Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog.

In vivo small doses of insulin inhibit lipolysis, lower plasma FFA, and stimulate glucose disposal. Lowering of plasma FFA, either in the absence of a change in insulin or during combined hyperglycemia and hyperinsulinemia, promotes glucose uptake by heart muscle in vivo. In the isolated perfused heart, large doses of insulin directly stimulate heart glucose uptake. To assess the effect of physiological elevations of plasma insulin upon myocardial glucose and FFA uptake in vivo independent of changes in plasma substrate concentration, we measured arterial and coronary sinus concentrations of glucose, lactate, and FFA, and coronary blood flow in conscious dogs during a 30 min basal and a 2 h experimental period employing three protocols: (a) euglycemic hyperinsulinemia (insulin clamp, n = 5), (b) euglycemic hyperinsulinemia with FFA replacement (n = 5), (c) hyperglycemic euinsulinemia (hyperglycemic clamp with somatostatin, n = 5). In group 1, hyperinsulinemia (insulin = 73 +/- 13 microU/ml) stimulated heart glucose uptake (7.3 +/- 4.4 vs. 28.2 +/- 2.8 mumol/min, P less than 0.002), lowered plasma FFA levels by 80% (P less than 0.05), and decreased heart FFA uptake (28.4 +/- 4 vs. 1.5 +/- 0.9, P less than 0.01). When the fall in plasma FFA was prevented by FFA infusion (group 2), hyperinsulinemia (86 +/- 10 microU/ml) provoked a lesser (P less than 0.05) stimulation of glucose uptake (delta = 8.2 +/- 4.2 mumol/min) than in group 1, and there was no significant change in FFA uptake (25.3 +/- 16 vs. 16.5 +/- 4). Hyperglycemia (plasma glucose = 186 +/- 8 mg/100 ml) during somatostatin infusion resulted in only a small rise in plasma insulin (delta = 12 +/- 7 microU/ml), and although plasma FFA tended to decline, heart glucose uptake did not rise significantly (delta = 5.5 +/- 3.2 mumol/min, P = NS). There was no significant change in coronary blood flow during any of the three study protocols. We conclude that, in the dog, insulin at physiologic concentrations: (a) stimulates heart glucose uptake, both directly and by suppressing the plasma FFA concentration, and (b) does not alter coronary blood flow. Hyperglycemia per se has little effect on heart glucose uptake.

Regulation of myocardial amino acid balance in the conscious dog.

The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.

Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity.

To assess the effect of chronic insulin-deficient diabetes on myocardial fuel substrate metabolism in vivo, we measured the myocardial balance of glucose, free fatty acids (FFAs), and amino acids in nine postabsorptive conscious dogs 4-6 wk after treatment with streptozocin. The acute effect of insulin on the myocardial balance of these same substrates was measured in six dogs by use of the euglycemic insulin clamp technique. To further examine the effect of insulin on heart amino acid balance, we studied three additional dogs given a constant infusion of amino acids during the insulin clamp to blunt the insulin-induced hypoaminoacidemia. In these dogs, the fasting plasma glucose concentration was markedly elevated (258 +/- 3 mg/dl). In the basal period, there was no significant glucose uptake by the heart [arterial vs. coronary sinus concentration difference (delta) = 1.0 +/- 2.0 mg/dl]; furthermore, physiologic hyperinsulinemia did not stimulate glucose uptake (delta = 2.0 +/- 2.5 mg/dl). Postabsorptively, arterial FFAs were elevated (1550 +/- 320 microM) in diabetic animals, and there was a significant net extraction of FFAs by the heart (net uptake 26 +/- 9 mumol/min; extraction ratio 30 +/- 8%). During the insulin clamp, arterial FFAs declined (645 +/- 240 microM), as did heart FFA uptake (11 +/- 6 mumol/min), and the net extraction ratio for FFAs was unchanged (30 +/- 7%). Similarly, the arterial branched-chain amino acid (BCAA) concentration was elevated in the postabsorptive state, and there was a significant myocardial uptake of these amino acids and of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Dilated cardiomyopathy and cocaine abuse. Report of two cases.

Two young patients with dilated cardiomyopathies associated with long-term use of cocaine are described. A 42-year-old male cocaine abuser with normal coronary arteries experienced recurrent myocardial infarction, with development of a dilated, globally hypocontractile left ventricle. The second patient, a 28-year-old woman with a prominent history of inhaling vaporized cocaine ("free-basing"), presented with symptoms and signs of biventricular heart failure and was found to have a dilated cardiomyopathy. The clinical spectrum of cocaine cardiotoxicity is reviewed, and pathophysiologic mechanisms of cocaine-induced cardiomyopathy are discussed. Long-term cocaine use may cause dilated cardiomyopathy and recurrent myocardial infarction, even in the absence of atherosclerotic epicardial coronary artery disease.

Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography.

To impact on the development of clinical congestive heart failure as a complication of doxorubicin therapy, left ventricular ejection fraction was monitored with serial resting radionuclide angiocardiography in 1,487 patients with cancer over a seven-year period in both university and community hospital environments. A high-risk subset of 282 patients was selected for retrospective analysis of their clinical outcome. High-risk patients were identified by one or two of the following three criteria: decline of 10 percent or more in absolute left ventricular ejection fraction from a normal baseline to 50 percent or less; high cumulative dose of doxorubicin (more than 450 mg/m2); abnormal baseline left ventricular ejection fraction (less than 50 percent). Clinical congestive heart failure occurred in 46 (16 percent) during the treatment period, and in an additional three patients (1.3 percent) at last follow-up examination 11.8 +/- 14.2 months following discontinuation of doxorubicin. Total cumulative dosages of doxorubicin that precipitated congestive heart failure (75 to 1,095 mg/m2) and those that did not (30 to 880 mg/m2) varied widely. Decline of 10 percent or more in absolute left ventricular ejection fraction to a value of 50 percent or less preceded administration of the final dose of doxorubicin that precipitated clinical congestive heart failure in the majority of patients in whom congestive heart failure developed. Clinical congestive heart failure improved in 87 percent given routine therapy with digitalis, diuretics, and/or vasodilators. Criteria for monitoring left ventricular ejection fraction and discontinuing doxorubicin were formulated. The occurrence of clinical congestive heart failure was compared in those patients whose management was concordant with proposed criteria (Group A) and in those whose management was not (Group B). Group A had a lower incidence of congestive heart failure compared with Group B (2.9 percent versus 20.8 percent, p less than 0.001) and had only mild congestive heart failure that resolved with treatment (n = 2) and no deaths due to congestive heart failure. Multivariate analysis with proportional-hazards regression (Cox's model) demonstrated a fourfold reduction in the incidence of congestive heart failure independent of other clinical predictor variables in those patients whose management was concordant with proposed guideline criteria. The incidence, persistence, late development, predictability, and reversibility of clinical congestive heart failure were comparable in university and community hospital settings.(ABSTRACT TRUNCATED AT 400 WORDS)

Radiation effects on left ventricular function and myocardial perfusion in long term survivors of Hodgkin's disease.

We evaluated systolic and diastolic indices of left ventricular performance by radionuclide angiocardiography and myocardial perfusion with exercise/rest thallium scintigraphy in 16 patients previously irradiated for Hodgkin's disease. These commonly used indices of left ventricular (LV) performance included LV ejection fraction (LVEF) as a measure of systolic function, and LV peak filling rate (PFR) as a measure of diastolic function. The presence of coronary artery disease (CAD) was evaluated by ECG treadmill testing (13 patients) and by quantitative planar thallium scintigraphy (12 patients). Patients were 16-38 years old (mean 24.9 +/- SD 6.2) at the tim eof irradiation, and were evaluated 2.5-21.5 years (mean 9.3 +/- 6.3) after radiation therapy (RT). RT was delivered with beam energies of 2-18 MV, equally weighted AP-PA mantle fields with both fields treated daily for most patients (13 patients), and fraction sizes of 1.5-2.0 Gy. Six patients received radiation to th entire cardiac volume, most commonly via left-sided partial transmission lung blocks (PTLB). Patient data were analyzed according to the volume of heart treated. Individuals who had the entire cardiac volume irradiated were assigned to group I (N = 6), and those patients who had some portion of the heart shielded throughout treatment comprised group II (N = 10). In this series, no perfusion defects were evident in either group by quantitative planar thallium scintigraphy. Mean LVEF for all patients studied was 60% (normal LVEF greater than or equal to 50%). Patients in group I had a lower mean LVEF than those in group II, 55 +/- 4% versus 63 +/- 6% (p = 0.01). Mean PFR for all patients studied was normal at 3.5 EDV/sec (normal PFR greater than or equal to 2.54 EDV/sec). Patients in group I had a lower mean PFR than those in group II, 3.0 +/- 0.6 vs 3.8 +/- 0.7 EDV/sec (p = 0.04). Thus, patients irradiated to large cardiac and pulmonary volumes had lower LVEF and PFR within the normal range compared to patients who had some portion of the cardiac volume shielded. These differences are statistically significant in the relatively small groups studied but do not appear to be associated at the present time with clinically significant effects.

