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Our study analyzes imaging results in near-hanging to determine what neuroimaging workup is necessary. We evaluate GCS as a clinical predictor to help guide imaging choice. This is a retrospective study of patients from a level one trauma center and from the National Trauma Data Bank (NTDB). We classified injuries into categories based on the likelihood that CT played an important role in their diagnosis and management. We assessed whether a normal Glasgow Coma Scale (GCS) could exclude clinically important injuries. Chi square was used to test for significance for categorical variables. Multivariate logistic regression was used for multivariate analysis. CT showed structural brain findings in 0% of patients from our facility (local patients) and 11.7% of NTDB patients. Of local patients and NTDB patients, 1.4% and 6.6% had blunt cerebral vascular injury (BCVI) respectively. Of local patients and NTDB patients, 1.4% and 3.3% had a cervical spine fracture or dislocation, respectively. Mortality for patients with GCS 15 versus GCS

Carbohydrate Responsive Element-Binding Protein (ChREBP) is a carbohydrate sensing transcription factor that regulates both adaptive and maladaptive genomic responses in coordination of systemic fuel homeostasis. Genetic variants in the ChREBP locus associate with diverse metabolic traits in humans, including circulating lipids. To identify novel ChREBP-regulated hepatokines that contribute to its systemic metabolic effects, we integrated ChREBP ChIP-seq analysis in mouse liver with human genetic and genomic data for lipid traits and identified Hepatocyte Growth Factor Activator (HGFAC) as a promising ChREBP-regulated candidate in mice and humans. HGFAC is a protease that activates the pleiotropic hormone Hepatocyte Growth Factor (HGF). We demonstrate that HGFAC KO mice have phenotypes concordant with putative loss-of-function variants in human HGFAC. Moreover, in gain- and loss-of-function genetic mouse models, we demonstrate that HGFAC enhances lipid and glucose homeostasis, in part, through actions to activate hepatic PPARγ activity. Together, our studies show that ChREBP mediates an adaptive response to overnutrition via activation of an HGFAC-HGF-PPARγ signaling axis in the liver to preserve glucose and lipid homeostasis.

Carbohydrate Responsive Element-Binding Protein (ChREBP) is a carbohydrate sensing transcription factor that regulates metabolic gene programs. Genetic variants in the ChREBP locus associate with diverse metabolic traits in humans, including circulating triglycerides (TG). The transcriptional targets that mediate its pleiotropic physiological effects are poorly understood. To identify novel ChREBP-regulated hepatokines that contribute to its effects on metabolism, we integrated ChIP-seq for ChREBP in mouse liver with human GWAS data for TGs and identified Hepatocyte Growth Factor Activator (HGFAC) as a promising candidate. HGFAC is a circulating zymogen that activates Hepatocyte Growth Factor (HGF), a multifunction cytokine involved in cellular growth, motility, and morphogenesis. High fructose feeding increased circulating HGFAC by 1.8-fold (p Disclosure A. Sargsyan: None. I. Astapova: None. L. T. Tsai: None. M. A. Herman: Research Support; Self; Eli Lilly and Company. L. Doridot: Employee; Spouse/Partner; Eli Lilly and Company. S. A. Hannou: None. W. Tong: None. H. Srinivasan: None. R. Ivison: None. R. Monn: None. H. H. Kou: None. J. Haldeman: None. Funding American Diabetes Association (1-19-PDF-088 to A.S.)

A number of factors in Western society, including inflammatory diets, sedentary lifestyles, vitamin D deficiency and chronic psychological stress, are known to induce inflammation and to be associated with neuropsychiatric disorders. One factor that is emerging as a potential inflammation inducing factor is biota depletion, or loss of biodiversity from the ecosystem of the human body as a result of industrialization. Originally known as the "hygiene hypothesis", biota alteration theory describes the effects of biota alteration on the human immune system. Work on this topic has pinpointed depletion of helminths as a key loss to the body's ecosystem in Western society, and suggests that some exposure to helminths, ubiquitous prior to the modern era, may be necessary for normal immune system development. Socio-medical studies of humans "self-treating" with helminths as well as limited studies in animal models strongly suggest that helminth therapy may be a productive approach toward treating a range of neuropsychiatric disorders, including chronic fatigue, migraine headaches, depression and anxiety disorders. However, helminth therapy faces some daunting hurdles, including the lack of a financial incentive for development, despite a tremendous potential market for the organisms. It is argued that benevolent donation for early trials as well as changes in regulatory policy to accommodate helminth therapy may be important for the field to develop. It is hoped that future success with some high-profile trials can propel the field, now dominated more by self-treatment than by clinical trials, forward into the main stream of medicine.

The Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes in response to oxidative and xenobiotic stress. A large number of Nrf2-antioxidant response element (ARE) activators have been screened for use as chemopreventive agents in oxidative stress-related diseases and even cancer. However, constitutive activation of Nrf2 occurs in a variety of cancers. Aberrant activation of Nrf2 is correlated with cancer progression, chemoresistance, and radioresistance. In this review, we examine recent studies of Nrf2-ARE inhibitors in the context of cancer therapy. We enumerate the possible Nrf2-inhibiting mechanisms of these compounds, their effects sensitizing cancer cells to chemotherapeutic agents, and the prospect of applying them in clinical cancer therapy.

Increased sugar consumption is a risk factor for the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor that responds to sugar consumption to regulate adaptive metabolic programs. Hepatic ChREBP is particularly responsive to fructose and global ChREBP-KO mice are intolerant to diets containing fructose. It has recently been suggested that ChREBP protects the liver from hepatotoxicity following high-fructose diets (HFrDs). We directly tested this hypothesis using tissue-specific ChREBP deletion. HFrD increased adiposity and impaired glucose homeostasis in control mice, responses that were prevented in liver-specific ChREBP-KO (LiChKO) mice. Moreover, LiChKO mice tolerated chronic HFrD without marked weight loss or hepatotoxicity. In contrast, intestine-specific ChREBP-KO (IChKO) mice rapidly lost weight after transition to HFrD, and this was associated with dilation of the small intestine and cecum, suggestive of malabsorption. These findings were associated with downregulation of the intestinal fructose transporter, Slc2a5, which is essential for fructose tolerance. Altogether, these results establish an essential role for intestinal, but not hepatic, ChREBP in fructose tolerance.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95 % confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

