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.

Identifying the Elderly at Risk for Falling 

D. Galinsky, V. Fried, A. Biderman, J. Cwikel, Y. Ben Moshe

Geriatric Dept., Soroka University Hospital and Depts. of Family Medicine and of Social Work, Faculty of Health Sciences, Ben-Gurion University of the Negev; and ESHEL, Beer Sheba

Falling is one of the main problems affecting the health of the elderly. A community project was carried out to detect elderly people at high risk for falls. One of its aims was also to develop tools allowing primary care professionals to detect the elderly at risk for falling. Such a screening test in the community-dwelling elderly (EFST) and a protocol for diagnosis and treatment of the elderly at risk for falls is presented.

Diabetic Ketoacidosis during the Ramadan Fast 

I. Friedrich, Y. Levy

Dept. of Medicine A, HaEmek Medical Center, Afula, and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

We report a 15-year-old Muslim boy with insulin-dependent diabetes mellitus (IDDM) who presented with diabetic ketoacidosis (DKA) during the Muslim Ramadan month of day-time fasting. DKA apparently occurred due to omitting pre-lunch insulin combined with dehydration and overeating during the permitted sunset-to-sunrise meals.

It is well-known that fasting accelerates development of lipolysis and ketosis and increases glucagon levels. Thus, these pathophysiological aberrations related to fasting in ketosis-prone patients, in conjunction with fasting, endanger metabolic control in IDDM.

Spinal and Extra-Spinal Tumors Mimicking Discal Herniation

E. Tamir, Y. Mirovsky, D. Robinson N. Halperin

Orthopedics Dept., Assaf Harofeh Medical Center, Zerifin

Low back pain radiating to a limb is usually caused by lumbar disc herniation. Tumors of the spinal cord or near the sciatic or femoral plexus can cause neural compression and clinical signs similar to those of disc herniation. Such tumors are usually misdiagnosed as discal herniation and appropriate treatment is delayed. We present 4 men who had tumors causing low back pain radiating to the leg: a 70-year-old with metastatic squamous cell carcinoma of the lung, a 20-year-old with aneurysmal bone cyst of the vertebral column, a 52-year-old with retroperitoneal sarcoma and a 32-year-old who also had retroperitoneal sarcoma. Diagnosis and trwere delayed because the clinical symptoms were ascribed to lumbar disc herniation. The latter 2 patients had CT-scans showing lumbar disc herniation, but similar findings are common among asymptomatic individuals.

The differential diagnosis of low back pain radiating to the leg should include tumor when there is a history of cancer, pain not relieved by conservative treatment nor by lying down, pain is increased at night, pain accompanied by weight loss, and when physical examination demonstrates injury to more than 1 nerve root. In these circumstances work-up should include EMG, radioisotope scan and CT of the pelvis.

Congenital Syphilis: Need for Adequate Antenatal Care

Mark Friedberg

Pediatrics B Dept., Soroka Medical Center, Beer Sheba

Congenital syphilis is well-known and treatable with penicillin. Diagnosis in the neonate and young child may be difficult and consequently morbidity and mortality can be high. Prevention in children is of utmost importance and can be achieved by proper antenatal care and adequate follow-up of pregnant women. This includes identification of pregnant women at risk for contracting syphilis. The case presented demonstrates this need.

Breast Conservation: Safe for Early Breast Cancer

Gil Bar-Sella, Georgetta Fried, Zipora Brotman, Anna Ravkin, Riva Borovik, Abraham Kuten

Dept. of Oncology, Rambam Medical Center; Dept. of Oncology, Lin Medical Center; and Rappaport Faculty of Medicine, Technion, Haifa

Between 1981-1993 581 women with primary breast cancer were treated by breast conservation. Their mean age was 56‏12 years and 63% were postmenopausal and 37% pre- or perimenopausal. The median follow-up time was 56 months. 45% had pathological Stage I disease, 49% Stage II, 2.5% Stage III and 3.5% clinical Stage I-II disease. 54% of lesions were excised with good margins, 10% with close margins (<0.5 cm), 9% with microscopic residual, 3% with macroscopic residual, and in 24% margins were not reported. Adjuvant therapy, consisting of combination chemotherapy and/or hormones, was given to 69%.

Radiotherapy, usually 50 Gy tangential photon irradiation to the whole breast, was given to 564 (97%); an electron or photon "boost" to the tumor with a median dose of 17.5 Gy was given to 378 (65%). Most of those with positive nodes received 50 Gy to the lymphatic drainage system.

1 year after radiotherapy cosmetic results were rated as "good" or "excellent" in 80%, "moderate" in 17% and "poor" in 3%. The 5-year actuarial survival was 97% in Stage I and 88% in Stage II. 37 patients (6.5%) developed breast recurrence; 11 of these (2%) had simultaneous distant metastases. 5 (<1%) developed axillary or supraclavicular lymph node metastases, and 81 (14%) developed distant metastases. Most local recurrences were in those younger than 40, and in those with primary tumors >1.75 cm.

The satisfactory level of local control achieved is attributed to the high doses of radiation (up to 75 Gy) administered to those with high risk lesions.

Ferritin in Adult Still's Disease

E. Flatau, N. Reichman, N. Kaufman

Dept. of Medicine B, Central Hospital of the Emek, Afula and Technion Faculty of Medicine, Haifa

Adult-onset Still's disease (AOSD) is characterized by a spiking fever and diverse clinical findings; the diagnosis is often delayed for months or even years. The only positive laboratory finding is neutrophilic leukocytosis. Since 1987, the diagnostic importance of elevated serum ferritin levels has been discussed in numerous papers, but is not yet among the diagnostic criteria for AOSD. We describe a case in which the finding of extreme hyperferritinemia enabled prompt diagnosis and treatment.

Propafenone Dose for Emergency Room Conversion of Paroxysmal Atrial Fibrillation

D. Antonelli, A. Darawsha, S. Rimbrot, N.A. Freedberg, T. Rosenfeld

Dept. of Cardiology and Emergency Room, Central Emek Hospital, Afula

Paroxysmal atrial fibrillation (AF), a frequent cause of repeated hospitalization, is effectively treated with propafenone. The time to conversion to sinus rhythm is a consideration when managing AF in the emergency room. We investigated the conversion rates of paroxysmal AF by 3 different oral propafenone (P) regimens, in terms of time to conversion.

188 patients with onset of AF within 48 hours were treated with propafenone (P): 48 received 600 mg as a first oral dose followed after 8 hrs by 150 mg (Group A); 82 received 300 mg as a first dose, followed by the same dose 3 and again 8 hrs later (B); 58 received 150 mg every 3 hrs, up to a total dose of 600 mg (C). P was stopped when sinus rhythm was achieved.

Rates of conversion to sinus rhythm after 3 hrs in the 3 groups were: 46%, 41% and 26% respectively; after 8 hrs: 77%, 78% and 70%; and after 12 hrs: 81%, 84% and 76%. Treatment was discontinued in 8. There was excessive QRS widening (>25% of the basal value) in 1 in group A, 1 in group B and 2 in group C; wide-QRS tachycardia occurred in 4 in group B. In Group A there was a higher rate of early successful conversion, with a lower incidence of side-effects than with the other regimens.

Acute Malaria in an Israeli Tourist to Kenya

Doron Zamir, Chen Zamir, Shimon Storch, Moni Litmanovich, Paltiel Weiner

Dept. of Internal Medicine A, Hadera Sub-District Health Office and Nephrology Dept. and Intensive Care and Infectious Disease Units, Hillel Yaffe Medical Center, Hadera

Malaria is 1 of the main causes of death in third world countries. It has become extinct in Israel and imported cases are rare, since most visitors to endemic countries take anti-malarial prophylaxis. We report an Israeli tourist to Kenya infected with falciparum malaria complicated by severe metabolic acidosis, renal failure and adult respiratory distress syndrome. After intensive care treatment this preventable condition improved.

Tension-Free "Plug and Patch" Inguinal Hernia Repair

Y. Mintz, D. Goitein, M. Muggia-Sullam

Dept. of General Surgery, Hadassah-Hebrew University Hospital, Jerusalem

Inguinal hernias are common and have highly variable clinical presentations, ranging from the asymptomatic to surgical emergencies when incarcerated, sometimes necessitating bowel resection. Several techniques have been described for repair of inguinal hernias based on the unique anatomic structure of the inguinal region. In 1989 Lichtenstein and co-workers described a "tension free" repair based on using a synthetic mesh patch to reinforce the inguinal canal floor and as a plug to prevent recurrence through the internal inguinal ring. This technique has been used in many centers worldwide with good rates of success.

Epidural Spinal Abscess

E. Tamir, Y. Mirovsky, N. Halperin

Orthopedics Dept., Assaf Harofeh Medical Center, Zerifin

A 42-year-old man was admitted for fever and severe low back pain radiating to both legs. On MRI, an epidural spinal abscess from S1 to D10 was seen. Treatment included laminectomy, drainage of the abscess and antibiotics. Recovery was complete without neurological damage. Increased awareness of this disease may lead to diagnosis and treatment.

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Willingness to Donate Organs: Attitude Survey among Israeli Jews

Peri Kedem-Friedrich, Rina Rachmani

Psychology Dept., Bar-Ilan University, Ramat Gan and Information and Education Unit, Israel Transplant Center

A public opinion survey of Israeli Jewish adults (September) showed a large potential willingness to donate organs after death, while only a third of the sample was opposed. Nevertheless, only a very minor proportion held donor's cards, and over half expressed opposition to holding a donor card. As to next-of-kin's organs, when the wishes of the relative were not known, a quarter of the sample opposed, a quarter agreed, and the remaining half hesitated to make a decision.

Willingness to donate was not correlated with gender, age or income, but was related to religiosity: the more religious, the less willing to donate. And the religious reason was the salient one given for hesitation about donating, although there were many who could give no reason for their hesitation. Family members, doctors and rabbis (in ascending order) influenced willingness to consent to next-of-kin donations.

Epidemiology of Invasive Hemophilus Influenzae B Infections in Bedouins and Jews; Conjugate Hib Vaccines

Limor Gortzak-Uzan*, Drora Fraser, Ron Dagan

Pediatric Infectious Disease Unit and Dept. of Epidemiology, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba

From 1989 to 1996, 139 cases of invasive Hemophilus influenzae B (Hib) infections were identified in children in the Negev, 110 of which occurred before introduction of the conjugate vaccine (1989-92). At that time there were 60.5 cases of Hib per 100,000 in the Negev among children under 5 years of age. During 1995-1996, when Hib conjugate vaccine was part of the regular immunization program, Hib decreased to 6.5 cases per 100,000 in that age group. The effectiveness of PRP-OMP vaccine was 96.5% among Jews and 89% among Bedouins, and the efficacy of the immunization program was 99.99%. This degree of success exceeded all expectations based on the literature. During the whole study period, Hib infections were more frequent among Bedouins than Jews. There was no significant difference in the occurrence of Hib among Jews in the Negev before and after the vaccine was introduced. Hib among Bedouins in the Negev was significantly more frequent than in the Israeli population as a whole before the vaccine was introduced. That gap narrowed after the vaccine was introduced because of the decrease in morbidity among the 2 groups.

* Medical student.

Pheochromocytoma Multi-Organ Crisis: Nonseptic Hyperthermia and Shock

Michael Y. Shapira, Elena Zuckerman, Taufic Zuebi, Oded Jurim

Divisions of Medicine and Surgery, Hadassah-University Hospital; Geriatrics Dept.; Herzog Hospital, Jerusalem; and Dept. of Medicine, Yoseftal Hospital, Eilat

Pheochromocytoma usually presents with nonspecific symptoms such as headache, palpitation, chest pain and hypertension. We present a 48-year-old woman hospitalized due to a pheochromocytoma multi-organ crisis (PMC). It consists of a tetrad of symptoms: multi-organ failure, hyperthermia, encephalopathy and unstable blood pressure. Distinguishing PMC from septic shock may be difficult, and requires needs a high clinical index of suspicion.