bluuebunny/crossref_metadata_2025 huggingface dataset:
Findings on Routine Abdominal Ultrasonography in Cystic Fibrosis Patients
Authors: Wilschanski Michael , Fisher Drora , Hadas‐Halperin Irit , Picard Elie , Faber Joseph , Goldberg Shmuel , Branski David , Kerem Eitan
Published: February 2024

Background:

Right lower quadrant abdominal pain may pose a diagnostic problem in patients with cystic fibrosis. Abdominal ultrasound examination, used commonly in the diagnostic work‐up, may reveal abnormalities of the appendix. However, interpretation of such findings is problematic, because the appearance of the gastrointestinal system during routine examination has not been documented in patients with cystic fibrosis. The purpose of this study was to investigate the findings during routine abdominal ultrasound scans in our cohort of patients with cystic fibrosis and in control subjects.

Methods:

Abdominal ultrasound scans were performed prospectively during routine clinic visits in a cohort of patients with cystic fibrosis.

Results:

Fifty patients aged 10 ± 6 years, (range, 0.5‐28 years) were examined; 45 had pancreatic insufficiency. Four patients (3 with pancreatic insufficiency) reported right lower quadrant pain at the time of the scan. According to standard ultrasound criteria, the appearance of the appendix was abnormal in 8 patients (16%), 6 had a mucoid appendix, and 2 had a pathologically thickened appendiceal wall. Only 1 of these 8 patients mentioned abdominal pain at the time of the study. Other incidental findings included gallstones (3 patients), intussusception (2 patients), and pancreatic cyst (1 patient).

Conclusions:

Abnormalities can be observed during routine abdominal ultrasonographic studies in cystic fibrosis. These findings may not be associated with abdominal pain; their clinical relevance needs further investigation.
Intestinal Barrier Function and Cow's Milk Sensitization in Guinea Pigs Fed Milk or Fermented Milk
Authors: Terpend Kathleen , Blaton Marie‐Agnès , Candalh Céline , Wal Jean‐Michel , Pochart Philippe , Heyman Martine
Published: February 2024

Background:

The respective effect of milk and fermented milks on intestinal barrier capacity and on sensitization to β‐lactoglobulin was studied using a guinea pig model of cow's milk allergy.

Methods:

Guinea pigs were fed a control diet or the same diet supplemented with milk, fermented milk (Streptococcus thermophilus and Bifidobacterium breve), or dehydrated fermented milk. Intestinal barrier capacity to macromolecules was assessed in an Ussing chamber, and sensitization to cow's milk protein was measured by systemic anti‐β‐lactoglobulin immunoglobulin G1 titers and by intestinal anaphylaxis, the latter assessed by the β‐lactoglobulin‐induced increase in short‐circuit current of jejunal fragments (ΔIscβ‐LG).

Results:

The electrical resistance of jejunum was similar in the four groups (∼80 Ω/cm2) suggesting the same paracellular permeability. The transport of 14C‐β‐lactoglobulin from mucosa to serosa was significantly decreased in the animals fed dehydrated fermented milk (403 ± 131 ng/hr·cm2) compared with that in control animals or animals fed milk (767 ± 250 ng/hr·cm2 and 749 ± 475 ng/hr·cm2, respectively; p < 0.05). Milk fermentation did not modify native β‐lactoglobulin concentration but anti‐β‐lactoglobulin immunoglobulin G1 titers were higher in fermented milk and dehydrated fermented milk (log10 titer = 2.86 and 2.79, respectively) than in guinea pigs fed milk (log10 titer = 2.5; p < 0.007). However, β‐lactoglobulin‐induced intestinal anaphylaxis remained the same in the three groups (ΔIscβ‐LG, 9.6 ± 4.1 µA/cm2, 8.5 ± 4.3 µA/cm2, and 8.5 ± 3.4 µA/cm2 in milk‐fed, fermented milk‐fed, and dehydrated fermented milk‐fed guinea pigs, respectively).

Conclusions:

The intestinal barrier capacity to milk proteins seems to be reinforced by dehydrated fermented milk, but milk and fermented milks are equally efficient in inducing cow's milk allergy in guinea pigs.
Disaccharidase Activities in Children: Normal Values and Comparison Based on Symptoms and Histologic Changes
Authors: Gupta Sandeep K. , Chong Sonny K. F. , Fitzgerald Joseph F.
Published: February 2024

Background:

The relationship between symptoms, intestinal mucosal histology, and disaccharidase activities is not well defined. An analysis of disaccharidase activities was performed in children grouped by age, symptoms, and intestinal mucosal histology and normal values established.

Methods:

Disaccharidase activities and histology of 246 endoscopically obtained duodenal biopsies in 232 patients (121 girls; age range, 0.08‐17 years; mean, 5.9 years) in a 3‐year period were reviewed. Patients were divided into two groups based on absence (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided by age into, less than 24 months of age and 24 months of age or more. Histologic changes within groups were classified as (A) normal, (B) mild, or (C) moderate to severe based on villus height abnormalities. A questionnaire was sent to 34 patients with hypolactasia to assess the efficacy of lactose avoidance and/or lactase supplementation.

