(Neo)adjuvant strategies of advanced gastric carcinoma: time for a change?

Despite surgical R0 resections, patients with gastric cancer stage UICC II-III have a high risk of recurrence and metachronic metastases. Preliminary evidence exists that adjuvant chemotherapy or neoadjuvant chemo(radio)therapy protocols may improve the prognosis of these patients undergoing surgery of gastric cancer with curative intention. As for palliative regimens, 5-fluorouracil and cisplatin are integral components of such (neo)adjuvant strategies. Upcoming cytostatic agents, i.e. irinotecan, docetaxel, oxaliplatin, and oral fluoropyridines are currently under investigation in new multimodality treatment regimens and may further increase R0 resection rates and may prolong disease-free and overall survival in the treatment of advanced localized gastric cancer.     

Reactive oxygen species-dependent hypertension in dopamine D2 receptor-deficient mice

Dysfunction of D2-like receptors has been reported in essential hypertension. Disruption of D2R in mice (D2-/-) results in high blood pressure, and several D2R polymorphisms are associated with decreased D2R expression. Because D2R agonists have antioxidant activity, we hypothesized that increased blood pressure in D2-/- is related to increased oxidative stress. D2-/- mice had increased urinary excretion of 8-isoprostane, a parameter of oxidative stress; increased activity of reduced nicotinamide-adenine dinucleotide phosphate oxidase in renal cortex; increased expression of the reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits Nox1, Nox2, and Nox4; and decreased expression of the antioxidant enzyme heme-oxygenase-2 in the kidneys, suggesting that regulation of reactive oxygen species (ROS) production by D2R involves both pro-oxidant and antioxidant systems. Apocynin, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, or hemin, an inducer of heme oxigenase-1, normalized the blood pressure in D2-/- mice. Because D2Rs in the adrenal gland are implicated in aldosterone regulation, we evaluated whether alterations in aldosterone secretion contribute to ROS production in this model. Urinary aldosterone was increased in D2-/- mice and its response to a high-sodium diet was impaired. Spirolactone normalized the blood pressure in D2-/- mice and the renal expression of Nox1 and Nox4, indicating that the increased blood pressure and ROS production are, in part, mediated by impaired aldosterone regulation. However, spironolactone did not normalize the excretion of 8-isoprostane and had no effect on expression of Nox2 or heme-oxygenase-2. Our results show that the D2R is involved in the regulation of ROS production and that, by direct and indirect mechanisms, altered D2R function may result in ROS-dependent hypertension.     

Usefulness of noninvasive cardiac imaging using dual-source computed tomography in an unselected population with high prevalence of coronary artery disease

The aim of the present study was to evaluate the diagnostic accuracy of a new dual-source computed tomographic scanner generation with 83-ms temporal resolution in cardiac imaging. Fifty-one unselected consecutive patients (mean age 64 +/- 10 years) scheduled for invasive coronary angiography because of suspected or known coronary artery disease (CAD) were examined with dual-source computed tomography (DSCT). All coronary segments were analyzed regarding the presence of coronary artery lesions. The findings were compared with invasive coronary angiography. During computed tomographic examination, mean heart rate was 65 +/- 14 beats/min. Thirteen of 51 patients (25%) did not have sinus rhythm. Mean Agatston score equivalent was 779 (median 358, range 0 to 3,898). Prevalence of CAD was 75%. Based on a coronary segment model, sensitivity was 96%, specificity 87%, positive predictive value 61%, and negative predictive value 99% for the detection of significant lesions (> or =50% diameter stenosis). The main reason for false-positive results was an overestimation of mild lesions by DSCT. In conclusion, our initial data indicate that DSCT allows a high accuracy to exclude relevant coronary stenosis in unselected patients with a high prevalence of CAD and a relevant number with heart rhythm irregularities. However, overestimation of stenosis, especially in cases of calcifications, is still a limitation.     

Manganese porphyrin reduces retinal injury induced by ocular hypertension in rats

This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP⁵⁺) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP⁵⁺ (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP⁵⁺ were measured via LC-MS/MS. Latencies of all VEP components (P₁, N₁, P₂, N₂, P₃) were significantly prolonged (p < 0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p < 0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP⁵⁺ treatment and NOS inhibition in ocular hypertension.     

Collinear contextual suppression in schizophrenic patients

Schizophrenic patients show aberrancies of contextual processing over a broad range. Of particular importance are low level contextual deficiencies since they might cause higher level processing deficits. It was previously found that schizophrenic patients reveal diminished contextual facilitation in visual detection tasks taken as an indication of a modified neural circuitry. Here, we show that contextual suppression is not affected. Sixteen schizophrenic patients and sixteen healthy controls participated in a backward masking task in which a vernier target was followed by a masking grating. In accordance with a previous publication, schizophrenic patients needed longer SOAs between the vernier and the grating onset to obtain a performance level comparable to healthy controls. To study contextual processing we added single collinear lines to the grating. These lines yielded a strong impairment of performance in patients and controls. This impairment is comparable between the two groups if SOAs were individually adjusted. Hence, whereas contextual facilitation is deficient, contextual suppression seems to be intact in schizophrenic patients.     

Comparative studies on the anorectic activity of d-fenfluramine in mice,rats, and guinea pigs

Summary The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d-norfenfluramine show anorectic activity at increasing doses (ED₅₀) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities are reached with different brain levels of d-fenfluramine and d-norfenfluramine, guinea pigs being the most sensitive species, followed by rats then mice. The metabolite most probably plays a major role in the anorectic effect of d-fenfluramine in guinea pigs, contributes to the anorectic activity in rats, but adds little to the action of the parent drug in mice. The different sensitivity to d-fenfluramine and d-norfenfluramine in these three species does not appear to be explained by a number of biochemical parameters, including serotonin uptake or release, receptor subtypes, or ³H-d-fenfluramine binding and uptake. Send of fprint requests to T. Mennini at the above address     

Venous air embolism during radical perineal prostatectomy

An abrupt decrease in end-tidal carbon dioxide (CO₂) occurred in an anesthetized male who was placed in the head down position during radical perineal prostatectomy. The end-tidal CO₂ was restored after insertion of a wet pack into the operative site, which strongly indicated venous air embolism as the cause. Predisposing factors, detection, and treatment of venous air embolism in this setting are discussed.     

Proteinuria and Albumin Homeostasis in the Nephrotic Syndrome: Effect of Dietary Protein Intake

Nephrotic syndrome is analyzed in the light of interventions designed to decrease proteinuria and renal injury. The effect of dietary protein intake on urinary protein losses and albumin homeostasis are discussed on the basis of the pathophysiologic mechanisms known to account for changes in renal function of nephrotic patients. In addition, the effect of angiotensin-converting enzyme inhibitors for reduction of proteinuria is discussed in terms of the modulation of glomerular permselectivity and hemodynamics.