Esophageal manometry

Esophageal manometry offers estimations of actual pressure values of the esophagus and its sphincters provided that optimal equipment such as a low compliance pump is used. By means of these techniques, it has been shown that normal pressure values exist in the lower esophageal sphincter of newborns and infants. Peristalsis during deglutition in infants exhibits normal propulsive waves. A delay in peristaltic maturation may be observed in some newborns and infants with gastroesophageal reflux (GER). The upper esophageal sphincter has a slightly lower pressure in infants than in adults. A rarely reported but important manometric finding is the common cavity phenomenon (CCP): it is induced by relaxation of the lower esophageal sphincter, which allows reflux of gastric contents into the esophagus. Patients with pathological reflux exhibit the CCP more frequently and for longer periods of time than normal controls. Thus, this phenomenon offers an additional parameter in patients with GER. Together with simultaneous pH monitoring, esophageal manometry offers a comprehensive view of esophageal function under normal and disturbed conditions. Offprint requests to: M. E. Höllwarth     

Barrett's oesophagus in children and adolescents

This paper describes 12 cases of Barrett's oesophagus (BE) selected out of a population of 364 refluxing children studied by X-ray, manometric, pH-metric, endoscopic, and bioptic methods in one single institution from 1986 to 1990. Their mean age was 14 years, the male-female ratio was 5:7, and all had had gastro-oesophageal reflux (GER) symptoms since infancy. At the time of diagnosis 9 (75 %) had vomiting, 6 (50 %) respiratory tract disease, 3 (25 %) hæmorrhage, and 1 (8 %) peptic stenosis. Seven were cared for in special institutions for brain-damaged patients and 2 had been operated upon for oesophageal atresia at birth. Lower oesophageal sphincter pressure was very low in 8 out of 9 children studied and propulsive peristalsis was markedly decreased. Excessive acid exposure was documented in 8 out of 10 patients studied and simultaneous gastric and oesophageal pH-monitoring demonstrated massive duodeno-gastric alkaline reflux in 3 (2 of them with normal oesophageal pH studies). Histological and histochemical studies, including special mucin staining revealed that the columnar-lined epithelium was of the fundic type in 2 cases, the junctional type in 7, and the specialised type in the remaining 3. Helicobacter pylori was found in the mucosa of 8 patients (in massive amounts in 3). All patients had a Nissen fundoplication with good results in terms of disappearance of the GER symptoms. The present series confirms that BE should be looked for endoscopically in children with GER and supports the hypothesis that long duration of GER and excessive acid-alkaline chemical exposure of the oesophageal lining contribute to the pathogenesis of mucosal changes. The role of H. pylori is not clear, but its intriguing presence in the majority of our cases indicates that further research along these lines is warranted.     

Effect of baclofen on esophagogastric motility and gastroesophageal reflux in children with gastroesophageal reflux disease: a randomized controlled trial

OBJECTIVE: To evaluate the effect of baclofen, a gamma-amino-butyric-acid B receptor agonist that inhibits transient lower esophageal sphincter relaxation (TLESR), on the rates of TLESR, gastroesophageal reflux (GER), and gastric emptying (GE) in children with GER disease. STUDY DESIGN: The efficacy of 0.5 mg/kg baclofen was evaluated in a randomized, double-blinded, placebo-controlled trial in 30 children. Patients were intubated with a manometric/pH assembly and given 250 mL of cow's milk. Esophageal motility and pH were then measured for 2 hours (control period). Baclofen or placebo was then administered, and 1 hour later 250 mL of milk was given again and measurements performed for another 2 hours (test period). The GE rate was measured by the (13)C octanoate breath test. RESULTS: Baclofen significantly reduced the incidence of TLESR (mean, 7.3 +/- 1.5 vs 3.6 +/- 1.2 TLESR/2 hours; P < .05) and acid GER (mean 4.2 +/- 0.7 vs 1.7 +/- 1.0 TLESR + GER/2 hours; P < .05) during the test period compared with the control period. Baclofen significantly accelerated the GE rate (median [interquartile range], GE(t1/2), 61 minutes [39, 81 minutes] vs 114 minutes [67, 170 minutes]; P < .05). Baclofen had no effect on the swallowing rate, pattern of esophageal peristalsis, or lower esophageal sphincter pressure. CONCLUSIONS: Baclofen reduces GER in children by inhibiting the triggering of TLESR. Baclofen also accelerates GE.     

