Elevated cortisol levels in Cushing's disease are associated with cognitive decrements.

OBJECTIVE: The objective of this study was to use Cushing's disease as a unique human model to elucidate the cognitive deficits resulting from exposure to chronic stress-level elevations of endogenous cortisol. METHODS: Forty-eight patients with a first episode of acute, untreated Cushing's disease and 38 healthy control subjects were studied. RESULTS: Scores for four of five verbal IQ subtests were significantly lower in patients with Cushing's disease; their scores were significantly lower for only one nonverbal performance IQ subtest (block design). Verbal, but not visual, learning and delayed recall at 30 minutes were significantly decreased among patients with Cushing's disease. Although verbal delayed recall was significantly lower in these patients, the retention index (percentage), which compares the amount of initially learned material to that recalled after the delay, was not significantly decreased. There was no significant association between depression scores and cognitive performance. A higher degree of cortisol elevation was associated with poorer performance on several subtests of learning, delayed recall, and visual-spatial ability. CONCLUSIONS: Chronically elevated levels of glucocorticoids have deleterious effects on particular domains of cognition. Verbal learning and other verbal functions seem more vulnerable than nonverbal functions. The results suggest that both the neocortex and hippocampus are affected.

Unexplained exertional limitation: characterization of patients with a mitochondrial myopathy.

Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V O(2) 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI(max) 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/V CO(2); 55 versus 42) and hypercirculatory (maximum heart rate - baseline heart rate/V O(2)max - baseline V O(2)max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H(2)O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V Emax/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.

Disentangling measures of individual perceptions of community social dynamics: results of a community survey.

This study examined how different measures of individual perceptions of community social dynamics relate to each other and how these measures relate to self-reported general health and depressive symptoms. Results of a principal components analysis conducted to investigate the interrelationships between these individual measures suggest that these measures measure separate phenomena. In addition, in results of multiple-regression analyses conducted to examine associations between the various measures of individual perceptions of community social dynamics and the dependent variables of self-reported general health and depressive symptoms, sense of community, perceived neighborhood control, and neighborhood participation were all associated with the outcome variables in separate regression models. In a regression model with these three variables added to control variables, only sense of community was significantly, albeit modestly, associated with depressive symptoms and self-reported general health.

Factors influencing quality of life in older women with heart disease.

BACKGROUND: Better understanding of factors influencing the quality of life (QOL) of cardiac patients can guide treatment decisions. OBJECTIVES: To describe the impact of clinical and psychosocial factors on the QOL of older women with heart disease. RESEARCH DESIGN: Baseline and 12-month data from women participating in an intervention study. SUBJECTS: Eligible participants, identified from medical records, were female, > or = 60 years of age, and diagnosed with cardiac disease. A volunteer sample of 570 women (87% white) completed baseline interviews, with 485 women completing the 12-month assessment. MEASURES: Utilizing Wilson and Cleary's conceptual framework (1995), measures of clinical, psychosocial, and functional status were examined for their associations with QOL. RESULTS: At baseline, General Health Perceptions and Symptom Status accounted for 38% and 26%, respectively, of the variation in the QOL rating. Using logistic regression models, seven measures were significant predictors (P < 0.05) of maintenance/improvement versus decline in QOL over 12 months: baseline QOL rating; baseline value and change in satisfaction with social activities over 12 months; change in satisfaction with physical activities; change in satisfaction with mental activities; and baseline value and change in perceived stress. For women who maintained or improved their satisfaction with social activities, the odds for also maintaining or improving QOL were 4.5 times the odds for women whose satisfaction with social activities deteriorated. CONCLUSIONS: Satisfaction with social activities and perceived stress are important predictors of subsequent QOL. Consideration of the impact of treatments on these factors may help to prevent deterioration of QOL among older female cardiac patients.

Short-term and long-term outcomes after bilateral lung volume reduction surgery : prediction by quantitative CT.

