Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Critical Pathways”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1997

Cholecystokinin cells.

Cholecystokinin (CCK) is an important hormonal regulator of the digestive process. CCK cells are concentrated in the proximal small intestine, and hormone is secreted into the blood upon the ingestion of food. The physiological actions of CCK include stimulation of pancreatic secretion and gallbladder contraction, regulation of gastric emptying, and induction of satiety. Therefore, in a highly coordinated manner, CCK regulates the ingestion, digestion, and absorption of nutrients. CCK is produced by two separate cell types: endocrine cells of the small intestine and various neurons in the gastrointestinal tract and central nervous system. Accordingly, CCK can function as either a hormone or a neuropeptide. This review focuses on the physiology of the CCK cell in the intestine and, in particular, on how the CCK cell is regulated to secrete its hormone product. The effects of ingested nutrients on the CCK cell and the intracellular messenger systems involved in controlling secretion are reviewed. A summary is provided of recent studies examining the electrophysiological properties of CCK cells and newly discovered proteins that act as releasing factors for CCK, which mediate feedback pathways critical for regulated secretion in the intact organism.

Animals↗
PubMed1999

MAP kinase cascade is required for p27 downregulation and S phase entry in fibroblasts and epithelial cells.

The present report delineates the critical pathway in the G(1) phase involved in downregulation of p27(Kip1), a cyclin-dependent kinase inhibitor, which plays a pivotal role in controlling entry into the S phase of the cell cycle. In resting CCL39 fibroblasts and IEC-6 intestinal epithelial cells, protein levels of p27(Kip1) were elevated but dramatically decreased on serum stimulation, along with hyperphosphorylation of pRb and increased CDK2 activity. In both cell types, expression of ras resulted in an increase of basal and serum-stimulated E2F-dependent transcriptional activity and a reduction in p27(Kip1) protein levels as well. The role of the mitogen-activated protein (MAP) kinase cascade in p27(Kip1) reduction and S phase reentry was reinforced by the blockades of serum-induced E2F-dependent transcriptional activity and p27(Kip1) downregulation with the MKK-1/2 inhibitor PD-98059. In both cell lines, downregulation of p27(Kip1) was associated with a repression of its synthesis, an event mediated by the p42/p44 MAP kinase pathway. Using an antisense approach, we demonstrated that p27(Kip1) may control cell cycle exit in both cell types. These data indicate that activation of the MAP kinase cascade is required for S phase entry and p27(Kip1) downregulation in fibroblasts and epithelial cells.

Animals↗
PubMed2004

Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry.

Transient receptor potential (TRP) cation channels are a critical pathway for Ca2+ entry during pulmonary artery (PA) smooth muscle contraction. However, whether canonical TRP (TRPC) subunits and which TRP channel isoforms are involved in store depletion-induced pulmonary vasoconstriction in vivo remain unclear. This study was designed to test whether overexpression of the human TRPC1 gene (hTRPC1) in rat PA enhances pulmonary vasoconstriction due to store depletion-mediated Ca2+ influx. The hTRPC1 was infected into rat PA rings with an adenoviral vector. RT-PCR and Western blot analyses confirmed the mRNA and protein expression of hTRPC1 in the arterial rings. The amplitude of active tension induced by 40 mM K+ (40K) in PA rings infected with an empty adenoviral vector (647 +/- 88 mg/mg) was similar to that in PA rings infected with hTRPC1 (703 +/- 123 mg/mg, P = 0.3). However, the active tension due to capacitative Ca2+ entry (CCE) induced by cyclopiazonic acid was significantly enhanced in PA rings overexpressing hTRPC1 (91 +/- 13% of 40K-induced contraction) compared with rings infected with an empty adenoviral vector (61 +/- 14%, P < 0.001). Endothelial expression of hTRPC1 was not involved since the CCE-induced vasoconstriction was also enhanced in endothelium-denuded PA rings infected with the adenoviral vector carrying hTRPC1. These observations demonstrate that hTRPC1 is an important Ca(2+)-permeable channel that mediates pulmonary vasoconstriction when PA smooth muscle cell intracellular Ca2+ stores are depleted.

Adenoviridae↗
PubMed2003

Microarray-based discovery of highly expressed olfactory mucosal genes: potential roles in the various functions of the olfactory system.

