A novel treadmill protocol for exercise testing in children: the British Columbia Children's Hospital protocol.

BACKGROUND: Exercise testing in children is widely recommended for a number of clinical and prescriptive reasons. Many institutions continue to use the Bruce protocol for treadmill testing; however, with its incremental changes in speed and grade, it has challenges for practical application in children. We have developed a novel institutional protocol (British Columbia Children's Hospital (BCCH)), which may have better utility in paediatric populations. AIM: To determine if our institutional protocol yields similar peak responses in minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), metabolic equivalents (METS) and heart rate (HR) when compared with the traditional Bruce protocol. METHODS: On two different occasions, 70 children (boys=33; girls=37) aged 10-18 years completed an exercise test on a treadmill using each of the protocols. During each test, metabolic gas exchange parameters were measured. HR was monitored continuously during exercise using an HR monitor. RESULTS: Physiological variables were similar between the two protocols (median (IQR); rs): VE (L/min) (BCCH=96.7 (72.0-110.2); Bruce=99.2 (75.6-120.0); rs=0.95), peak VO2 (mL/min) (BCCH=2897 (2342-3807); Bruce=2901 (2427-3654); rs=0.94) and METS (BCCH=16.2 (14.8-17.7); Bruce=16.4 (14.7-17.9); rs=0.89). RERs were similar (BCCH=1.00 (0.96-1.02); Bruce=1.03 (0.99-1.07); rs=0.48). Total exercise time (in seconds) was longer for the BCCH protocol: BCCH=915 (829-1005); Bruce=810 (750-919); rs=0.67. CONCLUSION: The BCCH protocol produces similar peak exercise responses to the Bruce protocol and provides an alternative for clinical exercise testing in children.

A Doppler Echocardiographic Study of the Myocardial Inotropic Response to Peak Semisupine Exercise in Healthy Children: Development of a Simplified Index of Myocardial Reserve.

BACKGROUND: Stress echocardiography has been advocated for the detection of abnormal myocardial function and unmasking diminished myocardial reserve in pediatric patients. The aim of this study was to create a simplified index of myocardial reserve, derived from the myocardial inotropic response to peak semisupine exercise in healthy children, and illustrate its applicability in a sample of pediatric oncology patients. METHODS: In this prospective analysis, children (7-18 years of age) with normal cardiac structure and function performed semisupine stress echocardiography to volitional fatigue. The quotient of wall stress at peak systole and heart rate-corrected velocity of circumferential fiber shortening were calculated at baseline and at peak exercise, the difference of which was termed the index of myocardial reserve (IMR). The IMR was also calculated in a retrospective sample of pediatric oncology patients with normal resting left ventricular function who had received anthracycline treatment and had performed the same exercise protocol to illustrate utility. RESULTS: Fifty healthy subjects (mean age, 13.2 ± 2.6 years) and 33 oncology patients (mean age, 12.7 ± 4.0 years) were assessed. In the healthy children at peak exercise, heart rate-corrected velocity of circumferential fiber shortening significantly increased (from 1.17 ± 0.17 to 1.58 ± 0.24 circ · sec-1, P < .001), while the quotient of wall stress at peak systole significantly decreased (from 75.3 ± 17.1 to 55.3 ± 13.8 g · cm-2, P < .001), shifting the plot of the relationship between the two parameters upward and to the left. The mean IMR was -30.8 ± 17.8, and the normal distribution ranged from -4.7 (fifth percentile) to -67.3 (95th percentile). The IMR was abnormal in 10 oncology patients who were treated with anthracyclines. CONCLUSIONS: The authors have developed a novel IMR. Relative to the normal distribution of this IMR in healthy subjects, it is possible to identify patients with abnormal myocardial reserve. Thus, this study demonstrates the application of the IMR to aid in clinical decision making in individual patients.

