Autologous Chondrocyte Transplantation - from Science Fiction to Routine Clinical Practice

Dror Robinson, Hana Ash, David Aviezer, Gabriel Agar, Nahum Halperin, Zvi Nevo

Dept. of Clinical Biochemistry, Sackler Medical School, Tel Aviv University, Ramat Aviv; Dept. of Orthopedic Surgery, Assaf Harofeh Medical Center, Zerifin; and CTI Ltd., Science Park, Kiriat Weizmann, Nes Ziona

Adult articular cartilage lacks the capacity for self-repair. The limiting factor appears to be the inability of chondrocytes to proliferate while embedded in the extracellular matrix typical of hyaline cartilage. Cartilage defects larger than 1 cm² change articular biomechanics and lead to eventual osteoarth-ritis and joint destruction.

During the past decade, several competing techniques have evolved to stimulate articular cartilage repair. Small lesions can be successfully treated by either micro-fracture or osteochondral cylinder grafting. The latter technique allows immediate weight bearing but leads to damage of previously uninvolved areas of articular cartilage, which limits its application to lesions of less than 2 cm².

When the damaged area is more extensive, grafting of autologous chondrocytes should be considered. First a diagnostic arthroscopy is performed to assess the damaged area and a small cartilage biopsy is taken. 6 weeks later, arthrotomy and chondrocyte transplantation are performed. In the interval, the antologous chondrocytes have expanded by 2 to 3 orders of magnitude. Our experience to date includes 10 cases with follow-up of 6 months to 5 years. Preoperative complaints of crepitation and locking disappear. There is functional improvement and pain reduction of approximately 50%. This procedure, currently limited to patients under 55 years of age with limited damage to an articular surface, for the first time allows reconstruction of damaged articular areas without resorting to allografts.

Pulmonary Involvement in Osler- Weber-Rendu Syndrome 

Efrat Bron-Harlev, Benjamin Zeevi, Ben-Zion Garty

Dept. of Medicine B and Cardiac Catheterization Unit, Schneider Children's Medical Center, Petah Tikva

Hereditary hemorrhagic telangiectasia (Osler-Weber-Ren-du syndrome) is a group of autosomal dominant diseases with variable penetration, characterized by vascular malformations. Recently hereditary hemorrhagic telangiectasia has been found to be a phenotypic expression of mutations in genes located on chromosomes 9 and 12, and possibly of other genes located on other chromosomes.

We describe 2 patients with hereditary hemorrhagic telangiectasia and pulmonary involvement who presented with repeated complaints of dyspnea and cyanosis and were diagnosed as having long-standing asthma. Both were treated with therapeutic catheterization and embolization with good clinical outcomes.

Favorable Outcome of Hyperacute Epidural Hematoma in an Octogenarian

A. Rakier, I. Orlovsky, M. Feinsod

Center for Applied Research in Head Injuries, Neurosurgery Dept. Rambam Medical Center, and B. Rappaport Faculty of Medicine, The Technion, Israel Institute of Technology, Haifa

Acute epidural hematoma is very rare in the elderly after head injury. It is usually associated with extremely high mortality or severe disability. In an 87-year-old woman a large, hyperacute, epidural hematoma was diagnosed. She was treated promptly and enjoyed an uneventful, complete recovery. This exceptional case should encourage an intensive approach even in seemingly minor head trauma in the elderly.

Unconventional Treatment of Severe Heart Failure in the Elderly

Z. Fidelman, Z. Korshun

Geriatric Medical Center, Natanya

In the elderly, congestive heart failure is common and associated with significant morbidity and mortality.

Comprehensive management of heart failure improves functional status and decreases mortality. Diuretics remain the mainstay in treating congestive heart failure. However, some patients are resistant to diuretics. This is a serious problem as it seems to represent a final manifestation of congestive heart failure.

In an 85-year-old woman diuretic resistance was recognized as the cause of failure of conventional diuretic therapy. When the dose of furosemide was rapidly increased from 120 mg per os to 1000 mg IV within 4 days, diuresis began and there was dramatic improvement in her condition. The dose was then gradually decreased until a conventional maintenance dose of 200 mg/day per os was reached. This dose was sufficient to keep her heart failure under control.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.

Cilazapril for Essential Hypertension Treated in the Community 

Reuven Zimlichman

Dept. of Medicine and Hypertension Institute, Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University

In a multicenter study in community clinics, 413 patients with mild to moderate essential hypertension were treated with cilazapril (Vasocase), 2.5 mg daily. Patients had either been untreated or had developed side-effects from previous antihypertensive treatment. When response was inadequate the dose was either increased to 5 mg or another antihypertensive medication was added, or both.

Treatment significantly reduced systolic and diastolic blood pressures. Pulse rate decreased significantly from the second month of treatment onwards. At the end of the 3rd month of treatment blood pressure was normalized or had decreased by more than 10 mmHg in 91.9% of patients. Physicians' evaluations revealed improvement in 62%; patients' self-evaluations suggested improvement in 61%. Efficacy was equal in all age groups and in both obese and nonobese patients. Antihypertensive response was superior in those with normal renal function. Side-effects were rare and similar to those reported in the literature.

Smoking by an Israeli Hospital Staff, its Attitude to Smoking in Hospitals and to “Smoke-Free” Hospitals

Shabtai Varsano, Giora Hevion, Mila Garenkin

Depts. of Pulmonary Medicine, Asthma Care-Education Unit, Hospital Management Office, and Epidemiology and Medical Data Unit; Meir General Hospital, Sapir Medical Center, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University

Smoking within hospitals is common in general hospitals in Israel. It has a strong negative educational impact, has a negative image and curing its ill effects help keep our hospitals busy. An anonymous questionnaire was answered by 128 members of our hospital staff (28%). Their distribution, according to occupation and sex was representative of the rest of our hospital staff.

19% of our workers are smokers, a much lower proportion than in our general adult population. The proportion was highest among maintenance (40%) and sanitary-help staff (36%). 23% of nurses and 15% of physicians were smokers. This situation is better than that among Italian or Japanese medical staff, but much worse than among North American medical staff.

75% of our workers who smoke declared that they smoke outside the room in which they work. 66% and 72% of the staff believe that hospital workers and visitors, respectively, should smoke outside hospital buildings. Only 19% of all workers do not believe that a "smoke-free hospital" is attainable. 34% believe that a "smoke-free hospital" is achievable, and 47% said that it is perhaps achievable. 86% of all the workers, and 41% of the smokers, expect the hospital director to implement an effective policy of enforcing the law limiting smoking within hospitals (and other public buildings) in Israel. 60% are willing to contribute actively to this effort.

We believe these results strongly suggest that the time is ripe for implementation of the "smoke-free hospital" in Israel. This requires a strong and effective central policy, like that in the USA. We suggest measures that the Israel Ministry of Health take measures to successfully implement this policy.

Sclerosing Mesenteritis: An Unusual Cause of Abdominal Pain

Meir Mouallem, Zehavit Turok, Danny Rosin, Bruria Shalmon

Depts. of Medicine E, General Surgery and Transplantation, and of Pathology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

Sclerosing mesenteritis (SM) is rare and fewer than 300 cases had been reported up to 1997. We describe a 29-year-old woman who had abdominal pain for 1 year and presented with a palpable abdominal mass. The diagnosis of SM was made only after diagnostic laparoscopy and biopsy of the peritoneum.

Incidence of Insulin Dependent Diabetes in Youth in Israel 

Israel IDDM Registry Study Group

Recent reports from different countries have shown an increasing incidence of insulin-dependent diabetes mellitus (IDDM, type I diabetes). In Israel, several surveys of the incidence of IDDM have been conducted. During 1996, a national juvenile diabetes register was founded by specialists in endocrinology, and the Israel Center for Disease Control (ICDC).

This is the first report of the national incidence of IDDM in the 0-17 year age group in Israel. New cases of juvenile diabetes were reported using an anonymous form. The ICDC was responsible for data collection, control and statistical analyses.

During 1997, 162 new cases of diabetes mellitus were reported in the age group 0-17, 154 of them diagnosed as IDDM. The annual incidence in the total population of Israel in 1997 was 7.7/100,000. Age-specific incidence was 7.3/100,000 in boys and 8.1 in girls. A family history of IDDM was found in 14.3% of the cases. Incidence was higher for Jews (9.2/100,000) than Arabs (3.6/100,000). Among Jews, children whose fathers were born in Yemen had the highest incidence and those born to fathers born in Israel the lowest incidence.

IDDM incidence rates for 1997 are higher than reported in previous surveys. It will be possible to draw conclusions regarding possible trends in incidence from data to be gathered in the next few years.

Prioritizing Suspected Diagnosis of Both Brain and Abdominalinjuries: Is it a Problem?

Leon Levi, Moshe Michaelson

Dept. of Neurosurgery and Trauma Unit, Rambam Medical Center, Haifa

Current guidelines for management of suspected head and abdominal injuries are based on retrospective studies like that of Wisner & al, Following a recent review in this journal by Y. Kluger & al, which was based on non-Israeli data, we decided to define the current status at our trauma center.

We compare our data of 18 months of hospital admissions for acute trauma in which head CTs were done with those of 5 articles advocating specific protocols for decisions in pre-laparotomy diagnosis.

In the 861 cumulated cases, compared with the 800 of Wisner & al, craniotomy was required in 15% vs 7% (p<0.05); laparotomy was much less frequent, 2.7% vs 12.9% (p<0.05). The chance of finding a case requiring both craniotomy and laparotomy was 1 in 300.

As the clinical condition of multiple trauma involving the head and abdomen is becoming less frequent and includes diverse situations, a comprehensive algorithm might be inaccurate. Good clinical judgment of the clinician and teamwork are therefor preferable.

