Limitations to the 6-minute walk test in interstitial lung disease and pulmonary hypertension in scleroderma.

Objective: To determine factors that influence 6-minute walk distance (6MWD) in patients with scleroderma (systemic sclerosis, SSc)-interstitial lung disease (ILD), SSc-pulmonary hypertension (PH), and idiopathic pulmonary fibrosis (IPF).

Methods: We retrospectively evaluated all patients with SSc or IPF who performed a 6-minute walk test (6MWT) at a university hospital between 1999 and 2003. Chi-square, ANOVA, simple linear regression, and backwards elimination multivariable regressions were performed.

Bronchoalveolar lavage fluid in scleroderma interstitial lung disease: technical aspects and clinical correlations: review of the literature.

Objectives: Bronchoalveolar lavage (BAL) has been used for clinical and research purposes in scleroderma interstitial lung disease (SSc-ILD). However, inconsistencies regarding technical aspects of BAL are obstacles in the reproducibility and interpretation of BAL results. This review summarizes clinical correlations and methodological issues of using BAL in the assessment of patients with SSc-ILD.

Human alveolar macrophage gene responses to Mycobacterium tuberculosis strains H37Ra and H37Rv.

H37Rv and H37Ra have been widely used as models of virulent and avirulent strains, respectively, of Mycobacterium tuberculosis. Since the sequencing of H37Rv, microarrays have been used to investigate gene expression of M. tuberculosis strains under various conditions, and to compare gene expression of specific isolates of the organism.

Through-focus scanning-optical-microscope imaging method for nanoscale dimensional analysis.

We present a novel optical technique that produces nanometer dimensional measurement sensitivity using a conventional bright-field optical microscope, by analyzing through-focus scanning-optical-microscope images obtained at different focus positions. In principle, this technique can be used to identify which dimension is changing between two nanosized targets and to determine the dimension using a library-matching method. This methodology has potential utility for a wide range of target geometries and application areas, including nanometrology, nanomanufacturing, semiconductor process control, and biotechnology.

Proteomic analysis of CTGF-activated lung fibroblasts: identification of IQGAP1 as a key player in lung fibroblast migration.

Connective tissue growth factor (CTGF, CCN2) is overexpressed in lung fibroblasts isolated from patients with interstitial lung disease (ILD) and systemic sclerosis (SSc, scleroderma) and is considered to be a molecular marker of fibrosis. To understand the significance of elevated CTGF, we investigated the changes in lung fibroblast proteome in response to CTGF overexpression. Using 2-dimensional gel electrophoresis followed by in-gel proteolytic digestion and mass spectrometric analysis, we identified 13 proteins affected by CTGF.

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.

Purpose: Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition.

The utility of maternal depression screening in the third trimester.

Objective: The purpose of this study was to estimate the prevalence of maternal depressive risk in patients during the third trimester and to determine whether unique at-risk women are identified when the data are compared with postpartum screening.

Study Design: As part of a comprehensive program for universal perinatal depression screening and behavioral health referral of at-risk women, patients completed the Edinburgh Postnatal Depression Scale both during pregnancy (24-28 weeks of gestation) and again at 6 weeks after delivery. Based on Edinburgh Postnatal Depression Scale scores of > or =12, the prevalence of antepartum depressive risk and the rates of concordant/discordant risk status with the corresponding postpartum results were calculated.

Reducing high-order perineal laceration during operative vaginal delivery.

Objective: This study was undertaken to assess the impact of a focused intervention on reducing high-order (third and fourth degree) perineal lacerations during operative vaginal delivery.

Study Design: The following recommendations for clinical management were promulgated by departmental lectures, distribution of pertinent articles and manuals, training of physicians, and prominent display of an instructional poster: (1) increased utilization of vacuum extraction over forceps delivery; (2) conversion of occiput posterior to anterior positions before delivery; (3) performance of mediolateral episiotomy if episiotomy was deemed necessary; (4) flexion of the fetal head and maintenance of axis traction; (5) early disarticulation of forceps; and (6) reduced maternal effort at expulsion. Peer comparison was encouraged by provision of individual and departmental statistics.

Linewidth measurement technique using through-focus optical images.

We present a detailed experimental study of a new through-focus technique to measure critical dimension linewidth with nanometer sensitivity using a bright field optical microscope. This method relies on analyzing intensity gradients in optical images at different focus positions, here defined as the focus metric (FM) signature. The contrast of an optical image of a structured target, where a particular structure is repeated several times, varies greatly as it is moved through-focus if the spacing between the structures is such that the scattered field from the features interferes.

Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo.

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by alpha-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF).

Down-regulation of collagen and connective tissue growth factor expression with hepatocyte growth factor in lung fibroblasts from white scleroderma patients via two signaling pathways.

Objective: To study the mechanisms by which hepatocyte growth factor (HGF) down-regulates collagen and connective tissue growth factor (CTGF) in scleroderma (systemic sclerosis [SSc]) lung fibroblasts.

Methods: CTGF, type I collagen, and IkappaBalpha expression, together with MAPK phosphorylation, were studied by immunoblotting of lung fibroblasts derived from white SSc patients. Matrix metalloproteinase 1 (MMP-1) expression in cell culture medium samples was measured by enzyme-linked immunosorbent assay, MMP-1 activity was studied using an MMP-1 assay, and NF-kappaB DNA binding activity was determined using a transcription factor assay.

A prospective, randomized, multicenter trial of amnioreduction vs selective fetoscopic laser photocoagulation for the treatment of severe twin-twin transfusion syndrome.

Objective: The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin transfusion syndrome (TTTS).

Study Design: This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients.

Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease.

Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease.

Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness.

Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity.

Interstitial lung disease in systemic sclerosis.

We reviewed the literature concerning pathogenesis, clinical features, diagnosis and treatment of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). ILD is detectable in approximately 70% of patients at autopsy. Nonspecific interstitial pneumonia (NSIP) is the most common pathologic finding.

Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease.

Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear.

Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment.

Impairment of the antifibrotic effect of hepatocyte growth factor in lung fibroblasts from African Americans: possible role in systemic sclerosis.

Objective: To compare the composition of cytokines in African American and Caucasian patients with systemic sclerosis (SSc; scleroderma) and in healthy individuals, particularly the expression and function of hepatocyte growth factor (HGF).

Methods: Bronchoalveolar lavage (BAL) fluid samples were analyzed using cytokine array techniques. HGF in plasma and cell culture medium samples was measured by enzyme-linked immunosorbent assay.

Scatterfield microscopy for extending the limits of image-based optical metrology.

We have developed a set of techniques, referred to as scatterfield microscopy, in which the illumination is engineered in combination with appropriately designed metrology targets to extend the limits of image-based optical metrology. Previously we reported results from samples with sub-50-nm-sized features having pitches larger than the conventional Rayleigh resolution criterion, which resulted in images having edge contrast and elements of conventional imaging. In this paper we extend these methods to targets composed of features much denser than the conventional Rayleigh resolution criterion.

Ethnic disparities among patients with pulmonary hypertension associated with systemic sclerosis.

Objective: To examine a cohort of patients with systemic sclerosis (SSc) and pulmonary hypertension (PH) for ethnic disparities in clinical presentation, disease detection, or management.

Methods: Encounters of patients with SSc seen at the Medical University of South Carolina were recorded in a computerized database from November 1997 through January 2004. Patients were evaluated for discrepancy in disease manifestation and treatment.

Scleroderma lung study (SLS): differences in the presentation and course of patients with limited versus diffuse systemic sclerosis.

Objectives: Pulmonary fibrosis is a leading cause of death in systemic sclerosis (SSc). This report examines the differences at baseline and over 12 months between patients with limited versus diffuse cutaneous SSc who participated in the Scleroderma Lung Study.

Methods: SSc patients (64 limited; 94 diffuse) exhibiting dyspnoea on exertion, restrictive pulmonary function and evidence of alveolitis on bronchoalveolar lavage and/or high-resolution computed tomography (HRCT) were randomised to receive cyclophosphamide (CYC) or placebo and serially evaluated over 12 months.

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study.

Objective: To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment.

Methods: One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D.

Amplification refractory mutation system, a highly sensitive and simple polymerase chain reaction assay, for the detection of JAK2 V617F mutation in chronic myeloproliferative disorders.

An acquired mutation in Janus kinase 2 (JAK2), V617F, has recently been identified in human myeloproliferative disorders. Detection of the mutation is helpful in differential diagnosis, prognosis, and predication of therapeutic response. Because the mutation can be present in a small proportion of granulocytic populations in myeloproliferative disorder patients, a highly sensitive detection method is required.

Examination of platelet function in whole blood under dynamic flow conditions with the cone and plate(let) analyzer: effect of erythrocytosis and thrombocytosis.

We studied cone and plate(let) analysis (CPA) for evaluating global platelet function in whole blood under arterial flow conditions (approximately 1,800 seconds(-1)). CPA allows direct visualization and quantitation of platelet adhesion (surface coverage [SC]) and determination of average aggregate size (AS) following brief shearing of a small blood sample (3.2% sodium citrate) in plastic wells.