Tetrofosmin imaging in the detection of myocardial viability in patients with previous myocardial infarction: comparison with sestamibi and tl-201 scintigraphy

BACKGROUND: Technetium 99m tetrofosmin has been introduced as a myocardial perfusion agent, providing similar results to those of thallium 201 and sestamibi in the identification of patients with coronary artery disease. No data are available comparing tetrofosmin and sestamibi imaging in the identification of reversible left ventricular (LV) dysfunction in the same patients. This study compared the results of tetrofosmin, thallium, and sestamibi single photon emission computed tomography at rest in detection of myocardial viability in patients with previous myocardial infarction. METHODS AND RESULTS: Seventeen patients with previous myocardial infarction who were undergoing coronary revascularization were studied. Echocardiography was performed at baseline and 3 months after revascularization to evaluate recovery of LV function. The optimal threshold cutoffs to separate reversible from irreversible dysfunction, as determined by receiver operating characteristic analysis, were 55% of peak activity for both tetrofosmin and sestamibi and 60% for thallium. In all asynergic segments (n = 77) analyzed, tetrofosmin uptake correlated with both sestamibi (r = 0.90, P <.0001) and thallium (r = 0.85, P <.0001) activity. The sensitivity and specificity for reversible dysfunction were, respectively, 70% and 70% for tetrofosmin, 70% and 66% for sestamibi, and 60% and 68% for thallium imaging (all P = not significant). The areas under the receiver operating characteristic curves constructed for tetrofosmin, thallium, and sestamibi activity were 0.74 +/- 0.06 (mean +/- SD), 0.75 +/- 0.06, and 0.74 +/- 0.06, respectively (all P = not significant). Concordance for detecting myocardial viability between tetrofosmin and thallium imaging was found in 67 regions (87%) (kappa = 0.74), and concordance between tetrofosmin and sestamibi imaging was found in 69 regions (90%) (kappa = 0.79). CONCLUSIONS: The diagnostic performance of quantitative rest tetrofosmin single photon emission computed tomography in predicting functional recovery after revascularization is comparable to that of both thallium and sestamibi scintigraphy in patients with myocardial infarction and chronic LV dysfunction.     

The renin-angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease

The renin-angiotensin system (RAS) plays an important homeostatic role in BP regulation, water and salt balance, and tissue growth control under physiologic conditions. On the other hand, a pivotal involvement of the RAS in the pathophysiology of cardiovascular and renal disease is extensively supported by both basic and clinical evidence. In particular, it is today recognized that angiotensin II (AngII), the biologic effector of the RAS, may prompt a number of relevant structural and functional abnormalities through the activation of a complex of cellular effects mostly mediated via its binding with the AT(1) subtype receptors. The key role of these AngII-linked mechanisms of disease is strongly corroborated by large interventional studies. In fact, pharmacologic interference with RAS activity, by both preventing AngII formation with angiotensin-converting enzyme inhibitors or antagonizing its binding to cell membrane receptors by selective antagonists, is associated with highly beneficial outcomes in major disease conditions (hypertension, diabetes, renal failure, heart failure, myocardial infarction, stroke, and others). This article briefly reviews the current views on the biologic organization of RAS evidence supporting a pathogenic role of the RAS activity in promoting cardiac, vascular, and renal disease, and finally provides the basis for considering inhibition of RAS activity a major target for therapeutic interventions in these conditions.     

Motion sickness and postoperative vomiting in children

BACKGROUND: Motion sickness is considered an important risk factor for postoperative nausea and vomiting in children. The aim of this study was to verify the impact of motion sickness on the incidence of vomiting after routine surgery in children, and to compare the incidence of vomiting, after combined regional/general anaesthesia, using either halothane or sevoflurane. METHODS: We prospectively studied 420 children (369 males and 51 females) who received general anaesthesia and inguinal field block for common paediatric surgery. The children were randomly allocated into one of two groups (halothane or sevoflurane). In the 200 children in the first group (H), general anaesthesia was induced and maintained with halothane, whereas in the 220 children in the second group (S), anaesthesia was induced and maintained with sevoflurane. RESULTS: There were 79 children with a prior history of motion sickness (MS+) and 341 without such a history (MS-). In the MS+ population, the incidence of vomiting was similar in both H and S groups, being around 33%. However, repeated episodes of vomiting in MS+ children were more frequent when halothane was used. In the MS- group, the incidence of vomiting was significantly greater in the H group (19%) than in the S group (8%). CONCLUSIONS: In the postoperative period, we found that MS+ children vomit more than MS- children, regardless of the inhalation anaesthetic used. However, MS- children displayed a higher incidence of vomiting when halothane was used rather than sevoflurane.     