A review of 15-year experience with anomalous origin of the left coronary artery.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare condition presenting in infancy with acute myocardial ischaemia. AIMS: A retrospective study was undertaken to assess the presenting features and long-term outcome of all cases of ALCAPA presenting to our institution over a 15-year period. METHODS: All the cases were located using the hospital discharge system and charts were reviewed. RESULTS: The mean age at diagnosis was 4.5 months (2 weeks to 16 months). The predominant presenting symptoms were irritability, pallor, and tachypnoea. The predominant electrocardiogram findings were Q waves and ST segment changes in the anterolateral chest leads. One died from the 11 patients in our series. CONCLUSION: The outcome for surgical re-implantation in infants with a diagnosis of ALCAPA is very good however, early diagnosis is crucial to survival. Although once successfully repaired, patients in general were free of symptoms, ventricular dysfunction was usually present, requiring long-term follow-up.

Calcified occlusion of the right coronary artery in Kawasaki disease: evidence of myocardial ischaemia using cardiac technetium-99m-tetrofosmin perfusion single-photon emission computed tomography.

We report the case of a 14-year-old boy who developed Kawasaki disease at 5 months of age. The patient developed severe aneurysmal disease of both the left and right coronary arteries. He eventually developed total calcified occlusion of the right coronary artery despite long-term treatment with aspirin. Catheterisation showed no antegrade flow into the right coronary artery, with retrograde flow from the left coronary system into the right coronary. At the most recent follow-up he was asymptomatic, with normal exercise tolerance and a negative exercise stress test. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging was carried out during stress and at rest using intravenous persantine (dipyridamole) and technetium-99m tetrofosmin. During stress, there were prominent left ventricular apical and anteroseptal defects, which normalised at rest. SPECT during stress and at rest may detect subclinical ischaemia and influence further management options in such patients.

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior.

Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

Guidelines for the medical management of Irish children and adolescents with Down syndrome.

Down syndrome (DS) is the most common chromosomal cause of developmental disability in Ireland. Children with DS have a high incidence of associated treatable medical disorders where early intervention carries a better outcome. Currently there are no agreed protocols for the screening and management of children and adults with DS in Ireland. A cross-sectional study of 394 children and adolescents was undertaken in the Eastern Regional Health Authority (ERHA) to assess the medical needs of children and adolescents with DS, in order to develop medical management guidelines. This study provides evidence-based data that children and adolescents with DS have a high incidence of treatable medical disorders, which supports the need for the medical management guidelines presented.

Perinatal-lethal Gaucher disease.

Gaucher disease is a lysosomal storage disease caused by glucocerebrosidase deficiency. Although purely visceral in most cases, some Gaucher disease patients have neurological signs. Signs of Gaucher disease appear after a symptom-free period, except in rare cases with fetal onset. The description of such cases was based mainly on single reports and siblings. We report here a series of perinatal-lethal Gaucher disease cases highlighting the specificity of this phenotype. We retrospectively studied eight original cases of proven Gaucher disease with fetal onset. Non-immune hydrops fetalis was present in all cases but one, and associated with hepatosplenomegaly, ichthyosis, arthrogryposis, and facial dysmorphy. The similarities between our cases and 33 previously described cases allow us to better delineate the perinatal-lethal Gaucher disease phenotype. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurological involvement begins in the first week and leads to death within three months. Hepatosplenomegaly is a major sign, and associated with ichthyosis, arthrogryposis, and facial dysmorphy in some 35-43% of cases. Perinatal-lethal Gaucher disease is a specific entity defined by its particular course and signs that are absent in classical type 2 Gaucher disease. Our study provides clues to the diagnosis of this likely underdiagnosed condition, which must be biochemically confirmed in order to propose appropriate genetic counselling.

Review article: altered states of consciousness, theories of recovery, and assessment following a severe traumatic brain injury.

The causes and consequences of severe traumatic brain injury are reviewed, including mechanical injury and neurochemical changes following focal and diffuse injuries. A discussion of terminology seeks to clarify current nomenclature and descriptions of behaviours during emergence from coma. Theories of recovery following severe brain injury are reviewed including diaschisis, plasticity and compensation, redundancy, environmental regulation, and excess disability. Several assessment tools that have been recommended for use with this population of individuals in an altered state of consciousness following coma are discussed and critiqued. They include the Glasgow Coma Scale, Ranchos Los Amigos Levels of Cognitive Functioning Assessment Scale, Western Neuro Sensory Stimulation Profile, Coma Near Coma Scale, Freeman Questionnaire, and the Sensory Modality Assessment Rehabilitation Technique.

