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עמוד בית
Thu, 26.12.24

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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

Eytan Mor MD, Rachel Michowiz RN MA, Tamar Ashkenazi RN MSc Ethi Shabtai PhD, Richard Nakache MD, Ahmed Eid MD, Aaron Hoffman MD, Solly Mizrahi MD, Moshe Shabtai MD and Zaki Shapira MD1 for the Israel Transplant Center

Background: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors.

Objective: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation.

Methods: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring >1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor’s death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts.

Results: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n=13, 9.3%) or DGF (n=25, 17.9%). On regression analysis, donor age >50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors >50 years old, 21 (37.5%) developed either PNF (n=9) or DGF (n=12).

Conclusions: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from “aged” donors may help to choose appropriate donors from that pool.

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PNF = primary graft non-function

DGF = delayed graft function

March 2000
Shlomo Vinker MD, Sasson Nakar MD, Michael A. Weingarten BM BCh, and members of the Israeli General Practice Research Network

Background: Most countries today are experiencing an accelerated pace of population aging. The management of the elderly housebound patient presents a special challenge to the family physician.

Objectives: To investigate a series of home visits to housebound patients, the therapeutic procedures used, the equipment needed, and the diagnostic conclusions reached.

Methods: The details of 379 consecutive home visits to housebound patients were recorded by 91 family doctors serving 125,000 patients in Israel.

Results: The average age of the patients was 76.1 years. The vast majority of the visits were during office hours (94%). In 24.1% it was the doctor who decided to make the home visit on his/her own initiative. The most common initial reason for a home visit was undefined general symptoms, but the doctor was usually able to arrive at a more specific diagnosis after the visit. Medications were prescribed in 59.1% of the visits, and in 23.5% the medication was administered directly by the physician. The commonest drugs used were analgesics and antibiotics. In 19.3% of visits no action at all, other than examination and counseling, was undertaken. The equipment needed included prescription pads (73%), a stethoscope (81%), sphygmomanometer (74.9%), and otoscope/torch (30.6%). Only 15% of visits resulted in referral to hospital.

Conclusions: Home visits to housebound patients serve as a support to caregivers, provide diagnostic information, and help the family with the decision as to when hospitalization is appropriate. The specific medical cause for the patient being housebound had little effect on the process of home visiting.
 

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

Rolando Cimaz, MD, Luca Catelli, MD, Cristina Luzzana, MD, Paola Panzerei, PhD and Pierluigi Meroni, MD
December 1999
Eduard Kaykov MD, Benyamine Abbou MD, Scott Friedstrom MD, Doron Hermoni MD and Nathan Roguin MD
 Background: Previous work has suggested an association between Chlamydia pneumoniae infection and coronary artery disease. The infection was demonstrated by titers of antibodies - enzyme-linked immunosorbent assay or immunofluorescence, and polymerase chain reaction - and by the findings of C. pneumoniae in the atherosclerotic plaque.

Objectives: To evaluate the association between chronic infection with C. pneumoniae, as measured by a high titer of IgG antibody, and CAD. Our study was designed to explore the relationship between seropositivity to C. pneumoniae and serious coronary events, and to assess whether or not there may be an additional association between established cardiovascular factors and infection with this organism.

Methods: The serum of 130 patients with proven CAD was tested for the presence of IgG antibodies to C. pneumoniae using an ELISA test. A titer ≤1:64 using the microinfluorescence method, the recognized "gold standard," correlates with a positive result when using the ELISA method. The mean age was 57 (40-65 years). The patients, 82% male and 18% female, had either myocardial infarction (n=109) or unstable angina (n=21) 6 months before the investigation (range 3-24 months). The serum for the control group was obtained from 98 blood donors from the same area matched for age 52 (40-58 years) and sex. The donors had no known cardiac history.

Results: In the CAD group 75% of patients were positive for C. pneumoniae compared to 33% in the control group (P=0.001). No increased correlation could be demonstrated between traditional risk factors and C. pneumoniae infection, except in those patients with diabetes mellitus. We found a lower prevalence of IgG antibody to C. pneumoniae in the diabetes subgroup than in other subgroups (P<0.006), but a higher prevalence than in the control group.

Conclusions: We demonstrated a more than twofold increase in seropositivity to C. pneumoniae among patients suffering serious coronary events, and this trend was independent of gender, age or ethnic group. These findings suggest that chronic C. pneumoniae infection may be a significant risk factor for the development of CAD, but this correlation should be investigated further.

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CAD= coronary artery disease

Tsila Hefer, MD, Henry Zvi Joachim, MD, Joshua Danino MD, and Jacob Brown MD
November 1999
Gideon Paret MD, Tamar Ziv MD, Arie Augarten MD, Asher Barzilai MD, Ron Ben-Abraham MD, Amir Vardi MD, Yossi Manisterski MD and Zohar Barzilay MD, FCCM

Background: Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity.

Objectives: To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome.

Methods: The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS1. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by <200 partial pressure of oxygen during ³6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO22 /forced expiratory O2, alveolar–arterial O2 difference, and ventilation index.

Results: We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO23 on the second day after diagnosis. Non-survivors had significantly lower PaO2/FIO2 (116±12 vs. 175±8.3, P<0.001), and higher A-aDO2 (368±28.9 vs. 228.0±15.5, P<0.001) and ventilation index (43.3±2.9 vs. 53.1±18.0, P<0.001) than survivors.

Conclusions: Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population. 

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1ARDS = acute respiratory distress syndrome

2 PaO2 = partial pressure of oxygen

3A-aDO2 = alveolar–arterial O2 difference

Ehud I. Goldhammer MD, Leonid Kharash MD, PhD and Edward G. Abinader MD
October 1999
September 1999
Moshe Salai, MD, Moshe Pritsch, MD, Yehuda Amit, MD, Amnon Israeli, MD and Aharon Chechick, MD.
 Background: Bone banking and the clinical use of banked tissue are the most common forms of allopreservation and transplantation in modern medicine.

Objectives: This article reviews 25 years (1973–98) of experience in bone banking in Israel.

Methods: A nationwide survey on the clinical application of the banked musculoskeletal tissues during 1996 was conducted by means of a written questionnaire sent to all orthopedic departments in Israel.

Results:  The response rate to the questionnaire was 84%. A total of 257 cases were allocated bone allografts: the majority comprised 225 spongy bones, 26 were massive bone allografts and 6 were soft tissue allografts.

Conclusion:  Improvement of quality control and quality assurance of the banked tissues, together with development of skills in the use of osteoinductive and osteoconductive materials, cast the future of musculoskeletal tissue banking.

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 * A Tribute to Professor Henry Horoszowski

Hertzel Salman, MD, Pearl I. Herskovitz, MD, Simcha Brandis, MD, Michael Bergman, MD, Dror Dicker, MD, and Izhar Zahavi, MD.
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