We sought to gain a global view of tissue-specific gene expression in the olfactory mucosa (OM), the major site of neurogenesis and neuroregeneration in adult vertebrates, by examination of its overexpressed genes relative to that in 81 other developing and adult mouse tissues. We used a combination of statistical and fold-difference criteria to identify the top 269 cloned cDNAs from an array of 8,734 mouse cDNA elements on the Incyte Mouse GEM1 array. These clones, representing known and poorly characterized gene transcripts, were grouped according to their relative expression patterns across the other tissues and then further examined with respect to gene ontology categories. Approximately one-third of the 269 genes were also highly expressed in developing and/or adult central nervous system tissues. Several of these have been suggested or demonstrated to play roles in neurogenesis, neuronal differentiation, and/or neuronal migration, further suggesting that many of the unknown genes that share this expression pattern may play similar roles. Highly OM-specific genes included a palate, lung, and nasal epithelium carcinoma-associated gene (Plunc); sphingosine phosphate lyase (Sgpl1), and paraoxonase 1 (Pon1). Cell-type-specific expression within OM was established using in situ hybridization for several representative expression pattern clusters. Using the ENSEMBL-assembled mouse genome and comparative genomics analyses to the human genome, we assigned many of the unknown expressed sequence tags (ESTs) and poorly characterized genes to either novel or known gene products and provided predictive classification. Further exploration of this database will provide additional insights into genes and pathways critical for olfactory neurogenesis, neuronal differentiation, olfaction, and mucosal defense.

Aging↗
PubMed2004

Combined targeting of epidermal growth factor receptor and MDM2 by gefitinib and antisense MDM2 cooperatively inhibit hormone-independent prostate cancer.

PURPOSE: The epidermal growth factor receptor (EGFR) may play a relevant role in the progression, hormone therapy resistance, and prognosis of prostate cancer patients. Also MDM2, a negative p53 regulator that interacts with retinoblastoma (Rb), E2F, p19(arf) and the ras-mitogen-activated protein kinase(MAPK) cascade plays an important role in prostate cancer progression and prognosis. On the basis of the EGFR and MDM2 role in integrating signaling pathways critical for prostate cancer progression, we investigated whether their selective combined blockade may have a cooperative antitumor effect in prostate cancer. For this purpose, we have used the EGFR tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) and a second generation hybrid oligonucleotide antisense MDM2 (AS-MDM2), respectively. EXPERIMENTAL DESIGN: Gefitinib and AS-MDM2 were administered to hormone-refractory and hormone-dependent human prostate cancer cells in vitro and to mice bearing tumor xenografts, evaluating the effects on growth, apoptosis, and protein expression, in vitro and in vivo. RESULTS: We demonstrated that the combination of gefitinib and AS-MDM2 synergistically inhibits the growth of hormone-independent prostate cancer cells in vitro. This effect is accompanied by the inhibition of MDM2, phosphorylated Akt (pAkt), phosphorylated MAPK (pMAPK), and vascular endothelial growth factor (VEGF) expression and by Rb hypophosphorylation. The combination of the two agents in nude mice bearing the same hormone-independent tumors caused a potent cooperative antitumor effect. Tumor samples analysis confirmed the inhibition of MDM2, pAkt, pMAPK, VEGF, and basic fibroblast growth factor expression. CONCLUSIONS: This study shows that EGFR and MDM2 play a critical role in the growth of prostate cancer, especially hormone-dependent, and that their combined blockade by gefitinib and AS-MDM2 causes a cooperative antitumor effect, supporting the clinical development of this therapeutic strategy.

Animals↗
PubMed2004

Promoter hypermethylation profile of kidney cancer.

