Infusion of platelets transiently reduces nucleoside overload in MNGIE.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by thymidine phosphorylase (TP) deficiency, which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). In this work, we report that infusion of platelets from healthy donors to patients with MNGIE restored transiently circulating TP and reduced plasma dThd and dUrd levels, suggesting that treatments to achieve permanent restoration of circulating TP such as allogeneic stem cell transplantation or gene transfer might be therapeutic.

Relevance of genetically determined host factors to the prognosis of meningococcal disease.

To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, P<0.0001), and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval, 1.1-11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

Improvement in quality of life in patients with advanced Parkinson's disease following bilateral deep-brain stimulation in subthalamic nucleus.

In this article we investigate the changes observed in the scales that quantify the quality of life (PDQ-39) in patients that have already completed 1 and 2 years of bilateral subthalamic stimulation (DBS-STN). Fourteen patients were evaluated 1 year after DBS-STN; the evaluation was repeated on 11 of them, 2 years after surgery. All of them suffered from Parkinson's disease with a 14.3 (+/-5.7) years history of motor complications. Patients were selected according to CAPSIT criteria. All of them were implanted bilateral electrodes in the subthalamic nucleus. The parameters applied were UPDRS II, UPDRS III, PDQ-39, and the scale of quality of life for caregivers (SQLC). Scorings in motor scales (UPDRS III) improved 45% in relation to the first year, and 48% in relation to the second year (P < 0.001). Patient's quality of life (PDQ-39 summary index) improvement was 62% 2 years after surgery (P < 0.001), and caregivers' quality of life improvement was 68% (P = 0.002) by the same time. DBS-STN is a therapy that efficiently improves the quality of life of selected patients with Parkinson's disease. This improvement is still present 2 years after surgery and has a positive impact on caregivers quality of life.

Cutaneous ulcers with type I cryoglobulinemia treated with plasmapheresis.

Severe necrotic cutaneous ulcers and kidney involvement secondary to type I cryoglobulinemia can be a therapeutic challenge. Plasmapheresis has been reported useful to treat autoimmune diseases such as thrombotic thrombocytopenic purpura, systemic lupus erythematosus, myasthenia gravis and Goodpasture's syndrome. We report the case of a patient who presented necrotic lesions with kidney involvement due to type I cryoglobulinemia (Ig G kappa) that evolved to a multiple myeloma. Treatment with high doses of corticosteroid plus cyclophosphamide did not control the disorder. Therapy with plasmapheresis produced a marked decrease in cryoglobulin levels and a subsequent relevant clinical improvement of cutaneous lesions and renal function. In cryoglobulinemia, plasmapheresis can be used as effective adjunt therapy to minimize cutaneous, renal and/or neurologic involvement.

[Bilateral subthalamic nucleus deep-brain stimulation (STN-DBS) in Parkinson's disease: initial experience in Cruces Hospital]. / Estimulación bilateral del núcelo subtalámico en la enfermedad de Parkinson. Experiencia inicial en el Hospital de Cruces.

INTRODUCTION: Clinical outcomes of Parkinson's disease patients treated for 12 months with STN-DBS were analyzed. PATIENTS ADN METHODS: Twelve patients were selected using the CAPSIT protocol criteria and placement of electrodes in the appropriate target was performed according to results of fusion image techniques and intraoperative microrecording. RESULTS: A reduction in motor UPDRS (44 %) and activities of daily living (58 %) scores during <> phases were observed. <> time with dyskinesias was reduced (86 %), while severe dyskinesias disappeared. Levodopa dosage was also lowered (44 %). Patients and caregivers showed a clear-cut benefit on quality of life (58 % and 61 % respectively). No cognitive deterioration was observed and morbidity was in the same range as that published by other teams. CONCLUSION: Bilateral STN-DBS is an effective symptomatic therapy for complicated Parkinsons disease patients. It improves the quality of life of patients and their caregivers and allows a reduction of levodopa dosage.

