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Biomedical subjects

E Granot

Publications and source records attributed to E Granot.

At least 19 recordsLinked to original sources

Lymphocyte subset profile of young healthy children residing in a rural area: possible role of recurrent gastrointestinal infections.

BACKGROUND: Lymphocyte subsets in healthy children are currently characterized by age-related standards. Because antigenic stimuli play a role in maturation of the immune system after birth, there is a question of whether cellular immune development differs in infants whose living conditions entail extensive antigenic exposure and infants growing up in a more protected environment. METHODS: Peripheral blood lymphocyte subsets were studied in two populations of children of similar age and nutritional status; children belonging to a rural population residing in proximity with farm animals and children from an economically privileged urban population. In each population, children studied included a group with an acute diarrheal episode and a healthy control group. RESULTS: Among rural population children, 65% had experienced at least one episode of gastroenteritis within the previous 3-month-period, compared with less than 10% of urban population children. In the rural population group 15% had experienced two or more episodes of gastroenteritis. The proportion of helper T cells was similar in rural population and urban population children. Among helper T cells, the proportion of CD29+ "memory" cells of the total CD4+ helper T cells was more than two times higher than those in rural population children. The proportion of CD8 cells was higher in rural population children than in urban population children, and the proportion of natural killer cells, CD56+ and CD57+, was two to three times higher in rural population children. Within each population, peripheral blood lymphocyte subsets did not differ between the healthy control group and those with acute diarrhea. CONCLUSIONS: In young children exposure to environmental pathogens and specifically to gastrointestinal antigenic stimuli is a major factor affecting development of the cellular immune response. Young children who have experienced enhanced infectious exposure have a peripheral blood lymphocyte profile similar to that of adults.

Acute Disease

Lipoprotein changes in children after liver transplantation: mild hypertriglyceridemia and a decrease in HDL3/HDL2 ratio.

Hyperlipidemia is frequently observed in patients who undergo renal, cardiac, bone marrow, or liver transplantation, and its contribution to the long-term morbidity and survival of patients with organ transplants may be substantial. In the few studies that have focused on the pediatric age group, findings have been inconsistent. The lipoprotein profile of 10 children after liver transplantation was characterized and compared with those in normal population controls and 10 healthy siblings. Plasma triglyceride and cholesterol concentrations were determined, lipoprotein fractions (very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoproteins [HDL2 and HDL3]) were isolated, their chemical compositions were analyzed (protein, phospholipids, triglycerides, free cholesterol, and cholesteryl ester), and the percent relative weight composition of the particles was calculated. Plasma triglyceride and VLDL cholesterol levels were higher post-liver transplantation (P < .05): triglycerides (mean +/- SD), 115.1 +/- 58.7 mg% versus 76.6 +/- 20.9 mg% in siblings and 60.0 +/- 25.0 mg% in normal population controls; very-low-density lipoprotein cholesterol (VLDL-C), 23.0 +/- 11.7 mg% versus 15.3 +/- 4.7 mg% and 13.0 +/- 8.0 mg%, respectively. Plasma triglyceride levels did not correlate with the length of the period after liver transplantation. Levels of LDL-C and total HDL-C and the relative weight composition of VLDL, LDL, HDL2, and HDL3 particles did not differ between post-liver transplantation children and controls. Posttransplantation, levels of HDL3, the normally predominant HDL subfraction, were decreased relative to HDL2 levels (HDL3, 1.3; HDL2, 2.3). Because this observed relative increase in larger cholesteryl ester-rich HDL particles (HDL2) may result from inhibition of cholesteryl ester-triglyceride transfer processes, cholesteryl ester transfer protein activity was assayed. Cholesteryl ester transfer protein activity did not differ between patients and controls. Thus, the lipoprotein changes observed in children post-liver transplantation are mild hypertriglyceridemia and a significant increase in HDL2 relative to HDL3. Because HDL2 is regarded as protective against atherosclerosis, this may be of clinical relevance.

Child

Immunologic response to infection with Giardia lamblia in children: effect of different clinical settings.