Writing for publication.

A discussion of the benefits and obstacles of authoring a paper for a nursing journal is followed by an explanation of the process of writing for publication. Benefits include advancing nursing knowledge and professional recognition of the individual author. The barriers addressed are time, failure to recognize expertise, a reluctance to subject one's work and ideas to the public arena for scrutiny, and lack of confidence with scholarly writing. The discussion focuses on choosing a suitable journal and subject, the role of the editor and peer reviewers in a refereed journal, and a procedure for planning, writing, and editing a paper. The process is addressed both in a generic sense, and specifically when writing a paper for AXON. Strategies to get nurses started with writing, such as critical reading of journal articles individually or with a peer group, writing with a mentor or group, and starting with small projects, are also included.

Directiveness in teachers' language input to toddlers and preschoolers in day care.

Five subtypes of directiveness were examined in the interactions of day care teachers with toddler and preschooler groups. The instructional context (book reading, play dough) yielded significant differences across all five subtypes of directiveness, indicating that these two activities elicited different types of teacher-child discourse. Book reading was characterized by significantly more behavior and response control and less conversation control in comparison with the play-dough activity. Correlations between teachers' directiveness and child language productivity indicated that behavior control and turn-taking control were associated with low levels of productivity, whereas conversation control was associated with the highest levels of productivity. The results of this study confirm that instructional context is an important mediator of teachers' directiveness and suggest that subtypes of directiveness have differential effects on child language output.

Stress incontinence in women under 50: does urodynamics improve surgical outcome?

The aim of the study was to determine whether urodynamic testing improves the outcome of retropubic surgery in women aged 50 or younger. A retrospective study was undertaken of 212 women aged 50 or younger who underwent retropubic surgery at a medical school-affiliated hospital between February 1991 and July 1997. Excluded were patients with prior retropubic urethropexy and known low urethral closure pressures. The surgery was performed by one urogynecologist and two urologists. The minimal evaluation by the urogynecologist was a focused incontinence questionnaire, pelvic neurologic examination, pelvic floor grading, cough stress test, urinalysis, postvoid residual, cotton swab test and supine empty stress test. Full urodynamics consisted of uroflowmetry, subtracted cystometry, urethral closure pressure, cough leak-point pressure and cystourethroscopy. Subjective postoperative follow-up at 14 years was by annual questionnaire. The urogynecologist's patients were in group I (95 women with full urodynamic studies) and group II (36 women with minimal testing). The urologists' patients were in group III (81 women with a very minimal workup and cystourethroscopy). A review of seven variables revealed no difference between the groups. In terms of cured, improved and failed, there was also no difference in outcome. There was a difference in postoperative voiding problems (though not stress incontinence) in group III compared to group I (P= 0.005) and group II (P=0.002). Our conclusion was that all women with stress incontinence should undergo a careful minimal evaluation. In women aged 50 or younger urodynamic studies may be avoided unless there is significant stress incontinence, complex symptoms, a positive supine empty stress test, marked prolapse, or a history of prior retropubic urethropexy.

Spontaneous contractions in elasmobranch vessels in vitro.

