer. med. Assoc. 2S 1:617, 1975.
  • 5. CALLAWAY, J.L.; FLOWER Jr., A.H.; HIRSCHMANN, V.R. & OLANSKY, S. - A fou-year study of penicillin treatment of syphilis of the central nervous system. S h. med. J. 43:412, 1950.
  • 6. CHU, A.B., SEVER, J.L.; MADDEN, D.L.; LEON, M.; IIVANAINEN, M.; WALLEN, N.; BROOKS, B.R.; LEE, Y.J. & HOUFF, S. - Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases. Ann. Neurol. 13:434, 1983.
  • 7. COLLART, P.; BOREL, L.J. & DUREL, P. - Significance of spiral organisms found after treatment in late human and experimental syphilis. Brit. J. vener. Dis. 40:81, 1964.
  • 8. COLLART, P. & POITEVIN, M. - Persistance des tréponèmes pâles après traitment au cours de la syphilis expérimentale et humaine. Ann. Med. Int. 126:223, 1975.
  • 9. COLLART, P. & POITEVIN, M. - Is penicillin always infallible in syphilis? J. clin. Neuro-ophthal. 2:77, 1982.
  • 10. COLLART, P. & POITEVIN, M. - La syphilis. I: Actualités physio-biologiques Sem. Hop. Paris 57:857, 1981.
  • 11. COLLART, P. & POITEVIN, M. - La syphilis: actualités physio-biologiques. II: Processus évolutif de l'infection syphilitique expérimentale et humaine. Sem. Hôp. Paris 57:989, 1981.
  • 12. COLLART, P. & POITEVIN, M. - La syphilis: actualités physio-biologiques. IV: Le problème de la penicillinothérapie. Sem. Hôp. Paris 57:1161, 1981.
  • 13. CONFERENCE on therapy: treatment of neurosyphilis. Amer. J. Med. 9:373, 1950.
  • 14. CURTIS, A.C.; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis: III. Evaluation after three, years of treatment with penicillin alone and with a combination of penicillin and malaria. Amer. J. Syph. 33:527, 1949.
  • 15. CURTIS, A.C.; KRUSE, W.T. & NORTON, D.H. - Neurosyphilis: IV. Post-treatment evaluation four to five years following penicillin and penicillin plus malaria. Amer. J. Syph. 34:554, 1950.
  • 16. DATTNER, B. - Penicillin failures in neurosyphilis. Amer. J. Syph. 33:571, 1949.
  • 17. DATTNER, B. ; THOMAS, E.W. & WEXLER, G. - The Management of Neurosyphilis. Grune & Stratton, New York, 1944.
  • 18. DATTNER, B. ; THOMAS, E.W. & MELLO, L. de - Criteria for the management of neurosyphilis. Amer. J. Med. 10:463, 1951.
  • 19. FAGGI, L.; CITTERIO, A.; FRIGO, G.M.; PERUCCA, E. LECCHINI, S. & GIANETTI, A. - Penicillin CSF levels following intravenous therapy in syphilitic patients. Ital. J. neurol. Sci. 4:423, 1983.
  • 20. GAGER, W.E.; ISRAEL, C.W. & SMITH, J.L. - Presence of spirochaetes in paresis despite penicillin therapy. Brit. J. vener. Dis. 44:227, 1968.
  • 21. GANTI, S.R. ; COHEN, M. ; SANE, P. & HILAL, S.K. - Computed tomography of cerebral syphilis. J. comp. assist. Tomogr. 5:345, 1981.
  • 22. GILES, A.J.H. - Tabes dorsalis progressing to general paresis after 20 years despite routine penicillin therapy. Brit. J. vener. Dis. 56:368, 1980.
  • 23. GJESTLAND, T. - The Os'o study of untreated syphilis. Acta derm-venereol. (Stockholm) 35 (suppl. 34) :1, 1955.
  • 24. GODT, P.; STOEPPLER, L.; WISCHER, U. & SCHROEDER, H.H. - The value of computed tomography in cerebral syphilis. Neuroradiology 18:197, 1979.
  • 25. HAHN, R.D. - Some remarks on management of neurosyphilis. J. chron. Dis. 13:1. 1961.
  • 26. HOLLAND, B.A.; PERRET, L.V. & MILLS, CM. - Meningovascular syphilis: CT and MR findings. Radiology 158:439, 1986.
  • 27. HOOSHMAND, H.; ESCOBAR, M.R. & KOPF, S.W. - Neurosyphilis: a study of 241 patients. J. Amer. med. Assoc. 219:726, 1972.
  • 28. JAFFE, H.W. & KABINS, S.A. - Examination of cerebrospinal fluid in patients with syphilis. Rev. infect. Dis. 4 (suppl.) :5842, 1982.
  • 29. JENSEN, J.R. & FROM, E. - Alterations in T-lymphocytes and T-lymphocyte subpopulation in patients with syphilis. Brit. J. vener. Dis. 58:18, 1982.
