A novel missense mutation responsible for factor VII deficiency in research Beagle colonies

BACKGROUND: Canine factor VII (cFVII) deficiency, an autosomal recessive trait originally identified in research Beagles, is associated with a mild to moderate bleeding tendency. OBJECTIVE: Our aim was to identify and characterize the mutation causing cFVII deficiency. METHODS: In order to sequence the coding regions of the cFVII gene, we cloned the cFVII cDNA. Genomic DNA and plasma from FVII-deficient Beagles and obligate carriers were utilized. RESULTS: In all FVII-deficient dogs, we identified a single causative G to A missense mutation in exon 5, encoding the second epidermal growth factor-like domain, resulting in substitution of glycine 96 by glutamic acid, with plasma FVII coagulant activity of 相似文献   

Assessment of the Chronotropic Response at the Anaerobic Threshold: An Objective Measure of Chronotropic Function

MEINE, M., et al. : Assessment of the Chronotropic Response at the Anaerobic Threshold: An Objective Measure of Chronotropic Function. The evaluation of the heart rate response to exercise is important for the diagnosis of chronotropic incompetence and the assessment of a rate responsive algorithm of sensorcontrolled pacemakers. The aim of the present study was to examine a classification of the chronotropic response at an individually moderate exercise level. Sixteen pacemaker patients (patient group, age 62.9 ± 7.6 years ) with sick sinus syndrome and 15 age‐matched healthy subjects (control group, age 57.6 ± 9.4 years ) underwent a maximum cardiopulmonary exercise test on a treadmill after a protocol with individually selected incremental steps. To analyze the patients' intrinsic heart rate response, the rate responsive mode of the pacemaker was switched off. Chronotropic incompetence was diagnosed in eight patients whose maximal heart rate was < 80% of the age‐predicted heart rate. The heart rate at the anaerobic threshold was significantly lower in the chronotropically incompetent subgroup than in the chronotropically competent patients and the healthy subjects (85.9 ± 6.6 beats/min vs 100.3 ± 9.9 beats/min and 112.9 ± 11.7 beats/min , respectively). The chronotropic slope of the heart rate reserve as a function of the metabolic reserve was significantly higher in the control group than in the patient groups with either mild or severe chronotropic incompetence (0.94 ± 0.17 vs 0.64 ± 0.08 and 0.43 ± 0.14 , respectively). Furthermore, the chronotropically incompetent response could be divided into a linear type with and without a threshold, an exponential, and a logarithmic type. The anaerobic threshold was an objectively detectable breakpoint at an individually moderate exercise level that could be used for characterization of chronotropic function. At the anaerobic threshold, a physiological heart rate response was about 220 ‐ age – 50 beats/min. A deviation of more than 10 beats/min below this physiological value characterized chronotropic incompetence.     

Ventriculoatrial Conduction Time During Bundle Branch Reentrant Beat Initiating Orthodromic Tachycardia: A Simple and Reliable Method for Localization of Accessory Pathways

