Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September-December 2006.

Following the clinical diagnosis of the first case of mumps on September 22, 2006 at the University of Virginia (UVA), 52 suspected cases were identified through active surveillance for mumps by the end of December 2006. Samples were collected from 47 students who presented with parotitis despite a documented history of two doses of measles, mumps, and rubella (MMR) vaccine. Six of 47 serum samples (13%) were positive for mumps IgM, and 46/47 specimens were positive for mumps IgG. Endpoint titration of acute phase serum samples from laboratory-confirmed cases did not provide evidence that elevated serum IgG is a consistent marker for infection among cases due to secondary vaccine failure. Buccal swab samples from 39 of the 47 students were tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) and/or viral culture. Mumps virus or mumps RNA was detected in 12 of 39 buccal samples (31%). Genetic analysis of the virus from the outbreak at UVA indicated that the outbreak was not linked to the large mumps outbreak in the Midwestern US that occurred earlier in 2006. Our findings support the use of viral detection to improve laboratory diagnosis of mumps among persons who have received two doses of MMR.

[Influence of ACE inhibitor spirapril on left ventricular hypertrophy]. / Beeinflussung der Linksherzhypertrophie durch den ACE-Hemmer Spirapril.

BACKGROUND: In view of the prevalence of left ventricular hypertrophy (LVH) in patients with essential hypertension, (15-30%), with an increased risk (2-4 x) of developing myocardial infarction, heart failure or malignant arrhythmia, possibly even leading to sudden cardiac death, effective reversal of LVH is a major aim of treatment. For this purpose, angiotensin-converting enzyme (ACE) inhibitors have proved to be most suitable. METHOD: In an open bicentric study involving 37 hypertensive patients with LVH confirmed by echocardiography, the effect of spirapril in reversing the left ventricular mass index (LVMI) and diastolic left ventricular wall thickness was investigated after 3 and 6 months. RESULTS: The LVMI decreased by 14.7% after 3, and by 27.3% after 6 months, irrespective of whether spirapril was given alone or in addition to other antihypertensive pre-medication. The results may be due to the proven 24-hour effect of spirapril in conjunction with the very long half-life.

Transvenous biventricular defibrillation halves energy requirements in patients.

BACKGROUND: Defibrillation thresholds (DFT) with standard implantable cardioverter-defibrillator leads in the right ventricle (RV) may be determined by weak shock field intensity in the myocardium of the left ventricle (LV). Adding a shocking electrode in a coronary vein on the middle of the LV free wall, thereby establishing biventricular defibrillation, substantially reduced defibrillation requirements in animals. We investigated the feasibility of this approach in 24 patients receiving an implantable cardioverter-defibrillator using a prototype over-the-wire temporary LV defibrillation lead. METHODS AND RESULTS: The LV lead was inserted through the coronary sinus, using a guide catheter and guidewire, into a posterior or lateral coronary vein whose location was determined by retrograde venography. Paired DFT testing compared a standard system (RV to superior vena cava plus can emulator [SVC+Can], 60% tilt biphasic shock) to a system including the LV lead. The biventricular system was tested with a dual-shock waveform (20% tilt monophasic shock from LV-->SVC+Can, then 60% tilt biphasic shock from RV-->SVC+Can). Twenty patients completed DFT testing. Venography and LV lead insertion time was 46+/-40 minutes. The biventricular system reduced mean DFT by 45% (8.9+/-1.1 J versus 4.9+/-0.5 J, P<0.001). Twelve patients (60%) had a standard system DFT >/=8 J, and the biventricular system gave a lower DFT in all patients. There were no adverse events related to the use of the LV lead, which was removed after testing. CONCLUSIONS: Internal defibrillation using a transvenously inserted LV lead is feasible, produces significantly lower DFTs, and seems safe under the conditions tested. Biventricular defibrillation may be a useful option for reducing DFTs or could be added to an LV pacing lead for heart failure.

Investigation of coronary venous anatomy by retrograde venography in patients with malignant ventricular tachycardia.

BACKGROUND: The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. METHODS AND RESULTS: The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. CONCLUSIONS: The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.

Transvenous biventricular defibrillation.