PURPOSE: Promoter hypermethylation is an important mechanism of inactivation of tumor suppressor genes in cancer cells. Kidney tumors are heterogeneous in their histology, genetics, and clinical behavior. To gain insight into the role of epigenetic silencing of tumor suppressor and cancer genes in kidney tumorigenesis, we determined a hypermethylation profile of kidney cancer. EXPERIMENTAL DESIGN: We examined the promoter methylation status of 10 biologically significant tumor suppressor and cancer genes in 100 kidney tumors (50 clear cell, 20 papillary, 6 chromophobe, 5 collecting duct, 5 renal cell unclassified, 7 oncocytoma, 6 transitional cell carcinomas of the renal pelvis, and 1 Wilms' tumor) by methylation-specific PCR. The hypermethylation profile was examined with regard to clinicopathological characteristics of the kidney cancer patients. RESULTS: Hypermethylation of one or more genes was found in 93 (93%) of 100 tumors. A total of 33% of kidney tumors had one gene, 35% two genes, 14% three genes, and 11% four or more genes hypermethylated. The frequency of hypermethylation of the 10 genes in the 100 tumor DNAs was VHL 8% (all clear cell), p16(INK4a) 10%, p14(ARF) 17%, APC 14%, MGMT 7%, GSTP1 12%, RARbeta2 12%, RASSF1A 45%, E-cadherin 11%, and Timp-3 58%. Hypermethylation was observed in all of the histological cell types and grades and stages examined. No hypermethylation was observed in specimens of normal kidney or ureteral tissue from 15 patients. Hypermethylation of VHL was specific to clear cell tumors. RASSF1A methylation was detected at a significantly higher frequency in papillary renal cell tumors and in high-grade tumors of all cell types. MGMT methylation was more frequent in nonsmokers. Simultaneous methylation of five or more genes was observed in 3 (3%) of 100 tumors and may indicate a methylator phenotype in kidney cancer. In addition, the CpG island in the promoter of the fumarate hydratase (FH) tumor suppressor gene was bisulfite sequenced and was found to be unmethylated in 15 papillary renal tumors. CONCLUSIONS: Promoter hypermethylation is common, can occur relatively early, may disrupt critical pathways, and, thus, likely plays an important role in kidney tumorigenesis. A hypermethylation profile may be useful in predicting a patient's clinical outcome and provide molecular markers for diagnostic and prognostic approaches to kidney cancer.

Adult↗
PubMed2005

Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC.

Valproic acid is a well-tolerated anticonvulsant that has been identified recently as a histone deacetylase inhibitor. To evaluate the antitumor efficacy and mechanisms of action of valproic acid in medulloblastoma and supratentorial primitive neuroectodermal tumor (sPNET), which are among the most common malignant brain tumors in children with poor prognosis, two medulloblastoma (DAOY and D283-MED) and one sPNET (PFSK) cell lines were treated with valproic acid and evaluated with a panel of in vitro and in vivo assays. Our results showed that valproic acid, at clinically safe concentrations (0.6 and 1 mmol/L), induced potent growth inhibition, cell cycle arrest, apoptosis, senescence, and differentiation and suppressed colony-forming efficiency and tumorigenicity in a time- and dose-dependent manner. The medulloblastoma cell lines were more responsive than the sPNET cell line and can be induced to irreversible suppression of proliferation and significantly reduced tumorigenicity by 0.6 and 1 mmol/L valproic acid. Daily i.p. injection of valproic acid (400 mg/kg) for 28 days significantly inhibited the in vivo growth of DAOY and D283-MED s.c. xenografts in severe combined immunodeficient mice. With Western hybridization and real-time reverse transcription-PCR, we further showed that the antitumor activities of valproic acid correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, and suppression of TP53, CDK4, and CMYC expression. In conclusion, valproic acid possesses potent in vitro and in vivo antimedulloblastoma activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, valproic acid may represent a novel therapeutic option in medulloblastoma treatment.

Acetylation↗
PubMed2002

Candidate gene association studies in sporadic Alzheimer's disease.

The genetics of Alzheimer's disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the epsilon4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-beta, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE epsilon4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.

Age of Onset↗
PubMed2006

Angiotensin-converting enzyme II in the heart and the kidney.

The renin-angiotensin system (RAS) has been recognized for many years as critical pathway for blood pressure control and kidney functions. Although most of the well-known cardiovascular and renal effects of RAS are attributed to angiotensin-converting enzyme (ACE), much less is known about the function of ACE2. Experiments using genetically modified mice and inhibitor studies have shown that ACE2 counterbalances the functions of ACE and that the balance between these two proteases determines local and systemic levels of RAS peptides such as angiotensin II and angiotensin1-7. Ace2 mutant mice exhibit progressive impairment of heart contractility at advanced ages, a phenotype that can be reverted by loss of ACE, suggesting that these enzymes directly control heart function. Moreover, ACE2 is also found to be upregulated in failing hearts. In the kidney, ACE2 protein levels are significantly decreased in hypertensive rats, suggesting a negative regulatory role of ACE2 in blood pressure control. Moreover, ACE2 expression is downregulated in the kidneys of diabetic and pregnant rats and ACE2 mutant mice develop late onset glomerulonephritis resembling diabetic nephropathy. Importantly, ACE2 not only controls angiotensin II levels but functions as a protease on additional molecular targets that could contribute to the observed in vivo phenotypes of ACE2 mutant mice. Thus, ACE2 seems to be a molecule that has protective roles in heart and kidney. The development of drugs that could activate ACE2 function would allow extending our treatment options in diabetic nephropathy, heart failure, or hypertension.