Results:

All group 1 patients had normal findings in analysis of mucosal specimens, and their disaccharidase activities showed normal values because they had no diarrhea. The geometric means (95% confidence interval) in children aged less than 24 months are (in micromoles of substrate hydrolyzed per minute at 37°C per gram protein) (units [U]) lactase, 36.7 (13.4‐100.4); maltase, 178.5 (88.9‐356.3); palatinase, 12.7 (3.8‐41.5); and sucrase 60.0 (24.0‐148.1). In children 24 months of age or more, the values are 23.2 (3.9‐108.1), 167.6 (78.8‐355.9), 12.7 (4.9‐32.9), and 51.0 (20.5‐126.0), respectively. Only lactase activity decreased with age (p < 0.05). No differences in disaccharidase activities were noted in patients with and without diarrhea if the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea, values were commensurate with the degree of mucosal injury, especially in the older group. Twenty‐two of 27 patients (81%) who responded to the questionnaire had benefited from lactase supplementation and/or lactose avoidance.

Conclusions:

We have established normal values for disaccharidase activities in the pediatric population. Although the disaccharidase activities correlate more with degree of intestinal mucosal injury than with symptoms, their activities are difficult to predict accurately based on these criteria. If required, disaccharidase activities should be measured biochemically.
Helicobacter pylori and Type 1 Diabetes Mellitus in Children
Authors: Salardi Silvana , Cacciari Emanuele , Menegatti Marcello , Landi Fabiana , Mazzanti Laura , Stella Felicia A. , Pirazzoli Piero , Vaira Dino
Published: February 2024

Background:

Helicobacter pylori is a recognized gastroduodenal pathogen and H. pylori infection is one of the most common bacterial infections, usually acquired during childhood. However, diabetes mellitus is characterized by an increased susceptibility to infections.

Methods:

We compared the prevalence of H. pylori infection as well as cytotoxin‐associated gene A‐CagA‐and vacuolating cytotoxin gene A‐VacA‐positivity in 103 children and adolescents with type 1 diabetes mellitus and in 236 nondiabetic children. We used a novel Recombinant ImmunoBlot Assay‐Strip (RIBA SIA) with individual band for whole H. pylori lysate and recombinant CagA and VacA.

Results:

H. pylori‐positive subjects, both diabetics and controls, were significantly older than negative subjects. In the whole group of diabetic patients the prevalence of each of the three reactivities was higher than in control subjects, reaching significance only for lysate. Only diabetic patients over 12 years of age, with a longer disease duration, had a higher prevalence of positive cases, although not significantly so.

Conclusion:

In the first few years of disease, diabetic children do not differ from the nondiabetic population. Subsequently they show an H. pylori seroprevalence tendentially higher than that of control of the same age. Therefore, H. pylori infection acquired in childhood and lasting several years, could be one of the causes of chronic atrophic gastritis, which is more frequent in longstanding diabetes mellitus.
Increased Expression of Transforming Growth Factor‐β1 and Thrombospondin‐1 in Congenital Hepatic Fibrosis: Possible Role of the Hepatic Stellate Cell
Authors: El‐Youssef Mounif , Mu Yan , Huang Lijun , Stellmach Veronica , Crawford Susan E.
Published: February 2024

Background:

Congenital hepatic fibrosis is a rare disease characterized by portal tract fibrosis and biliary duct ectasia. It is associated with autosomal recessive polycystic kidney disease and rarely progresses to cirrhosis. The activated stellate cell has been implicated in the pathogenesis of alcohol‐ or inflammation‐mediated cirrhosis through fibrogenic proteins such as transforming growth factor‐β1; however, the role of the stellate cell in pure, noninflammatory fibrosis is unknown. It has been hypothesized that fibrosis in congenital hepatic fibrosis may be caused by upregulation of transforming growth factor‐β1 and thrombospondin‐1, and that the hepatic stellate cell may be the mediator of these proteins.

Methods:

Human liver tissue samples from patients with congenital hepatic fibrosis (n = 9) and from normal patients (n = 3) were analyzed. Tissue homogenates from both groups were analyzed for transforming growth factor‐β1 protein and mRNA by Western blot analysis and in situ hybridization, respectively. Immunolocalization studies were performed in fixed tissue sections from both groups. Stellate cells were cultured from livers exhibiting congenital hepatic fibrosis and confirmed by desmin staining. The cells were cultured in serum‐free medium for 48 hours, and media were collected and analyzed by Western blot analysis for thrombospondin‐1 and transforming growth factor‐β1.

Results:

Congenital hepatic fibrosis liver tissue homogenates had higher levels of thrombospondin‐1 and transforming growth factor‐β1 protein than in normal livers. In congenital hepatic fibrosis tissue, transforming growth factor‐β1 was more highly expressed in the ectatic biliary epithelium and the perisinusoidal space, whereas thrombospondin‐1 localized most intensely to the hepatocytes and spared the bile ducts. Congenital hepatic fibrosis‐derived stellate cells secreted both thrombospondin‐1 and transforming growth factor‐β1 in vitro.

Conclusions:

Transforming growth factor‐β1 and thrombospondin‐1 may play a role in the pathogenesis of liver fibrosis in patients with congenital hepatic fibrosis. One potential source of these fibrogenic proteins is the hepatic stellate cell.
Incidence of Dysplasia in Pelvic Pouches in Pediatric Patients After Ileal Pouch‐Anal Anastomosis for Ulcerative Colitis
Authors: Sarigol Samra , Wyllie Robert , Gramlich Terry , Alexander Frederick , Fazio Victor , Kay Marsha , Mahajan Lori
Published: February 2024

Background:

The purpose of this study was to evaluate the incidence of dysplasia and the mucosal adaptation patterns of pelvic pouches in children and adolescents who had undergone ileal pouch‐anal anastomosis for ulcerative colitis.

