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Biomedical subjects

E Granot

Publications and source records attributed to E Granot.

At least 19 recordsLinked to original sources

Tacrolimus immunosuppression - an association with asymptomatic eosinophilia and elevated total and specific IgE levels.

De novo development of food allergy is an infrequent but potentially serious complication of transplantation. An increased prevalence of food allergy noted specifically in children receiving tacrolimus immunosuppression supports the hypothesis that selective suppression of Th1 lymphocytes by the IL-2 inhibitor immunosuppressants CsA, and the more potent drug, tacrolimus , promotes Th2 lymphocytes and an allergic immune response. This study was undertaken to characterize the IgE-mediated immune response, in CsA and tacrolimus-treated, post-OLT children. Thirty children and adolescents aged 1.9-21 yr, mean: 10.6 yr, (6.4 yr post-tx.) were studied. Immunosuppression-CsA: 10 patients, tacrolimus; 20 patients. Blood eosinophils, total IgE levels and specific IgE antibodies (Immulite 2000 Allergy; Diagnostic Products Corp., Los Angeles, CA, USA) to a panel of food and inhaled allergens were measured and correlated with clinical symptoms of allergy. Eosinophilia (>500/mm(3)) range: 599-3125, mean: 1294, was present in 10/20 of patients treated with tacrolimus and 1/10 treated with CsA. IgE levels were elevated in eight of these 10 tacrolimus-treated patients and in two CsA patients ; five were <3 yr of age and IgE levels ranged from 54 to 111 IU/mL (mean: 83), normal for age <45 IU/mL and five were > or =9 yr and IgE levels ranged from 134 to 1606 IU/mL (mean: 557), normal for age <87 IU/mL. Specific IgE levels to a wide panel of food allergens were positive in five tacrolimus-treated patients and to both food and inhaled allergens in three patients (two tacrolimus-treated, one CsA). Four children (tacrolimus-treated) had symptoms of food allergy . None had a family history of allergy. Eosinophilia is present in up to 50% of children and adolescents receiving tacrolimus immunosuppression. The majority of these patients also have elevated levels of total and specific (mainly to food allergens) IgE antibodies. Most patients are asymptomatic and do not manifest food allergy or asthma.

Adolescent↗

Prevalence and risk factors of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in an Israeli long-term care facility.

The purpose of this study was to ascertain the prevalence of extended-spectrum beta-lactamases (ESBLs) among Escherichia coli and Klebsiella pneumoniae strains obtained from urine samples of residents of a long-term care facility and to determine the risk factors for acquisition of ESBL-producing strains. All urine samples collected from January 2003 to October 2003 that were positive for E. coli or K. pneumoniae were tested for the presence of ESBL. Records of patients with ESBL-positive (ESBL-P) samples were analyzed for clinical and demographic data. The records of a matched control group of patients whose urine samples were positive for E. coli or K. pneumoniae but were ESBL-negative (ESBL-N) were also analyzed. The overall rate of ESBLs among the E. coli and K. pneumoniae samples was 25.6%. Of 350 urine samples that grew E. coli, 77 (22%) were positive for ESBL; 34 of 84 (40.5%) samples that grew K. pneumoniae were ESBL-P. Male sex, treatment in the subacute care unit, recent antimicrobial treatment, pressure sores, (percutaneous endoscopic gastrostomy) PEG tube, anemia, hypoalbuminemia, permanent urinary catheter, and any recent invasive procedure were all associated with ESBL-P bacteria in the univariate analysis. The multivariate analysis revealed three independent risk factors for the presence of an ESBL-producing strain: anemia, permanent urinary catheter, and previous antibiotic use. Fluoroquinolones were most strongly associated with the development of ESBL-producing bacteria. The prevalence of ESBL-producing E. coli and K. pneumoniae in the long-term care facility investigated was unexpectedly high and corroborates the notion that long-term care facilities could be important reservoirs of resistant bacteria. Identification of the risk factors for ESBLs is the first step in formulating an effective strategy to curtail the spread of ESBL resistance in long-term care facilities.

Age Distribution↗

Usefulness of blood cultures in the management of febrile patients in long-term care facilities.

The aims of the study presented here were to identify the risk factors associated with bacteremia in a long-term-care facility and to evaluate the role of blood cultures in the management of elderly patients with sepsis. All blood cultures performed during a 2-year period (3,177 from 1,588 patients) were screened, and 252 (15.8%) of them grew a pathogen. The first 100 bacteremic patients identified were enrolled in the study together with a control group of 100 non-bacteremic patients matched by sex, age and functional status. Chronic renal failure, urinary tract infection, severe sepsis, leukocytosis, eosinopenia and thrombocytopenia were identified as risk factors associated with bacteremia. Five bacteremic patients died during the first 48 h following the onset of infection, while all of the non-bacteremic patients survived this time period. Of 58 bacteremic patients receiving adequate treatment, 17 patients died, and of 39 receiving inadequate treatment, 12 patients died. These results indicate the usefulness of performing blood cultures in elderly patients with sepsis is questionable.

