Israel Medical Association Journal

Background: Training in geriatric psychiatry constitutes a fundamental element toward further development of this relatively new branch of medicine. However, it varies both in quantity and quality among different countries, healthcare providers and medical schools.

Objectives: To describe the demographic and professional characteristics of participants in postgraduate diploma courses in geriatric psychiatry, and the perceived contribution of the courses; and to compare these variables among the participants in 1 year and 3 year courses, and between psychiatrists and non-psychiatrists.

Methods: A retrospective self-administered questionnaire was mailed to the 153 physicians who participated in the two courses. The 60 questionnaires completed and returned were analyzed.

Results: Participants in the courses constituted a heterogenous group in terms of demographic and professional characteristics, with no differences between 1 year and 3 year course participants, or between psychiatrists vs. non-psychiatrists (with the exception of more involvement of non-psychiatrists and 1 year course participants in old-age homes). Most responders indicated both the theoretical and practical benefits and application to daily practice of the material learned. Similarly, most responders indicated that after the courses they definitely used general assessment scales to a much greater extent, particularly cognitive scales, as well as operational diagnostic criteria for dementia. Participants in the 3 year course reported more significant use of assessment scales compared with 1 year participants, and 3 year participants and psychiatrists used the cognitive scales more often. There were no other significant differences between 1 year and 3 year participants and between psychiatrists’ and non-psychiatrists’ reports regarding general and more specific contributions of the courses.

Conclusion: Postgraduate diploma courses in geriatric psychiatry seem to have a favorable effect on participants, irrespective of course duration or specialty. However, course duration positively influenced the implementation of assessment scales in general, and cognitive scales in particular. A prospective comparative study on this subject is warranted, with stricter definitions of participants’ pre-course and post-course background, attitudes, knowledge and benefits.
 

Matrix metalloproteinases are a family of enzymes that degrade different components of extracellular matrix. They play an important role in normal physiologic processes of maintaining tissue integrity and remodeling, as in wound healing, processes of development, and regeneration. However, excessive expression of MMP[1] has been observed in many disease states, including rheumatoid arthritis and osteoarthritis, vascular remodeling in atherosclerosis and aortic aneurysm formation, neoplastic processes, macular degeneration and many others.

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Background: The frequent systemic side effects associated with the use of systemic carbonic anhydrase inhibitors have adversely affected the compliance to treatment in glaucoma patients, obviating their long-term use. The introduction of the topical CAI[1], dorzolamide, has further reduced their use. However, the tolerability of dorzolamide in patients who have been intolerant to systemic CAIs has not been evaluated prospectively.

Objectives: To study the tolerability and efficacy of dorzolamide (a topical CAI) in a selected group of glaucoma and ocular hypertensive patients who have been intolerant to systemic CAI.

Methods: A 3 month prospective study was conducted in 39 patients. Following recruitment, patients were evaluated on the day of switching from systemic CAI to dorzolamide and for five more visits. The SF-36 health assessment questionnaire was used to evaluate changes in well-being and quality of life, and the intraocular pressure was measured periodically.

Results: Within 4 weeks of switching from systemic CAI to dorzolamide, the mean health assessment scores improved significantly in seven of the eight categories of the SF-36, and remained generally unchanged for the rest of the study. No significant differences were noted between the mean IOP[2] on day 0 and the following measurements throughout the 84 days of dorzolamide therapy.

Conclusion: In glaucoma patients who were intolerant to systemic CAI, topical CAI dorzolamide offers a similar efficacy and better tolerability.

Background: High frequency oscillatory ventilation has proved valuable in recruiting and sustaining lung volume; the combined treatment may augment nitric oxide delivery to target vessels. NO[1] therapy lowers pulmonary resistance and improves oxygenation.

Objective: To retrospectively review data on changes in oxygenation – indicated by arterial/alveolar PO₂ ratio, oxygenation index, and outcome – in a cohort of 10 infants with hypoxemic respiratory failure in whom nitric oxide inhalation was instituted in a compassionate-use protocol after deteriorated oxygenation.

Methods: NO inhalation was administered at a range of 0.12–122 days of life using the SensorMedics system in 10 infants who developed hypoxemic respiratory failure associated with a variety of lung diseases while on HFOV[2].

Results: The infants' birthweight was 1,717 ± 1,167 g and their gestational age 31.1 ± 6.5 weeks. Mean exposure to NO inhalation was 14.2 days and ranged from 3–59 days. Oxygenation index decreased from 39.3 ± 13.2 to 12.7 ± 6.9 (P < 0.0002) after NO therapy. Despite an initial prompt response to NO inhalation, two patients died of progressive intractable respiratory failure and one term infant died of extrapulmonary complications (hypoxic ischemic encephalopathy grade III and multiorgan failure).

Conclusion: Our results indicate that the combined treatment of HFOV and NO inhalation is superior to HFOV alone for improving oxygenation in a selected cohort of infants ventilated for a variety of lung diseases.

Background: Venous thromboembolic diseases are treated initially with low molecular weight heparin followed by oral coumarins.

Objectives: To investigate an orally available direct thrombin inhibitor for the acute treatment of venous thromboembolism as well as for prophylaxis of recurrent events.

Methods: The direct thrombin inhibitor ximelagatran was compared with subcutaneous LMW[1] heparins followed by oral warfarin in a double-blind randomized prospective multicenter trial in patients with acute VTE[2]. A pharmacokinetic study was performed in the VTE patients. For assessing the prevention of recurrent VTE, double-blind prospective randomized studies were conducted as follows: a) ximelagatran compared to warfarin for 6 months, and b) prolonged anticoagulation of ximelagatran vs. placebo for 18 months after termination of 6 months coumarin therapy.

Results: Two dose-finding studies and the pharmacokinetic analysis of ximelagatran in acute VTE were completed. About 2,500 patients were randomized to investigate 2 x 36 mg ximelagatran versus 2 x 1 mg/kg body weight enoxaparin followed by warfarin. The study hypothesized that the efficacy was equal in both treatment regimens for recurrent VTE documented by objective methods. The second study, with 1,234 patients, aimed to demonstrate a reduced incidence of recurrent thromboembolic events documented by objective methods after 18 months of treatment with 2 x 24 mg ximelagatran daily compared to placebo.

Conclusion: These large-scale clinical trials will soon yield the results of the comparison between oral ximelagatran and subcutaneous LMW heparin for treatment of acute VTE, and of warfarin for prophylaxis of recurrent events for 6 months and for a prolonged prophylaxis for another 18 months.

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[1] LMW = low molecular weight

[2] VTE = venous thromboembolism

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  

Background: The importance of health promotion and disease prevention in health policy and clinical practice is widely accepted in many countries. However, a large number of medical schools do not dedicate a significant part of their curriculum to these aspects. In Israel, there are no reports on the training of the future physician towards his or her role as health promoter in general, or in the areas of cardiovascular and cancer diseases specifically.

Objectives: To examine the preparation of Israel medical students for the role of health promoter in cancer and cardiovascular diseases.

Methods: The study was carried out over 2 years in two of the four medical schools in Israel: the Sackler Faculty of Medicine at Tel Aviv University and the Faculty of Health Sciences at Ben Gurion University in Beer Sheva. The students (n=172, 70% response rate) were surveyed during 1999-2000 by means of a questionnaire, which included assessment of their training towards the role of health promoter, their clinical experiences and exposure to patients at different stages of illnesses at various medical sites, and the specific skills and relevant knowledge they acquired.

Results: Most of the students’ learning experiences occurred in hospitals with patients at the treatment stage and little time was dedicated to prevention, especially in the community. They demonstrated better knowledge, skills and satisfaction with their learning experiences in CVD than in cancer; and reported having insufficient exposure to several common cancer diseases and lacking examining skills for early detection of cancer. The students in Beer Sheva had significantly more interaction with patients at different stages of CVD and acquired more examination skills than the Tel Aviv students.

Conclusions: A change in the curriculum is urgently needed: namely training medical students in community settings and preparing them to promote the well-being of their patients, including prevention. Attention should be given to launching new learning modes in the pre-clinical and clinical curriculum. We propose that: a) pre-clinical courses include prevention techniques in CVD and cancer, problems of cancer patients, and some examining skills; and b) the clinical phase should integrate oncology concepts and total cancer and CVD care into existing clerkships in the hospitals and in the community.