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AIM: Canakinumab (CAN), a selective, fully human, anti-IL-1ß monoclonal antibody, has demonstrated long-term benefits in gouty arthritis (GA) patients, who have contraindications for, or are unresponsive or intolerant of, non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine (two trials:ß-RELIEVED [n = 228]; ß-RELIEVED II [n = 226]). The trials collected different responses, including patient-reported outcomes (PRO). A composite response end-point (CRE) was used to interpret each patient's overall response to treatment. METHODS: Data from ß-RELIEVED trials were pooled for this retrospective analysis. The CRE representing overall change in GA-related health outcomes, from baseline to 12 weeks, included clinical markers; PROs from the Gout Impact Scale (GIS); and the SF-36 bodily pain scale. Response to each variable (i.e. markedly important difference) was determined a priori. Variable values [1 (responder) or 0 (non-responder)] were summed to create a CRE score for each patient. RESULTS: For eight of 12 variables measured, the percentage of CAN responders was significantly greater than for TA (p < 0.05). On average, patients receiving CAN met a higher percentage of response criteria (65%) than patients receiving triamcinolone acetonide (TA) (49%), p < 0.001. Mean CRE scores were significantly higher for CAN vs. TA (mean [SD]; 4.7 [2.7] vs. 3.7 [2.4], p < 0.001). Treatment differences remained even after serially removing individual responder variables and domains from the composite end-point, indicating that the differences between CAN and TA were robust. CONCLUSION: CAN was superior to TA across multiple health-outcome variables comprising clinical markers and PRO over 12 weeks in patients contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine.
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Anticuerpos Monoclonales/uso terapéutico , Artritis Gotosa/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Adulto , Anciano , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Artritis Gotosa/mortalidad , Femenino , Humanos , Interleucina-1beta/farmacología , Interleucina-1beta/uso terapéutico , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Estudios Retrospectivos , Triamcinolona Acetonida/farmacologíaRESUMEN
OBJECTIVE: To study health care utilization patterns in patients with gout. METHODS: In a gout population from primary care and rheumatology clinics in 3 U.S. metropolitan cities, we collected data on gout-related utilization (primary care, rheumatology, urgent care, emergency room, and other) in the past year. We evaluated the association of comorbidities, age, gender, gout characteristics (time since last gout attack and tophi), and gout severity ratings (mean of serum uric acid, patient-rated, and physician-rated gout severity) and with emergency/urgent care and primary care utilization using regression and correlation analyses. RESULTS: Of the 296 patients who reported visiting at least 1 type of health practitioner for gout in the past year, the percentage of patients utilizing the service at least once and annual utilization rates among utilizers were as follows: primary care physician, 60%, 3.0 ± 3.4; nurse practitioner/physician assistant, 26%, 2.7 ± 2.5; rheumatologist, 51%, 3.7 ± 5.7; urgent care, 23%, 2.1 ± 2.2; emergency room, 20%, 2.0 ± 1.7; and hospitalization, 7%, 2.1 ± 1.4. Higher overall gout severity was associated with greater use of each resource type and with overall gout-related utilization. Nonemergency/nonurgent care utilization (primary care physician, nurse practitioner, physician's assistant, and rheumatologist for gout) was the strongest predictor of gout-related emergency/urgent care utilization. Patients with more comorbidities had greater gout-related primary care utilization. CONCLUSIONS: Overall gout severity was associated with all types of gout-related utilization. This may help to screen high utilizers for targeted behavioral and therapeutic interventions. Having a higher number of comorbid conditions was a risk factor for higher gout-related primary care utilization.
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Atención a la Salud/estadística & datos numéricos , Gota/terapia , Personal de Salud/estadística & datos numéricos , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Comorbilidad/tendencias , Femenino , Gota/patología , Gota/fisiopatología , Humanos , Masculino , Índice de Severidad de la Enfermedad , Estados Unidos , Salud UrbanaRESUMEN
This review examines the impact of moderate to severe dry eye disease on daily life and medical-resource utilization. The results suggest that current treatment paradigms can lead to unacceptable costs in both quality of life and progressive use of healthcare resources. Evidence linking this disease to T-cell-mediated inflammatory processes lays the foundation for understanding the clinical benefits of topical cyclosporine, an immunomodulatory and anti-inflammatory agent.
