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Biomedical subjects

L Castle

Publications and source records attributed to L Castle.

At least 55 records · Page 3Linked to original sources

IFN-gamma increases cathepsin H mRNA levels in mouse macrophages.

Expression of major histocompatibility complex (MHC) class II molecules and ability to present antigen to T lymphocytes is acquired upon activation of the macrophage by interferon-gamma (IFN-gamma). Little information is available concerning immune regulation of protease gene expression in mouse macrophages. We have isolated a cDNA clone for cathepsin H, a lysosomal cysteine proteinase from a cDNA subtraction library of mouse macrophage genes induced by IFN-gamma, and have characterized its expression. The level of cathepsin H mRNA increased in mouse peritoneal macrophages following addition of IFN-gamma. Cathepsin H mRNA levels began to increase 8 h after the addition of IFN-gamma and was maximal at 24-48 h. This increase was concordant in time with appearance of MHC class II E beta mRNA and Ia invariant chain mRNA. The increase in cathepsin H mRNA levels by IFN-gamma was dose dependent. Cycloheximide treatment of peritoneal macrophages inhibited the increase in cathepsin H mRNA levels induced by IFN-gamma, suggesting that the increase in cathepsin mRNA levels requires de novo protein synthesis. Lipopolysaccharide and cytokines interleukin-2 (IL-2), IL-4, IL-10, and tumor necrosis factor alpha were found to have no effect on cathepsin H mRNA levels in mouse peritoneal macrophages.

Amino Acid Sequence↗

The cytotoxic T lymphocyte gene FIBLP with homology to fibrinogen beta and gamma subunits is also induced in mouse macrophages by IFN-gamma.

To identify genes induced in mouse macrophages by IFN-gamma, a cDNA subtraction library of IFN-gamma-induced genes was screened. One of the clones, 36F2, was identified by DNA sequencing as the FIBLP gene. The FIBLP (fibrinogen-like protein) gene is a T-lymphocyte-specific gene that is expressed in mouse cytotoxic T lymphocytes but not in helper T lymphocytes or B lymphocytes. The protein sequence shows a high homology to fibrinogen beta and gamma subunits. The FIBLP gene is not expressed in unstimulated mouse peritoneal macrophages but is induced by IFN-gamma to high levels. FIBLP mRNA is detected by 1 hr after the addition of IFN-gamma and maximal levels are reached by 12 hr. Expression of FIBLP mRNA was not induced by IL-2, IL-4, IL-10, or TNF-alpha. Though the function of this gene is unknown, its expression in both cytotoxic T lymphocytes and activated macrophages suggests that FIBLP may play an as yet undefined role in the cytotoxic function of these cells.

Animals↗

An assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a limited population study.

The plasticizer di-2-(ethylhexyl) adipate (DEHA), which may be present in food-contact films, can migrate into certain foodstuffs. Results from plasticizer migration studies into food have enabled an indirect estimate of the maximum daily dietary intake of DEHA. A previous study of the metabolism and pharmacokinetics of DEHA in humans identified the urinary metabolite 2-ethylhexanoic acid (EHA) as a useful marker metabolite for assessing DEHA intake. The present study was designed to investigate urinary EHA concentrations following a controlled dose of DEHA presented with food, and to assess the average daily intake of DEHA in a limited population survey. The urinary elimination profile of EHA, following a dose of DEHA in food, showed that in order to extrapolate DEHA intake from EHA measurements, a 24-hr urine sample was required. In the survey the elimination of EHA was determined in 24-hr urine samples in 112 individuals from five different geographical locations in the UK. No restrictions were placed on age or gender. Estimates of daily intake of DEHA show a skewed distribution with a median value of 2.7 mg. This is similar to an estimated maximum daily intake of 8.2 mg/day, derived using an indirect method by the UK Ministry of Agriculture, Fisheries and Food.

Adipates↗

HIV/AIDS policies and sports: the National Football League.