The recent success of biventricular pacing with transvenously implantable left ventricular leads suggests that left ventricular leads may be useful for other modes of therapy. Animal studies showed small leads inserted into a left ventricular vein dramatically reduced defibrillation strength requirements. This article describes a human investigation of the feasibility of biventricular defibrillation. Fifty-one patients undergoing implantable cardioverter defibrillator (ICD) implantation were enrolled. After insertion of a standard ICD lead, a prototype over-the-wire left ventricular defibrillation lead was inserted through the coronary sinus and into a vein on the left ventricle. Lead insertion was guided by retrograde venography. The left ventricular lead's location was randomized to the anterior or posterior vein. Randomized, paired defibrillation threshold (DFT) testing was performed to compare a standard ICD shock configuration (Control: right ventricle- --> superior vena cava+ + CAN+) to 1 of 3 biventricular shock configurations. In the anterior vein, the left ventricular lead was tested with either a single biphasic shock from right ventricle + left ventricle- --> superior vena cava+ + CAN+ or a dual biphasic shock. In the posterior vein, the left ventricular lead was tested with a dual biphasic shock. Dual shocks consisted of a 40% tilt biphasic shock from right ventricle- --> superior vena cava+ + CAN+ followed by another 40% tilt biphasic shock from left ventricle- --> superior vena cava+ + CAN+, delivered from a single 225 microF capacitance. Left ventricular lead positioning was successful in 41 of 46 patients (89%). Mean left ventricular lead insertion time was 17 +/- 17 minutes and 13 +/- 15 minutes for anterior and posterior locations, respectively. Mean DFTs were not statistically lower for the left ventricular shock configurations, but retrospective analysis showed a well-defined region of the posterolateral left ventricle where consistent DFT reduction was achieved with dual shocks (14.0 +/- 2.7 J vs 7.8 +/- 0.9 J; n = 5; p = 0.04). There were no adverse events requiring intervention due to the use of the left ventricular lead. Biventricular defibrillation is feasible and safe under the conditions used in this study. Additional studies are needed to verify whether dual shocks with posterolateral left ventricular lead positions consistently reduce DFTs.

[Pacemaker therapy of hypertrophic obstructive cardiomyopathy. PIC (Pacing in Cardiomyopathy) Study Group]. / Schrittmacher-Therapie der hypertroph-obstruktiven Kardiomyopathie. PIC-Studiengruppe.

Clinical management of patients with symptoms caused by pharmacological refractory hypertrophic obstructive cardiomyopathy must consider surgical myectomy, percutaneous transluminal septal myocardial ablation and implantation of a DDD pacemaker. Until now, no prospective, double blind, randomized studies have yet been carried out to determine the merits of each of these treatment alternatives. However, uncontrolled studies have shown that short atrioventricular delay dual-chamber pacing reduces outflow tract obstruction. Aim of the study was to investigate the results of the pacemaker therapy in a prospective, double blind randomized crossover procedure. All patients with hypertrophic obstructive cardiomyopathy included in this multicenter study were either refractory or intolerant to drugs and typically had pressure gradients higher than 30 mm Hg. In 83 patients, mean age 53 (18 to 82) years who responded favorably to a temporary pacing test, a DDD pacemaker was implanted. After echo- and echo-Doppler-based measurements of hemodynamic parameters the patients were randomized into 2 groups, those with an implanted pacemaker in the inactivated mode (AAI) and those with a pacemaker in the activated mode (DDD with optimized short AV delay). A crossover of these groups was performed after 12 and 24 weeks, respectively. Both objective parameters of echo including Doppler, and spiroergometry, and subjective parameters of angina, dyspnea, and quality of life were recorded. Additionally, subgroups based on age decades were analyzed. After 12 weeks in the DDD mode, regardless of the randomization sequence, a decrease of the pressure gradient from 59 +/- 36 mm Hg (median) to 30 +/- 25 mm Hg was proven significant (p < 0.001). The endurance of the patients who, during screening, achieved less than 10 minutes of exercise by the Bruce protocol improved by 21% under DDD mode. The main symptoms, as measured by the NYHA classification, improved statistically significant from a mean of 2.4 to 1.7 for functional class, from a mean of 2.4 to 1.4 for dyspnea and from a mean of 1.0 to 0.4 for angina. Subgroup analysis showed improvements depended significantly upon age, with a marked improvement between the ages of 60 and 70, which was statistically significant as compared to other decades. Subjective improvements in the quality-of-life of patients was measured using a specially developed questionnaire. These findings justify, by all means, the intention to implant a DDD pacemaker in older patients. In younger and/or such patients with elevated pressure gradients, the results of ongoing randomized studies comparing myectomy, PTSMA and pacing have to be considered.