健康儿童及病理性胃食管反流患儿食管动力功能研究

目的了解小儿食管运动的生理学,探讨小儿病理性胃食管反流(GER)发生的食管动力学基础。方法对60例健康儿童和62例经食管pH监测诊断为病理性GER的患儿用低顺应性毛细管灌注系统进行食管测压研究,并对健康儿童组不同年龄段之间,两组同一年龄段之间进行食管动力功能比较。结果健康儿童组下食管括约肌长度(LESL)随着年龄的增加而增长,胸内段和腹内段也相应增加(P＜0.01),下食管括约肌压力(LESP)以～1岁组为高(P＜0.05);上食管括约肌长度(UESL)随年龄的增加而增长(P＜0.01),上食管括约肌压力(UESP)以～1岁组和～3岁组为低(P＜0.01)。病理性反流患儿的食管动力功能,除～7岁组食管蠕动传导速度低于同一年龄段健康儿童外(P＜0.05),其余指标两组同一年龄段间的差异均无显著性。结论LESP的抗反流功能与年龄关系不大,LESL、UESL和UESP的功能3岁以后逐渐成熟,小儿病理性GER的发生与LESP、LESL关系不大。     

Nonspecific esophageal motility disorders in children without gastroesophageal reflux.

BACKGROUND: Nonspecific esophageal motility disorders (NEMDs) have been identified in up to 50% of adults with noncardiac chest pain or dysphagia. This study sought to determine the incidence of NEMDs in children with upper gastrointestinal tract symptoms and to evaluate the clinical course of pediatric patients with these manometric abnormalities. METHODS: The study involved 154 children aged 4 to 18 years (mean age, 11.6+/-2.6 years [SE]) who had upper gastrointestinal, swallowing-related symptoms. The children were evaluated by 24-hour intraesophageal pH monitoring, esophageal manometry, and esophagogastroduodenoscopy. RESULTS: Gastroesophageal reflux (GER) was diagnosed by pH study in 109 (71%) of 154 patients, and examination of biopsy specimens demonstrated esophagitis in 70 children with GER. Results of esophageal manometry were abnormal in 30 (67%) of 45 children without GER. A variety of motility disorders were diagnosed in 17 of the patients without GER, whereas NEMDs were diagnosed in the remaining 13 children (mean age, 10.6+/-2.7 years; 10 boys, 3 girls). Patients with GER showed normal esophageal wave propagation; however, mean lower esophageal sphincter pressure was significantly lower in patients with GER than in children with NEMDs. The children with NEMDs exhibited a diverse array of symptoms, including esophageal food impaction in 4 of the 13 patients. During a 36.2+/-4.3-month follow-up period, no correlation was found between therapeutic intervention and clinical course in the 13 patients with NEMDs. Symptomatic improvement occurred in 6 of 13 patients, including 3 children for whom no pharmacologic therapy was prescribed. CONCLUSIONS: These data indicate that NEMDs represent a common group of esophageal manometric abnormalities in children with upper gastrointestinal tract symptoms and without GER. Food impaction appears to be a relatively frequent complication, and NEMDs should be considered in children who have this finding.     

