Estudio aleatorio, doble ciego, controlado con placebo para evaluar la eficacia nutricional de Omeno 1. Resultados finales del estudio / Double-blind, randomised, placebo-controlled study to evaluate the nutritional efficacy of Omneo 1. Final study results

Antecedentes. Los problemas digestivos menores que no requieren una atención médica seria se presentan frecuentemente durante los primeros meses de vida de los recién nacidos. Entre éstos se encuentran los gases, cólicos, estreñimiento y el hambre. Una nueva fórmula infantil ha sido especialmente desarrollada para resolver estos problemas mediante la incorporación de los siguientes componentes a su formulación:• Ácidos grasos conteniendo lípidos estructurados,• Fracción de carbohidrato con un contenido reducido en lactosa y con almidón añadido, • Oligosacáridos prebióticos• Hidrolizado de proteínas. Aunque los ensayos clínicos han demostrado que los innovadores ingredientes utilizados en Omneo 1 son inocuos y adecuados para los recién nacidos, la eficacia nutricional de la composición final de la nueva fórmula todavía debe ser evaluada. Objetivo. Este estudio fue elaborado para investigar la eficacia nutricional de Omneo 1 en recién nacidos a término sanos, de acuerdo con los estándares internacionales y con los requerimientos de los comités internacionales. Resultados. 154 recién nacidos a término no alimentados con lactancia materna fueron reclutados en 4 centros en Alemania. Durante las dos primeras semanas de vida, fueron seleccionados aleatoriamente para recibir bien Omneo 1 o bien una fórmula estándar hasta la edad de 12 semanas. El análisis de los datos de este estudio reveló que los dos grupos de recién nacidos alimentados con fórmula, experimentaron un crecimiento igualmente correcto. El incremento de peso y talla así como la circunferencia craneal y el espesor del pliegue cutáneo desde el momento del estudio hasta las 12 semanas de edad estuvieron dentro del rango normal en comparación con los valores aceptados internacionalmente. Una muestra de sangre pre-prandial fue obtenida de un subgrupo de 40 recién nacidos a la edad de 6 semanas, para verificar los diversos indicadores de la condición de las proteínas. Los niveles de albúmina, de albúmina de suero y de urea así como los demás parámetros estuvieron dentro de los rangos normales para los recién nacidos alimentados con lactancia artificial. Asimismo, los niveles de los aminoácidos en plasma fueron similares en los dos grupos y reflejaron la ingesta de aminoácidos de las respectivas fórmulas en estudio.A las 6 y 10 semanas de vida, los lactantes alimentados con Omneo 1 presentaron unas heces significativamente mas blandas en comparación con los lactantes alimentados con la fórmula de control (p<0,01). En el grupo Omneo, la bifidobacteria fecal se incrementó desde 2,3 x 109 bacteria/g heces en la inclusión a 1,0 x 10'° bacteria/g heces a las 6 semanas. La bifidobacteria fecal como un porcentaje del total de microorganismos se incrementó desde 31 a 59 por ciento (p<0,01), mientras que no se observó ningún cambio en el grupo control. Estos resultados confirman la esperada bifidogenicidad de la fórmula con prebióticos añadidos. Conclusiones. Los datos de este estudio amplio y multicéntrico confirman que la nueva fórmula infantil Omneo 1 aporta unos valores antropométricos y bioquímicos muy similares a los obtenidos con una fórmula infantil estándar con una reputación establecida. Estos datos se suman a la evidencia disponible que demuestra que Omneo 1 es nutricionalrnente adecuado, bien aceptado y tolerado y efectivo para resolver problemas digestivos y alimentarios menores (AU)

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. In 22 infants, 364 GER episodes were recorded by IMP. One hundred and sixty five apneas were documented by visual validation of polygraph records. Forty-nine apneas (29.7%) were associated with GER; 11 (22.4%) of these showed acid reflux (pH < 4). A significant correlation between the time spent apneic and GER was found (P < 0.001). There is marked association between apnea and gastroesophageal reflux in infants. Patients potentially at risk cannot be reliably identified by pH metry. Its exclusive use is therefore not suitable for the detection of all GER-associated apneas in infants. The pH-independent intraluminal impedance technique has proven to be a sensitive diagnostic tool for this approach.

Intraluminal impedance: an ideal technique for evaluation of pediatric gastroesophageal reflux disease.