Methods:

Between 1982 and 1996, 176 pediatric patients with ulcerative colitis underwent ilial pouch‐anal anastomosis. Seventy‐six patients were followed up after surgery at the Cleveland Clinic. Pouch biopsy specimens were reviewed for dysplasia and to determine mucosal adaptation patterns. Fifty‐eight of the 76 patients had an average of three mucosal biopsies during a mean follow‐up of 5 years. Demographic and surgical data were abstracted from archives of medical records. All previously obtained pouch biopsy specimens were re‐evaluated by a single pathologist to ensure standardized interpretation.

Results:

No dysplasia was identified in screening specimens of 76 children and adolescents including 5 patients who showed dysplasia in resected colon specimens. The pattern of mucosal adaptation was categorized using previously reported criteria. Type A was defined as normal mucosa or mild villous atrophy with no or mild inflammation. Type B mucosa showed transient atrophy with temporary moderate inflammation followed by normalization of architecture. Type C mucosa was defined as a pattern of persistent atrophy with severe inflammation. In the study cohort, the patterns of mucosal adaptation, type A (56.9%; n = 33), type B (32.8%; n = 19), and type C (10.3%; n = 6), were comparable with those reported in adults. The rate of pouch failure and diagnosis of Crohn's disease were similar in each group and were not related to the specific adaptation pattern. Most of the patients with type C mucosa had clinical symptoms of pouchitis requiring periodic antibiotic therapy. No dysplasia was identified in any biopsy specimen reviewed.

Conclusions:

Similar morphologic changes can be seen in ileal pouches in pediatric and adult patients. There seemed to be no increased risk of dysplasia in children and young adults who had undergone ilial pouch‐anal anastomosis surgery for ulcerative colitis during a 5 year follow‐up. Because the long‐term risk of development of dysplasia is unknown, an initial screening should be performed 5 years after the creation of a pelvic pouch in children or when the total disease duration exceeds 7 years. Once identified, patients with Type C mucosa should have annual screening for dysplasia until further data become available.
Concentrations and Anti‐Haemophilus influenzae Activities of β‐Casein Phosphoforms in Human Milk
Authors: Kroening Terry A. , Baxter Jeffrey H. , Anderson Steven A. , Hards Robert G. , Harvey Linda , Mukerji Pradip
Published: February 2024

Background:

The distribution and concentrations of six phosphorylated forms of human β‐casein, a major source of nutrition among breast‐fed infants, have not been examined in milk samples without prior fractionation. In this study, the levels of β‐casein phosphoforms in untreated human milk samples were analyzed and their antiadhesion activities determined against Haemophilus influenzae, a pathogen implicated in middle ear infection in infants.

Methods:

Human milk samples were analyzed using ureapolyacrylamide gel electrophoresis of whole‐milk samples and scanning densitometry to determine the concentrations of β‐casein and its phosphoforms. A nontypable H. influenzae strain was radiolabeled to monitor its attachment to human pharyngeal cells in microtiter plates. Purified phosphoforms of β‐casein were preincubated for 15 minutes with radiolabeled bacteria to determine their antiadhesion activities.

Results:

The average β‐casein concentration in 151 human milk samples was 5.37 ± 2.26 mg/ml. On average, the phosphoforms in untreated milk are present in the following order ranked by concentration: tetra‐ > di‐ > non‐ > mono‐ > tri‐ > pentaphosphorylated β‐casein. The tri‐, tetra‐, and pentaphosphorylated forms of human β‐casein exhibited more than 60% inhibition of H. influenzae in the antiadhesion assay when used at a concentration of 0.6 to 0.9 mg/ml.

Conclusion:

The β‐casein level in untreated human milk is significantly higher than previously reported. The phosphoform distribution of β‐casein in individual donors varies widely. Anti‐H. influenzae activity was detected in vitro among human β‐casein molecules with three or more phosphate groups.
Infant Formula With Protein‐Energy Ratio of 1.7 g/100 kcal Is Adequate but May Not Be Safe
Authors: Fomon Samuel J. , Ziegler Ekhard E. , Nelson Steven E. , Rogers Ronald R. , Frantz Joan A.
Published: February 2024

Background:

An adequate protein‐energy ratio of infant formulas has been defined as one that permits growth similar to that of infants fed relatively generous protein‐energy ratios, and serum concentrations of albumin and urea nitrogen no less than those observed in breast‐fed infants. A safe ratio has been defined as one with no detectable adverse effects. The hypothesis was that a protein‐energy ratio of 1.7 g/100 kcal is adequate and safe.

Methods:

Healthy male infants were fed Formula 1.7, a milk‐based formula, as the sole source of energy from the 8th to the 112th day of life. Weight, length, and energy intake were measured; serum albumin and urea nitrogen were determined; and the results were compared with data from appropriate reference groups of infants.

Results:

Energy intake from 8 through 55 days was significantly higher than that of infants in the formula‐fed reference group. Gain in weight was significantly more than that of the formula‐fed reference group or of a breast‐fed reference group, whereas gain in length was similar to that of the formula‐fed reference group. Body mass index was significantly higher than that of either reference group, suggesting more fat accumulation in infants fed Formula 1.7. Plasma concentrations of albumin and urea nitrogen were similar to those of the breast‐fed reference group.

