Israel Medical Association Journal

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.

______________________________

In 2001 the number of residents aged 65 and over in Israel was 639,000, or 10% of the population. The rate of increase of the elderly population is twice that of the general population, thus the predicted number of elderly for 2020 is around 1,025,000, representing a 60% increase. While this process is determined by a decline in both fertility and mortality, in Israel, immigration has also been a central factor in the process of aging. Life expectancy stands at 76.7 for men and 80.9 for women; at age 65 it is 16.4 years for men and 18.5 for women. The major factor influencing the increase in life expectancy during the past two decades has been the prevention of death among older people. Population aging, or “the demographic transition,” also represents an "epidemiological transition” – from high rates of infectious and communicable diseases, to high rates of chronic diseases among older people. During the past two decades, the number of disabled elderly has increased more than 2.5 times. In 2001, there were about 97,400 disabled elderly in Israel, constituting about 15% of all elderly. By the year 2010, the number of disabled elderly is expected to reach 120,100. The rate of increase of the disabled elderly population is almost double that of the total elderly population, due to changes in this population’s composition. However, recent research indicates that new cohorts of elderly are healthier than earlier cohorts but experience a decline in health at older ages. While advances in standard of living, medicine, and technology have made this possible, a greater allocation of resources is required to prevent disability and maintain the quality of life.

The Arab population of Israel is relatively young. However, a significant increase is expected in the number of elderly Arabs in the coming years. At the end of 2001 there were 38,500 Arab elderly, but their number is expected to reach 92,100 by 2020. This will represent a nearly 2.5-fold increase in absolute numbers. As the population ages, the number and percentage of people with chronic diseases and related disabilities will rise significantly. While the Arab elderly are much younger than the Jewish elderly, they are more disabled and therefore have greater medical and nursing needs. An extremely important measure of the need for formal services is an elderly person’s functional ability, especially the ability to live independently. The percentage of Arab elderly who are disabled and need help with activities of daily living is two times higher than that of the Jewish elderly population. At present, 30% of the Arab elderly (39% of the women and 20% of the men), compared to 14% of Jewish elderly (17% of the women and 11% of the men), need help in at least one ADL[1] (bathing, dressing, eating, mobility in the home, rising and sitting, getting in and out of bed). Concomitant with demographic changes are forces that affect the ability of informal support systems to provide care. For example, the rising number of Arab women in the labor force together with changes in elderly peoples' living arrangements have increased the need for formal services to share responsibility for the elderly with families. As services are developed, questions arise regarding the extent to which they have been adapted to the culture and norms of Arab society and meet that society’s unique needs. This paper elaborates on some of these issues.

Background: Little information is available on the clinical practice and implementation of guidelines in treating acute myocardial infarction patients in Israel.

Objective: To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI[1] patients hospitalized in Israel during a 2 month period in 2000.

Method: We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form.

Results: During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG[2] in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively.

Conclusions: This nationwide survey shows that one-third of the AMI patients in Israel are elderly (≥ 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.

Background: The incidence of malignant musculoskeletal tumors during pregnancy is very low. The paucity of data precludes the drawing of solid conclusions regarding a standard approach.

Objectives: To summarize our experience treating 13 pregnant women with malignant soft tissue or bone tumors.

Methods: We conducted a retrospective analysis of 13 cases of patients with either soft tissue or bone sarcoma that developed or progressed during pregnancy or immediately after delivery.

Results: The clinical presentation of the tumors was either a growing mass and/or increasing pain and disability. Most of the masses were located in the lower part of the body and of considerable size. Treatment given during gestation was limited to wide excision of the mass in the 28th week of gestation in one patient. All the patients reported disease progression during gestation. Vaginal delivery was possible in eight patients with no complications, cesarean section was carried out in three women, spontaneous miscarriage occurred in one and termination of pregnancy was performed in one patient.

Conclusions: The diagnostic and therapeutic approaches should be tailored specifically in every pregnant woman in whom sarcoma is suspected.
 

Background: Current clinical guidelines restrict catheterization laboratory activity without on-site surgical backup. Recent improvements in technical equipment and pharmacologic adjunctive therapy increase the safety margins of diagnostic and therapeutic cardiac catheterization.

Objective: To analyze the reasons for urgent cardiac surgery and mortality in the different phases of our laboratory’s activity in the last 11 years, and examine the impact of the new interventional and therapeutic modalities on the current need for on-site cardiac surgical backup.

Methods: We retrospectively reviewed the mortality and need for urgent cardiac surgery (up to 12 hours post-catheterization) through five phases of our laboratory’s activity: a) diagnostic (years 1989–2000), b) valvuloplasties and other non-coronary interventions (1990–2000), c) percutaneous-only balloon angioplasty (1992–1994), d) coronary stenting (1994–2000), and e) use of IIb/IIIa antagonists and thienopiridine drugs (1996–2000).

Results: Forty-eight patients (0.45%) required urgent cardiac surgery during phase 1, of whom 40 (83%) had acute coronary syndromes with left main coronary artery stenosis or the equivalent, and 8 (17%) had mechanical complications of acute myocardial infarction. Two patients died (0.02%) during diagnostic procedures. In phase 2, eight patients (2.9%) were referred for urgent cardiac surgery due to either cardiac tamponade or severe mitral regurgitation, and two patients (0.7%) died. The combined need for urgent surgery and mortality was significantly lower in phase 4 plus 5 as compared to phase 3 (3% vs. 0.85%, P = 0.006).

Conclusion: In the current era using coronary stents and potent antithrombotic drugs, after gaining experience and crossing the learning curve limits, complex cardiac therapeutic interventions can safely be performed without on-site surgical backup.
 

Background: Concomitant mitral valve regurgitation is often present in patients with aortic stenosis. The additional MV[1] replacement is associated with high operative risk. Previous studies have shown an amelioration of MV regurgitation after aortic valve replacement but most of the patient groups were heterogenous.

Objectives: To determine whether AV[2] replacement for aortic stenosis has any effect on MV regurgitation.

Methods: We reviewed two-dimensional echocardiography and color flow Doppler assessment of both aortic stenosis and MV regurgitation severity in 30 patients. Patients with previous MV surgery, organic MV disease, occlusive carotid artery disease, ejection fraction < 50%, and coexisting significant AV regurgitation were excluded. Preoperatively, MV regurgitation was mild in 23 patients (77%) and moderate in 7 (23%); in no patient was the condition severe. All patients had severe atrial stenosis (peak average aortic gradient was 86  ± 22 mmHg in the mild MV regurgitation group, and 83 ± 26 mmHg in the moderate group). The patients were divided into two groups according to the severity of MV regurgitation (associated mild, and moderate). Group 2, with moderate MV regurgitation, was the most problematic in terms of decision making for concomitant MV surgery. Therefore, additional assessment of several parameters was required.

Results: There was a significant decrease in MV regurgitation area (7.6 ± 1.9 vs. 3.0 ± 1.2 cm², P £ 0.012) and percent (28 ± 5% vs. 12 ± 6%, P £ 0.001) between pre- and postoperative evaluation. Thus, the severity of the condition in all patients with moderate MV regurgitation decreased after AV replacement; in the mild group it remained unchanged in 53% or improved in 47%. There was no association between the preoperative gradient on the aortic valve and the degree of MV regurgitation.

Conclusions: In our population of patients with severe atrial stenosis there were no patients with coexisting severe MV regurgitation. The decision to repair or replace a severely leaking mitral valve is an easy one, as in mild MV regurgitation. The clinical problem often presents in patients with severe aortic stenosis and moderate MV regurgitation. We believe that additional MV surgery is not necessary, at least in patients with preserved left ventricular function and without organic MV disease.

Background: With the introduction of surgery and percutaneous balloon valvuloplasty for relieving severe mitral stenosis the natural history of the disease has markedly altered.

Objectives: To determine the natural history of patients with moderate mitral valve stenosis.

Methods: Demographic, clinical and echocardiographic data were evaluated in 36 patients with moderate mitral stenosis during a follow-up of 71 ± 15 months.

Results: The 36 patients comprised 32 women and 4 men with a mean age of 43.7 ± 12.2 years; 28 were Jewish and 8 were of Arab origin. During follow-up, there was a significant decrease in mitral valve area, with an increase in mean mitral valve gradient and score. Mean loss of mitral valve area was 0.04 ± 0.11 cm²/year. No correlation was found between disease progression and age, past mitral valve commissurotomy, baseline mean gradient or mitral valve score. Larger baseline mitral valve area (P = 0.007) and Arab origin (P = 0.03) had an independent correlation to loss of mitral valve area. Fifteen patients (42%) did demonstrate any loss in mitral valve area during the follow-up period.

Conclusions: The rate of mitral valve narrowing in patients with moderate mitral stenosis is variable and cannot be predicted by patient’s age, past commissurotomy, valve score or gradient. Secondly, larger baseline mitral valve area and Arab origin showed an independent correlation to loss of mitral valve area; and finally, in many patients valve area did not change over a long observation period.
 

Background: Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers.

Objective: To present our results of computed tomography-guided core needle biopsy with assessment of the accuracy of the technique.

Methods: Between July 1998 and October 2000, 215 CT-guided core needle biopies were performed and histologically examined in the Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center. There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist.  To assess the accuracy of the procedure, we compared the diagnosis at biopsy with the diagnosis after definitive surgery (when available).

Results: Bone core needle biopsy (n = 135) showed malignancy in 89 cases (primary or recurrent bone sarcoma, lymphoma, myeloma, metastatic carcinoma or melanoma). There were 29 benign lesions. In 17 cases the result was inconclusive and an open incisional biopsy was performed. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, 6 lymphomas, 4 metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma and others), and 5 were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures.

Conclusions: CT-guided CNB[1] of musculoskeletal lesions is a safe and effective procedure that assures sufficient and proper material for histologic examination. The accuracy of this method in our center was 90%. Tumor sampling is extremely important, especially in soft tissue sarcomas, and cores should be taken in different directions, including areas of necrosis. The processing is quick, especially for bone CNB, and diagnosis can be achieved within 24 hours. The material undergoes excellent fixation and the immunostains are reliable.