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Síndromes de Ojo Seco , Adulto , Anciano , Costo de Enfermedad , Síndromes de Ojo Seco/economía , Síndromes de Ojo Seco/epidemiología , Síndromes de Ojo Seco/inmunología , Síndromes de Ojo Seco/terapia , Femenino , Humanos , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire. METHODS: Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining. RESULTS: Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach alpha) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage. CONCLUSIONS: The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.
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Síndromes de Ojo Seco/diagnóstico , Técnicas de Diagnóstico Oftalmológico , Síndromes de Ojo Seco/clasificación , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
The role of oxidative damage in neurodegenerative disease was investigated in mice lacking cytoplasmic Cu/Zn superoxide dismutase (SOD), created by deletion of the SOD1 gene (SOD1(-/-)). SOD1(-/-) mice developed a chronic peripheral hindlimb axonopathy. Mild denervation of muscle was detected at 2 months, and behavioral and physiological motor deficits were present at 5-7 months of age. Ventral root axons were shrunken but were normal in number. The somatosensory system in SOD1(-/-) mice was mildly affected. SOD1(-/-) mice expressing Cu/Zn SOD only in brain and spinal cord were generated using transgenic mice expressing mouse SOD1 driven by the neuron-specific synapsin promoter. Neuron-specific expression of Cu/Zn SOD in SOD1(-/-) mice rescued motor neurons from the neuropathy. Therefore, Cu/Zn SOD is not required for normal motor neuron survival, but is necessary for the maintenance of normal neuromuscular junctions by hindlimb motor neurons.
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Cobre/fisiología , Miembro Posterior/inervación , Neuronas Motoras/enzimología , Unión Neuromuscular/fisiología , Superóxido Dismutasa/fisiología , Zinc/fisiología , Animales , Axones/enzimología , Axones/fisiología , Conducta Animal , Técnicas de Cultivo , Modelos Animales de Enfermedad , Electrofisiología , Ratones , Ratones Noqueados , Modelos Genéticos , Neuronas Motoras/fisiología , Músculos/anatomía & histología , Músculos/metabolismo , Conducción Nerviosa , Unión Neuromuscular/enzimología , Perfusión , Nervios Periféricos/fisiología , Regiones Promotoras Genéticas , Tinción con Nitrato de Plata , Factores de Tiempo , Distribución TisularRESUMEN
The effects of dietary cholesterol on brain amyloid precursor protein (APP) processing were examined using an APP gene-targeted mouse, genetically humanized in the amyloid beta-peptide (Abeta) domain and expressing the Swedish familial Alzheimer's disease mutations. These mice express endogenous levels of APP holoprotein and abundant human Abeta. Increased dietary cholesterol led to significant reductions in brain levels of secreted APP derivatives, including sAPPalpha, sAPPbeta, Abeta1-40, and Abeta1-42, while having little to no effect on cell-associated species, including full-length APP and the COOH-terminal APP processing derivatives. The changes in levels of sAPP and Abeta in brain all were negatively correlated with serum cholesterol levels and levels of serum and brain apoE. These results demonstrate that secreted APP processing derivatives and Abeta can be modulated in the brain of an animal by diet and provide evidence that cholesterol plays a role in the modulation of APP processing in vivo. APP gene-targeted mice lacking apoE, also have high serum cholesterol levels but do not show alterations in APP processing, suggesting that effects of cholesterol on APP processing require the presence of apoE.
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Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Colesterol en la Dieta/farmacología , Enfermedad de Alzheimer/genética , Animales , Apolipoproteínas E/farmacología , Células Cultivadas , Colesterol/sangre , Marcación de Gen , Humanos , Ratones , Fragmentos de Péptidos/metabolismoRESUMEN
We examined patients' experiences with nausea and vomiting after they were discharged from outpatient surgical centers. Data were collected on 211 surgical outpatients at 24-48 h after discharge via a telephone interview conducted by outpatient surgery nurses, and at 5 days after discharge via a patient-completed questionnaire. Telephone interviews were conducted with 193 patients. Questionnaires were completed by 154 patients. Over 35% of patients experienced postdischarge nausea and vomiting. Most had not experienced nausea and vomiting in the recovery room. The severity of nausea for these patients averaged 5 on a 10-point scale (10 indicating very severe nausea). During the 5 days after discharge, these patients reported experiencing nausea for an average of 1.7 days and vomiting for 0.7 days. Patients who experienced postdischarge nausea and vomiting were not able to resume their normal daily activities as quickly as those who did not. Patients managed postdischarge nausea and vomiting with little contact or intervention from health professionals and with minimal product purchases. The results indicate that postdischarge nausea and vomiting is common after outpatient surgery, and that it results in substantial distress and impairment for patients who experience it.
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Procedimientos Quirúrgicos Ambulatorios , Náusea/etiología , Alta del Paciente , Complicaciones Posoperatorias , Vómitos/etiología , Adulto , Anestésicos/efectos adversos , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
STUDY OBJECTIVE: To estimate the financial costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting (PONV). DESIGN: Prospective, observational study. SETTING: 6 hospital-based outpatient surgery centers. PATIENTS: 211 adult patients undergoing outpatient surgery for laparoscopy, dilatation and curettage, knee arthroscopy, or hernia repair. MEASUREMENTS AND MAIN RESULTS: Of the 211 patients studied, 34 experienced PONV in the recovery room. For those patients experiencing PONV, personnel, supply, and drug costs for management of this condition averaged $14.94 per patient. In addition, PONV increased the centers' operating costs by delaying patient discharge by an average of 24 minutes. A minimum estimate of this cost, based on nurses' wage rates, was $7.12. This estimate is appropriate only for short-run considerations in outpatient surgery centers that operate at low capacity. An appropriate valuation for long-run considerations and for centers operating near capacity is based on the revenue that centers lose as a result of extended stays. Lost revenue was estimated to be $415 per patient experiencing PONV. CONCLUSIONS: PONV substantially increases the costs incurred by outpatient surgical centers.
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Procedimientos Quirúrgicos Ambulatorios/economía , Costos de Hospital , Náusea/economía , Náusea/prevención & control , Servicio Ambulatorio en Hospital/economía , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/prevención & control , Centros Quirúrgicos/economía , Vómitos/economía , Vómitos/prevención & control , Adulto , Procedimientos Quirúrgicos Ambulatorios/enfermería , Costos de los Medicamentos , Equipos y Suministros de Hospitales/economía , Femenino , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Náusea/enfermería , Alta del Paciente/economía , Enfermería Posanestésica/economía , Complicaciones Posoperatorias/enfermería , Estudios Prospectivos , Sala de Recuperación/economía , Vómitos/enfermería , Recursos HumanosRESUMEN
Bioactive brain-derived neurotrophic factor (BDNF) and neurotrophin-3 were produced using the baculovirus expression system and purified to homogeneity using ion-exchange and reversed-phase chromatography. Yields of purified neurotrophin-3 (300-500 micrograms/L) were similar to levels reported for baculovirus-expressed nerve growth factor (NGF), whereas initial yields of BDNF were significantly lower (20-50 micrograms/L). Improved production of BDNF (150-200 micrograms/L) was achieved by expressing BDNF from a chimeric prepro-NGF/mature BDNF construct using the Trichoplusia ni insect cell line. Tn-5B1-4. Examination of the distribution of BDNF protein from both the non-chimeric prepro-BDNF and the chimeric prepro-NGF/mature BDNF viruses in Sf-21- and Tn-5B1-4-infected cells suggests a specific deficiency in the Tn-5B1-4 cells in processing the nonchimeric precursor. In addition, the vast majority of the BDNF protein at 2 days after infection was intracellular and insoluble. N-terminal amino acid sequencing of purified recombinant BDNF and neurotrophin-3 demonstrated that the insect cells processed their precursors to the correct N-terminus expected for the mature protein. Bioactivity was characterized in vitro on primary neuronal cultures from the CNS and PNS.
