Journal of investigative medicine : the official publication of the American Federation for Clinical Research
-
Comparative Study
Validation of Duruöz Hand Index for diabetic hand dysfunction.
Duruöz Hand Index (DHI) is a functional disability scale that can be used successfully to assess the functional disability with different hand arthropathies. The hands are frequently involved in diabetic patients. We aimed to examine the use of DHI for its accuracy and ease in assessing these patients. ⋯ The DHI is a practical scale that is efficient in accurate assessment of hand dysfunction in diabetic patients.
-
Review
Pharmacologic therapies on the horizon for acute lung injury/acute respiratory distress syndrome.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of diseases that are commonly encountered in the intensive care unit and are associated with high mortality. Although significant advances have been made with respect to the ventilatory management of patients with ALI/ARDS with proven beneficial effects on outcomes, pharmacologic therapies remain nonexistent. ⋯ These agonists all have in common the ability to directly mediate endothelial cell signaling and induce characteristic actin cytoskeletal rearrangement leading to endothelial cell barrier protection. Our in vitro findings have been extended to animal models of ALI/ARDS and suggest that effective pharmacologic therapies for patients with ALI/ARDS may soon be available.
-
Acute lung injury (ALI) and its most severe form the acute respiratory distress syndrome occur in patients who have a predisposing severe inflammatory insult to the lung. Most often ALI is due to sepsis from bacterial infection, but ALI can occur with any infection and with noninfectious insults such as severe trauma, acute pancreatitis, aspiration, and near-drowning. After any of these insults, the interindividual risk of progression to ALI and the risk of death remain difficult to predict. ⋯ There is substantial evidence for heritable predispositions to severe infections and an emerging body of literature implicating genetic factors in ALI pathogenesis. A paradigm is emerging that the genetic risk for ALI can be best understood in terms of factors that control 3 overlapping stages of ALI pathogenesis: risk for the acquisition of a predisposing condition (such as a severe pneumonia), risk for progression to lung injury during systemic inflammatory states (such as severe sepsis), and risk for failure of endogenous mechanisms to resolve the lung injury. The evidence supporting this paradigm is herein reviewed, along with potential treatment strategies that could be directed by knowledge of specific genetic factors in an individual patient.
-
Fragile X-associated tremor/ataxia syndrome is a late adult onset neurodegenerative disorder that affects individuals who carry a premutation CGG repeat expansion (55-200 CGG repeats) in the 5' untranslated portion of the fragile X mental retardation 1 (FMR1) gene. Affected individuals display cognitive decline, progressive intention tremor, gait ataxia, neuropathy, psychiatric symptoms, and parkinsonism; the severity of both clinical and neuropathological phenotypes is positively correlated with the extent of the CGG expansion. ⋯ This mechanism is entirely different from the mechanism giving rise to fragile X syndrome, which is due to transcriptional silencing and consequent loss of FMR1 protein. Much of the research in the field has focused on understanding the link between the pathogenic FMR1 messenger RNA and the potential proteins that interact with it.
-
Comparative Study
MUC7 polymorphisms are associated with a decreased risk of a diagnosis of asthma in an African American population.
Mucin glycoproteins contribute to lung pathophysiology in asthma. The protein backbone of mucin glycoproteins is encoded by specific MUC genes, which exhibit a high degree of polymorphisms that generate a variable number of tandem repeat (VNTR) domains. MUC7 typically encodes for 6 VNTRs, each with 23 amino acids. In a northern European cohort, a polymorphism encoding MUC7*5 (5-VNTR) is in 100% linkage disequilibrium with the single nucleotide polymorphism rs9982010 and associated with a decreased risk of being asthmatic and having better lung function. African Americans have a 5- to 10-fold increase in incidence of asthma relative to whites, who are believed to be partially associated with higher genetic susceptibility. Occurrence of the rs9982010 and MUC7 allelic frequencies was evaluated in inner-city African Americans to test their association with a diagnosis of asthma. ⋯ These data extend the association of MUC7*5 allelic polymorphisms and asthma to inner-city African Americans.