bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Safety of a New Solution of Vitamin K1(20) in Children with Cholestasis
Authors: Amédée‐Manesme Olivier , Lambert Willy E. , Alagille Daniel , De Leenheer André P. 
Published: January 2024

SummaryIn cholestatic diseases, the absorption of fat‐soluble compounds, including vitamin K1(20), is low and periodic administration of vitamin K1(20) is often necessary. Due to the low absorption of vitamin K1(20) from the Konakion formulation, late hemorrhagic disease of the newborn also occurs especially after oral vitamin K1(20) prophylaxis with Konakion. We investigated the pharmacokinetics and the safety of a new formulation of vitamin K1(20) in a mixed micelles (MM) solution. Compared to the old formulation (Konakion) using Cremophor EL as a solubilizer, the higher vitamin K1(20) levels (as measured by HPLC) in serum obtained after oral administration of the MM formulation clearly demonstrate a superiority of this new formulation. Additionally, the elimination of Cremophor EL as well as of propylene glycol from the formulation avoids possible adverse effects associated with intravenous or intramuscular administration. Furthermore, in most cases, the discomfort of parenteral injections can be overcome by simple oral administration even in children with severe cholestasis.
Intestinal Permeability to 51Cr‐EDTA and Orocecal Transit Time in Cystic Fibrosis
Authors: Escobar H. , Perdomo M. , Vasconez F. , Camarero C. , del Olmo M. T. , Suarez L. 
Published: January 2024

SummaryIntestinal permeability was investigated in 16 children with cystic fibrosis and 14 age‐matched controls, making use of 51Cr‐EDTA as probe molecule. Orocecal transit time was also evaluated using the lactulose/ hydrogen breath test. There was an increase in permeability to 51Cr‐EDTA in patients with cystic fibrosis (mean 13.62%) compared with the control group (mean 1.08%). The orocecal transit time was prolonged in patients with cystic fibrosis compared with controls. Mean fasting breath hydrogen concentration was significantly greater in cystic fibrosis patients (13 ppm) compared with control patients (3 ppm). There was no correlation between the percentage of 51Cr‐EDTA excreted and the orocecal transit time in either control or cystic fibrosis patients.
Valproate Use Associated with Persistent Hyperammonemia and Mitochondrial Injury in a Child with Down's Syndrome
Authors: Kane Robert E. , Kotagel Suresh , Bacon Bruce R. , Vogler Carole A. 
Published: January 2024

SummaryValproate is a commonly prescribed anticonvulsant drug that may cause potentially fatal hepatotoxicity, bone‐marrow toxicity, and pancreatitis. Toxicity usually resolves, though, after discontinuation of the medication. We report a 9‐year‐old boy who had Down's syndrome and who developed valproate‐associated bone marrow toxicity, and hepatotoxicity that persisted > 2 years after discontinuation of valproate therapy. Three years after starting valproate, he developed erythrocyte aplasia with a severe, normochromic, macrocytic anemia requiring several blood transfusions. Several months later while still receiving valproate, he developed progressive hyperammonemia and decreased hepatic synthetic function. The macrocytic anemia resolved and hepatic synthetic function improved after discontinuation of valproate therapy. However, hyperammonemia, steatosis, mitochondrial injury, and marked hepatic iron accumulation persisted > 2 years after the valproate was discontinued. The persistent hyperammonemia was responsive to lactulose therapy. A decrease in hepatic iron content by serial phlebotomies did not result in any improvement in the hyperammonemia or hepatic synthetic function. This is the first report of persistent hyperammonemia and hepatic mitochondrial injury after valproic acid therapy.
Successful Late Kasai Portoenterostomy
Authors: Bielamowicz Anne , Weitzman Jordan J. , Alshak Najeeb S. , Rosenthal Philip 
Published: January 2024