Infection with Giardia lamblia varies in both its severity and duration. A high incidence of giardiasis in immunoglobulin-deficient individuals suggests a role for the humoral immune response in resistance to Giardia infection. Levels of specific anti-Giardia antibodies were determined in three populations of children infected with the parasite: in children attending a day-care centre in which strict hygiene measures were practised and in whom all Giardia infections were asymptomatic; in a rural population residing under poor hygienic conditions in close proximity to farm animals in which children with Giardia-associated diarrhoeal episodes were studied; and in Bedouin infants followed from birth and in whom a previous study has shown that Giardia infection is almost universal by the age of 2 years. In day-care children, infection was accompanied by a significant increase in anti-Giardia IgM levels, compatible with an initial exposure to the parasite. In populations in which exposure to the parasite occurs at an early age and the prevalence of infestation is high, the pattern of specific antibodies to the parasite is rather uniform and cannot differentiate between current infection and previous exposure. Thus, other immune parameters such as salivary or urinary secretory IgA, which reflect the intestinal IgA response, should be studied in order to delineate further the humoral immune response to Giardia.

Animals

Gastroesophageal reflux in infants with hydrocephalus before and after ventriculo-peritoneal shunt operation.

Gastroesophageal reflux (GER) is common in neurologically impaired children, especially those with central nervous system disorders. The cause of GER in these children has not yet been defined, but in animal studies, acute elevation of intracranial pressure (ICP) has been shown to result in a decrease in lower esophageal sphincter pressure. Ten infants with hydrocephalus underwent esophageal pH monitoring prior to and after a ventriculoperitoneal (V-P) shunt operation. A significant degree of reflux was present in 5 patients with hydrocephalus prior to shunt operation and reverted to normal in 2. In the other 3 infants, the degree of reflux decreased as evidenced by fewer abnormal parameters and lower scoring in each of the parameters measured. Our study supports the contention that increased ICP in infants is indeed associated with GER. As 4 of the 5 infants with significant reflux suffered from an Arnold-Chiari malformation, a causal relation between increased ICP due to defects involving the fourth ventricle floor and GER is suggested.

Acute Disease

Crohn's disease in late adolescence: acute onset or long-standing disease?

We studied retrospectively a group of 53 patients with Crohn's disease, diagnosed between 18 and 21 years of age. They had all undergone a thorough medical evaluation at age 17 before military service. They thus served as a unique group in whom the natural course of the disease, duration of signs and symptoms before diagnosis, and delay in diagnosis could be assessed. Other than a more frequently elicited history of nonspecific mild recurrent abdominal pain in childhood in the patient group, medical history, physical growth, sexual development, and laboratory parameters of inflammation did not differ in the patient group and the healthy control group. Crohn's disease in this group of young adults is likely one of acute onset and did not begin as an exacerbation of a more subtle and prolonged process.

Acute Disease

[Endoscopic retrograde cholangiopancreatography in diagnosis of biliary atresia].

The differential diagnosis between neonatal hepatitis and biliary atresia in the newborn is difficult and has therapeutic implications. Despite important advances in diagnostic tools, 10-20% of newborns with jaundice remain without definitive diagnosis. In recent years ERCP has played a decisive role in achieving definitive anatomic diagnosis, thus avoiding unnecessary exploratory laparotomy. We present our experience with ERCP using a pediatric duodenoscope in 18 newborns with inconclusive diagnoses of neonatal cholestasis.

Biliary Atresia

Failure of exogenous apoprotein E-3 to enhance cholesterol egress from J-774 murine macrophages in culture.

HDL has been shown to enhance the removal of cholesterol from cultured fibroblasts, smooth muscle cells and macrophages, but fails to stimulate cholesterol removal from J-774 macrophages. Since J-774 macrophages do not synthesize or secrete apolipoprotein E, the effect of exogenous apolipoprotein E on HDL-mediated cellular cholesterol efflux was studied in this cell line. In cholesterol loaded J-774 macrophages total cellular cholesterol increased up to 6-7-fold, mainly cholesteryl esters. HDL3 removed up to 30% of total cellular cholesterol with a decrease in cholesteryl ester levels while free cholesterol levels remained unchanged. HDL3 was slightly superior to albumin in promoting cellular cholesterol removal. Exogenous apo E, over a wide range of apo E concentrations, did not enhance the ability of HDL3 to remove cellular cholesterol from cholesterol loaded J-774 cells. Exogenous apo E did not promote HDL-mediated cholesterol efflux from cells, thus suggesting a possible role for the intracellular route of newly synthesized apo E in these processes.

