Israel Medical Association Journal

Background: Despite current treatment protocols, the long-term complications of insulin-dependent diabetes mellitus have prompted the investigation of strategies for the prevention of IDDM.

Objectives: To investigate the effect of oral vanadate in reducing diabetes type I in non-obese diabetic mice.

Methods: Sodium metavanadate, 3.92 mmol/L, was added to the drinking water of 8-week-old female NOD mice. Blood glucose levels, water consumption and body weight were measured, and the end point of the study was judged by the appearance of hyperglycemia in the mice.

Results: Treatment with vanadate did not significantly reduce the incidence of type I diabetes as compared to the control group. However, oral vanadate therapy significantly reduced the blood glucose levels after the fourth week of treatment compared to the control group (3.83±10.67 vs. 4.44±10.83 mmol/L, P<0.03). There was a consistent and significant increase in body weight of the vanadate-treated pre-diabetic NOD mice compared to the controls. Diabetic mice treated with vanadate had significantly lower levels of serum insulin as compared to control diabetic mice (104±27 vs. 151±36 mol/L, P<0.03). Histologically, no significant differences were found in inflammatory response of the islets of Langerhans between the control and treated groups.

Conclusions: This study suggests that the post-receptor insulin-like effect induced by vanadate is not sufficient to prevent the development of diabetes and insulitis in pre-diabetic NOD mice.

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IDDM= insulin-dependent diabetes mellitus

NOD= non-obese diabetic

Background: Dyslipidemia and obesity serve as risk factors for the development of atherosclerotic cardiovascular disease. Fasting is sometimes recommended for treating these conditions. This study was undertaken to try to resolve conflicting results reported in the literature.

Objectives: To study the effect of fasting (0 calories, with free intake of fluids) for 3-5 days on plasma concentration of triglyceride, cholesterol and apolipoprotein B.

Methods: Physicians, about to begin a hunger strike, were divided into four groups: normolipidemic non-obese men (group 1), two moderately obese men and two men with type IV hyperlipidemia (group 2), healthy non-obese women (group 3), and healthy non-obese women on oral contraceptives (group 4). Adherence to fasting was monitored daily by detailed interviews, loss of weight, drop in plasma glucose, presence of ketonuria, progressive rise in serum creatinine and uric acid, and decrease in plasma pH. We monitored their serum glucose, electrolytes, liver function, lipids, lipoproteins and apolipoprotein B on days 0, 3, and 5.

Results: Physicians who adhered to complete fasting lost more than 1.5% of their body weight after 3 days of fasting (n=12), and more than 3.2% at 5 days (n=5). All non-obese normolipidemic males and females (groups 1 and 3) showed an increase in plasma triglyceride (by 28-162%) and very low density lipoprotein cholesterol (by 22-316%) after 3 days of fasting. The obese and hyperlipidemic men (group 2) showed a decrease of 17-63% in their VLDL cholesterol, and the women on oral contraceptives (group 4) showed a 20% decrease in their plasma triglyceride on day 3. Low density lipoprotein cholesterol increased by 13% in group 2, decreased by 7.3% in group 4, and remained unchanged in group 1 and 3. Apolipoprotein B level correlated well with LDL cholesterol in all groups. High density lipoprotein cholesterol changes were inconsistent.

Conclusions: These results help to explain and reconcile previous published reports. The metabolic background of the individual together with the amount of energy consumed affect the behavior of plasma lipids and lipoproteins levels during fasting.

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VLDL= very low density lipoprotein

LDL= low density lipoprotein
 

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.
 

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
 

Background: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians. Typically it is a multisystem disease diagnosed by increased chloride levels on sweat testing, with mortality due mainly to progressive respiratory disease. The clinical spectrum of CF has recently been much expanded.

Genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFTR function is shown using nasal potential difference measurement.

Objectives: To highlight the diagnostic and therapeutic dilemmas in cases of atypical cystic fibrosis.

Methods: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children’s Medical Center of Israel. 

Results: Two patients had severe lung disease but little expression in other organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health but have symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these patients, careful counseling is needed to avoid unnecessary upheaval, inappropriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide.

Conclusion: It is our obligation as clinicians - at the level of both primary physician and referral center - to maintain an ever higher index of suspicion for CF, tempered by a rational program of counseling and management appropriate to the individual.

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CF= cystic fibrosis

CFTR= CF transmembrane regulator

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.

Background: Recurrent abdominal pain is a common pediatric diagnostic problem.  Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology.

Objectives: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP.

Patients and Methods: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months.

Results: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P<0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P<0.01 between the H. pylori-associated gastritis and each of the other groups).

Conclusions: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

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RAP = recurrent abdominal pain

Background: Small bowel obstruction with perforation is an unusual and rare complication of bezoars.

Objective: To describe our use of emergency laparotomy to treat intestinal obstruction caused by bizarre bezoars.

Conclusions: An aggressive surgical approach to intestinal obstruction in the pediatric disabled or mentally retarded population is recommended.
 

Background: Multiple organ injury in children is an increasingly frequent phenomenon in the modern emergency room. Adrenal hemorrhage associated with this type of trauma has received little attention in the past.

Objectives: Using computed tomography, we sought to determine the rate and nature of adrenal gland injury in children following blunt abdominal trauma due to motor vehicular accident.

Methods: A total of 121 children with blunt abdominal trauma were examined and total body CT was performed in cases of multi-organ trauma or severe neurological injury.

Results: Of all the children who presented with blunt abdominal trauma over a 51 month period, 6 (4.95%) had adrenal hemorrhage. In all cases only the right adrenal gland was affected. Coincidental injury to the chest and other abdominal organs was noted in 66.7% and 50% of patients, respectively.

Conclusions: Traumatic adrenal injury in the pediatric population may be more common than previously suspected. Widespread application of the more sophisticated imaging modalities available today will improve the detection of damage to the smaller organs in major collision injuries and will help in directing attention to the mechanism of trauma. 

Background: Erythema nodosum, although uncommon in children, is the most frequent form of panniculitis in pediatrics.  EN has been associated with various infections and chronic inflammations, and its course varies with age, gender, and racial and geographic factors.  There is no information on EN in Israeli children.

Objectives: To examine the clinical course of EN and the conditions with which it is associated in Israeli children.

Methods: We conducted a retrospective study of 24 children with a diagnosis of EN who presented at our Center over a 10 year period (1989–98).

Results: EN was more frequent in females than males (ratio 2:1) due to a cluster of adolescent girls. The mean duration of the skin manifestation was 18 days. The course was benign in all patients. Streptococcal infection was the most common cause (25%), followed by Epstein-Barr virus infection (18%) and inflammatory bowel disease (13%).  In one-third of cases, no specific cause could be identified. Tuberculosis, an important cause of EN in the past, was not found in our patients.

Conclusions: Most cases of EN in Israeli children are related to streptococcal and EBV infections or to chronic inflammatory conditions. Despite the increase in tuberculosis morbidity in Israel during recent years, we found no association of EN and tuberculosis in our study.

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EN = erythema nodosum

EBV = Epstein-Barr virus