Hypozincaemia in febrile convulsion

To understand further the role of trace elements in the pathogenesis of febrile convulsions, serum zinc (Zn), copper (Cu), magnesium (Mg) and CSF Zn, Cu, Mg and protein levels were measured by spectrometry in patients with febrile convulsion (n=19), bacterial meningitis (n=9), viral CNS infection (n=16) and in the control groupn=10) which consisted of children with signs of meningeal irritation due to upper respiratory tract infection but normal CSF findings. Samples were obtained within 6 h after admission to hospital. Mean serum and CSF Zn levels in the febrile convulsion group were significantly lower than in the other groups (for serum Zn: 0.66±0.03 mg/l vs 0.98±0.07 mg/l, 1.06±0.08 mg/l, 1.05±0.09 mg/lP<0.05; for CSF Zn: 22.96±1.62 g/l vs 75.47 ±6.9 g/l, 50.32±5.235 g/l, 39.85 ±2.81 g/lP<0.05). A linear relationship was established between serum Zn and CSF Zn levels (P<0.001). Mean CSF Zn, Cu and protein levels in the bacterial meningitis group were significantly higher than in the other groups (for CSF Cu 63.94±6.33 g/l vs 38.77±2.70 g/l, 35.84±3.48 g/l, 33.86±2.88 g/lP<0.05; for CSF protein 0.80 ± 0.12 g/l vs 0.22±0.02 g/l, 0.53±0.08 g/l, 0.19±0.01 g/lP<0.05). In children with meningitis, the elevation of the mean CSF Zn and Cu levels may result from the breakdown of the blood-brain barrier and subsequent leakage of trace elements and protein from serum to CSF. There was no significant difference between the four groups in terms of mean serum Mg and mean CSF Mg levels.Conclusion Serum and CSF Zn levels are decreased in children with febrile seizures. Zinc deprivation may play a role in the pathogenesis of febrile seizures.     

Contribution of the His angle to the gastroesophageal antireflux mechanism

The high pressure zone (HPZ) is a result of a series of combative forces that converge in the gastroesophageal junction and contribute to generate the pressure barrier. Recognized factors in this function are the positive intra-abdominal pressure transmitted to the lower esophagus, thoracic suction, the diaphragmatic hiatus, the intrinsic lower esophageal sphincter, and the effect of gastric fundus acting on the distal esophagus through the His angle. The exclusive and quantitative role of the His angle is evaluated with the help of two experimental models (in vivo and in vitro) in the dog. By manometric procedures the gastric pressure at which the sphincter opens (OP) is studied under overloaded conditions, both in the living animal and in a gastroesophageal specimen, varying the His angle from 90° to 0°. In the in vivo model the pressure of the barrier with a His angle of 90° was 7.33 ± 3.4 mm Hg and the OP of 8.66 +- 4.1 mm Hg, while with the His angle at 0° the pressure of this barrier was 10.66 +- 2.9 mm Hg and the OP 16 +- 6.9 mm Hg (p < 0.05). In the in vitro model the His angle at 0° multiplied the OP two or three times. We conclude that the His angle at 0° allows transmission of the fundic pressure extrinsically to the sphincter, giving way to a higher OP, and increasing the degree of competence. Offprint requests to: J. Boix-Ochoa at the above address     

Intraesophageal pressure monitoring and the severity of respiratory distress syndrome

The intraesophageal pressure difference (P _es) was measured in 46 preterm infants, 36 with respiratory distress (RDS). It was 12.7±2.9 mm Hg (mean±SEM) in severe RDS, 9.6±3.2 mm Hg in moderate RDS, and 5.2±1.6 mm Hg in infants with mild disease, measured at the age of 8 h. These intergroup differences were highly significant (P<0.001). During the first 96 h of life the P _es decreased to 6.1±1.1 mm Hg in severe RDS and to 4.8±1.2 mm Hg in moderate RDS. These changes were also highly significant (P<0.001) when compared with respective initial values. In infants with mild disease and in healthy preterm infants, the P _es did not alter significantly during the first 96 h of life.The correlations between gastric aspirate L/S ratio and the P _es at the age of 8 h (r=-0.65, P<0.001) and at the age of 24 h (r=-0.73, P<0.001) were highly significant.It is concluded that intraesophageal pressure monitoring is a valuable tool in the intensive care evaluation of the severity of RDS.Supported by grants from the Foundation for Paediatric Research and from the Medical Research Council, Academy of Finland     

Esophageal motility and gastroesophageal reflux in children with chronic respiratory diseases