Pulmonary Vein Arrhythmias. Introduction: Recent studies demonstrated that atrial arrhythmias may be generated within pulmonary veins. The purpose of this study was to compare the endocardial activation times at effective and ineffective ablation sites during radiofrequency catheter ablation of arrhythmias initiated or generated within pulmonary veins. Methods and Results: Twenty-one of 28 patients without structural heart disease underwent successful ablation of 23 arrhythmogenic foci within a pulmonary vein. Electrograms were recorded at 75 pulmonary venous sites and categorized into three groups: 23 successful ablation sites; 28 unsuccessful target sites within an arrhythmogenic pulmonary vein; and 24 sites within nonarrhythmogenic pulmonary veins. The endocardial activation time of premature depolarizations arising at successful target sites was significantly earlier than at other sites. During premature depolarizations, an endocardial activation time of -75 msec or earlier had a sensitivity of 83% and a specificity of 79% for identification of a successful ablation site. Endocardial activation times earlier than -100 msec were recorded only at successful ablation sites, and endocardial activation times later than -30 msec were recorded only at sites within nonarrhythmogenic pulmonary veins. The presence of a split potential during sinus rhythm or premature depolarizations was not a specific indicator of a successful ablation site. Conclusion: The endocardial activation times of premature depolarizations that arise within pulmonary veins and initiate atrial tachycardia/fibrillation are useful in identifying successful ablation sites.

Prior studies have demonstrated that sympathetic tone may influence the effects of adenosine on His-Purkinje automaticity, and that enhanced vagal tone may influence its effects on the sinus node. However, the interaction between autonomic tone and the effects of adenosine on the sinus node in humans remains unknown. Therefore, this study was designed to investigate the interaction between different states of autonomic tone and the bradycardiac response of the sinus node to adenosine. In 11 patients without structural heart disease who underwent a clinically indicated electrophysiology procedure, the sinus cycle length was measured before and after a 12-mg bolus of adenosine in the baseline state, during an infusion of 2 mcg/min of isoproterenol, after the administration of 0.2 mg/kg of propranolol, and again after the administration of 0.04 mg/kg of atropine. Adenosine significantly lengthened the sinus cycle length in the baseline state (760 +/- 165 vs 909 +/- 188 ms, P < 0.05), during isoproterenol infusion (516 +/- 67 vs 766 +/- 146 ms, P < 0.05), after propranolol (850 +/- 153 vs 914 +/- 143 ms, P < 0.05) and after the combination of propranolol and atropine (662 +/- 76 vs 801 +/- 121 ms, P < 0.05). The degree of lengthening in sinus cycle length was significantly greater (P < 0.05) during isoproterenol infusion (253 +/- 157 ms, or 51% +/- 40%) than in the baseline state (149 +/- 85 ms, or 20% +/- 12%), after propranolol (68 +/- 53 ms, or 8% +/- 8%), and after propranolol and atropine (140 +/- 110 ms, or 21% +/- 18%). The negative chronotropic effect of adenosine is influenced by autonomic tone. The effect of adenosine on the sinus node is accentuated by beta-adrenergic stimulation and unaffected by beta-adrenergic blockade or combined beta-adrenergic and cholinergic blockade.

White spot baculovirus (WSBV) is the causative agent of a disease which decimated some cultured penaeid shrimp populations and inflicted severe economic damage in Taiwan. Until very recently, the giant freshwater prawn Macrobrachium rosenbergii was thought to be unaffected by this virus, but now signs closely resembling white spot syndrome (WSS) have been observed on its exoskeleton. In this paper, WSBV was established as the causative agent by using the diagnostic polymerase chain reaction (PCR) with WSBV-specific primers. WSBV was found in M. rosenbergii larvae, postlarvae, juveniles, and adults. The amplified product from the DNA of the naturally-infected WSS M. rosenbergii was similar to that of WSBV-infected Penaeus monodon. Furthermore, comparison of the restriction profiles of these two PCR products by HaeIII, HpaII, RsaI, and Sau3AI revealed no differences, suggesting that WSBVs from the infected P. monodon and M. rosenbergii are closely related, if not identical. A homogenate positive in one-step WSBV diagnostic PCR was prepared from frozen P. monodon for the challenge experiment. Dilutions were added to tanks of healthy M. rosenbergii larvae and postlarvae. After 2 days, some of the dead specimens were positive for WSBV by diagnostic PCR.

Since 1992, mass mortalities among cultured giant tiger shrimp, Penaeus monodon (Fabricius), and kuruma shrimp, Penaeus japonicus (Bate), have been observed in Taiwan. The condition is known as ‘white spot disease’ (WSD), based on the characteristic white spots on the cuticle of diseased shrimp. With the scanning electron microscope, two sizes of white spots were observed. Each spot represented a protrusion on the inside surface of the carapace. The composition of white spots was similar to that of the cuticule, most calcium, as determined with an energy dispersive spectrometer. Histological studies of moribund, infected specimens revealed degenerated cells, characterized by hypertrophied nuclei, in various meso- and ectodermal tissues. Infected tissues included cuticular epidermis, connective tissue, lymphoid organ, antennal gland, and haematopoietic, gill and nervous tissue. Nuclei were Feulgen-positive and no occlusion body was found in the necrotic tissue. Transmission electron microscopy revealed the presence of rod-shaped and enveloped virions in the hypertrophied nuclei. The virions measured 298 ± 21 × 107 ± 8 nm in the giant tiger shrimp and 248 ± 12 × 104 ± 8 nm in the kuruma shrimp. In an experimental infection trial, cumulative mortality was 40% within 14 days under stress conditions. No mortality was observed in controls or in non-stressed infected shrimp. Experimental infections show that environmental stressors such as ammonia may enhance the severity of WSD virus infections in cultured shrimp.

Mass mortalities of hatchery-reared juvenile groupers have occurred in southern Taiwan. The diseased fish swam in a darting, corkscrew fashion. Light microscopy revealed vacuolation in the brain tissue. Electron microscopy showed numerous non-enveloped, cytoplasmic viral particles (20–25 nm in diameter) in the brain cells, and many virions were enclosed in the membrane-bound organelles of the cells. Two structural proteins of the purified grouper virus, with molecular weights of 44 and 43 kDa, were revealed by SDS-PAGE. Moreover, the results of RT-PCR and nested PCR diagnosis using primers specific to the T2 and T4 target segments of striped jack nervous necrosis virus (SJNNV) RNA2 genes suggest that this virus is a fish nodavirus, and is designated as GNNV 9410 strain (grouper nervous necrosis virus strain 9410). This is the first case report of viral nervous necrosis among marine fish in Taiwan.

