Israel Medical Association Journal

Background: Hyperbilirubinemia of the newborn is common. Rarely is an underlying disease other than physiologic hyperbilirubinemia considered the cause of high bilirubin levels. Some of the laboratory tests recommended by the American Academy of Pediatrics are expensive and do not always lead to diagnosis.

Objective: To evaluate the efficacy of standard laboratory tests performed on newborn infants requiring phototherapy for hyperbilirubinaemia.

Methods: We conducted a retrospective chart review that included neonates born during a 6 month period with birth weight > 2500 g treated with phototherapy for hyperbilirubinemia (n=282) according to published guidelines. The main outcome measures were primary and maximal bilirubin values (mg/dl), time to jaundice (in days), the number of bilirubin tests undertaken and whether the patient showed abnormal functioning, and the number of days in follow-up.

Results: Thirty-three neonates (11.7%) were positive in at least one laboratory test (defined as "Abnormal" in our study), 45.5% of whom met the criteria for phototherapy during the first 48 hours of life. Among the newborns who were negative for all laboratory tests (defined as "Normal"), only 6.8% met phototherapy criteria within their first 48 hours of life (P < 0.001). In the Normal group there was a consistent decrease in total serum bilirubin values shortly after phototherapy was begun, while the Abnormal group presented an increase in serum bilirubin values during the first 12 hours of phototherapy. None of the infants had conjugated (direct) hyperbilirubinemia during the study period.

Conclusions: Most neonates presenting with a laboratory identifiable etiology for hyperbilirubinemia (i.e., hemolysis) can be distinguished from those who test negative, mainly based on the timing of presentation and response to phototherapy. A more meticulous selection of patients and reduction in the magnitude of routine laboratory testing can safely reduce discomfort to infants with hyperbilirubinemia as well as costs.

Background: Streptococcus pneumoniae is now the predominant pathogen causing meningitis. The resistance of S. pneumoniae to penicillin and third-generation cephalosporins has grown steadily.

Objectives: To assess the antibiotic susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children with meningitis, and determine the antibiotic regimen appropriate for suspected bacterial meningitis in Israel.

Methods:  The study group included 31 children with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae isolates from the cerebrospinal fluid were tested for susceptibility to penicillin and ceftriaxone.

Results: Of the 35 isolates, 17 (48.6%) showed resistance to penicillin (minimum inhibitory concentration ≥ 0.12 µg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone (≥ 0.5 and < 2 μg/ml), and none showed complete resistance (MIC[1] ≥ 2 μg/ml). The rates of antibiotic resistance were higher in children who were treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P = 0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156).

Conclusions:  The rate of penicillin resistance is high in children with S. pneumoniae meningitis in Israel, especially in those treated with oral antibiotics prior to admission. Resistance to ceftriaxone is infrequent though not negligible. On the basis of these findings, current recommendations to empirically treat all children with suspected bacterial meningitis with ceftriaxone in addition to vancomycin until the bacterial susceptibility results become available are justified also in Israel.

Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) and in the ICD-10 (International Classification of Disease) as an impulse control disorder. The association between impulsivity and pathological gambling remains a matter of debate: some researchers find high levels of impulsivity within pathological gamblers, others report no difference compared to controls, and yet others even suggest that it is lower. In this review we examine the relationship between pathological gambling and impulsivity assessed by various neurocognitive tests. These tests – the Stroop task, the Stop Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the Wisconsin Card Sorting Test, the Tower of London test, and the Continuous Performance Test – demonstrated less impulsivity in gambling behavior. The differences in performance between pathological gamblers and healthy controls on the neurocognitive tasks could be due to addictive behavior features rather than impulsive behavior.

Background: Epidemiological data show significant associations of vitamin D deficiency and autoimmune diseases. Vitamin D may prevent autoimmunity by stimulating naturally occurring regulatory T cells.

Objectives: To elucidate whether vitamin D supplementation increases Tregs[1] frequency (%Tregs) of circulating CD4+ T cells.

Methods: We performed an uncontrolled vitamin D supplementation trial among 50 apparently healthy subjects including supplementation of 140,000 IU at baseline and after 4 weeks (visit 1). The final follow-up visit was performed 8 weeks after the baseline examination (visit 2). Blood was drawn at each study visit to determine 25-hydroxyvitamin D levels and %Tregs. Tregs were characterized as CD4+CD25++ T cells with expression of the transcription factor forkhead box P3 and low or absent expression of CD127.

Results: Forty-six study participants (65% females, mean age ± SD 31 ± 8 years) completed the trial. 25(OH)D[2] levels increased from 23.9 ± 12.9 ng/ml at baseline to 45.9 ± 14.0 ng/ml at visit 1 and 58.0 ± 15.1 ng/ml at visit 2. %Tregs at baseline were 4.8 ± 1.4. Compared to baseline levels we noticed a significant increase of %Tregs at study visit 1 (5.9 ± 1.7, P < 0.001) and 2 (5.6 ± 1.6, P < 0.001).

Conclusions: Vitamin D supplementation was associated with significantly increased %Tregs in apparently healthy individuals. This immunomodulatory effect of vitamin D might underlie the associations of vitamin D deficiency and autoimmune diseases. Hence, our finding provides a rationale for further studies to investigate vitamin D effects on autoimmunological processes.

Background: Renal artery stenosis is one of the most frequent causes of secondary hypertension. Appropriate methods for screening, diagnosis and therapy are currently under debate.

Objectives: To evaluate and recommend methods for screening and diagnosing renal artery stenosis, and to assess the clinical outcomes of renal artery stenting.

Methods: A total of 450 patients undergoing non-emergent coronary angiography fulfilled the selection criteria for selective renal arteriography; those with severe (luminal narrowing ≥ 70%) renal artery stenosis underwent percutaneous transluminal renal angioplasty with renal artery stenting.

Results: Of 166 patients (36.9%) with renal artery stenosis, 41 (9.1%) had severe stenosis that required renal artery stenting, and 83% had ostial renal stenosis. The primary success rate was 100% and there were no complications. During the follow-up period, two patients required a second PTRA[1]. After stent deployment, significant reductions were observed in systolic and diastolic pressures (P < 0.001 and P = 0.01, respectively) and in the number of antihypertensive drugs used by the patients (P < 0.001). These reductions were sustained during follow-up. Hypertension was cured (systolic blood pressure < 130 mmHg) in 9 (21.4%) and improved in 27 (64.3%) patients. Plasma creatinine did not change significantly.

Conclusions: Selective renal angiography is an effective diagnostic tool for identifying symptomatic cases of renal artery stenosis in patients undergoing coronary angiography. Our finding of a high success rate and low complication rate supports the use of primary renal artery stenting in symptomatic patients with renal artery stenosis.

Background: High frequency oscillatory ventilation based on optimal lung volume strategy is one of the accepted modes of ventilatory support for respiratory distress syndrome in very low birth weight infants. In 1999 it was introduced in our unit as the primary ventilation modality for RDS[1].

Objectives: To evaluate if the shift to HFOV[2] influenced the outcome of ventilated VLBW[3] infants in the neonatal intensive care unit of Carmel Medical Center.

Methods: Data were obtained from the medical charts of VLBW infants born at Carmel Medical Center, and late mortality data were taken from the Israel Ministry of Internal Affairs records. A retrospective analysis and a comparison with a historical control group ventilated by the conventional method were performed.

Results: A total of 232 VLBW infants with RDS were mechanically ventilated, from 1995 to 2003: 120 were ventilated using HFOV during the period 1999–2003 and 102 infants using CV[4] during 1995–1999. The mean gestational age of survivors was 27.4 ± 2 weeks in the HFOV group and 28.4 ± 2 in the conventional ventilation group (P = 0.03). The sub-sample of infants with birth weights <1000 g ventilated with HFOV showed higher survival rates than the infants in the conventional ventilation group, 53 vs. 25 (64.6% vs. 44.6%) respectively (P < 0.05). A trend for lower incidence of pulmonary interstitial emphysema was observed in the HFOV group.

Conclusions: The introduction of HFOV based on optimal lung volume strategy proved to be an efficient and safe method of ventilation support for VLBW infants in our unit.

Background: Left atrial volume and exercise capacity are strong predictors of cardiovascular risk. Decreased exercise capacity is expected when LAV[1] is increased due to its association with abnormal left ventricular filling pressure. However, LAV enlargement is expected in chronic mitral regurgitation as well.

Objectives: To examine the linkage between LAV and exercise capacity in chronic MR[2] and to determine whether larger LAV has indeed better exercise capacity in patients with chronic severe degenerative MR and good LV systolic function.

Methods: The study included asymptomatic patients with severe chronic degenerative MR and normal LV[3] systolic function that underwent stress echocardiography. LAV was measured at rest using the biplane Simpson’s method and indexed to body surface area. The cutoff of good exercise capacity was determined at 7 METS.

Results: The patient group comprised 52 consecutive patients (age 60 ± 14 years, 36 males). Two subgroups (19 vs. 33 patients), age- and gender-matched, were formed according to LAVi[4] cutoff of 42 ml/m². Those with higher LAVi had lower exercise capacity (P = 0.004) albeit similar MR grade, baseline blood pressure, LV function and size. Receiver-operator curve analysis revealed indexed LAV value of ≤ 42 as 51% sensitive and 88% specific for predicting exercise capacity > 7 METS (AUC[5] = 0.7, P = 0.03). In multivariate analysis, age, gender and LAVi were identified as independent predictors of exercise capacity.

Conclusions: In asymptomatic patients with severe chronic degenerative MR and normal LV systolic function, mild enlargement of the left atrium (≤ 42 ml/m²) is associated with good exercise capacity.

Background: Infants who have experienced an apparent life-threatening event typically undergo an extensive evaluation to rule out serious underlying conditions.

Objectives: To evaluate the yield of different tests performed after an apparent life-threatening event and to identify high risk groups in which more extensive diagnostic tests are required.

Methods: A retrospective study was conducted in a children's hospital over a 4 year period during which the charts of infants who were admitted with an apparent life-threatening event were reviewed. The yield for each diagnostic test was established according to the ratio of positive results contributing to the diagnosis of the apparent life-threatening event.

Results: The study included 69 infants between the ages of 1 week and 1 year. There were abnormal findings in 36% of the cases. Gastroesophageal reflux was the most common diagnosis (60%). In the remaining patients the diagnosis was either seizures (12%) or respiratory tract infections (28%). Tests used for the diagnosis of cardiac, metabolic and non-respiratory infections had no yield. A positive correlation was found between abnormal test results and abnormal physical examination (P = 0.001), an abnormal perinatal history (P = 0.017), and age older than 2 months (P = 0.002).

Conclusions: The yield of most of the tests performed after an apparent life-threatening event is low, especially in infants with a normal perinatal history and physical examination.