Israel Medical Association Journal

Background: In both adjuvant arthritis and rheumatoid arthritis edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a signicant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats.

Objectives: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats.

Methods: Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day) and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, whole body mineral density and X-ray scans of synovial joints were evaluated as markers of inflammation and destructive changes associated with arthritis.

Results: Long-term prophylactic treatment with low dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of BMD[1] in AA[2] rats was significantly lower only in the group treated with the combination of Detralex+methotrexate.

Conclusion: Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Background: As high dietary n-6 polyunsaturated fatty acids and n-6:n-3 PUFA[1] ratio may contribute to many western ailments, increasing n-3 PUFA in foods could be beneficial. The nutritional significance of n-3 PUFA-fortified egg vs. enzymatically competitive high n-6 PUFA diets is debatable.

Objectives: To evaluate the dietary contribution of 'field fortification' of eggs by adding n-3 PUFA to high n-6 PUFA hen feed and whether it meets consumer preferences.

Methods: Laying hens (n=3500) were fed n-3 PUFA-fortified (5% extruded linseed) feed or standard (control) feed for 5 weeks. Nutritional significance was evaluated for western (American, Israeli) populations.

Results: Compared to regular (control) eggs, fortified eggs yielded a 3.8-fold increase in total n-3 PUFA, 6.4-fold alpha-linolenic acid (18:3), and 2.4-fold docohexaenoic acid 22:6). N-6:n-3 PUFA ratio decreased 3.6-fold, and n-6:n-3 long chain PUFA ratio threefold (P < 0.0003). Sensory evaluations were not significantly different. Egg cost increased by 1.0–1.5%. Fortified egg n-3 PUFA content averaged 14.3% of the current intake of Americans and 15.9% of Israelis – 9.8 and 10.5% of upper Dietary Reference Intakes, respectively. Egg DHA content averaged 32.9 and 41.1% of upper DRI[2]. Current cholesterol intakes average 281 and 263 mg/day (median 214 and 184 mg/day) including 0.7 and 0.5 egg/day; reported hypercholesterolemia rates are 17.7 and 16.5%, respectively.

Conclusions: Effective concentration and transformation of supplemental n-3 PUFA/LCPUFA[3] from feed to egg substantially enhanced egg n-3 PUFA %DRI, particularly of DHA[4], critical for health but often deficient. Such land-based n-3 PUFA/LCPUFA fortification may be applicable to high n-6 PUFA diets, fitting within cholesterol limitations and market criteria. It may contribute to general health and specific requirements (i.e., pregnancy and lactation), with possibilities of wide accessibility and standardization.

Background: Based on the outcome of several randomized controlled trials, the orally active leukotriene receptor antagonist montelukast (Singulair®, Merck) has been licensed for treatment of asthma. The drug is favored for treating childhood asthma, where a therapeutic challenge has arisen due to poor compliance with inhalation therapy.

Objectives: To assess the efficiency of and satisfaction with Singulair® in asthmatic children under real-life conditions.

Methods: Montelukast was prescribed for 6 weeks to a cohort of 506 children aged 2 to 18 years with mild to moderate persistent asthma, who were enrolled by 200 primary care pediatricians countrywide. Four clinical correlates of childhood asthma – wheeze, cough, difficulty in breathing, night awakening – were evaluated from patients' diary cards.

Results: Due to under-treatment by their physicians, almost 60% of the children were not receiving controller therapy at baseline. By the end of the study, which consisted of montelukast treatment, a significant improvement over baseline was noted in asthma symptoms and severity, as well as in treatment compliance. The participating pediatricians and parents were highly satisfied with the treatment.

Conclusions: The results of this extensive study show that the use of montelukast as monotherapy in children presenting with persistent asthma resulted in a highly satisfactory outcome for themselves, their parents and their physicians.
 

Background: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve prognosis in congestive heart failure and are the treatment of choice in these patients; despite this, the rates of ACE-I[1] usage in heart failure patients remain low in clinical practice.

Objectives: To evaluate the rate of ACE-I/ARB[2] treatment in hospitalized patients with CHF[3], and analyze the reasons for non-treatment.

Methods: We prospectively evaluated 362 consecutive patients hospitalized with CHF. Patients were evaluated for ACE-I/ARB usage at discharge and were followed for 1 year.

Results: At hospital discharge 70% of the patients were prescribed ACE-I/ARB treatment. Only 69% received recommended target or sub-target dosages, proven to improve prognosis. This decreased to 63% and 59% at 6 months and 12 months of follow-up respectively, due to a shift from sub-target levels to low dosages. Justified reasons for under-treatment were apparent in only 25% not optimally treated discharged patients and this decreased to 12% and 4% at 6 and 12 months follow-up, respectively. Common reasons for non-treatment at discharge were hyperkalemia and elevation in serum creatinine, while hypotension and cough were more prominent at follow-up. Clinical parameters associated with increased treatment rates were ischemic heart disease and the absence of chronic renal failure. Patients receiving treatment had lower hospitalization and mortality rates.

Conclusions: ACE-I/ARB treatment is still underutilized in patients discharged from hospital with a diagnosis of CHF. Increasing the awareness of the importance of these drugs may increase the number of patients treated.

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: Babies born with extreme prematurity and low birth weight (< 1000 g) present a unique treatment challenge. In addition to the complexity of achieving survival, they may require surgical interventions for abdominal emergencies. Usually, these infants are transferred to a referral center for surgery treatment. Since 2000 our approach is bedside abdominal surgery at the referring center.

Objectives: To evaluate whether the approach of bedside abdominal surgery at the referring center is safe and perhaps even beneficial for the baby.

Methods: We retrospectively reviewed our data since 2000 and included only babies weighing < 1000 g who were ventilated, suffered from hemodynamic instability and underwent surgery for perforated bowel at the referring neonatal unit. Results were analyzed according to survival from the acute event (> 1 week), survival from the abdominal disease (> 30 days) and survival to discharge.

Results: Twelve babies met the inclusion criteria. Median weight at operation was 850 g (range 620–1000 g) and median age at birth was 25 weeks (range 23–27). Eleven infants survived the acute event (91.7%), 9 survived more than 30 days (81.8%), and 5 survived to discharge.

Conclusions: Our results show that bedside laparotomy at the referring hospital is safe and feasible. A larger randomized study is indicated to prove the validity of this approach.

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment. 

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.