G. Heimann

Association of apnea and nonacid gastroesophageal reflux in infants: Investigations with the intraluminal impedance technique*

An association of apnea and gastroesophageal reflux (GER) was proposed previously. However, pH metry as the standard diagnostic tool for GER only measures acid reflux (pH < 4). It is difficult to interpret studies in infants with a presumed association between apnea and GER based on pH metry because the buffering effect of feeding may result in predominantly nonacid GER. The aim of this study was to investigate the temporal association of apnea and GER with the pH‐independent intraluminal impedance technique (IMP). Infants with recurrent regurgitation or respiratory symptoms suggestive of apnea were investigated simultaneously with IMP, pH monitoring, and polygraphy. IMP patterns, pH, oronasal flow, and chest wall movement were recorded and analyzed.

Gastroesophageal reflux in infants : Evaluation of a new intraluminal impedance technique

In this study, pH metry was simultaneously applied with a new technique, the intraluminal multiple electrical impedance (IMP) procedure, for measuring gastrointestinal motility for gastroesophageal reflux (GER) detection. Seventeen infants with clinical symptoms of GER disease such as recurrent apnea, aspiration pneumonia, wheezing, and failure to thrive were investigated during two feeding periods. A single catheter combining a pH electrode with seven electrodes for impedance measurements over a distance of 8.5 cm was used for the investigation. In all patients, 185 acid episodes were detected by pH metry. In 106 of these 185 acid episodes, a unique pattern in the IMP readings was noted, indicated by a retrograde esophageal volume flow. These episodes were regarded as acid GER episodes. Seventy-one of the 185 acid episodes occurred during the clearance process of a preceding acid GER characterized by typical IMP readings of an anterograde bolus transport. Eight of 185 acid episodes were missed in the IMP readings for technical reasons. The IMP pattern described as characteristic for a GER was observed in 490 other episodes not detected by pH metry. More than 75% of all GER detected by IMP reached the pharyngeal space; 73% of all GER occurred during feeding and the first 2 postprandial hours and 27% occurred during the remaining time until the next feeding. Even during the latter period, 34% of GER were detected by IMP only; they were missed by pH metry. Volume clearance indicated by IMP was always completed earlier than acidity clearance. The results show that IMP technique facilitates the detection of all GER, whereas pH metry is confined to the measurement of acid GER. Therefore, this technique might improve the evaluation of GER disease and detection of GER in conditions with gastric hypoacidity.

Esophageal pH monitoring and impedance measurement: a comparison of two diagnostic tests for gastroesophageal reflux.

Background pH monitoring is the standard diagnostic tool for gastroesophageal reflux in infants. However, this method does not document the reflux of all kinds of fluid from the stomach into the esophagus, but only documents acid material. The parameters that define reflux episodes by pH monitoring have been derived empirically from observations of many infants considered healthy and ill. Acid reflux is a continuum, some reflux is normal and doubt exists as to how much reflux is abnormal. In this study, one of the standardized protocols for analyzing pH recordings was evaluated and compared with simultaneously obtained intraesophageal impedance measurement (IMP), a pH-independent method of detecting bolus movement within the esophagus. Methods The esophagi of 50 infants with reflux symptoms were measured, using both standard pH probe and multiple-site impedance measurement. A standard protocol for analyzing esophageal pH records was used. The sampling rate for pH values was 15/min. Acid reflux was defined as pH less than 4.0 (threshold pH) for at least 15 seconds (minimal duration) with at least 30 seconds (latency time) between separate episodes. The software used could adjust independently or in combinations the sampling rate and these reflux criteria. Thereby it was determined whether changes in the criteria for acid reflux improved the sensitivity and predictive value of pH monitoring when compared with reflux episodes defined by IMP. Results During 318 hours of recording in 50 infants, 1,887 episodes of reflux occurred according to IMP. Only 282 (14.9%) of the IMP-determined episodes were acid reflux episodes. No alkaline reflux episodes occurred. Among the 270 pH probe–determined episodes using the standard criteria of acid reflux, only 153 (sensitivity, 54.3%; positive predictive value, 56.7%) were accompanied by unmistakable retrograde bolus movement using IMP measurements. Retrograde bolus movement did not accompany the other 117 episodes. Using a sampling rate of 15/min, a pH threshold of 4.0, a minimal duration of reflux episodes of 8 seconds, and a latency time of 60 seconds, the positive predictive value of pH probe results increased to 60.7%. Variations in the sampling rate or criteria for defining acid reflux did not significantly improve the accuracy of the pH probe results versus IMP-defined episodes. Conclusions Most reflux episodes that occur in infants are undetectable by standard pH probe monitoring. pH monitoring does not detect all reflux in the esophagus but is useful for detecting acidity in the esophagus and determining the duration of its presence. Combining pH monitoring with impedance measurement is a valuable diagnostic tool for gastroesophageal reflux in infants.

Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique.

BACKGROUND The coincidence of recurrent respiratory symptoms and gastroesophageal reflux (GER) is a well-known phenomenon in infants. Twenty-four-hour pH metry is the presumed gold standard of diagnostic tools for this symptom complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be detected. Gastroesophageal reflux with an esophageal pH in the physiological range (pH 5-6.8) may represent many cases of clinically relevant GER unrecognized by pH metry. In this study the intraluminal multiple electrical impedance (IMP) procedure for complete registration of GER was compared with pH metry for its diagnostic value in the presence of respiratory symptoms. METHODS Twenty-two infants with recurrent regurgitation or pulmonary problems were investigated simultaneously with IMP, pH metry, and polygraphy during two feeding periods. Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded, among other parameters. RESULTS Three hundred sixty-four occurrences of GER were detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances were accompanied by a decrease of oxygen saturation of more than 10% of the initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16 reflux episodes were recognized by IMP only. After software-aided preselection, 165 instances of apnea were visually validated, 49 of which were accompanied by GER. Thirty-eight (77.6%) of these were exclusively recorded by IMP. CONCLUSIONS The use of pH metry alone cannot detect most GER incidents accompanied by respiratory symptoms and therefore does not appear to be suitable for this approach. The pH-independent IMP technique promises to be a reliable tool for presumably GER-associated respiratory symptoms.

Treatment of nasopharyngeal carcinoma in children and adolescents: definitive results of a multicenter study (NPC-91-GPOH).

Preliminary results of combined neoadjuvant chemotherapy, radiotherapy, and postradiation interferon beta (IFN‐β) in children and adolescents with nasopharyngeal carcinoma, especially in high‐risk patients, have been promising.

Diagnostic yield of noninvasive high spatial resolution electromyography in neuromuscular diseases

High Spatial Resolution electromyography (HSR‐EMG), a new kind of noninvasive surface EMG based on a spatial filtering technique, was evaluated with respect to the diagnosis of neuromuscular diseases. HSR‐EMG measurements were recorded from 61 healthy subjects and 72 patients with different neuromuscular diseases and analyzed quantitatively. The results indicate that a few parameters such as muscular conduction velocity, dwell time over root mean square, autocorrelation function, and chi‐value are sufficient to recognize and classify specific signal alterations due to neuromuscular disorders. A diagnostic evaluation procedure calculating automatically the most probable diagnosis from the parameter results could assign the correct diagnosis to about 81% of the investigated patients and healthy subjects. Myopathic disorders were recognized with a sensitivity of 85% (specificity: 97%), neuropathic disorders with a sensitivity of 68% (specificity: 98%). We conclude that HSR‐EMG shows a diagnostic validity similar to that described in literature for needle EMG. Moreover, the noninvasive technique provides the advantage of a simple and painless application.

A New C-Terminal Located Mutation (V272ter) in the PIT-1 Gene Manifesting with Severe Congenital Hypothyroidism

Objective: We describe a newborn with clinical signs of severe hypothyroidism and combined pituitary hormone deficiency due to a new mutation in the PIT-1 gene. Patient and Methods: Endocrine stimulation test revealed a deficiency for PRL, TSH and GH, suggesting a defect in the pituitary transcription factor PIT-1. Genetic analysis of the PIT-1 gene was performed by exon-specific PCR, followed by SSCP mutation screening and DNA sequencing of the abnormal migrating fragments. Results: DNA sequencing revealed a new mutation (V272ter) in direct neighborhood to a known mutational hot spot (R271W) in the C-terminal part of the PIT-1 molecule. Conclusions: Whereas the R271W mutation has a dominant negative effect on the mutant protein, the newly described mutation is inherited in an autosomal-recessive way. The biological consequences of these two different mutations are discussed.