Aged↗

Complicated endoscopic pediatric procedures using deep sedation and general anesthesia are safe in the endoscopy suite.

BACKGROUND: Complicated upper and lower endoscopic procedures of the gastrointestinal tract are performed in children for a variety of diagnostic and therapeutic reasons. Unlike adult patients, who receive conscious sedation, children usually require deep sedation (DS) or general anesthesia (GA). The aim of this study is to assess the safety parameters of complicated endoscopic procedures under DS or GA performed in children in the endoscopy suite rather than in the operating theatre. METHODS: Between May 1997 and December 2002, 296 patients (mean age 4.5 years, range 3 weeks to 16 years), defined as ASA I-III, underwent either DS or GA for endoscopic foreign body extraction, endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous endoscopic gastrostomy (PEG) insertion. ASA physical status I was found in 15%, II in 57% and III in 28%. The pathologies included neuromuscular diseases, genetic syndromes, nesidioblastosis, biliary atresia, hematologic, respiratory (cystic fibrosis) and cardiac disorders. Propofol was the drug of choice (63%) followed by a combination of propofol and midazolam (16%). RESULTS: Transient desaturation (O2 saturation <90%) was the only complication recorded in 21/296 (7.09%) patients. Only two patients with severe respiratory underlying disease were hospitalized for follow-up for a 24-h period. CONCLUSIONS: The use of DS and GA for complicated endoscopies in a moderately high-risk pediatric population was found to be safe. The very low complication rate found in this study suggests that complicated pediatric patients can be managed successfully outside the operating theatre, provided that all the safety criteria for ambulatory DS or anesthesia are present.

Adolescent↗

Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients.

PURPOSE: To assess the long-term efficacy of combined vitamin A and E treatment in preventing retinal degeneration in patients with abetalipoproteinaemia (ABL) or homozygous hypobetalipoproteinaemia (HBL). METHODS: Ten patients with ABL and 3 with homozygous HBL who were treated with oral supplements of vitamins A and E were studied. Systemic, ophthalmological and electroretinographic follow-up for a mean of 11.7 years (range 4-20 years) after onset of treatment was evaluated. RESULTS: Despite vitamin A and E treatment, 7 of 10 patients who began treatment prior to 2 years of age and all 3 patients who began treatment later in life manifested unusual fundoscopic pigmentary changes over time. At the end of follow-up, 11 of 13 patients had subnormal mixed cone-rod electroretinogram amplitudes. Seven of 10 patients for whom perimetry was available had mild to severe constriction of the visual fields. CONCLUSIONS: Combined oral vitamin A and E supplementation that is initiated prior to 2 years of age can markedly attenuate the severe retinal degeneration that is associated with untreated ABL or homozygous HBL. Yet, fundoscopic and functional retinal changes do occur despite early initiation of vitamin treatment. Therefore, the adequacy of the present treatment protocol for ABL and homozygous HBL should be re-evaluated.

Abetalipoproteinemia↗

Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients.

OBJECTIVE: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)) and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy. METHODS: In 55 patients with chronic hepatitis C virus (HCV), 33 treated with interferon (IFN) and 22 treated with IFN + ribavirin, sera was collected prior to treatment, at 3 + 6 months of therapy and 6 months post-treatment. Levels of ICAM-1, VCAM-1 and hyaluronic acid were correlated with alanine aminotransferase levels, HCV-RNA-polymerase chain reaction status and histological fibrosis scoring. RESULTS: A decrease in ICAM-1 levels at 3 and 6 months of therapy, compared with pretreatment levels, was observed in responders to IFN + ribavirin therapy but this decrease in ICAM-1 levels was not evident following cessation of treatment. Hyaluronic acid levels, in both treatment groups, did not differ significantly between responders and non-responders. Hyaluronic acid levels did correlate, significantly, with degree of fibrosis whereas VCAM-1 levels were marginally increased only in patients with moderate (grade III) fibrosis. CONCLUSIONS: Monitoring of VCAM-1 and hyaluronic acid, during antiviral therapy, does not differentiate between responders and non-responders. A decrease in ICAM-1 levels during IFN + ribavirin treatment is associated with response to therapy, and its efficacy in predicting long-term response should be further substantiated.

Adult↗

Oxidative stress is not enhanced in non-malnourished infants with persistent diarrhea.

Increased concentrations of reactive oxygen species (ROS) and depleted antioxidant defences have been implicated in a cycle of infection, malabsorption and malnutrition, leading to persistent diarrhea. In order to determine whether in non-malnourished children oxidative stress predisposes to the development of persistent diarrhea, infants with acute diarrhea (< 7 days) (n = 39) were compared to infants with persistent diarrhea (> 14 days) (n = 38). Lipid peroxidation was assessed by the TBARs assay and expressed as malondialdehyde equivalent content (nmol MDA/ml plasma), and levels of plasma antioxidants vitamin A and vitamin E were determined. In infants with acute and persistent diarrhea nutritional status, as assessed by weight/height and height-for-age, hemoglobin levels, serum albumin and immunoglobulin levels, did not differ between groups. Serum vitamin A and vitamin E levels did not differ in infants with acute or persistent diarrhea. TBARs, expressed as nmol MDA/ml plasma did not differ between infants with acute or persistent diarrhea and furthermore did not differ from levels in a healthy, similar age, control group. Non-malnourished infants with persistent diarrhea do not exhibit plasma antioxidant depletion or enhanced lipid peroxidation. In these infants, oxidative stress, as reflected in plasma, does not play a role in the pathogenesis of persistent diarrhea.

