Obstructive sleep apnea in children with epilepsy: prospective pilot trial.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in adults with epilepsy, especially refractory, but limited data exist in children with epilepsy. AIMS: We conducted a prospective pilot study in children with epilepsy to identify the prevalence of OSA and its relationship to the use of antiepileptic drugs (AEDs) and epilepsy types. METHODS: We used Michigan Pediatric Sleep Questionnaire (PSQ) in children with epilepsy. Patients were classified by seizures frequency as mild (0-1 seizure/month) or severe, refractory epilepsy (> 1 seizures/month). We used PSQ ≥ 0.33 as a cutoff point to assess the risk of OSA. RESULTS: Of 84 children, 52 were classified as mild and 32 as severe. Prevalence of OSA was significantly higher in the severe (43.8%) vs the mild group (30.7%, P < 0.05). Children on >1 AED had significantly higher prevalence of OSA (45.8%) than children on ≤1 AED (30.6%, P < 0.05). There was no significant correlation between the prevalence of OSA and seizure types. CONCLUSIONS: OSA is more prevalent in refractory epilepsy and in children who are on multiple AEDs. While further studies are needed to confirm these findings and to assess the consequences of OSA, we believe it is important to screen the children with epilepsy for OSA.

Optical response of high-dielectric-constant perovskite-related oxide.

Optical conductivity measurements on the perovskite-related oxide CaCu3Ti4O12 provide a hint of the physics underlying the observed giant dielectric effect in this material. A low-frequency vibration displays anomalous behavior, implying that there is a redistribution of charge within the unit cell at low temperature. At infrared frequencies (terahertz), the value for the dielectric constant is approximately 80 at room temperature, which is far smaller than the value of approximately 10(5) obtained at lower radio frequencies (kilohertz). This discrepancy implies the presence of a strong absorption at very low frequencies due to dipole relaxation. At room temperature, the characteristic relaxation times are fast (less than or approximately 500 nanoseconds) but increase dramatically at low temperature, suggesting that the large change in dielectric constant may be due to a relaxor-like dynamical slowing down of dipolar fluctuations in nanosize domains.

Acetylsalicylic acid reduces vegetation bacterial density, hematogenous bacterial dissemination, and frequency of embolic events in experimental Staphylococcus aureus endocarditis through antiplatelet and antibacterial effects.

BACKGROUND: Platelets are integral to cardiac vegetations that evolve in infectious endocarditis. It has been postulated that the antiplatelet aggregation effect of aspirin (ASA) might diminish vegetation evolution and embolic rates. METHODS AND RESULTS: Rabbits with Staphylococcus aureus endocarditis were given either no ASA (controls) or ASA at 4, 8, or 12 mg. kg-1. d-1 IV for 3 days beginning 1 day after infection. Vegetation weights and serial echocardiographic vegetation size, vegetation and kidney bacterial densities, and extent of renal embolization were evaluated. In addition, the effect of ASA on early S aureus adherence to sterile vegetations was assessed. In vitro, bacterial adherence to platelets, fibrin matrices, or fibrin-platelet matrices was quantified with either platelets exposed to ASA or S aureus preexposed to salicylic acid (SAL). ASA at 8 mg. kg-1. d-1 (but not at 4 or 12 mg. kg-1. d-1) was associated with substantial decreases in vegetation weight (P<0.05), echocardiographic vegetation growth (P<0.001), vegetation (P<0.05) and renal bacterial densities and renal embolic lesions (P<0.05) versus controls. Diminished aggregation resulted when platelets were preexposed to ASA or when S aureus was preexposed to SAL (P<0.05). S aureus adherence to sterile vegetations (P<0.05) or to platelets in suspension (P<0.05), fibrin matrices (P<0.05), or fibrin-platelet matrices (P<0.05) was significantly reduced when bacteria were preexposed to SAL. CONCLUSIONS: ASA reduces several principal indicators of severity and metastatic events in experimental S aureus endocarditis. These benefits involve ASA effects on both the platelet and the microbe.