With the assistance of highly respected experts in the field of HIV/AIDS, the NFL has developed a comprehensive policy that should decrease the spread of HIV and any other blood-borne pathogens among its players and medical staff. Transmission of HIV infection is likely to be rare in the NFL. This is supported by the fact that in over 10 yr of the AIDS epidemic, the CDC has not attributed one AIDS case to athletic competition. Whatever the rate of HIV infection, on-the-field transmission is certainly less frequent than hepatitis B, which is manyfold more transmissible than HIV. Based on these facts, a player with HIV infection poses virtually no threat to others or himself by further athletic participation in the NFL. In addition, the relatively short average playing career of an NFL player and the extended period between HIV contraction and development of AIDS symptoms decrease the prospect that a player's HIV-positive status would affect his athletic performance. Consequently, HIV testing should remain voluntary, and continued participation in the NFL of HIV-infected players should remain a private decision between the player and his physician.

AIDS Serodiagnosis↗

Effect of atrioventricular synchrony on stroke volume during ventricular tachycardia in man.

The hemodynamic consequences of atrioventricular (AV) synchrony during ventricular tachycardia were evaluated during cardiac electrophysiologic testing. The relationship between stroke volume and the AV interval was investigated on a beat-by-beat basis in six patients during induced monomorphic ventricular tachycardia. Stroke volume was calculated either (1) in the right ventricle using impedance catheter method (four patients) or (2) in the left ventricle using Doppler measurement of aortic blood velocity (two patients). The impedance catheter method underestimated stroke volume by a factor of 4.2 +/- 2.4 compared with the thermodilution cardiac output method. However, there was a highly linear relationship between both methods for computing stroke volume (r greater than 0.9). Five patients had complete AV dissociation during ventricular tachycardia, and different AV intervals spanned the entire tachycardia cycle lengths. Largest stroke volumes were associated with optimal AV intervals within 120 and 230 msec, resulting in a 97 +/- 59% increase in stroke volume over ventricular tachycardia cycles not associated with atrial activity. Customized atrial pacing during ventricular tachycardia may provide a valuable means for artificially establishing the hemodynamically optimal AV interval and eliminating the ventricular tachycardia cycles not preceded by atrial activity.

Atrioventricular Node↗

Automatic implantable cardioverter-defibrillator implantation without thoracotomy using an endocardial and submuscular patch system.

The automatic cardioverter-defibrillator lead system is implanted by a thoracotomy procedure that may result in atelectasis, pleural effusion, cardiac tamponade and lengthy convalescence. A new defibrillator lead system that allows selection of different defibrillating current pathways is implanted without a thoracotomy. Ten patients requiring a cardioverter-defibrillator for recurrent sustained ventricular tachycardia (five patients) or aborted sudden cardiac death (five patients) were evaluated for implantation of this lead system. A lead configuration with a bidirectional defibrillating current pathway was implanted in nine patients. The defibrillation threshold with this lead configuration was 15 J in five patients, 20 J in three and 30 to 35 J in one patient. In the remaining patient the lead system had a 40 J defibrillation threshold and was not implanted. No perioperative complications occurred. Induced ventricular fibrillation was successfully terminated at the predischarge and intermediate follow-up (8 to 12 weeks) electrophysiologic studies. During the follow-up period, there were three deaths (one sudden, two due to heart failure) and two lead system failures (oversensing with inappropriate shocks in one patient and patch lead fracture in another). Implantation of the cardioverter-defibrillator lead system by a nonthoracotomy approach is feasible, has no significant perioperative complications and is well tolerated by patients. Effective defibrillation was demonstrated immediately as well as at intermediate follow-up study. The occurrence of patch lead fracture and oversensing requires improvement in the present (nonthoracotomy) lead system technology.

Cardiac Pacing, Artificial↗

Clinical performance of the implantable cardioverter defibrillator: electrocardiographic documentation of 101 spontaneous discharges.

