Israel Medical Association Journal

Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Seroconversion to cytomegalovirus occurs in 1%-4% of pregnant women, most of whom are seropositive prior to pregnancy. In 0.2%-2.5% of their newborn infants there is evidence of intrauterine infection; most are born without any clinical findings The typical clinical symptoms of symptomatic congenital CMV[1] are observed in 10-20% of infected neonates. They include intrauterine growth restriction, microcephaly, hepatosplenomegaly, petechiae, jaundice, thrombocytopenia, anemia, chorioretinitis, hearing loss and/or other findings. Long-term neurodevelopmental sequelae include mental retardation, motor impairment, sensorineural hearing loss and/or visual impairment. These may occur even in infants who are free of symptoms at birth. Most infants born with severe neonatal symptoms of congenital CMV are born to mothers with primary infection during pregnancy. However, since about half of the infants infected with CMV in utero, including those with severe neonatal symptoms, are born to mothers with preconceptional immunity, we have to conclude that congenital CMV may be a significant problem even in children born to mothers with pre-pregnancy immunization. This may justify the use of invasive methods for the detection of possible fetal infection even in cases of non-primary CMV infection. This should also be a consideration when deciding upon population screening or immunization for CMV.

Background: Unconscious adults with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32–34ºC (ILCOR recommendations, 2003) when the initial rhythm is ventricular fibrillation.

Objectives: To assess the technique, safety and efficacy of mild induced hypothermia in patients after OHCA[1] due to VF[2].

Methods: Patients were cooled using the MTRE CritiCoolÔ external cooling system. Cold intravenous fluids were added to achieve faster cooling in 17 patients. Data were collected prospectively and patients were analyzed according to their neurological outcome on discharge, defined by their cerebral performance category.

Results: From February 2002 to September 2006, 51 comatose VF patients with OHCA underwent MIH[3]. Treatment was discontinued early in five because of hemodynamic instability; goal temperature was reached in 98% and maintained for an average of 19.5 hours; 61% had a favorable outcome (CPC[4] 1–2) and 37% died. Improved outcome was observed with longer hypothermia time and possibly when time from collapse to return of spontaneous circulation was < 25 minutes.

Conclusions: MIH, using an external cooling system, is simple and feasible, reduces mortality and protects neurological function. Four major factors seem to influence outcome: age, co-morbidities, duration of hypothermia, and possibly the length of time from collapse to ROSC[5].

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: 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.  
 

Objectives: To investigate the incidence of splenic emboli treated in a single general internal medicine department over the last 3 years.

Methods: We examined the records of a 35 bed internal medicine department in a hospital in the center of Israel.

Results: Over a period of 3 years 13 patients admitted to one internal medicine department developed acute abdominal pain and areas of hypoperfusion in the spleen on contrast computed tomography imaging. The patients were treated with anticoagulants, their course was benign and there were no long-term sequelae.

Conclusions: Embolus to the spleen is not rare in an internal medicine department. Diagnosis can be easily made by contrast CT scanning and treatment with anticoagulants results in a good prognosis. 

Background: The Muslim Circassians in Israel represent a unique ethnic community, distinct from Jews and Arabs. This endogamous group has a limited genetic variability that allows studying risk factors associated with type 2 diabetes.

Objectives: To estimate the prevalence of type 2 diabetes among Israeli Circassians and its correlation to obesity and genetic susceptibility.

Methods: Israeli Circassian women (n=450) and men (n=289) older than 35 were included in the study. They were classified as having or not having diabetes, and their risk factors, including hypertension, body mass index, family history of diabetes, and laboratory tests, were examined retrospectively.

Results: The age-adjusted prevalence of diabetes among the 739 participants was 12% (men 14.6%, women 10.7%). It was higher among those with BMI[1] > 30 than in those with lower BMI and a family history of diabetes without high BMI. But the risk of diabetes with BMI > 30 plus a family history was three times higher than when these factors were missing (odds ratio 2.96, 95% confidence interval 1.30–6.6). Multivariate analysis, however, found familial history of diabetes to be the strongest risk factor, independent of obesity (OR[2] 2.47, 95% CI[3] 1.45–4.20).

Conclusions: The results yielded by this homogeneous Circassian population, sharing the same environmental influences and having an endogamous pattern of marriage, suggest a role of genetic risk factors for diabetes. Israeli Circassians are suitable for additional genetic studies that may lead to the identification of susceptibility genes for type 2 diabetes.

Objectives: To assess the prevalence of reversible and treatable cardiovascular risk factors among 26’477 healthy Israeli adults: 23’339 men and 3138 women aged 25-55 years.

Methods: We collected data during routine examinations performed as part of a screening program for Israel Defense Force personnel.

Background: The degree of left ventricular dysfunction determines the prognostic outcome of patients with acute myocardial infarction.

Objectives: To define the clinical, angiographic and procedural variables related to LV[1][1] dysfunction in patients with  with anterior wall AMI[1][2] referred for primary percutaneous coronary intervention.

Methods: The sample included 168 patients treated by primary PCI[1][3] for first anterior wall AMI. Clinical, demographic and medical data were collected prospectively into a computerized registry, and clinical outcome (death, reinfarction, major cardiovascular event) were evaluated during hospitalization and 30 days after discharge. Patients were divided into three groups by degree of LV dysfunction (mild, moderate, severe) and compared for clinical, angiographic and procedural variables.

Results: LV dysfunction was associated with pre-PCI renal failure (serum creatinine > 1.4 mg/dl), peripheral vascular disease, high peak creatine kinase level, longer door to balloon time, low TIMI flow grade before and after PCI, and use of an intraaortic balloon pump. On multivariate analysis adjusted for baseline differences, peak creatine kinase level (r = 0.3, P = 0.0001) and door to needle time (r = 0.2, P = 0.008) were the most significant independent predictors of moderate or severe LV dysfunction after anterior AMI.

Conclusion: Abnormal LV function after first anterior AMI can be predicted by door to balloon time and the size of the infarction as assessed by creatine kinase levels. Major efforts should be made to decrease the time to myocardial reperfusion.

[1][1] LV = left ventricular

[1][2] AMI = acute myocardial infarction

[1][3] PCI = percutaneous coronary intervention 

Objectives: To describe the technique of CEL[1] and present our clinical results in the management of patients with CSM[2] due to multilevel compressive disease.

Methods: All patients undergoing CEL during the period 1984–2000 were identified. Of these, 24 of 25 patients had complete clinical information. Mean follow-up was 18 months (range 4–48). Mean age was 60 years (range 45–72). One patient underwent CEL at three levels, 22 at four to five levels and 1 patient at six levels The primary outcome measure was improvement in spinal cord function (according to the Nurick classification).

Results: Twenty-three (96%) of the patients experienced relief of their symptoms. Of these, 11 patients showed improvement in their Nurick grade, 12 patients were unchanged and one had worsening. Intraoperative complications (epidural bleeding and dural tear) occurred in six patients. Two patients developed a late kyphosis.

Conclusions: Our treatment of choice for multilevel CSM is canal expansive laminoplasty as initially described by Hirabayashi. It provides the ability for posterior surgical decompression without compromising the mechanical stability of the spine. This approach has the benefit of not requiring internal fixation and fusion. Our clinical outcome and surgical complication rate is comparable to other studies in the literature.