Estimulación bilateral del núcleo subtalámico en la enfermedad de Parkinson. Experiencia inicial en el Hospital de Cruces / Bilateral subthalamic nucleus deep-brain stimulation (STN-DBS) in Parkinson's disease: initial experience in Cruces Hospital

Introducción: Se presentan los resultados clínicos tras 1 año de evolución en 12 pacientes con enfermedad de Parkinson tratados con estimulación bilateral de núcleo subtalámico. Pacientes y métodos: Los pacientes han sido seleccionados y estudiados de acuerdo con el protocolo CAPSIT y la colocación de los electrodos se ha realizado con el apoyo de técnicas de fusión de imagen y microrregistro intraoperatorio. Resultados: Se ha observado una mejoría clínica significativa en la intensidad del off, tanto en actividades de la vida diaria (58 por ciento) como en el aspecto motor (44 por ciento), ha disminuido el tiempo de discinesias (86 por ciento), con desaparición total de las discinesias graves, y se ha reducido en un 44 por ciento la dosis equivalente de levodopa del tratamiento médico. Se ha observado también una mejoría del 58 por ciento en la calidad de vida de los pacientes, así como un beneficio de un 61 por ciento en la calidad de vida de los cuidadores. No se ha observado deterioro cognitivo y la morbilidad ha sido similar a la de otros equipos quirúrgicos. Conclusión: La estimulación bilateral del núcleo subtalámico en la enfermedad de Parkinson evolucionada es una terapia eficaz que mejora la calidad de vida de los pacientes y de sus cuidadores y permite la reducción de dosis de levodopa (AU)

[Neuropsychological changes and bilateral subthalamic deep brain stimulation in Parkinson's disease]. / Efectos cognitivos de la estimulación cerebral profunda sobre el núcleo subtalámico en la enfermedad de Parkinson.

INTRODUCTION: To investigate neuropsychiatric changes in Parkinson's disease (PD) patients after 12 months of bilateral subthalamic deep brain stimulation (DBS-STN). SUBJECTS: Nine out of 23 patients with PD subjected to DBS-STN were included. The mean follow-up of this cohort was 12 months, mean disease duration 14.2 5.5 years and mean UPDRS motor score in <> 43.2 13.7. METHODS: Patients were selected on the basis of CAPSIT criteria. They underwent bilateral implant of stimulators in STN under stereotactic conditions. Quality of life scale (PDQ 39), depression scale (Brev-Cet), frontal function test (Stroop, Wisconsin, verbal fluency) and memory evaluation (Barcelona test) were monitored at baseline in <> medication and after 12 months in <> medication/<> stimulation. RESULTS: The patients' motor scores improved on an average of 40.2 % (p = 0.0002) in <> medication situation and 58 % in quality of life scores. We observed a benefit in depression scores (52 %, p = 0.003). Immediate verbal memory improved as well, 25 % (p = 0.04) in recall memory and 14 % (p = 0.02) in recognition memory. No changes were observed in visual memory, verbal fluency and/or global cognitive tests. CONCLUSION: DBS-STN in PD patients seems to be an effective tool for improving their quality of life, due to its benefits on motor function, verbal memory and mood. Bilateral DBS-STN did not affect either verbal fluency or executive functions in our patients. Neuropsychological assessment is a good tool for selection and study of the operated patients.

Efectos cognitivos de la estimulación cerebral profunda sobre el núcleo subtalámico en la enfermedad de Parkinson / Neuropsychological changes and bilateral subthalamic deep brain stimulation in Parkinson's disease

Introducción: Se investigan cambios en la esfera cognitiva en pacientes con enfermedad de Parkinson (EP) tras 12 meses de estimulación cerebral profunda en el núcleo subtalámico (ECP NS). Pacientes: La serie recoge nueve de 23 pacientes con EP sometidos a ECP NS, con 12 meses de seguimiento. La duración media de la enfermedad era 14,2 ñ 5,5 años y la puntuación de UPDRS III en situación off de 43,2 ñ 13,7. Métodos: Se utilizaron los criterios CAPSIT para la inclusión de pacientes. Se les implantaron electrodos (bilateralmente) mediante cirugía estereotáctica. Se monitorizaron en situación basal (on medicación) y al año (on medicación, on estimulación) los siguientes parámetros: calidad de vida (PDQ 39), depresión (Brev-Cet), funciones frontales subcorticales (Stroop, Wisconsin, fluencia verbal) y valoración de la memoria (test de Barcelona). Resultados: Las puntuaciones en escalas motoras mejoraron un 40,2 por ciento (p = 0,0002) en off/on y un 58 por ciento en calidad de vida. Se observó una mejoría del 52 por ciento en escalas de depresión (p = 0,003). La memoria verbal inmediata también mejoró, un 25 por ciento en evocación (p = 0,04) y un 14 por ciento en reconocimiento (p = 0,02). No se observaron modificaciones en memoria visual, fluencia verbal y parámetros cognitivos globales. Conclusiones: La ECP NS es un tratamiento eficaz para mejorar la calidad de vida de enfermos parkinsonianos avanzados, debido a la mejoría que se produce en síntomas motores, depresivos y memoria verbal. En nuestra serie no hemos detectado cambios en las funciones ejecutivas ni en la fluencia verbal. El estudio neuropsicológico ayuda a una mejor selección y estudio de los pacientes intervenidos (AU)

Fallecimiento inexplicable de una adolescente con epilepsia generalizada primaria / Sudden unexpected death in an adolescent girl with idiopathic generalized epilepsy

Describimos una paciente que fallece súbitamente a los 13 años de edad, sin causa alguna que lo justifique, y cuyo único antecedente patológico es una epilepsia generalizada primaria, de baja frecuencia, carácter familiar y escasa traducción electroencefalográfica. Refieren también el antecedente de convulsiones febriles en la infancia temprana. Los exámenes complementarios y la autopsia judicial fueron negativos. Existe una distocia social pero la investigación del ambiente familiar descarta una causa intencional, ingesta de drogas o hábitos perjudiciales. Los exhaustivos estudios cardiológicos a los familiares con la misma sintomatología clínica descartan una cardiopatía familiar o un Síndrome de QT prolongado. El síndrome epiléptico familiar pudiera tratarse de una epilepsia generalizada primaria con crisis Gran Mal no forzosamente relacionadas con el sueño (random gran mal), o formar parte del grupo de epilepsias generali-zadas con convulsiones febriles plus (GEFS+). Desde el punto de vista clínico, la explicación mas razonable del fallecimiento es la de una muerte súbita e inesperada en epilepsia (SUDEP), cuya frecuencia en este tipo de epilepsias es inferior al 1 por mil personas-año, y cuyo mecanismo de acción mas probable es una bradicardia ictal, o una apnea central, seguida de asistolia, durante la crisis (AU)

Mobilization kinetics of peripheral blood progenitor cells after IAPVP-16 salvage chemotherapy plus G-CSF in lymphoproliferative disorders.

We have explored the efficacy of salvage chemotherapy combination, IAPVP-16 (ifosfamide 5 g/m2 on day 1; VP-16 100 mg/m2 on days 1-3; ara-C 1.2 g/m2/12 h on days 1 and 2; methylprednisolone 80 mg/m2 on days 1-5) plus G-CSF for PBPC mobilization. This protocol was used in 45 patients with relapsed or refractory lymphoproliferative diseases who underwent 85 leukaphereses. In 41 patients > 2 x 106/kg CD34+ cells were obtained after a median of two procedures. The median number of CD34+ cells harvested was 3.2 x 106/kg per apheresis and 8.4 x 106/kg per patient. Seven of 10 patients who had failed previous mobilization attempts achieved more than 2 x 106 CD34+ cells/kg in a maximum of three aphereses. A history of previous mobilization failure and a low platelet count (<150 x 109/l) negatively influenced the CD34+ cell yield in univariate and multivariate analyses. A good correlation was found between the circulating CD34+ cells/microl and the CD34+ cells and CFU-GM in the leukaphereses products (r = 0.93 and r = 0.73, P < 0.001), and > or =17 CD34+ cells/microl predicted the achievement of > 2 x 106/kg CD34+ cells in a single leukapheresis in more than 90% of cases. IAPVP-16 plus G-CSF may be specially indicated in tandem transplantations or CD34+ selection and in patients who have failed previous mobilization attempts.

Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time.

Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in individuals with blood type O compared with individuals with other ABO blood types. However, this relationship has been demonstrated only by association studies and not by linkage studies. Also, it is not clear whether the ABO locus exerts a functional effect directly on these plasma factors or whether the ABO locus is in linkage disequilibrium with another locus that controls these factors. To distinguish between these 2 possibilities, we applied new statistical methods combining linkage and association tests in a pedigree-based sample. In contrast to most previous studies that used the ABO phenotypes, our study used the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our results clearly showed significant linkage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phenotypes showed significant differences between OO and non-OO genotypes. In addition, vWF antigen exhibited significant differences between O heterozygotes and non-OO homozygotes. This study is unique because it used a combined linkage and association test, which indicated that the ABO locus itself has a functional effect on these plasma phenotypes.

Informe sobre la cirugía de la epilepsia / Report on the surgery of epilepsy

No disponible

[Opercular epileptic syndrome: an unusual form of benign partial epilepsy in childhood]. / El síndrome opercular epiléptico: una forma peculiar de epilepsia parcial benigna de la infancia con paroxismos rolándicos.

INTRODUCTION: Functional opercular syndrome in childhood is an exceptional form of presentation of benign partial epilepsy with centro-temporal rolandic spikes (BECRS). CLINICAL CASES: We studied the evolution of four patients, three of them followed for more than 15 years. Two were siblings, and their father suffered from BECRS with permanent language problems (verbal dyspraxia) and difficulty of protunding his tongue in adulthood. A third patient suffered benign familial neonatal convulsions (BFNC). In all four patients the actual illness begun as a BECRS with opercular troubles as an ictal phenomena. At about four years of age, the opercular disfunction became evident, with severe drooling, facial hypomobility and speech disturbance which waxed and vanished along weeks, months or years, apparently not ictal. Antiepileptic drugs not only were unable to control this situation but also, some of them, like carbamazepine, even worsened the opercular disfunction, increased the number of seizures and enhanced the neuropsychologic disfunction. Only clobazam could achieve the control on opercular disfunction. After 16 years, no further treatment was needed for all patients. There were some permanent sequelae, as speech and orolingual dyspraxia and different neuropsychologic problems. CONCLUSION: Of noteworth the best performance was attained by the patient treated with clobazam on monotherapy.

The placental blood program of the Barcelona Cord Blood Bank.

Cord blood has recently become an alternative to bone marrow transplantation, generating the need for cord blood banks where large numbers of frozen cord blood units can be stored. The Barcelona Cord Blood Bank (bcB) was created in October 1995. Initially, several methods for volume reduction were tested, including Ficoll, Percoll, Gelatin and HES sedimentation. Of these, HES sedimentation (88% +/- 11 CD34+ cells recovery) was the one chosen for routine banking. Up to November 1997, the bank has processed 754 units with a median of 1.05 x 10(9) nucleated cells and 2.5 x 10(6) CD34+ cells stored per unit. Nine of these units have been shipped for transplantation.

Collection of peripheral blood progenitor cells for autografting with low-dose cyclophosphamide plus granulocyte colony-stimulating factor.

BACKGROUND AND OBJECTIVE: The combination of high or intermediate-dose cyclophosphamide (CY) plus granulocyte colony-stimulating factor (G-CSF) is useful to mobilize hematopoietic progenitor cells to peripheral blood, but the patients require hospitalization. The aim of this study was to evaluate the efficiency of low-dose CY plus G-CSF (5 ug/kg/day s.c.) as an outpatient treatment in order to collect enough progenitor cells for hematopoietic rescue in autologous peripheral blood transplantation (APBSCT). DESIGN AND METHODS: We analyzed twenty-eight consecutively treated patients with lymphoma or multiple myeloma. The number of CD34+ cells in blood samples was determined from day +7. Leukapheresis (LKP) began when the absolute number of CD34+ cells in peripheral blood was > 2500/mL and the apheresis product was assayed for mononuclear cells (MNC), granulocyte-macrophage colony-forming units (CFU-GM), total nucleated cells (tNC) and CD34+ cells. RESULTS: Twenty-eight outpatients with advanced hematologic malignancies (13 non-Hodgkin lymphoma, NHL; 10 Hodgkin's disease, HD; and 5 multiple myeloma, MM), median age 44 years (range 23-65) received a single dose of CY (1.5 g/m2 i.v. day 0) followed by G-CSF (5 ug/kg/day s.c.) from day +1 to the end of LKP. Considering patients who had successful mobilization (64%), a median of 7.1 x 10(6)/kg CD34+ cells (range 3.5-11.9), 5.7 x 10(5)/kg CFU-GM (range 1.5-9.2), 4.4 x 10(8)/kg MNC (range 1.9-7.9) were collected. Treatment was well tolerated and none of these patients was hospitalized due to neutropenic fever. Only one patient received two packed red blood cells following chemotherapy. Autologous peripheral blood stem cell transplantation (APBSCT) has been performed in 18 patients (64%). The mean number of days to achieve > 0.5 x 10(9) PMN/L and > 20 x 10(9) PLT/L was 12 (10-17) and 12.6 (8-24), respectively. INTERPRETATION AND CONCLUSIONS: Considering a pre-established threshold of 2.5 x 10(6)/kg CD34+ cells to proceed to APBSCT, the mobilization therapy was successful in 64% of the patients but was unsuccessful in 10 patients (5 NHL, 4 HD and 1 MM). Hematopoietic recovery was complete and stable in all patients. Low-dose CY plus G-CSF is efficient to collect enough PBSC for hematopoietic rescue after myeloablative therapy in patients with lymphoprolipherative disorders or multiple myeloma.