SummaryThis article describes an infant with extrahe‐patic biliary atresia who underwent a successful hepato‐portoenterostomy at age 132 days in spite of a delay in diagnosis. Contributing to the delay in diagnosis of this case were the lack of appreciation of acholic stools, the presence of a gallbladder and distal common bile duct on ultrasound examination, and insufficient biopsy material for interpretation. This case emphasizes the variability in presentation and potential difficulties in diagnosis and the need for intraoperative cholangiogram and exploratory laparotomy in such cases. An approach to the patient with extrahepatic biliary atresia who is diagnosed late is discussed. A successful outcome can be achieved for such patients.
Reference Values of the Steatocrit and Its Modifications in Diarrheal Diseases
Authors: Guarino A. , Tarallo L. , Greco L. , Cesarano L. , Guandalini S. , Rubino A. 
Published: January 2024

SummaryConflicting results have been reported on the use of the steatocrit to measure fecal fat excretion. Aiming to assess the reliability of this method and its usefulness in the diagnosis of intestinal enteropathies, we measured the steatocrit in 747 healthy children and 442 children with diarrhea grouped according to diagnosis. The steatocrit was found to correlate strictly (r = 0.93) with the chemical measurement of fecal fat. Reference values and ranges were established. The maximal steatocrit was observed in neonates; afterwards, it progressively decreased to an undetectable level in children older than 2 years of age. A steatocrit abnormally high for age was found in 20% of patients with acute diarrhea and in 53% of those with chronic diarrhea. All celiac patients with a gluten‐containing diet showed a marked increase of steatocrit. We conclude that the steatocrit is a reliable and easy‐to‐perform test, which quickly provides valuable information in the diagnostic workup of the child with diarrhea.
Somatic Gene Therapy in Gastroenterology
Authors: Ledley Fred D. 
Published: January 2024

SummarySomatic gene therapy represents a new approach for treating a variety of genetic and acquired diseases and has many potential applications in gastroenterology. Somatic gene therapy is based on the ability to transfer recombinant genes efficiently into somatic tissues, such as the liver or intestine, and achieve expression of the recombinant gene product. Gene transfer could be used to replace genetically defective gene functions or prevent the progression of acquired or multifactorial diseases. The therapeutic application of gene transfer technologies requires development of methods for achieving efficient transfer and expression of recombinant gene products, research directed at developing strategies for altering the course of disease, and clinical research aimed at assessing both the technical feasibility and therapeutic efficacy of this approach.
Milk‐Stimulated PGE2 Production by Isolated Gastric Cells
Authors: Ducroc R. , Wirbel A. , Garzon B. , Vilar J. , Brunel‐Riveau B. , Geloso J. P. 
Published: January 2024

SummaryThe effects of a milk diet on gastric acid secretion of rats fed raw bovine milk for 4 days were examined using dispersed gastric cells. Parietal cell acid secretion was estimated by the accumulation of 14C‐aminopyrine (AP), an index of secretory function. Basal AP accumulation was significantly increased (60%) by the milk diet. There was a marked upward shift in the dose‐response curve of histamine (HA; 10−8 to 10−3M) in milk‐fed rats, indicating enhanced sensitivity of parietal cell‐H2 receptor to exogenous HA. In contrast, the dose‐dependent inhibition of HA‐induced AP accumulation by prostaglandin (PG) E2 was significantly reduced, indicating that the parietal cells of milk‐fed rats were less sensitive to exogenous PGE2. The PGE2 content of bovine milk was low (<20 pg/ml), but the production of endogenous PGE2 by the gastric cells was dramatically increased by the milk diet and exhibited maximal control production rate in the presence of 10 μM arachidonic acid. The increased responsiveness to histamine and the decreased responsiveness to PGE2 indicated that the milk diet induced low histamine and high PGE2 availability in the vicinity of the parietal cell basolateral membrane. This regulation, which involves stimulation of PGE2 production in the gastric mucosa, may underly the inhibition of acid secretion observed in vivo in chronically milk‐fed adult rats.
Comparison of Two Preterm Formulas With or Without Addition of Medium‐Chain Triglycerides (MCTs). I
Authors: Sulkers E. J. , v Goudoever J. B. , Leunisse C. , Wattimena J. L. D. , Sauer P. J. J. 
Published: January 2024