Brain delivery of neurotrophic factors via the systemic route is limited by the presence of blood brain barrier. Direct infusion into the intraventricular space is currently the mode of administration available clinically. Alternatively, controlled release systems can be the delivery system of choice using bioerodible polymers such as poly(d,l-lactic-co-glycolic acid) (PLGA). To utilize this concept, one has to establish the safety profile of the polymer and degradation products in brain. This report presents the results on the brain biocompatibility of PLGA implant using a rat model. In vitro erosion studies showed that the test PLGA rods eroded almost completely over a period of one month. Upon implantation into the rats' brains, these polymer rods and their breakdown products were well tolerated by the brain tissue. The overall presentation suggested that the brain tissue response to the implanted polymer was typical of those following mechanical trauma and exposure to foreign body. Tissue reaction was more pronounced around 14 days after implantation and largely subsided by day 28 when polymer erosion was near completion. There was no adverse cellular reactions in the parenchymal tissue adjacent to the implanted polymer. These results suggest that the PLGA materials are biocompatible and can be used to construct drug delivery devices for brain implantation.

A humoral response of Japanese eel, Anguilla japonica Temminck & Schlegel, to the microsporean Pleistophora anguillarum Hoshina was demonstrated using immunoblotting and an enzyme-linked immunosorbent assay (ELISA). Japanese eel immunoglobulin was purified by affinity chromatography. The immunoglobulin was composed of 25-kDa light chains and 72-kDa heavy chains. The ELISA values of P. anguillarum antibodies in naturally infected fish sera were significantly higher than those of clinically healthy fish. Spore proteins from the microsporean were separated by electrophoresis and subjected to analysis by Western blot. Sera from naturally infected fish showed different reaction patterns to the spore proteins. While the sera randomly selected from naturally infected eels all showed a significant positive reaction to P. anguillarum antigens, the mucus from only three out of the nine infected eels reacted positively in the ELISA test. Subsequent analyses indicated that there was no significant difference in the amount of mucus immunoglobulin among the tested eels. Therefore, the generally lower ELISA values of mucosal anti-P. anguillarum antibodies from the infected eels tested were evidently not caused by a lack of immunoglobulin per se, but seem to be the result of a lack of anti-P. anguillarum antibodies in the mucus and/or a lower affinity in the anti-P. anguillarum antibodies that were present.

A continuous cell line, designated NTU-PN-HH, was established from the pupal ovary ofPerina nudaFabricius (Lepidoptera: Lymantriidae). The cells have been through more than 300 passages during 4 years in TNM-FH medium supplemented with 10% FBS, at a constant temperature of 28°C. The cell line consists of four major morphologic types: polymorphic cells, spindle-shaped cells, round cells, and squamous cells. The characterization of this cell line showed that NTU-PN-HH is a newly established cell line. It is the first cell line that is permissive to PnNPV (P. nudamultiple nuclear polyhedrosis virus).

The Accufix (Telectronics Pacing Systems, Englewood, Colo.) atrial active fixation pacemaker lead has a preformed J stiff retention wire than can fracture and erode through the atrium. We screened 85 patients with digital fluoroscopy and detected 18 (21%) lead fractures. Fourteen (16%) leads were successfully extracted by percutaneous techniques. The mean time for extraction and placement of a new atrial lead was 109 ± 53 min, and a lead > 1 year old but not in the presence of a fracture was associated with a significantly longer extraction time. There were two extraction complications. One patient had a fever following the extraction, and one patient had a focal sensory deficit 1 week after the extraction probably caused by a paradoxical embolus. Standard percutaneous extraction tools can be used for successful and safe removal of a fractured Accufix lead.

The present study demonstrates the first discovery of a yellow head disease-like virus (YHDLV) in Penaeus japonicus that were diagnosed as white spot disease and describes the histological changes and the characters of the virus under electron microscopical observation. In histological studies, cells with the basophilic inclusion bodies and hypertrophied nuclei were found in various tissues, including the lymphoid organ, interstitial hepatopancreatic tissue, cardiac tissue, gill tissue, connective tissue, cuticular epidermis and hematopoietic tissue. Transmission electron micrographs revealed the presence of rod-shaped, enveloped virions in the cytoplasm of the necrotic cells. The virus was 150-200 nm in length and 40-50 nm in width, but extraordinarily long viruses were also detected in the cells. The features of the YHDLV were very similar to yellow head disease virus of Penaeus monodon in Thailand.

Previous studies have reported a significant morbidity and mortality associated with coronary artery bypass graft (CABG) surgery in conjunction with the placement of an implantable cardioverter defibrillator (ICD) with an epicardial lead system. In the absence of a control group, how significantly the component of concomitant placement of the ICD system contributes to these untoward outcomes remains unknown. The purpose of this study was to assess the short- and long-term complications in patients undergoing CABG surgery in conjunction with the placement of an ICD with epicardial leads and to compare these complications with those of patients who had only CABG surgery (control group). The study group (group A) consisted of 56 patients who underwent CABG surgery and placement of an ICD pulse generator with epicardial leads. A control group (group B) consisted of 56 patients who underwent CABG surgery only during the same time period. The two groups were matched for age, sex distribution, left ventricular function, surgical approach, number of bypass grafts per patient, bypass pump time, and length of follow-up period. The early mortality for group A was 7.1% versus 1.8% for group B (p > 0.05). The incidence of early morbidity (congestive heart failure, infection, supraventricular and ventricular arrhythmias) for groups A and B was similar (26.8% vs 25.0%, p > 0.05). The incidence of late mortality and morbidity (progression of congestive heart failure, recurrence of coronary events, chronic atrial fibrillation) for groups A and group B were 7.7% versus 5.5% (p > 0.05) and 23.1% versus 21.8% (p > 0.05), respectively. However, death caused by cardiopulmonary difficulties was more frequent in group A than group B (12.5% vs 1.8%, p < 0.05). With the availability of the nonthoracotomy lead system and the pulse generator capable of delivering biphasic shock waveform, to place such an ICD system at a later time after the CABG surgery appears to be the preferred approach to treat patients who need both surgical coronary revascularization and ICD.