Influence of cardiac motion on Doppler measurements using in vitro and in vivo models.

OBJECTIVES: Using both in vitro and in vivo techniques, we investigated the extent to which cardiac motion alters Doppler-measured blood flow velocity and thus potentially can alter the calculation of valve areas or pressure gradients. BACKGROUND: Blood flow velocity measured by Doppler ultrasound represents the net motion of the blood relative to the transducer. It is widely assumed that the measured velocity represents the actual flow. It has been demonstrated that cardiac motion generates regularly occurring low velocity Doppler signals that are commonly treated as artifact. METHODS: We used an in vitro model that allowed us to measure and independently control the flow of a liquid through a chamber and the motion of the chamber relative to the Doppler beam. A cornstarch-water slurry was driven by a pulsatile pump through tubing to simulate the blood flow within the heart, and the tubing was cyclically moved by a piston to simulate the heart motion. We also measured cardiac motion using M-mode and two-dimensional echocardiography and compared the results with the Doppler signal derived from cardiac motion in subjects without cardiac disease. RESULTS: In the in vitro model, alteration in the motion of the tubing resulted in apparent changes in the measured maximal velocity of the fluid. The Doppler spectrum of the combined motion of the tubing and the fluid was the algebraic sum of their Doppler signals. In human subjects, the maximal slope of the M-mode tracing of the aortic annular motion and the peak Doppler signal due to cardiac motion were compared and were highly correlated. CONCLUSIONS: Cardiac motion alters the Doppler signal derived from blood flow. This effect can be demonstrated in vitro and in vivo.

Responses to constant work rate bicycle ergometry exercise in primary pulmonary hypertension: the effect of inhaled nitric oxide.

OBJECTIVES: The purpose of this study was to investigate the responses of patients with primary pulmonary hypertension (PPH) to constant work rate exercise and to examine the effect of nitric oxide (NO) inhalation. BACKGROUND: Maximal exercise tolerance is reduced in PPH, but gas exchange responses to constant work rate exercise have not been defined. We hypothesized that increased pulmonary vascular resistance in PPH would reduce the rate of rise of minute oxygen consumption in response to a given work rate. Because NO may lower pulmonary vascular pressures in PPH, we also postulated that inhaled NO might ameliorate gas exchange abnormalities. METHODS: Nine PPH patients and nine matched normal subjects performed 6-min duration constant work rate cycle ergometry exercise (33.9+/-13.4 W). Patients performed two experiments: breathing air and breathing air with NO (20 ppm). Preexercise right ventricular systolic pressure was assessed by Doppler echocardiography. Normal subjects performed the air experiment only. Gas exchange and heart rate responses were characterized by fitting monoexponential curves. RESULTS: In PPH patients, resting right ventricular systolic pressure fell after NO inhalation (from 83.8+/-16.9 to 73.9+/-21.6 mm Hg, p<0.01, analysis of variance with Tukey correction), but not after breathing air alone (from 88.0+/-20.8 to 86.7+/-20.6 mm Hg, p = NS). Nitric oxide did not affect any of the gas exchange responses. Minute oxygen consumption was similar by the end of exercise in patients and normals, but increased more slowly in patients (mean response time [MRT]: air, 63.17+/-14.99 s; NO, 61.60+/-15.45 s) than normals (MRT, 32.73+/-14.79, p<0.01, analysis of variance, Tukey test). Minute oxygen consumption kinetics during recovery were slower in patients (MRT air: 82.50+/-29.94 s; NO, 73.36+/-15.87 s) than in normals (MRT, 34.59+/-7.11 s, p<0.01). Heart rate kinetics during exercise and recovery were significantly slower in patients than in normals. CONCLUSIONS: The cardiac output response is impaired in PPH. Nitric oxide lowered pulmonary artery pressure at rest, but failed to improve exercise gas exchange responses.

Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion.