SummaryMedium‐chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on nitrogen and fat balances and macronutrient oxidation were investigated in 28 healthy very‐low‐birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There were no differences in nitrogen absorption or in excretion. Median nitrogen retention was 74% (MCT) vs. 71% (LCT) of intake. Fat absorption was higher (p < 0.05) in the MCT group (88%) vs. 79% in the LCT group (median values). MCTs did not stimulate fat oxidation as measured by indirect calorimetry, so fat deposition was also higher on the MCT formula. As weight gain was not different between groups, the percentage of weight gain consisting of fat accretion was significantly (p < 0.005) higher with the MCT formula (24% vs. 21%). On the other hand, there was no increase in percent protein accretion (both 15% of weight gain). We conclude that the existence of a slightly lower fat absorption in the healthy growing neonate fed a LCT formula compared with a MCT formula does not impair growth or nitrogen retention, but merely induces a slight decrease in the high relative fat accretion encountered in the preterm neonate.
Cytokeratin Immunohistochemical Examination of Liver Biopsies in Infants with Alagille Syndrome and Biliary Atresia
Authors: Treem W. R. , Krzymowski G. A. , Cartun R. W. , Pedersen C. A. , Hyams J. S. , Berman M. 
Published: January 2024

SummaryIdentifying bile duct epithelium is sometimes difficult with standard histologie techniques. The availability of antibodies to specific cy tokeratin (CK) intermediate filaments has allowed identification of CK expressed by bile duct epithelium. Formalin‐fixed, paraffin‐embedded liver tissue from five infants (aged 1–12 months) with Alagille syndrome and five infants with biliary atresia (aged 1.5–11 months) were pepsin digested then reacted with a combination of anti‐cytokeratin monoclonal antibodies using an avidin‐biotin immunoper‐oxidase technique. Liver tissue obtained at autopsy from infants without primary liver disease (aged 22 weeks gestation to 24 months) was treated similarly for comparison. Control specimens showed progression from prominent immunoreactivity of the ductal plate cells at the rim of the portal tract (22–24 weeks gestation) to incorporation of tubular ductal structures into portal tract mesenchymal tissue (26–34 weeks gestation) and formation of intensely immunoreactive mature discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity of the ductal plate cells (1–24 months). In contrast, biopsies from infants with Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from infants with Alagille syndrome less than 2 months old showed only immunoreactivity of single ductal plate cells or small ductules at the periphery of the portal tracts. Biopsies from some infants greater than 3 months old showed increased numbers of immunoreactive cells in groups and anastomosing bands lacking true lumens and extending into the fibrous bridges between adjacent portal areas (neoductular proliferation). Biopsies from infants with biliary atresia showed strongly immunoreactive interlobular bile ducts and prominent peripheral ductules. Neoductular proliferation was already present in the earliest biopsies, and as fibrosis and cirrhosis increased, interlobular duct staining decreased, and ductal plate cells extending into fibrous bands became more immunoreactive. Anti‐cytokeratin monoclonal antibodies appear to be a useful tool for identification of bile duct epithelium in infants with a paucity of interlobular bile ducts and biliary atresia. Compared to age‐matched controls and patients with biliary atresia, infants with Alagille syndrome may fail to fully develop interlobular ducts. In both Alagille syndrome and biliary atresia, chronic cholestasis is a stimulus for proliferation of epithelium at the limiting plate which expresses a bile ductular cytokeratin pheno‐type.
Esophagitis of Likely Traumatic Origin in Newborns
Authors: Deneyer M. , Goossens A. , Pipeleers‐Marichal M. , Hauser B. , Blecker U. , Sacre L. , Vandenplas Y. 
Published: January 2024

