A pedigree-based genetic appraisal of Boxer ARVC and the role of the Striatin mutation.

The objective of this paper was to investigate by pedigree-based genetic means the origins and inheritance of arrhythmogenic right ventricular cardiomyopathy (ARVC) in UK Boxers and assess the role of the proposed causal mutation in the gene, Striatin (STRN). All ARVC cases traced back to a small number of imported American dogs deriving from the group of Boxers studied by Harpster (1983) to define the disease, strongly suggesting that the disease is the same in the two countries. Dogs with and without the STRN mutation were found in both ARVC affected and normal Boxers showing that the mutation is not responsible for the disease. Evidence was found that the STRN mutation is, however, genetically linked with the gene responsible on the same chromosome. The linkage implies that the two genes can separate by meiotic recombination such that both ARVC-affected and ARVC-unaffected lines of dogs may carry either the STRN mutation or its wild-type allele. These have been found. Homozygotes for the STRN mutation tended to be severely affected at early ages, suggesting that there is an interaction between the known effects of the STRN mutation on the cardiomyocyte and ARVC.

Cardiac risk assessment before the use of stimulant medications in children and youth: A joint position statement by the Canadian Paediatric Society, the Canadian Cardiovascular Society, and the Canadian Academy of Child and Adolescent Psychiatry.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and pediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac subspecialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Cardiac risk assessment before the use of stimulant medications in children and youth.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and paediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac sub-specialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Distribution and dynamics of Japanese beetles along the Indianapolis Airport perimeter and the influence of land use on trap catch.

As part of a program to minimize the accidental transportation of Japanese beetles (Popillia japonica) through cargo aircraft to areas where they are not established, a 4-yr trapping project was initiated to study the relative distribution and dynamics of the beetles along a trap line around the Indianapolis International Airport. Land use influence on beetle abundance (trap catch) was assessed using a geographic information system. Trap catch was consistently high in some locations and low in others. In general, high trap catches occurred near agronomic land planted with corn or soybeans, which are both preferred hosts of adult beetles. Low trap catches generally occurred in areas lacking preferred host plants. The amount of agronomic land within 500 m of the traps was always positively correlated with trap catch. Average trap catches were highly correlated by location from year to year, indicating stability of the relative distribution of the beetles along the trap line. Because high trap catches consistently occurred in the same locations, it can be inferred that trapping can be an effective method to monitor Japanese beetle populations. Taking airport-owned agronomic land out of corn and soybean production near the cargo terminals may reduce beetle activity in these areas.

Efficacy of signal-averaged electrocardiography in the young orthotopic heart transplant patient to detect allograft rejection.

Endomyocardial biopsy is the gold standard survey for cardiac graft rejection. Signal-averaged electrocardiography (SAECG) identifies slowly conducting, diseased myocardium. We sought to determine whether SAECG is a sensitive, noninvasive transplant surveillance method in the young.Ninety-four SAECGs recorded prior to biopsy in 20 young transplant (OHT) patients and those from 15 healthy age-matched controls (CTL) were analyzed. In the OHT group, 56 no-rejection (NOREJ) (ISHLT grades 0 or 1 A) and 37 acute rejection (REJ) (ISHLT grades IB, 2, and 3A) SAECGs were compared, SAECGs were filtered at 40-255 Hz. Total QRS duration (QRSd), duration of terminal low amplitude of QRS under 40 microV (LAS), and root mean square amplitude of terminal 40 msec of QRS (RMS40) were compared.SAECGs were significantly different in CTL vs NOREJ but not in NOREJ vs REJ: QRSd, 81.7 +/- 8, 107.2 +/- 18.4, and 112.3 +/- 21.6 msec, respectively; LAS, (18 +/- 5.8, 23.6 +/- 10.7, and 27 +/- 14.8 msec, respectively; and RMS40, (169.3 +/- 100.4, 68 +/- 48.8, and 57.5 +/- 45.6 microV, respectively. Children following OHT exhibited significant differences in the SAECG compared to controls. Differences between the NOREJ and REJ groups were negligible. Therefore, SAECG may not be effective in detecting OHT rejection in the young.

Assessment of fetal atrioventricular time intervals by tissue Doppler and pulse Doppler echocardiography: normal values and correlation with fetal electrocardiography.