OBJECTIVES: This study sought to determine the long-term effects of continuous infusion of epoprostenol (epo) therapy on survival and pulmonary artery pressure in patients with primary pulmonary hypertension (PPH). BACKGROUND: PPH is a progressive disease for which there are few effective therapies. METHODS: Patients with PPH and New York Heart Association functional class III or IV symptoms of congestive heart failure underwent right heart catheterization and Doppler-echocardiography to measure the maximal systolic pressure gradient between the right ventricle and right atrium (delta P) and cardiac output (CO). Doppler-echocardiography and catheterization data were compared. Patients were followed up long term with Doppler-echocardiography. RESULTS: Of 69 patients who went on to receive epo, 18 were followed up for > 330 days (range 330 to 700). During long-term follow-up, there was a significant reduction in delta P, which decreased from 84.1 +/- 24.1 to 62.7 +/- 18.2 (mean +/- SD, p < 0.01). A Kaplan-Meier plot of survival of our study patients demonstrated improved survival compared with that of historical control subjects. The 1-, 2- and 3-year survival rates for our patients were 80% (n = 36), 76% (n = 22) and 49% (n = 6) compared with 10- (88%, n = 31), 20- (56%, n = 27) and 30-month (47%, n = 17) survival rates in historical control subjects. CONCLUSIONS: Patients receiving continuous infusion of epo for treatment of PPH experience a decrease in pulmonary artery pressure. Long-term follow-up of this single-center patient group demonstrated improved long-term survival during epo therapy compared with that in historical control subjects and confirms predicted improved outcomes based on shorter follow-up periods.

Evaluation of new clinical criteria for the diagnosis of infective endocarditis.

PURPOSE: The clinical diagnosis of infective endocarditis (IE) can be difficult. A new diagnostic schema for IE (the Duke criteria) has been proposed, utilizing clinical, microbiologic, and echocardiographic data. We evaluated the Duke criteria in a cohort of prospectively enrolled patients suspected of having IE and compared the diagnostic efficiency of these criteria with the previously published criteria of von Reyn. PATIENTS: Sixty-three febrile patients with suspected IE at a non-referral, municipal hospital were evaluated. All patients had the following parameters defined: the presence and nature of underlying heart disease; recent abuse of intravenous drugs; peripheral stigmata of IE; blood culture results; findings on two-dimensional transthoracic and transesophageal echocardiography (TTE, TEE); and the results of open heart surgery. RESULTS: Twelve of 63 patients underwent open heart surgery, at which time IE was pathologically confirmed in 10 patients and excluded in 2 patients. All 10 patients with pathologically confirmed IE were classified as "clinically definite" by Duke criteria, whereas 5 of 10 were rejected by von Reyn criteria (p < 0.05). Among the remaining 51 patients suspected of IE and evaluated by both von Reyn and Duke clinical criteria, significantly more cases were classified as "definite" IE by Duke criteria than by von Reyn criteria (p < 10(-5)). Similarly, significantly fewer cases were rejected as IE by the Duke criteria as compared with the von Reyn criteria (p < 10(-6). Duke criteria were also significantly better at diagnosing IE than von Reyn criteria in the following clinical settings: suspected right-sided IE (p < 0.01); suspected left-sided IE (p = 0.014); suspected culture-negative IE (p < 10(-2); and IE complicating Staphylococcus aureus or viridans streptococcal bacteremias (p < 10(-5); p < 0.05, respectively). Among 30 cases defined as clinically definite by the Duke criteria, the presence of blood culture positivity and echocardiographically defined vegetations was important in this classification of 77% and 57% of cases, respectively. Among the 17 patients in the clinically definite category with vegetative endocarditis observed by echocardiography, 7 (41%) had vegetations defined only by TEE. CONCLUSION: The Duke criteria are superior to the von Reyn criteria for the clinical diagnosis of IE, predominantly reflecting use of two-dimensional echocardiographic demonstration of valvular vegetations in the Duke schema.

