Duodenal levodopa/carbidopa infusion therapy in patients with advanced Parkinson's disease leads to improvement in caregivers' stress and burden.

BACKGROUND: Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson's disease (PD). However, the impact of DLI on caregivers' stress and burden has not been reported. METHODS: We evaluated prospectively open-label seven advanced PD patients (65.7 ± 9.6 years, 71.4% men) treated with DLI. Schwab & England Activities of Daily Living Scale (ADLS), 39-item Parkinson's disease QoL Questionnaire Summary Index score (PDQ-39SI), Zarit Caregiver Burden Interview (ZCBI), and Caregiver Strain Index (CSI) were used. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 31.4 ± 7.9 months (range, 23-42). RESULTS: In patients, mean ± SD ADLS was increased from 50 ± 8.2 to 80 ± 11.6 (P = 0.014), and mean ± SD PDQ-39SI was decreased from 53.7 ± 11.9 to 33.6 ± 12.8 (P = 0.018). In caregivers, ZCBI decreased from 43 ± 13.3 to 20.7 ± 12.1 (P = 0.018) and CSI from 6.3 ± 2.5 to 1.6 ± 0.9 (P = 0.018). At baseline, 57.1% of caregivers reported moderate to severe burden (ZCBI 41-88) compared to 28.6% at the end of the follow-up (P = 0.015); at that time, no caregiver reported high level of stress (CSI ≥ 7) compared to 57.1% at baseline (P = 0.046). There were significant correlations between ZCBI and CSI improvement (r = 0.813, P = 0.026), ZCBI and PDQ-39SI (r = 0.875, P = 0.01), and ZCBI and ADLS (r = 0.813, P = 0.026). CONCLUSIONS: Duodenal levodopa infusion-related clinical improvement in patients with advanced PD leads to substantial reductions in caregivers' stress and burden.

Long-term exposure to duodenal levodopa/carbidopa infusion therapy improves quality of life in relation especially to mobility, activities of daily living, and emotional well-being.

BACKGROUND: Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson's disease (PD). However, in which aspects improve the patients their QoL has been poorly documented. METHODS: We evaluated 39-item Parkinson's disease Quality of Life Questionnaire Summary Index score (PDQ-39SI) changes analyzing its different domains in nine patients with advanced PD treated with DLI. RESULTS: All the patients (64.7 ± 11.1 years, 55.5% men) improved PDQ-39SI 6 months after beginning with DLI (29.7 ± 8.6, P = 0.008) and after median duration infusion of 25.3 ± 8.8 months (34.8 ± 11.2, P = 0.008) compared with baseline (55.6 ± 11.5). All domains except social support improved significantly at 6 months. Mobility (P = 0.012), activities of daily living (P = 0.015), and emotional well-being (P = 0.008) improved significantly at the end of the follow-up. CONCLUSIONS: DLI improves QoL in patients with advanced PD after short- and long-term exposure. Whereas all domains except social support improve after 6 months under DLI, only mobility, activities of daily living and emotional well-being improve significantly after long-term exposure to DLI.

Experiencia con la infusión continua de levodopa intraduodenal (Duodopa®) en pacientes con enfermedad de Parkinson avanzada en un hospital de segundo nivel asistencial / Experience with continuous levodopa enteral infusion (Duodopa®) in patients with advanced Parkinson's disease in a secondary level hospital

Introducción: La infusión continua de levodopa intraduodenal (Duodopa®) constituye una alternativa a la infusión subcutánea de apomorfina y a la cirugía en pacientes con enfermedad de Parkinson (EP) avanzada. Describimos nuestra experiencia con Duodopa® en pacientes con EP avanzada.Métodos: Realizamos un estudio epidemiológico, observacional, no intervencionista, poblacional, descriptivo, y retrospectivo, en el que se incluyen todos aquellos pacientes con EP avanzada tratados con Duodopa® por parte de la Sección de Neurología del Hospital A. Marcide de Ferrol hasta abril de 2010. Resultados: Once de un total de 12 pacientes seleccionados fueron tratados con Duodopa® [63,6% varones; edad media 62,7±10,6 (44-74) años]. En el momento de ser seleccionados para recibir Duodopa® presentaban: tiempo medio de evolución de enfermedad de 14,5±8,9 (3-34) años, dosis media de levodopa oral de 918,2±277,7 (450-1300) mg/día, y un estadio de Hoehn y Yahr de 3,7±0,5 (3-4). Nueve pacientes mantienen el tratamiento con Duodopa®. Hubo mejoría en las fluctuaciones motoras (72,7% gran mejoría) y discinesias (55,5% gran mejoría) con reducción del tiempo off/día (90,9%) y tiempo con discinesias/día (66,6%) después de un tiempo total de seguimiento con Duodopa® de 170,5 (3-31) meses. La mejoría en las escalas PDQ-39 y Schwab&England fue de 38,5±19,8 y 24±12,5 puntos respectivamente (p<0,05). La dosis media equivalente oral de levodopa (abril 2010) fue de 1683,4±295,8 (1234-2216) mg/día.Conclusiones: Duodopa® pudiera ser un tratamiento efectivo, seguro, y bien tolerado alternativo a la cirugía y apomorfina subcutánea en pacientes con EP avanzada adecuadamente seleccionados (AU)

