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1.
Milbank Q ; 97(2): 543-582, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30957311

RESUMEN

Policy Points Individuals with behavioral health (BH) conditions comprise a medically complex population with high costs and high health care needs. Considering national shortages of BH providers, primary care providers serve a critical role in identifying and treating BH conditions and making referrals to BH providers. States are increasingly seeking ways to address BH conditions among their residents. States funded by the Centers for Medicare and Medicaid Services under the first round of the State Innovation Models (SIM) Initiative all invested in BH integration. States found sharing data among providers, bridging professional divides, and overcoming BH provider shortages were key barriers. Nonetheless, states made significant strides in integrating BH care. Beyond payment models, a key catalyst for change was facilitating informal relationships between BH providers and primary care physicians. Infrastructure investments such as promoting data sharing by connecting BH providers to a health information exchange and providing tailored technical assistance for both BH and primary care providers were also important in improving integration of BH care. CONTEXT: Increasing numbers of states are looking for ways to address behavioral health (BH) conditions among their residents. The first round of the State Innovation Models (SIM) Initiative provided financial and technical support to six states since 2013 to test the ability of state governments to lead health care system transformation. All six SIM states invested in integration of BH and primary care services. This study summarizes states' progress, challenges, and lessons learned on BH integration. Additionally, the study reports impacts on expenditure, utilization, and quality-of-care outcomes for persons with BH conditions across four SIM states. METHODS: We use a mixed-methods design, drawing on focus groups and key informant interviews to reach conclusions on implementation and quantitative analysis using Medicaid claims data to assess impact. For three Medicaid accountable care organization (ACO) models funded under SIM, we used a difference-in-differences regression model to compare outcomes for model participants with BH conditions and an in-state comparison group before-and-after model implementation. For the behavioral health home (BHH) model in Maine, we used a pre-post design to assess how outcomes for model participants changed over time. FINDINGS: Informal relationship building, tailored technical assistance, and the promotion of data sharing were key factors in making progress. After three years of implementation, the growth in total expenditures was less than the comparison group by $128 (-$253, -$3; p < 0.10) and $62 (-$87, -$36; p < 0.001) per beneficiary per month for beneficiaries with BH conditions attributed to an ACO in Minnesota and Vermont, respectively. Likewise, there were reductions in emergency department use for ACO participants in all three states after two to four years of implementation. However, there was no improvement in BH-related quality metrics for ACO beneficiaries in all three states. Although participants in the BHH model had increased expenditures after two years of implementation, use of primary care and specialty care services increased by 3% and 8%, respectively, and antidepressant medication adherence also improved. CONCLUSIONS: The SIM Round 1 states made considerable progress in integrating BH and primary care services, and there were promising findings for all models. Taken together, there is some evidence that Medicaid payment models can improve patterns of care for beneficiaries with BH conditions.


Asunto(s)
Prestación Integrada de Atención de Salud , Trastornos Mentales , Modelos Organizacionales , Atención Primaria de Salud , Reforma de la Atención de Salud , Humanos , Medicare , Trastornos Mentales/diagnóstico , Derivación y Consulta , Estados Unidos
2.
JAMA Dermatol ; 150(6): 621-7, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24696010

