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Biomedical subjects

S M Schwarz

Publications and source records attributed to S M Schwarz.

At least 19 recordsLinked to original sources

Diagnosis and treatment of feeding disorders in children with developmental disabilities.

OBJECTIVES: To determine the results of diagnostic evaluation and the effects of nutritional intervention on energy consumption, weight gain, growth, and clinical status of children with neurodevelopmental disabilities and suspected feeding disorders. METHODS: We studied 79 children with moderate to severe motor or cognitive dysfunction (male:female, 38:41; age, 5.8 +/- 3.7 years) who were referred for diagnosis and treatment of feeding or nutritional problems. Initial assessments included a 3-day calorie intake record, videofluoroscopic swallowing study (VFSS), 24-hour intraesophageal pH monitoring, milk scintigraphy, and esophagogastroduodenoscopy. RESULTS: These studies demonstrated gastroesophageal reflux (GER) with or without aspiration in 44 of 79 patients (56%), oropharyngeal dysphagia in 21 (27%), and aversive feeding behaviors in 14 (18%). Diagnosis-specific approaches included medical GER therapy in 20 patients (25%), fundoplication plus gastrostomy tube (GT) in 18 (23%), oral supplements in 17 (22%), feeding therapy only in 14 (18%), and GT only in 10 (13%). After 24.6 +/- 3.0 months, relative calorie intake, expressed as intake (kcal/d)/recommended daily allowance (RDA, kcal/d), improved significantly (initial:final = 0.78 +/- 0.36:1.23 +/- 0.27). The z scores increased significantly for both weight (initial:final = -2.80 +/- 1.33:-0.81 +/- 0.69) and height (-3.14 +/- 0.98:-2.00 +/- 0.67). Improved subcutaneous tissue stores were demonstrated by increased thickness of both subscapular skinfolds (change = 71% +/- 26%) and triceps skinfolds (38% +/- 17%). After nutritional intervention, the acute care hospitalization rate, compared with the 2-year period before intervention, decreased from 0.4 +/- 0.18 to 0.15 +/- 0.06 admissions per patient-year and included only 3 admissions (0.02 per patient-year) related to feeding problems. CONCLUSIONS: In children with developmental disabilities, diagnosis-specific treatment of feeding disorders results in significantly improved energy consumption and nutritional status. These data also indicate that decreased morbidity (reflected by a lower acute care hospitalization rate) may be related, at least in part, to successful management of feeding problems. Our results emphasize the importance of a structured approach to these problems, and we propose a diagnostic and treatment algorithm for children with developmental disabilities and suspected feeding disorders.children, developmental disabilities, fundoplication, gastroesophageal reflux, gastrostomy, hospitalization, nutrition.

Adolescent↗

Nonspecific esophageal motility disorders in children without gastroesophageal reflux.

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

Adolescent↗

A role for intermediate filaments in the establishment of the primitive epithelia during mammalian embryogenesis.

Investigations of the cytoskeleton in mammalian eggs and embryos have revealed the existence of an unusual array of crosslinked intermediate filaments composed of cytokeratins 5, 6, 16, and 'Z' that are referred to as cytoskeletal sheets. We have been investigating the function of these cytoskeletal sheets during embryogenesis. In this investigation we report the rapid appearance of extensive arrays of tonofilaments extending across blastomeres and in association with intercellular desmosomal junctions appearing at the time the embryo hatches from its zona pellucida, through the time of implantation of the embryo into the uterine wall. Just prior to the time of gastrulation these tonofilaments disappear. Electron microscopy and immunoconfocal microscopy demonstrate that the tonofilaments are composed of cytokeratins characteristic of the type found earlier in development, that is types 5 and 6; whereas, cytokeratin type 8 which has been shown to be synthesized in blastocysts is localized primarily at perinuclear regions. Cytokeratins 8 and 18 are synthesized to about the same extent as actin at the time the tonofilaments appear whereas the synthesis of cytokeratins 5 and 6 is greatly reduced. Our results suggest that cytokeratins 5 and 6 in the tonofilaments may arise from the stored form of cytokeratins in the cytoskeletal sheets. Consequently, our results suggest that the sheets may serve as a maternal reserve of cytokeratin employed by the embryo at the time of implantation to form extensive arrays of tonofilaments in the embryo that likely provide structural integrity to the embryo as it is subjected to mechanical stress during invasion and implantation into the uterine wall.

