Yitzhak Lotem MD, Asher Barak MD, Huda Mussaffi MD, Mordechai Shohat MD, Michael Wilschanski MD, Yakov Sivan MD and Hannah Blau MD
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
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.
Erez Sharoni MD, Jacob Katz MD, Ovadia Dagan MD, Avraham Lorber MD, Rafael Hirsch MD, Leonard C. Blieden, Bernardo A. Vidne MD and Einat Birk MD
Background: The need for aortic valve replacement in children and young adults poses a special problem to cardiologists and surgeons. Replacing the sick aortic valve with the patient’s pulmonary valve as described by Ross has proven to be a good option in this special age group.
Objective: To review our initial experience in order to assess the short-term results.
Methods: From January 1996 to June 1999, 40 patients (age 8 months to 41 years) underwent aortic valve replacement with pulmonary autograft. Indications for surgery were congenital aortic valve disease in 30 patients, bacterial endocarditis in 5, rheumatic fever in 3, and complex left ventricular outflow tract obstruction in 3. Trans-esophageal echocardiography was performed preoperatively and post-bypass in all patients, and transthoracic echocardiography was done prior to discharge and on follow-up.
Results: There was no preoperative or late mortality. All patients remain in functional class I (New York Heart Association) and are free of complications and medication. None showed progression of autograft insufficiency or LVOT obstruction. Homograft insufficiency in the pulmonary position has progressed from mild to moderate in one patient, and three developed mild homograft stenosis.
Conclusions: The Ross procedure can be performed with good results in the young population and is considered an elegant surgical alternative to prosthetic valves and homografts.
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LVOT = left ventricular outflow tract
Amir Kimia MD, Ilan Zahavi MD, Rivka Shapiro MD, Yoram Rosenbach MD, Akiva Hirsh MD1, Tamara Druzd MD, Jacob Yahav MD and Gabriel Dinari MD
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
Idan Burstein, MD, Ran Steinberg, MD and Michael Zer, MD
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.
Ram Silfen MD, Michal Chemo-Lotan MD, Abraham Amir MD and Daniel J. Hauben MD
Background: Burn trauma occurs mostly in young children. Burn injury in the pediatric age group has multiple-aspect sequelae.
Objectives: To characterize the profile of the injured pediatric burn patient, thus targeting the most vulnerable pediatric group.
Methods: Between 1 January and 31 December 1996, a total of 9,235 pediatric patients were admitted for various traumatic injuries (burns, lacerations, fractures, etc.) to the Emergency Medicine Department of Schneider Children’s Medical Center. We conducted a retrospective study of the patients’ charts, including demographic data, which were stored in a computerized database, for statistical evaluation. The characteristics of pediatric burn patients were examined and compared with other pediatric trauma patients.
Results: Of the total patient population, 282 (3.1%) suffered from burns (37% females, 63% males). The most frequent burn injury was scald burn (58%). The pediatric group that was most exposed to burns was 13–18 month old males.
Conclusions: Having identified the high risk group among the pediatric burn patients, we suggest that prevention programs be directed towards this group in order to reduce further risk of burn injury.
Raz Somech MD, Vera Zakuth MSc, Ayala Assia MD, Uri Jurgenson MD and Zvi Spirer MD
Background: Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant.
Objective: To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin.
Methods: Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children’s Hospital for evaluation of unexplained fever or for sepsis work-up.
Results: The parallelism between procalcitonin and CRP was found to be highly significant (P<0.01).
Conclusion: The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.
Rivka Kauli MD, Rina Zaizov MD, Liora Lazar MD, Athalia Pertzelan MD, Zvi Laron MD, Avinoam Galatzer MA, Moshe Phillip MD, Yitzhak Yaniv MD and Ian Joseph Cohen MB ChB
Background: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on both the pubertal development and the final outcome of growth and sexual maturation.
Objective: To investigate the natural pattern of growth and puberty in patients with Gaucher disease type 1 and the effect of splenectomy and enzyme replacement therapy.
Methods: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we considered severity of disease, time of splenectomy, and start of enzyme replacement therapy.
Results: Deceleration of growth at age 3–5 years was observed in 30 of 57 patients followed since early childhood while untreated: height-SDS decreased from -0.34±0.42 at age 0–3 years to -1.93±0.95 (P<0.01) at age 7–10 years and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observed in 47 patients followed before and throughout puberty. No primary endocrine pathology was found. All patients, untreated as well as treated, with growth and pubertal delay had a spontaneous catch-up, achieved full sexual maturation, and most (83.3%) reached a final height within the range of parental height–standard deviation score. Splenectomy (partial and/or total) performed in 20 patients while still growing had a beneficial effect on growth, which was temporary in some and did not affect puberty. ERT improved growth in 11 patients who started therapy before puberty, as evidenced by a progressive increase in the height-SDS, and seemed to normalize the onset of puberty.
Conclusions: Growth retardation in childhood and delay of puberty are characteristic of Gaucher disease type 1 and are more frequent with severe disease. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement therapy apparently normalizes growth and possibly also the onset of puberty.