RESUMEN

IMPORTANCE: Topical corticosteroids are the current first-line therapy for vulvar lichen sclerosus (VLS). UV-A1 phototherapy may be a promising alternative treatment option, but controlled studies are lacking. OBJECTIVE: To compare the efficacy of high-potent topical corticosteroids with UV-A1 phototherapy in the treatment of VLS. DESIGN, SETTING, AND PARTICIPANTS: A 2-arm randomized clinical trial was conducted at a university hospital dermatology department according to the intention-to-treat principle with last observation carried forward. The study population comprised 30 female patients with VLS. INTERVENTIONS: Treatment of VLS with clobetasol propionate, 0.05%, ointment applied once daily for 3 months or medium-dose UV-A1 (50 J/cm²) home-based phototherapy, performed 4 times weekly for 3 months. MAIN OUTCOMES AND MEASURES: Mean relative reduction of the total clinician's score (TCS) was considered the primary outcome measure. Secondary outcome measures included the reduction of pruritus and burning and/or pain according to a visual analog scale (VAS), a health-related quality of life score (Skindex-29), 20-MHz ultrasonography, and histopathological analysis before and after 3 months of therapy. RESULTS: Fifteen patients were randomized in each treatment arm, and 2 patients dropped out in both treatment arms. After therapy, both therapies resulted in a significant decrease in mean TCS (51.4% [95% CI, 39.7% to 63.0%] for clobetasol ointment [P < .001] and 35.6% [95% CI, 18.2% to 53.1%] for UV-A1 phototherapy [P = .006]). No significant difference was found between both treatments (P > .05). The Skindex-29 (mean difference [MD], 29.6 [95% CI, 7.9 to 51.2] [P = .009]) and the VAS score for pruritus (MD, 4.6 [95% CI, 1.5 to 7.7] [P = .005]) and burning and/or pain (MD, 4.2 [95% CI, 1.9 to 6.6] [P = .001]) significantly decreased after clobetasol treatment. After UV-A1 phototherapy, the VAS score for burning and/or pain (MD, 3.2 [95% CI, 0.7 to 5.7] [P = .01]) was also significantly reduced; however, there was no significant reduction in pruritus (MD, 2.1 [95% CI, 0.5 to 3.7] [P = .16]) and in the Skindex-29 score (MD, 4.9 [95% CI, -12.6 to 22.4] [P > .99]). A significant reduction of the corium thickness and a significant increase in dermal density in 20-MHz ultrasonography as well as significant histopathological reduction of the inflammatory infiltrate was observed after clobetasol treatment but not after UV-A1 phototherapy. CONCLUSIONS AND RELEVANCE: Although resulting in a significant clinical improvement, UV-A1 phototherapy was inferior to the current gold standard treatment with topical high-potent corticosteroids with respect to practicability, relief of itch, and improvement in quality of life. UV-A1 phototherapy may be considered a potential second-line treatment for VLS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01400022.


Asunto(s)
Clobetasol/administración & dosificación , Glucocorticoides/administración & dosificación , Terapia Ultravioleta , Liquen Escleroso Vulvar/tratamiento farmacológico , Liquen Escleroso Vulvar/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven
4.
Clin Exp Immunol ; 171(2): 171-85, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23286944

RESUMEN

Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Linfocitos T Reguladores/inmunología , Vitamina D/sangre , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , Animales , Proliferación Celular , Células Cultivadas , Análisis Mutacional de ADN , Proteínas de Unión al ADN/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Interleucina-4/metabolismo , Activación de Linfocitos/genética , Ratones , Persona de Mediana Edad , Proyectos Piloto , Polimorfismo Genético , Factores de Transcripción/genética
5.
Klin Monbl Augenheilkd ; 229(10): 979-86, 2012 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-23096142

RESUMEN

BACKGROUND: The studies of Kämpf et al. suggested an efficiency of a computer-based stimulation therapy by drifting sinus gratings in patients with anisometropic and/or strabismic amblyopia but provided no clear evidence. This is the first trial with amblyopic patients without previous treatment at the beginning of amblyopia therapy. METHODS: A prospective, randomised, single-blinded, placebo-controlled study of n = 15 patients with anisometropic and/or strabismic amblyopia without previous treatment was performed. Age of the patients was between 4 and 10 years, mean 6.3 years (± 2.0), all after full correction of refraction errors and refractive adaptation. Stimulation therapy was performed 5 times a week over 4 weeks, respectively 2 × 20 min, a drifting sinus grating of constant spatial and temporal frequency was combined with computer games (n = 8). Control group had only computer games with a neutral background (n = 7). In both groups patching was only done in stimulation times. RESULTS: Stimulation and control group did not differ due to age, gender, and cause of amblyopie, baseline visual acuity, and time of wearing glasses. There was no significant difference in the development of visual acuity over the stimulation period between stimulation and control groups. CONCLUSIONS: Stimulation therapy with drifting sinus gratings did not improve the development of visual acuity in the first phase of amblyopia treatment combined with minimal occlusion therapy. Accordingly, the stimulation therapy is not adequate to replace sufficient occlusion therapy. Whether this therapy could support patching therapy and improve acuity development in later therapy phases cannot be assumed from this trial.