Long RP Tachycardia, introduction: The purpose of this study is to describe a simple and reliuhle diagnostic maneuver that allows for the rapid differentiation of atypical AV nodal reentrant tachycardia (AVNRT) from other causes of long KP tachycardia. Lonf^ KP tachycardias may he caused by atypical AVNRT, orthodrnmic reciprocating tachycardia (ORT) involving a .slowly conducting retrograde accessory pathway, or atrial tachycardia. The dilTerentiation of atypical AVNRT from ORT or atrial tachycardia may be difficult, especially when the differential diagnosis includes a posteroseptal accessory pathway or an atrial tachycardia arising in the posteroseptal right atrium. Methods and Results: Twelve patients with atypical AVNRT, 21 with ORT, and 12 with an atrial tachycardia diagnosed using conventiitnal criteria were enrolled In this study. The atrialHis (AH) interval was measured at the His-hundle position during the tachycardia and during atrial pacing from the high right atrium at the tachycardia cycle length in the setting of sinus rhythm. In patients with atypical AVNRT, the mean AH interval was 69 msec ± 50 msec (± SD) longer during high right atrial pacing than during the tachycardia (P < 0.001). In 10 of 12 patients with atypical AVNRT, the AH interval during atrial pacing was more than 40 msec longer than the .\H interval measured during the tachycardia. In contra.st. In patients with ORT or atrial tachycardia, the difYerences in .AH interval hetween atrial pacing and tachycardia were never more than 20 and 10 msec, respectively. Conclusion: The difference in the AH interval between atrial pacing and the tachycardia allows a simple and rapid means of difierentiating atypical AVNRT from other types of long RP tachycardias. (J Cardiovasc Electrophysiol, Vol. 6, pp. 700-710. September 1995)

Coronary revascularization has been suggested as sole therapy for secondary prevention of sudden cardiac arrest associated with ischemia. The use of implantable defibrillators (ICD) in combination with coronary revascularization for this patient population is unclear. Among 412 consecutive patients receiving an ICD, 23 (6%) were identified as sudden cardiac arrest survivors who were noninducible with programmed stimulation and had unstable angina or ischemia on a functional study; they underwent successful coronary revascularization. During a follow-up of 34 ± 18 months, 10 (43%) of the 23 patients received ICD shocks (8 ± 8 per patient, range 1 to 22 shocks), and nine of the 10 patients had syncope/presyncope associated with at least one ICD discharge. Patients with ICD discharges were compared with those without ICD discharges, and no clinical characteristics were statistically different between the two groups. In conclusion, revascularization alone may be inadequate therapy for survivors of sudden cardiac arrest associated with ischemia who are noninducible with programmed stimulation, and clinical variables cannot predict which patients are likely to have recurrent malignant ventricular arrhythmias.

No prospective studies have compared sotalol and amiodarone during electropharmacologic testing. The purpose of this prospective, randomized study was to compare the electrophysiologic effects of sotalol and amiodarone in patients with coronary artery disease and sustained monomorphic ventricular tachycardia (VT). Patients with coronary artery disease and sustained monomorphic VT inducible by programmed stimulation were randomly assigned to receive either sotalol (n = 17) or amiodarone (n = 17). The sotalol dose was titrated to 240 mg twice daily over 7 days. Amiodarone dosing consisted of 600 mg 3 times daily for 10 days. An electrophysiologic test was performed in the baseline state and at the end of the loading regimen. An adequate response was defined as the inability to induce VT or the ability to induce only relatively slow hemodynamically stable VT. During the follow-up electrophysiologic test, 24% of patients taking sotalol and 41% of those taking amiodarone had an adequate response to therapy (p = 0.30). Amiodarone lengthened the mean VT cycle length to a greater degree than sotalol (28% vs 12%, p < 0.01). There were no significant differences in the effects of sotalol and amiodarone on the ventricular effective refractory period. In patients with coronary artery disease, amiodarone and sotalol are similar in efficacy in the treatment of VT as assessed by electropharmacologic testing. The effects of the 2 drugs on ventricular refractoriness are similar, but amiodarone slows VT to a greater extent than sotalol.

Iodixanol, a new ratio 6 nonionic iodinated contrast agent with an osmolality equal to serum, was compared with iohexol in a randomized, double-blind, parallel study. Two hundred patients undergoing elective diagnostic cardiac angiography were randomized to iodixanol (n = 101) or iohexol (n = 99). There were no differences noted between the 2 agents in the mean changes in systolic or diastolic blood pressure or heart rate during or immediately after any angiography. However, significantly more patients had a decrease in diastolic blood pressure of20 mm Hg during left coronary angiography with iodixanol. The only significant differences in any electrophysiologic parameter were slightly more PR prolongation during left coronary angiography with iodixanol and more ST-segment depression with iohexol during coronary angiography. Neither was clinically significant. Injection-associated discomfort occurred with both agents, but more patients experienced moderate to severe discomfort with iohexol (52%) than with iodixanol (17%) (p0.001). Only 1 potentially serious adverse event, ventricular fibrillation with iohexol, was considered related to contrast, and there were no differences noted between the agents. Overall, angiographic quality was equal with all angiograms being assessed as good or excellent in both groups (p = 0.885). In this low-risk population undergoing cardiac angiography, iodixanol is safe and effective without clinically important differences from iohexol. Additional studies in patients at high risk for complications should help further define the role of iodixanol in cardiac angiography.

Eighty-seven, 72 and 30 kDa heat-shock proteins from color carp testis cell line, CCT, were purified, and rabbit antibodies were raised against them. After heat shock at 37°C, hsp87 appeared mainly in the cytoplasm and hsp72 and hsp30 appeared in the nucleus. When cells were restressed at 37°C for 8 hr after three recovery periods, the intensity and localization of the three anti-CCT hsps staining changed from those following an initial stress for 8 hr. The anti-CCT hsp87 and hsp72 antibodies crossreacted with proteins of similar molecular weights in all tested fish, lizard, mouse and human cell lines, but they showed various degrees in antigenic relevance.

Postlarval tiger shrimp (Penaeus monodon) were immersed in aerated beta-glucan suspensions for 3 h. Enhanced growth was observed in shrimp immersed in glucan at concentrations of 0.5, 1, and 2 mg/ml, but not at 0.25 mg/ml. Shrimp gill tissue became shrunken immediately after immersion in the 2 mg/ml suspension. On days 10, 18, and 43 after beta-glucan treatment, shrimp were immersed in a bacterial suspension containing Vibrio vulnificus cells at a concentration of 5×107 CFU/ml for 12 h at a density of 25 individuals per liter; deaths were recorded for one month following experimental infection. The protective effect of glucan treatment was observed in those shrimp treated with 0.5 and 1 mg/ml glucan, but not in shrimp treated with 0.25 and 2 mg/ml glucan. The protective effect lasted until day 18 following immersion. In vitro, beta-glucan treatment enhanced the phenoloxidase activity in shrimp hemocytes. It therefore appears that beta-glucan is a short-term immunostimulant for shrimp.