OBJECTIVE: To establish gestational age-specific reference values of normal fetal atrioventricular (AV) time interval by spectral tissue Doppler imaging (TDI) and pulse-wave Doppler (PD) methods, and to assess their correlation with signal-averaged fetal PR intervals (ECG). DESIGN: Cohort study. SETTING: Tertiary centre for fetal cardiology. PATIENTS AND MEASURES: 131 pregnant women between 14 and 42 weeks' gestation underwent 196 fetal echocardiograms and 158 fetal ECG studies. TDI-derived AV intervals were measured as the intervals from atrial contraction (Aa) to isovolumic contraction (IV) and from Aa to ventricular systole (Sa) at the right ventricular free wall. PD-derived AV intervals were measured from simultaneous left ventricular inflow/outflow (in/out) and superior vena cava/aorta (V/AO) recordings. RESULTS: Measurements were possible by ECG in 61%, by TDI in 100%, by in/out in 100% and by V/AO in 97% of examinations. Aa-IV correlated significantly better with PR intervals (y = 0.67x + 38.29, R(2) = 0.15, p < 0.0001, mean bias 8.0 ms) than did in/out (R(2) = 0.10, p = 0.002, bias 18.7 ms) and V/AO (R(2) = 0.06, p = 0.02, bias 12.4 ms). Gestational age and AV intervals were positively correlated with all imaging modalities (R(2) = 0.19-0.31, p < 0.0001). CONCLUSION: This study showed the feasibility of fetal AV interval measurements by TDI, and established gestational age-specific reference data. TDI-derived Aa-IV intervals track ECG PR intervals more closely than PD-derived AV intervals and thus should be used as the ultrasound method of choice in assessing fetal AV conduction.

Inter- and intraobserver variability in LVH and RVH reporting in pediatric ECGs.

BACKGROUND: Physicians' diagnoses are often used as the gold standard for evaluating computer electrocardiogram (ECG) interpretation programs. As part of a larger study to evaluate the Glasgow pediatric ECG analysis program, inter- and intraobserver variability in the ECG reporting of two pediatric cardiologists was examined. METHODS: The ECGs of 984 children were sent for reporting independently by two cardiologists with all identifying information except age and sex removed. Three hundred twenty ECGs had no clinical indication available, and they were thus reported "blind." For 664 ECGs, the clinical indication was known and included with the ECG trace. All ECGs reported as right ventricular hypertrophy (RVH) or left ventricular hypertrophy (LVH) were returned to the cardiologists without their knowledge for reporting a second time "blind" as to the clinical indication. RESULTS: When the cardiologists' reports were compared with each other, the provision of clinical information led to greater agreement between them for the diagnosis of LVH (kappa increased from 0.44 to 0.52) but did not substantially affect their agreement in diagnosing RVH (kappa fell from 0.66 to 0.63). Intraindividual comparisons in 166 ECGs revealed that one cardiologist was more consistent in diagnosing RVH and the other more consistent in diagnosing LVH. CONCLUSIONS: This study has demonstrated the difficulties in using cardiologists' diagnoses as the gold standard with which to evaluate pediatric ECGs.

Evaluation of pediatric electrocardiogram diagnosis of ventricular hypertrophy by computer program compared with cardiologists.

This study aimed to evaluate the diagnosis of pediatric left ventricular hypertrophy (LVH) and right ventricular hypertrophy (RVH) by the Glasgow electrocardiogram (ECG) interpretation program compared to interpretations provided by two pediatric cardiologists. ECGs had all identifying information removed and were sent to the cardiologists independently with the patient's age and sex and the clinical indication for the ECG, if known. A total of 984 ECGs were included in the study, of which 664 were reported "with clinical indication" and 320 were reported "blind." With respect to an averaged diagnosis of the two cardiologists, the sensitivity of the program for RVH was better when the cardiologists reported blind (73.3%) than with the clinical indication (53.5%), with the same trend for the program compared with individual cardiologists. The specificity of the program was at least 94.4% in all cases. For LVH, the program had high specificity (=95.8%) for "reported blind" and "with clinical indication" cases but low sensitivities throughout (the highest was 44.4% with respect to an averaged diagnosis of the two cardiologists reporting with the clinical indication). Subsequent discussion revealed that if the cardiologists had disagreed with one another initially, their consensus opinion was twice as likely to be in agreement with the program.

Mercury vapour levels in dental practices and body mercury levels of dentists and controls.