Gastroesophageal reflux (GER) in infants becomes gastroesophageal reflux disease (GERD) through association with distinct clinical symptoms. Monitoring of pH is considered the standard diagnostic tool through which episodes of acidity can be detected. Apparently, however, the major amount of GER occurs in the physiologic esophageal pH range, which is concealed to pHmetry. Intraluminal impedance is a new method for pH-independent detection of esophageal bolus movement. Long-term measurements and combination with other diagnostic methods, e.g., pHmetry or polygraphic recordings, are possible. Intraluminal impedance has proved especially useful in diagnosing GER and GERD in infants. It may develop into the ideal technique for this group of patients.

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.

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance.

UNLABELLED: Impaired glucose tolerance (IGT) is an increasingly frequent complication of cystic fibrosis (CF). In CF patients, a fast postprandial rise in plasma glucose is typically followed by a delayed but prolonged insulin response. Patients may develop symptoms of both hyper- and hypoglycaemia. The alpha-glucosidase inhibitor, acarbose, delays the hydrolysis and subsequent absorption of ingested carbohydrates. The aim of this study was to investigate the efficacy of acarbose in CF patients with IGT. During a 2-week inpatient period for treatment of Pseudomonas infection, 12 CF patients with IGT were studied in a double-blinded, randomized crossover trial. Each patient received acarbose (50 mg t.i.d.) for 5 days and placebo for 5 days (days 3-8 and days 10-14, respectively). Glucose, insulin and C-peptide responses to a standardized nutritional load were measured at baseline and at the end of each study period (Days 2, 8 and 14). Treatment with acarbose was associated with significant reductions in the mean value, mean peak values and the area under the curve of plasma glucose, insulin and C-peptide, compared to respective baseline values and placebo. Gastro-intestinal disturbances were recorded in 67% of patients during therapy with acarbose. CONCLUSION: Acarbose has a positive therapeutic effect on glucose tolerance in cystic fibrosis patients, as shown by attenuation of postprandial plasma glucose increase and a significant decrease in insulin secretion response. However, acarbose treatment was associated with adverse gastro-intestinal effects that may prevent patients from accepting long-term therapy.

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.

Transient myeloproliferative disorder with 11q23 aberration in two neonates with Down syndrome.

Infants with Down syndrome may develop a transient myeloproliferative disorder (TMD) with the features of acute leukemia but resolving in a spontaneous remission. Chromosomal aberrations in addition to trisomy 21 have only rarely been described. In many cases of infant acute leukemia band q23 of chromosome 11 is involved in nonrandom translocations, often resulting in a rearrangement of the ALL-1 (MLL, HRX, HTRX 1) gene. Generally, this translocation carries a bad prognosis. We describe two newborn girls with Down syndrome and TMD in whom the constitutional trisomy 21 was combined with an acquired abnormality of chromosome 11. During the TMD the morphological and immunologic features were consistent with those of megakaryoblastic leukemia. The chromosome 11 abnormalities were del(ll)(q23), but rearrangements of the ALL-1 gene were not found. Our patients had remissions that occurred spontaneously or after a mild chemotherapy. The important finding is that additional chromosomal changes may occur during TMD in Down syndrome. The fact that the abnormality was in region 11q23 raises the question of whether the risk for developing leukemia is increased under these conditions.

Pharmacokinetics of oral fluconazole in premature infants.

UNLABELLED: Systemic infections with Candida albicans in neonates are a frequent and well recognized problem. The therapeutic gold standard in this situation is the combined intravenous antimycotic treatment with amphotericin B and flucytosine. Potential adverse effects of this regimen have encouraged the search for desirable alternatives. We report on the use of oral fluconazole in neonates with Candida albicans septicaemia. Three premature infants were treated with four courses of therapy. Pharmacokinetic studies were performed during each course. At oral doses of 4.5-6 mg/kg once a day, serum levels of fluconazole were within the therapeutic range during the entire dosage interval. Follow up showed microbiological and clinical cure in all patients with no side-effects. In one patient a dosage of 4 mg/kg per day lead to a microbiological relapse with sub-therapeutic serum levels. CONCLUSIONS: Oral fluconazole seems to be a safe and effective treatment for Candida albicans septicaemia even in premature infants.

Herpes virus (KSHV) associated Kaposi sarcoma in a 3-year-old child with non-HIV-induced immunodeficiency.

UNLABELLED: A 3-year-old boy of German descent suffered from two episodes of Streptococcus pneumoniae meningitis within 2 months. One month previously, the first skin lesion of Kaposi sarcoma (KS) had been observed behind his right ear. During the following 2 years KS disseminated not only mucocutaneously but also to visceral organs. Immunological evaluation revealed severe lymphocytopenia with reduced helper/suppressor T-cell ratio and impaired humoral immune response to pneumococci. Extensive laboratory tests gave no evidence for known immunocompromising infections. However, recently described DNA sequences from a Kaposi sarcoma-associated herpesvirus (KSHV) could be identified within skin tissue. As chemotherapy failed to stop tumour progression the patient was referred for bone marrow transplantation. Eighteen months later the KS is in remission and the patient in a good general condition. CONCLUSION: The case supports the hypothesis that KSHV is involved in the aetiology of KS. Bone marrow transplantation is possibly a therapeutic option for KS in patients with immunodeficiency not related to human immunodeficiency virus infection.

