Israel Medical Association Journal

Background: The national program for the prevention of Down syndrome includes screening (using the triple test) and invasive diagnostic tests in women at risk for a Down syndrome pregnancy. However, despite the program, the majority of Down syndrome infants are born alive (approximately 1/1000 live births)

Objectives: To determine whether the relatively high incidence of Down syndrome at birth in Israel is the result of failure of the preventive program or due to informed choices of the mothers.

Methods: We conducted a retrospective study using the national registry of Down syndrome for the years 1997 and 2004, according to the mothers' religion and place of residence and the reasons for prenatal diagnosis.

Results: Most of the babies affected with Down syndrome are born in religious or traditional conservative communities where termination of pregnancy is usually not an option.

Conclusions: In a pluralistic society like Israel with its diverse communities and dissimilar religious backgrounds and traditions, the different attitudes concerning utilization of the national program should be respected. It is necessary to tailor different approaches and solutions for the various ethnic and religious communities according to their need.
 

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases with an unknown etiology. Interleukin-18 is a pro-inflammatory cytokine that is up-regulated in Crohn’s disease. IL-18[1] binding protein neutralizes IL-18. The relationship of IL-18 and IL-18BP[2] and disease activity in these diseases is not fully understood.

Objectives: To investigate the correlation of IL-18 and IL-18BP with disease activity and other disease parameters in inflammatory bowel disease.

Methods: IL-18 and IL-18BP isoform α were measured in 129 patients and 10 healthy individuals. Patients' mean age was 40.5 (range 15–70 years) and 43 were women; 58 Crohn's and 28 colitis patients were in remission and 52 and 14, respectively, were in exacerbation. Twenty-three (19 and 4 respectively) were studied in both remission and exacerbation.

Results: The mean level of free IL-18 was significantly different between healthy individuals and Crohn's patients, and between Crohn's patients during exacerbation and remission (167 ± 32 vs. 471 ± 88 and 325 ± 24 pg/ml, respectively, P < 0.05). Mean level of IL-18BP was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (2.1 ± 1.1, 7.5 ± 4 and 5.23 ± 2.8 ng/ml, respectively, P < 0.01). In the colitis patients, mean free IL-18 level and IL-18BP were significantly different between healthy individuals and patients, but not between disease remission and exacerbation (167 ± 32, 492 ± 247 and 451± 69 pg/ml for IL-18, and 2.1 ± 1.1, 7.69 ± 4 and 6.8 ± 7 ng/ml for IL-18BP, respectively, P = 0.05).

Conclusions: IL-18 and IL-18BP levels are higher in patients with inflammatory bowel disease compared to healthy individuals. In Crohn's disease, but not in ulcerative colitis, IL-18 (but not free IL-18) and IL-18BP levels are significantly higher during exacerbation compared to remission. This observation highlights the importance of IL-18 in the pathogenesis of inflammatory bowel diseases, especially in Crohn's disease.

Background: Studies have found ethno-cultural disparities in health care delivery in different countries. Minority populations may receive lower standards of care.

Objectives: To test a hypothesis that Jewish Ethiopian women may be receiving less preventive recommendations than other women in Israel.

Methods: A telephone survey was conducted using a structured questionnaire designed specifically for this study in Hebrew, Russian and Amharic (Semitic language of Ethiopia). The study group included 51 post-menopausal women of Ethiopian origin, aged 50–75. The control group included 226 non-Ethiopians matched by age, some of whom were immigrants from the former Soviet Union. The questionnaire dealt with osteoporosis and breast cancer screening and prevention.

Results: All the parameters measured showed that the general population received more preventive treatment than did Jewish Ethiopian women, including manual breast examination, mammography, osteoporosis prevention, bone density scans, and recommendations for a calcium-rich diet, calcium supplementation, hormone replacement therapy, biphosphonates and raloxifen. On a logistic regression model the level of knowledge of the Hebrew language, age, ethnicity and not visiting the gynecologist were significantly related to not having received any preventive medicine recommendations.
Conclusions: Differences in cultural backgrounds and language between physicians and their patients may become barriers in the performance of screening and preventive medicine. Recognizing this potential for inequity and using methods to overcome these barriers may prevent it in the future

Renal vein occlusion in adults is usually a result of vein thrombosis, which is frequently associated with the nephrotic syndrome. The anatomy of renal vascularization is of primary importance for understanding its pathophysiological responses and the clinical and diagnostic presentation of patients with this condition. The reaction of the kidney to its vein occlusion is determined by the balance between the acuteness of the disease, extent of the development of collateral circulation, involvement of one or both kidneys and the origin of the underlying disease. Renal vein occlusion is generally a complication of some other condition, but may also occur as a primary event. The main goals of therapy should be to conserve renal parenchyma in order to maintain renal function and prevent thromboembolic phenomena.

