MedWorm: Cystic Fibrosis

Isolation of Human Islets for Autologous Islet Transplantation in Children and Adolescents with Chronic Pancreatitis

Anesthesiology Research and Practice — Wed, 08 Feb 2012 12:16:29 +0100

We present here a technical approach for the isolation and preservation of the islets proven to be efficient to obtain high numbers of islets, favoring the successful treatment of young patients. (Source: Anesthesiology Research and Practice)

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Pulmonary Bacterial Communities in Surgically Resected Noncystic Fibrosis Bronchiectasis Lungs Are Similar to Those in Cystic Fibrosis

Clinical and Developmental Immunology — Wed, 08 Feb 2012 11:20:54 +0100

Conclusions. Our data indicate significant diversity in the pulmonary bacterial community of both CF and non-CF bronchiectasis patients and suggest that this community is similar in surgically resected lungs of CF and non-CF bronchiectasis patients. (Source: Clinical and Developmental Immunology)

Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.

Chronic Respiratory Disease — Wed, 08 Feb 2012 09:06:02 +0100

Authors: Sequeiros IM, Jarad N Abstract Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), ...

New cystic fibrosis drug highlights approval dilemma

New Scientist - Health — Tue, 07 Feb 2012 15:48:54 +0100

With drugs for rare diseases, regulators need to balance the consequences of side effects against the demands of patients with no other options (Source: New Scientist - Health)

Practical Laboratory Aspects of Cystic Fibrosis Microbiology: an Update, Part I

Clinical Microbiology Newsletter — Tue, 07 Feb 2012 02:10:40 +0100

This article provides an update of the major CF pathogens and offers a practical laboratory guide that addresses some of the issues encountered with these cultures. Part I of this two-part article reviews the new and most current information gathered from the literature since 2006 with respect to Pseudomonas aeruginosa, Burkholderia cepacia complex, and other glucose non-fermenting gram-negative rods. Part II of this article will complete the review of the key organisms associated with CF infections, including Staphylococcus aureus, nontuberculous mycobacteria, and fungi. Issues regarding susceptibility testing will also be addressed. Finally, a practical laboratory guide will be provided to address some of the confounding issues associated with CF microbiology. (Source: Clinical Microbiol...

Polysaccharides serve as scaffold of biofilms formed by mucoid Pseudomonas aeruginosa

FEMS Immunology and Medical Microbiology — Mon, 06 Feb 2012 05:00:00 +0100

AbstractChronic lung infection by mucoid Pseudomonas aeruginosa is one of the major pathologic features in patients with cystic fibrosis. Mucoid P. aeruginosa is notorious for its biofilm forming capability and resistance to immune attacks. In the present study, the roles of extracellular polymeric substances from biofilms formed by mucoid P. aeruginosa were investigated. Alginate is not an essential structure component for mucoid P. aeruginosa biofilms. Genetic studies revealed that Pel and Psl polysaccharides serve as essential scaffold and mediate macrocolony formation in mucoid P. aeruginosa biofilms. The Psl polysaccharide is more important than Pel polysaccharide in mucoid P. aeruginosa biofilm structure maintenance and phagocytosis resistance. The polysaccharides were further found ...

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The roles of biofilm matrix polysaccharide Psl in mucoid Pseudomonas aeruginosa biofilms

FEMS Immunology and Medical Microbiology — Mon, 06 Feb 2012 05:00:00 +0100

In this report, by using a variety of mutants in a mucoid P. aeruginosa background, we found that deletion of Psl‐encoding genes dramatically decreased their biofilm formation ability, indicating that Psl is also a critical matrix component of mucoid biofilms. Our data also suggest that the overproduction of alginate leads to mucoid biofilms, which occupy more space, whereas Psl‐dependent biofilms are densely packed. These data suggest that Psl polysaccharide may have significant contributions in biofilm persistence in CF patients and may be helpful for designing therapies for P. aeruginosa CF infection.© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved (Source: FEMS Immunology and Medical Microbiology)

DIY science: should you try this at home?

Guardian Unlimited Science — Fri, 03 Feb 2012 22:59:00 +0100

When Richard Handl was arrested for attempting to split the atom on his stove, he joined a growing band of home experimenters cooking up all kinds of trouble behind the kitchen doorÄngelholm is a pretty southern Swedish town, famed for its clay cuckoo manufacturing, a clay cuckoo being a kind of ocarina, which is a kind of flute. The crime rate here is practically zero. Except one of its residents was last year arrested for trying to split the atom in his kitchen. His name is Richard Handl and he buzzes me into his first-floor flat.I wanted to meet Richard because I keep seeing reports of home science experimenters clashing with the authorities. There's been a spate of them this past year or two.I glance into Richard's kitchen and recognise his cooker from the news. It was horrendously, a...

Improving test properties for neonatal cystic fibrosis screening in the Netherlands before the nationwide start by May 1st 2011

Journal of Inherited Metabolic Disease — Fri, 03 Feb 2012 07:20:33 +0100

Abstract When new technical possibilities arise in health care, often attunement is needed between different actors from the perspectives of research, health care providers, patients, ethics and policy. For cystic fibrosis (CF) such a process of attunement in the Netherlands started in a committee of the Health Council on neonatal screening in 2005. In the balancing of pros and cons according to Wilson and Jungner criteria, the advantages for the CF patient were considered clear, even though CF remains a severe health problem with treatment. Nevertheless, screening was not started then, mainly since the specificity of the tests available at that time was considered too low. Many healthy infants would have been referred for sweat testing and much uncertainty would arise in ...

Calcium-induced Alkaline Protease Folding [Molecular Biophysics]

Journal of Biological Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

Pseudomonas aeruginosa is an opportunistic pathogen that contributes to the mortality of immunocompromised individuals and patients with cystic fibrosis. Pseudomonas infection presents clinical challenges due to its ability to form biofilms and modulate host-pathogen interactions through the secretion of virulence factors. The calcium-regulated alkaline protease (AP), a member of the repeats in toxin (RTX) family of proteins, is implicated in multiple modes of infection. A series of full-length and truncation mutants were purified for structural and functional studies to evaluate the role of Ca2+ in AP folding and activation. We find that Ca2+ binding induces RTX folding, which serves to chaperone the folding of the protease domain. Subsequent association of the RTX domain with an N-termin...

Fucose-binding Lectin from Burkholderia ambifaria [Protein Structure and Folding]

Journal of Biological Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

Burkholderia ambifaria is generally associated with the rhizosphere of plants where it has biocontrol effects on other microorganisms. It is also a member of the Burkholderia cepacia complex, a group of closely related bacteria that cause lung infections in immunocompromised patients as well as in patients with granulomatous disease or cystic fibrosis. Our previous work indicated that fucose on human epithelia is a frequent target for lectins and adhesins of lung pathogens (Sulák, O., Cioci, G., Lameignère, E., Balloy, V., Round, A., Gutsche, I., Malinovská, L., Chignard, M., Kosma, P., Aubert, D. F., Marolda, C. L., Valvano, M. A., Wimmerová, M., and Imberty, A. (2011) PLoS Pathog. 7, e1002238). Analysis of the B. ambifaria genome identified BambL as a putative fucose-binding lectin. ...

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Ivacaftor approved by FDA to treat rare form of cystic fibrosis

Drug Topics - Top News — Thu, 02 Feb 2012 05:00:00 +0100

FDA approved ivacaftor (Kalydeco, Vertex Pharmaceuticals) for the treatment of a rare form of cystic fibrosis in patients aged 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator gene. (Source: Drug Topics - Top News)

FDA approves ivacaftor to treat rare form of cystic fibrosis

Drug Topics - Clinical News — Thu, 02 Feb 2012 05:00:00 +0100

Ivacaftor approved by FDA to treat rare form of cystic fibrosis

Drug Topics - Pharmacy News — Thu, 02 Feb 2012 05:00:00 +0100

Ursodeoxycholate modulates bile flow and bile salt pool independently from the cystic fibrosis transmembrane regulator (Cftr)in mice.

American Journal of Physiology. Gastrointestinal and Liver Physiology — Thu, 02 Feb 2012 05:00:00 +0100

Conclusion. Acute TUDCA infusion and chronic UDCA treatment both stimulate bile flow in CF conditions independently from Cftr function. Chronic UDCA treatment reduces the hydrophobicity of the bile salt pool in Cftr(-/-) mice. These results support a potential beneficial effect of UDCA on bile flow and bile salt metabolism in CF conditions. PMID: 22301109 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)

Drug breakthrough for handful of cystic fibrosis patients

CTV Health — Wed, 01 Feb 2012 14:34:19 +0100

The first drug that treats the root cause of cystic fibrosis won approval Tuesday, offering a life-changing treatment for a handful of patients with the deadly illness and broader hope for thousands more patients with the inherited disease. (Source: CTV Health)

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First Drug to Target Cause of Cystic Fibrosis Approved

MedicineNet Cancer General — Wed, 01 Feb 2012 07:00:00 +0100

Title: First Drug to Target Cause of Cystic Fibrosis ApprovedCategory: Health NewsCreated: 2/1/2012 11:01:00 AMLast Editorial Review: 2/1/2012 (Source: MedicineNet Cancer General)

F.D.A. Approves Cystic Fibrosis Drug

NYT — Wed, 01 Feb 2012 05:56:15 +0100

The Food and Drug Administration called Kalydeco a “breakthrough therapy” because it treats the underlying cause of the genetic disease, rather than just the symptoms. (Source: NYT)

Fungi and allergic lower respiratory tract diseases

Journal of Allergy and Clinical Immunology — Wed, 01 Feb 2012 05:00:00 +0100

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs,...

