Papillary renal cell carcinoma

The authors present a case of a papillary type renal cell carcinoma. The tumor is mostly discovered accidentally; a histopathological evaluation is indispensable for an exact diagnosis. Because of a better prognosis, differentiation of this tumor type from the classic variant of renal cell carcinoma is necessary, however, the contralateral appearance of a second tumor is not to be excluded, which necessitates a strict patient follow-up. Prevalence of this tumor is higher in patients with chronic dialysis.     

Differences in heart valve procedures between North American and European centers: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT)

BACKGROUND AND AIM OF THE STUDY: Differences in heart valve procedures between North American (NA) and European (EU) centers were evaluated in a multicenter trial. METHODS: Between July 1998 and January 2000, 807 patients from 12 NA (n = 446) and seven EU centers (n = 361) were randomized to receive either Silzone or conventional valves in the Artificial Valve Endocarditis Reduction Trial (AVERT). Subanalysis was performed to compare demographics, patient risk profile, surgical techniques and perioperative management of patients in NA and EU centers. RESULTS: Mean age was significantly younger and body mass index higher in NA. Patients' risk profiles showed significantly higher incidences of previous myocardial infarction, congestive heart failure, angina, prior cardiovascular surgery, and history of smoking in NA. A different distribution of implant position was observed between groups: aortic valve/mitral valve/double valve replacement in 54.0, 35.7 and 10.3% in NA, and 64.5, 27.4 and 8.0% in EU (p <0.01). Concomitant coronary artery bypass grafting was performed in 31.6% of NA patients and 19.4% of EU patients (p <0.001). Timing of surgery showed a higher incidence of urgent procedures in NA centers. Distribution of valve sizes and perioperative complication rate were similar, but length of hospital stay was longer in EU centers. CONCLUSION: Surprisingly, surgeons in NA and EU centers are faced by different patient populations requiring mechanical heart valve replacement. NA patients were younger, but required more extensive surgery. Surgical technique and perioperative management appear to differ in NA and EU centers. These differences in reporting heart valve procedures might have been influenced by variable interpretations of definitions and different patient expectations, although a uniform study protocol with consistent definitions was used at all sites.     

Interspecies differences in acetaminophen sensitivity of human, rat, and mouse primary hepatocytes

Most of the experiments studying acetaminophen (APAP) induced hepatotoxicity were performed using moue as model specie, right because its high sensitivity. While the toxic responses can be called forth easily in mice, the human relevancy of these results is questionable. In this study human, rat, and mouse primary hepatocytes were treated with increasing concentrations of APAP, and cell viability was measured by MTT cytotoxicity assay. Pronounced interspecies differences were obtained in cell viability following 24 h of APAP treatment starting at 24 h after seeding (EC₅₀: 3.8 mM, 7.6 mM, and 28.2 mM, in mouse, rat, and human hepatocyte culture, respectively). The longer time of culturing highly increased the resistance of hepatocytes of all species investigated. In rat hepatocyte culture EC₅₀ values were 6.0 mM, 12.5 mM, and 18.8 mM, when starting APAP treatment after 24, 48, and 72 h of seeding. Although N-acetylbenzoquinoneimine, a minor metabolite of APAP, which is mainly formed by CYP2E1 at high APAP concentration in every species studied, is thought to initiate the toxic processes, no correlation was found between CYP2E1 activities and hepatocyte sensitivity of different species. We conclude that the toxicity induced by APAP overdose highly depends on the animal model applied.     

Production of endothelium-derived contracting factor is enhanced after coronary reperfusion

To determine whether coronary reperfusion enhances the production of endothelium-derived contracting factor, we investigated dogs subjected to global cardiac ischemia (45 minutes) followed by reperfusion (60 minutes). Segments of reperfused and control coronary arteries were suspended in organ chambers to measure isometric force. Perfusate hypoxia caused endothelium-dependent contraction in the control and reperfused arteries. However, reperfused arteries exhibited hypoxic contraction that was significantly greater than control segments. The hypoxic contractions in both the control and reperfused arteries could be inhibited by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Thus, after reperfusion, augmented production of endothelium-derived contracting factor occurs by an L-arginine-dependent pathway. We hypothesize that nitric oxide produced by L-arginine metabolism combines with superoxide anion to produce the peroxynitrite anion (ONOO-), which is metabolized to endothelium-derived contracting factor or induces its synthesis. Augmented production of endothelium-derived contracting factor would favor vasospasm after reperfusion.     

Chronic benzylamine administration in the drinking water improves glucose tolerance,reduces body weight gain and circulating cholesterol in high-fat diet-fed mice

Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600 μmol/(kg day)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.     

