Clinical outcomes in patients with renal artery stenosis treated with stent placement with embolic protection compared with those treated with stent alone

Purpose: To compare the clinical outcomes in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS) following renal artery (RA) stent placement with and without embolic protection device (EPD) usage. Materials and Methods: Eighteen patients who had RA stent placement with EPD were matched to control patients (RA stent only). Blood pressure, number of hypertensive medications, and estimated glomerular filtration rate (eGFR) at 3 months before the procedure and after 12 months were determined. An increase of ≥ 20% in eGFR at 12 months from baseline was defined as "improvement," decrease of ≥20% as "deterioration," and an eGFR change between those values as "stabilization" at 12 months. Results: At 12 months, stage 4 patients treated with EPD had significantly higher eGFR than controls (P = .01). There was no statistical difference in blood pressure outcomes between the 2 groups. Conclusions: Patients with stage 4 CRI did significantly better with EPD than those treated without it.     

Cardioprotection by St Thomas' solution is mediated by protein kinase C and tyrosine kinase

BACKGROUND: Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). MATERIALS AND METHODS: Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. RESULTS: STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 +/- 2.9%, 9.6 +/- 2.1%, 14.0 +/- 4.4%) compared with controls (42.4 +/- 2.9%, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 +/- 4.1%, P < 0.05) and genistein (40.4 +/- 4.3%, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 +/- 1.4%, 60.4 +/- 4.7%, 57.2 +/- 4.6%) compared with control (33.8 +/- 3.6%, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 +/- 4.4%, 35.1 +/- 2.5%, P < 0.05) compared with STC treatment. CONCLUSION: Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.     

Association of interleukin-6 -174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients

BACKGROUND: Gene polymorphisms of proinflammatory cytokines, such as interleukin-6 (IL-6) and the chemokine receptor CX3CR1, have been found in association with cardiovascular disease in the general population. In dialysis patients, in whom the prevalence of cardiovascular comorbidity is strikingly high, these polymorphisms have not been investigated. METHODS: The -174G/C polymorphism of the IL-6 gene and the chemokine receptor CX3CR1 polymorphisms 249V/I and 280T/M were examined for their association with cardiovascular abnormalities in a cohort of 161 patients with end-stage renal disease (ESRD) treated by hemodialysis. Arterial blood pressure, electrocardiogram (ECG) ischemic changes, and left ventricular mass index (LVMI) were the parameters examined for the association study. The control group was made up of 169 healthy subjects. RESULTS: We found that for both IL-6 and chemokine receptor, genotype frequency and allelic distribution in both ESRD patients and controls were comparable. The genetic association study showed that in the whole group of dialysis patients, individuals with GC + CC genotype for the -174G/C polymorphism had a higher diastolic blood pressure (P = 0.008) and LVMI (P = 0.026) than GG homozygotes. The prevalence of left ventricular hypertrophy (LVH) in the former group was 58.6% vs. 39.2% in the latter (P = 0.02). The same analysis limited to diabetic patients in dialysis, showed that the prevalence of LVH in those with CG + CC genotype was 87.5% vs. 36.3% in those with GG genotype (P = 0.02). In diabetic patients, lower levels of serum albumin was found in the GC + CC genotypic group than in GG subjects; 34.63 +/- 5.18 g/L vs. 41.75 +/- 4.79 g/L (P = 0.003). CONCLUSION: These data demonstrate an association between the IL-6 promoter polymorphism -174G/C and high blood pressure and LVH in hemodialysis patients, especially those with diabetes. The results strengthen the hypothesis that chronic inflammation is a mechanism of cardiovascular damage in dialysis patients and the role played by the IL-6 system in this mechanism.     

Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats

BACKGROUND: Neutrophil activation with concomitant matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) release has been implicated in the development of sepsis-induced acute lung injury. We hypothesized that COL-3, a chemically modified tetracycline known to inhibit MMP-2 and MMP-9, would reduce lung injury and improve survival in rats following cecal ligation and puncture (CLP). METHODS: Sprague-Dawley rats were separated into five groups: 1) sham CLP+ carboxymethylcellulose (CMC; vehicle for COL-3, n = 6); 2) sham CLP + COL-3 (n = 6); 3) CLP + CMC (n = 10); 4) CLP + single-dose (SD) COL-3 administered concomitant with CLP (n = 9); and 5) CLP + multiple-dose (MD) COL-3 administered concomitant with CLP and at 24 h after CLP (n = 15). Rats were sacrificed at 168 h (7 days) or immediately after death, with survival defined as hours after CLP. Histological lung assessment was made based on neutrophil infiltration, alveolar wall thickening, and intraalveolar edema fluid. Lung MMP-2 and MMP-9 levels were assessed by immunohistochemistry. MMP-2 and MMP-9 levels were correlated with survival by simple regression analysis. RESULTS: The mortality of rats in the cecal ligation and puncture without treatment group (CLP + CMC) was 70% at 168 h. A single dose of COL-3 in the CLP + COL-3 (SD) group significantly reduced mortality to 54%. Furthermore, with a repeat dose of COL-3 at 24 h after CLP, mortality was significantly reduced to 33%. Pathologic lung changes seen histologically in the CLP + CMC group were significantly reduced by COL-3. A significant reduction in lung tissue levels of MMP-2 and MMP-9 was noted in both groups treated with COL-3. Reduction of MMP-2 and MMP-9 levels correlated with improved survival. CONCLUSION: Inhibition of MMP-2 and MMP-9 by COL-3 in a clinically relevant model of sepsis-induced acute lung injury reduces pulmonary injury and improves survival in a dose-dependent fashion. Our results suggest that prophylactic treatment with COL-3 in high-risk patients may reduce the morbidity and mortality associated with sepsis-induced acute respiratory distress syndrome.     

Gastroesophageal reflux disease in lung transplant recipients

BACKGROUND: Chronic allograft dysfunction after lung transplantation contributes to poor long-term survival. A link between gastric aspiration and post-transplant lung dysfunction has been suggested, but little is known about the significance of gastroesophageal reflux disease (GERD) after lung transplantation. METHODS: A retrospective study was performed to determine the prevalence of GERD in lung transplant recipients. Patients who underwent lung transplantation at Duke University, survived at least 6 months and had post-transplant 24-h pH studies were included in the analysis. Antireflux medications were discontinued prior to the pH study. Demographic data, pH study date and results, FEV1 at the time of the pH study, confirmed acute rejection episodes, and current medications were collected. The FEV1 ratio was calculated at the time of pH study (current FEV1/best post-transplant FEV1). RESULTS: Forty-three patients met entry criteria. Studies were performed at a median of 558 d post-transplant. Thirty of forty-three (69.8%) patients tested had abnormal total acid contact times (normal: <5%). The mean acid contact times for all patients were 10% total, 11.8% upright and 7.9% supine. A negative correlation was found between total or upright acid reflux and FEV1 ratio at the time of studies (-0.341 and -0.419; p = 0.025 and p = 0.005, respectively). The effect of acid reflux on FEV1 ratio remained significant after multivariable analysis. CONCLUSIONS: There is a high prevalence of GERD among selected lung transplant recipients who had pH studies performed and its presence is associated with worse pulmonary function. Future studies are needed to assess whether GERD contributes to the pathogenesis of bronchiolitis obliterans syndrome (BOS).     

Voxel-based diffusion tensor magnetic resonance imaging evaluation of low-grade hepatic encephalopathy

PURPOSE: To quantify the changes in brain water diffusivity in hepatic encephalopathy (HE) associated with cirrhosis using diffusion tensor imaging (DTI) and to correlate with neuropsychological (NP) scores. MATERIALS AND METHODS: DTI was performed in 14 patients with low-grade HE and age/gender-comparable 16 healthy controls. Whole brain mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated, normalized to common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance with age included as a covariate. The average MD and FA values were also calculated from individual subjects for selected brain regions and correlated with the neuropsychological scores. RESULTS: Patients with HE showed increased MD in the cortical gray and white matter and the internal capsule. Less extensive brain regions with decreased FA were observed in the bilateral frontal and occipital white matter. MD values from the corpus callosum correlated inversely with several NP scores among HE patients and controls. Positive correlations were observed with FA values and cognitive scores. CONCLUSION: Voxel-based DTI analysis showed widespread brain regions with increased MD values, indicating enhanced water content and decreased FA in cirrhotic patients with HE. The MD and FA values from selected regions correlated with the NP scores.     

