Immunogenicity of an interferon-beta1a product.

In order to determine whether Blastoferon®, a biosimilar interferon (IFN)- beta 1a formulation, shares epitopes with other known IFN-beta products, a series of neutralization bioassays were performed with a set of well-characterized anti-IFN- beta monoclonal antibodies and human sera (World Health Organization Reference Reagents). The bioassay was the interferon-induced inhibition of virus cytopathic effect on human cells in culture (EMC virus and A-549 cells). Computer-calculated results were reported as Tenfold Reduction Units (TRU)/ml. To further assess Blastoferon® immunogenicity, in vivo production of anti-IFN beta antibodies was determined in sera of patients included in the pharmacovigilance plan of Blastoferon® by the level of IFN- beta 1a binding antibodies (by enzyme immunoassay -EIA) and neutralizing antibodies (in the Wish-VSV system). The highly characterized neutralizing monoclonal antibodies A1 and A5 that bind to specific regions of the IFN- beta molecule reacted positively with the three beta 1a IFNs: Blastoferon®, Rebif®, and the IFN- beta WHO Second International Standard 00/572. As expected, the non-neutralizing monoclonal antibodies B4 and B7 did not neutralize any of the IFN- beta preparations. The commercially available monoclonal antibody B-02 reacted essentially equally with Rebif® and Blastoferon®. The WHO Reference Reagent human serum anti-IFN- beta polyclonal antibody neutralized all the IFN- beta products, whereas the WHO Reference Reagent human serum anti-IFN-alpha polyclonal antibody G037-501-572 appropriately failed to react with any of the IFN- beta products. On the basis of in vitro reactivity with known, well-characterized monoclonal and polyclonal antibody preparations, Blastoferon® shares immunological determinants with other human interferon- beta products, especially IFN- beta 1a. In vivo antibodies were detected by EIA in 72.9% of 37 chronically treated multiple sclerosis patients, whereas neutralizing antibodies were found in 8.1% of them. Blastoferon® appears to have immunological characteristics comparable to other IFN- beta 1a products.

Hemorragias obstétricas graves en el período periparto / Severe obstetric bleeding in the peri-delivery period

Objetivo: Evaluar la morbi-mortalidad actual en un grupo de pacientes con sangrado obstétrico severo en el período periparto. Diseño: Estudio retrospectivo y descriptivo. Marco: División Terapia Intensiva, en una clínica privada. Buenos Aires, Argentina. Pacientes: 45 pacientes gestantes con edad de 33,2ñ4,8 años, ingresadas a partir de marzo de 1991 hasta febrero de 1998. Método y resultados principales: El 64 por ciento de los casos presentaron shock hemorrágico. El promedio de hematíes sedimentados transfundidos fue 7,6ñ6,3 unidades, y el hematocrito alcanzado al cabo de 24-36 horas fue 23,6ñ4,9 por ciento. En 29 enfermas se recurrió a la histerectomía como última medida para controlar el sangrado masivo. Seis pacientes histerctomizadas presentaron hemorragia retro y/o intraperitoneal, debiéndose reintervenir quirúrgicamente a 5 por sangrados persistentes. Este subgrupo requirió mayor número de transfusiones (18ñ8 vs 5ñ8 unidades; p < 0,01). Diecisiete enfermas cursaron con coagulopatía por consumo, de ellas 6 con coagulación intravascular diseminada. Las 45 puérperas sobrevivieron. Conclusiones: 1. Optimo porcentaje de sobrevida materna vinculado con : a) disponibilidad de hemoderivados y resolución de estudios complementarios, y b) actuación de un equipo multidisciplinario. 2. Se aprecia una alta incidencia de histerectomías como última alternativa para controlar las hemorragias

Hemorragias obstétricas graves en el período periparto / Severe obstetric bleeding in the peri-delivery period