Asunto(s)
Ambliopía/diagnóstico , Ambliopía/rehabilitación , Biorretroalimentación Psicológica/métodos , Terapia Asistida por Computador/métodos , Juegos de Video , Niño , Preescolar , Femenino , Humanos , Masculino , Efecto Placebo , Método Simple Ciego , Resultado del Tratamiento
6.
Artículo en Inglés | MEDLINE | ID: mdl-22454689

RESUMEN

Objective. To investigate the effects of an 8-week meditation program on perceived stress, sleep, mood, and related outcomes in adults with cognitive impairment and their caregivers. Methods. Community-dwelling adults with a diagnosis of mild cognitive impairment or early-stage Alzheimer's disease, together with their live-in caregivers, were enrolled in the study. After a brief training, participants were asked to meditate for 11 minutes, twice daily for 8 weeks. Major outcomes included measures of perceived stress (Perceived Stress Scale), sleep (General Sleep Disturbance Scale), mood (Profile of Mood States), memory functioning (Memory Functioning Questionnaire), and blood pressure. Participants were assessed pre- and post-intervention. Results. Ten participants (5 of 6 dyads) completed the study. Treatment effects did not vary by participant status; analyses were thus pooled across participants. Adherence was good (meditation sessions completed/week: X = 11.4 ± 1.1). Participants demonstrated improvement in all major outcomes, including perceived stress (P < 0.001), mood (overall, P = 0.07; depression, P = 0.01), sleep (P < 0.04), retrospective memory function (P = 0.04), and blood pressure (systolic, P = 0.004; diastolic, P = 0.065). Conclusions. Findings of this exploratory trial suggest that an 8-week meditation program may offer an acceptable and effective intervention for reducing perceived stress and improving certain domains of sleep, mood, and memory in adults with cognitive impairment and their caregivers.

7.
Ann Rheum Dis ; 69(8): 1502-10, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20511611

RESUMEN

BACKGROUND: Oxidative stress is proposed as an important factor in osteoarthritis (OA). OBJECTIVE: To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. METHODS: SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin-Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. RESULTS: All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin-Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. CONCLUSION: This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function.


Asunto(s)
Artritis Experimental/enzimología , Regulación hacia Abajo , Osteoartritis de la Cadera/enzimología , Superóxido Dismutasa/biosíntesis , Animales , Secuencia de Bases , Cartílago Articular/enzimología , Células Cultivadas , Condrocitos/enzimología , Metilación de ADN , Progresión de la Enfermedad , Cuello Femoral/enzimología , Regulación Enzimológica de la Expresión Génica , Cobayas , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/biosíntesis , Metaloproteinasa 13 de la Matriz/biosíntesis , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Superóxido Dismutasa/deficiencia , Superóxido Dismutasa/genética
8.
J Nutr Health Aging ; 12(1): 18-21, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18165840

RESUMEN

The purpose of this paper is to grade research evidence supporting nutritional interventions for persons with early stage dementias and to report the recommendations of a consensus panel. Thirty four studies were reviewed in the areas of dietary restriction, antioxidants, and Mediterranean diet with strong support from epidemiological studies found in all three areas. The body of evidence to support nutritional interventions in the prevention and treatment of AD is growing and has potential as a treatment modality following translational studies.


