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1.
Ann Oncol ; 35(7): 656-666, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38583574

RESUMEN

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Terapia Recuperativa , Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Anciano , Terapia Recuperativa/métodos , Persona de Mediana Edad , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Antígeno Prostático Específico/sangre , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Clasificación del Tumor , Factores de Tiempo
2.
Sarcoidosis Vasc Diffuse Lung Dis ; 28(2): 139-45, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22117505

RESUMEN

BACKGROUND: Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. METHODS: We performed a prospective, open-label, proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks. RESULTS: No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters, p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale, serum brain naturetic peptide, diffusing capacity, and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21, 52%; social reasons: 3/21, 14%; medical reasons: 8/21, 38% because of dyspnea: 6/21, 29% and/or edema: 4/21, 19%. Of those who completed the 24 week study (10/21, 48%), there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size. CONCLUSION: Although ambrisentan was not well tolerated by many of these subjects with SAPH, in those who remained in this 24-week trial, improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Fenilpropionatos/uso terapéutico , Piridazinas/uso terapéutico , Sarcoidosis/complicaciones , Adulto , Antihipertensivos/efectos adversos , Prueba de Esfuerzo , Tolerancia al Ejercicio/efectos de los fármacos , Femenino , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , North Carolina , Fenilpropionatos/efectos adversos , Estudios Prospectivos , Piridazinas/efectos adversos , Calidad de Vida , Recuperación de la Función , Pruebas de Función Respiratoria , South Carolina , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento
3.
Pulm Circ ; 6(4): 557-562, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28090299

RESUMEN

Sarcoidosis-associated pulmonary hypertension (SAPH) is estimated to occur in at least 5% or more of sarcoidosis patients, and it contributes to significant morbidity and mortality. Optimal therapy for SAPH is not well established. We performed a 24-week open-label trial of tadalafil for SAPH at 2 academic medical centers. Subjects were required to have confirmed sarcoidosis plus a right heart catheterization within 12 months of enrollment showing a mean pulmonary artery pressure ≥ 25 mmHg, a pulmonary artery wedge pressure ≤ 15 mmHg, and a calculated pulmonary vascular resistance ≥ 3 Wood units. Subjects received 20 mg/day of tadalafil for the first 4 weeks and then 40 mg/day for the subsequent 20 weeks. Sixteen patients were screened, 12 of whom met criteria for enrollment. At 24 weeks, there was no overall improvement in 6-minute walk distance (6MWD). Five of the 12 subjects dropped out of the study early (2 for social reasons, 3 for medical reasons). There was no significant change in short form 36, St. George's respiratory questionnaire, or maximum Borg dyspnea scores over the 24 weeks. There were no significant adverse events or laboratory abnormalities clearly related to tadalafil in the cohort. The study did not meet the primary end point of change in 6MWD because of the small sample size. Tadalafil was generally safely administered in this cohort of SAPH patients. There was a relatively high dropout rate but no major adverse events and no clinical worsening. Larger studies are needed to explore this question further. (Trial registration: ClinicalTrials.gov identifier: NCT01324999).

4.
Arch Intern Med ; 140(2): 223-7, 1980 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7352817

RESUMEN

A retrospective study of 35 patients with Rocky Mountain spotted fever was undertaken to determine the frequency of respiratory symptoms, as well as to analyze the types of pulmonary problems encountered to hospital patients. Cough, present in only 33% of patients, led to an incorrect initial diagnosis and delay in therapy in eight individuals. Lower respiratory tract involvement (rales, abnormal chest roentgenograms, and abnormal gas exchange) was present in 42% of patients at some point during the illness. The conditions of nine patients deteriorated during the first week of hospitalization. Pulmonary edema (probably noncardiogenic) was the usual explanation for worsening gas exchange. Bacterial pneumonia and hemorrhage were detected in only two patients.


Asunto(s)
Infecciones del Sistema Respiratorio/etiología , Fiebre Maculosa de las Montañas Rocosas/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , North Carolina , Derrame Pleural/etiología , Estudios Retrospectivos , Fiebre Maculosa de las Montañas Rocosas/complicaciones , Fiebre Maculosa de las Montañas Rocosas/mortalidad , Fiebre Maculosa de las Montañas Rocosas/terapia
5.
Arch Intern Med ; 156(9): 984-8, 1996 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-8624178