Objetivo: Evaluar la morbi-mortalidad actual en un grupo de pacientes con sangrado obstétrico severo en el período periparto. Diseño: Estudio retrospectivo y descriptivo. Marco: División Terapia Intensiva, en una clínica privada. Buenos Aires, Argentina. Pacientes: 45 pacientes gestantes con edad de 33,2ñ4,8 años, ingresadas a partir de marzo de 1991 hasta febrero de 1998. Método y resultados principales: El 64 por ciento de los casos presentaron shock hemorrágico. El promedio de hematíes sedimentados transfundidos fue 7,6ñ6,3 unidades, y el hematocrito alcanzado al cabo de 24-36 horas fue 23,6ñ4,9 por ciento. En 29 enfermas se recurrió a la histerectomía como última medida para controlar el sangrado masivo. Seis pacientes histerctomizadas presentaron hemorragia retro y/o intraperitoneal, debiéndose reintervenir quirúrgicamente a 5 por sangrados persistentes. Este subgrupo requirió mayor número de transfusiones (18ñ8 vs 5ñ8 unidades; p < 0,01). Diecisiete enfermas cursaron con coagulopatía por consumo, de ellas 6 con coagulación intravascular diseminada. Las 45 puérperas sobrevivieron. Conclusiones: 1. Optimo porcentaje de sobrevida materna vinculado con : a) disponibilidad de hemoderivados y resolución de estudios complementarios, y b) actuación de un equipo multidisciplinario. 2. Se aprecia una alta incidencia de histerectomías como última alternativa para controlar las hemorragias (AU)

Vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage.

No data have been published on the role of vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage (PMSAH). In a case-control study we compared the prevalence of vascular risk factors in 40 consecutive patients who suffered a perimesencephalic subarachnoid hemorrhage with that in two controls groups: (a) 120 subjects registered with a general practitioner (GP: matched at a 3:1 ratio for age and sex) and (b) 81 proxies of patients of a hospital outpatient clinic. A conditional multivariate logistic regression model was performed taking into account the matched design. Hypertension was more frequent among PMSAH patients than among the two control group subjects for men and women. Among women, smoking was more common in PMSAH than in the GP control group. The conditional multivariate logistic regression model confirmed that hypertension was an independent risk factor for PMSAH (P = 0.036) Hypertension is a preventable risk factor of PMSAH.

[Thrombotic thrombocytopenic purpura and systemic lupus erythematous. Three cases presenting simultaneously]. / Púrpura trombocitopenica trombótica y lupus eritematoso sistémico. Tres casos con presentación simultánea.

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, neurological symptoms, and renal involvement. The relationship of TTP to systemic lupus erythematosus (SLE) has been recognized in the medical literature since 1939. The differential diagnosis is difficult because both diseases have similar clinical features. The mainstay for recognizing TTP in the context of active SLE is the presence of helmet red cells, marked reticulocytosis, and negative direct Coomb's test. We report three female patients with simultaneous presentation of TTP and SLE. We suggest combined treatment with immunosuppressive therapy and plasma exchange using fresh frozen plasma.

Púrpura trombocitopenica trombótica y lupus eritematoso sistémico. Tres casos con presentación simultánea. / [Thrombotic thrombocytopenic purpura and systemic lupus erythematous. Three cases presenting simultaneously]

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, neurological symptoms, and renal involvement. The relationship of TTP to systemic lupus erythematosus (SLE) has been recognized in the medical literature since 1939. The differential diagnosis is difficult because both diseases have similar clinical features. The mainstay for recognizing TTP in the context of active SLE is the presence of helmet red cells, marked reticulocytosis, and negative direct Coombs test. We report three female patients with simultaneous presentation of TTP and SLE. We suggest combined treatment with immunosuppressive therapy and plasma exchange using fresh frozen plasma.

Smoking and aneurysmal subarachnoid haemorrhage: a case-control study.

BACKGROUND: Despite recent advances in the management of subarachnoid haemorrhage, the mortality rate associated with the condition remains high. The identification of risk factors for subarachnoid haemorrhage may lead to the development of interventions aimed at its prevention. METHODS: We compared the prevalence of vascular risk factors using a case-control design in 141 consecutively admitted patients who had suffered a subarachnoid haemorrhage with that in age- and sex-matched subjects registered with a general practitioner in a western suburb of Lisbon. RESULTS: The prevalence of diabetes and hyperlipidaemia did not differ between the groups. Hypertension was 8.3 times more frequent among patients with subarachnoid haemorrhage (95% confidence interval 4.6-16.7) than in the control group, and smoking was four times more frequent (95% confidence interval 2.0-8.6). The association between smoking and subarachnoid haemorrhage persisted after controlling for the presence of hypertension (odds ratio for hypertensive participants = 10.5, 95% confidence interval 1.9-56.4; odds ratio for normotensive participants = 3.7, 95% confidence interval 1.6-10.1) and was independent of both age and sex. CONCLUSION: These results indicate that hypertension and smoking are both involved in the growth or rupture of cerebral aneurysms.

Transient global amnesia. A case control study.

