Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload

OBJECTIVES: We sought to determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated in patients with hemodynamically significant pressure and volume overload. BACKGROUND: It has been previously shown that TNF-alpha messenger ribonucleic acid (mRNA) and protein are rapidly expressed in the hearts of animal models subjected to abrupt hemodynamic overloading. The clinical significance of these experimental findings has not been tested in pathophysiologically relevant clinical models in human subjects. METHODS: We prospectively measured serum TNF-alpha levels and serum TNF receptor 1 and 2 levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to 4+ mitral regurgitation (MR) and in normal age- and gender-matched control subjects. Patients with AS and MR were either in New York Heart Association (NYHA) functional class I or II and had no significant coronary disease. We compared the cytokine levels among the groups using analysis of variance. We related cytokine levels to the severity of AS using simple regression analysis. RESULTS: Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21) and MR (1.3 +/-0.7 pg/ml, n = 26) were significantly higher than those in the control subjects (0.7 +/-0.2 pg/ml, n = 28). Serum TNF receptor 1 and 2 levels were also higher in patients with AS and MR than in control subjects. Cytokine levels were higher in patients in NYHA class II than in those in class I. In patients with a normal ejection fraction (>50%, n = 16), there was a mild positive correlation (r = 0.56, p = 0.025) between serum TNF-alpha levels and the mean gradient across the aortic valve. CONCLUSIONS: This study demonstrates that serum TNF-alpha is elevated in patients with chronic hemodynamic overloading and early cardiac decompensation. Furthermore, these findings suggest not only that peripheral TNF-alpha levels correlate with the severity of the hemodynamic pressure overload, but also that peripheral TNF-alpha and TNF receptor levels increase in direct relation to deteriorating NYHA functional class.     

Hypertension in patients with pheochromocytoma

Adrenal-dependent hypertension syndromes are uncommon forms of hypertension. They include primary aldosteronism, pheochromocytoma, Cushing"s syndrome, and congenital adrenal hyperplasia. Pheochromocytomas are the cause of hypertension in 0.1% to 0.2% of hypertensive patients. Excess catecholamine release and other neural and humoral mechanisms contribute to the pathophysiology of hypertension. Patients with pheochromocytomas have a potentially curable cause of endocrine hypertension and, if undetected, pheochromocytomas confer a high risk for morbidity and mortality, especially during surgical procedures and pregnancy. All patients with incidental adrenal tumors, regardless of tumor size, should be biochemically screened for pheochromocytoma (especially before resection or needle biopsy) to avoid precipitation of a lethal hypertensive crisis.     

Small-diameter (2 mm) laparoscopy in the evaluation of liver disease

Background: Percutaneous liver biopsy fails to demonstrate cirrhosis in approximately 32% of cases when compared with laparoscopy with liver biopsy. The aim of this study is to determine the usefulness of small-diameter (2 mm) laparoscopes compared with larger laparoscopes. Methods: Patients undergoing diagnostic laparoscopy for various liver diseases were evaluated with small-diameter (2 mm) laparoscopes either alone or in combination with a 5 or 10 mm laparoscope. Results: Twenty patients were enrolled in this study. Small-diameter laparoscopes provided appropriate visualization of the abdominal organs and proper guidance to liver biopsy in 9 cases. In the remaining 11 cases a larger laparoscope was used for the following reasons: short length of the trocar/introducer in a morbidly obese patient (1), liver mass located in the anterosuperior aspect of the liver precluding good visualization with forward lenses (1), and inability to properly visualize the anterosuperior aspect of the liver (9). No complications were noted with the use of the small-diameter laparoscopes alone. Conclusion: There is a need for an oblique-viewing minilaparoscope that allows visualization comparable to the larger laparoscopes.     

Optimal β-blocker for prevention of atrial fibrillation after on-pump coronary artery bypass graft surgery: Carvedilol versus metoprolol

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass graft (CABG) surgery. It has been shown that prophylactic oral beta-blocker administration reduces the incidence of post-CABG AF. However, the optimal beta-blocker has not been identified. OBJECTIVE: This study sought to determine whether oral carvedilol (with its unique anti-inflammatory and antioxidant properties) is more effective than oral metoprolol for prevention of AF after CABG surgery. METHODS: Between April 2006 and December 2006, 120 patients (63 men, mean age 61 +/- 9.4 years) who were scheduled to undergo their first on-pump CABG were enrolled in this study. The patients were randomized in a prospective 1:1 manner to receive either oral carvedilol (n = 60) or oral metoprolol (n = 60). The end point of the study was the occurrence of the new-onset AF during the first 5 days after CABG. RESULTS: AF occurred in 29 of 120 patients (24.0%). The incidence of postoperative AF was 15.0% (9 of 60) in the carvedilol group and 33% (20 of 60) in the metoprolol group (P = .022). The carvedilol group was treated with mean daily dose of 46 +/- 9 mg and metoprolol group with mean daily dose of 93 +/- 11 mg. There were no differences between the study groups regarding any known preoperative, perioperative, or postoperative characteristics (all values were P >.05). No significant adverse effect was observed in either group. CONCLUSION: This prospective study suggested that oral carvedilol is more effective than oral metoprolol in the prevention of AF after on-pump CABG. It is well tolerated when started before and continued after the surgery. However, further prospective studies are needed to clarify this issue.     

Insulin,proinsulin, proinsulin:insulin ratio,and the risk of developing type 2 diabetes mellitus in women

PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin:insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (< or =4.0 pmol/L, 4.01 to 6.99 pmol/L, > or =7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (> or =7.0 pmol/L vs. < or =4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin:insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A(1c) level < or =6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin:insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women.     

Cloning of Physarum actin sequences in an exonuclease-deficient bacterial host.

A genomic library of Physarum was constructed in the replacement vector EMBL3. Efficient propagation of the recombinant phages occurred only on the recBC-sbcB- host Escherichia coli CES200, which is deficient in the exonucleases I and V. Thirteen different recombinants with actin-related sequences were detected and 10 were purified from 90,000 plaques (the equivalent of 6 Physarum genomes) on strain CES200. Comparison of the plating efficiencies of the library and the actin-related isolates suggests that palindromic DNA sequences are responsible for the instability of Physarum DNA in E. coli. In one of these isolates, lambda PpA10, and in a 2.81-kilobase subclone of that isolate in plasmid pBR322, a deletion of 360 base pairs was detected that led to stable propagation of the recombinant DNA molecules in Rec+ E. coli. Electron microscopic analysis of the 2.81-kilobase fragment, after denaturation and self-hybridization, revealed secondary structures consistent with "foldback" structures. Restriction and DNA blot analysis of lambda PpA10 suggest that the unstable DNA segment is in close proximity to, if not part of, the previously defined actin-gene locus ardA.