SummaryWe describe 17 full‐term newborns presenting with vague symptoms related to the upper gastrointestinal tract (anorexia, poor feeding, retching, regurgitation, and incessant crying) during their stay in the maternity unit. After an esophagogastroduodenoscopy performed between days 2 and 5 of life, the babies could clearly be divided into two groups. Twelve babies (group 1) had an extremely severe esophagitis (circular ulcerations), without gastroduodenitis. In the remaining five babies (group 2), the upper gastrointestinal tract was unaffected. Allergic, infectious, metabolic, and toxic etiologies were excluded. Esophageal pH monitoring data were within normal ranges in all. All babies of group 1 were treated as follows: prone anti‐Trendelenburg position, cisapride, and cimetidine syrup. Symptoms and lesions disappeared within 48–72 h. Reendoscopy after 72 h showed an almost normal esophagus with greatly improved histology. These observations highlight four points of interest: (a) the existence of an extremely severe ulcerative esophagitis in apparently healthy newborns, (b) the very rapid clinical and histological recovery, (c) the difficulties in predicting esophagitis on clinical grounds, and (d) the mysterious origin despite thorough assessment. The distribution of the lesions (more severe in the upper esophagus), the early onset (almost at birth), the very rapid healing, and the absence of gastric and duodenal lesions are in favor of a possible “traumatic” origin (pharyngeal, esophageal, and gastric suction at birth). Finally, because the condition described is transient, questions arise regarding the necessity of treatment, and we currently do not recommend overtreating newborns presenting with similar symptoms and/or endoscopie findings.
Midazolam as a Sedative in Esophageal Manometry
Authors: Fung Kam Pui , Math Mahantayya V. , Ho Chin Onn , Yap Kian Mo 
Published: January 2024

SummaryMidazolam 0.5 mg/kg was given intravenously as a sedative to 19 infants and children undergoing esophageal manometry after oral choral hydrate treatment. The lower esophageal sphincter pressure and motility were measured by manometry before and after midazolam injection. Midazolam did not change the lower esophageal sphincter pressure, blood pressure and respiratory rate of the subjects (p > 0.18), and the motility patterns. However, the mean heart rate increased by 5 beats/min after midazolam injection (p < 0.05). One infant developed transient apnea, reversed promptly by intravenous flumazenil. Sedation occurred within l min after intravenous injection of the drug. No other side effects were noted. Midazolam is a relatively safe and effective sedative for accurate lower esophageal sphincter pressure measurement and esophageal manometry when a mild sedative such as choral hydrate does not work.
Efficacy of Massive Dose Oral Gentamicin Therapy in Nonbloody Persistent Diarrhea with Associated Malnutrition
Authors: Bhatnagar Shinjini , Bhan Maharaj K. , Sazawal Sunil , Gupta Usha , George Chechamma , Arora Narender K. , Kashyap Dharmendra K. 
Published: January 2024

SummaryOvergrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty‐eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post‐treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24–72, 72–120, and 120–168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post‐treatment in the antibiotic (1.0± 5.1) and placebo (1.4± 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic‐ (61.3%) and placebo‐ (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.
Short‐Chain Fatty Acid Absorption in Patients with Cystic Fibrosis
Authors: Vaisman Nachum , Tabachnik Elvan , Sklan David 
Published: January 2024

SummaryPatients with cystic fibrosis (CF) often exhibit malabsorption despite the use of supplemental pancreatic enzymes. Unabsorbed carbohydrates and amino acids can serve as substrates for large intestine anaerobic fermentation, thus increasing excretion of short‐chain fatty acids (SCFA) in the feces. Nine patients with CF on regular pancreatic enzyme supplementations in the age range of 5–11 years and one older patient were studied. Three‐day stool samples were collected, as were 72–h food records. Stools were analyzed for gross energy, total nitrogen, fat content, and SCFA concentration. A significant difference was found between CF and normal controls in total caloric excretion due to fat malabsorption. No significant difference was found between CF and normal controls in protein or SCFA excretion. Fat excretion as percentage of fat intake was significantly increased in CF patients: 35.3± 10.2% versus 8.0± 3.0%, respectively. These data suggest that carbohydrate supplementation could be more widely used to increase caloric intake in CF patients without causing secondary osmotic diarrhea.
Gliadin‐Specific and Cow's Milk Protein‐Specific IgA in Human Milk
Authors: Juto Per , Holm Stefan 
Published: January 2024

