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עמוד בית
Thu, 18.07.24

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December 2000
Eli Magen, MD and Reuven J. Viskoper, MD
 Renin-angiotensin-aldosterone systems play a critical role in the development and progression of cardiovascular diseases, and inhibitors of angiotensin-converting enzyme have proven effective for the treatment of these diseases. Since angiotensin II receptor antagonists can inhibit the effects of angiotensin II via ACE-independent pathways, e.g., chymase, they were considered to be more effective than ACEIs. On the other hand, ACE inhibitors can increase bradykinin, and thus, nitric oxide, which may cause potent cardioprotection, inhibition of smooth muscle proliferation and attenuation of inflammation mechanisms. It appears that angiotensin II receptor antagonists and ACEIs may mediate cardioprotection in different ways. This is the rationale to explore the possibility of a combined administration of both drugs for the treatment of chronic heart failure and other cardiovascular pathology. In this review we try to analyze the role of ACE, kinins and chymase inhibition in the pathophysiology and treatment of cardiovascular diseases.

November 2000
Avishay Elis, MD, Rivka Zissin, MD, Georges Leichtman, MD and Michael Lishner, MD
October 2000
Haim Paran, MD, Ivan Shwartz, MD and Uri Freund, MD
July 2000
Matityahu Lifshitz MD and Vladimir Gavrilov MD

Background: Childhood poisoning continues to challenge the diagnostic and treatment skills of the pediatrician. Generally, childhood poisoning can be attributed to suboptimal parental supervision and accessibility of products with poisoning potential.

Objective: To evaluate the pattern of acute poisoning in children with relation to different age groupings.

Methods: Pediatric patients hospitalized for acute poisoning at the Soroka Medical Center over a 5 year period (1994-98) were evaluated retrospectively. Special attention was given to poisoning in relation to age groupings.

Results: During the years 1994-98 a total of 1,143 children were admitted for acute poisoning to the Soroka Medical Center. The majority of cases occurred in children aged 2-5 and 14-18 years. Males under 14 had a higher frequency of poisoning, the poisoning usually being unintentional, whereas poisoning in females occurred mostly in the 14-18 age group and was intentional. Drugs were the most common agent of poisoning in infants (0-1 year), in older children (10-13 years), and in adolescents (14-18 years), while in children aged 2-5 and 6-9 years either cleaning products or drugs were the usual agents of poisoning. Most poisonings in children aged 2-13 occurred between 4 and 8 p.m., and for most adolescent patients (14-18 years old) between 4 p.m. and midnight. Poisoning in children aged 2-13 were usually due to accessible home products, and to medicinal errors such as overdose and improper drug administration.

Conclusions: This study defines the characteristic pattern of pediatric poisoning with respect to different age groups and gender. Unintentional childhood poisoning predominated in males and occurred mostly because of accessible home products and suboptimal parental supervision during critical hours of the day. Most adolescent poisoning occurred in females and was intentional. Parental education and intensified child supervision are indicated measures of prevention for unintentional poisoning.

Miguel Iuchtman MD, Ricardo Alfici MD, Ehud Sternberg MD, Leonid Trost MD and Menachem Litmanovitch MD

Background: Trauma is the leading cause of death in children. In abdominal lesions the spleen is the most commonly involved organ. During the last two decades much effort has focused on spleen tissue conservation.

Objectives: To analyze the rationale of a multimodality management policy that includes autotransfusion and mesh wrapping.

Methods: Data gathered over 14 years illustrate the introduction of new techniques and their impact on cases of severe spleen rupture.

Results: A total of 122 children were treated during the 14 year period, 1985-98. In 16 children an absorbable mesh wrapping, alone or in combination with other techniques, was used to obtain hemostatis and save spleen tissue.

Conclusions: Mesh wrapping, partial splenectomy and autotransfusion can be used, alone or in combination, to preserve severely injured spleens. According to our records, all children survived with a functional spleen. There were no cases of rebleeding. In only one case of prolonged postoperative fever could the cause be traced to an infected spleen hematoma that was drained transcutaneously. Autotransfusion is performed simply and without the use of a "cell saver." Its use can be crucial in small or field hospitals or in a situation of mass casualty.