Records of 105 patients, who received an automatic implantable cardioverter defibrillator (AICD), were studied to investigate the causes of spontaneous AICD discharges and to correlate the symptoms with the arrhythmias triggering AICD discharges. During a follow-up period of 13 +/- 8 months, 46/105 (44%) patients had 566 spontaneous AICD discharges. A total of 101 discharges were documented with Holter monitoring in 23 patients. In this study group, there were 8 (8%) AICD discharges for 5 episodes of ventricular fibrillation, and 68 (67%) discharges for 63 episodes of sustained ventricular tachycardia. Patients lost consciousness in all episodes of ventricular fibrillation, but were symptomatic prior to only 36 (53%) discharges in ventricular tachycardia. Nonsustained ventricular tachycardia persisting for a period of 7.5 +/- 2 seconds resulted in 20 AICD discharges; patients were symptomatic prior to 13 (65%) discharges. Supraventricular tachycardias triggered three discharges. One patient had two spurious discharges during sinus rhythm. In conclusion, most of the spontaneous AICD discharges were appropriate for the detected rhythms, but only clinically appropriate for the management of arrhythmias in 75% of the cases. A significant portion of the patients with sustained or nonsustained ventricular tachycardias triggering AICD discharges were asymptomatic prior to discharge, which requires further assessment of the physiology of the arrhythmia as a component of the detection algorithm.

Electric Countershock↗

The effects of percutaneous catheter ablation on preexisting permanent pacemakers.

STUDY OBJECTIVE: Determine the effect of percutaneous catheter ablation (CA) on permanent pacemakers. MEASUREMENTS AND RESULTS: Twenty-three patients who underwent CA at The Cleveland Clinic Foundation from September 1983 to January 1990, and had a previously implanted pacemaker were studied. Electrocardiographic data during the CA procedure and clinic data including pacemaker evaluations were analyzed. Fifty-two percent (12/23) of the pacemakers malfunctioned: five developed transient ventricular loss of capture; two undersensing; one oversensing; three could not be interrogated or programmed, and one did not respond to the magnet test. Four patients developed syncopal episodes and two severe dizziness after the procedure. All had their pacemakers replaced. In total, seven were explanted. Destructive analysis by the individual manufacturer identified pacemaker circuitry failure in five. Unipolar pacemakers and anodal ablation procedures had more frequent and severe malfunctions, but the difference was not statistically significant. CONCLUSIONS: Pacemaker malfunction is frequent during CA. It may be prevented by programming the pacemaker, when possible, to the nonfunctioning mode (000 mode). Temporarily disconnecting the pacemaker during ablation requires further evaluation as an alternative approach. Close follow-up can detect pacemaker malfunction and prevent complications.

Adult↗

Continuous right ventricular volume assessment by catheter measurement of impedance for antitachycardia system control.

Current implantable defibrillators are unable to differentiate between hemodynamically stable and unstable arrhythmias. This may result in unnecessary high energy shocks during arrhythmias that are better managed with other interventions. This study assessed the efficacy of the impedance catheter in sensing relative volumetric changes in the right ventricle as a measure of the hemodynamic status during an arrhythmia. During electrophysiological testing, 37 arrhythmias were induced in 12 patients aged 28-74 years. Rhythms recorded were: (A) hemodynamically stable tachyarrhythmias (supraventricular tachycardia and sustained monomorphic ventricular tachycardia)--21 episodes; and (B) hemodynamically unstable ventricular arrhythmias causing syncope (hypotensive ventricular tachycardia and ventricular fibrillation)--16 episodes. During unstable arrhythmias, stroke impedance (32 +/- 17%), arterial systolic pressure (40 +/- 11%), and right ventricular pulse pressure (15 +/- 20%), expressed as percentages of corresponding sinus rhythm values, were significantly lower than in stable arrhythmias (84 +/- 26%, 72 +/- 8%, and 111 +/- 37%, respectively); P less than 0.001. There was a good correlation between stroke impedance and mean arterial pressure during arrhythmia (r = 0.84). Impedance sensing is a practical method for distinguishing between hemodynamically stable and unstable arrhythmias. Implementation of hemodynamic sensing into the algorithm of future antitachycardia systems may improve the management of arrhythmias by adding options for selective pace termination or cardioversion.

