Dual-energy digital subtraction chest radiography: technical considerations

In the evaluation of asbestos-related pulmonary and pleural abnormalities, conventional chest radiography has been shown to have a low sensitivity for the detection of lung nodules and subtle interstitial disease. Pleural plaques may simulate pulmonary nodules, and interstitial processes can be masked by adjacent pleural abnormalities. Dual-energy digital subtraction chest radiography may enable investigators to characterize asbestos-related pulmonary and pleural abnormalities with greater accuracy. "Soft-tissue" images, designed to remove pleural calcifications, may allow for better evaluation of the lung parenchyma. "Bone" images, designed to remove soft-tissue structures, may enhance the detection of pleural calcifications. In this pictorial essay we illustrate the methods, technical considerations, and limitations of dual-energy digital subtraction chest radiography performed with global subtraction weighting factors.     

Unconscious sedation in children: a prospective multi-arm clinical trial

BACKGROUND: We report the evaluation of six sedative-hypnotic and analgesic combinations administered to children undergoing brief periods of unconscious (or deep) sedation for painful procedures. METHODS: In a prospective, open-label, randomized, controlled study of six groups of 27-30 children each, patients were randomly assigned to receive propofol or methohexital for sedation-hypnosis, and one of three incremental doses of fentanyl or remifentanil, respectively. RESULTS: An infusion of methohexital (10 mg.ml-1) combined with remifentanil (6.67 micro g.ml-1) provided significantly shorter geometric mean times to initial emergence, to eye-opening and to discharge, and required airway interventions that were not significantly more frequent than all groups sedated with propofol and fentanyl. CONCLUSIONS: The combination of methohexital and remifentanil appears to be a satisfactory method for unconcious sedation for short painful procedures in children.     

Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents. Rats were maintained on AIN-76A chow or supplemented with 0.4% UDCA or F(6)-D(3) (2.5 nmol/kg chow) and treated weekly with AOM 20 mg i.p./kg wt or saline x 2 weeks. F(6)-D(3) was continued for an additional 2 weeks and UDCA for the duration of the study. At 40 weeks, animals received bromodeoxyuridine (BrdUrd) i.p. 2 h before sacrifice. A portion of each tumor was fixed in formalin and the remainder flash frozen. Colons were divided longitudinally and half-fixed in formalin and half in ethanol. The size and location of methylene blue-stained ACF were recorded. Cell proliferation (BrdUrd labeling) and apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay) were measured in colonic crypts and tumors. Protein expression levels of several regulators of cell proliferation were analyzed by immunostaining and Western blotting. Colonic crypt cyclin D1 and E-cadherin mRNA levels were measured by real-time PCR. In saline injected controls, neither UDCA nor F(6)-D(3) alone had any effect on cytokinetic parameters or on the expression of mitogenic regulators. AOM significantly increased the proliferation (percentage of BrdUrd-positive cells) of both ACF (23.1 +/- 1.7%) and non-ACF crypts (17.6 +/- 1.6%), compared with normal colonic crypts (4.5 +/- 0.8%; P < 0.05). This hyperproliferation was accompanied by a 5-fold increase in cyclin D1 and >50% decrease in E-cadherin protein (P < 0.05) in ACF, both of which are predicted to be growth-enhancing alterations. UDCA and F(6)-D(3) significantly (P < 0.05) inhibited AOM-induced crypt cell hyperproliferation, ACF development, and tumor burden. These chemopreventive agents also significantly blocked AOM-induced alterations in cyclin D1 and E-cadherin protein in ACF and tumors. In ACF, changes in mRNA levels of cyclin D1, but not E-cadherin, paralleled alterations in protein expression. Cyclooxygenase-2 and inducible nitric oxide synthase were increased in AOM tumors but not in ACF, and these changes were blocked by UDCA and F(6)-D(3). UDCA and F(6)-D(3) significantly inhibited ACF development and hyperproliferation, in part, by preventing carcinogen-induced alterations in cyclin D1 and E-cadherin. In established tumors, UDCA and F(6)-D(3) also limited inductions of cyclooxygenase-2 and inducible nitric oxide synthase, which together with their effects on cyclin D1 and E-cadherin, contribute to their chemopreventive actions.     

Optimal classes of chemotherapeutic agents sensitized by specific small-molecule inhibitors of akt in vitro and in vivo

Akt is a serine/threonine kinase that transduces survival signals from survival/growth factors. Deregulation and signal imbalance in cancer cells make them prone to apoptosis. Upregulation or activation of Akt to aid the survival of cancer cells is a common theme in human malignancies. We have developed small-molecule Akt inhibitors that are potent and specific. These Akt inhibitors can inhibit Akt activity and block phosphorylation by Akt on multiple downstream targets in cells. Synergy in apoptosis induction was observed when Akt inhibitors were combined with doxorubicin or camptothecin. Akt inhibitor-induced enhancement of topoisomerase inhibitor cytotoxicity was also evident in long-term cell survival assay. Synergy with paclitaxel in apoptosis induction was evident in cells pretreated with paclitaxel, and enhancement of tumor delay by paclitaxel was demonstrated through cotreatment with Akt inhibitor Compound A (A-443654). Combination with other classes of chemotherapeutic agents did not yield any enhancement of cytotoxicity. These findings provide important guidance in selecting appropriate classes of chemotherapeutic agents for combination with Akt inhibitors in cancer treatment.     

Green Foot

Pseudomonas aeruginosa may infect the skin surface, nails, hair follicles, or deeper tissues. We report a 13-year-old male with an asymptomatic green discoloration of the toenails and sole of the right foot. Pseudomonas aeruginosa was cultured from the shoe, but not from the discolored skin. We suspect that constant wearing of occlusive, rubber-soled, basketball shoes associated with hyperhidrosis allowed colonization of his shoe with pseudomonas. This case is unique in that colonization resulted in a green color of the foot not associated with infection of the skin.     

Comparative evaluation of intravenous phenytoin,procainamide and practolol in the acute treatment of ventricular arrhythmias

Summary Ten patients with a persistent ventricular arrhythmia, but no other sign of heart disease, were studied by means of an exercise test performed 4 times with a fixed work load, over 30–40 min. No drug was given in the first exercise test and in the others phenytoin, procainamide or practolol were chosen at random for i. v. administration. Blood samples for determination of plasma concentration were frequently collected. The ECG was recorded continuously during the exercise test and was analysed minute by minute. Despite plasma levels within the suggested therapeutic range, only procainamide showed a statistically significant antiarrhythmic effect in this group of patients.