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Prognostic value of left ventricular diastolic function and association with heart rate variability after a first acute myocardial infarction.

OBJECTIVE: To study the prognostic value of left ventricular (LV) diastolic function and its relation with autonomic balance expressed by heart rate variability (HRV) in patients after a first acute myocardial infarction. DESIGN: The study population consisted of 64 consecutive patients with first acute myocardial infarction and 31 control subjects. Long and short term HRV indices were evaluated by 24 hour Holter monitoring, and LV systolic and diastolic function were assessed by two dimensional and Doppler echocardiography before discharge. Patients were divided into two groups: those with restrictive LV filling characteristics (deceleration time </= 140 ms) and those with non-restrictive LV filling characteristics (deceleration time > 140 ms). RESULTS: Both long and short term HRV indices were significantly reduced in patients with restrictive LV filling compared with the non-restrictive group and control subjects. Mitral deceleration time and isovolumetric relaxation time correlated weakly but significantly with all indices of HRV whereas ejection fraction correlated weakly with the long term HRV indices. The mean follow up time was 14.9 (8.7) months. Multivariate analysis showed that mitral deceleration time (chi(2) = 6.4, p < 0.001) and ejection fraction </= 40% (chi(2) = 4.4, p < 0.05) were independent predictors of cardiac death and readmission to hospital with congestive heart failure. CONCLUSIONS: A restrictive LV filling pattern was found to be the strongest predictor of adverse outcome independent of HRV and ejection fraction during follow up after a first acute myocardial infarction. Patients with restrictive LV filling characteristics had more reduced HRV than those with non-restrictive diastolic filling.

Adult↗

N-terminal proatrial natriuretic peptide correlates with systolic dysfunction and left ventricular filling pattern in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP). METHODS: 32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay. RESULTS: Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0. 001), left ventricular ejection fraction (r = -0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001). CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.

Aged↗

Comparative performance of playground surfacing materials including conditions of extreme non-compliance.

OBJECTIVE: A recent case series study found that only 4.7% of 402 playgrounds in which arm fractures occurred in Victorian schools complied with the recommended 20 cm depth of tanbark. Tanbark depths at fall sites varied between 0-27 cm and the mean was 11.1 (5.0) cm. The purposes of the present study were to (1) measure impact attenuation properties of shallow and compacted depths of tanbark; (2) validate laboratory measurements with in situ data; (3) compare impact attenuation properties of compacted tanbark with an Australian manufactured rubber based surface material; and (4) study the impact performance of rubber and tanbark hybrid surfacing. METHODS: A standard test headform was dropped on tanbark and rubber surfaces in a laboratory setting to measure peak impact deceleration and head injury criterion (HIC) values. Variations in surface depth ranged from 2 cm-20 cm (tanbark) and 2 cm-9 cm (rubber). Drop height ranged from 0.5 m-2.5 m. RESULTS: Peak deceleration and HIC increased with increasing drop height and decreasing surface depth. Laboratory measurements at depths less than 8 cm overestimated peak deceleration and HIC values compared with in situ playground measurements. Impact attenuation of a 9 cm thick bilaminate rubber material was comparable to that of an 18 cm depth of compacted tanbark. Rubber-tanbark hybrid surfaces showed improved impact attenuation over individual surfaces. CONCLUSIONS: Compacted tanbark of depth less than 8 cm is ineffective in attenuating playground falls, resulting in excessive impact deceleration and HIC values. Shallow and compacted tanbark found in many Victorian school playgrounds poses a high risk for severe head injury. This calls for stricter enforcement of playground surface depth compliance.

Accident Prevention↗

Development of heart rate irregularities in chick embryos.

Heart rate (HR) irregularities in chick embryos were defined as large fluctuations (>10 beats/min) comprising irregular, brief deceleration and/or acceleration of instantaneous HR (IHR). IHR was determined directly from the arterial blood pressure while adequate gas exchange was maintained through an eggshell and chorioallantoic membrane. Five embryos were examined on each day from day 11 to day 19 of incubation. Baseline HR was stable until day 12-13, and on around day 13-14 transient, rapid deceleration of HR (termed V pattern) began to appear, with a subsequent increase in its frequency and magnitude. The acceleration patterns (lambda, avian omega, and periodic patterns) appeared later, and the IHR became increasingly irregular, with additional, spontaneous deceleration and acceleration patterns toward hatching. Additional experiments with intravenous administration of autonomic drugs clearly showed that rapid deceleration of HR was mediated by parasympathetic nervous function but did not always show clear relations of sympathomimetic and sympathetic blocking agents to the acceleration patterns.