Isolated vessels from four elasmobranchs, yellow stingray (Urolophus jamaicensis), clearnose skate (Raja eglanteria), ghost shark (Hydrolagus novaezelandiae), and spiny dogfish (Squalus acanthias), were examined for the presence of spontaneous contractions (SC). SC were observed in otherwise unstimulated dorsal aortas (DA) from stingray and ghost shark, but not in skate DA. Unstimulated ventral aortas (VA) did not exhibit SC. After treatment of VA with a contractile agonist, SC appeared in stingray and skate but not ghost shark or dogfish. SC in stingray VA were subsequently inhibited by either epinephrine (10(-5) M) or indomethacin (10(-4) M). Agonist contraction also elicited strong SC in ductus Cuvier from stingray, but not from ghost shark or dogfish. SC in dogfish hepatic portal veins (HPV) produced a rhythmical oscillation in tension. The frequency of HPV SC was highest (approximately 1 min(-1)) in intact veins and lower (approximately 3 min(-1)) in vein segments, indicative of a dominant pacemaker in the intact vessel. SC in HPV were depressed during the first 30 min of hypoxia, but there was substantial recovery over an additional 30 min of hypoxia and complete recovery upon return to normoxia. Addition of 80 mM KCl completely inhibited HPV SC and lowered resting tone. These results show that SC are a common feature of elasmobranch vessels and there appears to be a correlation between swimming behavior and the propensity for SC. KCl inhibition of SC and tonus in HPV is highly unusual for vascular smooth muscle.

Striae and acne following cardiac surgery in a child.

We report a 13-year-old girl with extensive striae and an acneiform eruption following surgery for complex congenital heart disease. These findings were associated with elevated serum and urinary cortisol levels with loss of diurnal rhythm. The resolution of the eruption and the fading of her striae coincided in time with normalization of her blood parameters on day 72 postoperatively. We conclude that the cause of steroid excess in our patient was stress induced by the cardiac surgery and a complicated and protracted postoperative course. To our knowledge, this is the first report in the English language literature of skin changes due to endogenous hypercortisolaemia caused by intense physical and emotional stress.

The vocal athlete and endotracheal intubation: a management protocol.

Endotracheal intubation is associated with significant laryngeal sequelae that range in severity from mild hoarseness to life-threatening tracheal stenosis. Although the most severe trauma appears to be related to prolonged intubation, even short-term intubation (< 1 day) can adversely affect laryngeal and vocal function. Concern is warranted for all intubated patients, but particularly for the vocal athlete whose livelihood and identity depend on optimal vocal function. It is proposed that the vocal athlete faced with endotracheal intubation risk warrants careful multidisciplinary management. A number of intubation risk factors have been identified in the literature; however, clinical management of vocal athletes who undergo intubation has not been addressed. In medical settings where adverse intubation outcomes can lead to litigation, this clinical management protocol is expected to improve the probability of favorable voice outcome following endotracheal intubation.

Purification and cardiovascular activity of [Met1, Met5]-bradykinin from the plasma of a sturgeon (Acipenseriformes).

The sturgeons (Order Acipenseriformes) are extant representatives of a group of primitive Actinopterygian (ray-finned) fish that probably shared a common ancestor with present-day teleosts. Incubation of heat-denatured plasma from a sturgeon (a hybrid of the shovelnosed sturgeon Scaphirhynchus platorynchus and the pallid sturgeon Scaphirhynchus albus) with either trypsin or porcine pancreatic kallikrein generated bradykinin-like immunoreactivity. The primary structure of sturgeon bradykinin was established as Met-Pro-Pro-Gly-Met-Ser-Pro-Phe-Arg. This amino acid sequence contains two amino acid substitutions (Arg1 --> Met and Phe5 --> Met) compared with mammalian bradykinin. Bolus injections of synthetic sturgeon bradykinin in doses as low as 1 pmol/kg into the dorsal aorta of unanesthetized sturgeon resulted in an immediate and significant fall in arterial blood pressure with a maximum depressor response at 300 pmol/kg. Thus, the cardiovascular response of the sturgeon to bradykinin resembles more closely the response of mammals rather than the predominantly pressor response seen in teleost fish. Sturgeon bradykinin produced a strong and concentration-dependent (EC50 = 4.7 +/- 0.7 x 10(-10) M) relaxation of rings of vascular tissue from the sturgeon ventral aorta that had been pre-contracted with acetylcholine. The data indicate that sturgeon tissues are particularly responsive to native bradykinin and suggest that the kallikrein-kinin system may have evolved before the appearance of the neopterygians (gars, bowfin and teleosts).

New mutations in the KVLQT1 potassium channel that cause long-QT syndrome.