Asunto(s)
Enfermedad de Alzheimer/terapia , Dieta , Desnutrición/prevención & control , Terapia Nutricional , Anciano , Enfermedad de Alzheimer/complicaciones , Consenso , Progresión de la Enfermedad , Medicina Basada en la Evidencia , Humanos , Desnutrición/etiología , Medición de Riesgo , Factores de Riesgo
9.
AIDS Patient Care STDS ; 20(4): 238-44, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16623622

RESUMEN

Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum concentrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100-250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [OR(unadj)] 3.0, 95% confidence interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens (OR(unadj) 3.57; 95% CI, 0.72-24.1; p = 0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens (OR(adj) and 95% CIs undefined; p = 0.08). Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event--discontinuation for toxicity, treatment- emergent adverse event or abnormal laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI versus 13 (12%) of 105 on low-dose ddI developed any event (OR(unadj) 2.81; 95% CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was more frequently associated with drug-related toxicity, adverse events, and treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF was generally well tolerated in these HIV-infected persons.


Asunto(s)
Adenina/análogos & derivados , Didanosina/administración & dosificación , Didanosina/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Organofosfonatos/administración & dosificación , Organofosfonatos/efectos adversos , Adenina/administración & dosificación , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Didanosina/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Organofosfonatos/uso terapéutico , Estudios Retrospectivos , Tenofovir
10.
Eur J Cancer Care (Engl) ; 14(4): 342-52, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16098119

RESUMEN

In the UK, recent guidance on supportive and palliative care has acknowledged the contribution of voluntary organizations, including their role in palliative day care. Similarly, research has tended to focus exclusively on palliative day care as opposed to comparable care for people with cancer, regardless of prognosis. This paper describes a case record review study conducted at a nurse-led voluntary sector cancer day care centre. The study focused on referrals over a one-year period in terms of user demographics, referral sources/reasons and subsequent care given. It was found that 220 referrals (including 106 self-referrals) were made during the year. Of these, 70.9% were people with cancer and the remainder were carers/bereaved people. Those referred broadly reflected national statistics on age, gender and cancer diagnosis. Carers were rarely referred by professionals, few lived in inner-city neighbourhoods and some had no informal support. Non-specific referral reasons, such as 'support', tended to be translated into specific therapies, such as complementary therapies and counselling, at initial assessment. Care offered at the centre appeared to supplement and complement that provided by local statutory services. The study raised issues for practice and further research that may be relevant to those working in similar centres.


Asunto(s)
Instituciones Oncológicas/organización & administración , Cuidadores , Centros de Día/organización & administración , Neoplasias/enfermería , Derivación y Consulta , Voluntarios , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Aflicción , Cuidadores/estadística & datos numéricos , Terapias Complementarias/métodos , Consejo/métodos , Centros de Día/estadística & datos numéricos , Inglaterra , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Derivación y Consulta/estadística & datos numéricos , Trastornos Respiratorios/terapia , Distribución por Sexo , Factores Socioeconómicos
11.
Oecologia ; 134(1): 46-54, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12647178

RESUMEN

Stable isotopes were used to evaluate water sources for co-occurring Jeffrey pine (Pinus jeffreyi Grev & Balf.) and greenleaf manzanita (Arctostaphylos patula Greene) in the southern Sierra Nevada, California, where soils averaged only 75 cm thick but were underlain by up to 5 m of weathered granitic bedrock. Soils and underlying weathered bedrock were sampled three times during both the 1997 and 1998 growing seasons, in 25 cm increments, from 0 to 400 cm or until hard bedrock was reached, and plant stem tissue was sampled simultaneously. Extracted water from the soil/bedrock substrate and plant tissue was analyzed for delta(18)O and/or deltaD, and depth of water source was determined by inference in conjunction with moisture status of the substrate. Water source utilization over the growing seasons for both plants generally followed a pattern similar to that observed for water depletion. Predominant water use was initially from the surface soils. Progressively deeper water sources, including weathered bedrock to a depth of several meters, were exploited as the season progressed and the overlying substrate was depleted of moisture. Early in the growing season, stable isotope values were slightly lower for pine than for manzanita (e.g., average deltaD in June 1997 was -81 per thousand for pine and -77 per thousand for manzanita), and suggest that the functional rooting depth for pine may have been slightly greater than for manzanita. In September 1997, manzanita deltaD values averaged -57 per thousand while pine values averaged -85 per thousand, indicating that manzanita opportunistically utilized summer precipitation while pine used more dependable bedrock water. In 1998, soils remained moist through July due to a late snowfall. Unlike the previous year, pine and manzanita deltaD values were not significantly different in mid- and late-growing season, and both plants exploited bedrock-derived water as soil water was depleted. Water held within bedrock was essential for meeting plant transpirational requirements over the summer drought.