AIM: A study of 180 dentists in the West of Scotland was conducted to determine their exposure to mercury during the course of their work and the effects on their health and cognitive function. DESIGN: Data were obtained from questionnaires distributed to dentists and by visiting their surgeries to take measurements of environmental mercury. METHODS: Dentists were asked to complete a questionnaire including items on handling of amalgam, symptoms experienced, diet and possible influences on psychomotor function such as levels of stress and alcohol intake. They also completed the 12-item General Health Questionnaire. Dentists were asked to complete a dental chart of their own mouths and to give samples of urine, hair and nails for mercury analysis. The dentists were visited at their surgeries where environmental measurements were made in eight areas of the surgery and they undertook a computerised package of psychomotor tests. One hundred and eighty control subjects underwent a similar procedure, completing a questionnaire, having their amalgam surfaces counted, giving urine, hair and nail samples and undergoing the psychomotor test procedure. RESULTS: Dentists were found to have, on average, urinary mercury levels over 4 times that of control subjects although all but one dentist had urinary mercury below the Health and Safety Executive health guidance value of 20 mumol mmol(-1) creatinine. Urine was found to be a better biological marker for mercury exposure than hair or nails.Dentists were significantly more likely than control subjects to have suffered from disorders of the kidney but these symptoms were not significantly associated with their level of mercury exposure as measured in urine. One hundred and twenty two (67.8%) of the 180 surgeries visited had environmental mercury measurements in one or more areas above the Occupational Exposure Standard (OES) set by the Health and Safety Executive. In the majority of these surgeries the high levels of mercury were found at the skirting and around the base of the dental chair. In 45 surgeries (25%) the personal dosimetry measurement (ie in the breathing zone of dental staff) was above the OES. CONCLUSION: On the basis of these findings, it is recommended that greater emphasis should be made relating to safe handling of amalgam in the training and continuing professional development of dentists, that further studies are carried out on levels of mercury exposure of dental team members during the course of their working day, and that periodic health surveillance, including urinary mercury monitoring, of dental personnel should be conducted to identify possible effects of practising dentistry.

Predictors of refractory tachycardia in infants with supraventricular tachycardia.

Reentrant supraventricular tachycardia (SVT) is the most common arrhythmia in infants. There are few predictors as to which patients will have recurrent or refractory SVT. We retrospectively reviewed records of all infants with SVT evaluated at The Hospital for Sick Children, Toronto, between January 1, 1995, and December 31, 1999. Patients with reentrant SVT documented in infancy and structurally normal hearts were included. Patients were placed in two groups: the "simple" group consisted of patients with SVT completely controlled by not more than one medication, and the "complex" group consisted of patients with recurrent episodes requiring at least one medication change for control. Forty-two cases were analyzed-23 in the simple group and 19 in the complex group. One patient in each group died. Age at presentation was 50.4 +/- 13.2 days for the simple group versus 10.2 +/- 2.5 days for the complex group (p <0.01). Complex patients were treated with a median of three medications and were more likely to have echocardiographically reduced ventricular function. The surface electrocardiogram RP interval during SVT was significantly longer in complex patients (p <0.001). There were no differences between the groups in gender, cycle length in SVT or sinus rhythm, the presence of pre-excitation, initial medication choice, or duration of therapy. Recurrent SVT in infancy is associated with younger age and/or ventricular dysfunction at presentation and also with slower ventriculoatrial conduction. The similar duration of therapy for simple and complex patients suggests that the early clinical course of SVT in infancy is not predictive of long-term outcome.

Health and neuropsychological functioning of dentists exposed to mercury.