BACKGROUND: Long-QT syndrome (LQTS) is an inherited cardiac arrhythmia that causes sudden death in young, otherwise healthy people. Four genes for LQTS have been mapped to chromosome 11p15.5 (LQT1), 7q35-36 (LQT2), 3p21-24 (LQT3), and 4q25-27 (LQT4). Genes responsible for LQT1, LQT2, and LQT3 have been identified as cardiac potassium channel genes (KVLQT1, HERG) and the cardiac sodium channel gene (SCN5A). METHODS AND RESULTS: After studying 115 families with LQTS, we used single-strand conformation polymorphism (SSCP) and DNA sequence analysis to identify mutations in the cardiac potassium channel gene, KVLQT1. Affected members of seven LQTS families were found to have new, previously unidentified mutations, including two identical missense mutations, four identical splicing mutations, and one 3-bp deletion. An identical splicing mutation was identified in affected members of four unrelated families (one Italian, one Irish, and two American), leading to an alternatively spliced form of KVLQT1. The 3-bp deletion arose de novo and occurs at an exon-intron boundary. This results in a single base deletion in the KVLQT1 cDNA sequence and alters splicing, leading to the truncation of KVLQT1 protein. CONCLUSIONS: We have identified LQTS-causing mutations of KVLQT1 in seven families. Five KVLQT1 mutations cause the truncation of KVLQT1 protein. These data further confirm that KVLQT1 mutations cause LQTS. The location and character of these mutations expand the types of mutation, confirm a mutational hot spot, and suggest that they act through a loss-of-function mechanism or a dominant-negative mechanism.

Tissue and whole-body extracellular, red blood cell and albumin spaces in the rainbow trout as a function of time: a reappraisal of the volume of the secondary circulation

[58Co]EDTA, [51Cr]RBC and [125I]albumin spaces in the whole body and 28 tissue samples were examined at timed intervals over 16 h in rainbow trout Oncorhynchus mykiss. [58Co]EDTA space (which approximates extracellular fluid volume; ECF) in fins, skin, gallbladder and eye are reported for the first time. After a 16 h equilibration, ECF volume was large (376-726 microl g-1 wet tissue mass) in kidney, swimbladder, skin and fins, moderate (219-313 microl g-1 wet tissue mass) in stomach, skull, spleen, liver, intestine, gills, eye and cecum, and small (53-181 microl g-1 wet tissue mass) in red muscle, fat, brain, gallbladder and white muscle. Whole-body ECF was 387+/-10.6 microl g-1 (mean +/- s.e.m.; N=11). [51Cr]RBC space relative to [58Co]EDTA space was large in spleen, liver, intestine and gill, and low in skin, fins, stomach and skull. Whole-body [51Cr]RBC space was 9.9+/-0.6 microl g-1 body mass (N=17). Blood volume calculated from [51Cr]RBC space at 16 h and a dorsal aortic hematocrit of 24.5 % was 40.4 microl g-1 body mass. Whole-body [125I]albumin space at 16 h was 118.0+/-7.4 microl g-1 body mass (N=6), which resulted in an estimated blood volume of 156. 6 microl g-1 body mass, nearly four times that estimated from the [51Cr]RBC space. Tissue hematocrits, calculated from [125I]albumin and [51Cr]RBC spaces, were significantly lower than dorsal aortic hematocrit in all tissues except spleen, kidney and liver. [58Co]EDTA and [51Cr]RBC spaces reached equilibrium in nearly all tissues within 1 h, whereas [125I]albumin continued to accumulate in many tissues up 24 h. The disparity between [125I]albumin distribution kinetics compared with the kinetics of [58Co]EDTA and [51Cr]RBC distribution, as well as the accumulation of [125I]albumin in tissues not known to have a secondary circulation, indicates that [125I]albumin is a poor marker of plasma volume in trout and that previous studies based on [125I]albumin clearance from the plasma have overestimated both the volume and the turnover rate of the secondary system. Revised estimates of secondary circulation volume, based on [58Co]EDTA distribution rate, indicate that it is no more than 10-20 % of the volume of the primary circulation.