Animals↗

Esophageal dysmotility elicited by acid perfusion in children with esophagitis.

OBJECTIVE: To determine the importance of acid reflux-induced dysmotility in the genesis of noncardiac chest pain in children. METHOD: We performed esophageal manometries during intraesophageal perfusion with 0.9% NaCl or 0.1 N HCl in 19 children (age, 14.5 +/- 0.5 yr) with gastroesophageal reflux, biopsy-proven esophagitis, and complaints of at least one episode of chest pain per day. RESULTS: Baseline esophageal motilities were normal in all patients. Eight of 19 children (42%) complained of chest pain during intraesophageal acid perfusion. In three of these eight patients, complaints of chest pain during acid perfusion were temporally associated with "conversion" of previously normal motility patterns to manometric tracings, indicating esophageal dysmotility. Compared with findings during saline perfusion, esophageal acid exposure in these three children resulted in significant increases in both the duration (13.6 +/- 4.0 vs 3.2 +/- 0.2 s, p < 0.05) and amplitude (105.2 +/- 7.8 vs 61.2 +/- 2.1 mm Hg, p < 0.05) of esophageal contractions during wet swallows. Symptoms of chest pain resolved in all patients after therapy with H2-receptor antagonists. CONCLUSIONS: These data represent the first demonstration of acid-induced esophageal dysmotility in children with chest pain and suggest that reflux-induced motor abnormalities contribute to the onset and/or exacerbation of chest pain in pediatric patients with gastroesophageal reflux and esophagitis.

Adolescent↗

Effects of feeding on the small intestinal mucosa of beagle pups during the first 5 d of life.

To further define the effects of feeding on small intestinal ontogeny, naturally suckled and formula-fed beagle pups were studied over the first 120 h of life. In suckled animals, proximal jejunal and midintestinal mucosal weight and protein and DNA contents increased > 75% by 24 h (P < 0.005), with no further increases at 120 h. In formula-fed pups, no mucosal mass changes were found between 0 and 72 h of life. At 120 h, proximal jejunal mucosal weight and protein and DNA contents were significantly greater than in newborns (P < 0.005) and were similar to values for suckled animals at the same time. No significant mid-intestinal or terminal ileal growth was noted in formula-fed pups at any time. Specific and total activities of proximal jejunal brush border lactase, sucrase, and alkaline phosphatase were significantly greater in suckled vs formula-fed animals at 120 h. In a parallel study to assess postnatal effects of mature milk vs colostrum, significant mucosal growth at 24 h of life was demonstrated in pups suckled by surrogate dams who had whelped 21 d previously. These data indicate that both natural suckling (colostrum or milk) and formula feeding support enteric mucosal growth in newborn dogs; however, the two feeding regimens are characterized by unique ontogenic patterns of intestinal mucosal growth and function.

Alkaline Phosphatase↗

Protein kinase C, a pivotal regulator of hamster egg activation, functions after elevation of intracellular free calcium.

We investigated the signal transduction pathways that mediate activation of Syrian hamster eggs. Under conditions in which the concentration of intracellular free calcium ([Ca2+]i) is clamped low, activation of protein kinase C (PKC) can induce second polar body formation, reformation of the nuclear envelope, and decondensation of chromatin, as well as golgi reformation. However, calcium is necessary for normal transition from meiotic metaphase II to anaphase II. Conversely, under conditions in which the level of PKC activity is clamped low, induction of a rise in [Ca2+]i, using the calcium ionophore A23187, does not induce egg activation. These results strongly suggest that PKC acts after the calcium signal as a proximal inducer of egg activation. This suggestion is supported by the kinetics of egg activation; PKC stimulators activate the eggs at a significantly enhanced rate (P < 0.01) compared with activation by calcium ionophore. We show here that PKC stimulators induce emission of the second polar body, but that subsequently, with longer culture, the emitted polar body is absorbed. Our results suggest that the rise in [Ca2+]i serves two functions, to activate PKC and to induce the transition from metaphase II to anaphase II. PKC, once activated, mediates several other events of egg activation.