RESUMEN

OBJECTIVE: To determine whether cognitive status, hand strength, and demographic variables are predictive of correct use of metered-dose inhalers by older subjects. METHODS: Clinic patients (n = 29) and healthy volunteers (n = 42) older than 50 years with no previous or limited metered-dose inhaler use were enrolled. After cognitive (Mini-Mental State Examination) and hand strength assessments, subjects received extensive instruction in proper metered-dose inhaler technique. Technique was independently assessed by two evaluators immediately after instruction and 1 week later. Correct technique was defined as (1) activating the canister in the first half of inhalation, (2) continuing to inhale slowly and deeply, and (3) holding breath at full inspiration (5 seconds). Data for the two subject groups were pooled for analyses. RESULTS: The mean age of the subjects was 69.7 years. Forty subjects (56%) demonstrated correct metered-dose inhaler technique at 1 week. Logistic regression showed that hand strength measurement (odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84), Mini-Mental State Examination score less than 24 (odds ratio, 3.66; 95% confidence interval, 1.07 to 12.4), and male gender (odds ratio, 5.01; 95% confidence interval, 1.07 to 23.5) were significant predictors of incorrect inhaler use. Correct use of the metered-dose inhaler was unrelated to age, education, or subject status. CONCLUSIONS: Clinicians should consider cognitive status and hand strength when metered-dose inhaler therapy is initiated for an older adult. Patients with cognitive impairment and hand strength deficits may require more extensive training, frequent follow-up, or alternative dosage forms.


Asunto(s)
Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Nebulizadores y Vaporizadores , Autoadministración , Administración Intranasal , Anciano , Cognición , Femenino , Fuerza de la Mano , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad
6.
Clin Pharmacol Ther ; 39(5): 577-81, 1986 May.
Artículo en Inglés | MEDLINE | ID: mdl-3698466

RESUMEN

While most controlled studies in humans indicate that ranitidine does not alter drug metabolism, there is some evidence that ranitidine may have this property. If ranitidine does inhibit drug metabolism in a predictable manner, such an effect might be expressed at higher ranitidine doses. Our study was designed to contrast the effects of large doses of ranitidine (1200 and 4200 mg/day) and cimetidine (1200 mg/day) on theophylline elimination. Whereas cimetidine decreased theophylline clearance in 11 of 12 subjects by a mean of 19.4%, neither ranitidine dose affected theophylline disposition. While case reports indicate ranitidine may inhibit theophylline metabolism specifically and drug metabolism in general, we were not able in our controlled study to detect any effect of ranitidine on theophylline elimination even at ranitidine doses up to fourteenfold greater than are generally prescribed.


Asunto(s)
Cimetidina/farmacología , Ranitidina/farmacología , Teofilina/metabolismo , Administración Oral , Adolescente , Adulto , Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Femenino , Humanos , Cinética , Masculino , Teofilina/sangre
7.
Chest ; 118(5): 1294-302, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11083677

RESUMEN

STUDY OBJECTIVE: To compare the bronchodilator efficacy and safety of tiotropium and placebo. DESIGN: A 3-month, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Outpatient. PATIENTS: Four hundred seventy patients with stable COPD (mean FEV(1) = 38.6% predicted). INTERVENTIONS: Tiotropium 18 microg (N = 279) or placebo (N = 191) given once daily via a lactose-based dry-powder inhaler device. MEASUREMENTS AND RESULTS: Spirometry was evaluated on days 1, 8, 50, and 92. Data were expressed as the mean trough (ie, before morning dose; 23 to 24 h after previous dose) and average response observed in the 3 h after the dose was received. Tiotropium produced significant improvement in trough FEV(1) and FVC, averaging 12% greater than baseline on day 8; these improvements were maintained on days 50 and 92. The average postdose FEV(1) was 16% greater than baseline on day 1 and 20% greater than baseline on day 92; FVC was 17% greater than baseline on day 1 and 19% greater than baseline on day 92. Tiotropium was significantly more effective than placebo in both trough and average FEV(1) and FVC response (p < 0.001). These spirometric effects were corroborated by significant improvements in daily morning and evening peak expiratory flow rate, as well as a reduction in "as-needed" albuterol use. Symptoms of wheezing and shortness of breath were significantly less in patients receiving tiotropium, and the physician global assessment noted overall improvements with those treated with tiotropium relative to placebo. The most common reported adverse event after tiotropium was dry mouth (9.3% vs 1.6% relative to placebo; p < 0.05). CONCLUSIONS: These data demonstrate that tiotropium is a safe and effective once-daily anticholinergic bronchodilator and should prove useful as first-line maintenance therapy in COPD.