OBJECTIVES: A cross sectional survey of dentists in the west of Scotland and unmatched controls was conducted to find the effect of chronic exposure to mercury on health and cognitive functioning. METHODS: 180 dentists were asked to complete a questionnaire that included items on handling of amalgam, symptoms experienced, possible influences on psychomotor function, and the 12 item general health questionnaire. Dentists were asked to complete a dental chart of their own mouths and to give samples of urine, hair, and nails for mercury analysis. Environmental measurements of mercury in dentists' surgeries were made and participants undertook a package of computerised psychomotor tests. 180 control subjects underwent a similar procedure, completing a questionnaire, having their amalgam surfaces counted, giving urine, hair, and nail samples and undergoing the psychomotor test package. RESULTS: Dentists had, on average, urinary mercury concentrations over four times that of control subjects, but all but one dentist had urinary mercury below the Health and Safety Executive health guidance value. Dentists were significantly more likely than control subjects to have had disorders of the kidney and memory disturbance. These symptoms were not significantly associated with urinary mercury concentration. Differences were found between the psychomotor performance of dentists and controls after adjusting for age and sex, but there was no significant association between changes in psychomotor response and mercury concentrations in urine, hair, or nails. CONCLUSIONS: Several differences in health and cognitive functioning between dentists and controls were found. These differences could not be directly attributed to their exposure to mercury. However, as similar health effects are known to be associated with mercury exposure, it would be appropriate to consider a system of health surveillance of dental staff with particular emphasis on symptoms associated with mercury toxicity where there is evidence of high levels of exposure to environmental mercury.

Is electronystagmography of diagnostic value in the elderly?

We aimed to determine the diagnostic value of electronystagmography (ENG) in a community-based sample of dizzy subjects over 65 years old. A total of 96 asymptomatic controls and 149 dizzy subjects underwent ENG. Clinical diagnoses were made on standardized criteria. ENG results were classed as normal or abnormal, according to reference ranges derived from the controls. Rates of ENG abnormality in different diagnostic categories, sensitivities, specificities and predictive values were calculated. Central vascular disease was common (105 out of 149 subjects); peripheral vestibular disease was not (14). Spontaneous nystagmus had a positive predictive value of 95% for central vascular disease, but was only 18%-sensitive, and was usually detectable clinically. ENG had no other significant diagnostic value. ENG failed to discriminate dizzy subjects from controls and failed to differentiate various dizziness syndromes. ENG was of no practical value in this community-derived sample of dizzy elderly subjects.

Clinical use of permanent pacemaker for conversion of intraatrial reentry tachycardia in children.

The use of the implanted atrial-based pacemaker to overdrive postsurgical intraatrial reentry tachycardia (IART) was evaluated in a large group of pediatric patients over a 14-year study period. The authors sought to determine the feasibility of this noninvasive technique in the management of this specialized population and to determine factors associated with successful conversion. They examined 128 manual overdrive attempts performed on 22 consecutive patients. There were 10 patients with post-Fontan repair, 7 with post-Mustard/Senning procedure, and 5 with miscellaneous lesion types. The number of IART episodes for overdrive pacing per patient ranged from 1 to 15. The first overdrive pacing attempt was successful in 63% (14/22) of the patients. The mean IART cycle length was 278 +/- 59 ms. The mean pacing rate for effective conversion of IART was 66 +/- 10% faster than the IART rate. By controlling for repeated measures for individual patients, three factors were found to be independently associated with a successful outcome: (1) lesion type other than Fontan surgery (P = 0.007), (2) lack of acceleration of IART with the overdrive attempt (P < 0.001), and (3) patient use of amiodarone with attempt (P = 0.005). There were three procedural complications: two inadvertent overdrive pacing episodes, and one episode of acceleration of IART cycle length and conduction resulting in need for cardioversion. Manual pacemaker overdrive conversion of IART is a useful adjunct in the management of postsurgical IART in the pediatric population and should be considered as an initial treatment option.

Ultrastructural characteristics of the in vitro cell cycle of the protozoan pathogen of oysters, Perkinsus marinus.

Ultrastructural characteristics of vegetative and zoosporangial stages of cultured Perkinsus marinus, a pathogen of the eastern oyster, Crassostrea virginica, were examined by transmission electron microscopy. An axenic cell culture was propagated from infected Chesapeake Bay oyster hemolymph. Different stages of the in vitro cell cycle, including schizonts and different size trophonts, were examined. Trophonts had spherical nuclei with wide perinuclear spaces, mitochondria with tubular cristae, and vacuoles with vacuoplasts. There were micropores on the inside of cell walls. A tubular network in the cytoplasm connected lomasomes to vacuoles, and contained vacuoplast precursor material. Vacuoplasts and precursor material diminished when cell cultures were not fed, suggesting a function in metabolite storage. Cells divided by schizogony or binary fission. Daughter cells in a schizont were not alike, and may specialize for different functions. Some of the daughter cells in a schizont died. Some hypnospores, directly isolated from infected oyster hemolymph enlarged in Ray's fluid thioglycollate medium, and were induced to zoosporulate. Zoosporangia contained varicose, hypha-like structures, whose apical tips gave rise to prezoospores. Ultrastructural characteristics of the vegetative and zoosporangial stages did not resemble any apicomplexan parasites other than members of the genus Perkinsus.