Pharmacokinetics and metabolism in mice of IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III), a new oral c-seco-taxane derivative with antiangiogenic property effective on paclitaxel-resistant tumors.

IDN 5390 (13-(N-Boc-3-i-butylisoserinoyl)-C-7,8-seco-10-deacetylbaccatin III) is a new taxane, derived from 7,8-C-seco-10-deacetylbaccatin, selected for its ability to inhibit angiogenesis, mainly by acting on endothelial cell motility, and for its selective activity on class III beta-tubulin. In vivo, IDN 5390 shows activity against paclitaxel-sensitive and -resistant tumors when administered on a prolonged, continuous dosage schedule. We studied the pharmacokinetics and bioavailabilty of the drug in mice after single and repeated oral treatment. IDN 5390 was rapidly absorbed after oral administration, with good bioavailability (43%). After intravenous injection, it was extensively distributed in tissue, mainly the liver, kidney, and heart, with low but persistent levels in brain. The kinetics appear dose-dependent with a clearance of 2.6, 1.4, and 0.9 l/kg at, respectively, 60, 90, and 120 mg/kg, and a half-life 24, 36, and 54 min. After prolonged daily oral doses given for 2 weeks, we found that there was a decrease in drug availability; i.e., the area under the concentration-time curve value after p.o. daily administration on day 14 was 2-fold lower than that on day 1. Metabolism plays a major role in elimination of the drug, and at least 12 metabolites were identified in feces and urine. The percentage excreted as metabolites after an oral dose (42%) was higher than that after the i.v. dose (33%), suggesting a first-pass effect. Four metabolites were found in plasma at detectable levels; one of them, with restored taxane scaffold, is a species 3 times more potent than IDN 5390, possibly contributing to the observed anti-tumor activity.     

Yolk sac tumor in a young girl: a case report.

BACKGROUND: Yolk sac tumor is a rare neoplasm characterized by high malignancy given its premature metastasis, that is frequent in adolescence. CASE REPORT: A 21-year-old woman came to our observation for an ovarian cyst (13 cm in diameter). Following salpingo-oophorectomy, it was revealed as a yolk sac tumor by histological diagnosis. The patient exhibited a highly elevated level of alpha1-fetoprotein (AFP) (1156 UI/ml). She is now undergoing chemotherapy treatment. CONCLUSION: This is an interesting case of yolk sac tumor in a young girl, at an age typical for germ cell tumor. AFP represents a valid marker resulting in a useful diagnostic tool.     

Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants

In a previous study on formula-fed preterm infants, we were able to demonstrate that dietary oligosaccharides (a mixture of 90% galacto-oligosaccharides and 10% fructo-oligosaccharides in a concentration of 1 g/dl) stimulate the growth of faecal bifidobacteria. In the present explorative analysis of this study, we focus on the effect of the dominance of bifidobacteria on the presence of clinically relevant pathogens ( Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Proteus, Streptococcus group B, Clostridium difficile, Bacillus subtilis and Acinetobacter ).
Conclusion : The data demonstrate that stimulation of bifidobacteria by prebiotic oligosaccharides reduces the presence of clinically relevant pathogens in the faecal flora, indicating that prebiotic substances might have the capacity to protect against enteral infections.     

Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma.

PURPOSE: The aim of this study was to acquire further insights into the pathogenetic pathways of head and neck squamous cell carcinomas (HNSCC) that may be useful for identifying new biomarkers instrumental in developing more specific treatment approaches. EXPERIMENTAL DESIGN: Cell cycle regulators and epidermal growth factor receptor (EGFR) and BRAF genes were analyzed in a series of 90 oropharyngeal SCCs of a cohort of surgically treated patients from a single institution, and the results were matched with the presence of high-risk human papillomavirus (HR-HPV) DNA and the TP53 status. RESULTS: At least four distinct groups of tumors were identified sharing a common histology but displaying different molecular/cytogenetic patterns: (a) 19% were HPV-positive SCCs whose lack of alterations of the investigated genes could explain their particular natural history, which requires less aggressive treatment; (b) 37% were HPV-negative SCCs carrying TP53 mutations, which may be more effectively treated by drugs acting through p53-independent apoptosis; (c) 34% were HPV-negative SCCs carrying wild-type TP53 and loss of 9p21 (p16INK4a and p15INK4b) and/or cyclin D1 overexpression that justify treatment with DNA-damaging drugs followed by cell cycle inhibitors; and (d) 10% were HPV-negative lacking tumor suppressor genes and cell cycle alterations. The second, third, and fourth groups also showed an increased copy number of EGFR and chromosome 7 (43%) that might justify the additional or alternative use of EGFR inhibitors. CONCLUSIONS: Our findings suggest that assessing HPV, TP53, 9p21, and EGFR status may be crucial to finding more tailored and beneficial treatments for oropharyngeal SCCs.