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עמוד בית
Fri, 22.11.24

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April 2000
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

Hagit Cohen PhD, Moshe Kotler MD, Mike Matar MD and Zeev Kaplan MD

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.   

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HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Arnon Blum, MD, Subhi Jawabreh, MD, Marina Gumanovsky, MD and Soboh Soboh, MD
March 2000
Eli Somekh MD, Ron Dagan MD and Aaron Hanukoglu MD

Background: DHEAS, the most abundant steroid secreted by the adrenal cortex, is suggested to have an important role in the development of immune reaction by activating T cell function and increasing antibody response, and has been tried as a vaccine adjuvant in elderly people.

Objectives: We examined the correlation between endogenous DHEAS and antibody response in the neonatal period by comparing the serum DHEAS levels with the amount of antibody response against hepatitis B vaccination in neonates.

Methods: Vaccine was administered to 12 healthy infants within 24 hours of birth (day 0), and blood specimens were obtained on days 0 and 30 for determination of anti-hepatitis B surface antibody concentration and DHEAS levels.

Results: DHEAS levels varied widely (range 0.38-3.70 μg/ml, mean±SD 2.14±0.98). While we could identify two groups of patients - those with high DHEAS levels (2.90±0.56) and those with lower levels (1.30±0.56) - there was no correlation between DHEAS levels and the antibody response to hepatitis B vaccine (γ=-0.05).

Conclusions: In neonates, antibody response to hepatitis B vaccine does not correlate with DHEAS serum levels. These results do not support the usage of DHEAS as a vaccine adjuvant in neonates.

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DHEAS= dehydepiandrosterone sulphate

Michael A. Weingarten MA BM BCh, Irene Katzir MD, Elliot Sprecher PhD,Svetlana Kobzantsev MD, Cara Zelzer MD and Ernesto Kahan MD

Background: The pattern of diabetes and ischemic heart disease among emigrants from pre-industrialized societies to more developed countries may be explained by both genetic and environmental factors.

Objectives: To describe and interpret the pattern of diabetes and ischemic heart disease among Yemenite immigrants in Israel and their second-generation offspring.

Methods: Medical record charts of adult Yemenites were surveyed in a primary care health center, and the data were compared with prevalence rates derived from a non-Yemenite population.

Results: There was a marked excess of non-insulin dependent diabetes mellitus among Yemenite immigrants over 45 years of age, but not of hypertension or ischemic heart disease. Yemenites with diabetes were far less likely to develop ischemic heart disease than non-Yemenites with diabetes (odds ratio for non-Yemenites compared with Yemenites, 3.5; confidence interval 1.54<OR<7.77).

Conclusions: There was less of an association between diabetes and ischemic heart disease among Yemenites. This finding requires further investigation of the relative roles of genetic and environmental factors. 

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OR= odds ratio

Anabel Aharon-Maor, MD and Yehuda Shoenfeld, MD
Elias Toubi, MD, Johana E. Naschitz, MD, Aharon Kessel, MD and Milo Fradis, MD
February 2000
Dan Nemet, MD, Baruch Wolach, MD, Joanne Yacobovich, MD and Alon Eliakim, MD
Itamar Offer, MD, Shai Ashkenazi, MD, Gilat Livni, MD and Itamar Shalit, MD

Background: Bronchiolitis caused by respiratory syncytial virus is one of the major causes of hospitalization in young children, especially during the winter.  Recent evidence has shown that pharmacological treatment, especially nebulized epinephrine, in addition to the traditional supportive treatment, can alleviate symptoms and shorten hospitalization, but this approach is not yet widespread.

Objectives: To determine whether the management of bronchiolitis in Israel is moving toward a stronger emphasis on pharmacological care.

Methods: A questionnaire on the diagnosis and management of bronchiolitis was completed by 27 heads of pediatric departments throughout Israel.  The questionnaire dealt with the frequency of usage of diagnostic and selected therapeutic procedures.

Results: Chest X-ray and arterial blood gases are commonly used as a diagnostic aid in more than 75% of the departments, and antibiotics are prescribed routinely in 24%.  Corticosteroids are still in use: 48% use systemic steroids, and 19% nebulized steroids.  Nebulized epinephrine is used in 22% of the departments, while nebulized beta-agonists are used frequently in two-thirds of the departments.

Conclusions: Despite convincing data that beta-agonists and steroids have no positive effect on the outcome of bronchiolitis on the one hand, and that nebulized epinephrine has advantages in children on the other, we found significant use of the former two agents and sparse use of the latter.  Greater awareness is needed among pediatricians, and measures should be introduced to incorporate the new recommendations, with further study of the effect of the old and new drugs on bronchiolitis.

 

Erez Sharoni MD, Jacob Katz MD, Ovadia Dagan MD, Avraham Lorber MD, Rafael Hirsch MD, Leonard C. Blieden, Bernardo A. Vidne MD and Einat Birk MD

Background: The need for aortic valve replacement in children and young adults poses a special problem to cardiologists and surgeons. Replacing the sick aortic valve with the patient’s pulmonary valve as described by Ross has proven to be a good option in this special age group.

Objective: To review our initial experience in order to assess the short-term results.

