Israel Medical Association Journal

Background: Smoking is the most important preventable cause of chronic disease in the western world. Many smokers want to quit, but have difficulty overcoming the addictive effect of nicotine.

Objectives: To assess the quitting rate of smokers who participated in smoking cessation groups and to characterize predictors of success or failure over a 1-3 year follow-up period.

Methods: We studied 89 participants in 7 groups. Questionnaires were completed at baseline and after a follow-up period of 1 to 3 years. Smoking cessation was determined by self-report and a carbon monoxide breath test.

Results: Of the 89 participants in the support groups 76 (85%) were located. An intention-to-treat analysis was done for these participants. At follow-up 25 (33%) were non-smokers. There was a 95% agreement rate between self-report of smoking status and CO breath analysis. There were no differences between quitters and non-quitters in education level, gender, age at initiation of smoking, previous quit attempts, extent of participation in group meetings, concern about gaining weight, Fagerstrom index, or the number of close friends or relatives who smoke. Belief in one's ability to quit, satisfaction with group meetings, and spouse support were significantly associated with success (P<0.01).

Conclusions: The quit rate was 33%. Self-report is a reliable method for assessing smoking status. Smokers' belief in their ability to quit must be reinforced. Spouse participation in some group meetings may be beneficial, as may the involvement of a dietician and an expert on exercise. Follow-up "booster" meetings may also help.

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CO= carbon monoxide

* In partial fulfilment of the requirements for an MD degree.

Background: Osteoporosis is the most common human bone disease. It affects millions of persons throughout the world and its prevalence will increase as the population ages worldwide.

Objective: To assess Israeli physicians' attitudes and knowledge with regard to management of osteoporosis.

Methods: A questionnaire was mailed to 1,900 Israeli physicians concerning their attitudes to the management of osteoporosis, their prescribing habits, and their knowledge on the pharmacological treatment of the disease.

Results: Replies were received from 19% of the physicians. The respondents encouraged physical activity and cessation of smoking for all women, and prescribed estrogen replacement as the main treatment for 50-year-old women. A relatively low level of knowledge was found regarding the adequate dosage of several of the pharmacological treatments.

Conclusions: The findings of the present study stress the need to provide clear guidelines and to extend physicians' knowledge regarding the management of osteoporosis.

Background: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.

Objective: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.

Methods: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNFα and IL-6.

Results: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNFα was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).

Conclusions: Hyperoxia induces sequential production of pulmonary TNFα and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

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TNFα= tumor necrosis factor-alpha

IL-6= interleukin-6

Background: The arrival of 610,000 new immigrants to Israel from the former Soviet republics accounted for 58% of the population growth in the early 1990s.

Objective: To compare the coronary angiographic findings and risk factors between the new immigrants and local Jewish and Arab patients in this era of cost containment.

Methods and Results: A total of 550 consecutive patients - 314 Jews, 95 new immigrants and 141 Arabs - were catheterized and analyzed during a 5 month period in 1995. Of this group 403 were males (73%). The mean age was 63.6±10.2 years among new immigrants, 62.4±9.4 among Jews, and 55.1±10.9 among Arabs (P<0.05). Immigrants, including those under age 60, had the highest prevalence of multivessel disease (88.7%). Arabs had a high prevalence of single vessel disease (34.6%) and a low prevalence of multivessel (65.4%) and left main coronary disease (5.6%). Age, gender, risk factors and ethnic origin in descending order were determinants of the extent of coronary angiographic disease as revealed by multiple regression analysis.

Conclusion: New immigrants had the most extensive angiographic coronary involvement, while Arab patients were younger and had less severe coronary artery disease. More intensive risk factor modification may have a major impact on disease progression particularly in the new immigrant subgroup. 

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM.

Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor α-induced adhesion of CD4+T cells to ECM in a uremic milieu.

Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group.

Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10–11% vs. 24–29% for soluble chemokines, P<0.001; 12–13% vs. 37–39% for bound chemokines on resting cells, P<0.01; and 18–20% vs. 45–47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01).  Adherence of dialysis patients’ cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15–17% vs. 25–32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude.

Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients’ T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

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ECM = extracellular matrix

TNF-α = tumor necrosis factor-a

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.

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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.

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ACT = autologous chondrocyte transplantation