439
Immunoblotting patterns in experiments designed to detect CSL antibodies in CSF of patients with various neurological diseases. (a) Amido-black protein stain of partly purified CSL as antigen. Bands at 31 5,33, and 45 kD are
characteristic.
(b) Staining obtained by omitting CSF as first antibody and using labelled goat anti-human antibodies as second antibody. (c) Pattern obtained with CSF patients with meningeal haemorrhage due to mechanical trauma; note background staining with no defined bands. (d) and (g) Immunodetection of CSL bands using CSF of patients with multiple selerosis as source of CSL antibody. Stained CSL subunits vary from one patient to another, 31 5 kD band being revealed in (d) 1-3 and 45 kD in (d) 4-8 ; in some cases, 31and 33 kD subunits were strongly stained, with a different pattern of staining for 45 kD. (e) and (f) Same experiments with CSF from patients with neurological diseases other than multiple selerosis (non-infectious diseases not affecting blood-brain barrier in [e] and viral meningitis in [f]).In four cases band at 67 kD was immunostained. In one patient, this band was observed during acute phase only. Bands at 40 and 27 kD were detected in some cases. Arrows indicate position of molecular weight markers.
Quantitative differences in CSL antibodies in CSF are evident and not necessarily related to the protein concentration of CSF. Measurement of anti-CSL is possible, provided samples are not denatured by storage or handling. Our preliminary results with anti-CSL studies in plasma indicate high levels of CSL antibody in the plasma of patients having CSL antibody in the CSF but it is too soon to calculate the specificity and the sensitivity of this approach as a test for multiple selerosis on plasma or
serum.
CN RS Neurochemistry Centre and INSERM U44, 5 rue Blaise Pascal, 67084 Strasbourg, France
J.-P. ZANETTA
Cyclosporin treatment for severe active ulcerative colitis SIR,-We read with great pleasure Dr Lichtiger and Professor Present’s report (July 7, p 16) of the use of cyclosporin in the treatment of severe ulcerative colitis. We would draw attention to our
experience.
Between 1986 and 1989,10 patients with severe ulcerative colitis who were refractory to standard medical treatment (methylprednisolone 40 mg/day intramuscularly, hydrocortisone or 5-acetylsalicylic acid suppositories, total parenteral nutrition, and antibiotics) and were therefore candidates for surgical treatment were given cyclosporin according to an open protocol. In 2 men and 3 women (aged 27-40 years), cyclosporin was given orally at a mean dose of 8mg/kg daily for 5-6 weeks. In the other 5 patients (1 male, 4 female, 13-45), cyclosporin 4 mg/kg daily was given intravenously for at least 10 days. In the first group clinical condition greatly improved (substantial reduction of the number of daily defecations, disappearance of blood from faeces) after a mean of 4 weeks, and there was a striking reduction in the degree of inflammatory activity. Plasma cyclosporin concentrations remained within the normal therapeutic range (400-700 mg/ml) in all cases. This allowed the steroid dose to
progressively tanered and eventually discontinued, and cyclosporin was replaced by sulphasalazine. Patients then remained in complete remission for a mean of 3-6 months (range 2-8), after which, however, all patients had severe relapses needing
be
surgery. In 2 of the 5
patients in the second group the addition of cyclosporin to the drug regimen failed to modify the clinical severity of the colitis, and surgery could not be deferred. The other 3 patients showed a progressive clinical improvement after a mean of 7 days on cyclosporin, after which the steroid dose could be tapered and the drug eventually stopped. These 3 patients then received 2 mg/kg daily azathioprine; 2 patients are still in remission after 1 year and 3 months, respectively, whereas the third underwent surgery after 9 months’ follow-up owing to severe, acute exacerbation of ulcerative colitis. These data are in accord with those of Baker and J ewelF and seem to confirm that cyclosporin, whether given orally or parenterally, does not appear to have the capacity to prevent surgical treatment of the severe forms of ulcerative colitis. G. BIANCHI PORRO Gastrointestinal Unit, M. PETRILLO L. Sacco Hospital, S. ARDIZZONE 20157 Milan, Italy 1. Baker K, Jewell DD. Cyclosporin for the treatment of severe inflammatory bowel disease. Aliment Pharmacol Ther 1989; 3: 143-49.
GISSI-2: 10% reduction in mortality with heparin in acute myocardial infarction? SIR,-In GISSI-2 and its international extension (July 14, p 65; July 14, p 71), patients with suspected acute myocardial infarction (MI) were given a fibrinolytic agent and aspirin immediately, and were allocated randomly to receive either no routine anticoagulation or 12 500 U heparin twice daily, starting 12 h after the beginning of fibrinolytic infusion and continuing until hospital discharge. During the first 12 h, therefore, anticoagulant treatment in the "no heparin" and "heparin" groups should have been similar, and consequently any differences in mortality during this time are likely
Immunoblotting patterns in experiments designed to detect CSL antibodies in CSF of patients with various neurological diseases. (a) Amido-black protein stain of partly purified CSL as antigen. Bands at 31 5,33, and 45 kD are
characteristic.