Asunto(s)
Arctostaphylos/metabolismo , Sedimentos Geológicos , Pinus/metabolismo , Suelo/análisis , Agua/metabolismo , Adaptación Fisiológica , California , Transpiración de Plantas , Lluvia , Estaciones del Año , Factores de Tiempo
12.
Complement Ther Med ; 9(4): 246-9, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12184354

RESUMEN

Acupuncture treatment and control group interventions in parallel-group randomised trials of acupuncture are not always precisely reported. In an attempt to improve standards, an international group of experienced acupuncturists and researchers devised a set of recommendations, designating them STRICTA: STandards for Reporting Interventions in Controlled Trials of Acupuncture. In a further consensus-building round, the editors of several journals helped redraft the recommendations. These follow the Consolidated Standards for Reporting Trials (CONSORT) format, acting as an extension of the CONSORT guidelines for the specific requirements of acupuncture studies. Participating journals are publishing the STRICTA recommendations and requesting prospective authors to adhere to them when preparing reports for publication. Other journals are invited to adopt these recommendations. The intended outcome is that interventions in controlled trials of acupuncture will be more adequately reported, thereby facilitating an improvement in critical appraisal, analysis and replication of trials.


Asunto(s)
Terapia por Acupuntura , Ensayos Clínicos Controlados como Asunto , Edición/normas , Guías como Asunto , Humanos , Cooperación Internacional
13.
J Manipulative Physiol Ther ; 22(8): 523-9, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10543582

RESUMEN

OBJECTIVE: To determine to what degree chiropractic clinics are complying with the Americans with Disabilities Act (ADA), which mandates that health care clinics be accessible to the disabled. METHODS: A survey was developed and mailed to 200 chiropractic clinics in Orange and Los Angeles counties. The survey asked about the essential necessities for health care clinics to be accessible to the wheelchair-bound, the blind, and the deaf. It also sought to discover how many disabled patients these clinics were treating and the attitudes of practitioners and staff toward this population. RESULTS: The response rate was 50.5%. Accessibility for the wheelchair-bound was high. Accessibility for the blind was limited by a lack of Braille signs. Accessibility to the deaf was limited by lack of telecommunications device for the deaf or use of sign language interpreters. Most clinics were treating few or no disabled patients and did not perceive a need to become more accessible. CONCLUSION: There appears to be poor compliance with the ADA in chiropractic clinics in Los Angeles and Orange counties. Although data are lacking, it appears likely that the disabled population is being underserved by the chiropractic profession. Education for chiropractors on the rights and needs of the disabled population is necessary to give this group equal access to chiropractic health care.


Asunto(s)
Quiropráctica/estadística & datos numéricos , Personas con Discapacidad , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Actitud del Personal de Salud , Ceguera , California , Sordera , Encuestas de Atención de la Salud , Humanos , Encuestas y Cuestionarios , Silla de Ruedas
14.
Vaccine ; 16(6): 590-600, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9569470