Endothelial cell dysfunction after ischemic arrest and reperfusion: a possible mechanism of myocardial injury during reflow

To determine the mechanism(s) responsible for decreased coronary flow after global cardiac ischemia and reperfusion, we studied 40 isolated rabbit hearts before and after 30 minutes of normothermic ischemic arrest and reperfusion. In the control group (n = 10) we evaluated the time course of recovery of coronary flow, vascular reactivity, and myocardial function. In experimental groups A (n = 10) and B (n = 10), metabolic control of autoregulation was assessed by plots of myocardial oxygen consumption versus coronary flow generated by incremental increases in heart rate. The slope and intercept of these plots suggested that autoregulation of coronary flow was maintained after ischemia. In group B hearts (n = 10) hyperosmolar reperfusion with mannitol decreased myocardial water by 2% (p less than 0.01) but did not increase coronary flow. Endothelium-dependent function was assessed in group C (n = 10) by the administration of an endothelium-dependent vasodilator (serotonin) and a smooth muscle vasodilator (adenosine). Coronary artery smooth muscle function was comparable in hearts before and after ischemia. However, endothelium-dependent increases in coronary flow to serotonin were significantly impaired after ischemia (p less than 0.01), and this was accompanied by a significant decrease in prostacyclin synthesis by the endothelium (p less than 0.001). Global cardiac ischemia and reperfusion damages coronary artery endothelium, causing increased coronary vasomotor tone; this may be an important mechanism of decreased coronary perfusion and subsequent myocardial injury during reflow.     

Time to first new myocardial infarction in patients with mild angina and three-vessel disease comparing medicine and early surgery: a CASS registry study of survival. Coronary Artery Surgery Study

Two categories--patients alive and free from new myocardial infarction (MI) and time to first new MI (nonfatal and fatal)--were compared in medical and early surgical groups in the Coronary Artery Surgery Study (CASS) registry with Class I or II angina and three-vessel disease in a six-year follow-up. There were 413 in the medical group and 443 in the early surgical group. A broad definition of MI using ECG and clinical criteria on hospital discharge and follow-up was used to include as many new MIs as possible, including perioperative MIs. Stratification was by left ventricular wall motion score and number of proximal segment stenoses and by quintile of propensity score to reduce selection bias in therapy groups. Adjusted by propensity analysis, 79% of medical and 88% of surgical patients (p = .005) were free from new MI; death without diagnosis of new MI was censored. Similarly adjusted, 57% of medical and 76% of surgical patients (p less than .0001) were alive and free from new MI at six years. For patients with previous MI, surgery offered the probability of protection from new MI: with multiple prior MIs, 66% of medical and 88% of surgical patients were free from new MI at six years (p = .0019). This is a nonrandomized, observational study with the limitations of such studies: the need to adjust for differences in baseline traits in medical and surgical groups and the unknown effects of unobserved variables. Fifty-one variables, including therapy, were tested by Cox model with time to new MI as the end point. Early surgery was the strongest independent predictor of freedom from new MI (p = .002) with a relative risk of 51% compared with medical therapy (95% confidence limits of 33 to 78%). In patients with multiple prior MIs, the new MI risk with early surgery was 24% of that for medicine, with an upper 95% confidence point of 64%.     

Spectrum of reoperations after repair of aortic coarctation: importance of an individualized approach because of coexistent cardiovascular disease

OBJECTIVE: To determine the indications for and spectrum of late reoperations in adults who had previously undergone coarctation repair. PATIENTS AND METHODS: We reviewed clinical, cardiac catheterization, and echocardiographic data and criteria for reoperation, surgical procedures, and outcome in 43 patients who underwent 54 reoperations between 1972 and 1996. RESULTS: Of the reoperations for recoarctation or associated cardiovascular disease (or both), 20% were performed in asymptomatic patients and 80% in symptomatic patients. Associated cardiovascular disease included bicuspid aortic valve in 36 patients (84%), aortic arch hypoplasia in 12 (28%), true or false aortic aneurysm in 6 (14%), mitral valve disease in 6 (14%), and subvalvular aortic stenosis in 5 (12%). Surgical procedures included 22 recoarctation repairs and 32 other cardiovascular interventions. Simultaneous repair of recoarctation and associated cardiovascular disease was performed as a single-stage repair in 5 reoperations through a median sternotomy using an extra-anatomic, ascending-to-descending aortic bypass, with no complications. One patient died (surgical mortality, 1.9%) of preexisting severe pulmonary vascular obstructive disease. CONCLUSIONS: After coarctation repair, associated cardiovascular diseases are the most common cause for reoperation. An individualized surgical approach is important and may range from valve replacement or recoarctation surgery to extra-anatomic bypass combined with other cardiovascular procedures, enabling simultaneous repair of recoarctation and associated lesions. Despite complex surgical techniques and multiple reoperations, morbidity and mortality were low in our series.