Expression of Connective Tissue Growth Factor in Intra-Abdominal Adhesions

PURPOSE: Connective tissue growth factor stimulates fibroblast proliferation and extracellular matrix deposition in many fibrotic disorders. The aim of our study was to determine the expression pattern of connective tissue growth factor in postoperative intra-abdominal adhesions. METHODS: Adhesions were created in 46 Sprague-Dawley rats by complete dissection and resuturing of a peritoneal patch 2 cm in diameter, lateral from the midline incision. Animals were killed at postoperative Days 3, 6, 9, 12, 15, 18, and 21 and the adhesions scored on a scale of 0 to 5. Tissue samples from adhesion areas and from uninvolved peritoneum were evaluated by Northern and Western blotting for temporal connective tissue growth factor mRNA and protein expression, respectively. Immunohistochemical analysis was performed for connective tissue growth factor localization. RESULTS: Adhesions formed in all animals after surgery and were confined to the peritoneal patches. Adhesion formation increased across time, with significant correlation between adhesion scores and postoperative days (r = 0.329, P = 0.026). Connective tissue growth factor mRNA concentrations were significantly elevated in adhesion tissue throughout the three-week period when compared with normal peritoneum (P = 0.012); peak levels occurred between Days 6 and 15. Western blots demonstrated connective tissue growth factor protein expression in adhesions from Days 6 to 21, in contrast to negligible bands in normal peritoneum. Fibroblasts within the adhesive tissue, but not in uninjured peritoneum, stained positive for connective tissue growth factor by immunohistochemistry. CONCLUSIONS: We have demonstrated a specific temporal and spatial expression pattern for connective tissue growth factor in intra-abdominal adhesions during a three-week postoperative time course. According to what is known about the functional role of connective tissue growth factor in fibrogenesis, our findings warrant further investigations addressing a causal relationship between this growth factor and fibrous adhesion formation.     

Making choices: how older people living in independent living units decide to enter the acute care system

Older people living in independent living units make choices about where they live and the degree of support required to maximize their health and well-being. This can include when to enter the acute care system. Using a multimethod, multistage qualitative approach, this study aims to explore and describe the decision-making process of older people living in independent living units to enter the acute care system. Based on the findings, recommendations are provided which can ensure that older people do not enter acute care facilities until they need to, or if they do need to, they can access the care they require and leave with the best possible chance of not re-entering unnecessarily. The findings highlight that it is not enough to focus on the older person at the point of entry into the acute care system so the recommendations aim to assist in the development of best-practice initiatives for older people living in independent living units.     

The rural nurse work environment and structural empowerment

Rural health care organizations struggle to attract and retain nurses, yet much of the research has focused on characteristics of the nurse work environment or empowerment in urban hospitals. The purpose of this study was to examine the nurse work environment in rural areas across settings by describing the relationship between structural empowerment and characteristics of the nurse work environment. Nurses ( N = 97) working in home care agencies and hospitals were surveyed. Significant differences were found between the groups, with home care nurses having significantly higher empowerment scores than medical/surgical nurses. A strong correlation was found between characteristics of the nurse work environment and empowerment. Policy makers are using evidence to guide development of policies, but much of the research has been conducted in urban hospital settings. This study begins to provide evidence that differences exist between urban and rural areas and between practice settings.     

Women's HIV disclosure to immediate family

Previous researchers have comprehensively documented rates of HIV disclosure to family at discrete time periods yet none have taken a dynamic approach to this phenomenon. The purpose of this study is to address the trajectory of HIV serostatus disclosure to family members over time. Time to disclosure was analyzed from data provided by 125 primarily single (48.8%), HIV-positive African American (68%) adult women. Data collection occurred between 2001 and 2006. Results indicated that women were most likely to disclose their HIV status within the first seven years after diagnosis, and mothers and sisters were most likely to be told. Rates of disclosure were not significantly impacted by indicators of disease progression, frequency of contact, physical proximity, or relationship satisfaction. The results of this study are discussed in comparison to previous disclosure research, and clinical implications are provided.     

Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients

OBJECTIVE: To determine the safety and long-term efficacy of immune ablation and autologous hematopoietic stem cell transplantation (HSCT) in severe systemic lupus erythematosus (SLE). METHODS: Fifteen patients with persistently active SLE after intravenous (IV) cyclophosphamide (CYC) therapy underwent HSCT. Stem cells were mobilized with CYC (2.0 gm/m(2)) and granulocyte colony-stimulating factor (5 microg/kg/day). Lymphocytes were depleted from the graft by selection of CD34-positive cells. The conditioning regimen used was CYC (200 mg/kg), antithymocyte globulin (90 mg/kg), and methylprednisolone (3 mg/kg). Outcome was evaluated by the SLE Disease Activity Index (SLEDAI), serum complement levels, serologic features, function of diseased organs, and immunosuppressive medication requirements. RESULTS: Fifteen patients with persistent, severe SLE, 7 of whom were critically ill, were treated. No deaths occurred following treatment. The median followup after HSCT has been 36 months (range 12-66 months). All patients demonstrated a gradual, but marked, improvement. The SLEDAI score has declined to 1 year after HSCT, 10 have discontinued immunosuppressive medications, and the prednisone dosage has been tapered to 15 mg/day in 1. Only 2 patients have demonstrated clinical evidence of recurrence of active lupus. One of these patients currently requires no immunosuppressive medication and has a normal performance status. The other patient is currently receiving IV CYC. CONCLUSION: In patients experiencing the persistence of organ-threatening lupus following standard, aggressive therapy, HSCT may be performed safely, with marked improvement and sustained withdrawal of all immunosuppressive medication for most patients. A phase III randomized trial is warranted to determine the relative efficacy and durability of remission of HSCT compared with standard therapies.     

