Biomedical subjects

Michael A Perry

Publications and source records attributed to Michael A Perry.

6 recordsLinked to original sources

PubMed2006

S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity.

BACKGROUND: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products. OBJECTIVE: Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism. METHODS: Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting. RESULTS: S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor. CONCLUSION: This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases. CLINICAL IMPLICATIONS: MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.

Adult↗

PubMed2003

Improving vascular access outcomes: a systems approach to eliminating structural barriers.

Maximizing AV fistula creation, regular access monitoring, prompt outpatient interventions and minimizing catheter use are well-accepted approaches for vascular access management. Systemic barriers impede the application of these strategies. A misaligned reimbursement system coupled with educational deficits and a lack of accountability has contributed to the institutionalization of substandard vascular access care. The hallmark of performance management is to create systems in which incentives are aligned to produce desired behaviors. Realigning reimbursement through a combination of pre-ESRD funding, enhancements to the composite rate to reward outcomes and cover vascular access monitoring and updated reimbursement for outpatient vascular access procedures would improve care and decrease unnecessary hospitalizations. This should be coupled with clearly defined outcome standards and accountability incorporated into hospital accreditation and credentialing. Capitation may provide alternative solutions. A two-phased approach including reimbursement reform while exploring capitation represents a prudent course with the best likelihood of success.

Arteriovenous Shunt, Surgical↗

PubMed2002

Leukocytes extravasation in acute homocysteinemic rats.

Homocysteine may promote atherogenesis and thrombogenesis by enhancing leukocyte-endothelium interactions. We explored this hypothesis in an acute hyperhomocysteinemia rat model, which was created by a continuous venous homocysteine infusion (4 ml/h/kg body weight) with 2.5 and 10 mg/ml D,L-homocysteine upto 90 min. Venous homocysteine levels were monitored periodically and varied 65-276 micromol/l, a range observed frequently in homocysteinemic and homocystinuric patients. We measured hemodynamic parameters in mesentery by intravital microscopy in rats infused with homocysteine (N=5 for each dose) and saline (N=7). Homocysteine infusion for 90 min did not change the mean carotid arterial blood pressure, velocity of red blood cells and rolling leukocyte flux. However at the dose of 10 mg/ml the venular wall shear rate was reduced to 66-69% of the pre-infusion value (P<0.05). The leukocyte rolling velocity decreased to 78-82% (P<0.05). The number of leukocytes adhering to the venular wall increased 2.4-fold (P<0.05), and the leukocyte extravasation increased 4.7-fold (P<0.001). Each of these effects was time-dependent and homocysteine dose-dependent. But none were observed in saline infused rats. In conclusion, while homocysteine infusion did not change hemodynamic parameters, it significantly enhanced dose-dependent leukocyte-endothelium interactions, which may contribute to homocysteine induced endothelial dysfunction.

Acute Disease↗

PubMed2002

Homocysteine attenuates hemodynamic responses to nitric oxide in vivo.

Homocysteine is a significant but modifiable risk factor for vascular diseases. While several pathological processes may be involved, homocysteine can cause significant endothelial impairment and compromise vascular NO bioactivity. In the present study, we aimed to assess effects of homocysteine on NO-mediated hemodynamic responses in vivo. We created an acute hyperhomocysteinemia model (plasma homocysteine of 65-276 micromol/l) by continuous venous infusion of D,L-homocysteine to anaesthetized Sprague-Dawley rats. Vasodilators including NO donors: S-nitrosohomocysteine (SNOHcy), S-nitrosocysteine (SNOCys) and sodium nitroprusside (SNP), the endothelial NO synthase (eNOS) activator: acetylcholine (ACh), and calcium channel blocker: verapamil and nicardipine, were administered by one bolus injection to the homocysteinemic rats. While homocysteine infusion produced no change in the mean femoral arterial blood pressure, each of these vasodilators led to a rapid and substantial dose-dependent fall in blood pressure. Concurrent homocysteine infusion, however, attenuated the blood pressure lowering effects induced by NO donors (P<0.01), but not by the calcium channel blockers. Homocysteine inhibited not only the endothelial-derived NO as stimulated by ACh, but also the bioactivity of exogenously supplied NO by SNOHcy, SNOCys and SNP. Our findings indicate that homocysteine may have an effect on NO bioproduction and bioavailability. Vasodilating efficacy of commonly used NO donors such as nitroglycerine may be seriously compromised by hyperhomocysteinemia, which is common among ischemic heart disease patients.

Acetylcholine↗

PubMed2002

Systemic barriers to improving vascular access outcomes.

Vascular access dysfunction is the most frequent cause of hospitalization for end-stage renal disease (ESRD) patients. Our system of vascular access care and industry standards developed for historic reasons have resulted in a haphazard approach to access management. The Dialysis Outcome Quality Initiative has provided a road map for improving vascular access management. However, despite widespread acceptance, these recommendations are not routinely followed. This is largely the result of inertia coupled with systemic barriers to improving access outcomes. These barriers include lack of funded pre-ESRD care and preoperative imaging, lack of reimbursement for access monitoring, unavailable surgical and interventional suites, erosion of the real value of the composite rate, bundling of additional new services without rate adjustment, poor accountability of surgeons and hospitals, and a reimbursement system that rewards procedures and, in particular, graft and catheter placement. Currently, Center for Medicare and Medicaid Services is reevaluating the composite rate and its included bundle of services. To provide the best access care with the fewest complications while insuring multidisciplinary involvement and accountability, a realistic appraisal and realignment of incentives must be developed to insure improvement of access care in the United States.

Arteriovenous Shunt, Surgical↗

PubMed2002

The role of color flow Doppler ultrasound in dialysis access.

Color flow Doppler provides accurate imaging and access flow volume measurement of the hemodialysis vascular access. It can readily identify subsets of patients at high risk for future thrombosis. It is noninvasive, mobile, and allows convenient clinical evaluation at the dialysis facility. In Europe, Doppler ultrasound has become the standard of care for evaluation of arteriovenous (AV) fistula dysfunction and is essential in the preoperative evaluation for access placement. It also can diagnose the arterial inflow disease that has become more prevalent in our aging, diabetic, end-stage renal disease (ESRD) population. Access management programs based on Doppler ultrasound have been highly successful and have produced outcome data as good or better than provided with other techniques. In light of its proven clinical efficacy, reimbursement and regulatory agencies should allow its appropriate inclusion into integrated access management programs. In conclusion, Doppler ultrasound should be included as a part of an integrated vascular access management program. This is supported by clinical outcome data and direct comparisons with other modalities.

Arteriovenous Shunt, Surgical↗