Conclusion:

Infants fed Formula 1.7 received adequate intakes of protein. Because of the possibility that ad libitum feeding of diets with moderately inadequate protein‐energy ratios is associated with increased food intake leading to excess weight gain, it is not possible to conclude that a protein‐energy ratio of 1.7 g/100 kcal is safe.
Comparison Between Serum α‐Glutathione S‐Transferase and Aminotransaminases in Detecting Cytolysis in Hepatitis C‐Infected Children
Authors: Namour Farès , Morali Alain , Ilardo Claudio , Abballe Xavier , Maury Florence , Guéant Jean‐Louis
Published: February 2024

Background:

α‐Glutathione S‐transferase (αGST) has been proposed as a more sensitive indicator than serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in detecting hepatocellular damage due to chronic hepatitis C virus (HCV) infection.

Methods:

The accuracy of α‐GST was compared with that of ALT and AST in detecting cytolysis in 103 blood samples issued from 31 children positive for HCV RNA.

Results:

α‐GST had a lower sensitivity than ALT or AST (32% vs. 54.4% for each aminotransferase). The sensitivity of ALT and/or AST was 60.2%, whereas that of ALT and/or α‐GST and AST and/or α‐GST was lower (58.3% and 57.3%, respectively). Among 41 serum samples with negative ALT and AST, only 2 had positive α‐GST, whereas α‐GST failed to detect cytolysis in 31 samples with elevated ALT and/or AST. No correlation was found between α‐GST, ALT, or AST and the Knodell score.

Conclusions:

The combination of ALT with AST is actually the best compromise in detecting cytolysis in untreated HCV‐infected patients.
Diet Fat and Oral Insulin‐Like Growth Factor Influence the Membrane Fatty Acid Composition of Suckling Rat Small Intestine
Authors: Kit Shelley , Thomson Alan B. R. , Clandinin M. Thomas
Published: February 2024

Background:

Insulin‐like growth factor‐1 plays an important role in small intestine development. The presence of insulin‐like growth factor‐1 and the complexity of the fatty acid composition in breast milk suggests that intestinal development may be influenced by manipulating the levels of these components.

Methods:

To determine whether a physiological dose of insulin‐like growth factor‐1 would influence sucrase and lactase activity levels, 10‐day‐old suckling rat pups were treated with an oral gavage of insulin‐like growth factor‐1. Four diets differing in fat composition were fed to lactating dams. Brush border membranes were isolated from jejunal and ileal segments of suckling rat small intestine. Fatty acid analysis of choline and ethanolamine phospholipids was performed.

Results:

Insulin‐like growth factor‐1 was found to have no effect on the sucrase and lactase activities of suckling rats. Changes in the diet fat composition of the mother's diet indirectly influenced the fatty acid composition of suckling rat small intestine. Insulin‐like growth factor‐1 decreased ileal C20:4n‐6 levels. A correlation was observed between lactase activity and C20:4n‐6 and C22:6n‐3 levels. As C20:4n‐6 levels increased, lactase activity appeared to decline. Increased lactase activity was observed when C22:6n‐3 levels increased.

Conclusions:

The changes observed in C20:4n‐6 levels in response to oral insulin‐like growth factor‐1, combined with the apparent trend of increased lactase activity with declining levels of C20:4n‐6, may be of significance in the development of the small intestine in early life.
Gastric Emptying in Formula‐Fed and Breast‐Fed Infants Measured with the 13C‐Octanoic Acid Breath Test
Authors: Van Den Driessche Mieke , Peeters Kristel , Marien Paul , Ghoos Yvo , Devlieger Hugo , Veereman‐Wauters Gigi
Published: February 2024

Background:

The 13C‐octanoic acid breath test, a noninvasive method for measuring gastric emptying, was used to compare the gastric‐emptying rate of formula‐fed and breast‐fed infants. Octanoic acid, a medium‐chain fatty acid marked with the stable isotope 13C is immediately absorbed in the duodenum. Because gastric emptying is the rate‐limiting step for the absorption of medium‐chain fatty acids, the fraction of 13C expired in the breath indicates the rate of gastric emptying.

Methods:

Twenty‐nine newborn infants (16 boys, 13 girls) were investigated, with parental consent. The infants had a mean gestational age at birth of 34.5 weeks (range, 27‐41 weeks) and a birth weight of 2148 g (range, 960‐4100 g). Their mean weight on the day of the test was 2496 g (range, 1998‐4140 g), and their mean age was 23 days (range, 7‐74 days). Each infant received a test meal after a maximum fasting period of 3 hours. Fourteen infants were fed formula milk (Nutrilon Premium, NV Nutricia, Zoetermeer, The Netherlands) with 13C‐octanoic acid and 15 infants received expressed mother's milk mixed with 13C‐octanoic acid. After obtaining two basal breath samples and the feeding, breath samples were collected using a nasal prong, every 5 minutes during the first half hour and every 15 minutes during the next 3.5 hours. Analysis of the expired 13C fraction in the breath samples was performed using isotope‐ratio mass spectrometry, and the gastric emptying curve and gastric emptying parameters were determined.

Results:

The mean half‐emptying time determined by the 13C‐octanoic acid breath test was 65 minutes (range, 27‐98 minutes) for the formula fed infants and 47 minutes (range, 16‐86 minutes) for the breast‐fed infants. The difference between the half‐emptying times is significant (t‐test, p < 0.05).