Background: The decision to perform primary percutaneous coronary intervention in unconscious patients resuscitated after out-of-hospital cardiac arrest is challenging because of uncertainty regarding the prognosis of recovery of anoxic brain damage and difficulties in interpretation of ST segment deviations. In ST elevation myocardial infarction patients after OHCA[1], primary PCI[2] is generally considered the only option for reperfusion. There are few published studies and no randomized trial has yet been performed in this specific group of patients.

Objectives: To define the demographic, clinical and angiographic characteristics, and the prognosis of STEMI[3] patients undergoing primary PCI after out-of-hospital cardiac arrest.

Methods: We performed a retrospective analysis of medical records and used the prospectively acquired information from the Rambam Primary Angioplasty Registry (PARR) and the Rambam Intensive Cardiac Care (RICCa) databases.

Results: During the period March1998 to June 2006, 25 STEMI patients (21 men and 4 women, mean age 56 ± 11years) after out-of-hospital cardiac arrest were treated with primary PCI. The location of myocardial infarction was anterior in 13 patients (52%) and non-anterior in 12 (48%). Cardiac arrest was witnessed in 23 patients (92%), but bystander resuscitation was performed in only 2 patients (8%). Eighteen patients (72%) were unconscious on admission, and Glasgow Coma Scale > 5 was noted in 2 patients (8%). Cardiogenic shock on admission was diagnosed in 4 patients (16%). PCI procedure was successful in 22 patients (88%). In-hospital, 30 day, 6 month and 1 year survival was 76%, 76%, 76% and 72%, respectively. In-hospital, 30 day, 6 month and 1 year survival without severe neurological disability was 68%, 68%, 68% and 64%, respectively.

Conclusions: In a selected group of STEMI patients after out-of-hospital cardiac arrest, primary PCI can be performed with a high success rate and provides reasonably good results in terms of short and longer term survival.

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.

Background: Klippel-Trenaunay syndrome, a congenital disorder, is characterized by capillary malformation, varicosities and bony or soft tissue hypertrophy. Since there is no cure for this syndrome, treatment is directed towards secondary prevention of venous hypertension and preservation of functional integrity of the legs. Elastic stockings are the mainstay of treatment and are indicated in all cases. Surgery is reserved only for a few selected symptomatic patients, however the outcome is unsatisfactory in most cases, with recurrent pain, edema, poor cosmetic result and limb deformity. Ultrasound-guided foam sclerotherapy is a recently introduced minimally invasive ambulatory procedure for the treatment of chronic venous insufficiency. It was recently introduced to treat this disorder.

Objectives: To evaluate the efficacy of USFS[1] in the treatment of patients with Klippel-Trenaunay syndrome.

Methods: Seven patients diagnosed with Klippel-Trenaunay, with massive lower extremity involvement, were treated with USFS between October 2003 and October 2005. Sclerovein® (polidocanol, Resinag, Switzerland) 2–4% was used as the sclerosant. The signs, symptoms and overall patient satisfaction were assessed before, during and after the treatment.

Results: Patients' mean age was 26 years (range 15–54). The CEAP[2] clinical classification, with ascending severity ranging from 0 (no signs) to 6 (active venous ulcer), was C4 in 5 patients (71.5%) and C5 and C6 in one patient each. The average number of sessions was 14.5 (range 9–21). No major complications were encountered. All seven patients reported improvement in signs and symptoms. Five of the 7 patients (71%) were very satisfied with the cosmetic result.

Conclusion: USFS is an effective minimally invasive ambulatory technique, essentially pain-free and with excellent short-term results in patients with Klippel-Trenaunay syndrome (when the deep system is functional). Long-term results and larger study groups are warranted. 

Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies.

Background: Ethnicity has been associated with variance in warfarin treatment regimens in various settings.

Objectives: To determine whether ethnicity is associated with variance in patient management in Israel.

Methods: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender, specialty of attending physician, patient's age, and the country where the physician studied medicine.

Results: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients’ INR[1] tests within the target range was 62.3% among Jews (95% CI[2] 61.5–63.1) and 52.7% (95% CI 49.9–55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs.

Conclusions: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance.

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Background: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures.

Objectives: To evaluate the contribution of BMD[1], previous fractures, clinical and laboratory parameters to hip fracture risk assessment.

Methods: The study population included 113 consecutive hip fracture patients, aged 72.5 ± 9.4 years, discharged from the Department of Orthopedic Surgery113 consecutive patients, 87 women and 26 men, aged 50-90 years, mean ag. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores – compared to young adults and Z-scores – compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated.

Results: We observed T-scores ≤-2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty-eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 ± 5.8 ng/mg (normal 4–7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients.

Conclusions: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield.