Israel Medical Association Journal

Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.

Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM[1] in a transfer model of NOD mice.

Methods: Our vaccination technique involved the insertion of CD44s[2] or CD44v[3] cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN[4] were implanted 20 days before and 3 days after cell transfer.

Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.

Conclusions: These findings may open new opportunities for IDDM therapy in the future.

Background: In the western world, trauma is the leading cause of disability and mortality in the 1–39 years age group. Road accidents constitute the most frequent cause of mortality among children older than 1 year and falls from a height are the most frequent cause of injuries requiring hospitalization.

Objectives: To analyze the epidemiology and characteristics of severe pediatric trauma due to falls from a height in northern Israel. This analysis should aid in planning an effective intervention plan.

Methods: This observational study included all patients aged 0–14 who died or were admitted to an intensive care unit in northern Israel following a steep fall. Demographic and clinical data were collected retrospectively for 3 years and prospectively for 1 year.

Results: A total of 188 children were severely injured or died following such a fall, with an annual rate of 11.4 per 100,000 children. Over 85% of severe injuries due to falls occurred among non-Jewish children, with an incidence rate 6.36 times higher than among Jewish children (20.17 and 3.17 per 100,000 children, respectively). In the non-Jewish sector 93.7% of the falls occurred at or around the child’s home, mainly from staircases, balconies and roofs.

Conclusions: A very high incidence of severe trauma due to domestic falls from a height was found among non-Jewish children in northern Israel. Domestic falls represent an important epidemiological problem in the non-Jewish pediatric sector, and an effective prevention plan should include measures to modify parents’ attitudes towards safety issues and the creation of a safe domestic environment.
 

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Measurement of function is an essential component of routine rehabilitation work (mainly for quantifying function at different phases in the rehabilitation process), rehabilitation policy (admission and discharge criteria, length of stay in rehabilitation), goal setting, and outcome measurement.

Objective: To explore the scope of the scales used for function assessment by the various disciplines of rehabilitation medicine in rehabilitation facilities.

Method: A structured questionnaire was sent to 36 rehabilitation facilities. Respondents were asked to specify the scales they use for functional assessment for each of 15 selected pathologies. Also examined were satisfaction with the scales, as well as the existence of a computerized database of routine function assessment in the facility and the willingness to create a national agreed “common data set” of the assessments.

Results: The general response rate was 86.1% (31 of 36 questionnaires were returned). For the sake of data presentation, rehabilitation facilities were classified into four categories: general, geriatric, pediatric, and community. Most facilities performed function assessment using a total of 125 scales. Heterogeneity was found between facilities and between pathologies. The highest number of scales was found in the area of neurologic pathologies. For most pathologies, assessment of impairment was used more than assessment of disability. Most facilities in the survey did not have a computerized database of function assessments.

Conclusions: A “common data set” of function assessments in everyday clinical work would ensure standardization without necessarily limiting the use of additional scales and at the same time significantly minimize the current heterogeneity.
 

Background: Intramural duodenal hematoma generates partial or complete obstruction that develops slowly and progressively with a consequent delay in diagnosis. Many diagnostic and therapeutic measures remain debatable and justify a review of current management policy.

Objectives: To highlight the diagnostic and therapeutic steps in pediatric IDH[1].

Methods: The records of 12 children with post-traumatic IDH who were treated in the Hillel Yaffe Medical Center between 1986 and 2000 were retrospectively reviewed. Three of them had clotting disorders and were excluded. The interval between their admission and diagnosis as well as the therapeutic decisions were evaluated and analyzed.

Results: Nine children were treated for IDH. The interval between admission and diagnosis ranged from 24 hours to 6 days. Five children had associated traumatic pancreatitis. Initially, all the children were conservatively treated. In seven the hematoma resolved after 9–20 days. Two children were operated upon because the obstruction failed to resolve. All nine children recovered without permanent complications.