(b) Staining obtained by omitting CSF as first antibody and using labelled goat anti-human antibodies as second antibody. (c) Pattern obtained with CSF patients with meningeal haemorrhage due to mechanical trauma; note background staining with no defined bands. (d) and (g) Immunodetection of CSL bands using CSF of patients with multiple selerosis as source of CSL antibody. Stained CSL subunits vary from one patient to another, 31 5 kD band being revealed in (d) 1-3 and 45 kD in (d) 4-8 ; in some cases, 31and 33 kD subunits were strongly stained, with a different pattern of staining for 45 kD. (e) and (f) Same experiments with CSF from patients with neurological diseases other than multiple selerosis (non-infectious diseases not affecting blood-brain barrier in [e] and viral meningitis in [f]).In four cases band at 67 kD was immunostained. In one patient, this band was observed during acute phase only. Bands at 40 and 27 kD were detected in some cases. Arrows indicate position of molecular weight markers.
Quantitative differences in CSL antibodies in CSF are evident and not necessarily related to the protein concentration of CSF. Measurement of anti-CSL is possible, provided samples are not denatured by storage or handling. Our preliminary results with anti-CSL studies in plasma indicate high levels of CSL antibody in the plasma of patients having CSL antibody in the CSF but it is too soon to calculate the specificity and the sensitivity of this approach as a test for multiple selerosis on plasma or
serum.
CN RS Neurochemistry Centre and INSERM U44, 5 rue Blaise Pascal, 67084 Strasbourg, France
J.-P. ZANETTA
Cyclosporin treatment for severe active ulcerative colitis SIR,-We read with great pleasure Dr Lichtiger and Professor Present’s report (July 7, p 16) of the use of cyclosporin in the treatment of severe ulcerative colitis. We would draw attention to our
experience.
Between 1986 and 1989,10 patients with severe ulcerative colitis who were refractory to standard medical treatment (methylprednisolone 40 mg/day intramuscularly, hydrocortisone or 5-acetylsalicylic acid suppositories, total parenteral nutrition, and antibiotics) and were therefore candidates for surgical treatment were given cyclosporin according to an open protocol. In 2 men and 3 women (aged 27-40 years), cyclosporin was given orally at a mean dose of 8mg/kg daily for 5-6 weeks. In the other 5 patients (1 male, 4 female, 13-45), cyclosporin 4 mg/kg daily was given intravenously for at least 10 days. In the first group clinical condition greatly improved (substantial reduction of the number of daily defecations, disappearance of blood from faeces) after a mean of 4 weeks, and there was a striking reduction in the degree of inflammatory activity. Plasma cyclosporin concentrations remained within the normal therapeutic range (400-700 mg/ml) in all cases. This allowed the steroid dose to
progressively tanered and eventually discontinued, and cyclosporin was replaced by sulphasalazine. Patients then remained in complete remission for a mean of 3-6 months (range 2-8), after which, however, all patients had severe relapses needing
be
surgery. In 2 of the 5
patients in the second group the addition of cyclosporin to the drug regimen failed to modify the clinical severity of the colitis, and surgery could not be deferred. The other 3 patients showed a progressive clinical improvement after a mean of 7 days on cyclosporin, after which the steroid dose could be tapered and the drug eventually stopped. These 3 patients then received 2 mg/kg daily azathioprine; 2 patients are still in remission after 1 year and 3 months, respectively, whereas the third underwent surgery after 9 months’ follow-up owing to severe, acute exacerbation of ulcerative colitis. These data are in accord with those of Baker and J ewelF and seem to confirm that cyclosporin, whether given orally or parenterally, does not appear to have the capacity to prevent surgical treatment of the severe forms of ulcerative colitis. G. BIANCHI PORRO Gastrointestinal Unit, M. PETRILLO L. Sacco Hospital, S. ARDIZZONE 20157 Milan, Italy 1. Baker K, Jewell DD. Cyclosporin for the treatment of severe inflammatory bowel disease. Aliment Pharmacol Ther 1989; 3: 143-49.
GISSI-2: 10% reduction in mortality with heparin in acute myocardial infarction? SIR,-In GISSI-2 and its international extension (July 14, p 65; July 14, p 71), patients with suspected acute myocardial infarction (MI) were given a fibrinolytic agent and aspirin immediately, and were allocated randomly to receive either no routine anticoagulation or 12 500 U heparin twice daily, starting 12 h after the beginning of fibrinolytic infusion and continuing until hospital discharge. During the first 12 h, therefore, anticoagulant treatment in the "no heparin" and "heparin" groups should have been similar, and consequently any differences in mortality during this time are likely