FDA approves ivacaftor to treat rare form of cystic fibrosis

Drug Topics - Top News — Wed, 01 Feb 2012 05:00:00 +0100

A Decision-Tree Approach to Cost Comparison of Newborn Screening Strategies for Cystic Fibrosis

PEDIATRICS — Wed, 01 Feb 2012 05:00:00 +0100

This study contributes by offering a comparison of both costs, assessed comprehensively, and the consequences associated with the 2 most popular screening methodologies, immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, by using a decision-tree framework allowing variation in the model parameters. (Read the full article) (Source: PEDIATRICS)

Comparison of the US and Australian Cystic Fibrosis Registries: The Impact of Newborn Screening

PEDIATRICS — Wed, 01 Feb 2012 05:00:00 +0100

Registries have been established in a number of countries to monitor the health of patients with cystic fibrosis. Few international comparisons have been made between registries. International data registry comparisons may be useful for informing best practice and benchmarking. Registry comparisons are feasible but are limited by factors such as nonstandardization of data collection. Lung function was lower in Australian children with cystic fibrosis compared with their US counterparts after adjusting for the benefits of diagnosis after newborn screening. (Read the full article) (Source: PEDIATRICS)

A Decision-Tree Approach to Cost Comparison of Newborn Screening Strategies for Cystic Fibrosis

PEDIATRICS — Wed, 01 Feb 2012 05:00:00 +0100

CONCLUSIONS: The IRT/IRT screening algorithm reduces the costs to laboratories and insurance companies but has more system failures. IRT/DNA offers other advantages, including fewer delayed diagnoses and lower out-of-pocket costs to families. (Source: PEDIATRICS)

Comparison of the US and Australian Cystic Fibrosis Registries: The Impact of Newborn Screening

PEDIATRICS — Wed, 01 Feb 2012 05:00:00 +0100

CONCLUSIONS: Children diagnosed with CF after newborn screening benefited from better lung function and BMI than those diagnosed clinically. The benefit of newborn screening on lung function was significantly less in Australian children compared with US children. Statistical comparisons between CF registries are feasible and can contribute to benchmarking and improvements in care. (Source: PEDIATRICS)

FDA approves ivacaftor to treat rare form of cystic fibrosis

Drug Topics - Pharmacy News — Wed, 01 Feb 2012 05:00:00 +0100

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Nutritional outcomes following gastrostomy in children with cystic fibrosis

Pediatric Pulmonology — Wed, 01 Feb 2012 05:00:00 +0100

ConclusionOur study suggests that children with CF who receive GTs are more likely to achieve BMI ≥50th percentile than matched children without GTs. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)

Analytical quality of assays and comparison of procedures for the sweat test.

Annales de Biologie Clinique — Wed, 01 Feb 2012 05:00:00 +0100

In conclusion, comparison of methods highlighted that the less the sweat test is automatically controlled, the more the operator influence on results quality is important. Our study supports that sweat test result <50 mmol/L NaCl Eq is unlikely with CF diagnosis in absence of clinical arguments. PMID: 22294136 [PubMed - as supplied by publisher] (Source: Annales de Biologie Clinique)

New hope for cystic fibrosis sufferers

Health Facts and Fears — Wed, 01 Feb 2012 05:00:00 +0100

Vertex Pharmaceuticals, a relatively new biotech startup, has gained FDA approval for the first drug to target the underlying cause of a rare form of cystic fibrosis. (Source: Health Facts and Fears)

FDA Approves Cystic Fibrosis Drug

WSJ.com: Health — Wed, 01 Feb 2012 02:46:33 +0100

The FDA approved a new medicine treat an underlying cause of cystic fibrosis, a pill that targets a genetic mutation affecting a small minority of patients suffering from the breathing disorder. (Source: WSJ.com: Health)

First Drug to Target Cause of Cystic Fibrosis Approved

WebMD Health — Tue, 31 Jan 2012 23:03:41 +0100

The FDA has approved Vertex's Kalydeco, the first drug to treat the underlying cause of cystic fibrosis for 4% of patients. Vertex hopes the combination of Kalydeco with another new drug will help 90% of cystic fibrosis patients. (Source: WebMD Health)

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FDA OKs Drug That Targets Rare Form of Cystic Fibrosis

Pharmacy News - Doctors Lounge — Tue, 31 Jan 2012 22:00:00 +0100

Therapy zeroes in on defective protein, agency says (Source: Pharmacy News - Doctors Lounge)

FDA approves Vertex cystic fibrosis drug, shares jump

Reuters: Health — Tue, 31 Jan 2012 21:31:39 +0100

WASHINGTON/NEW YORK (Reuters) - Health regulators approved Vertex Pharmaceuticals' Kalydeco, the first drug designed to treat the underlying cause of cystic fibrosis, a rare genetic disease. (Source: Reuters: Health)

Kalydeco - A Cystic Fibrosis Treatment

Health News from Medical News Today — Tue, 31 Jan 2012 21:00:00 +0100

Kalydeco has been approved by the Food And Drug Administration (FDA) to treat a vicious type of Cystic Fibrosis (CF). CF is a deadly recessive disease which targets the lungs, but can also harm the liver, pancreas, and intestine. It occurs from the unusual transport of chloride and sodium across the epithelium, causing mucus buildup in the lungs, and thick secretions. In turn, many respiratory problems occur in patients with CF. Diabetes is also common among patients with CF and it is most common among Caucasians... (Source: Health News from Medical News Today)

FDA OKs Drug That Targets Rare Form of Cystic Fibrosis

MedlinePlus Health News — Tue, 31 Jan 2012 21:00:00 +0100

Therapy zeroes in on defective protein, agency saysSource: HealthDay Related MedlinePlus Pages: Cystic Fibrosis, Medicines (Source: MedlinePlus Health News)

The use of rpoB sequence analysis in the differentiation of Mycobacterium abscessus and Mycobacterium chelonae: a critical judgement in Cystic Fibrosis?

Clinical Microbiology and Infection — Tue, 31 Jan 2012 20:43:46 +0100

(Source: Clinical Microbiology and Infection)

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FDA approves Vertex cystic fibrosis drug, shares jump

Reuters: Health — Tue, 31 Jan 2012 19:42:29 +0100

F.D.A. Approves Cystic Fibrosis Drug

NYT Health — Tue, 31 Jan 2012 19:13:02 +0100

The federal agency called it a “breakthrough therapy” because current therapies treat only the symptoms of the genetic disease. (Source: NYT Health)

FDA Approves Vertex Drug for Cystic Fibrosis

WSJ.com: Health — Tue, 31 Jan 2012 18:48:08 +0100

The FDA approved a new medicine by Vertex Pharmaceuticals to treat a subset of patients with cystic fibrosis. (Source: WSJ.com: Health)

FDA Approves New Drug for a Form of Cystic FibrosisFDA Approves New Drug for a Form of Cystic Fibrosis

Medscape Today Headlines — Tue, 31 Jan 2012 18:42:02 +0100

The FDA has approved ivacaftor for patients aged 6 years and older with cystic fibrosis caused by the G551D mutation in the CFTR gene. FDA Approvals (Source: Medscape Today Headlines)

FDA Approves KALYDECO (Ivacaftor), The First Medicine To Treat The Underlying Cause Of Cystic Fibrosis

Pharmaceutical Online News — Tue, 31 Jan 2012 18:33:00 +0100

Vertex Pharmaceuticals Incorporated announced recently that the U.S. Food and Drug Administration (FDA) has approved KALYDECOTM (ivacaftor), the first medicine to treat the underlying cause of cystic fibrosis (CF), a rare, genetic disease. (Source: Pharmaceutical Online News)

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Cystic fibrosis drug Kalydeco approved by FDA: What does it mean for patients?