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.

Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group.

The anthracycline antibiotics, daunorubicin, doxorubicin, and the newer derivatives, are important components of many antineoplastic chemotherapeutic regimens. Their usefulness is limited by their cardiotoxicity. Sequential monitoring of cardiac function of patients undergoing chemotherapy allows identification of subclinical cardiotoxicity. In many patients monitoring can thus guide the modification of the chemotherapy to minimize cumulative cardiotoxicity, reducing acute and long-term clinical and subclinical sequelae. Such monitoring also aids in the comparison of cardiotoxicity produced by different drugs and different methods and schedules of drug administration. The considerable variability of monitoring regimens between institutions and in the literature has detracted from its usefulness. The Cardiology Committee of the Childrens Cancer Study Group has, therefore, reviewed the field and has formulated recommendations for standardized noninvasive monitoring of children during and immediately after chemotherapy and for the modification of the chemotherapy where indicated.

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.

Cost-benefit analysis of early return to work after uncomplicated acute myocardial infarction.

The economic consequences of an Occupational Work Evaluation designed to identify low risk patients recovering from uncomplicated acute myocardial infarction (AMI) and hasten their return to work was evaluated in a randomized trial. Two hundred one employed, clinically low risk men recovering from AMI were randomized to undergo an intervention (intervention group, 99 patients) consisting of an Occupational Work Evaluation or to receive usual care (usual care group, 102 patients). The time to return to work was reduced from 75 days in usual care patients to 51 days in intervention patients (p less than 0.002). Significant differences were found between groups for medical costs and occupational income during follow-up. Total medical costs per patient were lower in the intervention patients than in the usual care patients in the 6 months after AMI ($2,970 vs $3,472). Occupational income per patient was higher in intervention patients than in the usual care group in the 6 months after AMI ($9,655 vs $7,553). The per capita benefit accounting for medical costs and occupational income was $6,685 for intervention patients and $4,081 for usual care patients. Projected to the greater than 300,000 low risk, employed survivors of AMI annually in this country, the savings generated by the Occupational Work Evaluation could yield an annual economic benefit greater than 800 million dollars.

Reduced metabolic rate during beta-adrenergic blockade in humans.

We previously reported that 1 week of propranolol treatment (160 to 240 mg/d, orally) reduced resting metabolic rate (RMR) an average of 9% in healthy men. To determine whether this response was caused by the 25% reduction in serum triidothyronine (T3), rather than beta-adrenergic blockade, we examined the effect of nadolol on RMR in five healthy men. Nadolol is a nonselective beta-adrenergic antagonist that does not affect T3 production. After 6 to 10 days of nadolol treatment (240 mg/d), mean postabsorptive RMR declined 7% (P less than .01), with no significant change in serum T3 or thyroxine (T4) concentrations. This effect is significantly different from that of a hospitalized control group that received no drug and had no change in mean RMR, and was not different from the response to propranolol (previously published data). Nadolol slightly reduced the mean thermic response to a meal (12%), but this effect was not statistically significant. Mean postprandial RMR was 8% lower after nadolol treatment (P less than .01), mainly because of the reduced postabsorptive RMR, rather than a change in the response to the meal. These data suggest that beta-adrenergic activity makes a small but significant contribution to resting energy expenditure in man.

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.

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.

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.

Electric sympathetic block: a review of electrotherapy physics.

Electric sympathetic block is the procedure whereby blockage of the sympathetic nerve fiber is achieved by applying controlled electrical pulses via electrodes placed on the skin. An electric block of the sympathetic fiber can occur with a direct monophasic current to achieve an anodal block, a middle-frequency or Endosan current to effect sustained depolarization, or an interferential current to achieve a fatiguing effect. The physics and theoretical framework underlying the currents used in this procedure will be reviewed.

Electric sympathetic block: methods of measurement and a study assessing its effectiveness.

Electric sympathetic block is the procedure whereby sympathetic nerve fibers are blocked by application of controlled electrical impulses via electrodes placed on the skin. Methods of measuring the extent of sympathetic blockade and a clinical study using bipolar middle frequency currents to achieve electric sympathetic block are presented. Fifteen of 20 (75%) patients who underwent a 1-week series of electric sympathetic blocks reported at least 75% subjective relief from sympathetically mediated pain after completion of the series.

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.