Albumins

Effects of particle size on cell uptake of model triglyceride-rich particles with and without apoprotein E.

The effect of apoprotein E on cellular uptake of "VLDL-size" and "IDL-size" triacylglycerol-phospholipid emulsion particles was studied in J-774 macrophages and fibroblasts. In the absence of apoprotein E (apo E), uptake of the smaller IDL-size particles was up to 2-fold higher by mass and 100-fold higher as calculated by particle number. Apo E enhanced the uptake of both VLDL-size and IDL-size emulsion particles, but the effect was greater on the uptake of larger particles (4-5-fold) as compared to up to a 2-fold increase in the uptake of IDL-size particles. In fibroblasts, particle uptake was less than in macrophages (30-50%), but preferential uptake of smaller particles was similarly observed. Particle internalization was demonstrated by 125I-apo E degradation and resistance to particle release by heparin-suramin. In the absence of apo E, cholesteryl ester of emulsion particles (prepared with trace amounts of [3H]cholesteryl ester) was hydrolyzed to free cholesterol, proving internalization and intracellular metabolism. Double-label experiments using DiI-labeled emulsion particles, in the absence and presence of apo E, showed that emulsion particles are rapidly targeted to perinuclear lysosomes. Thus, at physiological concentrations of triglyceride-rich particles, non-receptor-mediated uptake is a mechanism for the uptake of VLDL-size and IDL-size particles into cells.

Apolipoproteins E

[Neonatal hepatitis and biliary atresia].

The differential diagnosis between intrahepatic and extrahepatic cholestasis in the newborn is difficult and has therapeutic implications. 61 cases of neonatal cholestasis were retrospectively analyzed to assess the efficacy of various tests and procedures in differentiating between the 2 types. Determination of serum gamma-glutamyl transpeptidase, ultrasonography and radionuclide scanning differed significantly in the 2 types (p '0.05 for all 3 determinations). A diagnostic program for evaluation of infants with neonatal cholestasis is proposed.

Biliary Atresia

[Reduced-size liver transplants in children].

Orthotopic liver transplantation is now used for children with end-stage liver disease, but the scarcity of size-matched liver allografts for children has limited its use. Reduced-size liver transplantation, in which only part of the liver is used as a graft, overcomes size disparity and increases significantly the potential donor pool for children. A 4-year-old boy with fulminating hepatic failure due to hepatitis became the first case of reduced-size liver transplantation in Israel. A left hepatic lobe allograft from an adult donor was used. The boy is home and well 9 months after transplantation. Reduced-size liver transplantation was first performed in a child by Bismuth and Houssin in 1984. Reports from several centers show that survival of recipients of reduced-size liver allografts and the rate of retransplantation does not differ significantly from that in recipients of full-sized livers.

Child

Salivary IgA antibodies to Giardia lamblia in day care center children.

An enzyme-linked immunosorbent assay was developed for the detection of specific salivary IgA antibodies to Giardia lamblia. Among 73 infants and children in a day care center 9 asymptomatic subjects had stools positive for G. lamblia. Salivary antigiardia IgA concentrations, expressed as OD units, were higher in the 2- to 4-year-old group: 0.899 +/- 0.03 vs. 0.660 +/- 0.03 in the < 2-year old group (P < 0.001). In both groups values were higher in the infected children (1.099 +/- 0.04 vs. 0.629 +/- 0.09 in the < 2-year-old group and 1.053 +/- 0.07 vs. 0.859 +/- 0.03 in the 2- to 4-year-old group). In children infected throughout the study period, salivary antigiardia antibodies remained consistently high and in 2 children whose stools were initially negative a significant rise in OD value was observed after stools tested positive. Total salivary IgA did not differ between the two age groups and did not correlate with specific salivary antigiardia antibodies in individual subjects. The enzyme-linked immunosorbent assay for detection of specific salivary antibodies to G. lamblia can be used in the study of the mucosal immune response to the parasite, and may serve as an screening tool in monitoring the exposure of various populations to G. lamblia.