The present study defines a culture system for heart tissue of hard clam,Meretrix lusoria (Roding). The tissue explants were cultured in six synthetic media supplemented with 10% fetal bovine serum and grown at 28° C. All of the media used in the present study support good cell migration and L15 medium gave the best result. Monolayer cell sheets of heart tissue established in 2X L15 growth medium consist of cardiac myocytes, epithelial-like, and fibroblastlike cells. Mitoses were observed in the culture system. To trigger the proliferation of cells, pronase, collagenase, insulin, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were used individually or combined in the L15 growth medium. The results showed pronase and collagenase at a concentration level of 100 μg/ml promoted cell proliferation. In contrast, insulin, FGF, and EGF gave no positive result. To date, cell cultures derived from the hard clam have been subcultured 6 times. Morphologic characterizations for the cells were also performed.

Typical atrioventricular (AV) nodal reentry tachycardia (AVNRT) is characterized by anterograde activation over a slowly conducting pathway and by retrograde activation through a rapidly conducting pathway. Preliminary reports suggest that radiofrequency catheter modification can eliminate typical AVNRT while preserving anterograde conduction. Radiofrequency catheter modification was used to treat 88 patients with typical AVNRT. After baseline electrophysiologic evaluation, the ablation catheter was positioned proximal and superior to the site of maximal His deflection. Radiofrequency energy was applied until there was significant attenuation of retrograde conduction, and elimination of AVNRT inducibility. Eighty-one patients were successfully treated and form the basis of this report. A new paroxysmal supraventricular tachycardia with RP greater than PR interval was induced at electrophysiologic testing after successful ablation in 9 patients (11%). Mean atrial-His activation time was 140 +/- 31 ms, and the ventriculoatrial activation time was 170 +/- 46 ms. This arrhythmia was induced only with ventricular pacing during isoproterenol infusion and appeared to be mediated by AV nodal reentry. New retrograde dual AV nodal physiology after modification was more frequent in patients with atypical tachycardia than in those without (4 of 9 vs 2 of 72; p less than 0.0001). Although none of the patients were treated, only 1 of 9 had an episode of spontaneous atypical tachycardia during a mean follow-up of 12 months. Results of this study confirm that typical AVNRT can be rendered noninducible without the complete destruction of reentrant pathways. Because induction of "atypical" AVNRT was not predictive of spontaneous arrhythmia recurrence, it should not be an indication for additional ablation sessions or long-term drug therapy.

The natural history of patients with ischemic cardiomyopathy, asymptomatic nonsustained ventricular tachycardia, and negative electrophysiologic studies was assessed in a retrospective analysis of 55 consecutive patients. The results suggest that the prognosis for arrhythmic death in these patients is not necessarily benign.

The cost of definitive therapy was compared in 25 patients who underwent radiofrequency catheter ablation of accessory pathways in 1990 and 25 patients who underwent surgical ablation of accessory pathways in 1989. In the radiofrequency group, 23 of 25 patients had a single accessory pathway and the remaining 2 patients each had 2 accessory pathways. In the surgical group, 20 patients had a single accessory pathway and 5 patients each had 2 accessory pathways. The success rate was 96% in each group. The mean duration of hospitalization was 3 +/- 1 days in the radiofrequency group and 9 +/- 4 days in the surgical group (p less than 0.0001). All the cost data are expressed in fiscal year 1990/1991 dollar values. The total cost of therapy in the radiofrequency group was $14,919 +/- $6,740 compared with $53,265 +/- $12,755 in the surgical group (p less than 0.0001). The cost of radiofrequency ablation consisted of a hospital charge of $7,753 +/- $3,472 and physician fees of $7,166 +/- $3,439. The hospital charge included charges for use of the electrophysiology laboratory, hospital stay, electrocardiograms, echocardiograms and blood studies. The cost of surgery consisted of a hospital charge of $37,708 +/- $10,179 and physician fees of $15,557 +/- $3,149. The hospital charge in the surgical group included the costs of a baseline electrophysiology study, in-hospital care and a follow-up office visit. In conclusion, radiofrequency catheter ablation of accessory pathways results in a dramatic reduction in the cost of definitive therapy in patients with the Wolff-Parkinson-White syndrome.

Seventy-four patients (16 women, 58 men, age 58 ± 21 years, mean ± standard deviation) who received an implantable Cardioverter de/ibrillator (ICD) after experiencing a single episode of ventricular tachycardia or ventricular fibrillation were followed to determine if antiarrhythmic drug therapy affects the incidence of ICD discharges. Thirty-three patients (group A) were treated with an antiarrhythmic drug that was either untested or previously demonstrated during electropharmacological testing to be ineffective in suppressing the induction of ventricular tachycardia. Forty-one patients (group B) were not treated with an antiarrhythmic drug. There were no significant differences between the two groups in regards to age, sex, incidence of coronary artery disease, left ventricular function or the type of ICD pulse generator used. During a mean follow-up of 14 months for the entire cohort, 15 patients (46%) in group A and 18 patients (44%) in group B experienced at least one ICD shock. The time to the first appropriate shock (5 ± 5 months in both groups) and the frequency of ICD shocks (0.3 ± 0.2/month in group A vs 0.4 ± 0.5/month in group B) were similar in both groups. The incidence of syncope at the time of ICD discharge was higher in group A than group B patients (31% vs 5%, P < 0.05). In conclusion, antiarrhythmic drugs that are untested or have failed electropharmacological testing do not appear to reduce the probability of ICD discharge over a short-term (mean 14 months) follow-up in patients who have had only one clinical episode of VT/VF and may increase the risk of syncope during ICD discharge. Studies with a larger sample size and longer follow-up period will be needed to confirm these findings.

Background. We conducted this study to determine the feasibility of an abbreviated therapeutic approach to the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia, in which the diagnosis is established and radiofrequency ablation carried out during a single electrophysiologic test. Methods. One hundred six consecutive patients were referred for the management of documented, symptomatic paroxysmal supraventricular tachycardias (66 patients) or the Wolff—Parkinson—White syndrome (40 patients). All agreed to undergo a diagnostic electrophysiologic test and catheter ablation with radiofrequency current. No patient had had such a test previously. Results. Among the 66 patients with paroxysmal supraventricular tachycardias, the mechanism was found to be atrioventricular nodal reentry in 46 (70 percent) (typical in 44 and atypical in 2), atrioventricular reciprocating tachycardia involving a concealed accessory pathway in 16 (24 percent), atrial tachycardia in 2 (3 percent), and no...

Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular refractory periods obtained using atrial and ventricular pacing with an atrioventricular (AV) interval of 160 ms were compared with those obtained with an AV interval of 0 ms in a group of 53 patients. The mean right ventricular effective refractory periods were longer at an AV interval of 160 ms than at an AV interval of 0 ms at pacing cycle lengths of 600 (mean 2.5 +/- 1.8 ms difference) and 400 ms (mean 3.8 +/- 2.4 ms difference; P less than 0.01). In a subset of 10 patients, left ventricular volumes measured by two-dimensional echocardiography demonstrated that pacing with an AV interval of 160 ms was associated with a higher end-diastolic volume and stroke volume than pacing with an AV interval of 0 ms (P less than 0.001). Autonomic blockade did not alter the relationship between AV interval and ventricular refractoriness. We conclude that 1) right ventricular refractory periods are shorter at an AV interval of 0 ms than at an AV interval of 160 ms; 2) these differences are not caused by changes in autonomic tone but are associated with differences in ventricular volumes; and 3) if precise determinations of ventricular refractoriness are desired, then the timing of atrial systole should be controlled by atrial pacing.

Inadequate drug plasma levels have been associated with the administration of phenytoin with enteral feedings through nasogastric (NG) tubes. It is demonstrated in this study that loss of phenytoin to tubing is a function of pH. Nonionized phenytoin is irreversibly bound to NG tubing from solution at the pH of enteral nutrient solutions while this is not the case for anionic phenytoin in unbuffered water or saline. In experiments pulsing phenytoin through glass vs NG tubing perfused with buffer at varying pH, reversible loss to tubing was observed at high pH while irreversible loss was observed at low pH. In addition, the irreversible loss of phenytoin was greater in NG tubing than glass particularly at low pH. It is suggested that in those cases where tubing is placed into the duodenum, inadequate gastrointestinal residence time for dissolution of phenytoin solid and suspension dosage forms coupled with irreversible drug loss from solution to NG tubing will result in decreased phenytoin absorption and subsequently lower drug plasma levels.

TOIVONEN, L.K., ET AL.: The Ventricular Excitability-Interval Relationship in Early Diastole in Humans: The Influence of the Electrode Configuration During Bipolar Stimulation. The purpose of this sludy was to determine (he relationship belween ventricular excitability and the extrastimuJus (S2) coupling interval in early diastole in humans. The influence of the electrode configuration during bipolar stimulation was examined. Ventricular strength-interval curves were constructed using an eight beat drive train at a cycle length 0/ 600 msec, 2-msec decrements in the S2 coupling interval, and 0.2-mA increments in the current intensity 0/ S2 at each coupling interval. A transient dip in ihe excitation threshold was observed in early diastole during bipolar pacing when the distal electrode was the anode in six of 17 patients {35%}. In contrast, this type of dip was not observed when the distal electrode was the cathode. The excitation threshold at the trough of the dip ranged from 1.0 to 2.2 mA. Unipolar strength-interval curves indicated that a dip occurred with anodal but not cathodal pacing. We postulated that the dip might inter/ere with the accurate determination of the ventricular ejfective refractory period hy resulting in transient loss of ventricular capture during decremental scanning of diastole with S2. A gap in ventricular capture was produced in all six patients who demonstrated a dip in the bipolar strength-interval curve by selecting an S2 current intensity that fell within the dip. In conclusion, the bipolar strength-interval curve may display an early diastolic dip in the excitation threshold, depending on the electrode conjiguration. During determination of the ventricular effective refractory period, if the stimulus intensity falls within the range of current intensities encompassed by the dip, a transient early diastolic gap in ventricular capture will he observed as diastole is scanned with S2. If this type of gap is not recognized, the ventricular effective refractory period may be overestimated. (PACE. Vol. 13, July 1990}

Drug release from a swelling hydrogel matrix is a complicated process where diffusion of drug molecules is coupled to the swelling kinetics. The swelling influences the diffusional flux of drug molecules by increasing the diffusion coefficient and diffusional pathlength. Release of phenylpropanolamine from apoly(hydroxyethy1 methacrylate-co-methacrylic acid) hydrogel, initially at low pH, is highly influenced by swelling in a neutral pH medium. Swelling in these ionizing gels is a very long process, even in the absence of a glassy core, indicating that the swelling is not a simple Fickian process. In this paper, a novel approach is introduced to model the phenylpropanolamine release from these swelling gels. Through a free volume relationship, the experimentally determined swelling kinetics are coupled to a diffusion mechanism for the drug molecules. This model was shown to give an accurate prediction of phenylpropanolamine release from poly(hydroxyethy1 methacrylate-co-methacrylic acid) gels.

The yield of sustained, monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation was compared, using basic drive trains of 400 ms, 600 ms and sinus rhythm, to identify the most efficient sequence of basic drive trains to use during programmed stimulation. Fifty-five patients with coronary artery disease and inducible sustained monomorphic VT not requiring countershock to terminate underwent 81 electrophysiology tests in which 1 to 3 extrastimuli were introduced during sinus rhythm and after basic drive trains of 600 and 400 ms. In 72 electrophysiology tests, sustained, monomorphic VT was induced at the right ventricular apex. The yield of VT using a drive cycle length of 400 ms was 63 of 72 (88%), compared to 46 of 72 (64%) when the drive cycle length was 600 ms, and 23 of 72 (32%) when the extrastimuli were introduced during sinus rhythm (p less than 0.001 for all pairwise comparisons). In 14 electrophysiology tests in which VT was not induced using a 400 ms basic drive cycle length at the apex, the yield of VT was higher using a 400 ms drive cycle length at a second right ventricular site (12 of 14) than with a 600 ms drive cycle length (3 of 12) or sinus rhythm (4 of 12) at the apex (p less than 0.05). The yield of sustained, monomorphic VT induced by 1 to 3 extrastimuli increases as the basic drive cycle length shortens. Whereas programmed stimulation is conventionally started during sinus rhythm or with a drive cycle length of 600 ms, the present results suggest that starting with a drive cycle length of 400 ms may be more efficient.

OBJECTIVES Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes. BACKGROUND The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy. METHODS We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353). RESULTS “Effective” antiarrhythmic drug therapy (i.e., the term “effective” was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment. CONCLUSIONS Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

We studied the immediate reproducibility of the results of the head-up tilt-table test in elderly patients (age > or =60 years). Twenty-seven consecutive men underwent 51 tests. The overall reproducibility was 98%, including 92% of a positive test and 100% of a negative test. The finding of this study validates the use of intravenous pharmacologic intervention in the elderly population.

Recognition of tachyarrhythmia by an implantable cardioverter-defibrillator (ICD) requires an intact rate-sensing lead. We retrospectively examined 266 consecutive patients requiring an ICD to characterize the incidence, clinical presentation, diagnosis, and management of a defective rate-sensing lead. To identify clinical parameters that may contribute to lead complications, we also assessed the effects of age, gender, type of rate-sensing lead, manufacturer of the lead, and surgeon. Over a follow-up period of 30 +/- 22 months (mean +/- standard deviation), a defective lead was found in 9 (3.4%) patients, in 9 (1.7%) of 514 leads over a period of 2 to 39 (mean 17 +/- 15) months after implantation. Except for 1 patient, in whom a lead fracture was incidently found during ICD generator replacement, these patients had multiple inappropriate shocks of recent onset. Clinical parameters were not helpful in identifying patients at risk for lead complication. An abnormal beeping signal obtained while the patients performed various maneuvers was helpful in confirming a defect. All of the defective leads were epicardial. These cases were managed by placement of a transvenous endocardial lead.

BACKGROUND Delivery of shocks within the right atrium has been reported to be more effective than conventional external shocks in converting atrial fibrillation (AF), but these two cardioversion techniques have never been compared prospectively. The purpose of this study was to compare the efficacies of external and internal cardioversion in patients with chronic AF unresponsive to prior attempts at electrical and/or pharmacological cardioversion. Low-dose amiodarone was used in all patients after cardioversion to suppress recurrences of AF. METHODS AND RESULTS One hundred twelve patients with AF of at least 1 month in duration were randomly assigned to undergo external cardioversion with 300-360-J shocks or internal cardioversion with 200-300-J shocks delivered through a standard electrode catheter within the right atrium. The patients were treated with amiodarone (200 mg/day 5-7 days/week) for 1 month before electrical cardioversion and afterward if the cardioversion was successful. The patients were evaluated at regular intervals during 1 year of follow-up. The efficacy of internal cardioversion was significantly greater than that of external cardioversion (91% versus 67%, p = 0.002). The only variable that was associated with the outcome of cardioversion was body weight. Among patients in whom sinus rhythm was restored, AF recurred as often after internal and external cardioversion; at 1 year of follow-up, 37% of patients in whom external or internal cardioversion had been effective were still in sinus rhythm. Patients who had undergone an attempt at electrical cardioversion before entry into this study were less likely to remain in sinus rhythm after cardioversion. The only complications of cardioversion were one instance of cerebral thromboembolism after external cardioversion and one instance of transient pulmonary edema after internal cardioversion. Therapy with amiodarone was discontinued because of an adverse drug effect in only three patients. CONCLUSIONS Internal cardioversion is more effective than external cardioversion in restoring sinus rhythm and is as safe as external cardioversion in patients with chronic AF. The recurrence rate of AF is the same after both types of cardioversion. If conventional electrical cardioversion is ineffective, internal cardioversion should be attempted. The combination of low-dose amiodarone and external or internal cardioversion may result in maintaining sinus rhythm long-term in patients with refractory AF.

BACKGROUND The purpose of this study was to report the results and complications of radiofrequency catheter ablation of accessory atrioventricular (AV) connections by using an abbreviated approach aimed at minimizing the duration of the procedure. METHODS AND RESULTS Two hundred fifty consecutive patients with the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia involving a concealed accessory AV connection underwent catheter ablation with the use of radiofrequency current. In 179 of the 250 patients, catheter ablation was performed at the time of an initial electrophysiology test. Two hundred thirty-five patients had one accessory AV connection and 15 patients had two or more. One hundred eighty-three accessory AV connections were manifest and 84 were concealed. One hundred sixty-one were were located in the free wall of the left ventricle, 47 were in the right free wall, 44 were posteroseptal, 10 were anteroseptal, and five were intermediate test, and the ablation procedure was recorded for each patient, as was the total duration of fluoroscopy. A follow-up electrophysiology test was performed 2-3 months after the ablation procedure. Ninety-four percent of patients had all accessory AV connections successfully ablated and remained free of symptomatic tachycardia during a mean follow-up of 10 +/- 4 months. Two hundred nineteen patients (88%) had all accessory AV connections ablated during the initial attempt at catheter ablation. Mean duration of the entire procedure was 134 +/- 75 minutes. Procedure duration was longest in patients with multiple accessory AV connections, shortest in patients with intermediate septal accessory AV connections, and similar in all other locations. A nonfatal complication occurred in nine patients (4%). CONCLUSIONS The results of this study indicate that catheter ablation of accessory AV connections with radiofrequency current can be performed safely and expeditiously in a majority of patients and confirm in a large series the feasibility of catheter ablation at the time of an initial diagnostic electrophysiology test. This abbreviated therapeutic approach avoids the need for electropharmacological testing, long-term antiarrhythmic drug therapy, and surgical therapy in the majority of patients with the Wolff-Parkinson-White syndrome or with symptomatic tachycardias involving accessory AV connections.

To evaluate the effect of sympathetic activation on the efficacy of the implantable cardioverter-defibrillator (ICD) in converting ventricular tachycardia (VT) or ventricular fibrillation (VF), 32 patients who received an ICD because of life-threatening VT/VF underwent 1 week postimplant ICD testing both before and after infusion of 25 (16 patients) or 50 (16 patients) ng/kg/min of epinephrine for greater than or equal to 12 minutes. These infusion rates are known to result in plasma epinephrine concentrations comparable to mild-moderate stress. The patients' mean age was 63 +/- 10 years; 26 had coronary artery disease, 2 had dilated cardiomyopathy and 4 had no evidence of structural heart disease. VT and VF were induced in 16 patients each by programmed stimulation or alternating current. Among the 16 patients with VT, the first ICD discharge (26 to 30 J) was effective in 15 patients in the baseline state and in all 16 patients during epinephrine infusion. Among patients with VF, the first ICD discharge (26 to 30 J) terminated VF in all patients in the baseline state, compared with 12 of 16 patients during epinephrine infusion (p less than 0.05). In 4 patients, VF was terminated during epinephrine infusion only by the second or third ICD discharge (30 J). In conclusion, physiologic increases in the plasma epinephrine concentration may increase the number and energy of shocks needed to terminate VF.