Idiopathic Growth Hormone Deficiency: A Vanishing Diagnosis?

Some non-organic causes for growth hormone (GH) deficiency (GHD) can be attributed to genetic defects within the hypothalamo-pituitary axis. Using modern molecular biology techniques micromutations within the GH and GH-releasing hormone receptor genes have been detected as a rare cause of isolated GHD. Combined pituitary hormone deficiencies (CPHD), on the other hand, are associated with defects that manifest during the organogenesis of the anterior pituitary gland. In recent years an increasing number of patients with CPHD has been reported, showing mutations within pituitary transcription factors Pit-1, Prop-1 and HesX1. Such defects can be observed with different frequencies in patients. Some disorders, such as CPHD due to Pit-1 mutations, display a hormonal phenotype that seems more or less invariable. In most other forms of genetic CPHD both the combination and severity of anterior pituitary hormone deficiencies vary considerably. Ongoing research concentrates on factors involved in the differentiation and proliferation of cells that belong to the hypothalamo-pituitary growth axis. As not every possible candidate turns out to be a frequent cause of GHD or CPHD in humans, it will be many more years before the term ‘idiopathic’ becomes a vanishing attribute to the clinical diagnosis of pituitary insufficiency.

Effect of Cisapride on Acid Gastro-Oesophageal Reflux during Treatment with Caffeine

About 50% of preterm infants and neonates receiving methylxanthines for respiratory stimulation will develop a pathological gastro-oesophageal reflux (GOR) pattern. In the face of potential GOR-related complications the effect of a concomitant treatment with a prokinetic agent, such as cisapride, should be evaluated. In this study 32 formerly preterm infants were studied simultaneously by 24-hour oesophageal pH monitoring and cardio-respirogram before the presumed end of caffeine treatment. In 14 of these infants a reflux index (RI; percentage of recording time) of more than 4% could be detected (pH <4). Ten of them were treated orally with cisapride (0.2 mg/kg t.i.d.). Data of pH monitoring, cardio-respirogram and caffeine serum concentrations were obtained before and 5 days after introducing cisapride. The RI and the frequency of GOR decreased significantly with cisapride. The steady-state serum concentrations of caffeine were not influenced by cisapride and the extent of periodic breathing remained unchanged. In conclusion, cisapride has a positive influence on GOR parameters during caffeine treatment without impairing the oral bioavailability or therapeutic effect of caffeine.

Einfluss des Ernährungsstatus auf die Absorptionskinetik von Vitamin E bei Mukoviszidose (CF)

Exocrine pancreatic insufficiency with varying severity must be anticipated in 85-95% of CF patients. It leads to fat maldigestion and malabsorption of the liposoluble vitamins - A, D, E, K - and fecal loss of fat. In general, supplementation with fat-soluble vitamins is recommended in CF patients. In this study an oral vitamin E tolerance test (100 mg/kg bodyweight) was performed in 5 healthy adult volunteers to elaborate a vitamin E absorption kinetics and additionally in CF patients on medication with pancreatic enzymes to evaluate the absorption of vitamin E. 19 CF patients (ages 4 to 19 years) were studied after cessation of any additional vitamin E supplementation for 7 days. Vitamin E serum concentrations were sampled over a 72 hour period. Serum vitamin E determinations were performed with a HPLC-fluorescence technique. The kinetics of Vitamin E in healthy volunteers can be described with an open 2 compartment model. CF patients revealed consistently an altered kinetics of absorption of vitamin E, which was not compatible with this model. Baseline (c*) and maximal serum concentrations (cmax) of vitamin E as well as the area outer the oral absorption curve (AUC) correlated with the nutritional status expressed by bodyweight percentiles in CF patients. The results of this study show that in normal weight CF patients on pancreatic enzymes medication vitamin E depletion is unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)