SummaryThe presence of gliadin‐specific IgA and IgG antibodies in colostrum and serum of 140 newly delivered mothers was assessed by enzyme‐linked immunosorbent assay. In addition, cow's milk protein (CMP)‐specific IgA was determined in the colostrum samples. From 14 of the mothers longitudinal milk samples were obtained after 1 and 2 months of lactation and from 12 mothers after 3 months. Gliadin‐specific IgA was found in 97.1% and gliadin‐specific IgG in 9.3% of the colostrum samples. Gliadin‐specific IgA was detected in mature samples but at significantly lower levels after 1, 2, and 3 months of lactation (p < 0.01) as compared with colostrum. Gliadinspecific IgA was found in 2.8% of the serum samples and gliadin‐specific IgG in 40%; however, the levels of both isotypes were low. CMP‐specific IgA was found in 78.1% of the colostrum samples. It is concluded that IgA antibodies to two common food proteins are frequently found in human milk and that food‐specific IgA present in milk may play a role in adapting the infant's immune reactions to food antigens in the gut.
Low Bone Mineral Content in Summer‐Born Compared with Winter‐Born Infants
Authors: Namgung Ran , Mimouni Francis , Campaigne Barbara N. , Ho Mona L. , Tsang Reginald C. 
Published: January 2024

SummaryPossible seasonal differences in newborn bone mineral content (BMC) have not been studied. Adult studies show seasonal variations with lower BMC in winter versus summer. Assuming that BMC variations may relate in part to vitamin D status, we hypothesized that newborn BMC would be lower in winter than summer. BMC of one third distal radius was measured in 55 healthy term newborns using a single beam photon absorptiometer [coefficient of variation (CV) for phantom standard 2.1%]. Infants were enrolled during summer (July‐September, 1988) and winter (January‐March, 1989) for a longitudinal nutrition study. Contrary to our hypothesis, there was a 12% lower BMC in summer versus winter (mean ± SD 75.94 ± 17.42 vs. 86.55 ± 17.54 mg/cm, respectively; p = 0.035). The difference remained significant after controlling for possible race and gender effects (p = 0.02). We conclude that BMC is lower in summer‐ compared with winter‐born infants. Since any seasonal effects on fetal bone are presumably related to effects through the mother, we speculate that if maternal vitamin D status influences fetal bone mineralization, the effect (possible sunshine deprivation in winter) may operate especially in early pregnancy, thus resulting in lower BMC, evident at birth in summer.
Liver Involvement in Infants with PiSZ Phenotype of α1‐Antitrypsin Deficiency
Authors: Pittschieler Klaus , Massi Guido 
Published: January 2024

SummaryBetween July 1985 and June 1989, 19,432 new‐borns were screened during the first days of life to determine their Pi (protease inhibitor) phenotype. Fourteen infants were identified to be carriers of the PiSZ phenotype. Their clinical and biochemical follow‐up data were recorded at 2, 5, and 12 months of age; only one case underwent a liver biopsy due to repeated abnormal liver enzymes. Three of 14 PiSZ infants showed some hepatic dysfunction at 2 and 5 months of age, but at 12 months all patients had normal liver function tests. None of them had clinical, biochemical, or morphological signs of neonatal cholestasis. The clinical and biochemical data related to the liver involvement are similar to those of the PiMZ phenotype, though the serum levels of α1‐antitrypsin in PiSZ carriers match those of the PiZZ group.
A Randomized Double‐Blind Clinical Trial of a Maltodextrin‐Containing Oral Rehydration Solution in Acute Infantile Diarrhea
Authors: Santos Ocampo Perla D. , Bravo Lulu C. , Rogacion Jossie M. , Battad Grace R. 
Published: January 2024

SummaryA double‐blind, randomized controlled study was used to compare the efficacy and safety of an oral rehydration solution either with minimally hydrolyzed maltodextrins or the standard recommended glucose. One hundred twenty pediatric patients with acute watery diarrhea (60 in each group) were studied, but only 116 patients were included in the final analysis. After rehydration, outcome variables did not differ significantly at p < 0.05. Mean duration of diarrhea was 52.5 ± 32.2 h for the control group (median, 50.8 h) and 57.2 ± hours for the study group (median, 45.3 hours). Comparisons of the mean stool output, weight gain, and ORS intake on the 24th h and from admission to discharge were not statistically significant. Differences in laboratory parameters consisting of mean serum sodium, potassium, total C02, hematocrit, plasma total solids, urine specific gravity, and random blood sugar were likewise not significant. Differences in stool pH and reducing sugars were statistically significant; however, the observed values were still within normal range. All laboratory values improved upon rehydration. Replacement of glucose with maltodextrins did not offer added advantages in reducing the duration and severity of diarrhea.