OBJECTIVES: To evaluate selection criteria and duration of benefit for patients undergoing lung volume reduction surgery (LVRS). METHODS: Eighty-nine consecutive patients with severe emphysema who underwent bilateral LVRS were prospectively followed up for up to 3 years. Patients underwent preoperative pulmonary function testing, 6-min walk, chest CT, and answered a baseline dyspnea questionnaire. CT scans in 65 patients were analyzed for emphysema extent and distribution using the percentage of emphysema in the lung, percentage of normal lower lung, and the CT emphysema ratio (CTR, an index of the craniocaudal distribution of emphysema). All patients underwent at least 6 weeks of pulmonary rehabilitation prior to surgery. Outcome measures were FEV(1), 6-min walk distance, and transitional dyspnea index (TDI). RESULTS: Compared to baseline, FEV(1) was significantly increased at 3, 6, 12, 18, 24, and 36 months after surgery (p < or = 0.008). The 6-min walk distance increased from 871 feet (baseline) to 1,110 feet (3 months), 1,214 feet (6 months), 1,326 feet (12 months), 1,342 feet (18 months), 1,371 feet (24 months), and 1,390 feet (36 months) after surgery. Despite a decline in FEV(1) over time, 6-min walk distance was preserved. Dyspnea as measured by TDI improved at 3, 6, 12, 18, 24, and 36 months after surgery. A high CTR was the best predictor of a 12% increase over baseline and an absolute increase of 200 mL in FEV(1), although with a low area under the receiver operating characteristic curve. In addition, the sensitivity and negative predictive value of the CTR were limited. No radiographic or physiologic predictor was able to consistently predict a successful increase in walk distance or TDI. CONCLUSION: LVRS improves pulmonary function, decreases dyspnea, and enhances exercise capacity in many patients with severe emphysema, although improvement wanes 36 months after surgery.

Neurodevelopmental outcome of patients after the fontan operation: A comparison between children with hypoplastic left heart syndrome and other functional single ventricle lesions.

OBJECTIVE: To compare neurodevelopmental outcome (NDO) in patients with hypoplastic left heart syndrome (HLHS), other functional single ventricle lesions, and the standard population and to investigate predictors of NDO in the population of children with functional single ventricle (FSV). STUDY DESIGN: A time- and age-defined cohort of patients with the Fontan circulation was recruited to participate in neurodevelopmental testing, behavioral evaluation, and imaging of the central nervous system. The Wechsler Intelligence test was the primary measure of NDO. Analysis included comparison of patients with HLHS with other patients with functional single ventricles. Other potential clinical predictors of NDO were investigated. RESULTS: The mean Full Scale Wechsler Intelligence score was 101.4+/-5.4. For the HLHS subgroup the mean Full Scale Wechsler score was 93.8+/-7.3, and for the non-HLHS subgroup it was 107.0+/-7.0. Although the HLHS group had significantly lower scores than the non-HLHS subgroup, neither subgroup scored significantly different from the standard population on the Wechsler Scales. Socioeconomic status, circulatory arrest, and perioperative seizures also were predictive of neurodevelopmental outcome. CONCLUSION: Neurodevelopmental and behavioral outcome in patients who have undergone the Fontan procedure including patients with HLHS is good in the preschool and early school years, with Wechsler Intelligence scores generally in the normal range.

The induction of congenital spinal deformities in mice by maternal carbon monoxide exposure.

Carbon monoxide (CO) has been shown to be teratogenic in mice. High altitude hypoxia has also been shown to induce congenital vertebral anomalies in mice. The purpose of this study was to investigate the effect of maternal hypoxia owing to CO exposure and the production of congenital spinal deformities in the offspring. Sixty DBA-1J mice were bred using polygamous timed breeding methods. Pregnant females were exposed to 200, 400, or 600 ppm CO using a custom-designed gas blender system. Seven-hour exposures were performed on day 8.5, 9.5, or 10.5 of the 21-day gestation cycle. The neonates were euthanized at birth; the specimens were fixed, eviscerated, and radiographed. Congenital spinal deformities were observed (wedge, hemi, fused, and missing vertebrae; fused ribs) and were located in all regions of the spine. There was a statistically significant difference in the number of spinal deformities between all groups, with no defects in the controls and a 77% incidence at 600 ppm (p < 0.0001). There was no apparent correlation between the time of exposure and defect location. The most sensitive time of gestation was 9.5 days. We identified an animal model of congenital spinal deformities that compares favorably with the evidence of human congenital spinal deformities in cases of maternal exposure to CO and other gas and chemical fumes.

Long-term effects of asthma education for physicians on patient satisfaction and use of health services.