  • 30. KAMPMEIER, R.H.; SWEENEY, A.; QUINN, R.W. ; LEFKOWITZ, L.B.; DUPONT, W.D. - A survey of 251 patients with acute syphilis treated in the collaborative study of 1943-1950. Sex. transm. Dis. 8:266, 1981.
  • 31. LINK, H. & TIBBL1NG, G. - Principles of albumin and IgG analyses in neurological disorders: II. Relation of the concentration of the proteins in serum and cerebrospinal fluid. Scand. J. clin. lab. Invest. 37:391, 1°77.
  • 32. LIVRAMENTO, J.A. - Contribuição de reações de imunofluorescência no liqüido cefalorraqueano ao estudo da neurocisticercose. Tese. São Paulo, 1980.
  • 33. LIVRAMENTO, J.A. - Síndrome do líquido cefalorraqueano na neurocisticercose: estudo crítico sobre a evolução da imunidade humoral. Tese. São Paulo, 1986.
  • 34. LÖWHAGEN, G.B. ; ANDERSSON, M.; GLOMSTRAND, C. & ROTJPE, C. - Central nervous system involvement in early syphilis: I. Intrathecal immunoglobulin production. Acta derm-venereol. (Stockholm) 63:409, 1983.
  • 35. LÖWHAGEN, G.B.; ROSENHALL, U.; ANDERSSON, M.; BLOMSTRAND, C.; LINDHOLM, L. & ROUPE, G. - Central nervous system involvement in early syphilis: II. Correlation between auditory brainstem responses (ABR) and cerebrospinal fluid abnormalities. Acta derm-venereol. (Stockholm) 63:530, 1983.
  • 36. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano. II: Técnica. Arq. Neuro-Psiquiat. (São Paulo) 41:132, 1983.
  • 37. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano. IIII: Valores normais. Arq. Neuro-Psiquiat. (São Paulo) 41:137, 1983.
  • 38. MACHADO, L.R. - Subpopulações linfocitárias do liqüido cefalorraqueano normal. I: Principais registros da literatura. Arq. Neuro-Psiquiat. (São Paulo) 41:119, 1983.
  • 39. MERRITT, H.H. ; ADAMS, R.D. & SOLOMON, H.C. - Neurosyphilis. Oxford Univ. Press, New York, 1946.
  • 40. MICHEL, D.; BLANC, A.; LAURENT, B.; FOYATIER, N. & PORTFAIX, M. - Étude biologique, psychométrique et tomodensimétrique de la neurosyphilis traitée. Rev. neurol. (Paris) 139:737, 1983.
  • 41. MOHR, J.A.; GRIFFITHS, W.; JACKSON, R.; SAADAH, H.; BIRD, P. & RIDDLE, J. - Neurosyphilis and penicillin levels in cerebrospinal fluid. J. Amer, med. Assoc. 236:2208, 1976.
  • 42. MÜLLER, F. & MOSKOPHIDIS, M. - Estimation of the local production of antibodies to Treponema pallidum in the central nervous system of patients with neurosyphilis. Brit. J. vener. Dis. 59:80, 1983.
  • 43. NICHOLS JR., F.T. & HEYMAN, A. - Penicillin therapy in asymptomatic neurosyphilis: a comparison of the, effects of amorphous penicillin in oil and wax, and crystalline penicillin G. Amer. J. Syph. 33:561, 1949.
  • 44. NITRINI, R. (a) Neurossífilis: análise de alguns aspectos clínicos e laboratoriais. Tese, São Paulo, 1981.
  • (b) Neurossífilis: penicilinoterapia intravenosa em altas doses. Tese. São Paulo, 1986.
  • 45. NITRINI, R. & SPINA-FRANÇA, A. - Penicilinoterapia intravenosa em altas doses na neurossífilis: estudo de 62 casos. I. Avaliação clínica. Arq. Neuro-Psiquiat. (São Paulo). 45:99, 1987.
  • 46. OSELKA, G.; LEVI, G.C.; LOPES, H.V.; MENDONÇA, J.S.; BALDY, J.L.S.; TRABULSI, L.R. & AMATO NETO, V. - Antibióticos na Prática Médica. Gremed, São Paulo, 1978.
  • 47. OXELIUS, V.A.; RORSMAN, H.; LAURELL, A.B. - Immunoglobulins of cerebrospinal fluid in syphilis. Brit. J. vener. Dis. 45:121, 1969.
  • 48. PEDERSEN N.S.; KAM-HANSEN, S.; LINK, H.; MAVRA, M. - Specificity of immunoglobulins synthesized within the central nervous system in neurosyphilis. Acta path, microbiol. scand. 90:97, 1982.
  • 49. POLNIKORN, N.; WITOONPANICH, R.; VORACHIT, M.; VEJJAJIVA, S. & VEJJAJIVA, A. - Penicillin concentrations in cerebrospinal fluid after different treatment regimens for syphilis. Brit. J. vener. Dis. 56:363, 1980.
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Datas de Publicação

  • Publicação nesta coleção
    22 Jun 2011
  • Data do Fascículo
    Set 1987
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