Relationship of peripheral arterial compliance and standard cardiovascular risk factors

Abnormalities of peripheral arterial compliance are clinically useful markers of atherosclerosis and risk of vascular events. Local peripheral arterial compliance can be easily and accurately assessed in the clinic by computer-controlled pulse volume recordings (air plethysmography). The purpose of this study was to investigate the relationship between clinical cardiovascular risk factors, a surrogate of atherosclerotic burden, and peripheral arterial compliance in the thigh and calf determined by quantification of local pulse volume recordings in patients undergoing coronary angiography. Peripheral arterial compliance in the thigh and calf was measured in 346 patients undergoing diagnostic cardiac catheterization at 4 centers. Demographic and cardiovascular risk factor data were collected, and their relationship to local arterial compliance examined using a new device that assesses maximal local arterial volume change in an extremity segment. Pulse volume recordings detected decreased local arterial compliance in the thigh associated with a history of hypertension (p < 0.0001), diabetes mellitus (p = 0.0001), and hyperlipidemia (p = 0.0007). In the calf, this arterial compliance measure was associated with a history of hypertension (p < 0.0001) and diabetes mellitus (p = 0.002). Females had lower arterial compliance than males in the thigh (p = 0.003) and calf (p < 0.0001). Limited evidence of lower arterial compliance in the thigh was found for those with obesity (p = 0.07). This procedure also demonstrated that subjects with multiple cardiovascular risk factors had lower arterial compliance in the thigh than subjects with no or 1 risk factor (p = 0.0001). Peripheral arterial compliance determined by air plethysmography is strongly associated with standard cardiovascular risk factors. The noninvasive measurement of local arterial compliance by regional pulse volume recording may be a useful adjunct for cardiovascular risk stratification early in the course of the disease as well as for monitoring vascular response to therapy.     

Alterations in immunocyte tumor necrosis factor receptor and apoptosis in patients with congestive heart failure

OBJECTIVE: To examine systemic immune cell proinflammatory receptor expression and apoptosis in patients with congestive heart failure (CHF). SUMMARY BACKGROUND DATA: Prior studies have demonstrated that CHF is associated with a chronic myocardial inflammatory state, including increased plasma proinflammatory cytokine and soluble receptor expression. By contrast, it has also been shown that tumor necrosis factor (TNF) receptor protein expression is decreased in the failing myocardium. However, no studies to date have examined systemic immune cell proinflammatory receptor expression or function as disease markers in patients with heart failure. METHODS: Twenty-nine patients were studied prospectively over an 8-month period at a single institution. One group (n = 16) had a history of clinical symptoms of CHF and moderate to severe left ventricular dysfunction. The second group (n = 13) consisted of patients who had coronary artery disease without symptoms of CHF and documented preservation of left ventricular function. Blood samples were analyzed for polymorphonuclear cell (PMN) and monocyte TNF and CD95 membrane-associated receptor expression, spontaneous and CD95 (Fas)-mediated PMN apoptosis, and plasma cytokine and soluble TNF receptor levels. Isolated PMNs were incubated for 6 hours with or without CH 11, a CD95 agonist. Propidium iodide/RNAase staining and flow cytometry was used to assess apoptosis, defined as PMNs expressing hypodiploid DNA (<2 n DNA). Membrane-associated TNF receptor and CD95 were also measured by flow cytometry. Plasma levels of TNF, interleukin (IL)-6, IL-10, and soluble TNF receptors 1 and 2 were quantified using enzyme-linked immunosorbent assay. RESULTS: Compared to patients without CHF, circulating PMN and monocyte TNF receptor levels were significantly decreased in patients with CHF. By contrast, PMN and monocyte CD95 expression was not significantly changed in patients with CHF versus those without CHF. Patients with CHF had a 60% decrease in spontaneous PMN apoptosis compared to patients without CHF, whereas no significant difference in CD95-mediated apoptosis was observed between the two groups. Pearson-product movement correlation of monocyte TNF receptor expression and spontaneous PMN apoptosis rates versus patients' ejection fraction was performed and was statistically significant. Plasma levels of soluble TNF receptor 2 (p75) were elevated in CHF patients versus patients without CHF, while there was no significant difference in soluble TNF receptor 1 (p55), TNF, IL-6, and IL-10 between the two groups. CONCLUSIONS: These data demonstrate a systemic alteration in immune cell phenotype and apoptosis in patients with CHF. These findings provide support for the concept that inflammatory mediators either contribute to myocardial dysfunction or are elaborated systemically by left ventricular compromise. This present study suggests that immune cell TNF receptor expression and diminished PMN apoptosis may serve as biologic markers of myocardial failure.     