Allantois↗

Comparing acceleration and speed tuning in macaque MT: physiology and modeling.

Studies of individual neurons in area MT have traditionally investigated their sensitivity to constant speeds. We investigated acceleration sensitivity in MT neurons by comparing their responses to constant steps and linear ramps in stimulus speed. Speed ramps constituted constant accelerations and decelerations between 0 and 240 degrees /s. Our results suggest that MT neurons do not have explicit acceleration sensitivity, although speed changes affected their responses in three main ways. First, accelerations typically evoked higher responses than the corresponding deceleration rate at all rates tested. We show that this can be explained by adaptation mechanisms rather than differential processing of positive and negative speed gradients. Second, we inferred a cell's preferred speed from the responses to speed ramps by finding the stimulus speed at the latency-adjusted time when response amplitude peaked. In most cells, the preferred speeds inferred from deceleration were higher than those for accelerations of the same rate or from steps in stimulus speed. Third, neuron responses to speed ramps were not well predicted by the transient or sustained responses to steps in stimulus speed. Based on these findings, we developed a model incorporating adaptation and a neuron's speed tuning that predicted the higher inferred speeds and lower spike rates for deceleration responses compared with acceleration responses. This model did not predict acceleration-specific responses, in accordance with the lack of acceleration sensitivity in the neurons. The outputs of this single-cell model were passed to a population-vector-based model used to estimate stimulus speed and acceleration. We show that such a model can accurately estimate relative speed and acceleration using information from the population of neurons in area MT.

Acceleration↗

Movement and electromyographic disorders associated with cerebellar dysmetria.

The objective of these experiments was to determine whether dysmetric elbow flexions, which occurred during cerebellar dysfunction, had the same kinematic and electromyographic characteristics as movements of the same amplitude and velocity performed under normal conditions. Reversible cerebellar lesions were produced by cooling through two probes implanted on either side of the dentate nucleus in five Cebus albifrons monkeys. Normal, fast, and accurate elbow flexions had single-peaked velocities and a bi- or triphasic EMG pattern in agonist and antagonist muscles. During cerebellar dysfunction movements became ataxic. Ataxic movements were classified into two categories: those with oscillations (tremor) during the movement and those without oscillations. A terminal tremor occurred after both types of movements. Oscillations during movements were more likely to occur when a constant force loaded the antagonist. Addition of mass to the handle attenuated or abolished the oscillations. Movements with oscillations reached the target with increased variability of end position, whereas movements without oscillations were often hypermetric. The movement parameters and EMG patterns associated with flexions without oscillations during the movement were studied in detail. A characteristic of these movements was that the acceleration and deceleration phases were asymmetric. Compared with control movements of the same peak velocity, they had smaller magnitudes of acceleration and larger magnitudes of deceleration. The large deceleration was abnormal because it initiated the terminal tremor. The disorder in acceleration was associated with agonist EMG activity that was less abrupt in onset, smaller in magnitude, and more prolonged in duration. The disorder in deceleration was associated with delayed onset of phasic antagonist EMG activity. The results show that hypermetric arm movements without oscillations have different properties than those of normal movements of similar velocity and amplitude. Thus it is unlikely that dysmetria results from inappropriate selection or triggering of an otherwise normal motor program. We conclude that normal function of the cerebellum is necessary for the generation of agonist and antagonist muscle activity that is both of the appropriate magnitude and timing to control the dynamic phase of arm movements.

Animals↗

Noninvasive evaluation of aortic regurgitation by continuous-wave Doppler echocardiography.

Continuous-wave Doppler echocardiography was used to examine the aortic regurgitant flow velocity pattern in 32 patients with aortic regurgitation (AR) and 10 patients without AR. The aortic regurgitant flow velocity patterns, characterized by a rapid rise in flow velocity immediately after closure of the aortic valve, high peak flow velocity, and a gradual deceleration until the next aortic valve opening, were successfully obtained in 30 of the 32 patients with AR (sensitivity 94%, specificity 100%). The velocity decline was greater in patients with severe AR; thus, the slope of the velocity decline (deceleration) and the time to decline to half the peak velocity (half-time index) were measured from the flow velocity pattern. The deceleration became greater and the half-time index shortened in accordance with angiographic grading of AR (p less than .01). The deceleration and the half-time index also correlated well with the aortic regurgitant fraction (r = .79, p less than .01; r = -.89, p less than .01). Because the half-time index could be measured easily and independently of Doppler incident angle, it seemed a simple and accurate index of assessing the severity of AR. Thus continuous-wave Doppler echocardiography permitted the noninvasive evaluation of AR.

