Neurophysiological indices of language impairment in children.

Recent investigations of children with specific language impairment (SLI) have found deviant anatomical asymmetry of the perisylvian cortex. These studies argue that this deviant anatomical asymmetry is linked to the language disorders of SLI children. To date no studies have examined whether deviant functional asymmetry underlies the processing of spoken language in these children. In the current study, brain-electrical activity was recorded from 31 scalp sites while children with SLI listened to auditorally presented stories and two different nonsense contexts. Electrical activity was time-locked to the grammatical word "the" in these contexts. The SLI children showed reversed asymmetry compared to control children from 200 ms to 400 ms in processing "the" in all contexts. More specifically, they showed depressed processing at the left temporal scalp site (T7) and enhanced processing at the right temporal site (T8). The second spatial derivative (the Laplacian) of the voltage activity was calculated to remove constant voltage potential and uniform changes in voltage potential across the scalp. The Laplacian analysis indicated that the sources of the positive electrical activity seen at the temporal electrode sites T7 and T8 are the lateral surfaces of the temporal cortices. A comparison of the scalp topography of the voltage potentials and Laplacian also suggests that children with SLI lack some contribution from a deep neural generator, possibly in the hippocampus or basal ganglia. This investigation is the first to demonstrate a direct link between deviant neurophysiological asymmetry and the processing of spoken language in children with SLI.

A preliminary account of phonological and morphophonological perception in young children with and without otitis media.

This investigation examined the effects of otitis media with effusion (OME) and its associated fluctuating conductive hearing loss on the perception of phonological and morphophonological /s/ and /z/ in young children. We predicted that children free of OME (OME-) would perform better than children with histories of OME (OME+). We also predicted that for the OME+ group morphological perception would be harder than phonological perception, because the former category carries an additional linguistic load (i.e., plurality). Sixteen children, ages 26 to 28 months (M = 26.5, SD = 0.6) were divided into two groups, the OME- (n = 8) and OME+ (n = 8) based on OME history during the first year of life. Subjects in the OME- group were free of the disease for 4/5 visits and pure tone average (PTA) was 12.6 dB HL (SD = 4.8). Subjects in the OME+ group had the disease on 3/5 visits and PTA was 23 dB HL (SD = 2.7). Experimental stimuli were six monosyllabic novel word-pairs. Members of each word-pair differed only in the presence of final voiced or voiceless fricative, marking the targets phonologically (e.g., [g [symbol: see text]]/[g [symbol: see text] s] as in 'law', 'loss') or morphophonologically (e.g., [daep]/[daeps] as in 'map' 'maps'). Subjects were taught the unfamiliar word pairs using a fast mapping procedure. Perception was tested with the bimodal preferential looking paradigm. Children in the OME- group performed significantly better than their OME+ counterparts. Individual word-pair analyses showed that OME+ group performed more poorly than the OME- group on one phonological and on two morphological targets, all ending with [s]. For the OME+ group, targets with final [s] posed greater difficulty than those with final [z], especially on morphophonological plural-(s) targets. The results suggested that the fluctuating hearing loss associated with OME might have a negative impact on speech perception.

Deviant neurophysiological asymmetry in children with language impairment.

Deviant anatomical asymmetry of perisylvian cortex is argued to be linked to specific language impairment (SLI). However, no studies have examined whether deviant functional asymmetry underlies the processing of spoken language. In the current study, brain-electrical activity was recorded from 31 scalp sites to the function word 'the' embedded in auditorally presented stories and nonsense contexts. The SLI children showed reversed asymmetry at electrode sites over temporal cortex compared to control children in processing this word in all contexts. They also appear to lack some contribution from a deep neural generator in processing 'the' in the story. This investigation is the first to demonstrate a direct link between deviant neurophysiological asymmetry and the processing of spoken language in children with SLI.

Speech perception and verbal memory in children with and without histories of otitis media.

Two groups of children, with (n = 7) and without (n = 7) first-year histories of otitis media, were participants in a longitudinal study that included periodic audiological and medical evaluations during the first year of life. At age 9, these children were tested on a series of speech perception and verbal short-term memory tasks using stimuli of varying degrees of phonetic contrast. Although the otitis-positive group performed less accurately than the otitis-free group, the pattern of errors was the same for the two groups. The performances of the children with and without positive histories of otitis media were negatively affected by an increase in phonetic similarity of the stimulus items. The two groups, however, did not differ on identification or on temporal-order recall when the speech sounds were differentiated by multiple features. These findings provide evidence of subtle, long-term effects of early episodes of otitis media on phonological representations and on working memory.

Cardiac function, perfusion, and morbidity in irradiated long-term survivors of Hodgkin's disease.