Health News: CBSNews.com — Tue, 31 Jan 2012 18:15:30 +0100

November study found Kalydeco improved lung function, reduced complications in patients with cystic fibrosis who have G551D mutation (Source: Health News: CBSNews.com)

Kalydeco Approved to Treat Rare Form of Cystic Fibrosis

Pharmacy News - Doctors Lounge — Tue, 31 Jan 2012 18:04:00 +0100

First drug to target underlying cause of chronic disease (Source: Pharmacy News - Doctors Lounge)

FDA Approves Kalydeco to Treat Rare Form of Cystic Fibrosis

Drugs.com - New Drug Approvals — Tue, 31 Jan 2012 18:01:18 +0100

TUESDAY, January 31, 2012 -- The U.S. Food and Drug Administration today approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic... (Source: Drugs.com - New Drug Approvals)

FDA approves Vertex cystic fibrosis drug

Reuters: Health — Tue, 31 Jan 2012 17:32:10 +0100

WASHINGTON (Reuters) - Health regulators approved Vertex Pharmaceuticals' Kalydeco, the first drug designed to treat the underlying cause of cystic fibrosis, a rare genetic disease. (Source: Reuters: Health)

FDA approves Kalydeco to treat rare form of cystic fibrosis

Food and Drug Administration — Tue, 31 Jan 2012 15:59:00 +0100

The U.S. Food and Drug Administration today approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. (Source: Food and Drug Administration)

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Dosable solvates of ivacaftor with high boiling point liquids

RSC - CrystEngComm latest articles — Tue, 31 Jan 2012 11:08:29 +0100

CrystEngComm, 2012, Advance ArticleDOI: 10.1039/C2CE06477D, PaperYuegang Zhang, James Evans, William Rowe, Kirk Dinehart, Brian Quinn, Patrick ConnellyIvacaftor, a small-molecule treatment for cystic fibrosis, forms butyric acid solvates that are stable and bioavailable in vivo.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - CrystEngComm latest articles)

Bronchoalveolar Lavage And Lung Clearance Index Detects Early Cystic Fibrosis Lung Disease

Health News from Medical News Today — Tue, 31 Jan 2012 08:00:00 +0100

The lung clearance index (LCI) is a sensitive non-invasive marker of early lung disease in young children with cystic fibrosis (CF), according to a new study from Australian researchers. "We found that LCI is elevated early in children with CF, especially in the presence of airway inflammation and Pseudomonas aeruginosa," said Yvonne Belessis, MBBS, MPH, PhD, respiratory staff specialist at the Sydney Children's Hospital. "LCI may not only be a marker of early CF lung disease, but may be useful as an objective outcome measure in future studies of young children with CF... (Source: Health News from Medical News Today)

Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel

AJP: Heart and Circulatory Physiology — Tue, 31 Jan 2012 05:00:00 +0100

Erythrocytes have been implicated as controllers of vascular caliber by virtue of their ability to release the vasodilator ATP in response to local physiological and pharmacological stimuli. The regulated release of ATP from erythrocytes requires activation of a signaling pathway involving G proteins (Gi or Gs), adenylyl cyclase, protein kinase A, and the cystic fibrosis transmembrane conductance regulator as well as a final conduit through which this highly charged anion exits the cell. Although pannexin 1 has been shown to be the final conduit for ATP release from human erythrocytes in response to reduced oxygen tension, it does not participate in transport of ATP following stimulation of the prostacyclin (IP) receptor in these cells, which suggests that an additional protein must be inv...

Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCOFormula Secretion

Physiological Reviews — Tue, 31 Jan 2012 05:00:00 +0100

Fluid and HCO3– secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO3– secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO3– secretion, in particular by secretory glands. Fluid and HCO3– secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl– and secrete HCO3–. The relative volume secreted by acin...

Multiple factors contribute to low BMD in cystic fibrosis patients

MedWire News - Bone Health — Tue, 31 Jan 2012 00:00:00 +0100

Low bone mineral density affects three-quarters of people with cystic fibrosis and is associated with lung function, physical function, and nutritional status, French researchers have shown. (Source: MedWire News - Bone Health)

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Teenager given days to live has life-saving lung transplant after spending 10 YEARS in hospital and planning her own funeral

the Mail online | Health — Mon, 30 Jan 2012 17:38:07 +0100

Casey Blunstone, from Walgherton, Cheshire East, was told by doctors that she had just days to live as cystic fibrosis has caused her lung function to drop to dangerous levels. (Source: the Mail online | Health)

Early Cystic Fibrosis Detected Using Bronchoalveolar Lavage And Lung Clearance Index

Health News from Medical News Today — Mon, 30 Jan 2012 17:00:00 +0100

According to a new Australian study published online before he print publication in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine, the lung clearance index (LCI) is a sensitive, non-invasive marker of early lung disease in young children with cystic fibrosis (CF). Yvonne Belessis, MBBS, MPH, PhD, respiratory staff specialist at Sydney Children's Hospital declared: "We found that LCI is elevated early in children with CF, especially in the presence of airway inflammation and Pseudomonas aeruginosa... (Source: Health News from Medical News Today)

Inhaled mannitol for the treatment of cystic fibrosis

Expert Review of Respiratory Medicine — Fri, 27 Jan 2012 17:40:20 +0100

Expert Review of Respiratory Medicine , February 2012, Vol. 6, No. 1, Pages 19-26. (Source: Expert Review of Respiratory Medicine)

Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index

EurekAlert! - Medicine and Health — Fri, 27 Jan 2012 05:00:00 +0100

(American Thoracic Society) The lung clearance index is a sensitive noninvasive marker of early lung disease in young children with cystic fibrosis, according to a new study from Australian researchers. (Source: EurekAlert! - Medicine and Health)

In vitro Activities of the Novel Ceragenin CSA-13, Alone or in Combination with Colistin, Tobramycin, and Ciprofloxacin, against Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients

Chemotherapy — Thu, 26 Jan 2012 23:00:00 +0100

Chemotherapy 2011;57:505–510 (DOI:10.1159/000335588) (Source: Chemotherapy)

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Interventions for fatigue and weight loss in adults with advanced progressive illness.

Cochrane Database of Systematic Reviews — Thu, 26 Jan 2012 08:18:08 +0100

CONCLUSIONS: There is a lack of robust evidence for interventions to manage fatigue and/or unintentional weight loss in the advanced stage of progressive illnesses such as advanced cancer, heart failure, lung failure, cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia and AIDS. The evidence contained within this overview provides some insight into interventions which may prove of benefit within this population such as exercise, some pharmacological treatments and support for self management.Researchers could improve the methodological quality of future studies by blinding of outcome assessors. Adopting uniform reporting mechanisms for fatigue and weight loss outcome measures would also allow the opportunity for meta-analysis of small studies.Researcher...

Preoperative blood transfusions for sickle cell disease.

Cochrane Database of Systematic Reviews — Thu, 26 Jan 2012 08:18:08 +0100

CONCLUSIONS: While in general, conservative therapy appears to be as effective as aggressive therapy in preparation for surgery in people with sickle cell disease, further research is needed to examine the optimal regimen for different surgical types, and to address whether preoperative transfusion is needed in all surgical situations. PMID: 22258951 [PubMed - in process] (Source: Cochrane Database of Systematic Reviews)

Expression, purification, crystallization and preliminary X-ray analysis of Pseudomonas aeruginosa PelD

Acta Crystallographica Section F — Thu, 26 Jan 2012 05:00:00 +0100

The production of the PEL polysaccharide in Pseudomonas aeruginosa requires the binding of bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) to the cytoplasmic GGDEF domain of the inner membrane protein PelD. Here, the overexpression, purification and crystallization of a soluble construct of PelD that encompasses the GGDEF domain and a predicted GAF domain is reported. Diffraction-quality crystals were grown using the hanging-drop vapour-diffusion method. The crystals grew as flat plates, with unit-cell parameters a = 88.3, b = 114.0, c = 61.9 Å, α = β = γ = 90.0°. The PelD crystals exhibited the symmetry of space group P21212 and diffracted to a minimum d-spacing of 2.2 Å. On the basis of the Matthews coefficient (VM = 2.29 Å3 Da−1), it was estimated th...

Investigation of bacterial resistance to the immune system response: Cepacian depolymerisation by reactive oxygen species.

Innate Immunity — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Cuzzi B, Cescutti P, Furlanis L, Lagatolla C, Sturiale L, Garozzo D, Rizzo R Abstract Reactive oxygen species (ROS) are part of the weapons used by the immune system to kill and degrade infecting microorganisms. Bacteria can produce macromolecules, such as polysaccharides, that are able to scavenge ROS. Species belonging to the Burkholderia cepacia complex are involved in serious lung infection in cystic fibrosis patients and produce a characteristic polysaccharide, cepacian. The interaction between ROS and bacterial polysaccharides was first investigated by killing experiments, where bacteria cells were incubated with sodium hypochlorite (NaClO) with and without prior incubation with cepacian. The results showed that the polysaccharide had a protective effect towards bact...

Therapeutic Liposomal Dry Powder Inhalation Aerosols for Targeted Lung Delivery

Lung — Tue, 24 Jan 2012 18:14:14 +0100

Abstract Therapeutic liposomal powders (i.e., lipospheres and proliposomes) for dry powder inhalation aerosol delivery, formulated with phospholipids similar to endogenous lung surfactant, offer unique opportunities in pulmonary nanomedicine while offering controlled release and enhanced stability. Many pulmonary diseases such as lung cancer, tuberculosis (TB), cystic fibrosis (CF), bacterial and fungal lung infections, asthma, and chronic obstructive pulmonary disease (COPD) could greatly benefit from this type of pulmonary nanomedicine approach that can be delivered in a targeted manner by dry powder inhalers (DPIs). These delivery systems may require smaller doses for efficacy, exhibit reduced toxicity, fewer side effects, controlled drug release over a prolonged time p...

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Children’s and Blue Cross Blue Shield usher in new age of quality-based benchmarks in pediatrics

Thrive, Children's Hospital Boston — Tue, 24 Jan 2012 13:27:29 +0100

Sandra Fenwick, president and COO I’ve worked at Children’s Hospital Boston for more than a decade, and I’m still inspired every day by the hope and strength I see on the faces of our patients and their families. As Children’s navigates a challenging and evolving health care landscape, I draw on that inspiration and determination, especially when many in our industry seem to imply that cost is the only measure of a hospital’s worth. At Children’s, our worth—our value—is so much more than just dollars and cents. It means being treated by pediatric experts—doctors, nurses and support staff—who understand that children are not small adults and their care needs to reflect that fact. It’s a commitment to care and innovation that produces programs like our Community As...

Homozygous CFTR mutation M348K in a boy with respiratory symptoms and failure to thrive. Disease-causing mutation or benign alteration?

European Journal of Pediatrics — Tue, 24 Jan 2012 12:27:32 +0100

Conclusion: We assume that the homozygous alteration M348K is a harmless variant rather than a CF-causing mutation. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s00431-012-1672-1Authors Julia Hentschel, Institute of Human Genetics, Jena University Hospital, Kollegiengasse 10, 07743 Jena, GermanyGabriele Riesener, Institute of Human Genetics, Jena University Hospital, Kollegiengasse 10, 07743 Jena, GermanyHeike Nelle, Institute of Human Genetics, Jena University Hospital, Kollegiengasse 10, 07743 Jena, GermanyManfred Stuhrmann, Institute of Human Genetics, Hannover Medical School, Jena, GermanyAnja Schöner, Institute of Human Genetics, Hannover Medical School, Jena, GermanyOlaf Sommerburg, Division of Pediatric Pulmonology & Allergy and CF Centre, Univer...

Structure–Activity Relationships of Cyanoquinolines with Corrector–Potentiator Activity in ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Protein

Journal of Medicinal Chemistry — Mon, 23 Jan 2012 20:17:45 +0100

Journal of Medicinal ChemistryDOI: 10.1021/jm201372q (Source: Journal of Medicinal Chemistry)

Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis

Clinical and Developmental Immunology — Mon, 23 Jan 2012 11:22:21 +0100

We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury. (Source: Clinical and Developmental Immunology)

Chemists Unlock Potential Target For Drug Development

Health News from Medical News Today — Mon, 23 Jan 2012 08:00:00 +0100

A receptor found on blood platelets whose importance as a potential pharmaceutical target has long been questioned may in fact be fruitful in drug testing, according to new research from Michigan State University chemists. A team led by Dana Spence of MSU's Department of Chemistry has revealed a way to isolate and test the receptor known as P2X1. By creating a new, simple method to study it after blood is drawn, the team has unlocked a potential new drug target for many diseases that impact red blood cells, such as diabetes, hypertension and cystic fibrosis... (Source: Health News from Medical News Today)

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Pulmonary function in individuals with cystic fibrosis from the U.S. cystic fibrosis foundation registry who had undergone liver transplant

Liver Transplantation — Mon, 23 Jan 2012 05:00:00 +0100

AbstractSevere liver disease (cirrhosis) affects between 4.5‐10% of individuals with cystic fibrosis (CF) and is the third leading cause of death and a significant cause of morbidity. Liver transplantation is an accepted therapy for severe liver disease, but the effects of liver disease and liver transplant on pulmonary function in CF are controversial. The aim of this study was to characterize changes in pulmonary function in liver transplanted CF patients. Using mixed effect models, we analyzed pulmonary function pre‐ and post‐transplant in 168 liver transplanted patients with CF versus 840 non‐transplanted CF patients, matched on age, gender, pancreatic status, and bacterial infections from the U.S. CF Foundation Patient Registry Data from 1989‐2007. The primary outcome was ch...

Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain

BMC Microbiology - Latest articles — Sun, 22 Jan 2012 05:00:00 +0100

Conclusions: Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients. (Source: BMC Microbiology - Latest articles)

Personalized medicine comes to cystic fibrosis

American Journal of Medical Genetics Part A — Sat, 21 Jan 2012 14:22:24 +0100

(Source: American Journal of Medical Genetics Part A)

Clarithromycin therapy for patients with cystic fibrosis: A randomized controlled trial

Pediatric Pulmonology — Sat, 21 Jan 2012 09:32:09 +0100

AbstractThe clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis (CF) lung disease have been well documented. In vitro and clinical data suggests that clarithromycin has immunomodulatory properties similar to other 14‐member macrolides, however two previously reported short term, open label trials of clairthromycin in small numbers of patients with CF failed to show significant benefits in modifying lung function or inflammation. We performed an international double blind, cross‐over trial in which 63 subjects with CF were studied while receiving either placeo or 500 mg oral clarithromycin twice daily for 5 months, with a 1‐month wash‐out. The primary efficacy end point was the change in lung function (FEV1 and FVC) during the clarithromyci...

Improved survival in cystic fibrosis patients with severely impaired lung function

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

A forced expiratory volume in one second (FEV1) less than 30% predicted has been accepted as the threshold at which 50% of patients with cystic fibrosis (CF) survive 2 years or less. However, this estimate, made in the early 1990s, does not take into account recent developments in treatment. This cohort study aimed to re-evaluate the survival of CF patients with severely impaired lung function. Two hundred and seventy-six CF patients whose FEV1 was first observed to be less than 30% predicted between 1990 and 2003 were included in the cohort. The patients were followed up in 2-year subcohorts until 2007 and their survival was assessed. The authors showed an important improvement in the average survival of CF patients with severely impaired lung function. Median survival for patients w...

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Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion The inflammatory response in the CF airway is compartmentalised. In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterised by the recruitment and accumulation of lymphocytes. (Source: Thorax)

Role of kinase suppressor of Ras-1 in Pseudomonas aeruginosa infections

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

In this study, by conducting a series of experiments on mice, the authors identified the key role of the kinase suppressor of Ras-1 (Ksr1), an enzymatic protein, in the innate host response to P aeruginosa infection. Ksr1 deficiency impairs the bactericidal activity of alveolar macrophages and, as a consequence, Ksr1-deficient mice were found to die of sepsis from failed clearance of P aeruginosa. The bactericidal activity of alveolar macrophages and neutrophils is mediated by the formation and release of nitric oxide (NO) and peroxynitrite, which is triggered by Ksr1. This occurs through a previously unidentified pathway where Ksr1 functions as a unique scaffold and mediates the interaction between inducible NO synthase (iNOS) and heat shock protein 90, thereby activating iNOS and releasi...

Should bronchoscopy be advocated to study airway remodelling and inflammation in adults with cystic fibrosis?

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

We read with interest the article by Regamey et al who reviewed the relationship of airway remodelling to inflammation in cystic fibrosis (CF).1 The authors suggested that endobronchial biopsy studies are useful for studying airway remodelling in CF. Four studies were conducted in 91 children who underwent bronchoscopy for clinical reasons or annual routine surveillance. These studies confirmed that airway remodelling in CF appeared early in life and this is indeed of more than academic interest. However, while the authors have previously shown and claimed that biopsy procedures are safe in infants and small children, the ethics of the procedure in children have been discussed by others.2 We would like to raise concerns about the procedure in adults as well. From 1987 to 2011, Regamey et a...

Authors' response

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

We thank Burgel and colleagues for their valuable comments.1 We agree that a cautious approach should be adopted when considering the use of bronchoscopy and biopsy in cystic fibrosis (CF) research. As stated in our review article,2 we have confirmed the safety of endobronchial biopsy in children and infants with CF. Reassuringly, we have encountered no complications even in children with advanced lung disease. We advocate the use of endobronchial biopsy to investigate mechanisms of airway remodelling events and their relationship to infection and inflammation in children, but claim no experience of bronchoscopy in adult CF. It would be inappropriate for us to comment on the role of bronchoscopy in adults. Competing interestsNone. ContributorsAll authors contributed to this letter equally...

Cystic fibrosis: An unusual neonatal presentation

Pediatric Pulmonology — Fri, 20 Jan 2012 05:00:00 +0100

In this report we describe a neonate born with cystic fibrosis (CF) who presented to us with hypoxic respiratory failure, pulmonary hypertension, and hypercarbia without lactic acedemia from sticky mucous plugging and massive lung collapse. Neonatal respiratory distress and wide spread pulmonary atelectasis has not been reported in infants born with CF. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)

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The management of bronchus intermedius complications after lung transplantation: A retrospective study

Journal of Cardiothoracic Surgery — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: BI complications after lung transplantation are still a significant problem. Stenosis or malacia following lung transplantation could be well managed with modified Montgomery T-tube. (Source: Journal of Cardiothoracic Surgery)

Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

Role of kinase suppressor of Ras-1 in Pseudomonas aeruginosa infections

Thorax — Fri, 20 Jan 2012 05:00:00 +0100

Requirements for Efficient Correction of ΔF508 CFTR Revealed by Analyses of Evolved Sequences

Cell — Fri, 20 Jan 2012 00:00:00 +0100

Juan L. Mendoza, André Schmidt, Qin Li, Emmanuel Nuvaga, Tyler Barrett, Robert J. Bridges, Andrew P. Feranchak, Chad A. Brautigam, Philip J. Thomas. Misfolding of ΔF508 cystic fibrosis (CF) transmembrane conductance regulator (CFTR) underlies pathology in most CF patients. F508 resides in the first nucleotide-binding domain (NBD1) of CFTR near.... (Source: Cell)

Lung transplantation for cystic fibrosis: a single center experience of 100 consecutive cases [TX [amp ] MCS]

European Journal of Cardio-Thoracic Surgery — Wed, 18 Jan 2012 05:00:00 +0100

CONCLUSION Improved results obtained in the early postoperative period since 2000 is most likely due to change in surgical management approach. Improved surgical outcome for CF patients can be obtained, especially in experienced transplant centers. (Source: European Journal of Cardio-Thoracic Surgery)

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Lung transplantation for Cystic fibrosis: satisfactory results in specialized centres [EDITORIAL COMMENT]

European Journal of Cardio-Thoracic Surgery — Wed, 18 Jan 2012 05:00:00 +0100

(Source: European Journal of Cardio-Thoracic Surgery)

Human-mouse cystic fibrosis transmembrane conductance regulator (CFTR) chimeras identify regions that partially rescue CFTR-{Delta}F508 processing and alter its gating defect [Medical Sciences]

Proceedings of the National Academy of Sciences — Tue, 17 Jan 2012 05:00:00 +0100

The ΔF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is the most common cause of cystic fibrosis. The mutation disrupts biosynthetic processing, reduces channel opening rate, and decreases protein lifetime. In contrast to human CFTR (hCFTR)-ΔF508, mouse CFTR-ΔF508 is partially processed to the cell surface, although it exhibits a functional defect similar to hCFTR-ΔF508. To explore ΔF508 abnormalities, we generated human–mouse chimeric channels. Substituting mouse nucleotide-binding domain-1 (mNBD1) into hCFTR partially rescued the ΔF508-induced maturation defect, and substituting mouse membrane-spanning domain-2 or its intracellular loops (ICLs) into hCFTR prevented further ΔF508-induced gating defects. The protective effect of the mouse ICLs ...

Glucocorticoids reduce inflammation in cystic fibrosis bronchial epithelial cells.

Cellular Signalling — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Rebeyrol C, Saint-Criq V, Guillot L, Riffault L, Corvol H, Chadelat K, Ray DW, Clement A, Tabary O, Le Rouzic P Abstract Reduction of lung inflammation is one of the goals of cystic fibrosis (CF) therapy. Among anti-inflammatory molecules, glucocorticoids (GC) are one of the most prescribed. However, CF patients seem to be resistant to glucocorticoid treatment. Several molecular mechanisms that contribute to decrease anti-inflammatory effects of glucocorticoids have been identified in pulmonary diseases, but the molecular actions of glucocorticoids have never been studied in CF. In the cytoplasm, glucocorticoids bind to glucocorticoid receptor (GR) and then, control NF-κB and MAPK pathways through direct interaction with AP-1 and NF-κB in the nucleus. Conversely, MAPK ca...

A novel respiratory symptom scoring system for CF pulmonary exacerbations

QJM — Mon, 16 Jan 2012 05:00:00 +0100

Conclusion: This new symptom score is simple and sensitive to change over a short period. It correlates with established quality-of-life questionnaires and with spirometry. The changes of symptom score over a short period correlate with changes in spirometry. This score can be used as an added tool to assess the outcome of CF PExs. (Source: QJM)

Lessons learned from 20 years of newborn screening for cystic fibrosis.

Med J Aust — Mon, 16 Jan 2012 05:00:00 +0100

CONCLUSION: Most babies with CF without meconium ileus, a family history or antenatal diagnosis are detected by newborn screening. Despite improved sensitivity with the 12-mutation analysis, most infants detected would have been diagnosed using the IRT/p.F508del protocol. PMID: 22256939 [PubMed - in process] (Source: Med J Aust)

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Respiratory Outbreak of Mycobacterium abscessus Subspecies massiliense in a Lung Transplant and Cystic Fibrosis Center.

American Journal of Respiratory and Critical Care Medicine — Sun, 15 Jan 2012 05:00:00 +0100

Authors: Aitken ML, Limaye A, Pottinger P, Whimbey E, Goss CH, Tonelli MR, Cangelosi GA, Dirac MA, Olivier KN, Brown-Elliott BA, McNulty S, Wallace RJ PMID: 22246710 [PubMed - in process] (Source: American Journal of Respiratory and Critical Care Medicine)

Functional performance on the six-minute walk test in patients with cystic fibrosis

Jornal Brasileiro de Pneumologia — Sat, 14 Jan 2012 21:08:57 +0100

CONCLUSIONS: In our sample, functional performance on the 6MWT was poorer among the cystic fibrosis patients than among the healthy controls in the same age bracket, and we found immediate repetition of the test to be unadvisable. (Source: Jornal Brasileiro de Pneumologia)

It Takes a Team: Creating the Duke Experience

DukeHealth.org: Duke Health Features — Sat, 14 Jan 2012 17:23:52 +0100

It was a team-based experience that won’t soon be forgotten. In June 2011, thousands of physicians, staff, and volunteers who work at Duke University Hospital came together for the 2011 All-Staff Event to recommit to caring for patients and their loved ones. For the second year in a row, the event was held at the Durham Performing Arts Center. Based on employee feedback, the theme continued to spotlight teamwork, with this year’s event specifically focused on creating the unique experiences that differentiate the care delivered at Duke University Hospital from the care received any other place in the world. Duke’s executive leaders showed comparative data to highlight organizational performance and then took the team beyond the numbers, inviting patients to tell their "Duke Experi...

Growth hormone in children and adolescents with cystic fibrosis

Arquivos Brasileiros de Endocrinologia e Metabologia — Sat, 14 Jan 2012 00:35:00 +0100

The objective of this study was to assess the benefits of rhGH in children and adolescents with CF. We conducted a systematic review in the database PubMed, Lilacs, SciELO and Cochrane, in the period 2000-2010, using the keywords: "cystic fibrosis", "growth hormone", "children" and "adolescents". We found 77 articles and included 11 randomized controlled trials, with 290 children and adolescents with CF. The short-term use (1-24 months) of rhGH improved the height, weight, growth rate, bone mineral content and components of pulmonary function. Adverse effects, like diabetes, were not observed in the studies. The short-term use of rhGH improved growth and body composition in patients with CF. (Source: Arquivos Brasileiros de Endocrinologia e Metabologia)

Nucleosome occupancy reveals regulatory elements of the CFTR promoter

Nucleic Acids Research — Fri, 13 Jan 2012 05:00:00 +0100

Access to regulatory elements of the genome can be inhibited by nucleosome core particles arranged along the DNA strand. Hence, sites that are accessible by transcription factors may be located by using nuclease digestion to identify the relative nucleosome occupancy of a genomic region. In order to define novel cis regulatory elements in the ~2.7-kb promoter region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, we define its nucleosome occupancy. This profile reveals the precise positions of nucleosome-free regions (NFRs), both cell-type specific and others apparently unrelated to CFTR-expression level and offer the first high-resolution map of the chromatin structure of the entire CFTR promoter in relevant cell types. Several of these NFRs are strongly bound by n...

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The decline of fertility in male uremic patients is correlated with low expression of the cystic fibrosis transmembrane conductance regulator protein (CFTR) in human sperm

Human Reproduction — Fri, 13 Jan 2012 05:00:00 +0100

CONCLUSIONS Sperm CFTR expression is depressed in uremic patients but recovers to some degree after renal transplant along with some improvement in fertility, indicating a ‘reversible’ change. These results suggest that the CFTR expression rate in sperm is correlated with the decline of uremic patients' fertility, and may be considered as a potential marker to assess the fertility of male uremic patients. (Source: Human Reproduction)

Growing radiation dose for CF patients highlights risks

AuntMinnie.com Headlines — Thu, 12 Jan 2012 17:33:48 +0100

Patients with cystic fibrosis (CF) receive substantial radiation doses from (more) (Source: AuntMinnie.com Headlines)

Erratum to: Psychometric evaluation of the Cystic Fibrosis Questionnaire-Revised in a national, US sample

Quality of Life Research — Thu, 12 Jan 2012 16:45:30 +0100

Conclusions The CFQ-R demonstrated robust psychometric properties and consistent associations with health outcomes in a large national, US sample. Normative data are available to aid in interpretation. Content Type Journal ArticleCategory ErratumPages 1-12DOI 10.1007/s11136-011-0091-5Authors Alexandra L. Quittner, University of Miami, 5665 Ponce de Leon Blvd., Coral Gables, FL 33146, USAGregory S. Sawicki, Children’s Hospital Boston, Boston, MA, USAAnn McMullen, University of Rochester Medical Center, Rochester, NY, USALawrence Rasouliyan, ICON Late Phase & Outcomes Research, San Francisco, CA, USADavid J. Pasta, ICON Late Phase & Outcomes Research, San Francisco, CA, USAAshley Yegin, Genentech, Inc., South San Francisco, CA, USAMichael W. Konstan, Rainbow Babies a...

Non-cystic fibrosis bronchiectasis

Interactive CardioVascular and Thoracic Surgery — Thu, 12 Jan 2012 05:00:00 +0100

Bronchiectasis is characterized by irreversible widening of the medium-sized airways, with inflammation, chronic bacterial infection and destruction of the bronchial walls. Exercise or inspiratory muscle training may improve quality of life and exercise endurance in people with non-cystic fibrosis bronchiectasis. Prolonged-use antibiotics improve clinical response rates, but may not reduce exacerbation rates or lung function. Surgery is often considered for people with extreme damage to one or two lobes of the lung who are at risk for severe infection or bleeding. In this review, the authors will focus on non-cystic fibrosis bronchiectasis, pointing out the differences in management when compared with the cystic fibrosis context, with special emphasis on surgical management. (Source: Inter...

Should cystic fibrosis patients infected with Burkholderia cepacia complex be listed for lung transplantation?

Interactive CardioVascular and Thoracic Surgery — Thu, 12 Jan 2012 05:00:00 +0100

A best evidence topic was constructed according to a structured protocol. The question addressed was whether lung transplantation remained a beneficial treatment for cystic fibrosis (CF) patients infected or colonized with Burkholderia cepacia complex (BCC) prior to lung transplantation (LTx). Of the 25 papers found using a report search, five presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, study type, group studied, relevant outcomes and results of these papers are given. We conclude that, on the whole, the five studies were clearly in favor of maintaining access to LTx lists for BCC infected or colonized CF patients. In other words, access to LTx should not be denied to BCC infected CF patients in that the beneficial eff...

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Generation of SV40-transformed rabbit tracheal-epithelial-cell-derived blastocyst by somatic cell nuclear transfer

Cell and Tissue Research — Wed, 11 Jan 2012 06:56:09 +0100

This study describes the successful establishment and characterization of two SV40-transformed rabbit tracheal epithelial cell lines. These cell lines, 5RTEo- and 9RTEo-, express the CF transmembrane conductance regulator (CFTR) gene, retain epithelial-specific differentiated morphology and show CFTR-based cAMP-dependent Cl− ion transport across the apical membrane of a confluent monolayer. Immunocytochemical analysis indicates the presence of airway cytokeratins and tight-junction proteins in the 9RTEo- cell line after multiple generations. However, the tight junctions appear to diminish in their efficacy in both cell lines after at least 100 generations. Initial SCNT studies with the 9RTEo- cells have revealed that SV40-transformed rabbit airway epithelial donor cells can be ...

Nitric oxide and L-Arginine deficiency in cystic fibrosis.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Grasemann H, Ratjen F Abstract The concentrations of nitric oxide are decreased in airways of patients with cystic fibrosis. The reasons for this nitric oxide deficiency are incompletely understood but may include reduced production from nitric oxide synthases due to decreased expression the enzymes in airway epithelial cells, reduced availability of L-arginine, the substrate for nitric oxide synthases, and the presence of endogenous inhibitors of the enzymes in the airways. As nitric oxide plays a role in a number of important physiological processes in the lung including host defense against pathogens such as Pseudomonas aeruginosa, inflammation and the regulation of vascular and broncho motor tone, the lack of nitric oxide may contribute to lung disease in cystic fibros...

New treatments for emerging cystic fibrosis pathogens other than Pseudomonas.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Waters V Abstract The development of antimicrobial treatments for respiratory pathogens in cystic fibrosis (CF) has been an integral component to the increased survival of CF patients over the past fifty years. Despite significant treatment advances, however, respiratory failure secondary to chronic bacterial pulmonary infection remains the primary cause of death in CF patients. The purpose of this review is to discuss emerging pathogens (other than Pseudomonas) in CF by describing the characteristics of the organism, their clinical significance in CF, their mechanisms of antimicrobial resistance and the current treatment approaches including newer pharmaceutical modalities. This review will focus on the following pathogens: Burkholderia cepacia complex, Stenotrophomonas m...

New Developments in Inhaled Antibiotics for the Treatment of Pseudomonas Aeruginosa.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Hofmann T Abstract The field of inhaled antibiotics that target Pseudomonas aeruginosa infections has made substantial contributions to the health, disease management, and life expectancies of individuals with cystic fibrosis (CF) over the last three decades [1-3]. This paper reviews some of the recent clinical developments in the field of inhaled antibiotics for CF and briefly describes formulations and ongoing developments for US and/or European regulatory approvals. Lung delivery technologies, in regards to inhaled antibiotics for CF, are also reviewed. PMID: 22229573 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design)

Modifier gene studies to identify new therapeutic targets in cystic fibrosis.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Dorfman R Abstract Since the discovery of the CFTR gene mutations which cause cystic fibrosis (CF) in 1989 the average life expectancy of CF patients has almost doubled and now exceeds 37 years. The advances in molecular diagnostics and medical treatments expanded beyond the CF patient population as some of the newest treatments are also being tested for treatment of complex diseases such as COPD and other inherited disorders. Rapid development of CF therapeutics is important for the cystic fibrosis community and is an excellent example for other nonprofit organizations, disease foundations and pharmaceutical companies alike. Better understanding of disease variability and underlying molecular mechanisms through genetic association studies aimed to identify novel CF modifi...

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Progress in Gene and Cell Therapy for Cystic Fibrosis Lung Disease.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Griesenbach U, Alton EW Abstract Although the development of gene therapy for cystic fibrosis (CF) was high priority for many groups in academia and industry in the first 10 to 15 years after cloning the gene, more recently active research into CF gene therapy is only being performed by a small number of committed, mainly academic, groups. However, despite the warning enthusiasm, which is largely due to the realisation that gene transfer into lungs is more difficult than originally thought and the fact that meaningful clinical trials are expensive and difficult to perform, gene therapy continues to hold promise for the treatment of CF lung disease. Problems related to repeat administration of adenovirus and adeno-associated virus-based vectors led to a focus on non-viral v...

New therapies in cystic fibrosis.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Ratjen F, Grasemann H Abstract Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to abnormalities in transepithelial ion transport in the airways of affected patients. Lung disease is the major contributor to morbidity and mortality in patients with cystic fibrosis but recommended therapeutic interventions so far have focused on symptom control rather than treatment of the underlying causes of the disease. New therapies that are currently in pre-clinical and clinical testing include CFTR pharmacotherapy, drugs targeting other ion channels, and hydrators of the cystic fibrosis airways. The current status of these and other new developments in the treatment of cystic fibrosis are reviewed. PMID: 222295...

New Developments in Pharmaceutical Treatments for Cystic Fibrosis.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Grasemann H PMID: 22229569 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design)

Effects of chest physiotherapy and aerobic exercise training on physical fitness in young children with cystic fibrosis.

Italian Journal of Pediatrics — Tue, 10 Jan 2012 05:00:00 +0100

Background: Cystic fibrosis is a multisystem disease where the main problems are existing in the respiratory system. Aerobic exercise programs are effective in increasing physical fitness and muscle endurance in addition to chest physiotherapy.ObjectiveThe aim of this study was to evaluate the effects of chest physiotherapy and aerobic exercise training on physical fitness in young children with cystic fibrosis. Methods: Sixteen patients with cystic fibrosis, between the ages 5-13 years, were included in this study. All children were assessed at the beginning and at the end of 6 week of the training. Modified Bruce protocol was used for assessing the cardiovascular endurance. The sit-up test was used to evaluate the dynamic endurance of abdominal muscles, standing long jump was used to tes...

Studies Identify Promising Genes And Small Molecules To Use Against Devastating Diseases

Health News from Medical News Today — Mon, 09 Jan 2012 08:00:00 +0100

Two related studies from Northwestern University offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis (ALS), cancer, cystic fibrosis and type 2 diabetes. To do its job properly within the cell, a protein first must fold itself into the proper shape. If it doesn't, trouble can result. More than 300 diseases have at their root proteins that misfold, aggregate and eventually cause cellular dysfunction and death... (Source: Health News from Medical News Today)

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DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity [Research Articles]

The Journal of Lipid Research — Mon, 09 Jan 2012 05:00:00 +0100

This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of 5- and 6-desaturases, leading to decreased flux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The findings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are related to intrinsic alterations of PUFA metabolism and that they may be reversed by supplementation with DHA and EPA. (Source: The ...

Double lumen bi-cava cannula for veno-venous extracorporeal membrane oxygenation as bridge to lung transplantation in non-intubated patient

Interactive CardioVascular and Thoracic Surgery — Mon, 09 Jan 2012 05:00:00 +0100

We report the case of a non-intubated patient who benefited from veno-venous (VV) ECMO. A 35-year old cystic fibrosis man presented a severe respiratory decompensation with refractory hypercapnia. We opted for an ECMO instead of mechanical ventilation (MV). We implanted a double lumen bi-cava cannula (DLC) (Avalon EliteTM) in the right jugular vein. Before ECMO implantation, the patient presented refractory respiratory failure (pH = 7.1, PaO2 = 83 mmHg, PaCO2 = 103 mmHg). We proposed that the patient be placed on the high emergency lung transplantation waiting list after failure to wean him from ECMO. This registration was effective 10 days after ECMO implantation. The patient was grafted the next day. Under ECMO, mean PaO2, PaCO2 and TCA were 80.6&n...

"This is the Best Fatal Illness That You Can Have": Contrasting and Comparing the Experiences of Parenting Youth With Cystic Fibrosis and Congenital Heart Disease

Qualitative Health Research — Mon, 09 Jan 2012 05:00:00 +0100

Despite the important instrumental and emotional role that parents play in the lives of children with cystic fibrosis (CF) and congenital heart disease (CHD), qualitative researchers have not examined the similarities and differences between caregivers’ experiences. Informed by thematic analysis, in this qualitative study I explored what it is like to care for a child with a chronic illness from the perspective of CF and CHD parents at a children’s hospital in Canada. Pediatric caregiver stress was qualitatively different between CF and CHD parents, whereas temporal dilemmas were unique sources of stress for CF parents only. To alleviate stress, all parents drew on a three-way, interrelated process to comprehend their child’s illness and acquire perspective. By opening up...

Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Arquivos Brasileiros de Endocrinologia e Metabologia — Sun, 08 Jan 2012 19:33:01 +0100

Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50% in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, p...

Effects of low salinity media on growth, condition, and gill ion transporter expression in juvenile Gulf killifish, Fundulus grandis.

Sun, 08 Jan 2012 05:00:00 +0100

Authors: Patterson J, Bodinier C, Green C Abstract The Gulf killifish, Fundulus grandis, is a euryhaline teleost which has important ecological roles in the brackish-water marshes of its native range as well as commercial value as live bait for saltwater anglers. Effects of osmoregulation on growth, survival, and body condition at 0.5, 5.0, 8.0 and 12.0‰ salinity were studied in F. grandis juveniles during a 12-week trial. Relative expression of genes encoding the ion transport proteins Na(+)/K(+)-ATPase (NKA), Na(+)/K(+)/2Cl(-) cotransporter(NKCC1), and cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel was analyzed. At 0.5‰, F. grandis showed depressed growth, body condition, and survival relative to higher salinities. NKA relative expression was elevate...

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Aztreonam lysine for inhalation: New formulation of an old antibiotic.

American Journal of Health-System Pharmacy : AJHP — Fri, 06 Jan 2012 20:30:45 +0100

Conclusion Inhaled aztreonam has shown efficacy and safety in patients seven years of age or older with CF who have P. aeruginosa airway infections. This product may complement existing therapies and offers the advantage of a new inhaled formulation to aid in treatment regimens. PMID: 22215356 [PubMed - in process] (Source: American Journal of Health-System Pharmacy : AJHP)

New hope for diseases of protein folding such as Alzheimer’s, Parkinson’s diseases, ALS, cancer and diabetes

ScienceDaily Headlines — Fri, 06 Jan 2012 18:59:59 +0100

Two related studies offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, ALS, cystic fibrosis, cancer and type 2 diabetes. The research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development. (Source: ScienceDaily Headlines)

Tiny worm points to big promise

EurekAlert! - Medicine and Health — Fri, 06 Jan 2012 05:00:00 +0100

(Northwestern University) Two related studies from Northwestern University offer new strategies for tackling the challenges of preventing and treating diseases of protein folding, such as Alzheimer's, Parkinson's and Huntington's diseases, ALS, cystic fibrosis, cancer and type 2 diabetes. The research identifies new genes and pathways that prevent protein misfolding and toxic aggregation, keeping cells healthy, and also identifies small molecules with therapeutic potential that restore health to damaged cells, providing new targets for drug development. (Source: EurekAlert! - Medicine and Health)

[Insulin resistance in overweight cystic fibrosis paediatric patients.]

Anales de Pediatria — Fri, 06 Jan 2012 05:00:00 +0100

CONCLUSIONS: Overweight CF patients do not have a higher incidence of glycaemic disorders, but their hyperinsulinism and insulin resistance may be additional diabetogenic risk factors. PMID: 22227349 [PubMed - as supplied by publisher] (Source: Anales de Pediatria)

The use of a two-gene sequencing approach to accurately distinguish between the species within the Mycobacterium abscessus complex and Mycobacterium chelonae

European Journal of Clinical Microbiology and Infectious Diseases — Thu, 05 Jan 2012 17:05:22 +0100

We describe here an accurate and robust method for distinguishing M. chelonae from M. abscessus, M. bolletii and M. massiliense, using polymerase chain reaction (PCR) and the sequencing of house-keeping gene targets (hsp65 and rpoB). Sequencing of the sodA gene is of little additional value in discriminating between species, but M. massiliense can be rapidly identified by amplification of the truncated erm(41) gene without the need for amplicon sequencing. We have applied the method to 81 isolates from 40 patients from two hospitals, the majority of whom were cystic fibrosis (CF) patients. Of these patients, 21 had previously been identified as M. chelonae and 59 as M. abscessus complex using commercial line probe assays. We identified these as 46 M. abscessus isolates, 20 M. massilie...

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Armonk's The Gym Supports Make a Wish Foundation

Cystic Fibrosis Worldwide — Thu, 05 Jan 2012 14:07:49 +0100

(Source: Cystic Fibrosis Worldwide)

Enhance mind, body and spirit in 2012

Cystic Fibrosis Worldwide — Thu, 05 Jan 2012 12:51:15 +0100

(Source: Cystic Fibrosis Worldwide)

Attractions open doors for a loonie to help charity

Cystic Fibrosis Worldwide — Thu, 05 Jan 2012 10:41:32 +0100

(Source: Cystic Fibrosis Worldwide)

Health-related quality of life of Spanish children with cystic fibrosis

Quality of Life Research — Thu, 05 Jan 2012 06:51:55 +0100

Conclusions Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have. Content Type Journal ArticlePages 1-9DOI 10.1007/s11136-011-0100-8Authors Iris F. Groeneveld, Department of Biomedicine, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, SpainElena S. Sosa, Department of Biomedicine, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, SpainMargarita Pérez, Department of Biomedicine, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, SpainCarmen Fiuza-Luces, Department of Biomedicine, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Madrid, SpainLaura Gonzalez-Saiz, D...

Risk of Post Lung Transplant Renal Dysfunction in Adults with Cystic Fibrosis.

Chest — Thu, 05 Jan 2012 05:00:00 +0100

ConclusionsRenal dysfunction is common following lung transplant in the adult CF population. Increased age, female gender, CF-related diabetes requiring insulin, and pre transplant renal impairment are significant risk factors. PMID: 22222189 [PubMed - as supplied by publisher] (Source: Chest)

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Growing up with cystic fibrosis: achievement, life satisfaction, and mental health

Quality of Life Research — Wed, 04 Jan 2012 06:59:59 +0100

Conclusions Most patients with cystic fibrosis achieve ordinary social and vocational development into adulthood. A favorable mental health status seems more important than pulmonary function to maintain a good satisfaction with life. Content Type Journal ArticlePages 1-7DOI 10.1007/s11136-011-0096-0Authors Tanja Besier, Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Steinhoevelstr. 5, 89075 Ulm, GermanyLutz Goldbeck, Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Steinhoevelstr. 5, 89075 Ulm, Germany Journal Quality of Life ResearchOnline ISSN 1573-2649Print ISSN 0962-9343 (Source: Quality of Life Research)

Azithromycin maintenance therapy in patients with cystic fibrosis: A dose advice based on a review of pharmacokinetics, efficacy, and side effects

Pediatric Pulmonology — Tue, 03 Jan 2012 05:00:00 +0100

AbstractAzithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules used in clinical trials in order to come to a dosing advise which could be generally applicable. We used data from a recently updated Cochrane meta analysis (2011), the reports of clinical trials and pharmacokinetic studies. Based on these data, it was concluded that a dose level of 22–30 mg/kg/week is the lowest dose level with proven efficacy. Due to the extended half‐life in patients with CF, the weekly dose of azithromycin can be divided in one to seven dosing moments, depending...

Invasive pneumonia and septic shock in infants as a presentation of cystic fibrosis with vitamin‐deficiency

Pediatric Pulmonology — Tue, 03 Jan 2012 05:00:00 +0100

AbstractHerein we describe three infants with the rare presentation of pneumonia with septic shock as their initial medical encounter leading to the diagnosis of cystic fibrosis (CF). At the time of their presentation all three children had significant nutritional deficiency. We initiated an aggressive treatment regimen including nutritional supplementation which resulted in improvement in their pulmonary status and no further recurrences.This series highlights the possible presentation of CF in infancy as a life‐threatening invasive infection of Staphylococcus aureus or Pseudomonas aeruginosa. It also supports neonatal screening and emphasizes the role of early attention to nutritional status and vitamin supplementation. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc. (Source: Pediatr...

Open‐label, follow‐on study of azithromycin in pediatric patients with CF uninfected with pseudomonas aeruginosa

Pediatric Pulmonology — Tue, 03 Jan 2012 05:00:00 +0100

ConclusionsDuring the open‐label study, we observed continued durability of treatment response to azithromycin, as measured by pulmonary exacerbations and continued weight gain, although use of oral antibiotics increased. There were no new safety concerns. Currently available data suggest that azithromycin reduces exacerbations and improves weight gain for 6–12 months among children and adolescents with CF uninfected with P. aeruginosa. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)

Comparison of quantitative sweat chloride methods after positive newborn screen for cystic fibrosis

Pediatric Pulmonology — Tue, 03 Jan 2012 05:00:00 +0100

ConclusionsGiven the performance of the MSCS, the Minnesota CF Center has implemented the MSCS as its method of choice for diagnostic sweat testing in infants following a positive state NBS. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)

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Adherence to the 2007 cystic fibrosis pulmonary guidelines: A national survey of cf care centers

Pediatric Pulmonology — Tue, 03 Jan 2012 05:00:00 +0100

ConclusionTargeting outcome expectancy and external barriers with multifaceted, ongoing interventions may improve guideline adherence. Pulmonologists are clearly looking for empirical evidence that these medications benefit their patients over the long‐term and offset patient treatment burden with improved health. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc. (Source: Pediatric Pulmonology)

Enrichment of the inositol 1,4,5-trisphosphate receptor/Ca(2+) channels in secretory granules and essential roles of chromogranins.

Cell Calcium — Tue, 03 Jan 2012 05:00:00 +0100

Authors: Yoo SH, Hur YS Abstract The high capacity, low affinity Ca(2+) storage protein chromogranins are marker proteins of secretory granules that contain the most Ca(2+) in secretory cells. Along with the abundantly expressed chromogranins, the IP(3)R/Ca(2+) channels, the major intracellular Ca(2+) channels, are also expressed in secretory granules the most. Chromogranins not only induce formation of secretory granules but also are suggested to produce the small IP(3)-sensitive nucleoplasmic Ca(2+) store vesicles in the nucleus. Chromogranins A (CGA) and B (CGB) also directly bind the IP(3)Rs and activate the IP(3)R/Ca(2+) channels at the intragranular pH 5.5. But at a near physiological pH 7.5 only CGB interacts with the IP(3)Rs due to stronger interaction of CGB for the IP(3)R...

Conformational properties of two exopolysaccharides produced by Inquilinus limosus, a cystic fibrosis lung pathogen.

Carbohydrate Research — Tue, 03 Jan 2012 05:00:00 +0100

Authors: Kuttel M, Ravenscroft N, Foschiatti M, Cescutti P, Rizzo R Abstract Inquilinus limosus is a multi-resistant bacterium found in the respiratory tract of patients with cystic fibrosis. This bacterium produces two unique fully pyruvylated exopolysaccharides in similar quantities: an α-(1→2)-linked mannan and a β-(1→3)-linked glucan. We employed molecular modelling methods to probe the characteristic conformations and dynamics of these polysaccharides, with corroboration from potentiometric titrations and circular dichroism experiments. Our calculations reveal different structural motifs for the mannan and glucan polysaccharides: the glucan forms primarily right-handed helices with a wide range of extensions, while the mannan forms only left-handed helices. This finding ...

New hope in cystic fibrosis fight as Scots patients first to test drug

Cystic Fibrosis Worldwide — Mon, 02 Jan 2012 12:59:11 +0100

(Source: Cystic Fibrosis Worldwide)

Bordetella bronchiseptica in a Paediatric Cystic Fibrosis Patient: Possible Transmission from a Household Cat

Zoonoses and Public Health — Mon, 02 Jan 2012 05:00:00 +0100

SummaryBordetella bronchiseptica is a zoonotic respiratory pathogen commonly found in domesticated farm and companion animals, including dogs and cats. Here, we report isolation of B. bronchiseptica from a sputum sample of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory illness. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly suggest that the kitten was the source of infection. (Source: Zoonoses and Public Health)

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Conformational change opening the CFTR chloride channel pore coupled to ATP-dependent gating.

Biochimica et Biophysica Acta — Mon, 02 Jan 2012 05:00:00 +0100

Authors: Wang W, Linsdell P Abstract Opening and closing of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are controlled by ATP binding and hydrolysis by its nucleotide binding domains (NBDs). This is presumed to control opening of a single "gate" within the permeation pathway, however, the location of such a gate has not been described. We used patch clamp recording to monitor access of cytosolic cysteine reactive reagents to cysteines introduced into different transmembrane (TM) regions in a cysteine-less form of CFTR. The rate of modification of Q98C (TM1) and I344C (TM6) by both [2-sulfonatoethyl] methanethiosulfonate (MTSES) and permeant Au(CN)(2)(-) ions was reduced when ATP concentration was reduced from 1mM to 10μM, and modification by MTS...

Erratum: hypersusceptibility to respiratory viruses as a shared mechanism for asthma, chronic obstructive pulmonary disease, and cystic fibrosis.

American Journal of Respiratory Cell and Molecular Biology — Sun, 01 Jan 2012 05:00:00 +0100

Authors: PMID: 22210827 [PubMed - in process] (Source: American Journal of Respiratory Cell and Molecular Biology)

Verification of performance specifications of a molecular test: cystic fibrosis carrier testing using the luminex liquid bead array.

Archives of Pathology and Laboratory Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Conclusions.-Protocols for verification of in vitro diagnostic assays may vary between laboratories. However, all laboratories must verify several specific performance specifications prior to implementation of such assays for clinical use. We provide an example of an approach used for verifying performance of an assay for cystic fibrosis carrier screening. PMID: 22208482 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

Long‐Term Impact of Liver Transplantation on Respiratory Function and Nutritional Status in Children and Adults with Cystic Fibrosis

American Journal of Transplantation — Sun, 01 Jan 2012 05:00:00 +0100

In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long‐term lung function and preserving nutritional status. (Source: American Journal of Transplantation)

Interleukin-17 and cystic fibrosis lung disease.

American Journal of Respiratory and Critical Care Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Brodlie M, Corris PA, Lordan J, Ward C PMID: 22210793 [PubMed - in process] (Source: American Journal of Respiratory and Critical Care Medicine)

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Multi‐Species Biofilms: Living with Friendly Neighbors

FEMS Microbiology Reviews — Sun, 01 Jan 2012 05:00:00 +0100

AbstractOur knowledge regarding the nature and development of microbial biofilms has grown significantly since the first report of these communities by Antonie van Leeuwenhoek in the late 1600s. Nevertheless, most biofilm studies examine mono‐species cultures whereas nearly all biofilm communities in nature comprise a variety of microorganisms. The species that constitute a mixed biofilm and the interactions between these microorganisms critically influence the development and shape of the community. In this review we focus on interactions occurring within a multi‐species biofilm and their effects on the nature of the mixed community. In general, inter‐species interactions involve communication, typically via quorum sensing, and metabolic cooperation or competition. Interactions amon...

Pseudomonas aeruginosa biofilm‐associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia

Cellular Microbiology — Sun, 01 Jan 2012 05:00:00 +0100

SummaryPseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis CF) patients, a process regulated by quorum sensing molecules including N‐(3‐oxododecanoyl)‐L‐homoserine lactone, C12. C12 (10‐100 µM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ?F508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (?ψmito) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca2+ and ER‐targeted GFP and oxidized contents into the cytosol). Effects began within 5 minutes and were complete in 1‐2 hrs. C12 caused similar activation of caspases and release of cytoC fro...

Type 3 secretion system effector genotype and secretion phenotype of longitudinally‐collected P. aeruginosa isolates from young children diagnosed with cystic fibrosis following newborn screening

Clinical Microbiology and Infection — Sun, 01 Jan 2012 05:00:00 +0100

This study provides new insight into the T3SS characteristics of P. aeruginosa isolated from the CF airway early in life. (Source: Clinical Microbiology and Infection)

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen.

Clinical Microbiology Reviews — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Brooke JS Abstract Summary: Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infectio...

Editorial

Journal of Cystic Fibrosis — Sun, 01 Jan 2012 05:00:00 +0100

Eradication of Pseudomonas aeruginosa by early antibiotic treatment has been one of the major advances in the last decade for subjects with CF . This fantastic success has let many people to forget that this pathogen is not the only one present in CF airways. The study by Vanderhelst and colleagues puts the finger on another dangerous bacterium, methicillin-resistant Staphylococcus aureus (MRSA) which rose in prevalence in CF from 0.1% in 1995 to 22% in 2007. Using registry data from 2002 to 2010, their retrospective case–control study showed that the prevalence of MRSA in chronically S. aureus infected patients, was 15.2% from which 12.6% were chronically infected. Importantly, MRSA caused a more rapid lung function decline compared with controls. (Source: Journal of Cystic Fibrosis)

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Nutritional management of cystic fibrosis.

JPEN Journal Of Parenteral And Enteral Nutrition — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Matel JL PMID: 22237878 [PubMed - in process] (Source: JPEN Journal Of Parenteral And Enteral Nutrition)

Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCOFormula Secretion.

Physiological Reviews — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Lee MG, Ohana E, Park HW, Yang D, Muallem S Abstract Fluid and HCO(3)(-) secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO(3)(-) secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO(3)(-) secretion, in particular by secretory glands. Fluid and HCO(3)(-) secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl(-) and sec...

Corrector-mediated rescue of misprocessed CFTR mutants can be reduced by the P-glycoprotein drug pump.

Biochemical Pharmacology — Sat, 31 Dec 2011 01:47:24 +0100

Authors: Loo TW, Bartlett MC, Shi L, Clarke DM Abstract The most common cause of cystic fibrosis is deletion of Phe508 in the first nucleotide-binding domain (NBD) of the CFTR chloride channel, which inhibits protein folding. ΔF508 CFTR can be rescued by indirect approaches such as low temperature but the protein is unstable. Here, we tested our predictions that (1) other CFTR mutants such V232D and H1085R were more stable at the cell surface than ΔF508 CFTR after low temperature rescue and (2) the advantages of rescue with specific correctors (pharmacological chaperones) are that they may stabilize ΔF508 CFTR and increase the effectiveness of the correctors by bypassing drug pumps such as P-glycoprotein (P-gp) (increased bioavailability). It was found that the stability of muta...

Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways

Histochemistry and Cell Biology — Fri, 30 Dec 2011 07:09:21 +0100

Abstract Epithelial sodium channels (ENaCs) are located on the apical surface of cells and funnel Na+ ions from the lumen into the cell. ENaC function also regulates extracellular fluid volume as water flows across membranes accompanying Na+ ions to maintain osmolarity. To examine the sites of expression and intracellular localization of ENaC, we generated polyclonal antibodies against the extracellular domain of human α-ENaC subunit that we expressed in E. coli. Three-dimensional (3D) confocal microscopy of immunofluorescence using these antibodies for the first time revealed that ENaCs are uniformly distributed on the ciliary surface in all epithelial cells with motile cilia lining the bronchus in human lung and female reproductive tract, all along the fimbrial end of th...