Adult↗

Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography. Effect of different loading conditions.

It has previously been demonstrated that predictable changes occur in mitral flow velocities under different loading conditions. The purpose of this study was to relate changes in pulmonary venous and mitral flow velocities during different loading conditions as assessed by transesophageal echocardiography in the operating room. Nineteen patients had measurements of hemodynamics, that is, mitral and pulmonary vein flow velocities during the control situation, a decrease in preload by administration of nitroglycerin, an increase in preload by administration of fluids, and an increase in afterload by infusion of phenylephrine. There was a direct correlation between the changes in the mitral E velocity and the early peak diastolic velocity in the pulmonary vein curves (r = 0.61) as well as a direct correlation between the deceleration time of the mitral and pulmonary venous flow velocities in early diastole (r = 0.84). This indicates that diastolic flow velocity in the pulmonary vein is determined by the same factors that influence the mitral flow velocity curves. A decrease in preload caused a significant reduction in the initial E velocity and prolongation of deceleration time, and an increase in preload caused an increase in E velocity and shortening of deceleration time. An increase in afterload produced a variable effect on the initial E velocity and deceleration time and was dependent on the left ventricular filling pressure. The change in systolic forward flow velocity in the pulmonary vein was directly proportional to the change in cardiac output (r = 0.60). The pulmonary capillary wedge pressure correlated best with the flow velocity reversal in the pulmonary vein at atrial contraction (r = 0.81). Use of pulmonary vein velocities in conjunction with mitral flow velocities can help in understanding left ventricular filling.

Aged↗

Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study.

BACKGROUND: We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. METHODS AND RESULTS: We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. CONCLUSIONS: Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.

Amyloidosis↗

Change in diastolic left ventricular filling after one year of antihypertensive treatment: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study.

BACKGROUND: It is well established that hypertensive patients with left ventricular (LV) hypertrophy have impaired diastolic filling. However, the impact of antihypertensive treatment and LV mass reduction on LV diastolic filling remains unclear. METHODS AND RESULTS: Echocardiograms were recorded in 728 hypertensive patients with ECG-verified LV hypertrophy (Cornell voltage-duration or Sokolow-Lyon) at baseline and after 1 year of blinded treatment with either losartan or atenolol-based regimen. Systolic and diastolic blood pressures (BP) were reduced on average 23/11 mm Hg; isovolumic relaxation time and E/A ratio became more normal, and LV inflow deceleration time prolonged (all P<0.001). Directionally opposite changes in isovolumic relaxation time (IVRT) and deceleration time indicate improvement in active LV relaxation and passive chamber stiffness during early diastole. Prevalences of normal LV filling increased, abnormal relaxation and pseudonormalization decreased, and restrictive filling pattern remained unchanged (P<0.05). Patients with reduction in LV mass had smaller left atrial diameter, shortened IVRT, increased E/A ratio, and prolonged LV inflow deceleration time (all P<0.001). Patients without LV mass reduction had no change in diastolic filling parameters (P=NS). IVRT shortening was independently associated with reduction in LV mass. Increase in E/A ratio was independently associated with reduction in diastolic BP, and increase in the deceleration time was independently associated with reduced end-systolic relative wall thickness. CONCLUSIONS: Antihypertensive therapy resulting in LV mass or relative wall thickness regression is associated with significant improvement of diastolic filling parameters related to active relaxation and passive chamber stiffness compared with patients without regression, independent of BP reduction; however, abnormalities of diastolic LV filling remain common.

Aged↗

Stress distribution in the superior labrum during throwing motion.