Conclusions: Intramural duodenal hematoma has many clinical and therapeutic puzzling aspects. Bicycle handlebar, road accidents and sports trauma are the main etiologic factors in children, but child abuse should be kept in mind. Associated traumatic pancreatitis is common. Gastroduodenal endoscopy may be useful to clarify doubtful cases. Pediatric surgeons should increase awareness regarding IDH in order to reduce delay in diagnosis and the need for surgical decompression.

Background: Since 1984, several waves of Ethiopian immigrants have settled in Israel. On arrival they were found to be highly infected with intestinal parasites and to have increased serum immunoglobulin E and eosinophilia. 

Objectives: To study serum IgE [1] levels in Ethiopian children growing up in the environment of Israel . 

Methods: We assessed four groups of children of Ethiopian origin: a) adolescents examined on their arrival to Israel (group 1, n=11); b) adolescents born in Ethiopia and living in Israel for more than 7 years (group 2, n=10); c) children of Ethiopian origin born in Israel, without a history of allergy or asthma (group 3, n=15); and d) asthmatic children of Ethiopian origin born in Israel (group 4, n=8). A thorough clinical interview and examination as well as serum IgE levels, stool parasites and absolute eosinophil count were performed. 

Results: Group 1 (11 newly arrived Ethiopian adolescents) had a mean eosinophil count of 688 cells/ml (0–1739) and a mean serum IgE of 1043 IU/ml (253–2932), P < 0.0009 as compared to group 2. Helminthic parasites were observed in 8/11 individuals; after 1 year of follow-up and anti-parasitic treatment, serum IgE levels did not change significantly. Group 2 (10 Ethiopian born adolescents living in Israel for on average 10 years, 7–15 years) had a normal leukocyte count, MEC [2] 192 cells/ml (range 54–289), serum IgE 142 IU/ml (range 14–399 IU/ml) and no parasites in stool. Group 3 (15 Ethiopian children born in Israel) had a normal leukocyte count, MEC 128 cells/ml (0–324), serum IgE 55 IU/ml (7–189 IU/ml), similar to age-matched Israeli controls. In group 4 (8 Israeli born children of Ethiopian descent diagnosed with asthma), serum IgE showed significant elevation compared to Israeli age-matched asthmatic children (P < 0.005).  

Conclusions: High levels of IgE found in Ethiopian children on arrival to Israel declined to Israeli control levels after several years of living in the new environment. Ethiopian children born in Israel had normal levels of IgE, suggesting that environment is the main factor affecting IgE levels in this population. Israeli born Ethiopian children with asthma had significantly increased serum IgE levels compared to asthmatics of Israeli origin. These findings suggest that both environmental and genetic factors determine the level of serum IgE in these children. 

 ________________________________________

 [1] Ig = immunoglobulin

 [2] MEC = mean eosinophil count
 

Objective: To provide comparative information in an international context on the level of outpatient drug expenditures in Israel, both total and those publicly financed, and to analyze how these have changed with time during the last decade.

Methods: Using definitions of the OECD (Organization of Economic Cooperation and Development), internationally comparable data on total expenditure and public expenditure on medicines in Israel are provided. The Israeli estimates are based on data from the Ministry of Health audited reports of financial activities of the health management organizations and from the family expenditure surveys carried out by the Central Bureau of Statistics. Per capita total and public expenditures in Israel are analyzed over time, as are their share of national expenditure on health and of gross domestic product. Israel expenditures are then compared with those for individual member countries of the OECD, as well as a 21 country average, from 1992 to 2002.

Results: Analysis of the Israeli expenditure data shows a considerable reduction in growth of per capita total and public expenditures on medicines since 1997. Growth in the share of total drug expenditure of NEH[1] and of GDP[2] has also been constrained since 1997. In an international context, per capita expenditure on medicines in Israel, particularly what is publicly financed, is one of the lowest. Furthermore, its share of NEH and GDP is also very low compared to other countries. This substantive gap in spending on medicines between Israel and other countries has increased since 1997.