Angiotensin-Converting Enzyme 2↗
PubMed2001

Cell cycle protein expression in vascular smooth muscle cells in vitro and in vivo is regulated through phosphatidylinositol 3-kinase and mammalian target of rapamycin.

Cell cycle progression represents a key event in vascular proliferative diseases, one that depends on an increased rate of protein synthesis. An increase in phosphatidylinositol 3-kinase (PI 3-kinase) activity is associated with vascular smooth muscle cell proliferation, and rapamycin, which blocks the activity of the mammalian target of rapamycin, inhibits this proliferation in vitro and in vivo. We hypothesized that these 2 molecules converge on a critical pathway of translational regulation that is essential for successful upregulation of cell cycle-regulatory proteins in activated smooth muscle cells. p70(S6) kinase, a target of PI 3-kinase and the mammalian target of rapamycin, was rapidly activated on growth factor stimulation of quiescent coronary artery smooth muscle cells and after balloon injury of rat carotid arteries. The translational repressor protein 4E-binding protein 1 was similarly hyperphosphorylated under these conditions. These events were associated with increases in the protein levels of cyclin B1, cyclin D1, cyclin E, cyclin-dependent kinase 1, cyclin-dependent kinase 2, proliferating cell nuclear antigen, and p21(Cip1) in vivo and in vitro, whereas inhibition of the PI 3-kinase signaling pathway with either rapamycin or wortmannin blocked the upregulation of these cell cycle proteins, but not mRNA, and arrested the cells in vitro before S phase. In contrast to findings in other cell types, growth factor- or balloon injury-induced downregulation of the cell cycle inhibitor p27(Kip1) was not affected by rapamycin treatment. These data suggest that cell cycle progression in vascular cells in vitro and in vivo depends on the integrity of the PI 3-kinase signaling pathway in allowing posttranscriptional accumulation of cell cycle proteins.

Angioplasty, Balloon↗
PubMed2001

Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality.

It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine which histopathologic features predict survival in IPF. We prospectively studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent and severity of specific histopathologic features. We used Cox proportional-hazards models to assess the effect of histopathologic patterns on patients' survival. The effects of age, sex, and smoking were also included in the analysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffness at presentation were also shown to be independent factors predicting survival. The extent of fibroblastic foci present on lung biopsy predicts survival in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelial damage and repair process associated with persistent fibroblastic proliferation. Controlling these processes, rather than stopping inflammation, appears most important in preventing progressive disease and the fatal outcome common in IPF.

Adult↗
PubMed1996

Receptors in the Pseudomonas aeruginosa adherence to injured and repairing airway epithelium.

In the normal respiratory tract, the airway epithelial surface is protected from pathogenic bacterial colonization by the mucociliary clearance. The mucins present in the gel mucus layer exhibit a high diversity of carbohydrate receptors that allow specific bacterial recognition followed by bacterial and mucus elimination. As soon as the mucociliary clearance mechanism is impaired, the bacterial attachment to mucins in association with mucus stasis represent critical pathways for bacterial colonization of the airway epithelium. Several sources of injury may damage the epithelial integrity and induce partial or complete epithelial shedding, exposing cellular receptors and unmasked extracellular matrix (ECM) components that can be recognized by bacterial adhesins. Laminin and type I and IV collagens represent sites of Pseudomonas aeruginosa attachment to the ECM components. During airway epithelium repair after injury, particularly in cystic fibrosis (CF), the repairing cells exhibit apical receptors such as asialylated gangliosides (asialo GM1) to which P. aeruginosa adheres. The identification of the different receptors for P. aeruginosa, present either on the ECM proteins or on the apical surface of the remodeled airway epithelium, particularly in repairing respiratory CF epithelial cells, is a prerequisite to further therapeutic strategies to prevent airway colonization by P. aeruginosa.

Adhesins, Bacterial↗
PubMed1998

CD49d expression and function on allergen-stimulated T cells from blood and airway.