An Intervention to Assist Men Who Have Sex with Men Disclose Their Serostatus to Family Members: Results from a Pilot Study

The purpose of this study was to evaluate the efficacy of an intervention to assist HIV positive men who have sex with men (MSM) in forming and executing strategies for the disclosure of their serostatus to their families of origin. Results indicate that the intervention was successful in assisting men with the primary outcome of disclosure. Participants reported no regret with disclosures occurring during the intervention and follow-up period. Effects on secondary outcomes including family functioning, depression, loneliness, and perceived social support were inconclusive. Implications, refinements of this intervention, and suggestions for future disclosure research are provided.     

Differential distribution of heparan sulfate glycoforms and elevated expression of heparan sulfate biosynthetic enzyme genes in the brain of mucopolysaccharidosis IIIB mice

The primary pathology in mucopolysaccharidosis (MPS) IIIB is lysosomal storage of heparan sulfate (HS) glycosaminoglycans, leading to complex neuropathology and dysfunction, for which the detailed mechanisms remain unclear. Using antibodies that recognize specific HS glycoforms, we demonstrate differential cell-specific and domain-specific lysosomal HS-GAG distribution in MPS IIIB mouse brain. We also describe a novel neuron-specific brain HS epitope with broad, non-specific increase in the expression in all neurons in MPS IIIB mouse brain, including cerebellar granule neurons, which do not exhibit lysosomal storage pathology. This suggests that biosynthesis of certain HS glycoforms is enhanced throughout the CNS of MPS IIIB mice. Such a conclusion is further supported by demonstration of increased expression of multiple genes encoding enzymes essential in HS biosynthesis, including HS sulfotransferases and epimerases, as well as FGFs, for which HS serves as a co-receptor, in MPS IIIB brain. These data suggest that lysosomal storage of HS may lead to the increase in HS biosyntheses, which may contribute to the neuropathology of MPS IIIB by exacerbating the lysosomal HS storage.     

Surprisingly high prevalence of anxiety and depression in chronic breathing disorders

STUDY OBJECTIVES: The objectives of this study were to assess the prevalence, screening, and recognition of depression and anxiety in persons with chronic breathing disorders, including COPD. DESIGN: Cross-sectional study. SETTING: The Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC). PARTICIPANTS: A large sample of 1,334 persons with chronic breathing disorder diagnoses who received care at the MEDVAMC. MEASUREMENTS: The prevalence of anxiety and depression was measured in a large sample of persons with a chronic breathing disorder diagnosis who received care at the MEDVAMC, using the Primary Care Evaluation of Mental Disorders (PRIME-MD) screening questions. The positive predictive value of the PRIME-MD questions was then determined. The prevalence of anxiety and depressive diagnoses in patients determined to have COPD was then measured, using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID). RESULTS: Of patients screened with the PRIME-MD, 80% screened positive for depression, anxiety, or both. The predictive value of a positive phone screen for either depression or anxiety was estimated to be 80%. In the subsample of patients who had COPD and received a diagnosis using the SCID, 65% received an anxiety and/or depressive disorder diagnosis. Of those patients, only 31% were receiving treatment for depression and/or anxiety. CONCLUSIONS: It is troubling that a mere 31% of COPD patients with depression or anxiety are being treated, particularly given their high prevalence in this population. Practical screening instruments may help increase the recognition of anxiety and depression in medical patients, as suggested by the excellent positive predictive value of the PRIME-MD in our study.     

Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus

Multidrug-resistant Staphylococcus aureus infections pose a significant threat to human health. Antibiotic resistance is most commonly propagated by conjugative plasmids like pLW1043, the first vancomycin-resistant S. aureus vector identified in humans. We present the molecular basis for resistance transmission by the nicking enzyme in S. aureus (NES), which is essential for conjugative transfer. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin, gentamicin, and mupirocin. The NES N-terminal relaxase–DNA complex crystal structure reveals unique protein–DNA contacts essential in vitro and for conjugation in S. aureus. Using this structural information, we designed a DNA minor groove-targeted polyamide that inhibits NES with low micromolar efficacy. The crystal structure of the 341-residue C-terminal region outlines a unique architecture; in vitro and cell-based studies further establish that it is essential for conjugation and regulates the activity of the N-terminal relaxase. This conclusion is supported by a small-angle X-ray scattering structure of a full-length, 665-residue NES–DNA complex. Together, these data reveal the structural basis for antibiotic multiresistance acquisition by S. aureus and suggest novel strategies for therapeutic intervention.