Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system.

A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.

Isolated, unruptured sinus of Valsalva aneurysm: serendipitous detection and correction.

Reaction of an isolated, unruptured sinus of Valsalva aneurysm is described. Detection was serendipitous in a patient with previous surgical resection and grafting of significant aortic coarctation. The philosophy and importance of proceeding with elective resection in these progressive lesions is emphasized.

Treatment of gastroesophageal reflux in children by Thal fundoplication.

The anterior fundoplication described by Thal has been used in treating gastroesophageal reflux surgically in 362 children at The Children's Mercy Hospital and at St. Luke's Hospital in Kansas City, Missouri, because medical therapy had failed or was inappropriate. Long-term results have been evaluated in regard to relief of reflux and relief of symptoms attributed to reflux. Of the 335 patients followed from 1 to 8 years, 90% had a satisfactory initial result. Five percent required reoperation for a recurrence of reflux due to failure of the fundoplication or development of a hiatus hernia. All recurrences developed with 5 months of the initial operation. Fifteen of 335 patients (4.5%) had persistent symptoms despite correction of the gastroesophageal reflux; in these patients, attributing the symptoms to reflux was incorrect. There were no deaths in this series of patients as a result of operation. The success rate of the Thal fundoplication in children compares favorably with that of the Nissen Fundoplication.

Care of infants with esophageal atresia, tracheoesophageal fistula, and associated anomalies.

One hundred consecutive patients with esophageal atresia or tracheoesophageal fistula, or both, were treated at The Children's Mercy Hospital during the past 14 years. Each patient was evaluated and a plan for therapy was formulated depending on the type and urgency of concomitant disease. Healthy patients were treated by primary repair. Those with respiratory disease were treated before repair by gastrostomy, upper pouch suction, and antibiotics. In the small premature infant and the patient with major associated anomalies, repair of the esophageal atresia and tracheoesophageal fistula was postponed by gastrostomy, upper pouch suction, and parenteral nutrition while the concomitant disease was treated. Fifteen patients with life-threatening associated anomalies required operation before esophageal repair and 13 of them survived. During the initial hospitalization two deaths related to esophageal atresia occurred, whereas three prerepair and two late (2 1/2 and 3 months) postrepair deaths related to associated anomalies occurred. Thus, 93 of the 100 patients left the hospital alive. The increased survival is due not only to improved care of esophageal atresia and tracheoesophageal fistula, but also to a more aggressive approach to the treatment of the serious associated anomalies.

Gastroschisis complicated by intestinal atresia.

Gastroschisis complicated by intestinal atresia is a complex problem. Six cases are presented. A review of the literature and of our own cases shows a high mortality rate. Success or failure is related more to the pathology present than to any specific method of operative management. Resection and primary anastomosis is the favored method of treatment, as the intestine heals well in spite of its appearance. Primary closure of the abdominal wall musculature and skin is done whenever possible. A gastrostomy is used uniformly. Intravenous hyperalimentation is critical to survival of these babies and should be used early. The use of this therapeutic modality allows for the onset of gastrointestinal function spontaneously (often over prolonged periods of time) without nutritional deprivation. Intestinal atresias almost always are easy to identify in babies with gastroschisis. Extensive dissection and mobilization of this friable intestine is contraindicated in those babies in whom an atresia is not obvious but only suspected. In such cases the gastroschisis defect should be managed by whatever method is deemed appropriate and the baby observed while receiving intravenous nutritional support. If an atresia is present, it can be managed later in the baby's course by resection and primary anastomosis.

Tracheal agenesis.

Tracheal agenesis is a rare cause of respiratory distress in the neonatal period. Temporary survival depends on ventilation through the esophagus. Thirty-eight case reports of tracheal agenesis (including one from this institution) have appeared in the literature. In this paper, we present the case reports of our 2 patients and review the literature. Tracheal agenesis is associated with a wide variety of congenital anomalies, the most frequent being ventricular septal defect. A new classification encompassing seven types of tracheal agenesis is described.

Vascular anomalies and tracheoesophageal compression: a single institution's 25-year experience.