Effect of metoprolol on the submaximal stress test performed early after acute myocardial infarction.

To determine the effect of beta-adrenergic blockade on the submaximal stress test after acute myocardial infarction (AMI), 36 post-AMI patients performed their treadmill test on 2 separate days, with and without metoprolol, in a double-blind, placebo-controlled, crossover design study. Rest and peak submaximal exercise heart rate was diminished by 100 mg of metoprolol administered twice daily (from 84 +/- 3 to 68 +/- 2 beats/min, p less than 0.001, and from 126 +/- 3 to 97 +/- 2 beats/min, p less than 0.001, respectively) compared with placebo. Rest and peak submaximal systolic blood pressure was also decreased (from 121 +/- 3 to 108 +/- 2 mm Hg, p less than 0.001, and from 151 +/- 4 to 124 +/- 3 mm Hg, p less than 0.001). Exercise-induced ST-segment depression of 1 mm or more from baseline occurred in 12 patients taking placebo. However, only 4 of these patients had ST depression when they exercised while taking metoprolol (p less than 0.05). Angina pectoris occurred in 4 patients taking placebo but in only 1 of these taking a beta-blocking drug. It is concluded that beta-blocking therapy renders the post-AMI submaximal stress test less sensitive for markers of exercise-induced ischemia than if the test is performed without the drug. Therefore, when using the prognostic information of published studies, it is important to define the conditions surrounding the exercise test.

Effects of exercise test results on physician perceptions of coronary artery disease probability using a threshold analysis.

The incremental diagnostic value of exercise electrocardiographic testing compared with clinical data alone in the diagnosis of coronary artery disease (CAD) was found to be of limited value in a previous study. That study used a computer algorithm for diagnosing disease. Thus, the strict use of the results apply only to computerized disease diagnosis rather than physicians' diagnoses. The aim of the present study was to determine whether exercise test data improve a physician's ability to detect the presence or absence of CAD and 3-vessel or left main CAD, and whether the data effect the decision to perform angiography. The study sample comprised a data base of 312 patients whose clinical data, exercise test results and coronary anatomy were known. Individual cases were presented to 8 cardiologists with and without exercise data. The cardiologists provided estimates of disease probability and were asked whether they would request coronary angiography. Receiver-operating characteristic curves and goodness-of-fit analysis showed better discrimination and calibration of the estimates for the presence of CAD and 3-vessel/left main CAD after exercise test results were known. Individualized probability thresholds for deciding whether to request angiography were determined for each physician. Forty-three percent of patients crossed greater than or equal to 1 threshold, with 64% of the crossings in the correct direction. For estimating the presence of any CAD, 84% of crossings from below to above a threshold were correct, whereas only 36% from above to below were correct. For 3-vessel/left main CAD, 36% of crossings from below to above a threshold were correct, whereas 88% from above to below were correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial-esophageal fistula shown by transthoracic echocardiogram.

Nontraumatic atrial-esophageal fistula is a catastrophic problem usually diagnosed postmortem and almost invariably fatal. We report the first case of a patient in whom the diagnosis of atrial-esophageal fistula was made from a transthoracic echocardiography antemortem. Echocardiography showed multiple microbubbles in the left atrium and ventricle emanating from the posterior aspect of the left atrium adjacent to the pulmonary veins. The literature is reviewed and the significance of the case and the echocardiogram is discussed.

An evaluation of the accuracy of Assess and MiniWright peak flowmeters.

With the advent of small inexpensive peak flowmeters, the at-home monitoring of peak flow rates has become an invaluable aid in the treatment of asthmatic patients. In this study, we evaluated the performance of the MiniWright and Assess peak flowmeters for accuracy and reproducibility. Measurements were made at varying peak flow rates and compared with those obtained simultaneously by a calibrated pneumotachograph. When this segment of the study was completed, the peak flow devices were subjected to 200 uses and were then retested. Four MiniWright peak flowmeters that had been extensively used in our clinic were tested as well. The Assess peak flowmeter was more accurate than the MiniWright at low flow rates (less than 300 L/min), while the MiniWright meter was more accurate at high flow rates (greater than 400 L/min). We also found that the accuracy of the MiniWright meter deteriorated after 200 uses and worsened further after extensive use, while the Assess meter retained its accuracy after 200 uses.