BACKGROUND: Superior labrum anterior posterior lesions are common among athletes participating in overhead throwing sports. One described mechanism of injury is application of high local stress via repetitive loading of the long head of the biceps tendon attached to the superior labrum; however, the stress environment within the labrum has not been investigated to date. HYPOTHESIS: Biceps origin locations and throwing phases determine the stress distributions causing lesions of the superior labrum within the labrum itself. STUDY DESIGN: Descriptive laboratory study. METHODS: Three-dimensional finite element models of the labrum glenoid complex with anterior, central, and posterior biceps origins were developed at 4 orientations to simulate the phases of pitching: early cocking, late cocking, acceleration, and deceleration. RESULTS: The stress magnitudes at the labrum glenoid interface for the deceleration phase were highest for all biceps origins. Anatomical variations of the biceps insertion affected the stress only during the deceleration phase. Both the biceps origin and throwing phase influenced the location of high stress. CONCLUSION: Deceleration could be the throwing phase that causes tearing at the superior labrum. This finding provides further understanding for localizing the possible initiation of superior labrum anterior posterior lesions.

Arm↗

Long-term experimental evolution in Escherichia coli. XI. Rejection of non-transitive interactions as cause of declining rate of adaptation.

BACKGROUND: Experimental populations of Escherichia coli have evolved for 20,000 generations in a uniform environment. Their rate of improvement, as measured in competitions with the ancestor in that environment, has declined substantially over this period. This deceleration has been interpreted as the bacteria approaching a peak or plateau in a fitness landscape. Alternatively, this deceleration might be caused by non-transitive competitive interactions, in particular such that the measured advantage of later genotypes relative to earlier ones would be greater if they competed directly. RESULTS: To distinguish these two hypotheses, we performed a large set of competitions using one of the evolved lines. Twenty-one samples obtained at 1,000-generation intervals each competed against five genetically marked clones isolated at 5,000-generation intervals, with three-fold replication. The pattern of relative fitness values for these 315 pairwise competitions was compared with expectations under transitive and non-transitive models, the latter structured to produce the observed deceleration in fitness relative to the ancestor. In general, the relative fitness of later and earlier generations measured by direct competition agrees well with the fitness inferred from separately competing each against the ancestor. These data thus support the transitive model. CONCLUSION: Non-transitive competitive interactions were not a major feature of evolution in this population. Instead, the pronounced deceleration in its rate of fitness improvement indicates that the population early on incorporated most of those mutations that provided the greatest gains, and subsequently relied on beneficial mutations that were fewer in number, smaller in effect, or both.

Adaptation, Physiological↗

Final height in girls with central idiopathic precocious puberty treated with gonadotropin-releasing hormone analog and oxandrolone.

CONTEXT: GnRH analogs (GnRHa) are considered the treatment of choice for central precocious puberty (CPP). During GnRHa administration, the suppression of the pituitary-gonadal axis results in decreased rates of linear growth and skeletal maturation and in improved adult height. However, in some patients, the growth deceleration is so marked that the expected improvement in predicted adult height is not achieved. OBJECTIVE: The objective of this study was to assess whether the addition of oxandrolone (Ox) may affect the height outcome of patients with CPP and growth deceleration during GnRHa treatment. DESIGN: This was an open-label, clinical study. SETTING: The study was performed at a pediatric endocrinology referral clinic. PATIENTS: Twenty patients with CPP and marked growth deceleration during GnRHa treatment were studied. INTERVENTIONS: Treatment consisted of GnRHa (Leuprorelina, 3.75 mg im every 28 d) alone (10 patients) or in combination with Ox (0.06 mg/kg.d by mouth) (10 patients). MAIN OUTCOME MEASURE: The main outcome measure was the patients' adult height. RESULTS: The adult height of the patients treated with GnRHa plus Ox was significantly higher than pretreatment predicted adult height (162.6 +/- 2.3 vs. 154.8 +/- 1.7 cm, mean +/- sem; P < 0.05) and target height (162.6 +/- 2.3 vs. 158.0 +/- 1.9; P > 0.05). Patients treated with GnRHa alone reached an adult height similar to the pretreatment predicted adult height (151.9 +/- 1.2 vs. 155.4 +/- 2.1 cm) but significantly lower than target height (151.9 +/- 1.2 vs. 156.6 +/- 1.4 cm; P < 0.005). No side effects were recorded in either group of patients. CONCLUSIONS: Combined GnRHa and Ox therapy is a viable treatment option for children with CPP and marked growth deceleration during treatment with GnRHa alone.

Anabolic Agents↗

Ventilation-perfusion distribution related to different inspiratory flow patterns in experimental lung injury.