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Insectos/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Animales , Baculoviridae , Secuencia de Bases , Factor Neurotrófico Derivado del Encéfalo , Línea Celular , Vectores Genéticos , Insectos/citología , Membranas Intracelulares/metabolismo , Ratones , Datos de Secuencia Molecular , Factores de Crecimiento Nervioso/aislamiento & purificación , Factores de Crecimiento Nervioso/farmacología , Sistema Nervioso/citología , Sistema Nervioso/efectos de los fármacos , Neuronas/efectos de los fármacos , Neurotrofina 3 , Oligonucleótidos/genética , Ratas , Proteínas Recombinantes , SolubilidadRESUMEN
PURPOSE/OBJECTIVES: To provide an overview of the current attitudes and perceptions of oncology nurses regarding the relevance and measurability of quality of life (QOL) in patients with cancer. DESIGN AND SETTING: Exploratory survey conducted at a scientific exhibit of QOL instruments at the 1990 Oncology Nursing Society Congress held in Washington, DC. SAMPLE: Convenience sample of 621 nurses visiting the exhibit. METHODS: Subjects completed two questionnaires addressing opinions regarding the impact of treatment on QOL, the importance of QOL as an outcome measure, the current status of QOL assessment, barriers to measuring QOL, and knowledge about QOL measurement tissues. MAIN OUTCOME MEASURES: Results of answers to questionnaire items overall as well as selected demographic variables. FINDINGS: Chemotherapy was thought to have the greatest negative impact on QOL, and vomiting, nausea, and tiredness were judged to be the side effects of treatment that most commonly affected QOL. QOL was judged as important an outcome measure as tumor response, toxicity, and survival. Generally, nurses were knowledgeable regarding QOL measurement issues; however, many of the respondents indicated that they believed valid QOL instruments did not exist or that QOL could not be objectively quantified. CONCLUSIONS: Nurses value QOL as an outcome measure of cancer treatment but lack knowledge regarding its measurability, particularly with respect to reliable tools and available time to assess it well. IMPLICATIONS FOR NURSING PRACTICE: Nurses can be instrumental in incorporating QOL measurement as an outcome of treatment and development of brief self-administered tools. Commentary on this research and author response is included at the conclusion of the article.
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Conocimientos, Actitudes y Práctica en Salud , Neoplasias/psicología , Neoplasias/terapia , Evaluación en Enfermería , Enfermería Oncológica/métodos , Calidad de Vida , Antineoplásicos/efectos adversos , Humanos , Neoplasias/mortalidad , Enfermería Oncológica/educación , Reproducibilidad de los Resultados , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Carga de TrabajoRESUMEN
It is evident from the data presented above that nausea and vomiting are frequent side effects which are often persistent and distressing to patients. Evidence suggests, and intuitively it appears that avoidance of nausea and vomiting is important to the patients' ability to maintain their quality of life during the treatment period. It is of particular interest to note that in the literature reviewed in this paper standard antiemetic prescribing and practice were followed. It would, therefore, appear that available antiemetic agents are not always effective or may not be adequately employed. The toxicities associated with dopamine receptor antagonists, the current standard of antiemetic regimens, limit their usefulness in the clinical setting. In fact, the contribution of antiemetic therapy toxicities to the incidence of anxiety, fatigue, and restlessness which were commonly reported by patients in the studies reviewed should be considered. Additional effort to characterise the impact of nausea and vomiting on cancer patients' quality of life is needed. Clearly, the data available suggest that these symptoms should be included as part of the physical domain component of quality of life instruments used in cancer patients. Ideally, the instrument used should contain separate items for nausea and vomiting. Major side effects of antiemetic therapy should also be assessed since these may be as debilitating as the effects of nausea and vomiting. Increased awareness of total patient impact of emesis and antiemetic therapy will serve as an impetus for improvements in antiemetic therapy strategies and practices.
