Ami Ballin

Association between Common Toll-Like Receptor 4 Mutations and Severe Respiratory Syncytial Virus Disease

BACKGROUND The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV. METHODS The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively. RESULTS Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found. CONCLUSIONS These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

Food allergy is a matter of geography after all: sesame as a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel.

Objective: To determine the prevalence, importance, and the order of frequency of IgE‐mediated food allergens among infants and young children in Israel.

The pattern of sesame sensitivity among infants and children.

Recently, we found sesame to be a major cause of severe IgE‐mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE‐mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients ‘outgrew’ their allergy within 1–2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same ‘noteriety and fate’ as peanut – a major cause of severe food allergic reactions.

Lactic acid as a predictor for erythrocyte transfusion in healthy preterm infants with anemia of prematurity

Elevated blood lactate levels that declined to normal after erythrocyte transfusion were observed in 17 of 37 otherwise healthy infants with anemia of prematurity (26.1 +/- 2.1 mg/dl vs 12.3 +/- 0.9 mg/dl; p < 0.001). Posttransfusion heart rate in this group decreased from 155 +/- 1 beats/min to 150 +/- 2 beats/min (p = 0.01). Blood lactate concentration may be a predictor of the need for transfusion in anemia of prematurity.

Increased number of peripheral blood CD34+ cells in lithium-treated patients

Eight adult patients with bipolar disorder were prospectively examined to find whether lithium carbonate increased their peripheral blood CD34+ haemopoietic stem cells. Following lithium therapy for 3–4 weeks their neutrophil counts increased by a mean of 88% (from 4625 ± 1350 × 109/l, mean ± SD pretreatment, to a peak of 8300 ± 3910 × 109/l). Concommitantly, there was a significant increment in their CD34+ cells (from 0.11 ± 0.01% to a peak of 0.18 ± 0.08%). There was a significant correlation between the rise in neutrophil count and that of the CD34+ cells (r = 0.795, P = 0.019). Lithium therapy may be used to mobilize peripheral blood CD34+ cells for marrow transplantation.

Use of quantitative ultrasound to assess osteopenia in children with Crohn disease.

Background and Aims Children with Crohn disease are at increased risk for osteopenia and osteoporosis. Early development of osteopenia can increase the lifetime risk for fractures and may be amenable to early intervention. The gold standard for measuring bone mineral density (BMD) and fracture risk is dual x-ray absorptiometry (DXA), but this involves some radiation and specialized programs for measuring BMD in children. Bone density Z scores were evaluated with quantitative ultrasound (QUS) using a novel portable device and were compared with DXA in children with Crohn disease. Methods Thirty-five children with documented Crohn disease (mean age 14.3 ± 2.3 years) had speed of sound measured at the left radius and left tibia. Normative values for QUS Z scores were calculated from a cohort of 1,110 healthy children. A subgroup of 26 children with Crohn disease underwent both QUS and DXA. Z scores were calculated and compared for both groups. Results The mean Z score using lumbar spine DXA was −1.04 ± 1.51 SD, compared with −0.15 ± 1.49 SD, using the lowest Z score for QUS (P < 0.05). Using height adjusted DXA, 50% of children with Crohn disease had osteopenia, whereas QUS detected only 19.2% of these children (P < 0.05). Significantly fewer cases of osteopenia were detected using QUS at Z scores up to −2 SD. Conclusions Quantitative ultrasound performed on the radius and tibia may not be sensitive enough to pick up osteopenia in children with Crohn disease.

Flare-Up of Squamous Cell Carcinoma of the Skin following Fludarabine Therapy for Chronic Lymphocytic Leukemia

We present a 72-year-old patient with chronic lymphocytic leukemia (CLL). About a year following therapy with chlorambucil and prednisone, he suffered from anemia, thrombocytopenia and organomegaly. The patient received fludarabine with a favorable response. Concomitantly with the clinical improvement of the CLL there was a remarkable flare-up of scalp squamous cell carcinoma (SCC) lesions, initially noted 4 years previously. The lesions were multiple and grew rapidly. Fludarabine depresses the T lymphocyte population, cells that play a pivotal role in the regression of the SCC. We suggest, that the flare-up and exacerbation of the SCC lesions of the patient were triggered by the fludarabine therapy.

Long-term results of the Israeli National Studies in childhood acute lymphoblastic leukemia: INS 84, 89 and 98

Long-term results of the Israeli National Studies in childhood acute lymphoblastic leukemia: INS 84, 89 and 98

Benign intracranial hypertension associated with budesonide treatment in children with Crohn's disease.

Oral budesonide in adult studies is a potent corticosteroid with decreased systemic bioavailability and an improved adverse effect profile in comparison with prednisone. It has recently been introduced for the treatment of inflammatory bowel disease in Europe, Canada, and Israel. Benign intracranial hypertension has rarely been associated with corticosteroid therapy but has not been reported in association with budesonide therapy. Three adolescents with Crohns disease and poor nutritional status developed benign intracranial hypertension while receiving oral budesonide. All three patients had previously received multiple courses of prednisone during the course of their disease, without developing intracranial hypertension. Benign intracranial hypertension resolved after medication withdrawal and did not recur with subsequent use of prednisone. Evaluation for benign intracranial hypertension should be considered in patients with inflammatory bowel disease who develop headache while receiving oral budesonide. This side effect may be associated with poor nutritional status. (J Child Neurol 2001;16:458-461).

Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid.