Image Analysis for Cystic Fibrosis: Computer-Assisted Airway Wall and Vessel Measurements from Low-Dose, Limited Scan Lung CT Images

Cystic fibrosis (CF) is a life-limiting genetic disease that affects approximately 30,000 Americans. When compared to those of normal children, airways of infants and young children with CF have thicker walls and are more dilated in high-resolution computed tomographic (CT) imaging. In this study, we develop computer-assisted methods for assessment of airway and vessel dimensions from axial, limited scan CT lung images acquired at low pediatric radiation doses. Two methods (threshold- and model-based) were developed to automatically measure airway and vessel sizes for pairs identified by a user. These methods were evaluated on chest CT images from 16 pediatric patients (eight infants and eight children) with different stages of mild CF related lung disease. Results of threshold-based, corrected with regression analysis, and model-based approaches correlated well with both electronic caliper measurements made by experienced observers and spirometric measurements of lung function. While the model-based approach results correlated slightly better with the human measurements than those of the threshold method, a hybrid method, combining these two methods, resulted in the best results

Cystic fibrosis and renal disease: a case report

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Treatment of anorexia and weight loss with megestrol acetate in patients with cystic fibrosis

Four patients with severe cystic fibrosis lung disease, anorexia and weight loss, received Megestrol Acetate (MA), as an appetite stimulant. The initial dose was 400–800 mg daily and was continued for 6–15 months. Appetite was improved, with significant weight gain in all patients and an increase in their weight for age percentile from <5% at the start of the study to approximately the 25 th percentile after 6 months of use and improvement in quality of life. One patient discontinued MA after 6 months, and subsequently appetite and weight were depressed. Pediatr Pulmonol. 1999; 28:380–382. © 1999 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35316/1/11_ftp.pd

Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes

Lung Function after the Minimal Invasive Pectus Excavatum Repair (Nuss Procedure)

Background The Nuss procedure was introduced at our center in 1999. The operation was mainly performed for cosmesis. Little information is available regarding the influence of this operation on lung function. Methods The aim of this study, a prospective analysis, was to analyze the effect of the Nuss procedure on lung function variables. Between 1999 and 2007 a total of 203 patients with pectus excavatum were treated with the Nuss procedure, of whom 145 (104 male, 41 female) were located at Emma Children’s Hospital. In the latter subset of consecutive patients, static lung function variables [total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC)] and dynamic lung function variables [forced expired volume in 1 s (FEV1), maximum expiratory flow (MEF50)] were performed using spirometry and body box measurements at four time points: prior to operation Some of these data were presented at the International Surgical Week

Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes

BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors

Growth And The Growth Hormone-Insulin Like Growth Factor 1 Axis In Children With Chronic Inflammation:Current Evidence, Gaps In Knowledge And Future Directions

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the growth hormone-insulin like growth factor axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate studies further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biologic therapy may lead to improvement of growth in some of these children but approximately one third continue to grow slowly. There is increasing evidence that the use of relatively high dose recombinant human growth hormone may lead to partial catch up growth in chronic inflammatory conditions, although long term follow-up data is currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis, systemic abnormalities of the growth hormone-insulin like growth factor axis and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human growth hormone in these conditions and discuss the role of recombinant human insulin like growth factor-1

Respiratory Morbidity and Lung Function in Preterm Infants of 32 to 36 Weeks' Gestational Age

Normal lung development follows a series of orchestrated events. Premature birth interrupts normal in utero lung development, which results in significant alterations in lung function and physiology. Increasingly, there are reports documenting the broad range of complications experienced by infants aged 34 to 36 weeks' gestational age (GA). Our objective was to summarize the evidence demonstrating respiratory system vulnerability in infants aged 34 to 36 weeks' GA and to review the developmental and physiologic principles that underlie this vulnerability. A comprehensive search for studies that reported epidemiologic data and respiratory morbidity was conducted on the PubMed, Medline, Ovid Biosis, and Embase databases from 2000 to 2009 by using medical subject headings “morbidity in late preterm infants,” “preterm infants and lung development,” “prematurity and morbidity,” and “prematurity and lung development.” Because the number of studies exclusive to infants aged 34 to 36 weeks' GA was limited, selected studies also included infants aged 32 to 36 weeks' GA. Of the 24 studies identified, 16 were retrospective population-based cohort studies; 8 studies were observational. These studies consistently revealed that infants born at 32 to 36 weeks' GA, including infants of 34 to 36 weeks' GA, experience substantial respiratory morbidity compared with term infants. Levels of morbidity were, at times, comparable to those observed in very preterm infants. The developmental and physiologic mechanisms that underlie the increased morbidity rate and alterations in respiratory function are discussed. We also present evidence to demonstrate that the immaturity of the respiratory system of infants 34 to 36 weeks' GA at birth results in increased morbidity in infancy and leads to deficits in lung function that may persist into adulthood