Analysis of Variance↗

Abrupt increase of tacrolimus blood levels during an episode of Shigella infection in a child after liver transplantation.

The authors report the case of an 8-year-old girl who underwent a liver transplant at the age of 18 months because of biliary atresia. She was treated with cyclosporin for more than 5 years. Increased hirsutism prompted a change to tacrolimus therapy. During 11 months the mean tacrolimus level was 8.2 ng/mL. The patient was hospitalized because of an episode of Shigella infection and a threefold increase in tacrolimus level was measured. Despite a reduction of tacrolimus dose, the trough tacrolimus levels were in the range of 16.5 to 22.0 ng/mL during the subsequent 2 weeks. On resolution of the diarrhea, tacrolimus levels returned to those observed before the Shigella infection. It is suggested that the marked increase in tacrolimus levels observed in this patient is a direct result of the damage produced to the gastrointestinal mucosa by the Shigella infection.

Child↗

Detection of inhomogeneities with ultrasound tagging of light.

Ultrasound modulated light for optical tomography is very useful, since it can provide three-dimensional data with minimal mathematical processing. Although several experimental studies have shown the potential of this method, the link between the ultrasound location and the modulated signal intensity at the detector is not yet fully understood. We derive an analytical formula relating the position of the ultrasound transducer and the optical signal at the detector. We also derive an expression for the signal-to-shot-noise ratio as a function of the transducer position. We show that in certain conditions this ratio is only slowly decreasing as a function of the light penetration depth, which makes this technique attractive for optical tomography.

Computer Simulation↗

Celiac disease and short stature--not always cause and effect.

Four children with familial short stature were diagnosed with celiac disease (CD) by positive serology for antigliadin and antiendomysial antibodies and characteristic intestinal biopsy findings. These patients complied well with their diet as evidenced by their parents' reports, increase in weight standard deviation scores in all but one child, and reversion to seronegativity for antigliadin and antiendomysial antibodies in all four. However, typical catch-up for linear growth did not occur. In our view, the poor response of linear growth is evidence that the original stunting was not due to CD. Since the advent of sensitive tests for antiendomysial antibodies, many asymptomatic children have been diagnosed as having CD. Some of these children are short and despite a history of familial short stature their growth stunting may be wrongly attributed to CD. This report highlights this new problem and emphasizes the need for caution when predicting growth response to a gluten-free diet.

Autoantibodies↗

Substance P in rectal mucosa of children with chronic constipation.

Substance P content was determined by radioimmunoassay in rectal mucosa of 17 children with idiopathic constipation and 9 with normal bowel movements who were used as controls. In children with chronic idiopathic constipation, rectal mucosa substance P levels were lower than levels in the control group: 47.6 +/- 11 vs. 79.4 +/- 11 pg/mg net weight respectively (differences not statistically significant). Substance P levels in rectal mucosa of children with soiling (11/17) did not differ from those of chronically constipated children without soiling (46.0 +/- 16 vs. 50.5 +/- 19 pg/mg net weight). In children with constipation, substance P levels did not correlate either with age or duration of symptoms. Substance P levels in normal controls were similar to levels previously observed in non-constipated adults, whereas levels in constipated children were intermediate between levels observed in healthy subjects and levels in adults with chronic constipation. These findings may point to a motility derangement as a possible factor in the pathogenesis of chronic constipation in childhood.

Case-Control Studies↗

[Acetaminophen toxicity in children as a "therapeutic misadventure"].

Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse. We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity. Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.

Acetaminophen↗

Transient transmission of hepatitis C virus from mothers to newborns.

A study was performed in Israel to determine the rate of mother-to-infant HCV transmission in newborns at risk. A group of 22 HCV-infected mothers and their 23 newborns were followed up from early after birth by testing their serum for the presence of HCV antibodies and HCV-RNA. Antibody against HCV was detected in the blood of all newborns immediately after birth, but dropped to low or undetectable levels by 7 months of age. HCV-RNA was detected 2 days after birth in the blood of five infants (22%) but fell to undetectable levels by 6 months. HCV-HVR1 sequence analysis performed in one mother-infant pair on the second day after birth revealed two nucleotide changes. Two months later the same sequence was detected again in the HVR1, suggesting a very low replication rate. Thus, the study showed that vertically transmitted HCV was eliminated in all newborn infants by 6 months after delivery, with concomitant disappearance of HCV antibodies. The mechanism of HCV elimination in newborns at risk remains to be elucidated.

Adult↗