Yehuda Nofech-Mozes MD, Yael Yuhas PhD, Elisabeth Kaminsky MSc, Abraham Weizman MD and Shai Ashkenazi MD MSc
Background: The pathogenesis of neurological symptoms, the most common extraintestinal complication ofchildhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role.
Objectives: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R.
Methods: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate.
Results: In our animal model of Shigella related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection.
Conclusions: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.
Ilan Zahavi MD, Olga Rosezki MD, Yerah Stolkarts MD, Raanan Shamir MD, Bruria Heckelman BSc, Hedva Marcus MSc and Gabriel Dinari MD
Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.
Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.
Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.
At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.
Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.
Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.
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TPN= total parenteral nutrition
Dan Nemet, MD, Baruch Wolach, MD, Joanne Yacobovich, MD and Alon Eliakim, MD
Ben Zion Garty MD, Yehudit Monselise PhD and Menahem Nitzan MD
Background: Inflammation is a major component in the pathogenesis of asthma. CD14 is an endotoxin (lipopolysaccharide) receptor, and is expressed mainly on monocytes and macrophages. Binding of LPS to CD14 activates the monocyte or macrophage and causes the release of different cytokines. The soluble form of CD14 is present in serum, and its concentration increases in several clinical conditions, including infections, auto-immune disorders, allergic disorders, and lung diseases. The possible role of CD14/sCD14 in asthma has been investigated in a few adult patients only.
Objectives: To measure serum concentrations of sCD14 in children with status asthmaticus.
Methods: We compared serum concentration of sCD14 in 10 children with status asthmaticus measured within 24 hours of admission and after recovery from the acute episode.
Results: Levels of sCD14 were significantly higher during acute asthma attacks than at recovery.
Conclusions: The elevated serum levels of sCD14 during status asthmaticus may be the result of the activation of monocytes, macrophages or other cells. The influence of medications on serum sCD14 cannot be ruled out. The possible use of sCD14 as a marker of lung inflammation in asthma warrants further investigation.
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LPS= lipopolysaccharide
SCD14= soluble form of CD14
Itamar Offer, MD, Shai Ashkenazi, MD, Gilat Livni, MD and Itamar Shalit, MD
Background: Bronchiolitis caused by respiratory syncytial virus is one of the major causes of hospitalization in young children, especially during the winter. Recent evidence has shown that pharmacological treatment, especially nebulized epinephrine, in addition to the traditional supportive treatment, can alleviate symptoms and shorten hospitalization, but this approach is not yet widespread.
Objectives: To determine whether the management of bronchiolitis in Israel is moving toward a stronger emphasis on pharmacological care.
Methods: A questionnaire on the diagnosis and management of bronchiolitis was completed by 27 heads of pediatric departments throughout Israel. The questionnaire dealt with the frequency of usage of diagnostic and selected therapeutic procedures.
Results: Chest X-ray and arterial blood gases are commonly used as a diagnostic aid in more than 75% of the departments, and antibiotics are prescribed routinely in 24%. Corticosteroids are still in use: 48% use systemic steroids, and 19% nebulized steroids. Nebulized epinephrine is used in 22% of the departments, while nebulized beta-agonists are used frequently in two-thirds of the departments.
Conclusions: Despite convincing data that beta-agonists and steroids have no positive effect on the outcome of bronchiolitis on the one hand, and that nebulized epinephrine has advantages in children on the other, we found significant use of the former two agents and sparse use of the latter. Greater awareness is needed among pediatricians, and measures should be introduced to incorporate the new recommendations, with further study of the effect of the old and new drugs on bronchiolitis.
Einat Birk MD, Alon Stamler MD, Jacob Katz MD, Michael Berant, Ovadia Dagan MD, Abraham Matitiau, Eldad Erez MD, Leonard C. Blieden and Bernardo A. Vidne
Background: Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital malformation that presents a diagnostic challenge to the pediatrician and pediatric cardiologist. Although surgical repair is always indicated, the optimal technique has yet to be determined.
Objectives: To review our experience with the diagnosis of children with ALCAPA and to assess short to midterm surgical results.
Methods: Between 1992 and 1998, 13 infants and children (2 months to 15 years) were treated for ALCAPA at our medical center. Eight were diagnosed during the first year of life; all were symptomatic and had severe dysfunction of the left ventricle. The five patients diagnosed at an older age had normal myocardial function. Diagnosis was established by echocardiography alone in seven patients; six required catheterization (one infant and all older patients). Surgery was performed in 12 patients to establish dual coronary artery system: 7 underwent the Takeuchi procedure and 5 had re-implantation of the anomalous left coronary artery.
Results: One infant died shortly after diagnosis before surgical repair was attempted, and one died postoperatively. Four patients required additional surgery: three for late complications of the Takeuchi procedure and one valve replacement for mitral insufficiency. Recent evaluation revealed good global left ventricle function in all patients except for one, who is still within the recovery phase and shows gradual improvement. However, most patients who presented with severe myocardial dysfunction upon diagnosis still display abnormal features such as echo-dense papillary muscles or evidence of small akinetic segments. In this group, early repair was associated with faster myocardial recovery.
Conclusions: The diagnosis of ALCAPA remains a clinical challenge to the pediatrician and cardiologist. Diagnosis can be established echocardiographically, and early diagnosis and treatment may lead to faster myocardial recovery. The preferred surgical method appears to be re-implantation of the ALCA. The chance for good recovery of global ventricular function is high even in the sickest patients, nonetheless abnormal myocardial features can be identified even years after surgery.
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ALCAPA= anomolous origin of the left coronary artery from pulmonary artery.