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Antineoplásicos/efectos adversos , Náusea/fisiopatología , Náusea/psicología , Neoplasias/fisiopatología , Neoplasias/psicología , Calidad de Vida , Vómitos/fisiopatología , Vómitos/psicología , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Vómitos/inducido químicamenteAsunto(s)
Abdomen/cirugía , Náusea/epidemiología , Complicaciones Posoperatorias/epidemiología , Vómitos/epidemiología , Adulto , Análisis de Varianza , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Náusea/complicaciones , Estudios Prospectivos , Análisis de Regresión , Vómitos/complicacionesRESUMEN
Nausea and vomiting following chemotherapy administration are common and often overlooked causes of impairment in cancer patients. The goal of this study was to explore the broad range of consequences associated with this specific acute toxicity of chemotherapy. Specific objectives were: (1) create and test scales specifically designed to assess the impact of chemotherapy-induced nausea and vomiting or patients' daily function; (2) examine changes in quality of life of cancer patients 3 days following chemotherapy administration; (3) assess the impact of chemotherapy-induced emesis on quality of life and patients' daily function; (4) identify medical and non-medical cost-related consequences associated with chemotherapy-induced emesis. Patients receiving intermittent bolus chemotherapy regimens on an outpatient basis were eligible for this survey. Four instruments were used: a patient maintained diary, the Functional Living Index-Cancer (FLIC), a newly created Functional Living Index-Emesis (FLIE) and an Item Check list for cost-related consequences. On Day 1, before chemotherapy, patients completed the FLIC and FLIE. Patients recorded episodes on vomiting, severity of nausea, anxiety, sedation, antiemetics self-administered, and adverse effects in diaries for 3 days following chemotherapy. The FLIC and FLIE were completed at the end of Day 3. The Item Check list of cost-related consequences was administered as a telephone survey on Day 5. Approximately 56% of 122 patients reported chemotherapy-induced emesis (CIE). A change in mean FLIC score indicating a decline in quality of life was observed for the CIE group (119 to 101) but not in the group who did not report emesis (124 to 122). Decline in FLIC and FLIE from before to after chemotherapy administration was greater for CIE patients (p = 0.001). FLIE scores indicated that CIE patients perceived that vomiting, and to a slightly lesser extent, nausea substantively influenced their ability to complete household tasks, enjoy meals, spend time with family and friends, and maintain daily function and recreation. Effect size calculations supported a significant negative relationship between occurrence of CIE and the direction and magnitude of functional living index change. An exploratory analysis (principal component followed by regression analysis) supported the hypothesis that side-effects produced by chemotherapy and antiemetic therapy significantly contributed to changes in quality of life observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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Antineoplásicos/efectos adversos , Calidad de Vida , Vómitos/psicología , Actividades Cotidianas , Adulto , Anciano , Antieméticos/uso terapéutico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/psicología , Neoplasias/psicología , Reproducibilidad de los Resultados , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológicoRESUMEN
Venous access has been a problem for the practicing oncologist. Previous approaches, such as arteriovenous fistulas, grafts, or percutaneous catheters, have not gained widespread acceptability. We report our experiences with 230 Port-a-Cath devices, a totally implantable venous access system. The catheters were placed in 218 general oncology patients for the administration of chemotherapy. One patient had three catheters placed and 10 patients had two catheters each. Most patients received standard bolus chemotherapy, while 25 patients were treated with continuous ambulatory infusions. The catheters were in place for an average of 271 days (range 2-1,427 days) for a total of 62,330 catheter days, representing the largest published experience with devices of this type in cancer patients. A total of 24 complications occurred in 22 patients. Catheter insertion was associated with four pneumothoraces, two of which required chest tube drainage. Five catheters were removed because of infection. There were 6 cases of venous thrombosis, but none resulted in pulmonary embolism. Other complications were manageable and included catheter occlusion, migration, and extravasation of chemotherapy agents. The Port-a-Cath is safe and is associated with a low rate of complications. Implantable venous access systems represent a significant advantage in the management of oncology patients with poor venous access.