Children with chronic respiratory diseases may be a high-risk population for gastroesophageal reflux (GER). In order to describe GER in this population, we systematically studied 7-h pH-metry and prolonged esophageal manometry (over 45 min) in 124 children admitted for respiratory disorders without digestive symptoms. The results showed that: (1) GER varied in significance before and after meals; (2) postprandial reflux was correlated with esophageal motor activity, but preprandial reflux was not; (3) moderate refluxers had reduced lower esophageal sphincter (LES) pressure, but severe refluxers had no significative decrease in LES pressure. The use of multivariate analysis permitted us to conclude that long-term esophageal manometry and pH-metry were complementary in defining severe GER. Offprint requests to: M. Bouchoucha     

Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters

Biliary atresia (BA) is a neonatal obliterative cholangiopathy of unknown etiology. Despite the Kasai procedure, hepatic fibrosis and portal hypertension (PH) still occur. Interleukin-8 (IL-8) is an important mediator of inflammation and immune response in human disease. The objective of this study was to investigate the potential role of IL-8 in the pathogenesis of the progressive, sclerosing, inflammatory process and fibrosis in BA. A total of 60 pediatric patients with BA and 15 healthy children were evaluated. The mean ages of BA patients and controls were 6.3±0.6 and 6.7±1.1 years, respectively. The patients were classified into two groups according to their clinical outcomes: patients with jaundice (total bilirubin ±25.5 mol/l) and patients without jaundice (total bilirubin <25.5 mol/l). The IL-8 levels in serum samples were determined by commercially available enzyme-linked immunosorbent assay. Serum IL-8 levels were higher in the BA patients than in healthy children (236.2±60.1 vs. 34.5±12.1 pg/ml, P<0.001). Patients with jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Serum IL-8 levels in the jaundice group were significantly higher than in those without jaundice (516.5±130.0 vs. 49.3±10.4 pg/ml, P<0.0005). Furthermore, patients with PH had higher IL-8 levels than those without PH (378.1±102.2 vs. 106.6±48.4 pg/ml, P<0.005). In the jaundice-free group, IL-8 levels were elevated in patients with PH compared with those without PH (79.0±17.4 vs. 19.7±5.8 pg/ml, P<0.005). The present study demonstrated elevation of serum IL-8 levels in children with BA. Serum IL-8 levels were also higher in patients with jaundice compared with patients without jaundice. These findings suggest that IL-8 may play a significant role in the pathogenesis of BA.     

Hemodynamic effects of ketamine in children undergoing cardiac catheterization

Summary Ketamine is used to supplement sedation during cardiac catheterization. We studied ketamine-induced circulatory changes in 28 acyanotic children (18 of whom had left-to-right shunts), aged 4–161 months (mean, 33 months). Oxygen consumption ( ) was measured continuously.In the 18 patients with shunts, the pulmonary to systemic flow ratio fell slightly (2.3±1.1 to 1.8±0.4,p<0.05). In all patients, the ratio of pulmonary (PVR) to systemic vascular resistance (SVR) rose from 0.16±0.09 to 0.28±0.21,p<0.001. Ketamine increases , heart rate, cardiac output, and pulmonary arterial pressure (PAP). The rise in PAP is more consistent than the rise in PVR; resistance changes were greatest in patients with elevated resting PVR (r=0.54). Caution should be used in administering ketamine to selected subjects; moreover, ketamine can confuse interpretation of cardiac catheterization data, especially if is assumed and not measured.     

Analysis of pH dynamics in the distal esophagus utilizing pH histograms and acid clearance values