PURPOSE: The incidence of cardiotoxicity and clinical cardiac events following mantle irradiation (RT) in patients with Hodgkin's disease using modern techniques is controversial. The use of quantitative, prognostically validated noninvasive tests to assess systolic and diastolic cardiac function and regional myocardial blood flow may reveal preclinical abnormalities associated with subsequent clinical events of myocardial infarction, cardiac death, or angina. The goals of this study are to determine, through noninvasive measures, the presence and time course of alterations in cardiac systolic and diastolic function and of relative myocardial blood flow in long-term survivors of Hodgkin's disease, and assess their correlation with subsequent clinical cardiac end points. METHODS AND MATERIALS: Equilibrium radionuclide angiocardiography (ERNA) was used to assess left ventricular (LV) systolic and diastolic function by measuring LV ejection fraction (LVEF) and peak filling rate (PFR), respectively, in patients without known ischemic heart disease who received RT. Electrocardiography was performed to assess electrical cardiac function under conditions of rest and either exercise or dipyridamole vasodilator stress. Quantitative rest/stress myocardial perfusion imaging with thallium-201 and/or Tc-99m sestamibi was used to assess myocardial perfusion. Patients at least 1.0 year after RT were eligible if they were <50 years old at RT, had no known cardiac disease, and remained free of clinical recurrence of Hodgkin's disease. Fifty patients, ages 10.2-46.1 years (mean 26.0 +/- 8.6) at RT, were tested 1.1 to 29.1 years (mean 9.1 +/- 7.5) after RT. Seventeen of these patients were tested two times separated by 1.1 to 8.1 years. The mean central cardiac RT dose was 35.1 +/- 7.8 Gy (range 18.5-47.5) in daily 15-2.0 Gy fractions. Twelve patients were concomitantly irradiated to the left ventricle, usually through partial transmission left lung shields (mean 17.0 +/- 2.2 Gy, range 14.3-21.3). RESULTS: No patients had signs or symptoms of cardiac disease at the time of evaluation. The mean LVEF at the time of initial testing was 59.6 +/- 6.2% (n = 50; range 42-73%; normal > or =50%), and the mean peak filling rate (PFR) was 3.46 +/- 0.88 end diastolic volumes per second (EDV/s) (range 1.5-5.4 EDV/s; normal > or =2.54 EDV/s). The 12 patients also treated to the left ventricle had a normal mean ejection fraction that was lower (56.6 +/- 5.0%) than that of the other 38 patients (LVEF = 60.6 +/- 6.3%, p = 0.051) when initially evaluated. Average PFR was similar in the two groups. For the 15 patients who had repeat tests, changes in LVEF were generally modest in individual patients, and there was no change in the group mean. For all patients, no significant association was found between cardiac function indices and age at RT, dose, or interval from RT to testing. Myocardial perfusion scintigraphy demonstrated mild ischemia in one or more segments in two patients, and borderline normal perfusion in three patients. Rest and stress ECG testing demonstrated mild repolarization abnormalities in three, and one patient was abnormal at rest and had nondiagnostic changes with stress. CONCLUSIONS: Patients irradiated to the heart incidental to the treatment of Hodgkin's disease using modern techniques have generally normal measures of left ventricular function and myocardial perfusion. Modest differences in the normal left ventricular ejection fraction observed may be attributable to the cardiac volume irradiated. Some patients may manifest improved cardiac function as time from RT elapses, while a significant deterioration of ejection fraction was not observed and reduction in diastolic peak filling rate is uncommon. The previously reported increased risk of cardiac death may relate to use of older techniques of RT employing higher doses and lack of cardiac shielding, and uncontrolled patient selection with additional behaviors and cardiac risk factors.

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease.

PURPOSE: a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients. METHODS AND MATERIALS: 475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis. RESULTS: Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at least one major vessel in 11 patients (73%), and no single artery was more commonly stenosed. Specifically, the left anterior descending and right coronary arteries were each greater than or equal to 60% stenosed in 10 out of 15 patients (67%), and either the left main or circumflex arteries were greater than or equal to 50% stenosed in 5 out of 15 patients (33%); triple vessel disease was present in seven patients. Risk factor data were available on all patients experiencing morbid cardiac events: 72% smoked, 72% were male, 78% had hypercholesterolemia, 61% were obese, 28% had a positive family history, 33% had hypertension, and 6% (one) had diabetes. The average number of risk factors per patient was 2.9; seven patients had at least four risk factors, and all patients had at least one risk factor. This frequency of risk factors is elevated when compared to the US population. CONCLUSIONS: In our institution, 5.5% of patients treated for Hodgkin's disease experienced a morbid cardiac event following RT to the central cardiac volume. The doses given were greater than commonly used today. Some patients experienced events at a young age, and the likelihood of experiencing CD was increased compared to the general population. This observation is consistent with RT as an additional risk factor in the induction of morbid cardiac events. Appropriate cardiac shielding and radiation doses, careful follow-up, which includes monitoring of cardiac function, and a preventative program of sensible dietary habits, exercise, and nonsmoking may be beneficial in reducing cardiac morbidity in long-term survivors of Hodgkin's disease.