Fifteen consecutive patients with drug-refractory, recurrent, sustained, monomorphic ventricular tachycardia and a history of remote myocardial infarction underwent catheter ablation of ventricular tachycardia. Shocks of 100 to 300 J were delivered to sites at which pacing during ventricular tachycardia resulted in concealed entrainment, in which the ventricular tachycardia accelerated to the pacing rate, there was a long stimulus to QRS interval and there was no change in the configuration of the QRS complex during pacing at several rates compared with the configuration during ventricular tachycardia, thus identifying a zone of slow conduction in the reentrant circuit. Concealed entrainment was demonstrated in nine (60%) of 15 patients, and the stimulus to QRS intervals were 90 to 400 ms. At sites of concealed entrainment, the endocardial activation time relative to the QRS complex during ventricular tachycardia ranged from -125 to +50 ms, the timing of the local electrogram relative to the QRS complex was the same during entrainment as during ventricular tachycardia and the pace map during sinus rhythm was discordant with that of the ventricular tachycardia in seven patients. In the six patients in whom a site of concealed entrainment could not be identified, the target site for ablation was selected on the basis of identification of an isolated mid-diastolic potential, activation mapping and pace mapping. The mean (+/- SD) cumulative number of joules delivered to the target site was 306 +/- 140. A successful long-term clinical outcome was achieved in 9 of the 15 patients (mean follow-up 20 +/- 7 months). The clinical success rate was the same whether the target site was selected on the basis of concealed entrainment (five of nine, 56%) or on the basis of the other mapping techniques (four of six, 67%). In conclusion, the responses to pacing suggest that sites at which there is concealed entrainment may be located within a zone of slow conduction in the ventricular tachycardia reentry circuit, although not necessarily in an area critical for the maintenance of reentry. The long-term clinical efficacy of catheter ablation targeted to sites of concealed entrainment is about 60%, similar to the results achieved when conventional mapping techniques are used.

BACKGROUND This study compared the sensitivity, specificity, and efficiency of a "conventional" and "accelerated" programmed stimulation protocol in 293 patients with coronary artery disease who had a history of sustained or nonsustained monomorphic ventricular tachycardia (VT). METHODS AND RESULTS In the conventional protocol, one and two extrastimuli were introduced during sinus rhythm and during basic drive trains at cycle lengths of 600 and 400 msec at the right ventricular apex and then at the outflow tract or septum. In the accelerated protocol, one, two, and then three extrastimuli were introduced at each of three basic drive train cycle lengths (350, 400, and 600 msec) at the right ventricular apex; the procedure was repeated at a second right ventricular site. Six hundred thirty-four electrophysiological tests were performed using one of these two protocols either in the baseline state (293 tests) or during drug testing (341 tests). The yield of sustained, monomorphic VT was 89% with the conventional protocol and 92% with the accelerated protocol during baseline tests in patients who had a history of sustained VT (p = 0.05); 20% and 34%, respectively, during baseline tests in patients with a history of nonsustained VT (p = 0.06); and 70% and 77%, respectively, during drug testing (p = 0.2). To induce sustained, monomorphic VT, 10.1 +/- 5.0 (mean +/- SD) protocol steps and 14.4 +/- 8.7 minutes were required with the conventional protocol, compared with 4.0 +/- 3.7 steps and 5.6 +/- 6.1 minutes with the accelerated protocol (p less than 0.001 for each comparison). Among the tests in which sustained, monomorphic VT was induced, sustained polymorphic VT or ventricular fibrillation was induced more often with the conventional protocol (3.6%) than with the accelerated protocol (0.9%, p = 0.05). CONCLUSIONS The efficiency of programmed stimulation can be improved by the early use of a basic drive train cycle length of 350 msec and three extrastimuli. Compared with a conventional stimulation protocol, the accelerated protocol used in this study reduces the number of protocol steps and duration of time required to induce monomorphic VT by an average of more than 50% and improves the specificity of programmed stimulation without impairing the yield of monomorphic VT.

Poly(hydroxyethyl methacrylate-co-methacrylic acid) hydrogels swell extensively at high pHs due to the ionization of the carboxyl groups. The swelling leads to an increase of the free volume of the system and, thus, the release rate of the entrapped drug. Potential applications of the pH sensitive systems include delayed and controlled oral delivery, altered gastrointestinal transit following gastric emptying and targeted delivery to the small intestine. Phenylpropanolamine was used as a model drug to study the diffusional release characteristics of the swelling polymeric network. It was found that the release was a strong function of swelling and the apparent diffusivity of phenylpropanolamine followed an exponential relationship with the fractional water content of the matrix. These findings led to the development of a mathematical model which, based on experimentally measured swelling kinetics and dimensional changes was capable of predicting release from a matrix undergoing pH induced swelling.

This study examines the changes in pacing threshold and R- or P-wave amplitude during the first 30 minutes after implantation of tined and screw-in leads. The leads examined were those of 1 manufacturer (Medtronic) and consisted of 3 ventricular pacing leads (model numbers 6957 unipolar screw-in [11 patients], 6961 unipolar tined [12 patients] and 6962 bipolar tined [7 patients]) and 1 atrial lead (model number 6957J unipolar screw-in [10 patients]). After optimal lead position was obtained fluoroscopically in the right ventricular apex or right atrium, the pacing threshold and R- or P-wave amplitudes were measured at 5-minute intervals for 30 minutes. The acute ventricular pacing threshold with the screw-in lead was significantly higher than with the tined lead (0.84 +/- 0.17 vs 0.58 +/- 0.15 volts; p less than 0.001). There was a significant (p less than 0.001) acute decrease in the ventricular pacing threshold with both lead types, with the maximum decrease occurring 5 minutes after lead implantation. There was a significant acute increase in R-wave size with the ventricular screw-in lead that peaked 20 minutes after lead implantation (11.9 +/- 3.0 to 14.7 +/- 4.1 mV; p less than 0.001). The atrial screw-in lead behaved in a manner identical to its counterpart in the ventricle. In conclusion, there are acute changes in the pacing threshold and R- or P-wave amplitude obtained with tined and screw-in pacing leads.(ABSTRACT TRUNCATED AT 250 WORDS)