Biomedical subjects

Shing M Lee

Publications and source records attributed to Shing M Lee.

15 recordsLinked to original sources

PubMed2006

Variability of spirometry in chronic obstructive pulmonary disease: results from two clinical trials.

OBJECTIVE: Our goal is to determine short-term intraindividual biologic and measurement variability in spirometry of patients with a wide range of stable chronic obstructive pulmonary disease severity, using datasets from the National Emphysema Treatment Trial (NETT) and the Lung Health Study (LHS). This may be applied to determine criteria that can be used to assess a clinically meaningful change in spirometry. METHODS: A total of 5,886 participants from the LHS and 1,215 participants from the NETT performed prebronchodilator spirometry during two baseline sessions. We analyzed varying criteria for absolute and percent change of FEV(1) and FVC to determine which criterion was met by 90% of the participants. RESULTS: The mean +/- SD FEV(1) for the initial session was 2.64 +/- 0.60 L (75.1 +/- 8.8% predicted) for the LHS and 0.68 +/- 0.22 L (23.7 +/- 6.5% predicted) for the NETT. The mean +/- SD number of days between test sessions was 24.9 +/- 17.1 for the LHS and 85.7 +/- 21.7 for the NETT. As the degree of obstruction increased, the intersession percent difference of FEV(1) increased. However, the absolute difference between tests remained relatively constant despite the severity of obstruction (0.106 +/- 0.10 L). Over 90% of participants had an intersession FEV(1) difference of less than 225 ml irrespective of the severity of obstruction. CONCLUSIONS: Absolute changes in FEV(1) rather than percent change should be used to determine whether patients with chronic obstructive pulmonary disease have improved or worsened between test sessions.

Aged↗

PubMed2006

Evaluating central corneal thickness measurements with noncontact optical low-coherence reflectometry and contact ultrasound pachymetry.

PURPOSE: To compare the central corneal thickness (CCT) measurements obtained with noncontact optical low-coherence reflectometry (OLCR) and ultrasound (US) pachymetry. DESIGN: Prospective, comparative observational study. METHODS: Three sequential ultrasonic measurements and a set of five OLCR scans of 52 eyes of 26 healthy subjects were recorded. Noncontact measurement was repeated five minutes after anesthetic drop instillation. RESULTS: Mean CCT values for noncontact OLCR and US pachymetry were 544.03 microm and 548.66 microm, respectively, with mean SDs of 0.97 microm and 4.63 microm, respectively. Noncontact OLCR measured on average 4.64 microm less than US pachymetry (95% confidence interval -7.56 to -1.72; P = .003). The OLCR measured 1.68 microm less than US pachymetry in the thinner cornea group (< or =548.7 microm, n = 24) and 7.48 mum less in the thicker group (n = 25). This difference was statistically significant (P = .04). CONCLUSIONS: There was agreement between the two pachymetric measurements. Noncontact OLCR appeared to measure slightly smaller than US pachymetry.

Adult↗

PubMed2006

Brain O2.

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Brain Chemistry↗

PubMed2005

The effects of pulmonary rehabilitation in the national emphysema treatment trial.

STUDY OBJECTIVES: Pulmonary rehabilitation is an established treatment in patients with chronic lung disease but is not widely utilized. Most trials have been conducted in single centers. The National Emphysema Treatment Trial (NETT) provided an opportunity to evaluate pulmonary rehabilitation in a large cohort of patients who were treated in centers throughout the United States. DESIGN: Prospective observational study of cohort prior to randomization in a multicenter clinical trial. SETTING: University-based clinical centers and community-based satellite pulmonary rehabilitation programs. PATIENTS AND INTERVENTION: A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation before and after randomization to lung volume reduction surgery (LVRS) or continued medical management. Rehabilitation was conducted at 17 NETT centers supplemented by 539 satellite centers. MEASUREMENTS AND RESULTS: Lung function, exercise tolerance, dyspnea, and quality of life were evaluated at regular intervals. Significant (p < 0.001) improvements were observed consistently in exercise (cycle ergometry, 3.1 W; 6-min walk test distance, 76 feet), dyspnea (University of California, San Diego Shortness of Breath Questionnaire score, -3.2; Borg breathlessness score: breathing cycle, -0.8; 6-min walk, -0.5) and quality of life (St. George Respiratory Questionnaire score, -3.5; Quality of Well-Being Scale score, +0.035; Medical Outcomes Study 36-item short form score: physical health summary, +1.3; mental health summary, + 2.0). Patients who had not undergone prior rehabilitation improved more than those who had. In multivariate models, only prior rehabilitation status predicted changes after rehabilitation. In 20% of patients, exercise level changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome. Overall, changes after rehabilitation did not predict differential mortality or improvement in exercise (primary outcomes) by treatment group. CONCLUSIONS: The NETT experience demonstrates the effectiveness of pulmonary rehabilitation in patients with severe emphysema who were treated in a national cross-section of programs. Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgical interventions such as LVRS.

