Israel Medical Association Journal

Background: Multiple case series, mostly highly selected, have demonstrated a very high mortality following acute basilar artery occlusion. The more widespread availability and use of non-invasive vascular imaging over recent years has increased the rate of ABAO[1] diagnosis.

Objectives: To estimate the proportion of diagnosed ABAO among all-cause ischemic stroke in an era of increasing use of non-invasive vascular imaging and to compare the characteristics and outcomes between these two groups.

Methods: We compared 27 consecutive cases of ABAO identified in a university hospital between 2003 and 2007 to 311 unselected cases of ischemic stroke from two 4 month surveys.

Results: ABAO diagnosis increased from 0.3% of all-cause ischemic stroke (2003–2004) to 1.1% (2007), reflecting the increased use of non-invasive vascular imaging. In comparison to all-cause ischemic stroke, ABAO patients were younger (mean age 60 vs. 71 years), were more likely to be male (89% vs. 60%), had less atrial fibrillation (7% vs. 26%), more severe strokes (baseline NIHSS over 20: 52% vs. 12%), higher admission white cell count (12,000 vs. 9000 cells/mm³) lower admission systolic blood pressure (140 ± 24 vs. 153 ± 27 mmHg), higher in-hospital mortality rates (30% vs. 8%) and worse functional outcome (modified Rankin scale ≤ 3, 22% vs. 56%) (P < 0.05 for all). Rates of reperfusion therapy for ABAO increased from 0 in 2003–2004 to 60% in 2007.

Conclusions: In this study, ABAO patients represented approximately 1% of all-cause ischemic stroke and were about a decade younger than patients with all-cause ischemic stroke. We report a lower ABAO mortality compared to previous more selected case series; however, most survivors had a poor functional outcome. Given the marked clinical heterogeneity of ABAO, a low threshold for non-invasive vascular imaging with a view to definitive reperfusion treatment is needed.

Background: Diabetes mellitus is a multi-organ disorder affecting many types of connective tissues, including bone and cartilage. Certain skeletal changes are more prevalent in diabetic patients than in non-diabetic individuals. A possible association of diabetes mellitus and lumbar spinal stenosis has been raised.

Objectives: To compare the prevalence of diabetes mellitus in patients with spinal stenosis, degenerative disk disease or osteoporotic vertebral fractures.

Methods: A cross-sectional analysis was performed of 395 consecutive patients diagnosed with spinal stenosis, degenerative disk disease or osteoporotic vertebral fractures. All the patients were examined by one senior author in the outpatient orthopedic clinic of a large general hospital between June 2004 and January 2006 and diagnosed as having either lumbar spinal stenosis (n=225), degenerative disk disease (n=124) or osteoporotic vertebral fractures (n=46).

Results: The prevalence of diabetes mellitus in the three groups (spinal stenosis, osteoporotic fracture, degenerative disk disease) was 28%, 6.5% and 12.1%, respectively, revealing a significantly higher prevalence in the spinal stenosis group compared with the others (P = 0.001). The higher prevalence of diabetes in the stenotic patients was unrelated to the presence of degenerative spondylolisthesis.

Conclusions: There is an association between diabetes and lumbar spinal stenosis. Diabetes mellitus may be a predisposing factor for the development of lumbar spinal stenosis.

Background: Studies from many countries have reported an increasing prevalence of autistic spectrum disorder in childhood. No comprehensive epidemiological studies of ASD[1] have been performed in Israel.

Objectives: To describe time trends in the reported number of patients with ASD in Israel and to characterize the demographic features of the reported patients.

Methods: We reviewed the charts of the National Insurance Institute of Israel from 1972 to 2004 for all children with a diagnosis of ASD receiving disability benefits.

Results: A total of 3509 children met the study criteria. Eighty percent were boys and 98% were Jewish. The incidence data showed an increase in the number of cases from zero in 1982–84 and 2 (1.2 per million capita under 18 years) in 1985 to a high of 428 cases in 2004 (190 per million).

Conclusions: This is the first comprehensive study of the incidence of ASD in Israel. According to data derived from official health records, the rate of occurrence of ASD has substantially increased in the last 20 years. Further studies are needed to determine if this is a true increase or if the findings were confounded by external factors, such as recent improvements in diagnostic measures and social stigmas.

The Ink4a-Arf locus, which encodes two distinct tumor suppressor proteins, is inactivated in many cancers. Whereas p16^Ink4a is an inhibitor of cyclin D-dependent kinases, p19^Arf (p14^ARF in humans) antagonizes the E3 ubiquitin protein ligase activity of Mdm2 to activate p53. We now recognize that Arf functions in both p53-dependent and -independent modes to counteract hyper-proliferative signals originating from proto-oncogene activation, but its p53-independent activities remain poorly understood. Arf proteins are highly basic (> 20% arginine content, pI > 12) and predominantly localize within nucleoli in physical association with an abundant acidic protein, nucleophosmin (NPM/B23). When bound to NPM[1], Arf proteins are relatively stable with half-lives of 6–8 hours. Although mouse p19^Arf contains only a single lysine residue and human p14^ARF has none, both proteins are N-terminally ubiquitinated and degraded in proteasomes. Through as yet uncharacterized mechanisms, p19^Arf induces p53-independent sumoylation of a variety of cellular target proteins with which it interacts, including both Mdm2 and NPM. A naturally occurring NPM mutant (NPMc) expressed in myeloid leukemia cells redirects both wild-type NPM and p19^Arf to the cytoplasm, inhibits Arf-induced sumoylation, and attenuates p53 activity. Thus, ubiquitination and sumoylation can each influence Arf tumor suppressor activity.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel.

Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was conducted using logistic regression analysis adjusting for confounders.

Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often, and infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale ≥3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3–0.8) and at 30 day follow-up (adjusted OR[1] 0.6, 95%CI[2] 0.3–0.9). A Functional Independence Measure score ≤90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2–0.8).

Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Various events occurring during pregnancy might influence the normal neurogenesis of fetus brain, including exposure to the influenza virus. Several studies have attempted to find a relationship between exposure to influenza virus and the onset of schizophrenic behavior in childhood or adulthood, however results remain contradictory. In this review we describe several animal and human studies that show or do not show a relationship between exposure to the influenza virus during pregnancy and the subsequent development of schizophrenia.

Background: In the developing child the nervous system undergoes a maturation process. The development and organization of any motor ability is the naturally adopted preference among the possibilities and constraints. The motor behavior of children with cerebral palsy is a personal automatic preference based on such constraints. One of the clinical measures designed for measuring the function of children with CP[1] is the Gross Motor Function Measure. Motor development curves for children with CP have been established based on the GMFM[2] instrument and Gross Motor Function Classification System.

Objectives: To examine the change over time in gross motor function for children with CP attending a special education school for handicapped children in Israel.

Method: We conducted a retrospective review of the medical records of children at various ages and with varying degrees of severity who were being treated by a multidisciplinary team. The study population comprised 106 children aged 3–8 years with CP who were attending the school of special education at Assaf Harofeh Medical Center. The GMFM-88 test was performed annually for the study children over a 7 year period (1995–2001).

Results: During the study period the GMFM measures scores improved significantly. The rate of improvement and top achievements over the years differed according to the severity of the motor impairment. The gross motor development reached a plateau at the age of 6–7 years.

Conclusions: The changes in gross motor development of the study population were similar to the profile of changes in the developmental process of children who develop normally. The nature of the curves of gross motor change for the children with CP should be borne in mind when designing individual treatment goals and strategies for a child.

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.