RESUMEN

Effective immunoprophylaxis directed against the pre-erythrocytic stages of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic background. In order for a synthetic peptide malaria vaccine to meet these requirements, problems associated with genetic restriction, peptide chemistry, adjuvant formulation and physiochemical characterization of the final synthetic vaccine product must first be overcome. To address these issues, five polyoxime vaccine candidates have been constructed by ligating purified peptide epitopes of the P. falciparum CS protein to a branched template via oxime bonds. All five constructs, including two based on templates containing the synthetic adjuvant tripalmitoyl-S-glyceryl cysteine (Pam3Cys), were of sufficient purity for characterization by mass spectrometry. The immunogenicity of the malaria polyoximes in different murine strains was compared to that of multiple antigen peptide (MAP) constructs synthesized by standard step-wise synthesis. A tri-epitope polyoxime-Pam3Cys construct, based on the repeats and a universal T-cell epitope that contains both helper and CTL epitopes of the CS protein, was shown to be a precisely-defined synthetic malaria vaccine candidate that was highly immunogenic in murine strains of diverse H-2 haplotypes.


Asunto(s)
Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Vacunas contra la Malaria/inmunología , Oximas/inmunología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Vacunas Sintéticas/inmunología , Adyuvantes Inmunológicos/farmacología , Compuestos de Alumbre/farmacología , Secuencia de Aminoácidos , Animales , Fenómenos Químicos , Química Física , Cisteína/análogos & derivados , Cisteína/farmacología , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Datos de Secuencia Molecular
15.
Proc Natl Acad Sci U S A ; 94(10): 4925-30, 1997 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-9144166

RESUMEN

Steroids produced locally in brain (neurosteroids), including dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s and potentially could play a role in neurosteroid metabolism. To examine the catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia virus vector. Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography. The expressed enzyme was less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol, with low to undetectable activity against progesterone, corticosterone, and testosterone. On gas chromatography and mass spectrometry of the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with Cyp7b extracts the extent of release of radioactivity into the medium suggested that hydroxylation was preferentially at the 7alpha position. Brain extracts also efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy pregnenolone.


Asunto(s)
17-alfa-Hidroxipregnenolona/metabolismo , Encéfalo/enzimología , Sistema Enzimático del Citocromo P-450/metabolismo , Deshidroepiandrosterona/análogos & derivados , Esteroide Hidroxilasas , 17-alfa-Hidroxipregnenolona/análogos & derivados , Animales , Sistema Enzimático del Citocromo P-450/biosíntesis , Familia 7 del Citocromo P450 , ADN Complementario , Deshidroepiandrosterona/metabolismo , Vectores Genéticos , Células HeLa , Hipocampo/enzimología , Humanos , Cinética , Ratones , Ratas , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Transfección , Virus Vaccinia
16.
J Nat Prod ; 60(4): 356-60, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9134744

RESUMEN

The pollen of rye (Secale cereale) was shown to contain a biologically highly active family of glycosides called the secalosides. Secalosides A and B (1), both of molecular formula C46H51-NO24, were found to be epimeric esters of (2-oxo-3-indolyl)acetic acid (4). They are made up, in addition to this heterocyclic aglycon I (4), of three hexose building blocks and a carbocyclic aglycon II, which is an indan-derived dicarboxylic acid (5). In aqueous solution, secalosides A and B interchanged by epimerization at the chiral center of 4. A further epimeric pair, secalosides C and D (2), contain one additional glucose building block. Secalosides A and B, the racemic aglycon I (4), and 2-oxo-1,2,3, 4-tetrahydroquinoline-4-carboxylic acid (3), which results from 4 by hydrolytic rearrangement, exhibited significant antitumor activity against S180 sarcoma in vivo. IC50 values obtained were about 5 micrograms/mouse for the secalosides and 1 microgram/mouse for 3 and 4.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Ácidos Indolacéticos/aislamiento & purificación , Polen/química , Secale/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cromatografía Líquida de Alta Presión , Glucósidos/química , Glucósidos/farmacología , Hidrólisis , Ácidos Indolacéticos/química , Ácidos Indolacéticos/farmacología , Isomerismo , Ratones , Peso Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Ultravioleta , Células Tumorales Cultivadas
17.
J Pept Sci ; 2(1): 66-72, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-9225247