BACKGROUND: Vascular rings are uncommon anomalies in which preferred strategies for diagnosis and treatment may vary among institutions. In this report, we offer a description of our approach and a review of our 25-year experience. METHODS: A retrospective review was conducted of all pediatric patients with symptomatic tracheoesophageal compression secondary to anomalies of the aortic arch and great vessels diagnosed from 1974 to 2000. RESULTS: Thirty-one patients (38%) of eighty-two patients (mean age, 1.7 years), were identified with double aortic arch, 22 patients (27%) with right arch left ligamentum, and 20 patients (24%) with innominate artery compression. Our diagnostic approach emphasized barium esophagram, along with echocardiography. This regimen was found to be reliable for all cases except those with innominate artery compression for which bronchoscopy was preferred, and except those with pulmonary artery sling for which computed tomography or magnetic resonance imaging, in addition to bronchoscopy, were preferred. Left thoracotomy was the most common operative approach (70 of 82; 85%). Ten patients (12%) had associated heart anomalies, and 6 (7%) patients underwent repair. Complications occurred in 9 (11%) patients and led to death in 3 (4%) patients. CONCLUSIONS: In our practice, barium swallow and echocardiography are sufficient in diagnosing and planning the operative strategy in the majority of cases, with notable exceptions. Definitive intraoperative delineation of arch anatomy minimizes the risk of misdiagnosis or inadequate treatment.

Effects of chronic salicylate on GABAergic activity in rat inferior colliculus.

It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.

GAD levels and muscimol binding in rat inferior colliculus following acoustic trauma.

Pharmacological studies of the inferior colliculus (IC) suggest that the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in shaping responses to simple and complex acoustic stimuli. Several models of auditory dysfunction, including age-related hearing loss, tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA neurotransmission in central auditory pathways. The present study attempts to further characterize noise-induced changes in GABA markers in the IC. Four groups (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post-exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined to the basal half of the cochlea. There was a significant decrease in glutamic acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with complete recovery by 30 days post-exposure (P>0.98). Observed decreases in cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor binding revealed a significant increase (+20%) in IC 30 days after sound exposure (P<0.05). These data suggest that changes in GABA neurotransmission occur in the IC of animals exposed to intense sound. Additional studies are needed to determine whether these changes are a result of protective/compensatory mechanisms or merely peripheral differentiation, as well as whether these changes preserve or diminish central auditory system function.

An absent right and persistent left superior vena cava in an infant requiring extracorporeal membrane oxygenation therapy.

A persistent left superior vena cava (PLSVC) is the most common anomaly of the major veins. However, an absent right superior vena cava and PLSVC is much less common; fewer than 100 cases have been reported in the world literature in patients with situs solitus. This rare variation was encountered in a newborn requiring extracorporeal membrane oxygenation (ECMO) for meconium aspiration and interfered with venous cannulation. The anomaly was not suspected before an unusual cannula position was observed on the chest radiograph, and it was confirmed by bedside venography. Adequate venous cannulation was obtained through the anomalous vessel using a flexible catheter, allowing for an uneventful ECMO course. The epidemiology and embryology of this incidental anomaly are reviewed, and the methods used to circumvent the difficulties it presented in this case are described.

Early recognition and aggressive treatment of gastroesophageal reflux following repair of esophageal atresia.

Twelve patients with gastroesophageal reflux following repair of esophageal atresia are presented. Reflux produced recurrent stricture, failure to thrive, repeated pneumonitis, and in one patient, respiratory arrest and nearly death. Treatment consists of positional therapy or fundoplication operation both of which seem less successful in this combination of lesions than with GER and a normal esophagus. There was one death as a late postoperative complication of fundoplication.

Levator repair and posterior suspension for rectal prolapse.

An operative procedure for the management of rectal prolapse is described. It has the advantanges of simplicity, relative safety, short hospitalization, and lack of recurrence in the four patients presented.

Neonatal genital reconstruction.

It is evident from studies of boys who suffered a surgical catastrophe at a young age and were then assigned a female sex role that cultural and environmental influence are a potent determinant of a child's gender identity. It is imperative that parents have their child's sex assignment firmly fixed in their minds as early as possible. Early surgical correction of a child with ambiguous genitalia to conform to the sex of assignment will serve greatly to reinforce appropriate behavior in the parent. Such surgical intervention for diagnostic and reconstructive purposes is both desirable and safe in the first weeks of life.

Hepatic hemangioma: resection using hypothermic circulatory arrest in the newborn.

Hepatic hemangioma (hemangioendothelioma) is a benign vascular tumor with significant morbidity and mortality. Two newborn infants underwent partial hepatectomy for treatment of massive hepatic hemangioma, one with atrial septal defect and secondary congestive heart failure, and the other with symptomatic marked hepatomegaly. Cardiopulmonary bypass with induced deep hypothermic circulatory arrest was used in both patients in order to facilitate resection and prevent sudden massive blood loss. One infant also had closure of an atrial septal defect in addition to the partial hepatectomy. Both infants survived without complication and showed complete resolution of preoperative symptoms. This technique coupled with the use of fibrin glue is of value in infants with large hepatic hemangiomata and cardiac decompensation in the neonatal period.

Abbreviated esophageal pH monitoring as an indication for fundoplication in children.

Intraesophageal pH recordings from 40 patients with abnormal studies who underwent fundoplication during a 1-year period were evaluated. Scores were recalculated for the first 12, 16, and 20 hours, respectively. Five of the recordings were for less than 24 hours, but were grossly abnormal and mathematically could not have normalized at 24 hours. The percentage of studies which were normal at 12, 16, and 20 hours were 20%, 15%, and 0%, respectively. One fifth of the patients would have been denied a fundoplication based on 12-hour results. In addition, 75 consecutive pH recordings were evaluated prospectively. Total scores were determined for the first 12, 16, and 20 hours with accuracies of 85%, 93%, and 92%, respectively. The sensitivity of 12-hour monitoring was only 78%. All abbreviated studies had a low rate of false positives; however, any false positives may be significant when used to determine the need for an operation. Abbreviated studies were associated with high false-negative rates (up to 52% for the 12-hour studies) for the calculated mean duration of sleep reflux, a parameter that has been found to be useful in identifying patients with respiratory symptoms secondary to gastroesophageal reflux. The use of abbreviated pH monitoring is discouraged.

Postradiation renovascular hypertension.

Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.

Esophageal atresia with double tracheoesophageal fistula.

Ninety cases of esophageal atresia (EA) with double tracheoesophageal fistula (TEF) from the literature and 4 new cases are examined. The incidence may be more common than is generally recognized with incidences up to 5.3% reported. The pre-, intra-, and postoperative diagnosis may be difficult, and half have been missed initially with almost half of these being first recognized at autopsy. During repair of EA and TEF the proximal esophagus should be mobilized looking for a proximal fistula. Many proximal TEF are missed at the initial operation and discovered in the postoperative period. The symptoms, diagnosis and treatment of the unrecognized proximal TEF are similar to that for isolated TEF. Results should be good since this problem occurs in large babies with fewer and less complex associated conditions.

The Thal fundoplication for gastroesophageal reflux.

The technique of anterior fundoplication for gastroesophageal reflux originally described by Alan Thal has been used in our institution in 605 patients. The description of the technique is the purpose of this paper. A brief description of the results in these 605 patients are also presented.

Neonatal renovascular hypertension - a complication of aortic monitoring catheters.

Two critically ill neonates with severe renovascular hypertension as a complication of aortic monitoring catheter are presented. They did not respond to intensive medical therapy for hypertension. In spite of their precarious general condition, nephrectomy was undertaken with complete relief of symptoms.

Thal fundoplication: a simple and safe operative treatment for gastroesophageal reflux.

One hundred patients with complications of severe gastroesophageal reflux were treated surgically by the Thal fundoplication. In all patients the symptoms of reflux were eliminated by the operation, although 4 recurred within 8 months. Two of these were due to disruption of the fundoplication and two were due to hiatus hernia not recognized and repaired at initial operation. There were 8 deaths, none related to gastroesophageal reflux or the operation. Four patients required re-operation for intestinal obstruction. The Thal fundoplication is a simple procedure which fixes the distal esophagus within the abdomen and produces an acute angle of His. It is effective in prevention of reflux and the patient is able to burp and vomit if necessary. It has not been associated with dysphagia or "gas bloat" which may follow the Nissen fundoplication.