Aged↗

PubMed2004

Active recruitment increased enrollment in a hereditary cancer registry.

BACKGROUND AND OBJECTIVE: The Mid-Atlantic Cancer Genetics Network (MACGN) targets individuals from cancer risk assessment clinics for recruitment into a national hereditary cancer registry. We sought to determine whether different recruitment methods used in a high-risk breast and ovarian cancer clinic yielded differences into enrollment into MACGN. METHODS: Two methods of recruitment were compared over an 8-month period. A passive recruitment technique, used during the first 4 months of recruitment, involved distribution of a brochure. An active recruitment method, used during the second 4-month period, required a MACGN recruiter to approach patients and initiate a brief discussion of the registry. RESULTS: During the first 4-month period, 158 eight patients were seen in the clinic and 142 were seen in the second 4-month period. During passive recruitment, 20% of available patients were approached, compared with 63% during active recruitment. Active recruitment also resulted in fourfold increase over passive recruitment in enrollment (from 15.6% to 67.4%). CONCLUSION: Allocating research staff specifically for recruitment and personal contact with potential participants is effective in achieving increased enrollment into a national hereditary cancer research registry.

Adult↗

PubMed2004

Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery.

BACKGROUND: The National Emphysema Treatment Trial, a randomized trial comparing lung volume reduction surgery with medical therapy for severe emphysema, included randomized and nonrandomized comparisons of the median sternotomy and video-assisted thoracoscopic approaches for lung volume reduction surgery. METHODS: Lung volume reduction surgery was performed by median sternotomy only at 8 centers and video-assisted thoracoscopy only at 3 centers; 6 centers randomized the approach to lung volume reduction surgery. Mortality, morbidity, functional status, and costs were assessed. RESULTS: In the nonrandomized comparison, 359 patients received lung volume reduction surgery by median sternotomy, and 152 patients received lung volume reduction surgery by video-assisted thoracoscopy. The 90-day mortality was 5.9% for median sternotomy and 4.6% for video-assisted thoracoscopy (P =.67). Overall mortality was 0.08 deaths per person-year for median sternotomy and 0.10 deaths per person-year for video-assisted thoracoscopy (video-assisted thoracoscopy-median sternotomy risk ratio, 1.18; P =.42). Complication rates were low and not statistically different for the 2 approaches. The median hospital length of stay was longer for median sternotomy than for video-assisted thoracoscopy (10 vs 9 days; P =.01). By 30 days after surgery, 70.5% of median sternotomy patients and 80.9% of video-assisted thoracoscopy patients were living independently (P =.02). Functional outcomes were similar for median sternotomy and video-assisted thoracoscopy at 12 and 24 months. Costs for the operation and the associated hospital stay and costs in the 6 months after surgery were both less for video-assisted thoracoscopy than for median sternotomy (P <.01 in both cases). Similar results were noted for the randomized comparison. CONCLUSIONS: Morbidity and mortality were comparable after lung volume reduction surgery by video-assisted thoracoscopy or median sternotomy, as were functional results. The video-assisted thoracoscopic approach to lung volume reduction surgery allowed earlier recovery at a lower cost than median sternotomy.

Aged↗

PubMed2004

Detection of GSTP1 methylation in prostatic secretions using combinatorial MSP analysis.