Asunto(s)
Broncodilatadores/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Pulmón/efectos de los fármacos , Derivados de Escopolamina/uso terapéutico , Anciano , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Antagonistas Colinérgicos/administración & dosificación , Antagonistas Colinérgicos/efectos adversos , Método Doble Ciego , Disnea/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Nebulizadores y Vaporizadores , Ápice del Flujo Espiratorio/efectos de los fármacos , Placebos , Ruidos Respiratorios/efectos de los fármacos , Seguridad , Derivados de Escopolamina/administración & dosificación , Derivados de Escopolamina/efectos adversos , Espirometría , Bromuro de Tiotropio , Capacidad Vital/efectos de los fármacos , Xerostomía/inducido químicamente
8.
Chest ; 115(4): 957-65, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10208192

RESUMEN

STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. INTERVENTIONS: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.


Asunto(s)
Agonistas Adrenérgicos beta/administración & dosificación , Albuterol/análogos & derivados , Broncodilatadores/administración & dosificación , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Administración por Inhalación , Agonistas Adrenérgicos beta/efectos adversos , Albuterol/administración & dosificación , Albuterol/efectos adversos , Broncodilatadores/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Volumen Espiratorio Forzado , Humanos , Ipratropio/administración & dosificación , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Persona de Mediana Edad , Calidad de Vida , Xinafoato de Salmeterol , Capacidad Vital
9.
Respir Med ; 97(9): 1014-20, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14509555

RESUMEN

Loss of bronchodilator effectiveness or tolerance has been observed with inhaled beta-agonists but not with inhaled anticholinergic medications. Initially, tolerance is reflected in loss of bronchial protection against stimuli followed by loss of bronchodilator properties. However, generally such observations have been reported in asthma. A 6-month randomized, double-dummy placebo-controlled trial comparing tiotropium to salmeterol provided the opportunity to examine spirometric tolerance to long-acting beta-agonists in patients with COPD. Spirometry was measured over 12h at baseline and at days 15, 57, 116 and 169. Changes over time from baseline were compared relative to changes observed with placebo. A total of 623 patients participated (tiotropium = 209, salmeterol = 213, placebo = 201). The groups were similar in age (mean = 65 years), gender (75% men), and baseline FEV1 (mean = 1.08 +/- 0.37l [40 +/- 12% predicted]). Relative to placebo, both active drugs improved morning pre-drug, peak and average FEV1 and FVC throughout the trial. However, from day 1 to 169, salmeterol was associated with a higher decline in average FEV1 and FVC (0-12h) (difference from placebo: -36 and -115 ml, P < 0.05), which was most prominent over the 8-12 h period (difference from placebo: -45 and -138 ml, P < 0.01). Significant declines in peak FVC relative to placebo (-83 ml, P < 0.05) but not FEV1 (-12ml) were observed with salmeterol. Tiotropium was associated with further improvements in spirometry from days 1 to 15 and no evidence of tolerance from day 15 to the end of the trial. In conclusion, tolerance to pharmacologic bronchodilation occurs with long-acting beta-agonists such as salmeterol and not with inhaled anticholinergics.


Asunto(s)
Albuterol/análogos & derivados , Albuterol/uso terapéutico , Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/uso terapéutico , Anciano , Análisis de Varianza , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Xinafoato de Salmeterol , Bromuro de Tiotropio , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacos
10.
Respir Med ; 107(10): 1538-46, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23830094

RESUMEN

STUDY OBJECTIVE: To examine the efficacy and safety of the once-daily, inhaled, long-acting muscarinic antagonist/ß2-agonist combination umeclidinium/vilanterol (UMEC/VI) compared with UMEC and VI monotherapies in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this 24-week, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov: NCT01313650) eligible patients were randomised 3:3:3:2 to treatment with UMEC/VI 62.5/25 mcg, UMEC 62.5 mcg, VI 25 mcg or placebo administered once daily via dry powder inhaler (N = 1532; intent-to-treat population). Primary endpoint was trough forced expiratory volume in one second (FEV1) on Day 169 (23-24 h post-dose). Additional lung-function, symptomatic, and health-related quality-of-life endpoints were assessed, including 0-6 h weighted-mean FEV1, rescue salbutamol use, Transition Dyspnoea Index (TDI), Shortness Of Breath With Daily Activity (SOBDA) and St. George's Respiratory Questionnaire (SGRQ) scores. Safety evaluations included adverse events (AEs), vital signs, 12-lead/24-h Holter electrocardiography parameters and clinical laboratory/haematology measurements. RESULTS: All active treatments produced statistically significant improvements in trough FEV1 compared with placebo on Day 169 (0.072-0.167 L, all p < 0.001); increases with UMEC/VI 62.5/25 mcg were significantly greater than monotherapies (0.052-0.095 L, p ≤ 0.004). Improvements were observed for UMEC/VI 62.5/25 mcg vs placebo for weighted-mean FEV1 on Day 168 (0.242 L, p < 0.001), rescue salbutamol use during Weeks 1-24 (-0.8 puffs/day, p = 0.001), TDI (1.2 units, p < 0.001), SOBDA (-0.17 units, p < 0.001) and SGRQ (-5.51 units, p < 0.001) scores. No clinically-significant changes in vital signs, electrocardiography, or laboratory parameters were observed. CONCLUSION: Once-daily UMEC/VI 62.5/25 mcg was well tolerated and provided clinically-significant improvements in lung function and symptoms in patients with COPD.