Anne Bordron, BSc, Ronan Revelen, BSc and Pierre Youinou, MD, DSc
Jonathan Cohen, FCP (S.A) Maury Shapiro, MD, Elad Grozovski, MD, Menashe Haddad, MD, Nissim Hananel, MD and Pierre Singer, MD,
June 2000
Paltiel Weiner MD, Joseph Waizman MD, Margalit Weiner PhD, Marinella Rabner MD, Rasmi Magadle MD and Doron Zamir MD

Background: Cigarette smoking is a major contributor to the risk of acute myocardial infarction and the subsequent morbidity and mortality. Physicians can play an important role in smoking cessation among patients with AMI because of their frequent contact with the patient during the event.

Objectives: To study the prevalence of smoking, age, localization of coronary occlusion, mortality and rate of smoking cessation in consecutive patients who were diagnosed with a first AMI in our center in 1989–93.

Methods: The study included 1,510 consecutive patients with first AMI: 973 men (512 smokers, 52.6%) and 537 women (215 smokers, 40%), whose mean age was 64.1±6.7 and 68.6±5.2 years respectively.

Results: The median age at the first AMI in non-smoking and smoking men differed significantly (70.4±6.8 vs. 56.6±6.1 years, P<0.001) while the difference in the women was smaller (70.4±6.9 vs. 66.8±7.2). The proportion of smokers/non-smokers among men was greater at a younger age and decreased proportionally with age. The overall mortality was 11.3% with a significant difference in mortality rate in the younger age groups between smokers and non-smokers (1% vs. 0% in the age group 31–40 years, P<0.05, and 6.1% vs. 0.8% in the 41–50 year age group, P<0.001). Only 62% of the smokers who survived the AMI declared that they had received anti-smoking advice from a physician during hospitalization. The cessation rate in this group was significantly higher than in smokers who had not been cautioned against smoking (56% vs. 18%).

Conclusions: Current smokers sustained their first AMI more than one decade earlier than non-smokers, and the younger smokers had a higher mortality rate. The majority of the smokers who received anti-smoking advice during their hospitalization for AMI quit smoking in the year following the acute event. 

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AMI= acute myocardial infarction

Guillermo Ruiz-Irastorza, MD, PhD, Munther A. Khamashta, MD, MRCP, PhD and Graham R.V. Hughes, MD, FRCP
May 2000
Dan Miron MD, Raul Colodner MSc and Yoram Kenes PhD

Background: Two recent studies found that the prevalence of cryptosporidiosis among children in Israel was 3.4-7.4%.

Objectives: To assess the cumulative infection rate by testing immunoglobulin A and G seroprevalence for Cryptosporidium in children and adults in Israel.

Patients and Methods: The seroprevalence of IgA and IgG anti-Cryptosporidium antibodies was determined by an enzyme-linked immunosorbent assay procedure in a group of 163 healthy children and adults.

Results: The overall seroprevalence rates for IgG, IgA, both IgA and IgG, and any immunoglobulin were 12.6%, 23%, 30% and 65.6% respectively. Half the children under the age of 12 years were already infected, with seroprevalence increasing to 95.6% in those over age 13 (P<0.05). Seropositivity for IgG or IgA did not significantly increase with age.

Conclusions: These results indicate that a large percentage of healthy children and adults in northern Israel have been infected with Cryptosporidium, and at early ages.

Perla Werner PhD and Iris Vered MD

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.

Josef Ben-Ari MD, Imad R. Makhoul MD DSc, Raymond J. Dorio MD, Sue Buckley MSc,David Warburton MD and Sharyn M. Walker

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

April 2000
Ella Zeltzer MD, Jacques Bernheim MD, Ze’ev Korzets MB BSc,, Doron Zeeli PhD, Mauro Rathaus MD, Yoseph A. Mekori MD and Rami Hershkoviz MD

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

chondrocyte transplantation, joint cartilage, articular surface, bioengineering, cartilage repair, dror robinson, hana ash, david aviezer, gabriel agar, nahum halperin, zvi nevo, robinson, ash, aviezer, agar, halperin, nevo

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

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