OBJECTIVES: To evaluate the utility of methylation-specific polymerase chain reaction analysis of the pi-class glutathione-S-transferase (GSTP1) gene promoter in prostatic secretions for cancer detection and prognostication. METHODS: Prostatic secretions were obtained from a total of 100 radical prostatectomy specimens immediately after surgical extirpation. GSTP1 promoter methylation was assessed by methylation-specific polymerase chain reaction analysis using two different primer sets. Correlations between GSTP1 promoter methylation and clinical and pathologic variables were examined. RESULTS: The sensitivity for detection of GSTP1 methylation in prostatic secretions from men with clinically localized prostate cancer using two different primer sets was 76% and 54%. Methylation of the GSTP1 promoter was detected by both primer sets in 44% and by at least one primer set in 86% of the prostatic secretion specimens. The degree of methylation detected in the prostatic secretions was associated with the extent of cancer (predominant involvement of one or both sides of the gland; P = 0.02) and increasing age (P = 0.009). CONCLUSIONS: Genomic DNA with GSTP1 promoter methylation can be detected in prostatic secretion specimens from the great majority of men with localized prostate cancer. Assays of GSTP1 promoter methylation in prostatic massage fluid or ejaculate may therefore serve as useful adjuncts to existing methods for prostate cancer screening and prognostication.

Acyltransferases↗

PubMed2004

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Clinical Protocols↗

PubMed2003

Six-minute walk distance in chronic obstructive pulmonary disease: reproducibility and effect of walking course layout and length.

The 6-minute walk test is used in clinical practice and clinical trials of lung diseases; however, it is not clear whether replicate tests need to be performed to assess performance. Furthermore, little is known about the impact of walking course layout on test performance. We conducted 6-minute walks on 761 patients with severe emphysema (mean +/- SD FEV1% predicted = 26.3 +/- 7.2) who were participants in the National Emphysema Treatment Trial. Four hundred seventy participants had repeated walks on a separate day. The second test was improved by an average of 7.0 +/- 15.2% (66.1 +/- 146 feet, p < 0.0001, by paired t test), with an intraclass correlation coefficient of 0.88 between days. The course layout had an effect on the distance walked. Participants tested on continuous (circular or oval) courses had a 92.2-foot longer walking distance than those tested on straight (out and back) courses. Course length had no significant effect on walking distance. The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease. Furthermore, the layout of the track may influence the 6-minute walk performance.

Aged↗

PubMed2003

Single-breath diffusing capacity of the lung for carbon monoxide: a predictor of PaO2, maximum work rate, and walking distance in patients with emphysema.

OBJECTIVE: The National Emphysema Treatment Trial (NETT) is a randomized, multicenter, clinical trial comparing two different methods of lung volume reduction surgery plus medical therapy to medical treatment alone in patients with advanced emphysema. The purpose of this article was to use the data obtained from the NETT to assess the ability of the single-breath diffusing capacity of the lung for carbon monoxide (DLCO) to predict the need for supplemental oxygen during rest and exercise, as well as overall exercise capacity. METHODS: One thousand seventy-one patients with a mean (+/- SD) FEV(1) of 0.76 +/- 0.24 L were studied. RESULTS: The mean DLCO was 8.0 +/- 3.1 mL/min/mm Hg (28 +/- 10% of predicted). The mean resting PaO(2) was 64 +/- 10 mm Hg. There was a positive association between DLCO and both resting PaO(2) and the requirement for oxygen during a walk at 1 mile per hour (mph). The odds of requiring supplemental oxygen while walking at 1 mph was nine times greater in patients with a DLCO of < or = 20% of predicted than for patients with a DLCO of > 35% of predicted, after adjusting for age and gender. Eighty four percent of individuals with a DLCO of < or = 20% required supplemental oxygen with low levels of exercise compared to 38% of those with a DLCO of > 35%. CONCLUSION: Our results demonstrated that patients with reduced DLCO, particularly when < or = 20% of predicted, are more likely to have reduced PaO(2) at rest and are more likely to require supplemental oxygen with low levels of activity. Thus, DLCO is useful in evaluating whether supplemental oxygen is required for exercise.

Aged↗

PubMed2003

Prostate cancer detection by GSTP1 methylation analysis of postbiopsy urine specimens.

