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AIM: A four-arm multicentre randomized double-blind placebo-controlled trial was undertaken to assess the effect and safety of suppositories containing recombinant streptokinase (rSK) at two dose levels (100,000 IU and 200,000 IU) with sodium salicylate (SS) compared with placebo and SS for the treatment of acute haemorrhoidal disease. METHOD: Patients with acute symptoms of haemorrhoids were randomized to four treatment groups: (I) placebo, (II) SS, (III) SS + rSK 100,000 IU and (IV) SS + rSK 200,000 IU per suppository. Inpatient treatment was by four suppositories given every 6 h to discharge at 24 h. Evaluations were made at the time of discharge (24 h) and at 3, 5 and 20 days later. The main end-point was the degree of relief of pain, oedema and reduction in the size of the lesion by 90% on day 5. Adverse events and the occurrence of anti-SK antibodies were also determined. RESULTS: Eighty patients were included. Respective response rates in the four groups were 16%, 30%, 25% and 52%. In the last group there was a significant difference (36.8%) compared with control (95% CI 7.0-58.4%). The time to response was significantly shorter (median 5 days) in the 200,000 IU rSK group with respect to the others. There were no adverse events attributable to the treatment. No increase in anti-SK antibodies was detected 20 days after treatment. CONCLUSION: Suppositories with 200,000 IU rSK showed a significant improvement in symptoms of acute haemorrhoids, with an adequate safety profile.

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Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-alpha and IFN-beta treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-gamma expression after IFN-alpha but not after IFN-beta treatments. The in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.

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INTRODUCTION: Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. OBJECTIVE: To assess the efficacy of IFN-alpha2b recombinant in the cognitive dysfunction of RR MS. PATIENTS AND METHODS: 57 RR-MS clinical definite patients from the randomised, double blind, placebo controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN-alpha2b (Heberon R) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. RESULTS: The initial comparison of the groups did not show any differences among the placebo (n=20), low dose (n=18) and high dose (n=19) considering age (p=0.234), gender, ethnic group (p=0.012), years ill (p=0.787), EDSS (p=0.203) and rate of relapses (p=0.432). The Luria's Test showed an improved in the low dose group from 2.50 +/- 1.34 to 1.39 +/- 1.85 (p=0.029) and in the high dose group from 3.22 +/- 1.89 to 2.17 +/- 1.50 (p=0.006) vs placebo 2.85 +/- 1.66 to 2.90 +/- 1.97 (p=0.723). The results of the Benton's test demonstrated that the low dose group had an improved from 5.50 +/- 1.10 to 6.22 +/- 1.31 (p=0.047), in the high dose group from 4.87 +/- 1.85 to 5.78 +/- 1.35 (p=0.005) where as in the placebo group worse from 5.15 +/- 1.76 to 5.05 +/- 2.11 (p=0.893). The WAIS test showed the same results, the low dose group increased from 5.17 +/- 1.34 to 6.06 +/- 1.21 (p=0.022), the high dose group from 4.56 +/- 1.38 to 5.39 +/- 1.29 (p=0.007) and the placebo group worse from 5.25 +/- 1.25 to 5.05 +/- 1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72 +/- 10.61 to 49.94 +/- 11.68 (p=0.015) in the low dose group, from 42.67 +/- 11.04 to 48.72 +/- 8.84 (p=0.03) in the high dose group, but in the placebo group worse from 44.55 +/- 10.86 to 41.95 +/- 13.74 (p=0.655). CONCLUSION: IFN-alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial.