Conclusions:

The results of the 13C‐octanoic acid breath test indicated faster gastric emptying of human milk than formula. Our findings are in accordance with those in earlier studies, using the invasive‐dilution technique; noninvasive and detailed ultrasonography, which is not easily used because it is operator dependent and the observation time is short; or cineesophagogastroscintigraphy, which is less suitable for infants (because of the radiation involved). The 13C‐octanoic acid breath test is a safe and noninvasive method for measuring gastric emptying in small infants and allows comparison of various feeding methods.
Systemic Bartonella henselae Infection with Hepatosplenic Involvement
Authors: Ventura Alessandro , Massei Francesco , Not Tarcisio , Massimetti Mauro , Bussani Rossana , Maggiore Giuseppe
Published: February 2024

Background:

Systemic manifestations of Bartonella henselae infection are rare in the immunocompetent host. The infection generally has initial symptoms of prolonged fever and multiple granulomatous lesions in liver and spleen.

Methods:

Retrospective analysis of the records of all patients with hypoechogenic lesions in the liver and/or spleen diagnosed from 1990 through 1996 in three pediatric clinics in northern Italy,

Results:

Among the 13 patients reviewed, 9 had evidence of B. henselae infection and hepatosplenic involvement: five had prolonged and unexplained fever lasting from 3 to 16 weeks, and four had typical cat‐scratch disease and peripheral lymphadenitis. All patients had increased sedimentation rate and normal aminotransferase serum activity. Five children had a liver biopsy, by laparotomy in three and by needle in two. In all, the predominant liver lesion was a necrotizing granuloma. All patients were treated with broad‐spectrum antibiotics. Fever lasted from 3 to 16 weeks, and hepatic and splenic lesions resolved in all with residual splenic calcification in one.

Conclusions:

Systemic B. henselae infection represents an important cause of inflammatory hypoechogenic hepatosplenic lesions in children. Serology provides rapid diagnosis, avoiding multiple and invasive investigations. Hepatosplenic involvement can be found even in children with typical cat‐scratch disease without apparent systemic manifestations. The frequency of liver and/or splenic involvement in cat‐scratch disease is probably underestimated.
Immunological and Nutritional Composition of Human Milk in Relation to Prematurity and Mothers' Parity During the First 2 Weeks of Lactation
Authors: Montagne Paul , Cuillière Marie Louise , Molé Claire , Béné Marie Christine , Faure Gilbert
Published: February 2024

Background:

To investigate the effect of prematurity and parity on the dynamics of the major immunologic and nutritional proteins of human milk over the first 2 weeks of lactation.

Methods:

Microparticle‐enhanced nephelometric immunoassays were developed for the quantification of α‐lactalbumin, β‐casein, serum albumin, lactoferrin, and lysozyme in human milk. These components, immunoglobulin A, and total proteins were assayed in 368 individual samples collected from 74 mothers.

Results:

The dynamics of the major immunologic and nutritional proteins in early lactation presented similar patterns in preterm and term human milks. In comparison with term milk, preterm milk was globally characterized by higher concentrations of immune proteins and lower concentrations of nutritive proteins. These differences were increased by the degree of prematurity, which, however, influenced the absolute and relative protein concentrations differently, depending on the stage of lactation. The protein composition of term milk was similar, whatever the mother's parity. Conversely, the influence of prematurity on the levels of milk proteins during the first days of lactation was even greater in primiparous mothers.

Conclusions:

This precise description of the composition of preterm and term milk, regarding the main nutritional and immunologic proteins, confirms the influence of both prematurity and parity on milk components and demonstrates the combined effect of these two conditions.
Effects of Red Blood Cell Transfusion on Resting Energy Expenditure in Adolescents with Sickle Cell Anemia
Authors: Harmatz Paul , Heyman Melvin B. , Cunningham John , Lee Philip D. K. , Styles Lori , Quirolo Keith , Kopp‐Hoolihan Lori , Ghiron Jim , Hintz Raymond L. , Vichinsky Elliott
Published: February 2024

Background:

Previous studies indicate that resting energy expenditure is elevated in children with sickle cell anemia, possibly caused in part by hemolysis and increased erythropoietic activity. The purpose of the present investigation was to determine whether erythrocyte transfusion normalizes resting energy expenditure in sickle cell anemia.

Methods:

Five adolescents with sickle cell anemia (12‐16 years old; 4 boys, 1 girl) were studied before and 1 week after erythrocyte transfusion before elective surgery or at the initial transfusion for growth failure. Resting energy expenditure was measured by indirect calorimetry, and laboratory measures were determined by routine, validated methods. Data comparisons were by nonparametric analysis.

Results:

After erythrocyte transfusion, total hemoglobin levels increased (difference (D = 15 g/l; p < 0.05), whereas hemoglobin S (D = ‐0.36; p < 0.05) and reticulocyte count (D = ‐0.12; p < 0.05) decreased. Mean pretransfusion resting energy expenditure was elevated to 124% above predicted levels (p < 0.05) and increased further to 134% above prediction (p < 0.05) vs. pretransfusion levels). Plasma triiodothyronine (T3) levels increased (D = 0.17 nmol/l; p < 0.05), reverse T3 (rT3) levels tended to decline (D = ‐0.04 nmol/l; p = 0.14), and rT3/T3 decreased (D = ‐0.03; p < 0.05). Plasma insulin‐like growth factor‐I (IGF‐I) levels were low‐normal before transfusion and did not change, despite the change in resting energy expenditure.