PURPOSE: We assess the feasibility of a urinary test for prostate cancer detection in a high-risk patient cohort based on methylation-specific PCR analysis of the pi class glutathione S-transferase (GSTP1) gene promoter. EXPERIMENTAL DESIGN: A total of 45 men underwent transrectal ultrasound-guided biopsy of the prostate for suspected malignancy. Clean-catch voided urine specimens were prospectively collected from each patient immediately after biopsy. Genomic DNA was isolated from urine specimens and subjected to sodium bisulfite modification. Methylation of the GSTP1 promoter was examined in a blinded manner by methylation-specific PCR analysis and correlated with pathology results, and clinical information was obtained from the patient record. RESULTS: Methylation of GSTP1 in the urine was detected in a total of 18 of 36 (50%) informative cases. A total of 7 of 18 (39%) patients with prostate adenocarcinoma identified on their initial biopsy had detectable urinary GSTP1 methylation (58% sensitivity among informative cases). Abnormal urinary GSTP1 methylation was also detected in 7 of 21 (33%) patients without evidence of cancer on biopsy and in 4 of 6 (67%) patients diagnosed with atypia or high-grade prostatic intraepithelial neoplasia. CONCLUSIONS: We have demonstrated the feasibility of a novel, noninvasive molecular approach for the detection of epigenetic changes associated with prostate cancer. A screening test based on GSTP1 methylation in the urine specimens of patients with suspected prostate malignancy may be a useful adjunct to serum screening tests and digital rectal examination findings for identification of men at increased risk of harboring cancer despite a negative biopsy. This molecular assay has potential application for stratification of patients into low- and high-risk groups for surveillance versus repeat biopsy.

Aged↗

PubMed2002

Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer.

BACKGROUND: Allelic imbalance (AI), the loss or gain of chromosomal regions, is found in many cancers. AI can be detected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentration, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers. METHODS: Plasma samples were obtained from 330 women (44 normal healthy control individuals, 122 patients with various cancers, and 164 control patients with non-neoplastic diseases). Plasma DNA concentration was determined in all samples. Allelic status was determined by digital single nucleotide polymorphism (SNP) analysis with eight SNP markers in plasma DNA from 54 patients with ovarian cancer and 31 control patients. CA 125 was determined in 63 samples. Receiver-operating characteristic (ROC) curves were plotted, and the areas under the ROC curves--a measure of the overall ability of a diagnostic test with multiple cutoffs to distinguish between diseased and nondiseased individuals--were determined. RESULTS: The area under the ROC curve for plasma DNA concentration was 0.90 for patients with neoplastic disease versus healthy control individuals and 0.74 for patients with neoplastic diseases versus control patients with non-neoplastic diseases. For control subjects given a specificity of 100% (95% confidence interval [CI] = 92% to 100%), the highest sensitivity achieved was 57% (95% CI = 49% to 67%). AI in at least one SNP was found in 87% (95% CI = 60% to 98%) of patients with stage I/II ovarian cancer and 95% (95% CI = 83% to 99%) of patients with stage III/IV ovarian cancer, but AI was not found in 31 patients with non-neoplastic diseases (specificity = 100%, 95% CI = 89% to 100%). The area under the ROC curve assessing AI was 0.95. Combining the serum CA 125 level with the plasma DNA concentration increased the area under the ROC curve from 0.78 (CA 125 alone) to 0.84. CONCLUSION: Plasma DNA concentration may not be sensitive or specific enough for cancer screening or diagnosis, even when combined with CA 125. AI was detected with high specificity in plasma DNA from patients with ovarian cancer and should be studied further as a screening tool.

Adult↗

PubMed2002

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging for acute myeloid leukaemia beyond first remission: a 10-year experience.

Between January 1987 and January 1997, 69 eligible patients with acute myeloid leukaemia (AML) in either second (CR2) or third (CR3) complete remission (CR2 = 60, CR3 = 9) underwent 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation (BMT) at the Johns Hopkins Oncology Center. The patients' median age was 27 years (range 1-62) and all received busulphan and cyclophosphamide as their preparative regimen. The probability of event-free survival (EFS) at 5 years was 30% [95% Confidence Interval (CI): 19-42%] for CR2 patients and 22% (3-51%) for those in CR3, with a median follow up of 8 years in the surviving group. The median time to an absolute neutrophil count of 0.5 x 109/l was 45 d (range 20-185). Relapse was the major cause of failure with a relapse rate of 55% in CR2 and 44% in CR3, while the non-relapse, transplant-related mortality rate was 15% in CR2 and 33% in CR3. In univariate analysis, patient age, cytogenetics, white blood cell count at presentation, CR1 duration and the sensitivity of clonogeneic leukaemia (CFU-L) in the graft to 4HC were all prognostic for EFS. Using each of these significant variables in multivariate modelling, patient age and sensitivity of CFU-L to 4HC were determined to be predictors of EFS. 4HC-purged autologous BMT produced results similar to allogeneic BMT for AML patients beyond first remission.

Acute Disease↗

PubMed2002

Prognostic significance of preoperative molecular serum analysis in renal cancer.

PURPOSE: We evaluated the postoperative clinical course of patients with renal cancer identified preoperatively by microsatellite analysis to examine the correlation between microsatellite alterations and risk of disease recurrence and patient mortality 2 years after nephrectomy. EXPERIMENTAL DESIGN: A panel of 28 microsatellite markers was used previously to assess loss of heterozygosity and microsatellite instability in urine, serum, and tumor DNA of 30 patients with clinically organ-confined renal masses who underwent partial or radical nephrectomy. The clinical reports and imaging data in the medical records of patients with a minimum follow-up of 2 years were retrospectively reviewed to determine their postoperative course. RESULTS: Two-year follow-up was available for the 30 patients (100%) who entered the study. Mean age was 61.6 +/- 12.9 years (range, 21-77 years). Tumor stage was associated with patient mortality (P = 0.03). Tumor grade was associated with mortality (P = 0.03) and disease recurrence (P < 0.01). The frequency of microsatellite alterations (loss of heterozygosity) found in the preoperative serum of patients with renal masses served as a prognostic indicator for disease recurrence (P < 0.01). CONCLUSIONS: Analysis of microsatellite alterations found in preoperative blood samples is a promising method for the detection of renal cancer. The presence of frequent molecular changes in preoperative serum was associated with disease recurrence. These findings suggest a role for microsatellite analysis in future studies attempting to stratify patients with clinically organ-confined renal cancer into low- and high-risk prognostic groups. Larger prospective randomized trials are needed to validate the clinical utility of this observation.

Adult↗

PubMedDate not supplied

The effect of lubricant eye drops on ocular wavefront aberrations.

PURPOSE: To study the effect of lubricant eye drop instillation on ocular wavefront aberrations. METHODS: The wavefront aberrations of the entire optical path of 30 eyes of 15 patients before and following instillation of lubricant eye drops (Bion Tears; Alcon Laboratories Inc, Ft Worth, Tex) were obtained over a 6-mm pupil using a Hartmann-Shack wavefront sensor (WaveScan; VISX Inc, Santa Clara, Calif). Additional computation of root-mean-square (RMS) errors of higher order aberrations from third to sixth order were done using Zernike Tool Software (VISX Inc). Main outcome measures include the mean changes of total higher order aberrations RMS, higher order aberrations, and point spread function (PSF) of the higher order aberrations. RESULTS: The mean changes of total higher order aberrations following instillation of lubricant eye drops on the right eyes were -0.07 microm (95% confidence interval [CI], -0.11 to -0.03) and -0.03 microm on the left eyes (95% CI, -0.07 to 0.01). Significant mean changes were noted for coma and trefoil aberrations with a magnitude of -0.08 microm (95% CI, -0.12 to -0.03) and -0.09 (95% CI, -0.13 to -0.05), respectively, as well as a mean change of the PSF of the higher order aberrations (-0.05 diopters, 95% CI, -0.08 to -0.02) on the right eyes. Although no significant changes in these parameters were demonstrated on the left eyes, a similar trend of changes was observed. CONCLUSIONS: Ocular wavefront aberrations may change following eye drop instillation as measured objectively by the WaveScan system. This effect should be taken into consideration in the assessment of patients for wavefront-guided laser vision correction procedures.

Adult↗