Adult↗

Preexcitation syndromes: surgical ablation therapy. The Cleveland Clinic experience.

Thirty-four patients with preexcitation syndrome had surgical ablation of the accessory atrioventricular connection. All presented with sustained symptomatic arrhythmias, which had resulted in syncope in seven patients and aborted sudden cardiac death in four. Arrhythmias induced at electrophysiologic evaluation included orthodromic reciprocating tachycardia in 32 patients, antidromic reciprocating tachycardia in five patients, and atrial fibrillation in 29 patients. A single accessory atrioventricular connection was located in 32 patients and two patients had multiple accessory connections. The accessory connection was located with intraoperative mapping in all patients and the pathway was successfully ablated in 32. Eleven patients underwent a transmural approach and 23 patients underwent an epicardial dissection. Cryotherapy was used in 22 patients. After a mean follow-up of 32 months, 28 patients were free from all arrhythmias without drug therapy. Six patients continued to have symptomatic arrhythmias but only one case was suspected to be secondary to unsuccessful ablation of the accessory connection. One patient with heart block induced at the surgical procedure is dependent upon a pacemaker.

Adolescent↗

The migration of propylene glycol, mono-, di-, and triethylene glycols from regenerated cellulose film into food.

Chocolates, boiled sweets, toffees, cakes and meat pies were wrapped in regenerated cellulose films (with or without coatings) that contained various mixtures of glycol softeners and which had been specially formulated for particular food applications. Samples were unwrapped at intervals (up to the end of the usual maximum shelf-life for the food) and analysed for their glycol content. Analysis involved homogenization of the food in hot water, removal of fats with hexane, precipitation of sugars with calcium hydroxide and analysis of the glycols by capillary gas chromatography with flame ionization detection (GC/FID) after trimethylsilyl (TMS) derivatization. Triethylene glycol was analysed by selected ion monitoring GC/mass spectrometry (GC/MS) as interference problems occurred with the GC/FID approach. The results of the study showed that higher levels of migration occurred for propylene glycol than for triethylene glycol and the presence of a coating reduced the migration of both softeners. Generally, mono- and diethylene glycol levels in the food samples were below 10 mg/kg, although some samples wrapped in polyethylene glycol-softened films contained levels approaching the current statutory limit of 50 mg/kg.

Cellophane↗

Effects of extracorporeal shock wave lithotripsy on cardiac pacemakers and its safety in patients with implanted cardiac pacemakers.

UNLABELLED: Effects of extracorporeal shock wave lithotripsy (ESWL) were studied on 15 pacemakers (standard single chamber n = 5, dual chamber n = 6, rate responsive single chamber [Activitrax] n = 4). In-vitro testing involved suspending the pacemakers in a bath of degassified, deionized water firmly taped to a platform at the point of maximal pressure, i.e., second focal point (F2), where they received pressure shocks (means = 1300) from the HM3 Dornier lithotriptor. The pacemakers, programmed to their most sensitive setting, were continuously pacing at nominal outputs (atrial and ventricular pacing in the DDD mode). All units were assessed by a pacing system analyzer before and after the study, then underwent destructive analysis. During standard single chamber pacing (VVI) the pacing stimulus triggered ESWL. For dual chamber devices, ESWL was triggered by the atrial paced event which induced inhibition of the ventricular output in two pacemaker. This was eliminated by reprogramming to a less sensitive setting. The pacemaker can, hermetic seal and internal circuitry were undamaged in all units. Two rate responsive single chamber pacemakers had their activity sensing piezoelectric elements shattered when placed at F2. Two other units placed 5 cm from F2 were stimulated to their maximum upper programmed pacing rate with ESWL therapy, but were otherwise unaffected. Subsequent to this study, six patients with pacemakers programmed to the VVI (five), DDD (one) modes implanted in the thorax underwent successful ESWL without pacemaker or arrhythmic event. CONCLUSIONS: (A) It is generally safe for patients implanted with standard single chamber devices in a ventricular application to undergo ESWL without modifying the pacing/sensing parameters. (B) Patients implanted with dual chamber devices who pace in the atrium should be reprogrammed to the VVI mode during ESWL. (C) Patients with piezoelectric activity sensing rate responsive single chamber pacemakers should have this feature programmed off during ESWL and, if implanted in the abdomen, probably should not undergo ESWL.

