Clinical Evaluation of Automatic Tachycardia Diagnosis by an Implanted Device

Reliable discrimination between sinus tachycardia (ST) and pathologic tachycardia has been a major problem for automatic implantable antitachycardia devices. In patients whose sinus response to activity is as rapid or faster than their pathologic tachycardia (rate crossover), these unsophisticated devices deliver the programmed tachycardia response to either the pathologic or sinus tachycardia. Over a one-year period, 50 Intermedics Intertach Model 262–12 antitachycardia pulse generators were implanted to evaluate the specificity of a new group of tachycardia recognition algorithms. Patients were subjected to exercise testing and noninvasive programmed stimulation to demonstrate the efficacy of this new approach. The five recognition algorithms tested were various combinations of the following criteria: high rate HR), sudden onset (SO), rate stability (RS), and sustained high rate (SHR). False positive rates (tachycardia response inappropriately triggered by ST) were as follows: HR (93%); HR + SO (3%); HR + RS (63%); HR + (RS or SHR) (87%); HR + HS + SO (8%). Pair-wise significance testing between HR only and HR + SO (p < 0.001), HR + RS (p = 0.01) and HR + SO + RS (p < 0.001), demonstrated a significant reduction in the rate of false positives through the use of the sudden onset and rate stability criteria in concert with the standard high rate criterion.     

Direct and Telemetered Lead Impedance

Objectives: We undertook this study to determine whether telemetered lead impedance measurements (LIM) can be correlated with direct LIM and to determine the stability of LIM over time when measured directly and via telemetry. Methods: Direct LIM and telemetered LIM were measured in 91 patients; 101 leads during initial implantation and 40 leads during pulse generator replacement. Differences in direct LIM measured during initial implant and pulse generator replacement (direct-direct) were compared in 41 patients (28 atrial leads and 37 ventricular leads). The stability of telemetered LIM obtained immediately postoperatively, at 1 month and 1 year, postimplantation was assessed in 50 patients (23 atrial and 49 ventricular leads). Results: In atrial leads acute direct LIM was 633.9 ± 18.4 Ω versus 575.8 ± 18.5 Ω for telemetered LIM (r = 0.58), and chronic direct LIM was 670.9 ± 49.3 Ω versus 607.0 ± 36.3 Ω for telemetered LIM (r = 0.87). In ventricular leads acute direct LIM was 747.3 ± 16.9 Ω and 684.7 ± 16.4 Ω for telemetered LIM (r = 0.69), and chronic direct LIM was 674.8 ± 29.9 Ω and 625.2 ± 28.5 Ω for telemetered LIM (r = 0.68). The mean direct–direct UM rose 124 Ω (P < 0.001) in atrial leads and 10 Ω (P = NS) in ventricular leads. Telemetered LIM for atrial leads was 581.0 ± 27.6 Ω immediately postimplantation compared to 625.7 ± 34.8 Ω at 1 month and 754.1 ± 43.0 Ω at 1 year. Telemetered LIM for ventricular leads was 661.3 ± 17.5 Ω at implant, 684.6 ± 20.7 Ω at 1 month and 724.7 ± 22.7 Ω at 1 year. Conclusions: There is a good but limited correlation between direct and telemetered LIM. Mean direct LIM obtained at initial implantation is similar to that measured at pulse generator replacement. The telemetered LIM is stable over the first month postimplantation but tends to rise during the first year of follow-up and substantial changes in impedance are not uncommon in individuals with normal function. There is a tendency for LIM to rise with lead maturation. If telemetered LIM is to be followed over time, a baseline telemetered value should be obtained immediately postoperatively.     

Chronic Morpholine Exposure of Rats

Chronic Morpholine Exposure of Rats. HARBISON, R. D., MARINO,D. J., CONAWAY, C. C., RUBIN, L. F., AND GANDY, J. (1989). FundamAppl. Toxicol. 12,491–507. The chronic toxicity and carcinogenicpotential of morpholine were evaluated in 60 Sprague-Dawleyrats/sex/group receiving morpholine at mean inhalation exposureconcentrations of 0, 10, 50 and 150 ppm for 6 hr/day, 5 days/week,for 104 weeks. Survival, body weight gains, organ weights, hematology,and clinical chemistries were normal in exposed groups and comparableto those of the control animals. The incidences of palpabletissue masses and of histologically confirmed neoplasia werecomparable among all groups, including the control groups, andwere typical of the strain and age of the rats tested. In-lifeclinical examinations revealed increased incidences of irritationaround the eyes and nares, chromadacryorrhea, and urine stainson the fur, predominately in high-dose animals. Morpholine exposurewas associated with corneal irritation seen by ophthalmoscopicexamination and confirmed microscopically as keratitis limitedto the highest exposure group. Irritation of the maxillary andnasoturbinates as indicated by infiltration of neutrophils,focal squamous metaplasia of the turbinate epithelium, and necrosisof the turbinate bone was observed in high-dose animals. Therefore,chronic exposure of rats to morpholine for 2 years at concentrationsof 150 ppm or less revealed no carcinogenic potential or chronicsystemic toxicity. Consistent with its known irritating properties,morpholine produced only local irritation, which was limitedalmost exclusively to high-dose animals.     