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Catéteres de Permanencia , Bombas de Infusión Implantables , Neoplasias/tratamiento farmacológico , Catéteres de Permanencia/efectos adversos , Estudios de Evaluación como Asunto , HumanosRESUMEN
The activity of octreotide acetate in a total nutrient admixture (TNA) and the effect of the drug on the stability of lipid emulsion in the TNA were studied. Octreotide acetate injection was added to a standard solution containing 3% lipids, amino acids, dextrose, electrolytes, vitamins, and trace elements to achieve a theoretical concentration of 45 micrograms/dL. Samples were stored at room temperature for 48 hours. Octreotide concentrations were determined in triplicate by radioimmunoassay; physical stability of the solutions was assessed by lipid particle-size determination, pH measurement, and visual observation of emulsion integrity at 0, 12, 24, and 48 hours. The activity of octreotide in two samples of each solution (with and without lipid) was analyzed immediately after preparation and after seven days under refrigeration. There was no evidence of emulsion breakdown or pH change in any solution over the study period. In addition, particle-size distributions at 48 hours and 7 days were comparable to those at time zero, suggesting physical stability. Octreotide acetate activity was not consistently greater than 90% (mean +/- S.D.) after storage for 48 hours. Octreotide acetate at a theoretical concentration of 45 micrograms/dL in a TNA solution containing 3% lipids appeared to be physically compatible for 48 hours at room temperature and for 7 days under refrigeration. However, the chemical activity of octreotide in TNA was not consistent after storage for 48 hours.
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Octreótido/farmacología , Nutrición Parenteral Total , Fenómenos Químicos , Química Física , Embalaje de Medicamentos , Estabilidad de Medicamentos , Emulsiones Grasas Intravenosas/química , Vidrio , Concentración de Iones de Hidrógeno , Lípidos/química , Octreótido/administración & dosificación , Tamaño de la Partícula , Plásticos , Radioinmunoensayo , TemperaturaRESUMEN
Patterns of intracranial signal intensity on magnetic resonance (MR) images were studied in nine patients undergoing long-term total parenteral nutrition therapy. The duration of therapy ranged from 5 months to 11 years (mean, 5.3 years). Symmetric increased signal intensity on T1-weighted MR images (hyperintense relative to white matter) was observed in the basal ganglia of all patients, without corresponding abnormality on T2-weighted images. Analysis of signal-intensity characteristics and distribution pattern suggests that the basis for these changes may be deposition of intravenously administered paramagnetic trace elements, especially manganese, and/or an astrogliotic reaction to such deposition.
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Ganglios Basales/anatomía & histología , Imagen por Resonancia Magnética , Nutrición Parenteral Total , Oligoelementos , Ganglios Basales/metabolismo , Femenino , Alimentos Formulados , Humanos , Masculino , Manganeso/administración & dosificación , Manganeso/farmacocinética , Persona de Mediana Edad , Factores de TiempoRESUMEN
A study of patients, physicians, and third party prescription plan administrators was conducted to identify those pharmacy services they believe are important and valuable and to determine whether third party plan administrators would reimburse pharmacists for such services. Patient and physician focus groups indicated that both wanted personalized services related to medications. Physicians believe that pharmacists are talking to patients about their medications, whereas patients want more drug information but report that pharmacists are not always providing such information. A mail survey of 41 third party prescription plan administrators indicated they believe that pharmacy services are important to consumers and that pharmacists are already providing most of the services identified. One-third of the third party administrators said their companies would consider implementing a structured pharmacist incentive plan to improve enrollee satisfaction. Those whose companies would not most often gave "increased cost" as the reason. No clear relationship was shown between number or type of services and the incentive value offered. Providing administrators with evidence that enhanced pharmacy services will increase overall program cost savings may lead to implementation of pharmacy incentives.