Aged↗

Sedation and pain management during pacemaker implantation, electrophysiologic testing, and related procedures.

A technique for the management of pain and anxiety during pacemaker implantation, electrophysiologic studies, and related procedures is described. The technique involves the intravenous administration of small amounts of the narcotic agonist-antagonist nalbuphine and the benzodiazepine diazepam. The small amounts of medication used induce relaxation while allowing the patient to interact and cooperate during the procedure. The absence of side effects facilitates outpatient treatment. This method of pain management not only improves the quality of patient care but also encourages earlier hospital discharge.

Adult↗

Therapy of ventricular tachycardia.

Therapeutic modalities for ventricular tachycardia include antiarrhythmic drugs, direct current cardioversion, electrical pacing and surgical intervention. Lidocaine, procainamide and bretylium are all capable of controlling recurrent ventricular tachycardia; bretylium has the advantage of also being antifibrillatory and of raising the threshold for ventricular fibrillation. Lidocaine and bretylium are available only in i.v. form. Procainamide is available in i.v. as well as oral form. Other oral antiarrhythmic agents include quinidine, disopyramide, beta-blockers such as propranolol and verapamil. The latter may be useful in ventricular arrhythmias induced by ischemia; of these, only beta-blockers appear to significantly raise the threshold for ventricular fibrillation. Control of ventricular ectopy does not always preclude ventricular tachycardia and ventricular fibrillation. In treating ventricular tachycardia, bretylium tosylate is generally given 5 to 10 mg/kg i.v. over 10 to 20 minutes. Given too rapidly, it may cause nausea and vomiting. Orthostatic hypotension, a common side effect, generally abates with continued use and may be ameliorated with tricyclic antidepressants such as protriptyline. Significant supine hypotension may be encountered in patients with acute myocardial infarction and may be managed with pressor agents or fluids, or both. The antiarrhythmic efficacy of bretylium was analyzed in 40 patients. Five etiologic groups were defined by cardiac catheterization: 19 patients had atherosclerotic heart disease, 6 had primary myocardial disease, 4 had mitral valve prolapse, 4 had rheumatic heart disease and 7 had miscellaneous or no heart disease. All patients had recurrent ventricular tachycardia (VT); 23 had ventricular fibrillation (VF) as well. Other antiarrhythmic agents had failed in 38 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of nuclear magnetic resonance on patients with cardiac pacemakers.

The effect of nuclear magnetic resonance (NMR) imaging on six representative cardiac pacemakers was studied. The results indicate that the threshold for initiating the asynchronous mode of a pacemaker is 17 gauss. Radiofrequency levels are present in an NMR unit and may confuse or possibly inhibit demand pacemakers, although sensing circuitry is normally provided with electromagnetic interference discrimination. Time-varying magnetic fields can generate pulse amplitudes and frequencies to mimic cardiac activity. A serious limitation in the possibility of imaging a patient with a pacemaker would be the alteration of normal pulsing parameters due to time-varying magnetic fields.

Magnetic Resonance Spectroscopy↗