Microlaparoscopy in Diagnostic and Operative Gynecologic Procedures 

Dov Dicker, Shmuel Nitke, Itai Bar-Hava, Raul Orvieto, Zion Ben-Rafael, Arie Dekel

Depts. of Obstetrics and Gynecology, Rabin Medical Center, Beilinson and Golda Campuses, Petah Tikva; and Sackler School of Medicine, Tel Aviv University

A recent further development in laparoscopic surgery is microlaparoscoopy. The technique is identical to standard 10 mm laparoscopy except for the use of small, 2 mm scopes and trocars. We used this technique in 19 patients treated from June 1998 to February 1999.

The advantages of microlaparoscopy are: smaller incisions, less risk of damage to pelvic organs and less postoperative pain. However, the use of microlaparoscopy for operative procedures is limited to simple operations due to the limited field of vision. We urge our colleagues to consider microlaparoscopy whenever diagnostic laparoscopy is needed.

Cortical Blindness Following Coronary Angiography 

Addie Ron, Simcha Meisel, Myra Shapiro-Feinberg,Herman O. Klein

Depts. of Medicine, Cardiology and Diagnostic Imaging,Meir Medical Center, Kfar Saba

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas.

We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

Early Detection of Glaucoma by a Mobile Unit

S. Kurtz, M. Goldenfeld, S. Melamed

Sam Rothberg Glaucoma Center, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer

Glaucoma, the third leading cause of blindness in the western world, is characterized by painless, gradual loss of visual fields which may lead to severe visual impairment or even blindness. In 4 years of operation of a mobile glaucoma unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95 years were screened (4504 women, 45%); 55% were under 50 years (Graph 1).

Ocular hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%, with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of those screened were normal (Fig. 4; age stratification, Graph 3).

POAG increased with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was no correlation between incidence of POAG and place of work except in the Sorek Nuclear Center (1.9% vs. 0.8%, p=0.11). Other conditions significantly more frequent in POAG than normals were diabetes mellitus (x 2.5), systemic hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

Endoscopic Sinus Surgery for Extracranial Complications of Sinusitis

E. Deutsch, I. Hevron

ENT Dept., Bikur Cholim Hospital, Jerusalem

Orbital subperiosteal abscess (SPA) and Pott's puffy tumor (PPT) are the major extracranial complications of acute sinusitis. These complications are aggravated by the close anatomic relationships between the nasal sinuses and the orbits and frontal bone. Furthermore, the rich diploic venous drainage of the region enhances the spread of the infection.

Between 1992 and 1997, 16 patients (mean age 12 years, range 2-15, 10 of them males), 11 of them with SPA and 4 with PPT were operated on by the senior author by means of endoscopic sinus surgery (ESS). Indications for operation included: CT findings of abscess formation and lack of clinical improvement after 48 hours of IV antibiotic therapy. Clinical resolution of symptoms was achieved in all and there were no operative or postoperative complications.

We emphasize and explain the advantages of ESS over external approaches in surgery for extracranial complications of acute sinusitis by several facts: the technique treats the source of the disease, clinical success rate is high, morbidity is low, and facial distortion and poor cosmetic results completely avoided.

Employment of Immigrant Russian Physicians 

Nurit Nirel

JDC-Brookdale Institute of Gerontology and Human Development, Jerusalem

This study examined trends in the employment of immigrant physicians from the former Soviet Union. We studied the changes in the proportion of immigrants employed as physicians between 1994 and 1998, job characteristics, positions, professional status, and improvement in employment characteristics, professional status, and in wages due to increased seniority.

The study population consisted of 7,000 physicians who had immigrated to Israel by June 1992 and had applied to the Ministry of Health for medical licensing. Of these, 726 were interviewed in 1994 and in 1998 all 726 were again approached and 84% were interviewed by telephone.

Of those interviewed in 1998, 63% were working as physicians, 21% in another occupation, and 16% were not working at all. Of those with medical licenses, 79% were working as physicians. Of those interviewed in 1994, 93% were still employed as physicians in 1998, and 88% of them had been so employed continuously. As of 1998, 85% of those interviewed had 5 or more years seniority as physicians in Israel, and half had been working for more than 5 years at their current place of employment.

The best predictor-variable for employment as a physician in 1998 was employment as a physician in 1994. The proportions of those employed by a public employer, of those earning monthly salaries, and of those with a tenured position, were greater in 1998 than in 1994.

In 1998, 70% reported being employed in a authorized staff position. Funding for the salaries of 75% of these physicians came from the budget of their place of employment, not from a grant, stipend, or temporary fund for the assistance of immigrants. These proportions increased with seniority. The proportions of specialists (22%) and residents (37%) had increased in 1998 relative to 1994 (when they were 8% and 23% respectively). In addition, since 1994 gross hourly wages had increased with seniority in real terms by more than 100%.

These findings are evidence of work stability and improvement in employment conditions of these immigrant physicians. Further, the 1998 follow-up indicated a trend toward becoming "established" and improvement in professional status. However, it also revealed models of temporary employment, not in compliance with physicians' collective work agreements, a situation that warrants examination. It is also important to examine the implications of the absorption of so many physicians for medical manpower in Israel, and for overall expenditure on health.