Biological neurotoxins.

The authors divide biological toxins into animal, plant, and bacterial classes and discuss each within a context of demographic, clinical and research examples. Advances in our knowledge are highlighted, and the authors relate the implications of this knowledge to target-specific neurologic involvement.

Significant improvement of quality of life following atrioventricular synchronous pacing in patients with hypertrophic obstructive cardiomyopathy. Data from 1 year of follow-up. PIC study group. Pacing In Cardiomyopathy.

AIMS: Atrioventricular synchronous pacing exerts beneficial effects, including reduction of left ventricular outflow tract gradients, in patients with hypertrophic obstructive cardiomyopathy. The Pacing in Cardiomyopathy study was initiated to explore the effects of pacing in a double-blind randomized crossover fashion. The aims were to ascertain the beneficial effects of pacing in a controlled study and to rule out a placebo effect by pacing. This paper deals with the outcome of pacing on quality of life during 1 year of follow-up. METHODS: Quality of life was evaluated with the Karolinska questionnaire, validated for patients paced for bradyarrhythmias and ischaemic heart disease. Drug-refractory patients with hypertrophic obstructive cardiomyopathy were recruited for the study and after a temporary pacing procedure implanted with permanent pacemakers. Patients were randomized to two study arms defining the sequence of pacemaker programming. In one arm the pacemaker was inactive, in the other active. After 3 months the pacemaker was reprogrammed to the alternate mode and a further 3 months followed. After this period subsequent pacemaker programming corresponded to the mode preferred by the patient. A last assessment was made 1 year after baseline examinations. RESULTS: Eighty patients completed the first crossover period and 75 completed the full 1 year of follow-up. Active pacing induced significant quality of life improvements, in the order of 9-44%, regardless of programming sequence. Discontinuation of pacing after a first active period resulted in the return of symptoms. Fourteen patients requested early reprogramming after having been programmed to inactive pacing after a first period of active pacing. Seventy-six patients preferred active pacing after the crossover period. A further 6 months of pacing induced progressive improvement in symptoms already favourably influenced. CONCLUSION: Atrioventricular synchronous pacing has a profound beneficial effect on most domains of quality of life in patients with hypertrophic obstructive cardiomyopathy refractory to drug treatment.

Clinical progress after randomized on/off pacemaker treatment for hypertrophic obstructive cardiomyopathy. Pacing in Cardiomyopathy (PIC) Study Group.

BACKGROUND: The therapeutic options for hypertrophic obstructive cardiomyopathy (HOCM) classically include medical treatment with beta-blockers and calcium antagonists or myectomy-myotomy as a surgical possibility for refractory cases. The observation that pacemaker activation of the heart in HOCM reduces the subaortic gradient is well known but less well investigated. METHODS: Eighty-three patients (33 female and 50 male) mean age 53 (18-82) years, with symptoms refractory to drug treatment and a resting gradient above 30 mmHg, who responded favourably to temporary pacing, were included in this prospective study and had a pacemaker (DDD) implanted. After an initial double-blind crossover phase of 6 months, patients were reinvestigated at 12 months and followed for a mean of 36 months. RESULTS: As observed during a screening investigation, the obstruction was significantly reduced from 72 +/- 35 mmHg to 29 +/- 24 mmHg (P < 0.01) when the pacemaker was on, while no major effect was seen during the sham phase. The effect was persistent at 1 year with a remaining resting gradient of 28 +/- 24 mmHg. In parallel, we documented an improvement in functional capacity, according to the NYHA classification and by quality of life analysis, and a significant improvement in dyspnoea and angina. Exercise on treadmill improved only in patients with reduced initial tolerance (< 8 min). During the mean follow-up of 36 months, 65 patients remained on pacing alone, with eight patients having additional AV-node ablation and five patients finally having surgery. CONCLUSION: This controlled multicentre study shows that pacemaker treatment is an option for HOCM patients; it is inoffensive and does not exclude alternative methods, but satisfies 79% of patients beyond 3 years.

Is the atrial high rate episode diagnostic feature reliable in detecting paroxysmal episodes of atrial tachyarrhythmias?