Transesophageal echocardiography in diagnosis of infective endocarditis.

STUDY OBJECTIVE: To determine whether transesophageal echocardiography (TEE) was superior to transthoracic echocardiography (TTE) in defining valvular vegetations and diagnosing clinical infective endocarditis (IE) in patients suspected of having this infection. PATIENTS AND METHODS: Between April 1989 and May 1991, 64 febrile patients with clinical and/or microbiologic risk factors for IE were prospectively enrolled. Patients underwent both TEE and TTE, which were interpreted in a blinded fashion as to the patient's clinical status. Clinical criteria for the diagnosis of IE were compared with TEE and TTE findings to delineate the ability of the two echocardiographic techniques to define valvular vegetations and to establish the clinical diagnosis of vegetative IE. RESULTS: Thirty-four valves had typical valvular vegetations demonstrated by either TEE or TTE. Transesophageal echocardiography was more sensitive than TTE in identifying valvular vegetations (33/34 vs 23/34 instances, respectively; p = 0.004). Also, TEE was better at identifying smaller vegetations (< 1 cm) than TTE; 12 patients with such vegetations were identified by TEE as compared with only 5 of 12 identified by TTE (p = 0.02). Of the 64 patients enrolled, 30 (47 percent) were classified as having "definite" or "probable" IE by modified von Reyn criteria. Among these 30 patients, TEE was significantly more sensitive than TTE at documenting vegetative valvular lesions (26/30 [87 percent] vs 18/30 [60 percent], respectively) (p < 0.01). Both TEE and TTE were highly specific (91 percent) in delineating valvular vegetations in this patient population; two of the three false-positive TEE studies for valvular vegetations occurred in patients with a history of IE. All nine periannular complications of IE were identified by TEE, as compared with only two being defined by TTE (p = 0.001). CONCLUSIONS: Transesophageal echocardiography is significantly more sensitive than TTE and highly specific in both confirming the clinical diagnosis of IE, as well as in identifying valvular vegetations in patients at risk for this infection. Our data also support the concept that TEE is the echocardiographic method of choice for defining small vegetations and periannular complications in IE.

Pathogenesis of cerebral air embolism during neodymium-YAG laser photoresection.

We describe a case of air embolism complicating neodymium-YAG laser resection of an endobronchial carcinoid tumor. A 27-year-old man experienced an acute neurologic syndrome during laser photoresection which responded to acute hyperbaric therapy.

Development of brainstem auditory evoked potentials in heterozygous and homozygous jaundiced Gunn rats.

Bilirubin toxicity is a significant clinical problem causing neurologic and audiologic sequelae. To better understand the pathogenesis of bilirubin toxicity in the immature nervous system we studied the development of brainstem auditory evoked potentials (BAEPs) in jaundiced (jj) Gunn rats and their non-jaundiced (Jj) littermates. Littermate pairs of Jj and jj rats were studied serially from early infancy to adulthood. Replicated BAEPs to click stimuli at two different intensities (45 and 75 dB SPL) and rates (33 and 89/s) were obtained from animals anesthetized with ketamine and acepromazine and maintained at a constant rectal temperature. Jaundiced (jj) rats had increased latencies of waves II and III and the I-II and I-III intervals, and decreased amplitudes of waves II and III from 17 days of age through adulthood. For both groups, all latencies and interwave intervals decreased with age (P less than 0.0001 for each wave and interwave interval by repeated measures ANOVA), and the amplitude of II increased with age (P less than 0.0001). No group differences were found in wave I latency or amplitude, or in the latency change of waves I, II or III as a function of intensity (about 11 microseconds/dB at all ages), suggesting that peripheral auditory function is normal in jj rats. Finally, there were no different effects of stimulation rate on BAEP wave latencies between groups. The findings suggest dysfunction of the central (brainstem) auditory pathways at and rostral to the cochlear nuclei, and are consistent with studies showing destruction of the cochlear nuclei in this animal model and in humans with bilirubin toxicity. The central abnormalities previously found in adult, jaundiced rats are now demonstrated in animals as early as 17 days of age, when serum bilirubin concentration is maximum. The BAEP findings are similar to changes found in hyperbilirubinemic human neonates, and support the use of the Gunn rat animal model for the study of bilirubin encephalopathy.