Animals↗

Treatment of Helicobacter pylori-associated gastroduodenal disease in children. Clinical evaluation of antisecretory vs antibacterial therapy.

The charts of 54 children diagnosed with antral H. pylori were reviewed, to establish the incidence of gastroduodenal inflammation and compare therapeutic efficacies of antisecretory vs. antibacterial therapy. Histology demonstrated normal mucosa in three cases (6%) and gastric/duodenal inflammation (> or = Whitehead grade 3) in 51 biopsies (94%). 23/43 children (53%) initially responded to H2-blockers; however, by 10 mo, 13 had relapsed clinically. All of these patients subsequently responded to amoxicillin plus bismuth subsalicylate. Of the 20 children who failed to enter remission after an initial course of H2-blockers, all became symptom-free after treatment with amoxicillin/bismuth. Compared to antisecretory agents, antibacterial treatment induced clinical remission in 11/11 patients (p < 0.001), who remained symptom-free for 10 +/- 0.2 mo. Clinical remissions were maintained in significantly more patients following amoxicillin/bismuth vs. H2-blockers (44/54 vs. 10/43 courses, p < 0.001); and, the cumulative probability of remaining asymptomatic was significantly greater in the antibiotic group (p < 0.001). These data suggest that gastric colonization by H. pylori is highly predictive of mucosal pathology in children. Initial therapy should be directed toward achieving bacterial eradication, as opposed to gastric acid suppression.

Adolescent↗

Respiratory methane excretion in children with lactose intolerance.

To evaluate the relationship between colonic methane production and carbohydrate malabsorption, we measured end-expiratory methane levels in 70 normal and 40 lactose-intolerant children. Time-dependent excretion of hydrogen and methane was determined every 30 min for 120 min following a fasting oral lactose challenge (2 g/kg). Mean breath hydrogen levels in normals (lactose-tolerant) equaled 3.7 parts per million (ppm) throughout the study, but increased to > 10 ppm by 60 min and remained elevated in lactose-intolerant subjects. Breath methane in normal children averaged 1.6 ppm from 0 to 120 min. In contrast, CH4 excretion by lactose-intolerant children averaged 5.1 ppm at 90 min; and, by 120 min levels increased significantly compared with control. Breath methane levels in lactose-intolerant subjects following a lactose load continued to increase, however, despite the coingestion of exogenous lactase in amounts calculated to result in complete hydrolysis of the disaccharide. These data demonstrate that lactase-deficient children manifest significant increases in breath methane excretion following lactose ingestion and that enhanced methane production may be a consequence of several factors, including altered fecal pH and increased methanogenic substrates provided by colonic lactose fermentation. Further studies are required to determine the clinical significance of elevated methane production in lactose intolerance.

Breath Tests↗

Lipid fluidity modulates platelet aggregation and agglutination in vitro.

To determine the effect of altered membrane fluidity on platelet aggregation/agglutination, fresh, washed human platelets were treated with A2C, a cyclopropyl fatty acid ester which is known to enhance mobility of intrinsic membrane bilayer constituents and increase membrane fluidity. Fluorescence polarization studies demonstrated A2C incubation time- and concentration-dependent increases in platelet membrane fluidity (decreased fluorescence anisotropy). Preincubation with A2C was associated with diminished collagen, thrombin and ristocetin-induced platelet aggregation/agglutination. Aggregation/agglutination was diminished by 93 +/- 5% for collagen (0.2 mg/ml), 53 +/- 3% for thrombin (1.0 U/ml) and 85 +/- 9% for ristocetin (1.1 mg/ml). These data suggest that membrane fluidity is involved in the regulation of platelet function.

Agglutination↗

Cholesterol screening in children: should obesity be a risk factor?