Conclusions:

The results confirm that resting energy expenditure is elevated in patients with sickle cell anemia. However, resting energy expenditure further increased after transfusion, despite decreased erythropoietic activity. A posttransfusion decrease in rT3/T3 may contribute to the increased resting energy expenditure. That there was no change in IGF‐I implies that the growth hormone‐IGF system is not involved in posttransfusion regulation of resting energy expenditure. Therefore, our data are not consistent with the hypothesis that increased resting energy expenditure in sickle cell anemia is directly related to erythropoietic activity. The mechanisms by which resting energy expenditure increases after transfusion in sickle cell anemia require additional investigation.
Prevalence of Protein‐Energy Malnutrition at Diagnosis in Children with Acute Lymphoblastic Leukemia
Authors: Reilly John J. , Weir Jennifer , McColl John H. , Gibson Brenda E. S.
Published: February 2024

Background:

The purpose of the present study was to test the hypothesis that protein‐energy undernutrition is common in patients with acute lymphoblastic leukemia at diagnosis. Previous studies have failed to establish whether undernutrition is a common feature at diagnosis.

Methods:

Body mass index (BMI, weight/height2), expressed as a standard deviation score (SDS) relative to contemporary United Kingdom reference data, was used as the index of nutritional status. The index was calculated in a national cohort of standard‐risk patients (n = 1019) treated in the same protocol in the United Kingdom.

Results:

Prevalence of undernutrition (defined as BMI SDS <‐2.0) exceeded expected frequencies in boys (7.6%) and girls (6.7%). These differences were statistically significant (p < 0.001), with a 95% confidence interval for the prevalence of undernutrition of 5.8% to 9.0%.

Conclusions:

Undernutrition is relatively common in patients with newly diagnosed acute lymphoblastic leukemia, with a threefold excess of patients below the cutoff used to define undernutrition. Screening for undernutrition at diagnosis of acute lymphoblastic leukemia is indicated, and the BMI SDS is a simple index of nutritional status that could be readily calculated using measurements routinely made at diagnosis. The same simple screening technique could also be used clinically to detect and manage or prevent overnutrition (obesity), which is common in these patients after diagnosis.
Primary Gastric Plasmacytoma: A Rare Cause of Hypertrophic Gastritis in an Adolescent
Authors: Goyal Alka , Langer Jacob C. , Zutter Mary , Swanson Paul , Kraus Madeleine D. , Bartlett Nancy , Shackelford Gary D. , Longtine Janina A. , Perlmutter David H.
Published: February 2024

Background:

This report describes a 16‐year‐old patient with gastric rugal hypertrophy caused by a primary gastric plasmacytoma. She had a 3‐month history of nausea and burning abdominal pain. Radiographic studies showed giant rugal hypertrophy. Superficial endoscopic gastric biopsies showed mild inflammation with plasma cells of polyclonal origin in the mucosa. When symptoms persisted, she underwent laparoscopic full‐thickness gastric biopsy. There was monoclonal plasma cell infiltration histologically diagnostic of plasmacytoma and inconsistent with Helicobacter pylori‐associated mucosa‐associated lymphoid tissue (MALT) lymphoma. There was no evidence for involvement of the bone marrow or regional lymph nodes. The tumor did not respond to radiotherapy, necessitating total gastrectomy.

Methods:

Blood samples were analyzed for interleukin (IL)‐6 by enzyme‐linked immunosorbent assay. Gastric biopsy and gastrectomy specimens were subjected to immunophenotyping for κ and λ light chains, CD45, CD20, and LN1 and to polymerase chain reaction analysis for herpes virus HHV8.

Results:

There was no elevation in circulating IL‐6 levels, militating against a pathogenesis akin to that of Castleman's disease. There was no evidence for infection with the Kaposi's sarcoma‐associated herpes virus HHV8, which has recently been found in patients with multiple myeloma.

Conclusions:

This diagnosis and the characteristics of the tumor are very unusual, if not unique, for a patient of this age. The diagnostic evaluation of this patient also demonstrates the importance of deep endoscopic or full‐thickness biopsies in some children with hypertrophic gastritis.
Variable Morbidity in Alagille Syndrome: A Review of 43 Cases
Authors: Quiros‐Tejeira Ruben E. , Ament Marvin E. , Heyman Melvin B. , Martin Martin G. , Rosenthal Philip , Hall Theodore R. , McDiarmid Sue V. , Vargas Jorge H.
Published: February 2024

Background:

Alagille syndrome is one of the most common inherited disorders that cause chronic liver disease in children. Early reports suggested a benign course in these patients. Subsequent reports showed significant morbidity and mortality. This study was designed to analyze the long‐term clinical course on Alagille syndrome.

Methods:

The records of children with Alagille syndrome seen during a 20‐year period were reviewed.

Results:

Forty‐three patients were identified. Liver disease was diagnosed before 12 months of age in 95%. The frequencies of renal anomalies (50%) and intracranial hemorrhage (12%) were significant. The high incidence of chronic otitis media (35%) has not been reported previously. One patient had a renal transplant. Vascular compromise as a pathologic mechanism for some characteristics of the syndrome is also suggested by the presence of small bowel stenosis and atresia, tracheal and bronchial stenosis, renal artery stenosis, middle aortic syndrome, and avascular necrosis of the humeral and femoral heads. Twenty (47%) patients underwent liver transplantation. Five of six who underwent Kasai procedure required liver transplantation. Twelve died (28%), five after liver transplantation. One patient died of intracranial bleeding. Sixteen (37%) without liver transplantation and 15 (35%) who underwent liver transplantation are alive.