Antiepileptic drugs and atypical evolution of idiopathic partial epilepsy.

Six patients with classic benign epilepsy of childhood with centrotemporal spikes, treated with carbamazepine (four patients) or sodium valproate (two patients) evolved atypically because the epileptic disorder, diffusion of the electroencephalographic (EEG) discharges during wakefulness, and continuous spike-and-wave during slow sleep associated with severe neuropsychologic abnormalities worsened. These features appeared after a seizure-free interval varying for 2 weeks to 1 year 6 months after initiating therapy and remitted when the previous anticonvulsant drug was discontinued and either substituted with another drug or the patient was left without any treatment. Once the initial antiepileptic drug was discontinued and after a period roughly proportional to the duration of the clinical-EEG complication, the evolution of the patients' seizures was not unusual for this type of epilepsy, with patients eventually becoming free of both seizures and medication and reaching normal school achievement. The clinical complications cannot be attributed solely to the drugs. It must also be related to the underlying substract (i.e., the specific epileptic syndrome involved) that in some patients becomes susceptible to atypical evolution when either product is administered.

Efficient peripheral blood stem cell mobilization with low-dose G-CSF (50 microg/m2) after salvage chemotherapy for lymphoma.

We compared the use of low-dose G-CSF (50 microg/m2/day), following salvage chemotherapy, for mobilization of PBSC with the results obtained in a comparable historical control group who received a standard dose of G-CSF (5 microg/kg/day, approximately 200 microg/m2/day). Thirty adult patients with relapsed or refractory lymphoma were treated with ifosfamide, VP-16, intermediate-dose Ara-C, methylprednisolone (IAPVP-16) and G-CSF 5 microg/kg/day (group A, n = 15) or 50 microg/m2/day (group B, n = 15) from day 6 until the end of leukaphereses. The duration of neutropenia and thrombocytopenia were equal in both groups. A median of two (1-3) leukaphereses were performed in both groups to harvest >3.5 x 10(6)/kg CD34+ cells. The numbers of circulating CD34+ cells on the first day of leukocyte recovery were similar in both groups in those patients mobilized after a first cycle of IAPVP-16. The numbers of circulating CD34+ cells were similar in patients mobilized after a first and after a second IAPVP-16 in group A. In the low-dose group (group B), however, the numbers of circulating CD34+ cells were significantly lower in those mobilized after a second than after a first course. Additionally, the product of the first leukapheresis contained significantly fewer CD34+ cells in those mobilized after a second course only in group B, with no differences in group A. Nevertheless, the final products harvested did not differ in the content of MNC, CFU-GM and CD34+ cells, suggesting that these differences are not clinically important. These results indicate that the use of low-dose G-CSF (50 microg/m2/day) is as effective as 5 microg/kg/day in accelerating neutrophil recovery and mobilizing CD34+ cells after a first cycle of IAPVP-16 salvage chemotherapy, resulting in a substantial decrease in costs, while more heavily pretreated patients may require higher doses of G-CSF for an equivalent mobilization.