Methods: From January 1996 to June 1999, 40 patients (age 8 months to 41 years) underwent aortic valve replacement with pulmonary autograft. Indications for surgery were congenital aortic valve disease in 30 patients, bacterial endocarditis in 5, rheumatic fever in 3, and complex left ventricular outflow tract obstruction in 3. Trans-esophageal echocardiography was performed preoperatively and post-bypass in all patients, and transthoracic echocardiography was done prior to discharge and on follow-up.

Results: There was no preoperative or late mortality. All patients remain in functional class I (New York Heart Association) and are free of complications and medication. None showed progression of autograft insufficiency or LVOT obstruction. Homograft insufficiency in the pulmonary position has progressed from mild to moderate in one patient, and three developed mild homograft stenosis.

Conclusions: The Ross procedure can be performed with good results in the young population and is considered an elegant surgical alternative to prosthetic valves and homografts.

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LVOT = left ventricular outflow tract

Lutfi Jaber MD, Bella Eisenstein MD and Mordechai Shohat MD

Background: Hypertension is one of the most prevalent vascular diseases in the adult population. It is an important determinant of atherosclerosis in adolescents and young adults. There is to date no information on blood pressure in children of the Israeli Arab population.

Objectives: To study blood pressure in Israeli Arab children and adolescents.

Methods: Blood pressure measurements were taken in the supine position in 4,488 Israeli Arab children and adolescents of both sexes aged 6–17 years. Height and weight were also determined. Correlation was investigated between systolic and diastolic blood pressure, body mass index, gender, and age.

Results: The systolic and diastolic blood pressures were similar in both sexes for all age groups up to 14 years of age. Systolic blood pressure was significantly (P<0.001) higher in males aged 15–17 years  (120±13 vs. 111±12 mmHg, 123±13 vs. 113±14.0 mmHg, and 123±18 vs. 111±14 mmHg, respectively). Diastolic blood pressure was higher in males aged 15–17, with a statistically significant difference for age 17 only (75±12 vs. 69±13 mmHg). Blood pressure was elevated in 322 students in the initial screening (7.17%), with a decrease to 2.18% when this group was rescreened 2 weeks later. The systolic blood pressure in our group is higher than that in Jewish Israeli children of Asian and North African origin, and in American children. It is similar to the systolic blood pressure of European children and Jewish children born in Israel. The diastolic blood pressure in our group is higher than that in all groups of Israeli Jewish children and American children of different ethnic groups.

Conclusions: Israeli Arab children and adolescents have higher blood pressure levels than their Israeli Jewish counterparts. Further studies are required to confirm this observation.

Arie Levine MD, Yoram Bujanover MD, Shimon Reif MD, Svetlana Gass, Nurit Vardinon, Ram Reifen MD and Dan Lehmann PhD

Background: Anti-endomysial antibodies are sensitive and specific markers for celiac disease. This antibody has recently been identified as an antibody to tissue transglutaminase, an enzyme that cross-links and stabilizes extracellular matrix proteins.

Objectives: To evaluate the clinical usefulness of an enzyme-linked immunoassay for anti-transglutaminase antibodies, and to compare the results with those of AEA, the current gold standard serological test for celiac disease.

Methods: Serum samples were collected from 33 patients with biopsy-proven celiac disease and AEA tests were performed. Control samples for anti-transglutaminase were obtained from 155 patients. An ELISA test for immunoglobulin A anti-transglutaminase utilizing guinea pig liver transglutaminase was developed and performed on all sera.  Cutoff values for the test were performed using logistic regression and receiver operating curves analysis.

Results: An optical density cutoff value of 0.34 was established for the assay. The mean value was 0.18±0.19 optical density for controls, and 1.65±1.14 for patients with celiac disease (P<0.001). Sensitivity and specificity of the assay were both 90%, while AEA had a sensitivity and specificity of 100% and 94%, respectively.

Conclusions: A tissue transglutaminase-based ELISA test is both sensitive and specific for  detection of celiac disease.

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AEA = anti-endomysial antibody

Michael Schwarz MD, Gadi Horev MD, Enrique Freud MD, Nizza Ziv MD, Amir Blumenfeld MD, Ran Steinberg MD and Liora Kornreich MD

Background: Multiple organ injury in children is an increasingly frequent phenomenon in the modern emergency room. Adrenal hemorrhage associated with this type of trauma has received little attention in the past.

Objectives: Using computed tomography, we sought to determine the rate and nature of adrenal gland injury in children following blunt abdominal trauma due to motor vehicular accident.

Methods: A total of 121 children with blunt abdominal trauma were examined and total body CT was performed in cases of multi-organ trauma or severe neurological injury.

Results: Of all the children who presented with blunt abdominal trauma over a 51 month period, 6 (4.95%) had adrenal hemorrhage. In all cases only the right adrenal gland was affected. Coincidental injury to the chest and other abdominal organs was noted in 66.7% and 50% of patients, respectively.

Conclusions: Traumatic adrenal injury in the pediatric population may be more common than previously suspected. Widespread application of the more sophisticated imaging modalities available today will improve the detection of damage to the smaller organs in major collision injuries and will help in directing attention to the mechanism of trauma. 

Yona Amitai MD, Yedidia Bentur MD, Matityahu Lifshitz MD, Pinhas Fainmesser MD, David Applebaum MD, Yehezkel Waisman MD, Nadine Cohen and Samuel D. Oman PhD

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.    

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IPIC = Israel Poison Information Center

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