Asunto(s)
Alcoholes Bencílicos/uso terapéutico , Broncodilatadores/uso terapéutico , Clorobencenos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Quinuclidinas/uso terapéutico , Anciano , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/efectos adversos , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Clorobencenos/administración & dosificación , Clorobencenos/efectos adversos , Método Doble Ciego , Esquema de Medicación , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Quinuclidinas/administración & dosificación , Quinuclidinas/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacos
15.
Respir Med ; 103(4): 516-24, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19208459

RESUMEN

PURPOSE: Current guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD. METHODS: COPD patients (mean FEV(1) 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15microg BID [n=76] or tiotropium 18microg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15microg BID and tiotropium 18microg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes. RESULTS: Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values <0.005). Peak FEV(1), peak FVC, 24-h trough FEV(1), and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events. CONCLUSION: In this study, the combination of nebulized arformoterol 15microg BID plus tiotropium 18microg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.


Asunto(s)
Broncodilatadores/administración & dosificación , Etanolaminas/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/administración & dosificación , Administración por Inhalación , Anciano , Albuterol/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Disnea/tratamiento farmacológico , Femenino , Volumen Espiratorio Forzado , Fumarato de Formoterol , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Bromuro de Tiotropio , Resultado del Tratamiento , Capacidad Vital
16.
Annu Rev Biomed Eng ; 10: 195-220, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18412536

RESUMEN

Inhalation of drug aerosols is a modern pathway to combat lung diseases. It is also becoming the preferred route for insulin delivery, pain management, cancer therapy, and nanotherapeutics. Popular delivery devices include nebulizers, metered-dose inhalers, and dry-powder inhalers. They are all nondirectional and hence have typically low particle deposition efficiencies in desired nasal or lung areas. Thus, for specific disease treatment with costly and/or aggressive medicine, it is necessary to provide targeted drug-aerosol delivery to predetermined sites in the human respiratory system. Experimental measurements and computer models of particle transport and deposition in nasal and lung airway models are presented. Furthermore, the underlying methodology and performance of pressurized metered dose inhalers as well as new smart inhaler systems are discussed. To maximize respiratory drug delivery to specific sites, an optimal combination of particle characteristics, inhalation waveform, particle release position, and drug-aerosol dosage has to be achieved.


Asunto(s)
Aerosoles/administración & dosificación , Aerosoles/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Modelos Biológicos , Preparaciones Farmacéuticas/administración & dosificación , Farmacocinética , Sistema Respiratorio/metabolismo , Animales , Simulación por Computador , Humanos
17.
Ther Adv Respir Dis ; 2(2): 37-48, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19124357

RESUMEN

INTRODUCTION: Concerns have been raised regarding the safety of extended use of long-acting beta2-agonists (LABAs). The safety of arformoterol (50 microg QD), and salmeterol (42 microg BID), was assessed over 12 months in subjects with COPD. The study also examined the occurrence of tolerance with these agents, i.e. whether improvement in airway function diminished or frequency of exacerbations increased with 12-months of use. METHODS: Subjects with COPD (mean FEV1 1.2 L, ~41% predicted) were enrolled in the study and randomized to receive nebulized arformoterol 50 microg QD (n = 528) or salmeterol 42 microg BID (MDI; n = 265) in a prospective, multicenter, open-label, 12-month trial. The frequency of adverse events, COPD exacerbations, and use of short-acting bronchodilator agents were assessed throughout the study period. Pulmonary function was also examined. RESULTS: Among treated subjects, the frequency of adverse events was similar for those taking arformoterol (90.5%) and salmeterol (88.3%). Tremor was more frequent among subjects treated with arformoterol (13.4%) than those treated with salmeterol (1.1%). The frequency of COPD exacerbations did not increase over 12 months for arformoterol and salmeterol (weeks 0-13: 15.7% and 11.7%, respectively; weeks 39-52: 10.0% and 9.4%, respectively). Supplemental ipratropium bromide and rescue racemic albuterol use decreased for both groups by 0.8 to 1.5 actuations/day, decreases that remained stable throughout the 52-week study. Mean predose (trough) FEV1 improved for arformoterol and salmeterol at week 13 (7.1% +/- 17.0 and 7.6% +/- 17.8, respectively) and the improvement continued at week 52 (5.9% and 6.2%, respectively). Mean peak percent predicted postdose FEV1 over the course of the 52-week study declined by about 2% for both treatments, but throughout was higher for arformoterol than for salmeterol. CONCLUSION: In this trial, both arformoterol 50 microg QD and salmeterol 42 microg BID were well tolerated in patients with COPD. Both LABAs produced effective bronchodilation and their use was not associated with the development of clinically meaningful tolerance over a 1-year treatment period.


