Israel Medical Association Journal

The plight and fate of German Jewish pediatricians during the Nazi period in Europe has not received much attention, yet the narratives of the victims still resonate today and they deserve to be remembered. The stories of two women serve as examples of the fateful turns taken by the lives of many German Jewish pediatricians between 1933 and 1945. The two women, Dr. Luci Adelsberger and Dr. Lilli Jahn, illustrate both the ordeals endured, and disparate ways the Nazi policies ultimately spared or ended lives.

The Ashkenazi-Jewish population is at increased risk for several recessively inherited disorders. While some of the disorders have severe or fatal symptom manifestations, others, such as non-neuronopathic Gaucher disease, do not usually pose a serious, life-threatening illness. Many healthcare centers in Israel offer prenatal panel screening. Controversy exists over the inclusion of Gaucher disease in the panel screening, especially since Gaucher disease screening lacks prognostic reliability. Most screening participants do not discriminate between the specific tests in the panel and are unable to discern between severe, life-threatening diseases and those that are less severe and even treatable. By including screening for Gaucher in the panel screening program, there is risk of a "panel effect," leading to termination of a pregnancy positive for Gaucher disease, without sufficient knowledge and understanding of the disease. Increasing medical and public awareness and knowledge of the disease, its prognosis and treatment options may reduce the rate of under-informed abortions associated with prenatal screening of Gaucher disease.

Background: In developed countries, the incidence of Sydenham’s chorea, a major sign of rheumatic fever has declined, but outbreaks are still encountered worldwide.

Objectives: To report the characteristics of a cohort of SC[1] patients in the Jerusalem area.

Methods: We conducted a prospective assessment of rheumatic fever and SC between 1985 and 2002. The diagnosis of rheumatic fever was based on the revised Jones criteria. Other etiologies of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were followed for 1 to 14 years following the initial SC episode, and at least one year after recurrence.

Results: Among 180 children with rheumatic fever, 24 had SC. Most of them came from large families of Ashkenazi origin. In 19 patients (79%) the chorea was associated with other rheumatic fever signs, while 5 had pure chorea. Due to the systematic use of two-dimensional color Doppler echocardiography, cardiac involvement was detected in 75% of the patients. Ten patients (42%, 7 females) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. At recurrence, chorea was the sole rheumatic sign in all nine patients who recurred once. None of the patients had persistent chorea.

Conclusions: SC is still prevalent in the pediatric population of Jerusalem, and may recur years later. Recognition of the disease and adequate treatment is necessary.

Background: Recent studies have suggested a possible association between Chlamydia pneumoniae infection and coronary heart disease.

Objectives: To determine titers of antibodies to Chlamydia pneumoniae in patients with acute  myocardial infraction compared with titers in several control groups.

Methods: This prospective case-control study investigated 209 individuals. We assessed the serum IgG antibody titers to Chlamydia pneumoniae in 57 consecutive patients admitted with AMI to our intensive coronary care unit during a 4 month period. A serum sample was drawn upon admission after 6 weeks. Results were compared with those of four control groups: a) patients admitted with community-acquired pneumonia (n=18), b) patients with community-acquired urinary tract infection (n=42), c) patients with angiographically normal coronary artery disease (n=44), and d) patients with stable coronary artery disease (n=48). Serum immunoglobin G antibody titers to C. pneumoniae were determined using standard micro-immunofluorescene technology.

Results: Of 57 patients with AMI, 32 (56%) had a high lgG titer to C. pneumoniae (>=1:256) on the initial test, which remained unchanged (62%) after 6 weeks. The percentage of patients with high titers was significantly lower in the control groups: 5 of 18 patients (28%) in the pneumonia group (P<0.01), 11 of 42 (26%) in the urinary tract infection group (P<0.01), 11 of 44 (25%) with normal coronary arteries (P<0.01), and 17 of 48 (35%) with stable chronic ischemic heart disease (P<0.05).

Conclusion: The detection of high titers of lgG antibodies to C. pneumoniae in many patients with AMI, compared to control groups, suggest that chronic Chlamydia pneumoniae infection plays a role in the pathogenesis of atherosclerosis and acute ischemic events.

Background: Recent genetic susceptibility findings in Jews of Eastern European descent, commonly called Ashke­nazi Jews, have led to concerns that they may be stigmatized as being more cancer prone than other groups.

Objective: To examine the hypothesis that site-specific or all-cancer incidence and mortality rates are higher than expected in Ashkenazi Jews worldwide when compared with referent populations.

Methods: A MEDLINE search was performed using keywords "Jews", "cancer", "incidence" and "mortality" to identify studies directly relevant to the primary study question.

Results: Little evidence suggested that all-cancer inci­dence or mortality is higher in Ashkenazi Jews than in North American non-Hispanic whites. Ashkenazi Jewish men appear to have relatively low cancer rates, which may be due to lower tobacco use. Colorectal cancer was shown to disproportio­nately overburden Ashkenazi Jews, who may also be at increased risk for ovarian, pancreatic and stomach cancer, and non-Hodgkin’s lymphoma. Little evidence was found support­ing an elevated risk of breast cancer in Ashkenazi Jewish women. Rates of lung, cervical, penile and prostate cancers appear low in this population. Rate disparities were generally attributed to lifestyle differences, particularly diet and tobacco use, rather than to genetic predisposition.

Conclusions: Ashkenazi Jews do not appear to have a higher total cancer burden than comparable North American populations. Any cancer rate differentials in this group are more likely to be related to lifestyle and dietary factors than to genetics. However, colorectal cancer rates in Ashkenazi Jews may be the highest of any ethnic group in the world and cancer controllers should consider this when developing future screening, diagnostic and policy strategies.

Objective: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family.

Family Description: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia.

Conclusion: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.

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: 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.