Israel Medical Association Journal

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: Fungal infection of the nail affects millions of people worldwide and has an estimated prevalence of more than 10% of the general population.

Objectives To determinate the prevalence of fungal infection in toenails, in order to decide the treatment policy in onychomycosis.   

Methods: We evaluated 331 patients with suspected clinical toenail onychomycosis affecting at least two toenails. Mycological examination of the affected nails was performed, both the KOH test and fungal culture were used. 

Results: Of 331 patients with psoriasis, 78.2% of the patients had at least three infected nails. The first toenail was the most affected. Trichophyton rubrum was by far the most common dermatophyte cultured from all samples.

Conclusions: Most of the patients had at least three affected toenails. Topical treatment is not effective or practical, and systemic treatment should therefore be considered.
 

Background: In contrast to the relative scarcity of donor kidneys and hearts, the potential supply of deceased donor pancreata is exceeding the demand. However, this potential organ surplus is not being fully realized because in current transplantation practice the duration of pancreas storage before transplantation is limited and many organs with established or anticipated cold ischemia time exceeding 8–10 hours are discarded owing to the extreme vulnerability of pancreatic tissue to anaerobic damage caused by preservation.

Objectives: To reduce cold ischemic injury in order to increase the utilization of donor pancreases in Israel for whole-organ and cell transplantation.

Methods: We evaluated a novel two-layer preservation oxygenated cold storage method that uses perfluorocarbon to continuously supply oxygen to the pancreas during preservation in conventional University of Wisconsin solution.

Results: Pancreatic tissue morphology, viability and adenosine-triphosphate content were serially examined during preservation of the pig pancreas for 24 hours either by a two-layer or by conventional simple cold storage. Already after 12 hours of storage, the superiority of the two-layer method over the University of Wisconsin method was apparent. Starting at this time point and continuing throughout the 24 hours of preservation, the tissue architecture, mitochondrial integrity, cellular viability and ATP[1] tissue concentration were improved in samples preserved in oxygenated UW[2]/PFC[3] as compared to controls stored in conventional UW solution alone.

Conclusions: The UW/PFC two-layer preservation method allowed tissue ATP synthesis and amelioration of cold ischemic tissue damage during extended 24 hour pancreas preservation. This method could be implemented in clinical practice to maximize utilization of pancreata for whole-organ and islet transplantation as well as for pancreas sharing with remote centers.

Background: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and increased dosage is not allowed. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease.

Objectives: To describe our experience with anti-TNF[1] therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results.

Methods: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects.

Results: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n=108), juvenile idiopathic arthritis (n=11), psoriatic arthritis (n=37), ankylosing spondylitis (n=29), adult Still's disease (n=4), overlap disease (RA[2] and scleroderma or polymyositis, n=6), temporal arteritis (n=1), polyarteritis nodosa (n=1), dermatomyositis (n=1), amyloidosis secondary to RA (n=1) and Wegener's granulomatosis (n=1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS[3] and PS[4] patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease.

Conclusion: Our daily practice data are generally in agreement with worldwide experience. The ‘deviations’ might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

Background: Bisphosphonates are effective in the prevention and treatment of osteoporosis, yet their use is suboptimal.

Objectives: To measure bisphosphonate compliance among first-time users and identify factors associated with compliance.

Methods: We conducted a prospective follow-up of all women aged 45+ in the second largest health management organization in Israel who were prescribed bisphosphonates for the first time. The 4448 women were classified by drug dosage. Persistence and adherence measures of compliance were calculated for each woman over a 1 year period.

Results: Mean bisphosphonate persistence over a year was 216 days, with a mean medication possession ratio of 66%. Women whose medication was changed, whether from weekly to daily or daily to weekly, always had better persistence rates than those who consistently took the original dose. Persistence rates were as follows: 264 days for women who switched back and forth between daily and weekly doses, 229 days for those who switched from daily to weekly, 222 days for those who took the dosage weekly only, 191 days for those who switched to daily dosage, and 167 days for those who took the dosage daily only (P < 0.001). Switchers were also more likely to have adequate adherence rates (MPR[1] ≥ 80%): 81.3%, 76.6%, 67.5%, 61.3% and 52.2% respectively (P < 0.001). More than 20% of women stopped taking their medication within the first month. Women with higher supplemental insurance (offering significant discounts for weekly dose medications) had better persistence rates: 221 vs. 208 days (P = 0.03). Younger women and women on national pension insurance had the lowest persistence rates: 204 and 209 days respectively.

Conclusions: While weekly bisphosphonate takers had better compliance rates, persistence and adherence rates were inadequate for all groups. Changing medication to meet the needs of the patient, discounting weekly medications, and providing follow-up within the first months of prescription may promote compliance. 

Background: Non-operative management following abdominal stab wounds is possible in selected patients who are both hemodynamically stable and do not have signs of peritonitis. However, the rate of failure of non-operative management is higher in Israel than in western countries.

Objectives: To assess the patterns of injury following abdominal stabbing.

Methods: Data from the Israeli Trauma Registry were used to identify all patients with abdominal stab injury admitted to eight different trauma centers between 1997 and 2004.

Results: The number of patients admitted per year more than doubled between 1997 and 2004, from 257 to 599. The percentage of patients with severe injury (Index Severity Score ≥ 16) increased from 9.4% to 19.0%. The incidence of multiple stab injuries almost doubled, from 37% to 62%.

Conclusions: Review of the data in the Israeli Trauma Registry indicates an increase in both absolute rate and relative incidence of serious stab injuries. This indicates that patterns of injury following stab wounds are not necessarily similar, not even within the same geographical area over time.
 

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

Background: Acute focal nephritis is an inflammatory process of the renal parenchyma affecting principally the cortex of the kidney. It is considered a midpoint in the spectrum of upper urinary tract infections, ranging from uncomplicated pyelonephritis to intrarenal abscesses, and until recently the hyperechoic sonographic appearance of this lesion was considered uncommon.  

Objectives: To determine the relative prevalence of hyperechoic and hypoechoic sonographic appearance of focal renal lesions in patients with the clinical diagnosis of acute pyelonephritis and to correlate the findings with those of the color Doppler examinations.

Methods: We reviewed the sonograms of 367 patients hospitalized with the clinical diagnosis of acute pyelonephritis. The sonograms were reviewed for acute renal inflammatory changes. When a focal lesion was detected, we noted the echogenicity, side, form, location and color Doppler characteristics.

Results: Abnormal sonographic findings related to the infection were found in 78 cases. In 52 patients a focal lesion was diagnosed. Forty-seven focal lesions appeared hyperechoic related to the adjacent parenchyma. These lesions were more frequently located at the upper pole and were wedge-shaped in most of the cases. The areas appeared hypo/avascular on the color Doppler examination.

Conclusions: Our data suggest that the most common appearance of acute focal nephritis is an area of increased echogenicity in the parenchyma of the affected kidney.
 

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.