To determine whether obesity should be added to the current American Academy of Pediatrics (AAP) criteria for cholesterol screening in childhood, the charts of 99 children referred for evaluation of either hypercholesterolemia (n = 53) or obesity (n = 45) were reviewed. Compared with obese children, nonobese hypercholesterolemic subjects were younger (8.4 vs 11.4 years) and had lower mean body mass index and % ideal body weight. Frequency of elevated (> 90th percentile for age) total and low-density lipoprotein cholesterols were similar in both groups. Fifty-three of 65 children who met the current AAP criteria were hypercholesterolemic, however, 23/76 hypercholesterolemic children failed to satisfy these screening criteria. Thirty-six of 45 obese children had cholesterol levels > 90th percentile, suggesting increased risk for hypercholesterolemia in this group. If obesity was added to the AAP criteria, 66/80 hypercholesterolemic subjects would have been identified. These modified criteria, vs AAP standards, significantly improved both their sensitivity (70 vs 87%, p < 0.02) and negative predictive value (45 vs 30%, p < 0.02). Pending further studies in larger pediatric populations, these data indicate that obesity should be considered a risk factor for hypercholesterolemia in childhood, and we recommend modifying the AAP screening criteria to include obese children.

Body Mass Index↗

Esophagitis and Helicobacter pylori in children: incidence and therapeutic implications.

The relationship between gastric Helicobacter pylori colonization and esophagitis was determined in 457 children undergoing endoscopic evaluation of abdominal pain and/or vomiting. In all patients, biopsies of the esophagus were examined histologically, and two antral biopsies were analyzed for the presence of H. pylori, using standard microbiological and histochemical techniques. The incidence of biopsy-proven esophagitis was similar in H. pylori-positive (15/56 patients) and -negative (94/401; p = NS) groups. Clinical improvement, after 2 months of antisecretory therapy with H2-receptor antagonists, was independent of H. pylori status (11/15 vs. 68/94 responders; p = NS). All 26 H. pylori-negative nonresponders became asymptomatic with a second course of H2-blockers. The 4/15 H. pylori-positive patients (all of whom had associated gastritis/duodenitis) who failed antisecretory therapy responded clinically to treatment with amoxicillin plus bismuth subsalicylate. These data indicate that primary treatment of biopsy-confirmed esophagitis in children should include anti-secretory agents, regardless of H. pylori status. A small percentage of H. pylori-positive patients with esophagitis and concomitant gastroduodenal inflammation may require additional antibacterial therapy, suggesting that presence of the organism should be assessed in all pediatric patients undergoing upper endoscopic evaluation.

Adolescent↗

Ontogeny of proximal colon basolateral membrane lipid composition and fluidity in the rabbit.

Basolateral membranes from rabbit proximal colon were prepared from isolated colonocytes throughout postnatal maturation, using a modification of published techniques. In suckling (14-20 day) and post-weaning/mature (35-49 day) animals, membranes were purified approx. 10-fold, based upon the enrichment of ouabain-sensitive, sodium-potassium dependent adenosine triphosphatase activity. Membrane lipid analyses demonstrated age-dependent increases in total cholesterol and the cholesterol/phospholipid molar ratio, as well as decreases in phosphatidylethanolamine content and the fatty acid unsaturation index. Fluidity of basolateral membranes and membrane liposomes, determined from fluorescence anisotropy measurements using the lipid probes 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, demonstrated significant, ontogenic decreases in fluidity; and, additional studies showed that fluidity changes occurred early in the weaning period (by day 24 postnatally). Arrhenius plots of liposome anisotropies suggested a bilayer lipid thermotropic transition temperature of 22 degrees C in sucklings 26 degrees C in mature rabbits. These findings demonstrate that ontogeny of colonic basolateral membranes is associated with significant modulations in lipid composition and fluidity.

Animals↗

Glucocorticoid-mediated alterations in fluidity of rabbit cardiac muscle microvessel endothelial cell membranes: influences on eicosanoid release.