Existing scoring systems for 24-h esophageal pH recording rely heavily on total duration of acid reflux; little is known or understood of the significance of dynamic aspects of esophageal acid clearance. The 24-h pH profile and rate of acid clearance in the lower esophagus was analyzed in children with clinical features of gastro-esophageal reflux (GER). Twenty-four-hour histograms of pH and time were developed with whole-pH data obtained by 24-h pH monitoring, and values for acid clearance were calculated from actual pH curves. The acid clearance value represented the average time in seconds to recover 1 pH unit from the lowest pH to pH 4.0. Clearance values greater than 100 s/pH were considered to be abnormal. Sixty-six recordings were analyzed. Five types of pH profile were characterized: (1) a normal pattern in which esophageal pH did not fall below pH 4.0 and the acid clearance value was 67.9 ± 41.1 s/pH (mean ± SD); (2) a long-tail pattern with a moderate number of reflux episodes and rapid acid clearance. The mean acid clearance value was 78.1 ± 46.4 s/pH; (3) an intermediate pattern with esophageal pH at or near 4.0 for prolonged periods where the mean acid clearance value was significantly delayed (285.6 ± 109.8 s/pH); (4) a pseudo-GER pattern with moderate reduction in pH during reflux episodes, but with prolonged acid clearance. The mean acid clearance value was 175.1 ± 93.0 s/pH; and (5) a GER pattern; this was associated with either infrequent acid reflux and delayed acid clearance, or frequent reflux episodes and rapid acid clearance. The mean acid clearance value was 160.3 ± 113.6 s/pH. Dynamic analysis of acid clearance in the esophagus may be useful therapeutically. Correspondence to: Y. Watanabe     

Circulating somatomedin-C levels and the effect of growth hormone-releasing factor on plasma levels of growth hormone and somatostatin-like immunoreactivity in obese children

The effect of growth hormone-releasing factor (GRF) 1-44 on growth hormone and somatostatin release in plasma has been studied in 20 obese children. Twenty age and sex-matched children with normal weight served as controls. Mean peak growth hormone response in obese children after 1 g/kg body wt. GRF 1-44 was significantly lower than in controls (23.7±3.6 ng/ml vs. 41.1±3.0 ng/ml;P<0.01), as were mean integrated growth hormone response areas (1544±272 ng×ml^-1×2 h vs. 2476±283 ng×ml^-1×2 h;P<0.01). Mean plasma levels of somatostatin-like immunoreactivity did not change after GRF in both goups. Mean somatomedin-C levels in obese children were significantly higher compared to controls (1.6±0.4 U/ml vs. 0.86±0.4 U/ml;P<0.01). Somatomedin-C levels were not related to the integrated growth hormone responses. In conclusion there is no relation between somatomedin-C levels and the reduced growth hormone-releasing effect of GRF in obese children. GRF does not alter peripheral somatostatin-like immunoreactivity levels either in normal or obese children.Abbreviations Sm-C somatomedin C - GRF growth hormone-releasing factor - GH growth hormone - SLI somatostatin-like immunoreactivity     

Calcitonin secretion in children with insulin-dependent diabetes mellitus

To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P<0.05) higher basal levels of both tCT (24.5±7.1 ng/l) and exCT (5.6±1.6 ng/l) than controls (tCT: 18.7±5.4 ng/l; exCT: 4.3±1.2 ng/l). Calcium stimulation test pointed out significant increase (P<0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic C cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test.     

A computerized vector manometry and MRI study in children following posterior sagittal anorectoplasty

The study was designed to evaluate computerized eight-channel vector manometry (8CVM) and pelvic floor magnetic resonance imaging (MRI) as methods to assess the anal sphincter following posterior sagittal anorectoplasty (PSARP) for anorectal malformations, in particular the functional capacity of the sphincter structures in correlation with postoperative MRI findings. Seventeen children had been operated upon for a rectovesical, -urethral, or -vaginal fistula including one female cloacal malformation; 4 had a secondary PSARP. Mean follow-up was 5.57 years. Continence was evaluated with a modified Kelly score. A CVM technique with an eight-channel perfusion catheter was used. In addition to software-supported data, the manometric parameters included a score-system assessing three different pressure zones of the anal canal qualitatively on the three-dimensional image of the anal sphincter profile. The same procedure was performed on sagittal, oblique axial, and oblique coronal MRI. Furthermore, the thickness of the sphincter muscle was assessed at the level of the maximal mean segmental pressure. All children had decreased absolute vector-volumetry values at rest and on squeezing. Correlation with the clinical score was poor. Correlation of the manometric score with the clinical course was similar to the correlation of MRI score with clinical course (R = 0.425; P = 0.1). Thirteen children demonstrated normal or increased sphincter length; 5 of these had a decreased high-pressure zone (HPZ). The position of the anorectum in the sphincter muscles could be evaluated by the vector-volumetry image as anatomic in 11 cases, nearly correctly positioned in 4, and ectopic in 1 child. MRI detected 2 cases of malposition, 10 anatomic, and 4 nearly-anatomic findings. Correlation of the manometric score with the MRI score and the thickness of the sphincter muscle at the HPZ was significantly high (R = 0.801; P < 0.0001). 8CVM is thus highly sufficient in illustrating the function of the sphincter musculature seen on pelvic floor MRI. Both methods only moderately reflect clinical follow-up, since continence depends on more than sphincter ability. Accepted: 9 March 2000     