Use of transesophageal echocardiography during thrombolysis with tissue plasminogen activator of a thrombosed prosthetic mitral valve.

Inadequate anticoagulation in patients with mechanical prosthetic heart valves can result in a significant incidence of thromboembolic complications. An even more life-threatening complication is massive thrombosis of the valve itself. Thrombolytic therapy was given to a moribund 22-year-old woman with intractable heart failure caused by a thrombosed St. Jude prosthetic mitral valve (St. Jude Medical, Inc., St. Paul, Minn.). Although this form of therapy has been used before, this is the first report of a case in which transesophageal echocardiography was performed during thrombolytic therapy to continually record successful thrombolysis of the clotted prosthetic valve. Serial imaging during thrombolysis displayed progressive dissolution of the thrombus and progressive improvement in valve function. Transesophageal echocardiography is helpful in the diagnosis of prosthetic valve thrombosis and has the ability to monitor continually the effect of treatment with thrombolysis. Although thrombolytic therapy with recombinant tissue plasminogen activator is effective in treating prosthetic valve thrombosis, it carries a high risk for serious thromboembolic complications and thus should be reserved for critically ill patients who are too sick to undergo immediate surgery.

Pulmonic valve endocarditis as an underdiagnosed disease: role of transesophageal echocardiography.

Pulmonic valve endocarditis is a rare clinical entity. In spite of an increase in the frequency of right-sided endocarditis, primarily it is the tricuspid valve that is involved. Two-dimensional transthoracic echocardiography has improved our ability to diagnose infective endocarditis but has not identified many cases of pulmonic valve endocarditis. With the use of transesophageal echocardiography, three recent cases of pulmonic valve endocarditis were diagnosed by our laboratory. Each of these patients had clinical evidence of right-sided endocarditis, yet routine transthoracic echocardiograms failed to identify any pulmonic valve abnormalities. The true incidence of pulmonic valve endocarditis may be higher than previously reported, and the transesophageal echocardiogram is the preferred method for identifying and evaluating pulmonic valve endocarditis in adults.

Binaural effects in brainstem auditory evoked potentials of jaundiced Gunn rats.

Bilirubin toxicity causes encephalopathy associated with lesions of the central auditory nervous system. Abnormal brainstem auditory evoked potentials (BAEPs) in jaundiced Gunn rats made acutely bilirubin toxic suggest abnormal input into the superior olivary complex, which might result in abnormal binaural interaction. Binaural difference waves (BDWs), obtained by subtracting the sum of two monaural BAEPs from a binaural BAEP, were obtained in 16- to 20-day-old jaundiced Gunn rats before and after injection of sulfadimethoxine, which produces bilirubin neurotoxicity by promoting net transfer of bilirubin out of the circulation into brain tissue. Reliable BDWs were recorded with onset 4.5 ms after the stimulus, followed by a large, often bimodal, positive peak occurring at about 6 ms. Following injection of sulfadimethoxine to produce bilirubin neurotoxicity, there was loss of BDW amplitude (21% +/- 14% of baseline, P less than 0.0001) and increase in latency (0.62 +/- 0.42 ms, P = 0.03) in bilirubin-toxic jaundiced rats compared to baseline, but no significant changes in nonjaundiced controls treated similarly. This documents abnormal BDWs in acute bilirubin encephalopathy suggesting that abnormalities of functions dependent on binaural processing of auditory information may be found as neurologic sequelae to bilirubin toxicity. BAEP BDWs may be a sensitive method for detecting neurophysiological abnormalities due to bilirubin toxicity.

Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups.

The relationship of brainstem structure and function in bilirubin encephalopathy is incompletely understood. The present experiments compare quantitative measures of brainstem structures with brainstem auditory evoked potentials (BAEPs) in infant jaundiced (jj) and nonjaundiced (Nj) Gunn rats. Ten jj's from 4 litters were injected with sulfadimethoxine at 11-12 days of age to raise their brain bilirubin concentration. Littermate controls were jj's given saline, and Nj's given sulfadimethoxine or saline. At 15-17 days of age BAEPs were recorded, and rats were prepared for histological examination, as was reported in the previous paper (Conlee and Shapiro, 1991). Significant differences between groups were seen for BAEP wave I latency (P = 0.002). I-II interwave interval (P = 0.001), and amplitudes of waves I, II, III, and IV (each P less than 0.0005) due to increased latencies and decreased amplitudes in the jj-sulfa group. Animals with the most severe BAEP abnormalities had the most severe histological abnormalities. Cochlear nucleus volume had a positive linear correlation with the amplitude of BAEP waves I, II, and IV, and an inverse correlation with wave I latency and I-II interwave interval (P less than or equal to 0.001). The highest correlations were BAEP I-II interwave interval and amplitude of waves I and II with cochlear nucleus volume (r = -0.78, 0.71 and 0.70, respectively, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups.

Mechanisms underlying bilirubin encephalopathy and hearing loss remain poorly understood, including the way bilirubin enters the nervous system and how bilirubin accumulates in circumscribed regions of the brain. The present experiments examined the auditory brainstem in heterozygous (Nj) and homozygous (jj) Gunn rats at an age when serum bilirubin levels were highest, and after brain bilirubin concentration was artificially raised by sulfadimethoxine administration. In four litters of 11-12 days old Gunn rats, Nj and jj littermates received a single intraperitoneal injection of sulfadimethoxine (100 mg/kg) or a comparable volume of saline. At 16-17 days of age, brainstem auditory evoked potentials were recorded to assess the severity of bilirubin toxicity in the Nj and jj animals. Following the recordings, each animal was perfusion-fixed and frozen sections of the brainstem were cut in the transverse plane from medullary through mesencephalic levels. Sections were mounted on slides, stained with thionin and coded to avoid observer bias. Quantitative analysis revealed no differences between saline and sulfa-treated Nj rats for cochlear nucleus volume, or for cell size in the cochlear nucleus or superior olive. In the sulfa-treated jj rats, cochlear nucleus volume, and cross-sectional areas of spherical cells in the anteroventral cochlear nucleus and principal cells in the nucleus of the trapezoid body, were all significantly smaller than in the combined groups of Nj animals. The affected areas in the cochlear nucleus and superior olive are innervated by large axosomatic end-bulbs of Held or calyceal endings, and were associated with bilirubin staining of glia in the most severely jaundiced jj sulfa-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin and the auditory system.

The auditory system is highly sensitive to bilirubin toxicity. Damage to the auditory nervous system includes auditory neuropathy or auditory dyssynchrony and auditory processing problems which may occur with or without deafness, hearing loss. Auditory dysfunction may occur in children with or without other signs of classical kernicterus. Bilirubin selectively damages the brainstem auditory nuclei, and may also damage the auditory nerve and spiral ganglion containing cell bodies of primary auditory neurons. The inner ear, thalamic and cortical auditory pathways appear to be spared. Noninvasive auditory neurophysiological tests such as the auditory brainstem response (ABR) or brainstem auditory response (BAER) play an important role in the early detection of bilirubin-induced auditory and central nervous system dysfunction in the neonate.