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.

[Antacids for postoperative prevention of stress ulcer in infants: a dose finding study]. / Antazida zur postoperativen Stressuljusprophylaxe bei Süglingen: Studie zur Dosisfindung.

UNLABELLED: In the prophylaxis of stress ulcers with antacids in young infants there are no recommendations of dosages that consider the physiologic maturation of gastric acid secretion. During the first six month of life the amount of gastric acid secretion in relation to body weight and body surface area increases exponentially. Therefore adult dosages of antacids cannot be transferred to infants. METHODS: In a cross over study 12 infants aged between 4 and 174 days, who had been undergoing a cardiosurgical intervention with the heart lung machine, were treated during 48 hours with 2 different antacid regimens over a period of 24 hours each, monitoring the gastric pH continuously. The used antacid consisted of an aluminium-magnesium complex (Al(OH)3, 90 mg/ml and Mg(OH)2, 60 mg/ml): Regimen A: 6 x 0.5 ml per kg body weight. Regimen B: 0.25 ml per kg body weight at a gastric pH less than 3, with the pH read every 30 minutes. RESULTS: Compared to 28 applications under regimen B, 72 single doses were given under regimen A, 58 of them at a gastric pH of higher than 3. Thus, the mean administered dose was significant lower under regimen B (2.2 ml) than under regimen A (12.0 ml). Consequently, the mean level of gastric pH was higher under regimen A (median: 5.96 +/- 1.31 versus 4.94 +/- 1.16). pH-values lower than 3 were more often measured under regimen B, whereas the phases at this pH-level were longer under regimen A. CONCLUSION: The usual body weight related dosage of antacids seems to be to high for early infancy. In the face of the discrepancy of the administered antacid quantity comparing regimen A with regimen B, it seems to be reasonable for the studied age group to reduce the single antacid dose to 0.25 ml/kg body weight while adhering to a high application frequency of 6 times a day.

[Laparoscopic resection of bleeding Meckel's diverticulum]. / Laparoskopische Resektion eines blutenden Meckel'schen Divertikels.

The most malformations of the gastrointestinal tract are the Meckel's diverticula. In 25% of all complications of this disease you will find a bleeding of the diverticulum. We report a case of a 12 year old boy treated laparoscopically for a bleeding diverticulum and we describe the technical procedure. The first choice in diagnosis in the scintigraphy with 99mTc-pertechnate, at which the proof of ectop stomach mucous membrane is necessary. Laparoscopic resection of a bleeding Meckel's diverticulum performed by an experienced surgeon is a safe and considerate procedure in laparoscopic technique.

Midazolam and ketamine as premedication in colonoscopies: a pharmacodynamic study.

As colonoscopy is often painful, a premedication appears to be indispensable. Commonly, benzodiazepines, i.e. midazolam, alone or in combination with analgesic drugs are used. Besides all advantages, midazolam especially is known to have the risk of oversedation and respiratory depression. Therefore it should be used at minimal dose. In a double-blind, randomized study, three premedication-schedules of midazolam (mid) plus ketamine (ket) were compared in 33 patients, aged between 8 and 60 years, with regard to safety and acceptance by patients and endoscopist. I: ket 1 mg/kg+mid 0.1 mg/kg, max. 5 mg II: ket 1 mg/kg+mid 0.05 mg/kg, max. 2.5 mg III: ket 0.75 mg/kg+mid 0.1 mg/kg, max. 5 mg Oxygen-saturation, heart rate and blood pressure were recorded as well as the evaluations of sedation, cooperation and complaint of pain. To assess the recovery-time of the patients, the reaction time and the attention were evaluated by "Wiener's determination apparatus" and "test d2", respectively, before and at 1, 2, 3 and 4 hours after premedication. Medication I resulted in heavy sedation, good cooperation and amnesia but had the strongest tendency towards hypoxemia. Under schedule III, reduced cooperation and acceptance were seen due to a strong experience of pain. The best conditions during the examination with regard to cooperation, experience of pain and acceptance were found after premedication II without relevant depression of vital parameters. It can be concluded that midazolam can be used at minimal recommended doses as premedication for colonoscopy if combined with ketamine in a sufficient analgesic dosage.