VA Interval Via Accessory Pathway During Bundle Branch Reentry. Bundle branch reentrant (BBR) complex is commonly induced during programmed ventricular stimulation with single ex-trastimulus. In patients with atrioventricular accessory pathway, BBR beat frequently triggers orthodromic tachycardia. This study was designed to determine whether evaluation of the ventriculoatrial conduction time during BBR (VA_BBR) induced with right ventricular extrastimulation (i.e., left bundle branch block morphology) can separate left free-wall (LFW) accessory pathways from left posteroseptal (LPS) or right-sided pathways. Thirty-eight patients with single atrioventricular accessory pathways were included. There were 28 men and 10 women with a mean age of 26 years. The accessory pathway was localized in LFW in 23 patients (group I) and LPS in seven (group ID. Eight patients (group III) had pathways located in the right side. In each patient, VA_BBR was determined and compared with the following: (1) V₂A₂ interval exclusively via accessory pathway; and (2) ventriculoatrial conduction time during orthodromic tachycardia with narrow QRS complex (VA_NQ), left bundle branch block plus normal axis (VA_LB-NA) or left axis (VA_LB-LA). In group I, VA_BBR values (170–245 msec, mean 196.1 ± 20.5 msec) were 0–25 msec longer than V₂A₂ (170–245 msec, mean 191.3 ± 19.1 msec) and 45–125 msec greater than VA_NQ (100–155 msec, mean 125.6 ± 14.1 msec). VA_BBR was identical to VA_LB-LA but 25–55 msec greater than VA,_LB-NA (140–205 msec, mean 160.9 ± 20.8 msec). In group II, VA_BBR values (100–140 msec, mean 118.6 ± 14.3 msec) were 15–30 msec shorter than V₂A₂ (125–165 msec, mean 140.7 ± 14.3 msec) and 15–25 msec longer than VA_NQ (85–120 msec, mean 100.7 ± 12.0 msec). Comparing VA_BBR with VA_LB-NA or VA_LB-LA did not show any statistically significant difference. In group III, VA_BBR values were consistently shorter than V₂A₂ and identical to VA_NQ. Thus, assessment of VA_BBR is a simple and useful method that can be reliably utilized to differentiate LFW pathways from LPS or right-sided pathways. Furthermore, these data provide new insights into the electrophysiological characteristics of bundle branch reentry. (J Cardiovasc Electrophysiol, Vol. 1, pp. 121–131, April 1990)     

Comparison of Two Antitachycardia Pacing Modes in Supraventricular Tachycardia

The comparative efficacy of two different antitachycardia pacing techniques was evaluated in 22 consecutive patients who received the pacemaker Intertach® with an atrial electrode for drug refractory, recurrent Supraventricular tachycardia (SVT). The Intertach® has two consecutive programmable primary and secondary termination modes. The termination programs investigated were adaptive autodecremental burst pacing and adaptive decremental scanning. Atrioventricular nodal reentrant tachycardia was present in 15 patients and atrioventricular reentrant tachycardia due to Wolff-Parkinson-White syndrome in seven patients. The prospective comparison was arranged in a randomized, cross-over study over a period of 12 months. To assess long-term efficacy, diagnostic data of the pacemakers were obtained in intervals of 3 months. In addition, noninvasive programmed stimulation was performed to compare the incidence of pacing-induced atrial fibrillation with both termination programs. During a follow-up of 12 months the overall success rate of autodecremental burst pacing and decremental scanning was 80% and 95%, respectively. Decremental scanning was more effective in 12 patients and less successful in two patients than autodecremental burst pacing. During noninvasive electrophysiological studies, pacing induced atrial fibrillation could be documented in three often patients (30%) using autodecremental burst pacing, compared to one often patients (10%) using decremental scanning. These data suggest that decremental scanning proved to be more successful in the long-term management of patients with recurrent S VT than autodecremental burst pacing. Furthermore, the occurrence of pacing-induced atrial fibrillation could be documented more frequently with autodecremental burst pacing compared to decremental scanning.     

Effects of Antiarrhythmic Drugs on Epicardial Defibrillation Energy Requirements and the Rate of Defibrillator Discharges

Antiarrhythmic drugs are commonly used with the implantable cardioverter/defibrillator to treat recurrent ventricular tachyarrhythmias. Since various antiarrhythmic drugs have been reported to alter defibrillation threshold, an important question is whether the device will provide adequate energy for defibrillation during long-term follow-up and to what extent antiarrhythmic drug treatment will affect defibrillation energy requirements. To answer these questions, the defibrillation thresholds were determined in 20 patients using an epicardial patch-patch lead configuration at the time of implantation and at the time of pulse generator replacement. During a mean follow-up period of 24 ± 6 months, the defibrillation threshold increased significantly from 14.2 ± 3.7 joules to 18.3 ± 5.5 joules in the entire group (P < 0.05). This increase in defibrillation threshold was due to a marked elevation of defibrillation energy requirements in the subgroup of patients taking amiodarone compared with patients receiving mexiletine. Based on these results it is mandatory to retest defibrillation threshold at any time of pulse generator replacement to guarantee continued effectiveness. In particular, if amiodarone treatment is initiated after implantation of a defibrillator, it is recommended to reevaluate defibrillation threshold to ensure an adequate margin of safety.     