Conclusions:

Some patients with early‐onset and more severe liver disease can benefit from liver transplantation. Careful and complete assessment should be made of infants with a cholestatic syndrome, to avoid misdiagnosis and unnecessary Kasai procedures. Our observation of vascular compromise in various organ systems suggests that notch signaling pathway defects affect angiogenesis in Alagille syndrome.
Bovine Colostrum Ameliorates Diarrhea in Infection with Diarrheagenic Escherichia coli, Shiga Toxin‐Producing E. coli, and E. coli Expressing Intimin and Hemolysin
Authors: Huppertz Hans‐Iko , Rutkowski Stefan , Busch Dirk H. , Eisebit Reinhard , Lissner Reinhard , Karch Helge
Published: February 2024

Background:

Diarrheagenic Escherichia coli may cause serious extraintestinal complications, but there is no specific treatment.

Methods:

Patients with diarrhea caused by diarrheagenic E. coli, specifically Shiga toxin‐producing E. coli and E. coli‐expressing intimin and enterohemorrhagic E. coli‐hemolysin were treated by administration of pooled bovine colostrum, rich in antibodies to Shiga toxin and enterohemorrhagic E. coli‐hemolysin, in a placebo‐controlled, double‐blind study. Symptom resolution and fecal excretion of infecting strains were assessed.

Results:

No side effects were attributable to colostrum. Stool frequencies in the group treated with bovine colostrum were significantly reduced compared with those in the placebo group. No effect of therapy on the carriage of the pathogens or on complications of the infection could be demonstrated.

Conclusions:

Bovine colostrum is well tolerated and diminishes frequency of loose stools in children with E. coli‐associated diarrhea. A prospective study should be conducted among a larger number of children with Shiga toxin‐producing E. coli identified early in illness, to determine the effectiveness of colostrum therapy.
Noninvasive Assessment of Essential Fatty Acid Status in Preterm Infants by Buccal Mucosal Cell Phospholipid Analysis
Authors: Koletzko Berthold , Knoppke Birgit , von Schenck Ursula , Demmelmair Hans , Damli Aynur
Published: February 2024

Background:

The dietary supply of long‐chain polyunsaturated fatty acids is receiving increased attention since a linkage to infant growth and development has been reported. To avoid repeated blood collections for determination of long‐chain polyunsaturated fatty acid status, the authors developed and evaluated a noninvasive method for analysis of buccal mucosal cell phospholipids.

Methods:

Oral mucosal cells were gently collected with a soft cotton swab, buccal cell lipids separated by thin‐layer chromatography, and fatty acid methyl esters of the phospholipid fraction prepared. Subsequently, the fatty acid methyl esters were analyzed by high‐resolution gas chromatography.

Results:

The method allowed reliable analysis from very small amounts of oral mucosal cells, and results were well reproducible. The intraindividual coefficients of variation in four samples of three subjects were less than 5% for both arachidonic and docosahexaenoic acid. Fatty acid composition was not altered by consumption of milk formula before and after sample collection. The method was applied in a clinical trial with preterm infants fed human breast milk or assigned by double‐blind randomization to preterm formula with or without arachidonic and docosahexaenoic acid. Buccal mucosal cells were collected in infants less than 14 days of age and at the postconceptional ages of 52 weeks and 64 weeks. Dietary long‐chain polyunsaturated fatty acids showed a lasting influence on buccal cell phospholipid composition. In the course of the study, arachidonic and docosahexaenoic acid decreased significantly in the nonenriched formula group, whereas stable or rising values were observed in the groups receiving breast milk or enriched formula.

Conclusions:

Buccal mucosal cell phospholipids are feasible for use as a noninvasive marker for long‐chain polyunsaturated fatty acid status in preterm infants and yield reliable results. Dietary long‐chain polyunsaturated fatty acids have a lasting influence on fatty acid composition of buccal cells in preterm babies.
Quality of Life in Inflammatory Bowel Disease: Background and Definitions
Authors: Ferry George D.
Published: February 2024

Defining and measuring quality of life is a relatively new dimension of health care for many clinicians. The traditional method of evaluating clinical status and response to treatment has been to look at disease‐specific symptoms, global assessments (e.g., impressions of the good, better, or worse condition of a patient), days missed at school, and a variety of disease activity scores. These impressions and techniques may or may not reflect how patients are functioning day to day and how they feel about the illness. To address these issues, health‐related quality of life questionnaires have been developed to measure the functional effect of an illness and its treatment on a patient, as perceived by the patient. There are four broad domains that are considered part of a health‐related quality‐of‐life questionnaire: 1) physical and occupational function, 2) psychologic state, 3) social interaction, and 4) somatic sensation. In the case of children, the perception of parents or caretakers may be added to complete the picture. Significant social and psychiatric problems have been described in children with IBD, including absenteeism from school, depression, suicide, and major disruption of family patterns. To understand fully the impact of inflammatory bowel disease and its treatment on patient and family function requires one or more quality‐of‐life instruments that are sensitive to the full range of symptoms, growth and development, and response (including side effects) to many new therapies.
Social Implications of Childhood Crohn's Disease
Authors: Moody Gill , Eaden Jayne A. , Mayberry John F.
Published: February 2024

Background:

Children with Crohn's disease may have an impaired quality of life.

Methods:

A validated questionnaire was mailed to the parents of all child members of Crohn's in Childhood Research Association (CICRA) (age range, 5‐17 years). It investigated aspects of the quality of life of children with Crohn's disease. Sixty‐four questionnaires were returned together with another 35 from those outside the defined age range. Patients in the latter group were not included in the analysis.