The alpha4 chain (CD49d), which constitutes one of the chains of alpha4beta1 (very late activating antigen-4 [VLA-4]) and alpha4beta7 integrins, mediates migration of T cells to extravascular spaces. The interaction between VLA-4 and vascular cell adhesion molecule-1 (VCAM-1) has been shown to be the critical pathway for the selective accumulation of eosinophils and basophils at sites of allergic inflammation. T lymphocytes are also specifically recruited into allergic sites, including the allergic asthmatic airway. Increased numbers of activated CD4+ cells expressing the DR antigen subset of the human leukocyte antigens (HLA-DR) appear in the allergic lung 48 h after allergen inhalation. The mechanisms by which these cells localize into the lung are still unknown. We report that stimulation of allergen-specific T cells with allergen in vitro resulted in enhanced expression of alpha4 chain (CD49d) as measured by receptor density on allergen-specific T-cell lines and T-cell clones. Kinetic studies showed that CD49d density was enhanced over a 24- to 48-h period in a time-dependent fashion, and was coordinately upregulated with HLA-DR expression. We also demonstrated that increased expression of CD49d on T-cell lines 24 h and 48 h after stimulation correlated with increased adhesion to the CS-1 fragment of fibronectin. In contrast, lymphocyte function-associated antigen-1b (LFA-1b) (CD11b), LFA-3 (CD58), and intercellular adhesion molecule-1 (ICAM-1) (CD54) expression did not change with allergen stimulation. We also showed that CD49d receptor density on T cells obtained by bronchoalveolar lavage (BAL) of allergic patients before and 48 h after allergen challenge was significantly higher than that on T cells taken from BAL of normal subjects and from controls with other inflammatory lung diseases. Taken together, these findings indicate that allergen stimulation activates allergen-specific T cells and coordinately induces increased CD49d receptor expression and binding to counterligands. We postulate that allergen-driven upregulation of CD49d, which together with the beta1 chain constitutes VLA-4 integrin, may be responsible for the selective accumulation of T cells in the allergic asthmatic lung.

Adult↗
PubMed2006

Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is characterized clinically by changes in the retinal pigment epithelium (RPE), formation of drusen between the RPE and the underlying vasculature, geographic atrophy, and choroidal neovascularization. Later clinical stages are accompanied by impaired central vision. A limited understanding of the molecular events responsible for AMD has constrained the development of effective treatments. A proteomics approach was used to investigate the underlying mechanisms of AMD and to identify proteins exhibiting significant changes in expression with disease onset and progression. METHODS: Human donor eyes were categorized into one of four progressive stages of AMD. Proteins from the RPE were resolved and quantified by two-dimensional (2-D) gel electrophoresis. Proteins exhibiting significant expression changes at different disease stages were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. 2-D and semiquantitative one dimensional (1-D) Western blot analyses were used to determine whether changes identified by the proteomic analysis were specific for a protein subpopulation or representative of the entire protein population. RESULTS: Proteins were identified from several critical pathways that changed at early and late disease stages, indicating potential causal mechanisms and secondary consequences of AMD, respectively. Proteins involved in protecting from stress-induced protein unfolding and aggregation, mitochondrial trafficking and refolding, and regulating apoptosis changed early in the disease process. Late-stage changes occurred in proteins that regulate retinoic acid and regeneration of the rhodopsin chromophore. CONCLUSIONS: These results provide the first direct evidence of AMD stage-specific changes in human RPE protein expression and provide a basis for functional investigation of AMD that may ultimately suggest new therapeutic strategies.

Adult↗
PubMed2006

Role of A2B adenosine receptor signaling in adenosine-dependent pulmonary inflammation and injury.

Adenosine has been implicated in the pathogenesis of chronic lung diseases such as asthma and chronic obstructive pulmonary disease. In vitro studies suggest that activation of the A2B adenosine receptor (A2BAR) results in proinflammatory and profibrotic effects relevant to the progression of lung diseases; however, in vivo data supporting these observations are lacking. Adenosine deaminase-deficient (ADA-deficient) mice develop pulmonary inflammation and injury that are dependent on increased lung adenosine levels. To investigate the role of the A2BAR in vivo, ADA-deficient mice were treated with the selective A2BAR antagonist CVT-6883, and pulmonary inflammation, fibrosis, and airspace integrity were assessed. Untreated and vehicle-treated ADA-deficient mice developed pulmonary inflammation, fibrosis, and enlargement of alveolar airspaces; conversely, CVT-6883-treated ADA-deficient mice showed less pulmonary inflammation, fibrosis, and alveolar airspace enlargement. A2BAR antagonism significantly reduced elevations in proinflammatory cytokines and chemokines as well as mediators of fibrosis and airway destruction. In addition, treatment with CVT-6883 attenuated pulmonary inflammation and fibrosis in wild-type mice subjected to bleomycin-induced lung injury. These findings suggest that A2BAR signaling influences pathways critical for pulmonary inflammation and injury in vivo. Thus in chronic lung diseases associated with increased adenosine, antagonism of A2BAR-mediated responses may prove to be a beneficial therapy.