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Introducción. Ensayos clínicos recientes indican que el interferón (IFN)alfa-2b recombinante, parece ser útil en la forma exacerbación-remisión (ER) de la esclerosis múltiple (EM). Un 70 por ciento los pacientes con EM en Cuba tienen disfunción cognitiva. Objetivo. Evaluar la eficacia del IFNa2b en los trastornos cognitivos de la EM. Pacientes y métodos. 57 pacientes con EM-ER clínicamente definida y confirmada por RM, del ensayo clínico en Cuba, fase III, multicentro, aleatorizado, doblemente ciego y controlado con placebo. Los pacientes se distribuyeron en: grupo I, con 10 millones (MI) de UI de IFNalf-a2b (Heberon-R ®) intramuscular; el grupo II, con 3 MI IFNalfa-2b y grupo III,con placebo, dos veces a la semana, durante dos años. Las evaluaciones fueron a ciegas, al inicio y al final, mediante la escala neuropsicológica de Luria, Benton visual retention test, escala verbal WAISR ( Weschler adult intelligence-revised) y el PASAT-3 (paced auditory serial addition test). La detección de anticuerpos neutralizantes (ACN) al IFNalfa-2b, se realizó semestralmente. Resultados. Los resultados iniciales no demostraron diferencias significativas entre los grupos para las variables demográficas, clínicas y de discapacidad. Los resultados del Luria fueron: placebo [inicial (I)/final (F)] 2,85 ñ 1,66/2,90 ñ 1,97 (p = 0,723); IFNalfa-2b 3 MI (I/F): 2,50 ñ 1,34/1,39 ñ 1,85 (p = 0,029); IFNalfa-2b 10 MI (I/F): 3,22 ñ 1,69/2,17 ñ 1,50 (p = 0,006). Al fusionar los dos grupos IFNa2b frente a placebo se obtuvo p = 0,021 frente a 0,367. En el Benton, los resultados fueron: placebo (I/F): 5,15 ñ 1,76/5,05 ñ 2,11 (p = 0,893); IFNalfa-2b 3 MI (I/F): 5,50 ñ 1,10/6,22 ñ 1,31 ( p = 0,047); IFNalfa-2b 10 MI (I/F): 4,67 ñ 1,85/5,78 ñ 1,35 (p = 0,005). Al unir los grupos IFNalfa-2b frente a placebo, se obtuvo p = 0,181 frente a 0,440. En el test WAIS se encontró: placebo (I/F): 5,25 ñ 1,25/5,05 ñ 1,57 (p = 0,354); IFNalfa-2b 3 MI (I/F): 5,17 ñ 1,34/6,06 ñ 1,21 ( p = 0,022); IFNalfa-2b 10 MI (I/F): 4,56 ñ 1,38/5,39ñ1,29 (p = 0,007). Al comparar los grupos IFNalfa-2b frente a placebo (I/F) se obtuvo p = 0,026 frente a 0,216. Los resultados del PASAT-3 fueron: placebo (I/F): 44,55 ñ 10,86/41,95 ñ 13,74 (p = 0,655); IFNa2b 3 MI (I/F), 45,72 ñ 10,61/49,94 ñ 11,68 ( p = 0,015); IFNalfa-2b 10 MI (I/F), 42,67 ñ 11,04/48,72 ñ 8,84 (p = 0,003). Al comparar los grupos IFN frente a placebo, con el PASAT-3, se obtuvo p = 0,033 frente a 0,621. Los ACN contra el IFNalfa-2b se detectaron en un 3,5 por ciento de los casos. Conclusiones. El IFNa2b mejora las alteraciones cognitivas en la EM-ER. Esta mejoría es dependiente de la dosis y la frecuencia de ACN es muy baja (AU)

Introduction. Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing-remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. Objective. To assess the efficacy of IFN-alpha 2b recombinant in the cognitive dysfunction of RR-MS. Patients and methods. 57 RR-MS clinical definite (Poser et al) patients from the randomised, double-blind, placebo-controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN alpha-2b (Heberon-R ®) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. Results. The initial comparison of the groups did not show any differences among the placebo (n= 20), low dose (n= 18) and high dose (n= 19) considering age (p= 0.234), gender, ethnic group (p= 0.012), years ill (p= 0.787), EDSS (p=0.203) and rate of relapses (p= 0.432).The Luria’s Test showed an improved in the low dose group from 2.50±1.34 to 1.39±1.85 (p= 0.029) and in the high dose group from 3.22±1.89 to 2.17±1.50 (p= 0.006) vs placebo 2.85±1.66 to 2.90±1.97 (p=0.723). The results of the Benton’s test demonstrated that the low dose group had an improved from 5.50±1.10 to 6.22±1.31 (p= 0.047), in the high dose group from 4.87±1.85 to 5.78±1.35 (p= 0.005) where as in the placebo group worse from 5.15±1.76 to 5.05±2.11 (p= 0.893). The WAIS test showed the same results, the low dose group increased from 5.17±1.34 to 6.06±1.21 (p= 0.022), the high dose group from 4.56±1.38 to 5.39±1.29 (p= 0.007) and the placebo group worse from 5.25±1.25 to 5.05±1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72±10.61 to 49.94±11.68 (p= 0.015) in the low dose group, from 42.67±11.04 to 48.72±8.84 (p= 0.03) in the high dose group, but in the placebo group worse from 44.55±10.86 to 41.95±13.74 (p= 0.655). Conclusion. IFN alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial (AU)

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