Israel Medical Association Journal

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

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ACT = autologous chondrocyte transplantation

Background: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors.

Objective: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation.

Methods: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring >1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor’s death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts.

Results: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n=13, 9.3%) or DGF (n=25, 17.9%). On regression analysis, donor age >50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors >50 years old, 21 (37.5%) developed either PNF (n=9) or DGF (n=12).

Conclusions: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from “aged” donors may help to choose appropriate donors from that pool.

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PNF = primary graft non-function

DGF = delayed graft function

Background: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only.

Objectives: To determine the rate of immunity to VZV in young Israeli adults.

Methods: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens.

Results: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant.

Conclusion: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

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VZV= varicella zoster virus

IDF= Israel Defense Forces

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: 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: 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.

 

Background: According to studies from different countries, the prevalence of natural rubber latex sensitization in healthcare workers ranges from 2.9 to 17%.

Objective: To estimate the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel.

Methods: Three hundred healthcare workers, mostly from a major pediatric tertiary care facility, and 15 non-healthcare workers completed a questionnaire on signs and symptoms of NRL allergy and other respiratory and food allergies. NRL-specific IgE antibodies were assayed with the DPC AlaSTAT-ELISA method.

Results: Seventy of the 300 workers (23.3%) reported symptoms of NRL allergy: hand eczema and pruritus in 63, upper respiratory tract and ocular symptoms in 10, shortness of breath in 2, and generalized rash in 6. None had anaphylaxis due to latex exposure. There was a significant correlation of symptoms of NRL allergy with atopy and job category (nurses, laboratory technicians, nurse assistants and dental medicine workers), but not with gender, age, or years of employment. The in vitro tests for specific IgE antibodies against NRL were positive (≥0.70 IU/ml) in five workers (1.66%).

Conclusions: This is the first study of the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. Our 1.66% sensitization rate is much lower than that reported for healthcare workers in other countries. This difference may be due to our inclusion of a study population with a relatively low exposure to latex gloves (pediatricians compared to surgeons). Further studies are needed in this and other high risk populations in Israel.  

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NRL = natural rubber latex

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

Background: Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity.

Objectives: To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome.

Methods: The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS¹. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by <200 partial pressure of oxygen during ³6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO2² /forced expiratory O2, alveolar–arterial O2 difference, and ventilation index.

Results: We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO2³ on the second day after diagnosis. Non-survivors had significantly lower PaO2/FIO2 (116±12 vs. 175±8.3, P<0.001), and higher A-aDO2 (368±28.9 vs. 228.0±15.5, P<0.001) and ventilation index (43.3±2.9 vs. 53.1±18.0, P<0.001) than survivors.

Conclusions: Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population. 

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¹ARDS = acute respiratory distress syndrome

² PaO2 = partial pressure of oxygen

³A-aDO2 = alveolar–arterial O2 difference

Background: Although the onset of fever in children often prompts parents to seek immediate treatment, the general level of parental knowledge on pediatric fever and administration of antipyretic medications is unknown. Parents without a basic understanding of treatment principles may give their children incorrect doses of medication. Overdosing may cause drug toxicity, while underdosing may lead to unnecessary, repeated clinic and/or emergency room visits.

Objectives: To assess parental decision-making with regard to treating fever in children, and its effectiveness, and to suggest methods for improving the level of treatment.

Methods: In this cross-sectional self-reported survey, questionnaires were completed by 650 parents who sought medical assistance for a child under the age of 10 years. Parents represented various socioeconomic levels, educational backgrounds and religious affiliations.

Results: Ninety-six percent of parents treated fevers that reached 38.5°C, and 77.6% treated fevers of only 38°C. Acetaminophen was the treatment of choice for 96% and dipyrone for 4%. Parental sources of information for managing and administering antipyretic drugs were medical personnel (40.7%), mother's or grandmother's experience (30%), and the enclosed leaflet or instructions on the bottle (29.3%). Forty-three percent of the parents administered the recommended dosage (10–20 mg/kg), whereas 24.3% used less and 32.7% used more; 11% exceeded a daily dosage of 120 mg/kg. 

Conclusions: A total of 57% of parents treated children with incorrect doses of antipyretic drugs. In 11% of the children treated, the daily dose was at a level that could cause severe toxicity. Parental knowledge of the treatment of fever must be improved.

 Background:  Pulmonary alveolar proteinosis is a rare disease in which a surfactant-like phospholipid-rich protein accumulates in the lungs. The disease is amenable to effective therapy by total lung lavage.       

Objectives: To investigate the prevalence, ethnic distribution and course of PAP  in Israel.

Methods: A countrywide survey was conducted during which pulmonologists were questioned about patients with PAP. The patients were examined and their charts, radiological images, pathological slides and physiological data were reviewed.

Results: The survey yielded 15 patients (8 females) during the period 1976–98 (14 in the last decade), giving a prevalence of 3.7x10⁶ and an incidence of 0.36x10⁶/year.

Mean age of the patients was 33±13 years (range 0.5–46 years). Seven patients were North African (two were siblings), four were from Iraq and two were Arabs; there was only one Ashkenazi Jew (a child). Symptoms at the onset were dyspnea and chest pain. Spontaneous remission occurred in at least 3 patients, and 10 patients required 1–4 bronchoalveolar lavage treatments. The subjective and physiological response was favorable, but there was less consistent radiological improvement.

Conclusion: The prevalence of PAP in Israel is approximately 3.7x10⁶. Most cases occurred in Jews who had immigrated from North Africa or Iraq, and two were siblings. The prevalence among the Arab population appears to be similar. This clustering suggests the existence of a genetic predisposition. The course of the disease appears to be similar to that reported elsewhere.

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PAP = pulmonary alveolar proteinosis