Sensitivity of an automatic external defibrillator for ventricular tachyarrhythmias in patients undergoing electrophysiologic studies

An automatic advisory external defibrillator (AED) was activated during all arrhythmias occurring at the time of 77 electrophysiologic studies in 45 patients. Sustained ventricular tachycardia (VT) occurred during 55 studies in 31 patients and nonsustained VT was induced during 10 studies in 9 patients. Ventricular fibrillation was induced 5 times in 5 patients and atrial arrhythmias with a rapid ventricular response occurred during 7 studies in 4 patients. The AED detection algorithm advised "shock" during 36 of 55 (65%) episodes of sustained VT and all 5 episodes of ventricular fibrillation. The device correctly advised "shock" for all 6 episodes of nonsustained VT that spontaneously terminated after analysis was complete. Thus, the sensitivity of the device for all ventricular arrhythmias analyzed was 47 of 66 (71%). The device recommended "shock" for all 31 episodes of rapid VT and 1 of 2 episodes of atrial fibrillation associated with systemic hypotension (32 of 33, 97%). The 19 episodes of VT for which "no shock" was advised were comparatively slow and were hemodynamically well tolerated. The device recommended "no shock" during all 21 episodes of normal sinus rhythm and all 20 episodes of rapid atrial pacing (cycle length 400 ms) analyzed. "No shock" was advised during 4 episodes of sustained narrow QRS complex supraventricular tachycardia and 4 brief episodes of nonsustained VT that terminated before analysis was complete. Thus, in this study the specificity of the AED for wide complex tachycardias was 100%.     

Tegaserod does not alter fasting or meal-induced biliary tract motility

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.     

Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure

Angiotensin-converting enzyme inhibitors had no significant effect on cardiopulmonary exercise function in 14 patients who had undergone a Mustard operation for transposition of the great arteries. In some patients aerobic capacity improved and maximum systolic blood pressure decreased.     

Soy phytoestrogens do not prevent bone loss in postmenopausal monkeys

The putative skeletal effects of dietary soy phytoestrogens (SPE) were examined in comparison with those of conjugated equine estrogens (CEE; Premarin) in a 3-yr longitudinal study in ovariectomized female monkeys. Controls received alcohol-extracted soy protein with low phytoestrogen content, and treatment groups received either CEE (admixed into the control diet) or unextracted soy protein isolate containing SPE. The acknowledged bone protective effect of CEE was reflected by higher bone mass (by dual energy x-ray absorptiometry) and lower bone turnover marker levels. In contrast, control and SPE groups lost significant lumbar spine bone mineral content and density and whole body bone mineral content within the first year, resulting in reduced bone mass for both groups compared with CEE (P < 0.0005). No effect of SPE was observed for any bone mass measure (P > 0.44), although transient, estrogen-like effects of SPE on serum alkaline phosphatase, calcium, and C-terminal cross-link of type I collagen were observed at 3 months (P < 0.02). These results suggest that SPE may be poor substitutes for mammalian estrogens in protecting against bone loss resulting from estrogen deficiency.     

Pancreatic tumor growth is regulated by the balance between positive and negative modulators of angiogenesis

There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo. In this study, we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo. The human pancreatic cancer cell line Hs-776T (HS-W) produces slow-growing tumors in SCID mice. Cells of a variant form (HS-R) of Hs-776T produced faster-growing tumors compared to HS-W. Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2, but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R. Cell proliferation was similar in both tumor types in vivo, whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells (EC). Subsequently, VEGF was over-expressed in Hs-776T cells (HS-VF), resulting in rapidly growing tumors and lowering tumor and EC apoptosis. Collectively, our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors.     

Concurrent use of transgenic plants expressing a single and two Bacillus thuringiensis genes speeds insect adaptation to pyramided plants

Transgenic plants expressing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) were grown on over 13 million ha in the United States and 22.4 million ha worldwide in 2004. Preventing or slowing the evolution of resistance by insects ("resistance management") is critical for the sustainable use of Bt crops. Plants containing two dissimilar Bt toxin genes in the same plant ("pyramided") have the potential to delay insect resistance. However, the advantage of pyramided Bt plants for resistance management may be compromised if they share similar toxins with single-gene plants that are deployed simultaneously. We tested this hypothesis using a unique model system composed of broccoli plants transformed to express different Cry toxins (Cry1Ac, Cry1C, or both) and a synthetic population of the diamondback moth (Plutella xylostella) carrying genes for resistance to Cry1Ac and Cry1C at frequencies of approximately 0.10 and 0.34, respectively. After 24-26 generations of selection in the greenhouse, the concurrent use of one- and two-gene plants resulted in control failure of both types of Bt plants. When only two-gene plants were used in the selection, no or few insects survived on one- or two-gene Bt plants, indicating that concurrent use of transgenic plants expressing a single and two Bt genes will select for resistance to two-gene plants more rapidly than the use of two-gene plants alone. The results of this experiment agree with the predictions of a Mendelian deterministic simulation model and have important implications for the regulation and deployment of pyramided Bt plants.     

Young children's understandings of cigarette smoking

Aims We explore young children's attitudes toward, beliefs about, and life‐style associations with cigarette smoking using direct and indirect measures. Design, setting and participants Second (n = 100) and fifth grade (n = 141) elementary school students (i.e. 7–8 and 10–11‐year‐olds) were excused from class and individually interviewed. Methods Participants selected pictures in response to the questions: who would like to smoke cigarettes the most and who would like to smoke cigarettes the least? Their picture choices were probed using open‐ended prompts designed to elicit the beliefs and life‐style associations underlying their choices. Survey‐based measures of attitudes and beliefs were also collected. Findings Second graders reported life‐style associations with cigarette smoking that were consistent with those of fifth graders. While their associations with smoking are generally negative, children appear to perceive that others feel that smoking makes them look cool and feel cool and also helps them to fit in. By fifth grade, many children believe that smoking can help to reduce stress and alleviate negative mood states. The presence of a smoker in the household does not appear to affect these associations, suggesting that they may be being shaped by external socialization agents. Conclusion Young children appear to be developing understandings of cigarette smoking that go beyond knowing that cigarettes are products that are smoked. As some of their perceptions appear likely to predispose them for future experimentation, young children need to be included in prevention research so that age‐appropriate interventions can be developed.     

Diesel exhaust exposure enhances the expression of IL-13 in the bronchial epithelium of healthy subjects

Epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is an important contributor to ambient particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, with an enhanced epithelial expression of IL-8, and Gro-alpha in healthy subjects. The present investigation was aimed to further characterise the epithelial response to DE in vivo, with particular reference to possible TH2 response, in non-atopic healthy subjects. To determine this response, 15 healthy, non-atopic non-smoking subjects with normal lung function were exposed to DE (PM10 300 microg/m3) and filtered air during 1 h on two separate randomised occasions. Bronchoscopy sampling of bronchial mucosal biopsies was performed 6 h after exposure. Immunohistochemical staining were performed using mAb for IL-10, IL-13 and IL-18 expression. DE exposure induced a significant increase in the expression of IL-13 in the bronchial epithelium cells, 2.1 (1.35-4.88) Md (Q1-Q3) vs. air 0.94 (0.53-1.23); P = 0.009. No significant changes were seen in IL-10 and IL-18 expression. This finding suggests an TH2-inflammatory response in the airways of non-atopic healthy individuals.