Delayed gastric emptying in gastroesophageal reflux disease: the role of malrotation

The association between gastroesophageal reflux (GER) and intestinal malrotation (IM) has been well described. Delayed or impaired gastric emptying in IM is thought to be a contributing factor in the development of gastroesophageal reflux disease (GERD). The current study assessed the role of malrotation in delayed gastric emptying in children with GERD. We also evaluated the interactions between GERD, malrotation, gastric pH abnormalities, and gastric dysmotility. Sixty-seven patients between 1 and 5 years of age (mean 3.08±1.2) and with symptoms of GER, such as emesis, reactive or recurrent lung disease, and/or growth retardation, were studied in 2001–2005. Upper and lower gastrointestinal contrast studies were performed for the diagnosis of malrotation. Gastric motility was evaluated with a liquid gastric emptying protocol. GER was documented by upper gastrointestinal studies, scintigraphy, and/or 24-h pH monitoring. In our series of 44 children with GERD, there was an unexpectedly high incidence of IM: 54.5% (24/44). IM has previously been known to occur in 25% of patients with GERD. GERD was found in 24 (82.7%) of 29 patients with IM. Mean nuclear gastric emptying (MNGE) was 51.6±8.04 min in patients with isolated GERD and 96.6±20.5 min in children with IM and GERD. There was a statistically significant difference in MNGE time (p<0.05) between children with primary GERD and in those with GERD and IM. Esophageal pH monitoring showed that mean fraction time below pH 4 was 7.06±1.1% in patients with isolated GERD and 14.7±4.1% in patients with IM and GERD. GERD is common in children between 1 and 5 years old. Using gastric emptying studies and esophageal pH monitoring, we have shown that gastric dysmotility and esophageal pH abnormalities are highly prevalent, especially in children with malrotation compared with children with isolated GERD. These findings suggest that malrotation is an important factor responsible for delayed gastric emptying in GERD. Hence, we recommend that all infants and children with GERD and delayed gastric emptying undergo careful evaluation for malrotation.     

Surface electrogastrography in children with esophageal atresia

Surface electrogastrography was performed in 18 patients with esophageal atresia (EA) and 10 normal controls to investigate the possible role of a congenital enteric nerve defect as a cause of gastroesophageal reflux (GER), which is common after repair of EA. The means of the dominant frequencies and ranges of the frequency distribution were compared. The dominant frequencies (0.047+/-0.007 Hz) in the EA group did not differ significantly from those of the controls (0.050±0.007 Hz,P >0.1), although 2 patients had bradygastria and 2 had tachygastria in the EA group. The range of the frequency distribution was significantly wider in the EA group compared with normal children (P = 0.002). The wide frequency distribution in children with EA suggests disturbed electrical activity of the stomach, which could be associated with poor electromechanical coupling and, hence abnormal gastric contraction.     

