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Whole-body plethysmography is not included in guidelines from regulatory authorities for the development of treatments or delivery devices for lung disease, despite its potential advantages compared to spirometry. Two separate studies were undertaken to assess the use of specific airway conductance (sGaw) as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery systems (a novel dry powder inhaler and a standard metered dose inhaler). The first pilot study involved delivery of a single dose of salbutamol (200 micrograms) to 12 healthy volunteers and determination of sGaw up to 120 min after treatment. The second study involved delivery of cumulative doses of salbutamol (100, 200 and 400 micrograms) to 19 healthy volunteers with demonstrated reversibility of sGaw to the bronchodilator and measurement of sGaw up to 240 min after treatment. In both studies, increases in sGaw after treatment were significant compared to placebo and larger than the recorded increases in FEV1. Increases in sGaw were similar for both delivery devices and support the therapeutic equivalence of the two products. Power calculations indicated that the second study had appropriate statistical power to discriminate between treatments. It is concluded that the assessment of sGaw in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.  相似文献   
274.
This study evaluated how different systems of feeding may influence the appearance, maintenance, or both of cryptosporidial infection. Animals reared with natural lactation, a traditional artificial feeding system, and a variety of the latter were studied for oocysts in feces. The diagnosis was made by examination of fecal smears stained with auramine-O. Morbidity and mortality were high, particularly in farms with bad hygienic conditions and natural feeding systems. The traditional artificial feeding system is not enough to reduce the presence of parasites. Isolation of newborns at birth and colostrum administration with a feeding bottle, obtained in the most aseptic conditions possible, seems to be an effective prophylactic method for cryptosporidiosis control.  相似文献   
275.
We have asked whether p75(NTR) may play a role in neuronal apoptosis by producing transgenic mice that express the p75(NTR) intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75(NTR) expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75(NTR) intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75(NTR)-dependent reduction in trk activation but instead indicate that the p75(NTR) intracellular domain may act as a constitutive activator of signaling cascades that regulate apoptosis in both peripheral and central neurons.  相似文献   
276.
OBJECTIVES: Although case-based payment is one of the main reimbursement mechanisms for hospitals, little is known about its effects in the general population. Prior studies have focused on Medicare or on all-payer systems in particular states. This study estimates the effect of a prospective payment system based on diagnosis-related groups (DRGs) nationwide in the Department of Veterans Affairs. METHODS: Multiple regression analysis was used to estimate the effect of Department of Veterans Affairs's diagnosis-related group system separately for 22 diagnoses. The dependent variables were length of stay, inpatient days per patient, and discharges per patient. Covariates included patient, hospital, and area characteristics. RESULTS: Department of Veterans Affairs's diagnosis-related group system reduced lengths of stay and inpatient days per patient. The largest impacts were for the psychiatric diagnoses and several surgical procedures. The magnitudes of the effects were generally moderate. Department of Veterans Affairs's case-based system had a negligible effect on discharges per patient. CONCLUSIONS: Per case reimbursement is a potentially useful tool for improving the efficiency of inpatient care for all types of diagnoses and age groups. The effect may be larger than estimated here because of institutional barriers and caps on financial impact.  相似文献   
277.
STUDY DESIGN: This prospective, multicenter study was designed to investigate the efficacy and outcome of spinal cord stimulation using a variety of clinical and psychosocial outcome measures. Data were collected before implantation and at regular intervals after implantation. This report focuses on 70 patients who had undergone 1 year of follow-up treatment at the time of data analysis. OBJECTIVES: To provide a more generalizable assessment of long-term spinal cord stimulation outcome by comparing a variety of pain and functional/quality-of-life measures before and after management. This report details results after 1 year of stimulation. SUMMARY OF BACKGROUND DATA: The historically diverse methods, patient selection criteria, and outcome measures reported in the spinal cord stimulation literature have made interpretation and comparison of results difficult. Although short-term outcomes are generally consistent, long-term outcomes of spinal cord stimulation, as determined by prospective studies that assess multidimensional aspects of the pain complaint among a relatively homogeneous population, are not well established. METHODS: Two hundred nineteen patients were entered at six centers throughout the United States. All patients underwent a trial of stimulation before implant of the permanent system. Most were psychologically screened. One hundred eighty-two patients were implanted with a permanent stimulating system. At the time of this report, complete 1-year follow-up data were available on 70 patients, 88% of whom reported pain in the back or lower extremities. Patient evaluation of pain and functional levels was completed before implantation and 3, 6, 12, and 24 months after implantation. Complications, medication usage, and work status also were monitored. RESULTS: All pain and quality-of-life measures showed statistically significant improvement during the treatment year. These included the average pain visual analogue scale, the McGill Pain Questionnaire, the Oswestry Disability Questionnaire, the Sickness Impact Profile, and the Back Depression Inventory. Overall success of the therapy was defined as at least 50% pain relief and patient assessment of the procedure as fully or partially beneficial and worthwhile. Using this definition, spinal cord stimulation successfully managed pain in 55% of patients on whom 1-year follow-up is available. Complications requiring surgical intervention were reported by 17% (12 of 70) of patients. Medication usage and work status were not changed significantly. CONCLUSIONS: This prospective, multicenter study confirms that spinal cord stimulation can be an effective therapy for management of chronic low back and extremity pain. Significant improvements in many aspects of the pain condition were measured, and complications were minimal.  相似文献   
278.
Infection of macrophages with human cytomegalovirus (HCMV) has been shown to be nonlytic and exclusively cell associated. Human T cell leukemia-lymphoma virus type I (HTLV-I) is capable of establishing productive infection in macrophages. We studied the interactions between HCMV and HTLV-I in monocyte-derived macrophages cultured in vitro. We found that coinfection of macrophages with HCMV and HTLV-I significantly enhanced HCMV replication, resulting in release of infectious HCMV from dually infected cells. On the other hand, HCMV inhibited HTLV-I replication in macrophages coinfected with both viruses. Reciprocal interactions between HCMV and HTLV-I were mediated by their trans-acting proteins. Results of transfection studies demonstrated that the tax gene product of HTLV-I alone was capable of upregulating HCMV production. In a transient gene expression assay the immediate-early 2 (IE2) protein of HCMV alone could inhibit HTLV-I replication, whereas the IE1 protein, which had no effect by itself, produced a synergistic inhibitory effect together with the IE2 protein. Results from this study suggest that in vivo double infection of macrophages with HCMV and HTLV-I may contribute to the dissemination of HCMV infection in patients suffering from HTLV-I-associated T cell leukemia-lymphoma.  相似文献   
279.
BACKGROUND: Degenerative mitral valve disease is the most common cause of mitral regurgitation in the United States. Mitral valve repair is applicable in the majority of these patients and has become the procedure of choice. OBJECTIVE: This study was undertaken to identify factors influencing the durability of mitral valve repair. PATIENTS AND METHODS: Between 1985 and 1997, 1072 patients underwent primary isolated mitral valve repair for valvular regurgitation caused by degenerative disease. Repair durability was assessed by multivariable risk factor analysis of reoperation. It was supplemented by a search for valve-related risk factors for death before reoperation. Three hospital deaths occurred (0.3%); complete follow-up (4152 patient-years) was available in 1062 of 1069 hospital survivors (99.3%). RESULTS: At 10 years, freedom from reoperation was 93%. Among 30 patients who required reoperation for late mitral valve dysfunction, the repair failed in 16 (53%) as a result of progressive degenerative disease. Durability of repair was adversely affected by pathologic conditions other than posterior leaflet prolapse, use of chordal shortening, annuloplasty alone, and posterior leaflet resection without annuloplasty. Durability was greatest after quadrangular resection and annuloplasty for posterior leaflet prolapse and was enhanced by the use of intraoperative echocardiography. Death before reoperation was increased in patients having isolated anterior leaflet prolapse or valvular calcification and by use of chordal shortening or annuloplasty alone. CONCLUSIONS: Repair durability is greatest in patients with isolated posterior leaflet prolapse who have posterior leaflet resection and annuloplasty. Chordal shortening, annuloplasty alone, and leaflet resection without annuloplasty jeopardize late results.  相似文献   
280.
Although the advent of endoscopic technology is expanding the fields of reconstructive and aesthetic surgery in adults, there have been few reports of the use of this technology in the pediatric population. Because of their minimally invasive nature, yet wide range of exposure, endoscopic techniques have much appeal for this age group. Here we present our experience with endoscopic pediatric plastic surgery. From February of 1995 to August of 1997, 104 patients underwent 139 procedures utilizing 5- and 10-mm endoscopes. There were 58 male and 46 female patients. The mean age at surgery was 5.6 years (range, 3 weeks to 19 years). The most common type of procedures performed were insertion of tissue expanders (n = 34), excision of benign head and neck masses (n = 27), torticollis release (n = 20), excision of vascular lesions (n = 13), and miscellaneous procedures, (n = 10). There were 26 complications in 139 procedures (19 percent). Seventeen (65 percent) were in the tissue expander group. The rest were scattered among the groups with other diagnoses. Although there did not appear to be a specific type of complication associated with endoscopy, 77 percent occurred in the first 2 months of our study. This suggests a relatively steep technical learning curve. These results demonstrate that endoscopic techniques are eminently applicable in the pediatric population, providing the benefits of small and remote incisional wounds, with complication rates that are comparable with those of conventional open surgical treatment.  相似文献   
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