Information level and young children's phonological accuracy.

The influence of information level on the production accuracy of 20 children (22 to 28 months) was examined. The data were children's productions of nouns in sets of utterances referring to triplets of pictures representing noun-verb-noun utterances. In each triplet one noun remained the same, thus decreasing in information value from the first to the third picture (new, moderately old, and old information). Words representing new information were produced more accurately than words representing old information. The types of errors did not differ. Further evidence of this effect was provided by an examination of the duration of new versus old word productions by 12 of the children. Productions encoding new information were consistently longer on average than those encoding old information. The result provide experimental evidence of an effect observed in adults that indicates early sensitivity to information level. However, because of the children's young age, the effects are characterized as a speaker-internal process that only serendipitously corresponds to listener needs.

Young children's production of syllable stress: an acoustic analysis.

The acoustic characteristics of stress were examined in young children's productions of minimal pairs of novel words (e.g., sofi versus so'fi). Fourteen 2-year-olds participated as subjects. Their productions were analyzed in terms of vowel duration, syllable duration, peak amplitude, and peak fundamental frequency. The analyses revealed that children produced stressed and unstressed syllables distinctly along each of the dimensions examined. The absolute and relative (unstressed/stressed) values of the children's productions were compared to those of the single adult experimenter, who modeled the novel words, permitting a unique comparison of input to children's productions. One systematic difference was the relative values; the children's stressed and unstressed syllables were less distinct than the adults along each of the acoustic correlates. Furthermore, the acoustic features of both stressed and unstressed syllables appear to be subject to developmental change. The results are discussed in terms of their implications for young children's production capabilities and for the relationship between input and children's production characteristics.

Persistent thallium-201 defect: can clinical, electrocardiographic and exercise hemodynamic variables predict defect normalization with reinjection?

This study was designed to assess the contribution of clinical, electrocardiographic and exercise hemodynamic variables to the prediction of normalization on resting reinjection scintigraphy of persistent thallium-201 (201Tl) myocardial perfusion defects seen with exercise and 2- to 4-hour delayed (redistribution) imaging. To evaluate this contribution, we studied 159 consecutive patients with persistent 201Tl myocardial perfusion defects on routine exercise and 2- to 4-hour-delayed scintigrams at the University of Rochester Medical Center who were classified as having moderate or greater ischemic normalization (group 1, n = 76) or minimal to no ischemic normalization (group 2, n = 83) by reinjection scintigraphy. Multiple logistic regression analysis with backward elimination was used to model the effects of clinical, electrocardiographic and exercise hemodynamic data on the odds ratio of a normalized defect. No difference was observed in the two groups with regard to gender, angina on exertion, rate-pressure product, exercise duration, resting or exertional ischemic ST changes on electrocardiogram, presence of Q waves or left ventricular hypertrophy on baseline electrocardiogram, or total number of stress thallium defects (2.8 +/- 1.5 segments). No single variable or combination of variables discriminated between groups 1 and 2 by logistic regression analysis. We conclude that defect normalization seen on resting 201Tl myocardial perfusion scintigraphy is prevalent in patients with persistent defects on routine exercise and delayed myocardial perfusion scintigraphy, and was not predictable from available clinical, electrocardiographic and exercise hemodynamic variables.

Otitis media, communication style of primary caregivers, and language skills of 2 year olds: a preliminary report.

The association between early otitis media, styles of primary caregivers, and language development was prospectively examined in 26 2-year-old children from lower socioeconomic backgrounds (of mixed perinatal status) followed prospectively since birth. Based on otoscopic evaluations during the first year of life, there were 14 children who were classified as bilaterally otitis-free (OM-) and 12 children who were classified as bilaterally otitis-positive (OM+). At 2 years of age, all children were administered standardized measures of cognitive and language function along with a 20-minute videotaped play session with one of their primary caregivers. The language of both the children and caregivers was analyzed. Results indicate that caregivers of OM+ and OM- children used language nearly identically when interacting with their children. However, caregivers of OM+ children whose communication style was marked by a high percentage of directives and a corresponding low percentage of both questions and information-giving had the children with the lowest scores on all measures of naturalistic language. Controlling for neonatal illness did not alter the relationships found. The results suggest that caregiver language may compensate for some of the auditory deprivations associated with otitis media.

Metrical patterns of words and production accuracy.