RESUMEN

Synthetic lipopeptides are showing promise as vaccine candidates, but until now it has been very difficult to prepare them in homogeneous form. We describe the synthesis and characterization of a new water-soluble, four-branched template with a built-in lipophilic adjuvant (Pam3Cys). Through the use of oxime chemistry, we attached four copies of an unprotected influenza virus peptide and characterized the product (13 kDa) by reversed-phase HPLC and electrospray ionization mass spectrometry. Several other such constructions were made using the new template and different peptides. We seem to have a general method for making synthetic lipopeptides in homogeneous form.


Asunto(s)
Adyuvantes Inmunológicos/metabolismo , Ácido Azetidinocarboxílico/análogos & derivados , Cisteína/análogos & derivados , Vacunas contra la Influenza/síntesis química , Lipoproteínas/metabolismo , Vacunas Sintéticas , Proteínas Virales/inmunología , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Cisteína/metabolismo , Espectrometría de Masas , Datos de Secuencia Molecular , Peso Molecular , Orthomyxoviridae , Conformación Proteica , Moldes Genéticos
18.
J Med Chem ; 38(4): 735-8, 1995 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-7861421

RESUMEN

One fraction, designated FV-7, in the water soluble ingredient of the pollen extract Cernilton was found to be inhibitory to the growth of a prostate cancer cell line. Characterization of FV-7 by high-resolution mass spectrometry and nuclear magnetic resonance identified the fraction as hydroxamic acid, 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA). To confirm this further, we synthesized an authentic sample of DIBOA and found subsequently that the synthetic DIBOA was structurally indistinguishable from FV-7. Furthermore, in a separate experiment we compared the in vitro effects of FV-7 and DIBOA on the growth of a prostate cancer cell line and found that in both cases the effect was inhibitory and that the inhibition curves obtained for both compounds were virtually identical.


Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Extractos Vegetales/química , Antineoplásicos Fitogénicos/aislamiento & purificación , División Celular/efectos de los fármacos , Humanos , Ácidos Hidroxámicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Neoplasias de la Próstata/patología , Secale , Espectrofotometría Ultravioleta , Células Tumorales Cultivadas
19.
J Manipulative Physiol Ther ; 17(3): 174-6, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-8006532

RESUMEN

OBJECTIVE: To discuss the case of a patient who received an electrical shock injury to the back of his head and was co-managed by a neurologist and a chiropractor. The common manifestations of electrical shock injuries are presented. CLINICAL FEATURES: The patient was a 31-yr-old man. His initial symptoms consisted of headaches, dizziness, pain in the suboccipital area, tingling down both arms to the hands, nausea, blurred vision, increased sweating, chest pain, loss of appetite and memory lapses. The patient received a neurological examination, MRI of the brain, EEG, brain stem auditory evoked response and EKG. The neurologist's diagnosis was post-traumatic head syndrome following electrocution. INTERVENTION AND OUTCOME: He was treated by a neurologist and a chiropractor, with fair results. Chiropractic treatments were directed toward correcting the fixations, fibrotic tissue and joint proprioception in his neck using manipulation, physical therapy and active care exercises. CONCLUSION: Electrical shocks commonly cause immediate damage to the heart, nervous system and musculoskeletal system. They can also cause delayed complications days to years later, including cholelithiasis, cataracts and nervous system conditions such as ALS. Chiropractors can play an important role in managing the musculoskeletal manifestations of electrical shock injuries.


Asunto(s)
Quiropráctica , Traumatismos Craneocerebrales/terapia , Traumatismos por Electricidad/terapia , Adulto , Encéfalo/patología , Vértebras Cervicales/fisiología , Traumatismos por Electricidad/diagnóstico , Electrocardiografía , Electroencefalografía , Humanos , Imagen por Resonancia Magnética , Masculino , Modalidades de Fisioterapia/métodos , Rango del Movimiento Articular
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