UNLABELLED: In acute lung injury (ALI), controlled mechanical ventilation with decelerating inspiratory flow (.V(dec)) has been suggested to improve oxygenation when compared with constant flow (.V(con)) by improving the distribution of ventilation and perfusion (.V(A)/.Q). We performed the present study to test this hypothesis in an animal model of ALI. Furthermore, the effects of combined decelerating and constant flow (Vdot;(deco)) were evaluated. Thus, 18 pigs with experimental ALI were randomized to receive mechanical ventilation with either .V(con), .V(dec) or a fixed combination of both flow wave forms (.V(deco)) at the same tidal volume and positive end-expiratory pressure level for 6 h. Hemodynamics, gas exchange, and .V(A)/.Q distribution were determined. The results revealed an improvement of oxygenation resulting from a decrease of pulmonary shunt within each group (P < 0.05). However, blood flow to lung areas with a normal .V(A)/.Q distribution increased only during ventilation with .V(con) (P < 0.05). Accordingly, PaO(2) was higher with .V(con) than with .V(dec) and .V(deco) (P < 0.05). We conclude that contrary to the hypothesis, .V(con)provides a more favorable .V(A)/.Q distribution, and hence better oxygenation, when compared with .V(dec) and .V(deco) in this model of ALI. IMPLICATIONS: In acute lung injury, mechanical ventilation with decelerating flow has been suggested to improve ventilation-perfusion distribution when compared with constant flow. We tested this hypothesis in an animal model. Contrary to the hypothesis, we found a more favorable ventilation-perfusion distribution during constant flow when compared with decelerating flow.

Airway Resistance↗

Ground forces applied by galloping dogs.

The gallop differs from most other quadrupedal gaits in that each limb plays a unique role. This study compares the ground forces applied by the four limbs and uses force differences between limbs to address the question of why the gallop is the fastest quadrupedal gait. Individual ground forces were recorded from each of the four limbs as six dogs galloped down a runway at constant speed. Trials were videotaped at high speed using a camera positioned perpendicular to the runway, and velocity was measured using photosensors. The trailing forelimb applied greater peak vertical forces than the lead forelimb, however the vertical impulses from the two forelimbs were similar because the lead forelimb had a longer contact interval. The trailing forelimb and lead hindlimb applied greater peak accelerating forces and accelerating force impulses than their contralateral limbs despite their tendency to have shorter contact intervals. The accelerating impulse of both forelimbs combined did not differ significantly from that of both hindlimbs. The forelimbs applied a greater decelerating impulse than the hindlimbs, such that their net fore-aft impulse was decelerating whereas that of the hindlimbs was accelerating. The greater accelerating impulse applied by the trailing forelimb and greater decelerating impulse applied by the lead forelimb are consistent with the forelimbs acting as elastic struts rather than being actively retracted. In contrast, greater accelerating forces were produced by the lead hindlimb while the center of mass was lifted, suggesting that the hindlimbs are more actively extended or retracted during stance. The differences in ground forces measured between paired limbs suggest that the lead forelimb and trailing hindlimb are limited in their ability to apply forces by their positions in the stride cycle rather than by their muscular capacity. Although a bound or half-bound would allow more limbs to produce their maximal forces, a gallop may generate higher speeds because it is more efficient. Galloping could be more efficient than other gaits involving sagittal bending if the increased number of ground contact intervals decreased either the decelerating forces applied at the onset of ground contact or the vertical motion of the center of mass.

Animals↗

Genetic study of the height and weight process during infancy.

Longitudinal height and weight data from 4649 Dutch twin pairs between birth and 2.5 years of age were analyzed. The data were first summarized into parameters of a polynomial of degree 4 by a mixed-effects procedure. Next, the variation and covariation in the parameters of the growth curve (size at one year of age, growth velocity, deceleration of growth, rate of change in deceleration [i.e., jerk] and rate of change in jerk [i.e., snap]) were decomposed into genetic and nongenetic sources. Additionally, the variation in the estimated size at birth and at 2 years of age interpolated from the polynomial was decomposed into genetic and nongenetic components. Variation in growth was best characterized by a genetic model which included additive genetic, common environmental and specific environmental influences, plus effects of gestational age. The effect of gestational age was largest for size at birth, explaining 39% of the variance. The differences between monozygotic and dizygotic twin correlations were largest for size at 1 and 2 years of age and growth velocity of weight, which suggests that these parameters are more influenced by heritability than size at birth, deceleration and jerk. The percentage of variance explained by additive genetic influences for height at 2 years of age was 52% for females and 58% for males. For weight at 2 years of age, heritability was approximately 58% for both sexes. Variation in snap height for males was also mainly influenced by additive genetic factors, while snap for females was influenced by both additive genetic and common environmental factors. The correlations for the additive genetic and common environmental factors for deceleration and snap are large, indicating that these parameters are almost entirely under control of the same additive genetic and common environmental factors. Female jerk and snap, and also female height at birth and height at 2 years of age, are mostly under control of the same additive genetic factor.