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ERT = enzyme replacement therapy
SDS = standard deviation score
Ronit Neudorf-Grauss MD, Yoram Bujanover MD, Gabriel Dinari MD, Efrat Broide MD,Yehezkiel Neveh MD, Ilan Zahavi MD and Shimon Reif MD
Objective: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy.
Methods: We retrospectively studied 51 patients (34 males, 17 females), aged 2–18 years, from several medical centers in Israel.
Results: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3–6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P<0.05).
Conclusions: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.
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HBV = hepatitis B virus
IFN = interferon
HBeAg = hepatitis B e antigen
Matti Erlichman MD, Ruth Litt MD, Zachi Grossman MD, Ernesto Kahan MD MPH and IPROS Network
Background: Streptococcal pharyngotonsillitis remains a common illness in children and can lead to serious complications if left untreated.
Objective: To evaluate the diagnostic and management approach of a sample of primary care physicians in the largest sick fund in Israel to streptococcal pharyngotonsillitis in children.
Methods: A questionnaire was mailed to all physicians who treat children and are employed by the General Health Services (Kupat Holim Klalit) in the Jerusalem District. The questionnaire included data on demographics, practice type and size, and availability of throat culture and rapid strep test; as well as a description of three hypothetical cases followed by questions relating to their diagnosis and treatment.
Results: Of the 188 eligible physicians, 118 (62.5%) responded, including 65 of 89 pediatricians (73%) and 53 of 99 family and general practitioners (53.5%). Fifty-six physicians (47.4%) had more than 18 years experience, and 82 (70%) completed specialization in Israel. Mean practice size was 950 patients. Fifty-three physicians (43%) worked in Kupat Holim community clinics, 25 (21%) worked independently in private clinics, and 40 (34%) did both. A total of 91 (77%) had access to laboratory facilities for daily throat culture. The time it took for the results to arrive was 48 to 72 hours. For the three clinical scenarios, 90% of the physicians accurately evaluated case A, a 1-year-old with viral pharyngotonsillitis, and 100 (85%) correctly diagnosed case C, a 7-year-old with streptococcal infection. As expected, opinions were divided on case B, a 3-year-old child with uncertain diagnosis. Accordingly, 75 (65.3%) physicians did not recommend treatment for case A, compared to 109 (92.5%) for case C. For case B, 22 (19%) said they would always treat, 43 (36%) would sometimes treat, and 35 (30%) would await the result of the throat culture. For 104 (88%) physicians the antibiotic of choice for case C was penicillin, while only 9 (7.5%) chose amoxicillin. However, the recommended dosage regimens varied from 250 to 500 mg per dose, and from two to four doses daily. For case C, 110 physicians (93%) chose a 10 day duration of treatment.
Conclusions: The primary care physicians in the sample (pediatricians, general practitioners and family physicians) accurately diagnosed viral and streptococcal pharyngotonsillitis. However, there was a lack of uniformity regarding its management in general, and the dosage regimen for penicillin in particular.
Ravit Arav-Boger MD, Shai Ashkenazi MD, Michael Gdalevich MD, Dani Cohen PhD and Yehuda L. Danon MD
Background: There is an increasing number of reports of pertussis among older children and adults. The development and licensure of an acellular pertussis vaccine offer the possibility of adult vaccination against the disease. Information on immunity to pertussis in this age group is needed before any vaccination policy can be considered.
Objectives: To study the seroepidemiology of pertussis antibodies in a random sample of adolescents.
Methods: Serum IgG antibodies to whole-cell lysate of Bordetella pertussis were measured by enzyme-linked immunosorbent assay in sera of 533 Israeli military recruits aged 17–18 years. Epidemiologic variables were collected by a questionnaire and analyzed for correlation with pertussis antibodies.
Results: Of the sera tested 58.6% were positive for pertussis IgG antibodies, while 35.4% were negative and 6% were borderline. The seropositivity rate was significantly higher among females and non-smokers than among males and smokers. Serum samples of subjects found negative to Bordetella pertussis on recruitment were tested again, using the same ELISA assay, 2–3 years later. Seroconversion during the 3 year military service was detected in 12.5% of 40 subjects. Using the pertussis toxin as the antigen in a subsample of 160 sera, the seroprevalence was lower than that detected by the whole-cell lysate on the same sera (45% vs. 58%).
Conclusions: A significant part of the adolescent population in Israel has low titer of serum IgG antibodies to the multiple antigens of B. pertussis. The relatively low concentration of anti-pertussis antibodies, together with the serological evidence of exposure to the disease indicates that booster immunization with the acellular pertussis vaccine of military recruits should be considered after more information on the incidence of clinical cases of pertussis will be available.
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ELISA = enzyme-linked immunosorbent assay
Jacob Bar MD, Raoul Orvieto MD, Yosef Shalev MD, Yoav Peled MD, Yosef Pardo MD, Uzi Gafter MD, Zion Ben-Rafael MD, Ronny Chen MD and Moshe Hod MD
Background: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial.
Objectives: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency.
Methods: Logistic regression models were formulated to predict successful outcome.
Results: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level.
Conclusions: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.