B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness.

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.

High-sodium food choices by southern, urban African Americans with heart failure.

BACKGROUND: Sodium restriction is important in the management of heart failure (HF). Although many low-sodium educational resources are available, few are directed specifically at urban African Americans. METHODS AND RESULTS: A registered dietitian prospectively interviewed 50 African-American and 25 white patients in an urban public hospital (derivation cohort) in Dallas, TX, using a food-frequency instrument that listed 146 food choices. Foods >300 mg sodium/serving consumed at least weekly by 50% of an ethnic group were classified as being a high-sodium core food for that group. Classification of foods (core or not core) was validated in a second African-American cohort (n = 144). Five high-sodium food choices were classified as core food in both the derivation and validation African-American cohorts (salt in cooking, canned vegetables, cheese, processed meats, and cold cereal) and another 3 when the derivation and validation cohorts were combined (fast food, fried chicken, and corn bread). Four of these 8 foods were not classified as core foods in whites. CONCLUSION: Eight high-sodium foods were frequently consumed by southern, urban African Americans with heart failure. Several of these foods were not commonly consumed by whites, emphasizing the need to be sensitive to ethnic differences in dietary habits when educating patients about sodium intake.

The use of MCP-1 and soluble CD40 ligand in a pathophysiology-guided approach to the management of coronary artery disease.

The management of coronary artery disease has become increasingly complex as additional factors are identified that play a role in the underlying pathophysiology of the disease and as the number of available therapies expands. Cardiac biomarkers play an increasingly important clinical role, and demonstrate value as tools to facilitate diagnosis, risk stratification and possibly to guide therapy. Monocyte chemoattractant protein-1 and soluble CD40 ligand are strongly implicated in the pathophysiology of coronary artery disease, from plaque formation to plaque rupture and thrombosis, and the measurement of these biomarkers has demonstrated promise in preliminary studies. Further investigation of these and other emerging biomarkers may offer further insight into the pathogenesis of coronary artery disease and its complications, may help to identify possible targets for future therapy, and lead to simple tests that are useful in clinical medicine.

Individualizing therapy in acute coronary syndromes: using a multiple biomarker approach for diagnosis, risk stratification, and guidance of therapy.

Patients with non-ST-elevation acute coronary syndromes (ACS) are typically grouped together and treated with similar approaches to therapy despite tremendous variability in clinical presentation and prognosis. The cardiac troponins are biomarkers of myocardial necrosis that have recently been evaluated in conjunction with markers of neurohormonal activation such as brain natriuretic peptide, and markers of systemic inflammation such as C-reactive protein, to further characterize risk in the individual patient presenting with ACS. Measurement of biomarkers that reflect different components of the underlying pathophysiology appears to provide independent and complementary risk stratification information in patients with non-ST-elevation ACS. This review summarizes the rationale for a multimarker approach to risk stratification in ACS and also discusses other cardiac biomarkers under active investigation. One of these of particular interest is soluble CD40 ligand, a biomarker that may not only indicate active inflammation and platelet activation associated with ACS, but may also exhibit direct prothrombotic properties that mediate early atherogenesis, plaque rupture, and thrombosis.

Disparity in pathologic and clinical lymph node staging in oral tongue carcinoma. Implication for therapeutic decision making.

BACKGROUND: Regional lymph node metastasis is the most reliable predictor of treatment outcomes for patients with squamous cell carcinoma of the oral tongue (SCCOT). A recent American Joint Committee on Cancer staging update of malignant melanoma has incorporated pathologic lymph node staging. The authors hypothesized that pathologic lymph node staging (pN) would be a more reliable predictor of treatment outcomes than clinical lymph node staging (cN). METHODS: The authors retrospectively reviewed 266 patients who received primary surgical treatment for SCCOT, including a neck dissection, from January 1980 to December 1995. Overall and disease-specific survival and disease-free interval were compared with respect to clinical and pathologic lymph node stages. RESULTS: Statistically significant survival differences were identified for both clinical (cN0-cN2) and pathologic lymph node stages (pN0-pN2). However, survival and disease-free interval differences for pathologic lymph node staging reached higher statistical significance (P < 0.0001) than for clinical lymph node staging (P < 0.002). This disparity can be explained by stage migration (i.e., patients with cN0-1 disease have a more advanced lymph node stage at the time of pathologic review compared with patients without cN0-1 disease). The authors found a 34% rate of occult lymph node disease in the cN0 group (19% of occult lymph nodes had extracapsular spread [ECS]). Similarly, 43% of cN1 patients had a higher stage than pN2b disease and 50% had ECS. CONCLUSIONS: Pathologic lymph node staging, based on a staging or therapeutic neck dissection, should be considered for patients treated for SCCOT to identify high-risk patients who may benefit from additional adjuvant therapy. Prospective studies are essential to validate these findings before pathologic lymph node staging is included in standard staging criteria.

Extent of extracapsular spread: a critical prognosticator in oral tongue cancer.

BACKGROUND: Extracapsular spread (ECS) of metastatic squamous cell carcinoma of the head and neck to regional lymph nodes is the most reliable predictor of poor treatment outcomes. Recently, the authors have shown that ECS is significantly associated with higher rates of locoregional recurrence, distant metastasis, and decreased survival in patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this review was to determine if the degree of ECS impacts distant metastasis rates and survival. METHODS: Two hundred sixty-six patients treated for SCCOT with surgery +/- adjuvant radiotherapy from 1980-1995 were reviewed. The setting was a tertiary referral center. The extent of ECS on histopathologic review of involved lymph nodes was measured from the capsular margin to the farthest perinodal extension in mm. Extent of ECS and the number of pathologic lymph nodes with or without ECS were analyzed for disease-free interval, survival rates, and distant metastases. RESULTS: No differences in the survival of patients with ECS of 2 mm was found (P = 0.92). Patients with both ECS and multiple positive lymph nodes had decreased overall survival (P = 0.0003), disease-specific survival (P = 0.0005), and a shorter disease-free interval (P = 0.019) when compared with those with a single positive lymph node with ECS. Those with multiple ECS+ lymph nodes had the worst prognosis (P = 0.001). CONCLUSIONS: Based on these findings, the authors recommended that all patients with SCCOT with ECS or multiple positive lymph nodes with or without ECS on pathologic review be considered for clinical trials that intensify regional and systemic adjuvant therapy.