Adolescent↗

GH and GnRH analog treatment in children who enter puberty at short stature.

It is well known that height at the onset of puberty is closely related to final height. To improve final height of short children who enter puberty at short stature, twenty-one short boys and six short girls were treated with a combination of GH and GnRH analog. The boys started the combination treatment at a mean age of 12.0 years when their mean height was 128.5 cm (-2.74 SD) and the girls at a mean age of 10.68 years when their mean height was 126.4 cm (-2.23 SD). The boys discontinued GnRH at a mean age of 16.88 years after a mean treatment period of 4.89 years when their height was 153.7 cm (-2.75 SD), and the girls at a mean age of 13.89 years after a mean treatment period of 3.20 years when their height was 143.3 cm (-1.94 SD). Bone age maturation significantly decelerated during the combination treatment. Bone age rarely exceeded 14 years in boys and did not exceed 13 years in girls. Bone age maturation during combination treatment decelerated after bone age 12 years in boys and 10.5 years in girls. On average, bone age matured at a mean rate of 0.48 years a year in boys and 0.56 years a year in girls during the combination treatment. During the combination treatment, height velocity did not decelerate rapidly and remained at 3-5 cm/year for a longer duration because of the bone age deceleration, although a definite pubertal growth spurt was not observed. As a consequence, the mean projected height SDS for bone age increased 1.50 (+/- 0.76) SD in boys and 1.24 (+/- 0.49) SD during the combination treatment. Although most of the patients have not yet reached their final height, combined GnRH analog and GH treatment should increase the pubertal height gain and the adult height in short children who enter puberty early for height, when the post-GST growth is taken into account. The combination treatment seems more effective in boys than in girls. This improvement is attributed to the lengthening of the treatment period by slower bone maturation and maintained growth velocity.

Administration, Intranasal↗

Innominate artery occlusive disease: sonographic findings.

OBJECTIVE: The objective of this study was to report the sonographic abnormalities in a group of patients with angiographically proven innominate artery stenosis and occlusion. MATERIALS AND METHODS: A review of all cerebrovascular sonograms at our institutions was undertaken to identify patients with complete or partial flow reversal in the right vertebral artery and reversal or midsystolic deceleration of flow in any one of the three major segments of the right carotid system (common, internal, or external carotid artery). The distribution and appearance of these abnormalities was evaluated, and the presence or absence of tardus-parvus waveforms was noted in any segment of the right carotid artery. Additionally, a left to right common carotid peak systolic velocity ratio (LCCA/RCCA) was calculated and compared to published normal values. All patients had correlative contrast or MR angiography. Correlation was made between the severity of stenosis as determined by angiographic images and waveform aberrations as well as the more objective LCCA/RCCA ratios. RESULTS: Twelve patients were identified as having the abnormalities described above in the right vertebral and carotid arteries. Doppler waveforms from the right vertebral artery revealed that eight of the 12 patients had complete reversal of flow at rest. Bidirectional flow was found in the remaining four as manifested by the presence of marked midsystolic deceleration. In the carotid arteries, one patient had complete reversal of flow in all segments of the right carotid system. Waveforms with midsystolic deceleration were identified in at least one of the carotid arteries of the remaining 11 patients: common carotid artery (8/11 = 73%), internal carotid artery (10/11 = 91%), external carotid artery (3/11 = 27%). The average LCCA/RCCA was 3.1 with a range of 1.7 to 5.7 (normal = 0.7-1.3). All patients had severe innominate artery disease (from 70% to occlusion) by contrast angiography or MR angiography. There was no correlation between the angiographically determined degree of stenosis and the Doppler findings. CONCLUSION: A distinctive pattern of hemodynamic alterations occurs in the right vertebral and carotid arteries of patients with severe innominate artery disease. Findings include reversed or bidirectional flow in the right vertebral artery, the presence of midsystolic deceleration in any of the branches of the right carotid system, and elevated LCCA/RCCA ratio.

Aged↗