Introduction: Continuous levodopa delivery by enteral infusion (Duodopa®) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa® therapy in 11 patients with advanced PD.Methods: We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa® was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain.Results: Nine patients received Duodopa® [62.7±10.6 (44-74) years, 63.6% male)]. Pre-Duodopa® clinical characteristics of patients were: disease duration 14.5±8.9 (3-34) years, oral levodopa dose 918.2±277.7 (450-1300) mg/day, and Hoehn and Yahr staging 3.7±0.5 (3-4). Nine patients are still receiving Duodopa®. Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3-31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5±19.8 and 24±12.5 respectively (P<0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4±295.8 (1234-2216) mg/day.Conclusions: Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease (AU)

[Experience with continuous levodopa enteral infusion (Duodopa(®)) in patients with advanced Parkinson's disease in a secondary level hospital]. / Experiencia con la infusión continua de levodopa intraduodenal (Duodopa(®)) en pacientes con enfermedad de Parkinson avanzada en un hospital de segundo nivel asistencial.

INTRODUCTION: Continuous levodopa delivery by enteral infusion (Duodopa(®)) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa(®) therapy in 11 patients with advanced PD. METHODS: We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa(®) was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain. RESULTS: Nine patients received Duodopa(®) [62.7±10.6 (44-74) years, 63.6% male)]. Pre-Duodopa(®) clinical characteristics of patients were: disease duration 14.5±8.9 (3-34) years, oral levodopa dose 918.2±277.7 (450-1300) mg/day, and Hoehn and Yahr staging 3.7±0.5 (3-4). Nine patients are still receiving Duodopa(®). Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3-31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5±19.8 and 24±12.5 respectively (P<0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4±295.8 (1234-2216) mg/day. CONCLUSIONS: Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Cell therapy: a therapeutic alternative to treat focal cartilage lesions.

BACKGROUND: Human mesenchymal stem cells (MSCs) are present in most of the tissue matrix, taking part in their regeneration when injury or damage occurs. The aim of this study was to investigate the presence of cells with pluripotential characteristics in synovial membranes from osteoarthritic (OA) patients and the capacity of these cells to differentiate to chondrocytes. METHODS: Synovial membranes (n = 8) from OA patients were digested with collagenase. Isolated cells were cultured with DMEM, 20% FBS, and FGFb10 ng/mL. Cells from second subculture were used to carry out phenotypic characterization experiments (flow cytometry analysis with 11 monoclonal antibodies) and chondrogenic differentiation experiments(micropellet cultured in chondrogenic medium). Chondrogenic differentiation of cells was assessment by quantification of cartilage extracellular matrix components by following techniques: Safranin O, Toluidine Blue, and Alcian Blue stains to detect proteoglycans and immunohistochemistry to detect type I and II collagen. RESULTS: Flow cytometry analyses showed that in our population more than 90% of cells were positive for MSC markers: CD29 (95%), CD44 (90%), CD73 (95%), CD90 (98%). Cells were negative for hematopoietic markers (CD11b, CD34, and CD45). Furthermore, cells showed positive stain to multipotent markers such as CD117 (c-kit) (98%), CD166 (74%), and STRO-1 (88%) and to quiescent satellite cells like PAX-7 (35%). The micropellet analyses showed that the culture of these cells with TGFbeta-3 for 2 and 3 weeks stimulates proteoglycan and collagen type II synthesis. Both molecules are characteristic of hyaline articular cartilage. CONCLUSION: In this work, we demonstrate the presence of a cellular population with MSC characteristics in synovial tissue from OA patients. As MSC takes part in reparative processes of adult tissues, these cells could play an important role in OA pathogenesis and treatment.