Adenosine↗
PubMed2003

Respiratory management of pediatric patients with spinal cord injuries: retrospective review of the duPont experience.

Pulmonary complications contribute to morbidity and mortality in spinal cord injuries (SCIs). A retrospective review of 20 years of experience with tracheostomy- and ventilator-dependent SCI children is presented. The authors developed and analyzed a database of 47 children (average age = 11.4 years). Of the patients, 27% had concomitant brain injuries, 6% had prior histories of reactive airway disease, and 2% had thoracic fractures. Injuries were caused by motor vehicle accidents (53%); gunshot wounds (19%); sports-related accidents (19%); and vascular injuries, transverse myelitis, or spinal tumors (8%). Of the injuries, 52% were high level (C1 to C2) and 48% were mid- or low level (C3 to C5). Two groups were analyzed for demographic information. Complications included tracheitis, atelectasis, and pneumonia. Mean tidal volume was 14 cm2/kg (maximum = 22 cm2/kg). Bedside lung function parameters were attempted to assess readiness and the rapidity of weans. T-piece sprints were used to successfully wean 63% of patients. Successfully weaned patients were compared with those not weaned. No deaths or readmissions for late-onset respiratory failure postwean occurred. The authors' clinical impression favors higher tidal volumes and aggressive bronchial hygiene to minimize pulmonary complications and enhance weaning. Successfully weaned patients had fewer complications. A critical pathway for respiratory management of SCI children is presented.

Adolescent↗
PubMedDate not supplied

What's happening in quality improvement at the local hospital: a state-wide study from the Cooperative Cardiovascular Project.

The objective of this study was to investigate what happened to improve the quality of care for acute myocardial infarction (AMI) at all 32 nonfederal hospitals in Connecticut and to assess the impact of the Cooperative Cardiovascular Project (CCP) on quality improvement (QI) activities for AMI. We performed a questionnaire study with secondary analyses using the CCP database. On-site interviews were conducted with QI directors at all 32 Connecticut nonfederal hospitals that participated in the Health Care Financing Administration's Cooperative Cardiovascular Project (CCP) in 1992-93 and 1995. The interviews sought information about the makeup of QI departments, specific approaches used to improve the care of patients with AMI, and the perceived value of the CCP to each individual hospital. Results showed that the number of full-time equivalents (FTEs) and FTEs per beds employed in QI departments ranged from 1 to 30 and from 0.4 to 7.9, respectively, with a registered nurse most often serving as the department head (27/32). Over half of the departments (17/32) had additional responsibilities. The majority (25/32) used some combination of physician champions, multidisciplinary QI teams, standing orders, or critical pathways to effect change in AMI care. Finally, 26 of the 32 hospitals believed the CCP was valuable because it provided credible benchmark data, a catalyst for change, or a specific focus on processes of care needing improvement in AMI. Despite great variability in institutional resources, all 32 hospitals used a similar combination of QI approaches to effect change in AMI care. However, there is variable scientific evidence supporting these approaches. Externally sponsored projects such as the CCP appear to play a useful role for individual hospitals. Defining the optimal methods of QI is difficult given that hospitals are using complex combinations of nonstandardized improvement interventions.

Connecticut↗
PubMed2005

Trade related infections: farther, faster, quieter.

Modern global trading traffics large volumes of diverse products rapidly to a broad geographic area of the world. When emergent infections enter this system in traded products their transmission is amplified. With truly novel emergent infections with long incubation periods, such as Human Immunodeficiency Virus (HIV) or variant Creutzfeld Jacob Disease (vCJD), this transmission may silently disseminate infection to far distant populations prior to detection. We describe the chronology of two such "stealth infections," vCJD and HIV, and the production, processing, and distribution changes that coincided with their emergence. The concept of "vector products" is introduced. A brief case study of HIV incursion in Japan is presented in illustration. Careful "multisectoral" analysis of such events can suggest ecologically critical pathways of emergence for further research. Such analyses emphasize the urgency of implementing safety measures when pathogens enter globally traded products.

Journal Article↗