This randomized clinical trial evaluated the long-term impact of an interactive seminar for physicians based on principles of self-regulation on clinician behaviour, children's use of health services for asthma, and parent's views of physician performance. Seventy-four general practice paediatricians, and 637 of their asthma patients aged 1-12 yrs, were randomized to treatment or control. Children and parents were blind to physicians' participation. Data were collected at baseline and follow-up through self-administered surveys (paediatricians), telephone interviews (parents) and medical records. The seminar focused on development of communication and teaching skills and use of therapeutic medical regimens for asthma as outlined in the National Asthma Education and Prevention Program guidelines. Approximately 2 yrs postintervention, treatment group physicians were more likely than control physicians to: use protocols for delivering asthma education (odds ratio (OR) 4.9, p=0.2), write down for patients how to adjust medicines when symptoms change (OR 5.7, p=0.05), and provide more guidelines for modifying therapy (OR 3.8, p=0.06). Parents scored treatment group physicians higher than control physicians on five specific positive communication behaviours. Children seen by treatment group physicians had fewer hospitalizations (p=0.03) and those with higher levels of emergency department (ED) use at baseline had fewer subsequent ED visits (p=0.03). No differences regarding the number of office visits were noted. There were no significant differences found between treatment and control group physicians in the amount of time spent with patients during office visits (26 versus 29 min) or in the number of patients treated with anti-inflammatory medicine. It is concluded that interactive asthma seminars for paediatricians had significant long-term benefits for their asthma care.

Minor salivary gland secretion in the elderly.

OBJECTIVE: Very little information exists on minor salivary gland output (MSGO) in health and disease. We investigated the minor salivary gland output of elderly subjects with different medical backgrounds and the relationship of that output with life practices, demographic variables, complaints of dry mouth, medication usage, functional status, medical treatments, and dental and medical variables. STUDY DESIGN: MSGO was measured with a special moisture-detecting paper on the lip, cheek, and palate, which comprised the total MSGO. A parsimonious linear regression model was developed to determine which of the many measured variables influenced the MSGO. RESULTS: There were significant differences in MSGO between the recruitment sites, with the non-Veteran Affairs (VA) Independent Living participants having significantly lower MSGO than the VA groups. A secretion rate for MSGO based on median values from all subjects of <4.6 microL/min was categorized as being low, whereas a secretion rate for MSGO >/=4.6 microL/min was categorized as high. A regression model was used to examine variables that could be associated with MSGO variability. The results show that being older, a woman, a current smoker, and having a complaint of dry mouth were associated with lower MSGO rates. CONCLUSIONS: An association between subjective complaints of dry mouth and a decrease in MSGO measured objectively was demonstrated in this elderly population. Furthermore, age and sex effects on MSGO were also demonstrated.

Changes in functional health status of older women with heart disease: evaluation of a program based on self-regulation.

OBJECTIVES: This study involving 570 women aged 60 years or older with heart disease, assessed the effects of a disease management program on physical functioning, symptom experience, and psychosocial status. METHODS: Women were randomly assigned to control or program groups. Six to eight women met weekly with a health educator and peer leader over 4 weeks to learn self-regulation skills with physical activity as the focus. Evaluative data were collected through telephone interviews, physical assessments, and medical records at baseline and 4 and 12 months post baseline. RESULTS: At 12 months, compared with controls, program women were less symptomatic (p < .01), scored better on the physical dimension of the Sickness Impact Profile (SIP; p < 0.05), had improved ambulation as measured by the 6-minute walk (p < 0.01), and lost more body weight (p < .001). No differences related to psychosocial factors as measured by the SIP were noted. CONCLUSION: A self-regulation-based program that was provided to older women with heart disease and that focused on physical activity and disease management problems salient to them, improved their physical functioning and symptom experience. Psychosocial benefit was not evident and may be a result of measurement error or due to insufficient program time spent on psychosocial aspects of functioning.

Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women.