Lower esophageal sphincter function in infantile hypertrophic pyloric stenosis

Esophageal manometry was performed in 18 infants between 29 and 105 days of age with hypertrophic pyloric stenosis. Continuous 24-h esophageal pH monitoring was also carried out in 9 cases before and after pyloromyotomy in order to study lower esophageal sphincter (LES) function in infantile hypertrophic pyloric stenosis (IHPS). The mean preoperative pressure and length of the LES in IHPS were 9.30 mmHg and 1.30 cm respectively, which were significantly lower and shorter than those in controls (P <0.01), and gastroesophageal reflux was highly significant. The esophageal manometric studies showed that LES pressure increased markedly on the 7th postoperative day to 12.58 ± 2.56 mmHg and returned to normal values within 2 to 11 months after operation. The pH monitoring indicated that in most cases reflux had disappeared on the 7th postoperative day and the reflux parameter decreased from 8.34% to 3.34%. Our data suggest that most cases of IHPS (12/18) were accompanied by LES incompetence, but LES competence as a pressure barrier at the gastroesophageal junction became normal after operation. Offprint requests to: Y. X. She     

Evaluation of growth hormone in thalassaemic boys with failed puberty: Spontaneous versus provocative test

Growth hormone (GH) secretion was determined by evaluating ultradian GH profiles for 12 h and GH responses to insulin stimulated hypoglycaemia (ITT) in 28 stunted boys with -thalassaemia major aged 15.2–17.4 years, who presented with pubertal failure (FP). Healthy non thalassaemia prepubertal boys (n=10) aged 7.5–8.8 years, were studied as controls. All patients had normal responses to ITT with peak GH levels 15 mU/l. Basal GH concentrations (mean±sem) (1.65±0.03 mU/l vs 2.58±0.27 mU/l;P<0.05) and the stimulated GH responses (peak GH=15.4±0.20 mU/l vs 21.08±0.78 mU/l;P<0.001) were significantly lower in the patients with failed puberty than in the controls, indicating that the FP patients had diminished GH reserve and secretory capacity. Moreover, all the GH peak parameters including the maximum spontaneous concentrations (MX-GH) and the area under the GH curve (AUC) were significantly lower in the thalassaemic patients than in the controls (MX-GH=5.2±0.21 mU/l vs 20.42±0.14 mU/l;P<0.001; AUCb=421.22±4.31 mU/l vs 712.20±3.42 mU/l;P<0.001). These observations suggest that the thalassaemic patients had endogenous neurosecretory GH deficiency (GHND). Priming with sex steroid did not cause any improvement in the spontaneous or stimulated GH secretory patterns in thalassaemic patients. It was noteworthy that in neither the patients nor the control subjects, was there a significant correlation between the maximum stimulated and the MX-GH concentrations. These data suggest that the provocative ITT underestimates spontaneous GH secretion and that measurement of spontaneous GH secretion was a more reliable method for identifying patients with GH insufficiency than the ITT.     

Tolerance,pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients

Twenty cystic fibrosis patients aged 1.8–22 years (mean ±SD: 9.6 ± 4.8 years) withPseudomonas aeruginosa pulmonary exacerbations were treated with amikacin (AM) (35 mg/kg/day in one daily 30 min infusion) associated with either ceftazidime (200 mg/kg/day in 3 i.v. injections) (n = 19) or imipenem (n = 1) at the same dose. Glomerular and tubular functions (creatinine clearance, 24-h proteinuria, ₂ microglobulinuria, lysozymuria) and audiometry remained within normal ranges from day 0 to day 14. A peak concentration of AM of 83 ± 19 mg/l and a trough concentration of 0.8 ±0.5 mg/l were observed in blood while AM levels in sputum were above the minimal inhibitory concentration 50 from 30 min to 16 h. No serum accumulation of AM was observed during the treatment. From day 0 to day 14, the following changes were observed: weight/height ratio: 96%–100% (P < 0.001); daily energy intake: 111%–128% of RDA (P < 0.001); prealbumin: 195–290 mg/l (P < 0.001); forced vital capacity (FVC): 66%–81% (P < 0.01); forced expiratory volume in 1 s: 60%–75% (P < 0.01); forced expiratory flow between 25% and 75% of FVC: 42%–56% (P < 0.01); nocturnal SaO₂ also improved significantly; cardiac rate decreased from 89 ±18/min to 76 ± 16/min (P < 0.001); respiratory rate decreased from 31 ±15/min to 26 ± 10/min (P < 0.05); inflammatory parameters (white blood cells, polymorphonuclear cells, erythrocyte sedimentation rate) also improved.