Asunto(s)
Albuterol/análogos & derivados , Broncodilatadores/uso terapéutico , Etanolaminas/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Albuterol/uso terapéutico , Arritmias Cardíacas/epidemiología , Bronquitis/epidemiología , Femenino , Volumen Espiratorio Forzado , Fumarato de Formoterol , Humanos , Ipratropio/uso terapéutico , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Nebulizadores y Vaporizadores , Estudios Prospectivos , Infecciones del Sistema Respiratorio/epidemiología , Xinafoato de Salmeterol , Temblor/epidemiología
18.
Urology ; 67(1): 80-3, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16413337

RESUMEN

OBJECTIVES: To evaluate formally the risk and levels of irrigant absorption during high-power potassium titanyl phosphate (KTP) laser vaporization of the prostate by the Greenlight PV system using the expired breath ethanol technique. METHODS: Forty consecutive patients underwent laser vaporization of the prostate. Of these patients, 17 had a preoperative transrectal ultrasound estimation of the prostate volume (mean 97 cm3). All procedures were performed under general anesthesia, by either of two consultants or a trainee. A 1% ethanol solution was used as irrigation fluid. Throughout the operation, the expired breath was analyzed for ethanol using a standard alcometer "plumbed" into the anesthetic circuit. Venous blood samples were taken immediately before and after the procedure for measurements of serum sodium and plasma alcohol levels. RESULTS: On average, 155,000 J of laser energy was delivered in 47 minutes. In all patients and on all occasions, the expired breath ethanol remained at 0. No statistically significant change was found in the serum sodium concentration during the procedure (P = 0.42), and no patient displayed any clinical evidence of transurethral resection syndrome. CONCLUSIONS: The results of this study have confirmed, for the first time, the lack of significant absorption of irrigation fluid during high-power KTP vaporization of the prostate using a recognized sensitive technique and the safety of using sterile water as that irrigant. This was the case even in those patients with very large prostates who are usually considered at high risk of experiencing the clinical consequences of fluid absorption during transurethral resection of the prostate and regardless of the experience of the surgeon.


Asunto(s)
Pruebas Respiratorias , Etanol/metabolismo , Terapia por Láser , Prostatectomía/métodos , Absorción , Pruebas Respiratorias/instrumentación , Diseño de Equipo , Espiración , Humanos , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Masculino , Fosfatos , Irrigación Terapéutica/efectos adversos , Titanio
19.
Genes Immun ; 6(6): 509-18, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15951742

RESUMEN

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.


Asunto(s)
Negro o Afroamericano/genética , Cardiomiopatías/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Sarcoidosis/genética , Cardiomiopatías/etnología , Cromosomas Humanos , Ligamiento Genético , Genoma Humano , Humanos , Sarcoidosis/etnología
20.
Curr Opin Pulm Med ; 1(2): 129-43, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15786603

RESUMEN

Chronic obstructive lung disease affects over 15 million people in the United States. The management of this disease in patients is complex, involving antibiotics, mucolytics, bronchodilators, corticosteroids, and rehabilitation. Several studies investigating controversial areas of management were published in 1993 and 1994. New developments in pulmonary rehabilitation, oxygen therapy, noninvasive ventilation, corticosteroids, bronchodilators, vasodilators for pulmonary hypertension, lung transplantation, lung surgery for bullae, and alpha-1-antitrypsin replacement therapy provide physicians with exciting new opportunities for managing chronic obstructive pulmonary disease.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/terapia , Agonistas Adrenérgicos beta/uso terapéutico , Bronquitis/terapia , Broncodilatadores/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Hipercapnia/fisiopatología , Hipertensión Pulmonar/fisiopatología , Trasplante de Pulmón , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Respiración Artificial , Teofilina/uso terapéutico , Deficiencia de alfa 1-Antitripsina/terapia
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