Animals

"Early" vs. "late" diagnosis of celiac disease in two ethnic groups living in the same geographic area.

Despite studies documenting existence of celiac disease worldwide, its prevalence in many parts of the world is underestimated and cases remain unrecognized. In Israel, celiac disease is relatively common among the Jewish population but considered to be rarer among the Arab population. We compared the manifestations of celiac disease in children of both ethnic groups and questioned whether differences in presentation relate to degree of awareness for celiac disease in each group. Age at presentation, time interval between onset of symptoms and diagnosis, prevalence of gastrointestinal symptoms, presence of signs of malabsorption and degree of growth retardation varied markedly between both groups. In populations in which there is a low index of suspicion for celiac disease, symptoms may be wrongly attributed to the post-gastroenteritis syndromes or protein-calorie malnutrition, thus resulting in a detrimental delay in diagnosis. Undiagnosed cases may in later childhood manifest predominantly as short stature.

Adolescent

Chronic diffuse varioliform gastritis in a child. Total gastrectomy for acute massive bleeding.

Chronic diffuse varioliform gastritis is an uncommon, subacute, inflammatory gastric mucosal disease characterized by swollen congested rugae and disseminated mucosal erosions. The entity is exceptionally rare in children. The spectrum of reported symptoms is broad; frank hematemesis has never been reported in childhood. We present a child in whom the disease had a remarkably unusual clinical course. Because many caretakers were unaware of the existence of the disease in children, the patient had numerous hospitalizations and surgical procedures, until massive gastric bleeding resulted in unavoidable emergency total gastrectomy. Microscopical examination and immunofluorescent staining of the gastric mucosa confirmed the diagnosis of chronic diffuse varioliform gastritis.

Child

Histological comparison of suction capsule and endoscopic small intestinal mucosal biopsies in children.

Small intestinal biopsies are part of the routine evaluation of children with chronic diarrhea and malabsorption, and are commonly performed via suction capsule. Because this technique entails x-ray exposure, longer procedure time, and technical failures, most small intestinal biopsies in adults are currently obtained via endoscopy. Endoscopy is believed to yield morphologically inferior specimens, and, therefore, its use for obtaining small intestinal biopsies in children has remained limited. The histological adequacy of biopsy specimens obtained in 30 children by endoscopy and in 30 children by suction capsule was compared. Biopsies were assessed for quality of orientation, size (length and depth), presence of Brunner's glands and crush artifact, and for the ability to confirm or exclude a mucosal abnormality. Small intestinal biopsies obtained via endoscopy were shown to yield tissue specimens that are histologically comparable to those obtained by suction capsule, and that are equally suitable for interpretation.

Biopsy

Familial hypobetalipoproteinemia--differences in lipoprotein structure and composition.

Familial hypobetalipoproteinemia represents a heterogeneous group of genetic defects in which the concentrations of plasma apolipoprotein B and apo-B-containing lipoproteins VLDL and LDL are abnormally low. To explore potential effects of different genotypes on plasma lipid patterns, the lipoproteins of two families with hypobetalipoproteinemia were compared using zonal ultracentrifugation and chemical analyses. Heterozygotes differed between families not only in level and composition of apo-B-containing lipoproteins but also in HDL subclass distribution. In one family, heterozygotes had very low apo B levels and their major HDL subfraction was HDL2 as in abetalipoproteinemia, whereas in the second family heterozygotes had apo B levels approximately half on normal and the major HDL subfraction was HDL3 with an HDL elution pattern intermediate between that observed in abetalipoproteinemia and normal subjects. Observations on the HDL system in these two families substantiate the role of cholesteryl ester/triglyceride exchange between HDL and lower-density lipoproteins in the remodelling of HDL in plasma.

Adolescent