The atrial high rate episode diagnostic in the Thera pacemaker reports frequency, duration, and date/time of atrial tachyarrhythmias according to programmed criteria. The aim of the study was to validate the atrial high rate episode diagnostic feature. Episodes of atrial fibrillation recorded by Holter monitoring were compared to episodes detected by the pacemaker. Forty five ambulatory (Holter) recordings were used for evaluation. Thirty of 45 ambulatory (Holter) recordings showed sinus rhythm. On 4 of these 30 ambulatory (Holter) recordings, the Thera detected 12 episodes of atrial tachyarrhythmias as false-positives (sinus rhythm was detected as atrial tachyarrhythmia). The main reason was far-field R and T was oversensing. On 15 of 45 ambulatory (Holter) recordings, 125 episodes of atrial tachyarrhythmias were recorded. Ninety-three of these events also were detected by the pacemaker, while for 32 events the Thera reported sinus rhythm. The main reason was that the episodes were of too short duration. Therefore, the Thera (programmed with detection rate 160 beats/min, detection beats 40, termination beats 10) was unable to detect atrial tachycardias. Software simulation of the diagnostic algorithm under several programming settings using the digitized Holter files demonstrated highly reliable detection of atrial tachyarrhythmias (sensitivity 98%, specificity 100%) when programmed as follows: detection rate 220 beats/min, detection beats 10, termination beats 20. It can be concluded that Thera's high rate episode monitor is a reliable tool for detection of atrial tachyarrhythmias, if programmed as recommended.

Pacing in hypertrophic obstructive cardiomyopathy. A randomized crossover study. PIC Study Group.

BACKGROUND: Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. METHOD: In order to evaluate the impact of pacing therapy, were performed a randomized multicentre double-blind cross-over (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22-87) years with symptoms refractory or intolerant to classical drug treatment. RESULTS: After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59 +/- 36 mmHg to 30 +/- 25 mmHg (P < 0.001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2.4 to 1.4 and 1.0 to 0.4, respectively (P < 0.007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. CONCLUSION: Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment.

[Diagnosis and clinical aspects of supraventricular tachycardia]. / Diagnostik und Klinik supraventrikulärer Tachykardien.

Supraventricular tachycardias are the most frequently occurring manifestations of arrhythmia. They make very high demands on the physician in respect of differential diagnosis and clinical assessment. Atrial tachycardias, atrial flutter and atrial fibrillation are mainly associated with an underlying cardiac disease. The isolated forms of atrial flutter and fibrillation without any detectable cardiac disease are a diagnostic challenge and are associated with a relatively high rate of complications. AV node reentry and AV tachycardias with accessory path are not associated with cardiac disease; they occur in 0.8% of the population and can be assessed with satisfactory accuracy in respect of mechanism and risk by means of the 12-lead ECG alone.

[Biological VA cross talk in an AAJ pacemaker]. / Biologisches VA-cross-talk bei einem AAJ-Schrittmacher.

On the basis of an observation in a female patient with atrial pacemaker the complication of the "cross-talk" phenomenon is explained, which up to now has been known above all in two-chamber pacemakers. The typical manifestation of ECG of the cross-talk is the change of the stimulation frequency or the total inhibition of the ventricular impulse output in DDD-pacemakers. Attention is paid to the importance of this phenomenon which increases in our country with growing number of the implanted two-chamber pacemakers.

Pancreatic islet arachidonic acid turnover and metabolism and insulin release in response to delta-9-tetrahydrocannabinol.

Isolated pancreatic islets from the rat secrete insulin in response to glucose or delta-9-tetrahydrocannabinol (THC). THC stimulated the basal release of insulin and also potentiated the secretory response to glucose. The exposure of control or glucose-stimulated islets to THC inhibited the incorporation of [14C]arachidonic acid (AA) into phospholipids. However, in islets prelabeled with [14C]AA, THC enhanced the glucose-induced loss of AA from phospholipids. The enhanced AA release from islet phospholipids in response to glucose and THC was accompanied by increased synthesis of 12-L-[5,6,8,9,11,12,14,15-3H(N)]-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2. The lipoxygenase inhibitor 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C) inhibited 12-HETE synthesis and insulin release in glucose and THC-challenged islets; nordihydroguaiaretic acid also inhibited insulin release in THC-treated islets. In contrast, the cyclooxygenase inhibitor, indomethacin, stimulated insulin release. In homogenized islet preparations, THC inhibited acyl-CoA acyltransferase, while it stimulated phospholipase A2 activity. The stimulatory effects of THC on islet cell AA hydrolysis from phospholipids, lipoxygenase product formation, and secretion suggests that these biochemical sequelae in cell activation are important modulators of insulin release.