Experiments were conducted to determine effects of the synthetic glucocorticoid, dexamethasone, on the lipid fluidity of cultured rabbit cardiac muscle microvessel endothelial cells and the possible role(s) for altered fluidity in the steroid inhibition of cellular eicosanoid production. Following a sixteen hour exposure to 10(-7) M dexamethasone, membranes prepared from treated cells exhibited a decreased fluidity compared to their control counterparts, as assessed by steady-state fluorescence polarization techniques using 1,6-diphenyl-1,3,5-hexatriene (DPH). Examination of the effects of temperature on the anisotropy values of DPH using Arrhenius plots revealed consistent differences in the steroid treated cells over the entire temperature range (40-5 degrees C). These dexamethasone-dependent fluidity changes were associated with increases in the cholesterol/phospholipid ratio of membrane lipids. Restoration of membrane fluidity to control values with the fluidizing agent, 2-(2-methoxyethoxy)ethyl-8-(cis- 2-n-octylcyclopropyl)octanoate (A2C), partially reversed dexamethasone induced inhibition of A23187-stimulated eicosanoid release. These observations suggest that at least part of dexamethasone's inhibitory actions on eicosanoid generation in microvessel endothelial cells are mediated by alterations in membrane composition and fluidity.

6-Ketoprostaglandin F1 alpha↗

Effect of low-density lipoprotein on endothelial cell membrane fluidity and mononuclear cell attachment.

To determine the effects of prolonged low-density lipoprotein (LDL) exposure in vitro on cultured endothelial cell (EC) lipid dynamics and cellular function, human umbilical vein ECs were incubated in LDL concentrations [cholesterol (Chol) = 240 mg/dl] associated with the premature development of atherosclerosis. After 4 days of incubation, cells were examined for changes in cellular lipid composition and for membrane fluidity. Results indicate that LDL-EC have increased Chol content (control EC vs. LDL-EC = 22.4 +/- 5.26 vs. 38.9 +/- 0.24 nmol/10(6) cells, P less than 0.05) and cellular Chol-to-phospholipid ratio (0.61 +/- 0.10 vs. 1.21 +/- 0.10 mol/mol, P less than 0.05). Augmentation of EC Chol content was accompanied by a marked decrease in EC cellular membrane fluidity as assessed by fluorescence polarization (anisotropy, r values, 0.172 +/- 0.019 vs. 0.226 +/- 0.014, P less than 0.0001). LDL-induced changes in EC lipid dynamics were associated with enhanced EC binding of monocytes (P less than 0.05) and U937 cells (P less than 0.01). Both LDL-induced decreases in membrane fluidity and enhanced attachment of mononuclear cells were reversed to control levels following a 2-min incubation of LDL-EC with the membrane mobility agent, A2C. These data therefore suggest that LDL-induced modulations in lipid dynamics play an important role in perturbation of EC function.

Cell Adhesion↗

Beta-galactosidase tablets in the treatment of lactose intolerance in pediatrics.

Lactose-intolerant children manifest diminished or nonexistent intestinal lactase activity, resulting in flatulence, abdominal pain, and diarrhea. To assess the hydrolytic capability of lactase-containing tablets taken immediately before oral lactose challenge, we studied 18 children previously identified as being lactose intolerant and having no underlying organic gastrointestinal disease. Subjects had a mean (+/- SEM) age of 11.4 +/- 3.4 years; 72% were male. At time of the study, lactase-containing tablets or placebo tablets were ingested (double-blind) immediately before drinking a solution of lactose. Breath samples were obtained for hydrogen analysis at 30-minute intervals during a 2-hour period, and clinical symptoms were monitored. In lactose-intolerant patients, hydrogen production was significantly greater following placebo (maximum hydrogen excretion, approximately 60 ppm) compared with lactase-containing tablets (maximum hydrogen excretion, 7 ppm). Increased hydrogen production was associated with clinical symptoms including abdominal pain (89% of subjects following placebo ingestion), bloating (83%), diarrhea (61%), and flatulence (44%). These results indicate, therefore, that coingestion of lactose and lactase-containing tablets significantly reduces both breath hydrogen excretion and clinical symptoms associated with lactose intolerance.

Abdominal Pain↗