Israel Medical Association Journal

Objective: To identify correlates for under-utilization of influenza immunization among the elderly.

Methods: A telephone survey was conducted among a random sample of patients aged 65 and over registered at a Jerusalem primary care community clinic. The 626 questionnaires were analyzed for associations of immunization receipt for the latest influenza season. Multivariate logistic regression was performed to identify independent correlates. Respondents were also asked what factors had influenced their decision about immunization.

Results: The most frequently reported influence on getting immunized was a physician's recommendation. Immunization was independently associated with the identity of the primary care physician (P0.0001) and with having visited the physician during the previous 3 months (P=0.0006). Immunization was more likely among persons who believed that it provides complete protection from influenza (P0.0001) and less likely among those who believed immunization can cause influenza (P0.0001). Higher immunization rates were also associated with being married (P=0.0031).

Conclusion: Through their influence on patient knowledge and the effect of their recommendation, primary care physicians play a pivotal role in determining immunization rates. Physicians should routinely discuss the effects of immunization and recommend it to the elderly.

Background: Although influenza is usually a mild self-limiting disease it can cause serious complications in high risk groups. The economic costs of influenza are large due to the burden on the health system and absenteeism from work. There is evidence that the vaccine is underused in groups targeted for vaccination.

Objectives: To estimate: a) the compliance rate with the influenza vaccination in Israel during the winter seasons of 1998/1999 and 1999/2000, b) the role of health care personnel and the media in influencing compliance, and c) the reasons for lack of compliance in the elderly.      

Methods: Two national population-based random telephone surveys of 1,500 households were performed during October 1999 and January 2000 to survey influenza vaccination compliance prior to the winters of 1998/1999 and 1999/2000 respectively. Each survey was performed during four successive evenings. The response rate was 78.1% for the first survey and 79.1% for the second.

Results: Vaccination compliance was similar in both surveys. The average rate of vaccination was 6% for the population under 65 years and 50% for the population of 65 years and above. The overall vaccination rate was around 10%. The family physician was the main authority to recommend the vaccination, followed by the community nurse. Absence of recommendation and lack of faith in the efficacy of the vaccine were the main reasons for non-compliance.

Conclusion: Compliance rates with influenza vaccine in targeted groups in Israel remain relatively low. Health care personnel should be more involved in promoting the vaccine.
 

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

____________________________________

PRL = prolactin

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.

__________________________________

ACT = autologous chondrocyte transplantation

Background: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

__________________________________

HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Background: In trials comparing different formulations of measles vaccine, excess non-specific mortality occurred in female children who received high titer vaccine. These findings suggest a gender-specific effect of measles vaccine.

Objectives: To determine whether gender differences exist in the rates of adverse reactions and morbidity in the month following immunization with measles-containing vaccine, and to evaluate whether there is a gender-specific association between the humoral immune response to measles vaccination and post-vaccination morbidity.

Methods: Parents completed questionnaires on the health status of 755 infants aged 15-20 months, during the month preceding and the month following the measles-mumps-rubella vaccination. Blood samples were tested for measles antibody titers in a subsample of 237 infants.

Results: After controlling background morbidity in the infants, the relative risk of fever and rash following vaccination was 2.35 in females and 1.36 in males. The geometric mean antibody titers against measles were similar in both sexes and there was no significant association between antibody titer and post-vaccination morbidity in either sex.

Conclusions: Our findings demonstrate higher rates of adverse effects in females following vaccination with MMR vaccine, irrespective of the humoral response. This study emphasizes the need to consider possible gender differences when evaluating new vaccines.

_______________________________

MMR= measles-mumps-rubella

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.

__________________________________

VZV= varicella zoster virus

IDF= Israel Defense Forces

Background: Extensive cleaning of homes in Israel before Passover may result in increased exposure of children to cleaning substances.

Objectives: To evaluate the potential danger of Passover cleaning to children, and to study the risk factors in order to identify areas for prevention.

Methods: All cases of poison exposure in Jewish and Arab children under the age of 15 years reported to the Israel Poison Information Center during 1990–95 (n= 5,583) were analyzed for the 6 weeks before and 6 weeks after Passover. Poison exposures in Jewish children <15 years old were studied in seven pediatric emergency rooms for the 2 weeks before and 6 weeks after Passover (n=123).

Results: The IPIC data showed a highly significant 38% increase in the average weekly poison exposure rate for the 2 weeks before Passover compared with the remaining 10 weeks.  Data recorded by the pediatric emergency rooms showed a twofold increase in cleaning substance poisoning during the 2 weeks before Passover compared with the following 6 weeks. The rise in exposures to cleaning substances was observed among children from secular, religious and ultra-orthodox families. In these exposures, the substance was found in open containers in 70% of cases. 

Conclusions: The extensive cleaning of homes among Jewish families in preparation for Passover poses the danger to young children of cleaning substance poisoning. Increasing public awareness, closer observation of children, and keeping these substances in closed containers should increase children’s safety during this annual cleaning.    

___________________________________

IPIC = Israel Poison Information Center

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.

____________________________________

ERT = enzyme replacement therapy

SDS = standard deviation score

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.

__________________________________

ELISA = enzyme-linked immunosorbent assay

Background: The growth plate increases its activity in response to exercise. Likewise, decreased physical activity exerts a negative effect on bone growth and development, leading to rarefaction of the subepiphyseal bone. Limb immobilization inhibits the growth plate’s activity, indirectly shown by a recorded arrest in longitudinal growth of the long bones. However, there is no direct evidence concerning the growth plate itself.

Objective: To determine whether the growth plate exhibits measurable microstructural changes in response to decreased levels of physical activity.

Methods: Histomorphometric analysis was used to qualitatively and quantitatively assess the changes in the epiphyseal plate in response to single hind limb immobilization in the rat. In 16 of 25 Sprague-Dawley male rats the left hind limb was immobilized for 3 weeks; the remaining 9 rats served as controls. The left proximal tibia of each animal was examined by computerized image analysis.

Results: There was a decrease in epiphyseal height, cell column density and subepiphyseal trabecular area - all indices of growth plate activity. Metaphyseal cortical thickness was also depressed, thereby confirming the efficacy of the immobilization method applied.

Conclusions: Limb immobilization in the rat induces inhibitory histological changes in the epiphyseal growth plate, which are in contrast to the excitatory microscopic changes seen with exercise. These changes can be assessed quantitatively. Their potential for reversibility remains to be determined by future experiments.