VARIATIONS IN LUNG VOLUME AND COMPLIANCE DURING PULMONARY SURGERY

Functional residual capacity (FRC) and breath-by-breath complianceof the ventilatory system (C₁₅) were measured in 10 mechanicallyventilated patients during anaesthesia for lung surgery (pneumonectomy,lobectomy, lung or pleural resections or exploratory thoracotomy).In eight patients not requiring pneumonectomy, FRC of the lowerlung decreased by 8±9% (mean± 1 SD) (P < 0.05)while that of the upper lung increased by 75±24% (P <0.001) when the patient was turned to the lateral position.When the pleura was opened, FRC of the lower lung decreasedby a further 10±10% (P <0.01). One-lung ventilation(OLV), however, increased FRC of the lower lung back to thevalue found in the supine position before surgery. When two-lungventilation was re-established, FRC of the lower lung was aboutthe same as during corresponding stages before OLV. In the twopatients who underwent pneumonectomy, FRC of the remaining lungwas about 30% greater after OLV than at corresponding stagesbefore surgery. In the patients not requiring pneumonectomy,C₁₅ decreased from 29±6ml/cm H₂O to 23±6ml/cmH₂O (P < 0.05) on the lower side when the patient was turnedon his side. The corresponding figures on the upper side were24±8 ml/cm H₂O and 30±5ml/cm H₂O respectively(P < 0.05). There was no further significant change whenthe pleura was opened. After surgery when the patient was turnedto the supine position, C₁₅ of the lung not operated on wasalmost the same as before surgery.     

Electrical Proarrhythmia: Induction of Inappropriate Atrial Therapies due to Far-Field R Wave Oversensing in a New Dual Chamber Defibrillator

R Wave Far-Field Sensing in Dual Chamber Defibrillators . This case report describes delivery of atrial therapies during a sinus tachycardia in a new dual chamber implantable cardioverter defibrillator inappropriately caused by far-field oversensing of ventricular beats in the atrial channel. Upon classification of the PR interval pattern, the rate criterion for an atrial tachycardia was fulfilled, and the device initiated high-frequency burst pacing as the first stage of programmed tiered atrial therapies. Atrial fibrillation subsequently was induced by high-frequency burst pacing, and eventually a programmed 10-J shock was delivered for successful termination of atrial fibrillation. The phenomenon of far-field oversensing of ventricular beats could be repeatedly observed during exercise testing and abolished by decreasing the atrial sensitivity.     

The course of Plasmodium chabaudi chabaudi infections in interferon-gamma receptor deficient mice

Interferon-gamma receptor (IFN-γR) deficient mice parasitized with blood-stage Plasmodium chabaudi chabaudi were used to assess the anti-malarial activity of interferon-gamma (IFN-γ). There was no significant difference in the parasitaemia between the two types of mice during the first peak of parasitaemia. However, IFN-γR deficient mice displayed an increased leucocytosis and a high mortality rate, whereas all of the wild type mice survived. IFN-γR deficient mice, unlike wild type mice, developed a pronounced second parasitaemia peak, 9 to 11 days after the first one, with a parasitaemia of up to 65% associated with mortality. Furthermore, increased serum levels of nitric oxide (NO) were only found in wild type mice at the peak of parasitaemia, whereas it remained at background levels in IFN-γR deficient mice. Parasite-specific antibody production was not significantly different in IFN-γR deficient mice, as compared to wild type mice. In addition, both wild type and IFN-γR deficient mice were equally protected upon reinfection. These results indicate a delayed development of protective immunity and imply a crucial function for the IFN-γR in the control of blood stage malaria during the initial three weeks of infection.