Incidental diagnosis of gastric cancer in transplant recipients improves patient survival

BACKGROUND: Gastric cancer in the United States is often diagnosed at advanced stages, resulting in dismal outcomes. In the immunosuppressed transplant recipient population, little is known about the clinical staging and outcome of these compromised patients. METHODS: All US cases reported to the Israel Penn International Transplant Tumor Registry were retrospectively examined for patient demographics, immunosuppressive therapy, tumor characteristics, therapeutic modalities, and mortality. Statistical analysis was performed with Students t test, chi-square analysis, and log-rank analysis by the method of Kaplan-Meier. RESULTS: Gastric cancer was identified in 34 recipients: 28 (82%) were male; 24 (71%) were white. Mean age at diagnosis was 58 +/- 11 years. Twenty-four (71%) patients received kidney transplants, 7 (21%) received heart transplants, and 3 (9%) received liver transplants. Fifty percent received induction therapy, whereas 94% were maintained on calcineurin inhibitors and corticosteroids. Thirty-five percent of patients were diagnosed during evaluation for gastrointestinal symptoms, with the remaining cases discovered incidentally during endoscopy (53%) or during computed tomography (12%) performed for other reasons. Stage varied at presentation as follows: stage I (n = 6), stage II (n = 11), stage III (n = 13), and stage IV (n = 4). Incidental diagnoses resulted in a lower stage malignancy (P <.001) and greater 1-year and 5-year survivals (P <.05) compared with those patients whose were diagnosed after being evaluated of gastrointestinal symptoms. CONCLUSION: In the United States, because gastric cancer in the transplant recipient is frequently identified at an earlier stage (50% were stages I and II) than in the general population, survivals are equivalent despite continued administration of immunosuppression. This early identification may be attributed to more frequent presymptom diagnosis and staging, resulting from incidental detection of these malignancies during posttransplant upper endoscopy or computed tomography. Early detection has resulted in a 29% 5-year survival for the entire transplant recipient group compared with a 5% to 15% 5-year survival in the general population.     

Management of shoulder dislocation--are we doing enough to reduce the risk of recurrence?

Young patients with shoulder dislocation are at high risk of recurrence. Traditionally, management has been conservative, but rehabilitative programmes are successful in fewer than 20% of patients. Recent studies suggest that early surgical intervention (arthroscopic lavage or stabilisation) can significantly reduce recurrence in young patients with primary traumatic anterior dislocation. This study demonstrated that in our region, 21% of all patients presenting with shoulder dislocation had already suffered recurrence at 1 year; in the 15-22 years age group this figure was 43%. We propose to offer young patients presenting with primary traumatic anterior dislocations arthroscopic lavage within 10 days of injury. The extra surgical workload is manageable within our current trauma service arrangements, and we believe that this form of treatment would be acceptable to patients.