A case control study of transient global amnesia (TGA), transient ischaemic attacks (TIA) and normal controls is described. Each of the 51 TGA patients, selected between January 1985 and March 1990, was compared with four controls (two TIAs and two normals) for the presence of vascular risk factors (hypertension, diabetes, smoking habits, cholesterol, triglycerides and haematocrit levels, heart disease, previous stroke), previous TGA, migraine, psychiatric illness and recent head trauma. Patients with TGA had less diabetes, hypercholesterolaemia and hypertriglyceridaemia than TIA. TGA subjects had significantly more hypertension (odds ratio = 3.31) and migraine (odds ratio = 8.67) than normal controls. During a mean of 17.4 mths of follow-up (range 1-96 mths), three subjects had recurrent TGA, one sustained a TIA and a minor stroke, but none had seizures. Thrombo-embolism and epilepsy are unlikely to be the cause of this benign disorder. The role is stressed of appropriate precipitants, including haemodynamic changes, and of individual susceptibility (of which migraine is probably a marker) in the genesis of TGA.

[Transverse myelitis and systemic lupus erythematosus. A case report]. / Mielitis transversa y lupus eritematoso sistémico. Presentación de un caso.

This study presents the case of a 32 year-old patient carrying a belatedly diagnosed systemic lupus erythematosus (SLE), who suddenly developed transverse myelitis. This complication had been preceded a few hours earlier by a sole neurological disorder consisting in a universal nystagmus. This neurological condition was accompanied by a renal syndrome revealed by a nephritic sediment with scarce functional repercussions. The patient was treated with a combination of high doses of methylprednisone and cyclophosphamide. The central neurological and renal disorder remitted, but it was impossible to reverse the patient's paraplegia, which became permanent. This paper includes a review of the 46 cases of transverse myelitis and SLE published so far with regard to diagnosis, treatment and results, a comparison with the case under study, and the conclusions drawn.

Mielitis transversa y lupus eritematoso sistémico: presentación de un caso / Transverse myelitis and systemic lupus erythematosus: report of a case

Se presenta el caso de un paciente de 32 años portador de lupus eritematoso sistémico (LES), tardíamente diagnosticado, que desarrolló una mielitis transversa de brusca instalación. Esta ampliación fue precedida en horas por un único trastorno neurológico, consistente en un nistagmus universal (horizontal, vertical y rotatorio). El cuadro neurológico fue acompañado por un síndrome renal, expresado por un sedimiento nefrítico con escasa repercusión funcional. El paciente fue tratado con una combinación de alta dosis de metilprednisona y ciclofosfamida. Se obtuvo remisión del compromiso central y renal, no logrando revertir su paraplejía, que se transformó en definitiva. Se revisan los 46 casos publicados hasta la fecha de mielitis transversa y LES en cuanto a métodos diagnósticos, tratamiento y resultados y se comparan con nuestro caso, con las conclusiones correspondientes

Mielitis transversa y lupus eritematoso sistémico. Presentación de un caso. / [Transverse myelitis and systemic lupus erythematosus. A case report]

This study presents the case of a 32 year-old patient carrying a belatedly diagnosed systemic lupus erythematosus (SLE), who suddenly developed transverse myelitis. This complication had been preceded a few hours earlier by a sole neurological disorder consisting in a universal nystagmus. This neurological condition was accompanied by a renal syndrome revealed by a nephritic sediment with scarce functional repercussions. The patient was treated with a combination of high doses of methylprednisone and cyclophosphamide. The central neurological and renal disorder remitted, but it was impossible to reverse the patients paraplegia, which became permanent. This paper includes a review of the 46 cases of transverse myelitis and SLE published so far with regard to diagnosis, treatment and results, a comparison with the case under study, and the conclusions drawn.

Mielitis transversa y lupus eritematoso sistémico: presentación de un caso / Transverse myelitis and systemic lupus erythematosus: report of a case

Se presenta el caso de un paciente de 32 años portador de lupus eritematoso sistémico (LES), tardíamente diagnosticado, que desarrolló una mielitis transversa de brusca instalación. Esta ampliación fue precedida en horas por un único trastorno neurológico, consistente en un nistagmus universal (horizontal, vertical y rotatorio). El cuadro neurológico fue acompañado por un síndrome renal, expresado por un sedimiento nefrítico con escasa repercusión funcional. El paciente fue tratado con una combinación de alta dosis de metilprednisona y ciclofosfamida. Se obtuvo remisión del compromiso central y renal, no logrando revertir su paraplejía, que se transformó en definitiva. Se revisan los 46 casos publicados hasta la fecha de mielitis transversa y LES en cuanto a métodos diagnósticos, tratamiento y resultados y se comparan con nuestro caso, con las conclusiones correspondientes (AU)