Conclusions: Israel, a medium-income country with a lower than average level of expenditure on health compared to OECD countries, has a particularly low level of expenditure on medicines. Whereas the share of health expenditure of GDP in Israel is similar to the international average, the share of drug expenditure of GDP is well below the average. In addition to structural and longer-term factors contributing to Israel's low per capita spending on medicines, such as the young population and the apparently low level of actual prices paid by most institutional purchasers, recent years are witness to the growing impact of National Health Insurance budgetary pressures on HMOs[3] as well as continual increases in prescription cost sharing by patients. The impact is felt both on the demand side (higher co-payments, administrative and prescribing restrictions) and perhaps more crucially on the supply side (price competition, mainly from generics). Substantial extra public funding for the addition of new drugs to the NHI[4] basket in recent years has had no overall impact on these longer-term spending patterns.

Background: Hypertrophic pyloric stenosis classically presents as projectile vomiting during the third to fourth week of life associated with good appetite. Additional classical presenting findings include palpation of the pyloric tumor, described as olive-shaped, a visible gastric peristaltic wave after feeding, and hypochloremic, hypokalemic metabolic alkalosis. It was recently claimed that this presentation has changed due to the easier access to gastrointestinal imaging.

Objective: To validate this contention and discuss possible reasons.

Methods: We conducted a retrospective chart review of all patients who underwent pyloromyotomy for HPS[1] between 1990 and 2000. Only patients with confirmed HPS at the time of surgery were included. We also performed a comprehensive review of older studies for comparison.

Results: Seventy patients underwent pyloromyotomy over the 10 year period. Overall, 81% of patients were male infants and the mean age at diagnosis was 40 days. The mean duration of symptoms was 8 days. A firstborn child was noted in 43% of the cases. The classical symptom of projectile vomiting was absent in one-third of the patients, a pyloric tumor was not palpated in one-half of the cases, bicarbonate was higher than 28 mEq/L in 20% and a pH of above 7.45 was present in 25% of patients. Hypochloremia was noted in about one-third. We found a good correlation between ultrasonographic width and length of the pylorus and the intraoperative findings. Pylorus length ≥ 24 mm correlated with significantly longer duration of symptoms. When compared with previous studies, the main findings were not significantly different; namely, mean age at diagnosis, percentage of male gender and duration to diagnosis. The decrease in the number of pyloric tumors palpated paralleled the increase in the use of upper gastrointestinal series and ultrasonography in particular.

Conclusions: The clinical presentation of HPS has not actually changed despite the easier accessibility of GI imaging studies. However, the one significant change is the low percentage of pyloric tumors palpated, probably due to declining clinical skills, accompanied by earlier utilization of imaging studies. The use of imaging and laboratory studies did not change the age at diagnosis but may have shortened the time for diagnosis and reduced the postoperative stay. Imaging and laboratory studies may be helpful for the subgroup with a non-classical clinical presentation.

Background: For centuries talismans and amulets have been used in many cultures for their legendary healing powers.

Methods: We asked the parents of every child (Jews and Arabs) admitted to the Pediatric Intensive Care Unit over a 2 month period to complete a questionnaire, which included demographic data on the patient and the family, the use of talismans or other folk medicine practices, and the perception of the effects of these practices on the patient’s well-being. A different questionnaire was completed by the ICU staff members on their attitude toward the use of amulets.

Results: Thirty percent of the families used amulets and talismans in the ICU, irrespective of the socioeconomic status of the family or the severity of the patient’s illness. Amulets and talismans were used significantly more by religious Jews, by families with a higher parental educational level, and where the hospitalized child was very young. The estimated frequency of amulet use by the children’s families, as perceived by the staff, was significantly higher than actual use reported by the parents. In Jewish families the actual use of amulets was found to be 30% compared to the 60% rate estimated by the medical staff; while in Moslem families the actual use was zero compared to the staff’s estimation of about 36%. Of the 19 staff members, 14 reported that the use of amulets seemed to reduce the parents' anxiety, while 2 claimed that amulet use sometimes interfered with the staff’s ability to carry out medical treatment.  

Conclusions: The use of talismans in a technologically advanced western society is more frequent than may have been thought. Medical and paramedical personnel dealing with very ill patients should be aware of the emotional and psychological implications of such beliefs and practices on patients and their families.

__________________________________

ICU = intensive care unit