BACKGROUND: Recent investigations have demonstrated that parotid salivary dysfunction is not a normal process of aging, but may be the consequence of systemic conditions and their treatment, including medications and menopause. The purpose of this study was to assess longitudinally the influence of age, menopausal status, hormone replacement therapy, and other medications on stimulated parotid flow rates (SPFRs) in healthy women. METHODS: Medical diagnoses, menopausal status, medication utilization, and 2% citric acid stimulated parotid salivas were collected from 396 women, aged 21 to 96 years, from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) over a 17-year span by three investigators. RESULTS: There was no overall longitudinal effect of time on SPFR. Age at first visit was a significant predictor of a decrease in SPFR when adjusted for time and xerostomic medications. However, the deleterious effect of taking one xerostomic medication was equivalent to approximately 14 years of aging. Menopausal status and hormone replacement therapy were not consistently associated with diminished SPFR. CONCLUSIONS: These results suggest that menopause and hormone replacement therapy are not associated with parotid salivary dysfunction. Aging may have a statistically significant yet small deleterious influence on SPFR; however, the adverse influence of xerostomic medications is much larger.

Intraocular pressure measurement in the conscious rat.

PURPOSE: To develop a method for measurement of intraocular pressure in conscious, unsedated rats. METHODS. The animal was gently held with a thick fabric mitten, topical anesthetic drops were instilled and the Tono-Pen was applied to the cornea. RESULT: Measurements in a total of 51 animals did not differ significantly among four strains studied: the overall mean intraocular pressure+/-standard deviation was 13.0+/-1.2 mm Hg. Several intraocular pressure tolerance limits were calculated from this conscious rat data to provide a baseline estimate for future studies. CONCLUSIONS: This measurement method in conscious rats may contribute to making this widely used laboratory animal available for intraocular pressure research.

Cognitive performance at school age of very low birth weight infants with bronchopulmonary dysplasia.

The hypothesis was that bronchopulmonary dysplasia (BPD) adversely affects cognitive performance at school age. This prospective cohort study examined three groups of children at 8 to 10 years of age. Group 1 (n = 311) consisted of very low birth weight (VLBW) infants without BPD and Group 2 (n = 95) consisted of VLBW infants with BPD. Group 3 (n = 188) consisted of term infants without BPD. Regression analysis determined the effect of BPD on eight performance measures while controlling for possible confounding variables. Children in Group 3 had the best performance and children in Group 2 had the poorest performance on all measures. These differences were significant (p = .0001) for the Full Scale IQ, Performance IQ, and reading and math grades and ages. Children in Groups 3 and 1 performed better than children in Group 2 for the Verbal IQ (p = .0001) and the Developmental Test of Visual-Motor Integration (p = .0012), but for these two measures there was no significant difference between children in Groups 3 and 1. Thus, poorer performance was found in VLBW infants with a history of BPD.

The impact of a disease-management program on the symptom experience of older women with heart disease.

This study describes the symptom experience of 570 older women with heart disease and evaluates a disease-management program's impact on symptoms over time. Women were randomly assigned to either usual care or a 4-week program ("Women take PRIDE") designed to improve self-regulation skills by focusing on increasing physical activity. At 4 months follow-up, program women, compared to controls, reported fewer total symptoms (p = 0.01) and decreased symptom frequency (p = 0.02) and bothersomeness (p = 0.02). By 12 months, positive intervention effects emerged within the common cardiac and sleep and rest symptom categories. Program group women reported more improvements in symptoms likely to be affected by increasing physical activity at both follow-ups (p < 0.05).

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

BACKGROUND: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. METHODS: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. RESULTS: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. CONCLUSIONS: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

Procaine spinal anesthesia: a pilot study of the incidence of transient neurologic symptoms.

STUDY OBJECTIVES: To determine the approximate incidence of transient neurologic symptoms (TNS) [formerly known as transient radicular irritation (TRI)] associated with procaine spinal anesthesia, and whether fentanyl prolongs the duration of procaine spinal anesthesia. DESIGN: Unrandomized pilot study. SETTING: Community teaching hospital. PATIENTS: 106 consecutive patients scheduled for spinal anesthesia for procedures anticipated to last less than 90 minutes. INTERVENTIONS: All patients received 5% procaine for spinal anesthesia. Fentanyl 20 micrograms was added for procedures anticipated to last longer than 45 minutes (but less than 90 min). Intraoperatively the adequacy of duration, level, and intensity of anesthesia were observed. Time from injection of local anesthetic until knee-bending was recorded. Three days postoperatively, patients were questioned intensively in an effort to determine whether back pain and/or symptoms consistent with TNS had occurred. MEASUREMENTS AND MAIN RESULTS: Duration of anesthesia was adequate in all but one instance. The intensity and the sensory level of anesthesia were satisfactory with one exception, a woman who had an unexpectedly low sensory level (L1) after 60 mg of procaine for cerclage, and who was also was the only patients to develop TNS. The incidence of TNS (0.9%) was markedly less than that reported after lidocaine and similar to the incidence observed after bupivacaine. Mild back pain without radiation occurred in 11 patients (10%), an incidence that is similar to that seen after bupivacaine and lidocaine. Compared with procaine alone, the addition of fentanyl significantly (p = 0.0001) prolonged the time to bending knees from 72 minutes to 97 minutes. CONCLUSIONS: Procaine may be a useful alternative to lidocaine for short procedures, and it is less likely to produce TNS. Fentanyl prolongs motor block when added to procaine.

Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.

Comparison of AIHA ISO 9001-based occupational health and safety management system guidance document with a manufacturer's occupational health and safety assessment instrument.

Numerous manufacturing and service organizations have integrated or are considering integration of their respective occupational health and safety management and audit systems into the International Organization for Standardization-based (ISO) audit-driven Quality Management Systems (ISO 9000) or Environmental Management Systems (ISO 14000) models. Companies considering one of these options will likely need to identify and evaluate several key factors before embarking on such efforts. The purpose of this article is to identify and address the key factors through a case study approach. Qualitative and quantitative comparisons of the key features of the American Industrial Hygiene Association ISO-9001 harmonized Occupational Health and Safety Management System with The Goodyear Tire & Rubber Co. management and audit system were conducted. The comparisons showed that the two management systems and their respective audit protocols, although structured differently, were not substantially statistically dissimilar in content. The authors recommend that future studies continue to evaluate the advantages and disadvantages of various audit protocols. Ideally, these studies would identify those audit outcome measures that can be reliably correlated with health and safety performance.

Idiopathic pulmonary fibrosis: predicting response to therapy and survival.

Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity and mortality despite aggressive therapy. Thirty-eight patients with biopsy-proven IPF were studied to identify pretreatment features that could be used to predict short-term improvement in pulmonary function and improved longer term survival. In all patients, a pretreatment clinical (dyspnea), radiographic (chest radiograph), and physiologic (pulmonary function including exercise saturation) score was generated (CRP). A high-resolution CT scan (HRCT) was independently scored by four radiologists for ground glass (CT-alv) and linear opacity (CT-fib) on a scale of 0-4. Open lung biopsy samples were scored for cellular infiltration, interstitial fibrosis, desquamation, and granulation by an experienced pulmonary pathologist. All patients were treated with 3 mo of high-dose steroids and the CRP scoring repeated. Patients were divided into three groups: responders with a greater than 10-point drop in CRP (n = 10); stable with +/- 10 point change in CRP (n = 14); and nonresponders with > 10 point rise in CRP or death (n = 14). Those responding to steroids were treated for 18 mo in a tapering fashion. In all others, steroids were tapered quickly and oral cyclophosphamide prescribed. Responders (10 of 38) had a lower age (45.1+/-4.3 yr) than nonresponders (61.4+/-3.5 yr) or those remaining stable (53.1+/-3.3 yr) (p = 0.01). Pretreatment CRP was higher in responders (58.8+/-5.6) than nonresponders (40.5+/-4.7) or stable individuals (37.6+/-4.7) (p = 0.01). Cellular infiltration score of the open lung biopsies was higher in responders (7.6+/-0.6) than stable individuals (5.7+/-0.5) (p = 0.04). The CT-alv scores were higher and CT-fib scores were lower in responders than nonresponders. Receiver operating curve (ROC) analysis was employed to identify pretreatment features of longer term survival (follow-up of 29.1+/-2.3 mo). Only CT-fib (p = 0.009) and pathology fibrosis score (p = 0.03) were able to predict mortality. A pretreatment CT-fib score > or = 2.0 demonstrated 80% sensitivity and 85% specificity in predicting survival. Those patients who did not respond to initial steroid therapy demonstrated a worse long-term survival and greater likelihood of decreased pulmonary function. We demonstrate that pretherapy pulmonary function, pathologic and radiographic parameters are different in individuals who respond to initial prednisone therapy. Only HRCT imaging and pathologic fibrosis were able to reliably predict long-term survival in patients with biopsy-proven IPF.