PREVALENCE OF SELF-REPORTED DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

The prevalence of self-reported depressive symptoms was investigatedin a case-control study of patients with rheumatoid arthritis(RA) attending an out-patient clinic at the Middlesex Hospital.Patients selected their own controls, matched for age and sex.Previous attempts to measure depressive symptoms in RA havesuffered from measurement error due to criterion contamination,where psychological symptoms augment depressive scores. A totalof 163 patients (77% of the sample) and 115 matched pairs completedthe Hospital Anxiety and Depression Scale (HADS). The resultsIndicated that RA patients are more depressed and anxious thancontrols. The prevalence of depression above the cut-point was15%. This figure is comparable to other reports adjusted forcriterion contamination, but is lower than that of other studieswhich employ ‘contaminated’ tools. The depressionscale of the HADS appeared to be relatively free of criterioncontamination. Subject to further reliability testing, the HADSmay be a practical screening tool for practitioners to assesspatients in need of psychological interventions. KEY WORDS: Depression, Rheumatoid arthritis, Criterion contamination     

Diesel Exhaust Is Not a Pulmonary Carcinogen in CD-1 Mice Exposed under Conditions Carcinogenic to F344 Rats

Differences among laboratory animal species in the pulmonarycarcinogenicity of chronic inhalation exposure to diesel exhausthave raised several important interpretive issues. Under similarheavy exposure conditions, it is clear that diesel exhaust isa pulmonary carcinogen in rats, but not in Syrian hamsters.Previous reports give conflicting views of the response of mice,which is presently considered equivocal. This report describescarcinogenicity results from a bioassay of CD-1 mice conductedin parallel with a previously reported bioassay of F344 rats(Mauderly et al. (1987) Fundam. Appl. Toxicol. 9, 208–221).Exposure to whole diesel exhaust 7 hr/day, 5 days/week for 24months at soot concen trations of 0.35, 3.5, or 7.1 mg/m³ causedaccumulations of soot in mouse lungs similar to those in lungsof rats and, like the results from rats, did not significantlyaffect survival or body weight. In contrast to the dose-relatedneoplastic response of rats, however, the exposures of micedid not increase the incidence of lung neoplasms. This findingis consistent with other data showing that mice, as well asSyrian hamsters, differ from rats in their lung neoplastic andnonneoplastic responses to heavy, chronic inhalation exposureto diesel exhaust soot and several other particles. Althoughrodents serve as useful indicators of potential human carcinogenichazards, it is not yet clear which, if any, rodent species havelung neoplastic responses that are useful for quantitative predictionsof human lung cancer risk from chronic inhalation of poorlysoluble, respirable particles.     

Mouse Liver Carcinogenesis: Mechanisms and Relevance

Symposium Overview: Mouse Liver Carcinogenesis: Mechanisms andRelevance. GOODMAN, J. I., WARD, J. M., POPP, J. A., KALUNIG,J. E., AND FOX, T. R. (1991). Fundam. Appl. Toxicol. 17, 651–665.     

The Application of Non-Default Uncertainty Factors in the U.S. EPA's Integrated Risk Information System (IRIS). Part I: UF L,UF S,and “Other Uncertainty Factors”

The United States Environmental Protection Agency's Integrated Risk Information System (IRIS) includes hazard identification and dose-response assessment values developed by Agency scientists. Uncertainty factors (UFs) are used in the development of IRIS values to address the lack of information in five main areas. The standard UFs account for interspecies uncertainty (UF_A) and intraspecies variability (UF_H). The UF_A addresses uncertainty related to the extrapolation of data from animals to humans, whereas the UF_H addresses variability amongst individuals (i.e., intrahuman). Additional UFs have been employed to account for database incompleteness, extrapolations from a lowest-observed-adverse-effect level in the absence of a no-observed-adverse-effect level (UF_L), and subchronic-to-chronic extrapolation (UF_S). A sixth UF designated as “other uncertainty factors” (UF_O) has also been applied in place of the UF_L to account for uncertainty with the adversity of points of departure obtained using benchmark dose modeling. This review will discuss how UF_L, UF_S, and UF_O have been applied in IRIS assessments, along with the rationale used to describe the choice of UF values that deviate from the standard default of 10.     

Utility and Safety of Axillo‐subclavian Venous Imaging with Carbon Dioxide (CO2) Prior to Chronic Lead System Revisions

Background: Prior to attempting placement of one or more electrodes to revise existing rhythm control devices, patency of the central veins should be documented, in view of a high incidence of significant chronic occlusions. Since iodinated contrast venography may be contraindicated in select situations, imaging of the axillo‐subclavian venous system with gaseous carbon dioxide (CO₂) was evaluated prospectively in 23 consecutive individuals who were considered for revision of previously implanted pacemaker or automatic cardioverter defibrillator lead systems. Methods: Approximately 20 mL of CO₂ were manually infused via CO₂ primed injection tubing into a vein at or above the level of the antecubital fossa ipsilateral to the side of prior lead placements. Digital subtraction imaging over the axillo‐subclavian region, lower neck, and mediastinum was performed. Formal interpretation was obtained from one of three interventional radiologists and at least one electrophysiologist. Results: Significant venous occlusions were identified in five (22%) patients. Vascular access utilized for the subsequent 18 revisions performed included the imaged patent ipsilateral vein in 14 patients and the contralateral, right‐sided subclavian venous system in three patients. One patient required epicardial left ventricular lead placement. There were no complications from venography. Conclusions: Axillo‐subclavian venography with gaseous CO₂ in patients undergoing pacemaker or implantable cardioverter defibrillator lead revisions is feasible and safe when use of iodinated dye is contraindicated. This technique should be employed in patients with azotemia, dye contrast allergies, or significant inflammation in the vicinity of the intravenous line insertion. (PACE 2010; 790–794)