Results:

Of the children investigated, 60% had significant absences from school, with a mean of 3 ± 2.8 months' absence in the previous year. Most (53%) thought that their teachers knew nothing about Crohn's disease, and 50% thought that teachers were unsympathetic. Of the 24 who had taken examinations 80% thought they had underachieved because of ill health. Sixty‐seven percent of children were unable to participate in sports on a regular basis, 60% felt unable to leave the house, and 50% were unable to play with their friends. Information about Crohn's disease had predominantly come from doctors (89%), information booklets (83%), and nursing staff (42%). The commonest questions asked by the children were: what is Crohn's disease (50%), why me (64%), will it affect my schooling (52%), and will it affect my chances of getting a job (67%).

Conclusion:

Children with Crohn's disease have a significantly impaired quality of life. They fear everyday childhood activities and fear for their future. These children need sympathetic management, and effort should be concentrated on improving their day‐to‐day existence to enable them to lead as normal a life as possible.
Behavior and Gastroesophageal Reflux in the Premature Neonate
Authors: Snel Antonie , Barnett Christopher P. , Cresp Trevor L. , Haslam Ross R. , Davidson Geoffery P. , Malbert Charles H. , Dent John , Omari Taher I.
Published: February 2024

Background:

The belief that behavioral observations assist in the clinical diagnosis of gastroesophageal reflux (GER) disease in premature neonates has not been formally tested. The purpose of this study was to determine whether esophageal acidification was associated with a recognizable pattern of behavioral changes in these infants.

Methods:

The behavior of 14 healthy premature infants was recorded by a video camera while esophageal pH was simultaneously monitored. For each of 20 acid GER episodes recorded, a 10‐minute video epoch, encompassing the onset of acid GER and lasting at least 4 minutes after the onset of GER, was examined. Two independent observers each scored reflux‐associated epochs of “general” infant behavior and behavior previously shown to be indicative of reflux in normal term infants.

Results:

The occurrence of esophageal acidification due to reflux did not significantly alter scores for general behavior. Infants frequently demonstrated reflux‐specific behavior, including discomfort, head retraction, and mouthing; however, none of these behavioral patterns was temporally associated with the occurrence of acid GER.

Conclusions:

These data indicate that reflux‐specific behavioral criteria, established in older term infants, may be inappropriate as diagnostic criteria for GER in premature neonates and may lead to the unnecessary use of antireflux therapy.
Duodenojejunitis: Is It Idiopathic or Is It Henoch–Schönlein Purpura Without the Purpura?
Authors: Gunasekaran T. S. , Berman James , Gonzalez Miguel
Published: February 2024

Background:

Henoch–Schönlein purpura is a small‐vessel vasculitic disease that most often affects the skin. Gastrointestinal manifestations have been well described, including duodenojejunal inflammation (DJI).

Methods:

Four children with DJI and clinical features of HSP are described, in whom the rash was either not present or appeared atypically late in the illness.

Results:

The characteristic rash did not develop in three children, and it developed much later in one. The patients (three boys and one girl) were aged between 7 and 9 years (mean, 7.5 years). Growth characteristics were normal. In all patients, pain occurred acutely with colicky abdominal pain in the spring or fall of the year, and all stools were positive for occult blood. No infectious cause was identified. Upper gastrointestinal endoscopic examinations demonstrated significant visual and histologic duodenitis in a pattern consistent with previous reports in children with known HSP. Factor XIII activity was absent. Immunoglobulin A levels were increased in three of four children. All children made a prompt recovery with the administration of intravenous glucocorticoids. In one child, the characteristic rash of HSP developed 18 weeks after the initial examination.

Conclusion:

Duodenojejunal inflammation may be the primary manifestation of HSP, even in the absence of the characteristic rash.
Normal Immune Responses to Ingested Foods
Authors: Husby Steffen , Simpson Hugh A. , Anderson John A.
Published: February 2024

This is a short review of the literature with a bias toward the author's work. Small amounts of dietary antigens are taken up into the circulation. B‐cell responses to foods (antibodies and antibody‐secreting cells) occur as a physiological event locally and in the circulation in all three major immunoglobulin classes. A low levels of IgE is also a normal phenomenon. IgA anti‐gliadin antibodies represent an exception. Antibody titers in general tend to decline with age. T‐cell responses specific for foods are low in the circulation of healthy subjects. T‐cell cytokines are more frequently produced in the gastrointestinal mucosa compared with the circulation. Results indicate that the phenomenon of oral tolerance takes place in humans. Oral tolerance within the T cell system may represent an important regulatory mechanism for normal immunity.
Evaluation of IgE‐Mediated Food Hypersensitivities
Authors: Bock S. Allan , Simpson Hugh A. , Anderson John A.
Published: February 2024

During the past 25 years the diagnostic assessment of IgE‐associated food hypersensitivity has improved substantially. The double‐blind placebo‐controlled food challenge has become the “gold‐standard” against which all other diagnostic approaches can be measured. Having a standard which gives a correct answer almost all of the time, has enabled us to move to more accurate diagnoses in both the clinic and the laboratory. Food allergy has gone from being a medical mystery to being a clear component of allergy evaluation. Histories are obtained from patients which may be used to design food challenges. The role of skin testing and its interpretation has moved from the fringe to having a central role in eliminating foods incriminated as causes of immediate‐onset allergic reactions. The material used for skin testing for foods has improved and we have learned when we must use fresh substances to supplement the commercial extracts. Recently the CAP radioallergosorbent test has shown promise in raising the probability of food reactions to the point that for a few foods in specific individuals, challenges may not be needed. Progress in this area will continue. We have been able to clarify which foods have a high probability of producing symptoms and which foods and which constellation of complaints are unlikely to be confirmed. These patterns of food allergic reactions have now been reproduced in many research centers throughout the world giving us confidence in their validity.