Reproducibility of a non-invasive real-time measure of cardiac parasympathetic activity.

The NeuroScope is a new device which produces a continuous real-time index of cardiac parasympathetic activity (the CIPA) and accurately measures RR intervals. The reproducibility of the CIPA has not yet been assessed. This study was designed to assess the reproducibility of a 5 minute recording of the CIPA using the NeuroScope and compare it with that of conventional heart rate variability (HRV) measures. 50 subjects (31 male, 19 female) aged 21-77 years were recruited. 11 of these were apparently healthy and 39 were patients with a variety of cardiological problems. Two 5 minute recordings of CIPA and RR intervals for each subject were made with a 2-3 minute break between recordings. The limits of agreement for the CIPA were such that the second estimate was between 72 and 140% of the first estimate, 95% of the time. The limits of agreement for other indices of HRV, namely SDNN, rMSSD, In low-frequency HRV and In high-frequency HRV, were 61-157%, 68-153%, 77-131% and 76-133%. The short-term reproducibility of a 5 minute recording of CIPA is moderate and better than simple time-domain but not frequency-domain measures of HRV.

Within-breath arterial PO2 oscillations in an experimental model of acute respiratory distress syndrome.

Tidal ventilation causes within-breath oscillations in alveolar oxygen concentration, with an amplitude which depends on the prevailing ventilator settings. These alveolar oxygen oscillations are transmitted to arterial oxygen tension, PaO2, but with an amplitude which now depends upon the magnitude of venous admixture or true shunt, QS/QT. We investigated the effect of positive end-expiratory pressure (PEEP) on the amplitude of the PaO2 oscillations, using an atelectasis model of shunt. Blood PaO2 was measured on-line with an intravascular PaO2 sensor, which had a 2-4 s response time (10-90%). The magnitude of the time-varying PaO2 oscillation was titrated against applied PEEP while tidal volume, respiratory rate and inspired oxygen concentration were kept constant. The amplitude of the PaO2 oscillation, delta PaO2, and the mean PaO2 value varied with the level of PEEP applied. At zero PEEP, both the amplitude and the mean were at their lowest values. As PEEP was increased to 1.5 kPa, both delta PaO2 and the mean PaO2 increased to a maximum. Thereafter, the mean PaO2 increased but delta PaO2 decreased. Clear oscillations of PaO2 were seen even at the lowest mean PaO2, 9.5 kPa. Conventional respiratory models of venous admixture predict that these PaO2 oscillations will be reduced by the steep part of the oxyhaemoglobin dissociation curve if a constant pulmonary shunt exists throughout the whole respiratory cycle. The facts that the PaO2 oscillations occurred at all mean PaO2 values and that their amplitude increased with increasing PEEP suggest that QS/QT, in the atelectasis model, varies between end-expiration and end-inspiration, having a much lower value during inspiration than during expiration.

Re-evaluation of normative electronystagmography data in healthy ageing.

Previous work by our group questions the validity of existing electronystagmography (ENG) reference ranges in the elderly. We aim to establish valid reference ranges for ENG in people over 65 on the Nicolet Nystar Plus system. Ninety-six healthy asymptomatic subjects over 65 underwent ENG, including spontaneous and positional nystagmus, saccades, smooth pursuit, optokinetic nystagmus and bithermal calorics; 95% reference ranges with confidence intervals were calculated. The newly determined reference ranges were far wider than those provided by the ENG equipment manufacturer for eight out of 11 parameters (all P < 0.001). Vestibular function is known to deteriorate and become more variable with age. The failure to reflect this change in currently used reference ranges may have contributed to the high rates of vestibular disease reported in some series of dizzy elderly patients. Clinical interpretation of ENG depends on valid reference ranges.

Accuracy of surface electrocardiograms for differentiating children with hypertrophic cardiomyopathy from normal children.

Most patients with hypertrophic cardiomyopathy have abnormal electrocardiograms. In this study of 37 matched pairs in the pediatric age group, the 12-lead electrocardiogram did not differentiate between affected and normal children reliably enough to allow it to be used as a screening test in the general population.