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Servicios Comunitarios de Farmacia , Actitud del Personal de Salud , Servicios Comunitarios de Farmacia/economía , Necesidades y Demandas de Servicios de Salud , Seguro de Servicios Farmacéuticos , North Carolina , MédicosRESUMEN
Drugs that bound to the peripheral-type or mitochondrial benzodiazepine receptors in rat kidney mitochondria produced several effects on mitochondrial respiration with succinate and malate/pyruvate as substrates. These drugs increased state IV and decreased state III respiration rates, which resulted in a significant decrease in the respiratory control ratio. ADP: O ratios were not affected. The receptor binding affinities of a set of 10 compounds (Ro5-4864, PK11195, diazepam, mesoporphyrin IX, flunitrazepam, deuteroporphyrin IX, dipyridamole, dibutylphthalate, cyclosporin A, and CL259,763) correlated over a concentration range of almost 4 orders of magnitude with their potencies at inhibiting respiratory control (r = 0.95). The anxiolytic benzodiazepine clonazepam had no effect on mitochondrial respiratory control and bound with negligible affinity to the receptor. The magnitude of the effect of Ro5-4865 on respiration increased in parallel with the density of mitochondrial benzodiazepine receptors in mitochondria from liver, kidney, and adrenal. These results suggest that ligand binding to mitochondrial benzodiazepine receptors results in inhibition of mitochondrial respiratory control. This effect may help to explain the pleiotropic effects of receptor ligands on intact cells.
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Mitocondrias/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Receptores de GABA-A/fisiología , Animales , Benzodiazepinonas/farmacología , Técnicas In Vitro , Canales Iónicos/fisiología , Isoquinolinas/farmacología , Mitocondrias/efectos de los fármacos , RatasRESUMEN
We have evaluated the affinity and density of binding sites for [3H]Ro5-4864 and [3H]PK11195 in intact and fragmented rat kidney mitochondria. These sites are known as peripheral-type or mitochondrial benzodiazepine receptors (MBR) and the preceding paper provided evidence that they function in vitro as modulators of mitochondrial respiratory control (1). In this report, MBR density, localization, and ligand specificity were investigated. In intact mitochondria, there were approximately the same number of binding sites for [3H]PK11195 as for [3H]Ro5-4864, and their apparent Kd values were identical. However, in mitochondrial fragments, there were 80% more binding sites for [3H]Ro5-4864 than for [3H]PK01195. Rat kidney mitochondria were fractionated by decompression and digitonin-based methods into outer and inner membrane-containing fractions before and after incorporation of the MBR-specific photoaffinity ligand [3H]PK14105. Assays of selective mitochondrial membrane markers and [3H]Ro5-4864 binding or specifically bound [3H]PK14105 revealed that the receptors were found in the mitochondrial outer membrane. We also evaluated the binding of a large number of structurally and pharmacologically diverse compounds to MBR by studying their ability to inhibit the binding of both 3H-ligands. These compounds had affinities ranging from 0.015 to 100 microM and, with a few exceptions, were similar in their abilities to bind to MBR in intact and fragmented mitochondria. However, there was considerable variation in the ratios between drug potencies at displacing [3H]Ro5-4864 and [3H]PK11195. This represents a new form of evidence that these two radioligands do not label identical sites on the receptor. Thirteen of the drugs, including [3H]Ro5-4864 and [3H]PK11195, were analyzed as to the nature of the inhibition and, with only two exceptions, were competitive inhibitors. One drug, Konig's polyanion, was uncompetitive whereas the other, cyclosporin A, was a noncompetitive inhibitor. These studies revealed several new classes of MBR ligands and suggest that the relationship between ligand structure and binding affinity is highly complex.