This investigation examined the influence of metrical patterns of words (syllable stress and serial position) on the production accuracy of 20 children (22 to 28 months). The data were productions of six pairs of individualized two-syllable experimental words that referred to unfamiliar objects. Members of each pair differed only in the placement of stress (e.g., ['soti] vs. [so'ti]). Unstressed syllables were much more likely to be omitted, particularly at the beginning of words. Very few stressed syllables and unstressed second position syllables were omitted. One fourth of the word initial unstressed syllables were omitted. Consonant omissions, though few in number, tended to occur in initial position. Assimilation errors were not influenced by stress or serial position. When segmental errors due to syllable omissions were excluded, other consonant errors were not affected by stress or serial position. These findings indicate that young children's productions of syllables are influenced by the metrical patterns of words. However, the trochaic pattern of English is a statistical tendency, not an absolute constraint on two-syllable words. Metrical pattern also does not affect the consonant accuracy in syllables produced.

Effect of familiarity on word duration in children's speech: a preliminary investigation.

Young children's productions of novel words were used to investigate the influence of word familiarity on vowel and word duration. Ten children, 18 to 21 months old, produced tokens of phonologically individualized words (from one to four words) over 12 experimental sessions. Comparisons of means for the individualized words revealed that productions in the second half of the sessions were significantly shorter (both in their vowel and overall duration) than those in the first six sessions. When mean durations of productions were derived for each child, the effect held for word durations. Vowel durations differed in the same direction, but the difference was not statistically significant. Under these controlled conditions, familiarity seemed to influence the duration of early productions of novel words. These findings are discussed as evidence of word-specific motor maturation in early lexical acquisition.

Prognostic significance of a fixed thallium defect one to six months after onset of acute myocardial infarction or unstable angina. Multicenter Myocardial Ischemia Research Group.

In a large prospective study of myocardial ischemia, exercise thallium studies were performed in 896 patients 1 to 6 months after an acute coronary event (acute myocardial infarction, 70%; unstable angina, 30%). Thallium images were analyzed quantitatively and classified as normal or demonstrating either a reversible defect after 2 to 4 hours or having only a fixed defect. The effect of the thallium findings on the time to end point (cardiac death, nonfatal infarction, or unstable angina) were examined by Kaplan-Meier curves and compared using the log-rank statistic. Follow-up averaged 23 months. The likelihood of cardiac death, nonfatal infarction, and unstable angina was similar in patients who had a normal exercise thallium test result or showed only a fixed defect. Moreover, cardiac events were not related to the size of a fixed defect. In contrast, both cardiac death and nonfatal infarction were increased in patients with the largest areas of reversible defects, although the sensitivity for nonfatal myocardial infarction was suboptimal. The presence of a fixed defect on exercise thallium in patients who are stable an average of 2.6 months after an acute cardiac event is associated with a prognosis similar to that of a normal exercise thallium test.

Limited usefulness of exercise testing and thallium scintigraphy in evaluation of ambulatory patients several months after recovery from an acute coronary event: implications for management of stable coronary heart disease. Multicenter Myocardial Ischemia Research Group.

OBJECTIVES: This study evaluated the value of noninvasive testing to predict cardiac events in patients with stable coronary disease after hospital admission (and risk stratification) for an acute coronary event. BACKGROUND: Exercise testing with thallium perfusion imaging identifies patients with obstructive coronary artery disease and has been used to stratify patients after myocardial infarction. Its usefulness for predicting cardiac events in patients with stable coronary disease after recovery from an acute coronary event was explored. METHODS: Nine hundred thirty-six patients were enrolled 1 to 6 months after hospital admission for a coronary event. Patients underwent exercise treadmill testing with planar thallium-201 scintigraphy and were followed up for an average of 23 months (range 6 to 43). End points were 1) unstable angina requiring hospital admission, nonfatal myocardial infarction or cardiac death; 2) nonfatal infarction or cardiac death; or 3) cardiac death alone. RESULTS: Twelve patients died of cardiac causes (1.2%); 32 had a nonfatal myocardial infarction (3.4%); and 79 patients (8.4%) developed unstable angina in the first year. Exercise testing improved proportional hazards models constructed from clinical variables for all three end points (p < 0.05). The perfusion scan further improved models for the end points (nonfatal infarction or cardiac death and cardiac death alone, p < 0.05). However, the exercise test with or without thallium added little to the overall prediction of primary events (area under the receiver operating curve increased from 0.649 to 0.663), and only 2% to 13% of patients with abnormal results either had a nonfatal infarction or died. CONCLUSIONS: Thallium-201 scintigraphy and exercise testing variables identify patients at risk for subsequent cardiac events. However, the poor predictive performance of these tests in this group of patients with stable coronary disease severely limits their usefulness. These results suggest a limited role for exercise and thallium testing in predicting cardiac events in patients with known coronary disease.

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans.

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.