Israel Medical Association Journal

It is common knowledge that in addition to the slaughter of millions of innocent civilians, Nazism caused direct damage to patient care by euthanasia of the handicapped, gruesome human experimentation, and ethnic cleansing of German medical schools. In gastroenterology, 53 prominent academicians living in Nazi-occupied Europe were persecuted by the Nazis. Prior studies analyzed this persecution as it related to gastroenterologists rather than to patient care. What is not known, however, is that Nazi persecution led to a delay of more than one generation in the clinical application of major inventions by these gastroenterologists. These included flexible fiberoptic endoscopy, which was delayed from 1930 to 1957. Fiberoptic transmission was invented by Heinrich Lamm in 1930. Lamm was exiled from Nazi Germany in 1936, and this technique was clinically applied to endoscopy by Hirschowitz only in 1957. Another innovation was fecal occult blood testing for early colon cancer detection, which was devised by Ismar Boas before 1938. Boas committed suicide under Nazi oppression in 1938 and this modality was clinically applied by Greegor only in 1967. The acceptance of refugees from Nazi Germany or Austria into America or into the future State of Israel helped mitigate some of this damage. For example, eight eminent academic gastroenterologists who fled Nazi-occupied countries to then mandatory Palestine made major contributions to the development of academic gastroenterology in the soon-to-be established State of Israel.

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: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs[1].

Objectives: To evaluate the effect of 20 weeks of EPO[2]-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.

Methods: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate.

Results: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC[3] and PMNL counts and ALP[4] activity following treatment. EPO retarded the deterioration in GFR[5]. The percent of PMNLs expressing EPO-R[6] was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.

Conclusions: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

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: Reports of burn injuries in children are usually made by highly specialized burn units. Our facility admits children with burns < 20% total body surface area, while those with major burns are transferred to burn units at tertiary care facilities.

Objectives: To review our experience with thermal burns.

Methods: We conducted a retrospective review of all thermal burns admitted to our hospital during a 5 year period.

Results: Among 266 patients (69.2% boys) aged 3.5 ± 3.6 years, children < 3 years old were the most frequently injured (64.7%). Scalds (71.4%) were the most common type of burn. Partial thickness burns were sustained by 96.6% of children and TBSA[1] burned was 4.2 ± 3.6%. The mean hospital stay was 3.8 ± 4.5 days, and was significantly prolonged in girls (4.6 ± 4.8 vs. 3.5 ± 4.3 days, P = 0.01). Percent TBSA burned was correlated with patient age (r = 0.12, P = 0.04) and length of hospital stay (r = 0.6, P < 0.0001). Six patients (2.3%) (mean age 3.4 ± 2.3 years) were hospitalized in the Pediatric Intensive Care Unit due to toxin-mediated illness.

Conclusions: Children under the age of 3 years are at increased risk for burn injury, but older children sustain more extensive injuries. Prevention and awareness are needed for child safety.

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: Iron deficiency and lead poisoning are common and are often associated. This association has been suggested previously, mainly by retrospective cross-sectional studies.

Objective: To assess the impact of short-term lead exposure at indoor firing ranges, and its relationship to iron, ferritin, lead, zinc protoporphyrin, and hemoglobin concentrations in young adults.

Methods: We conducted a clinical study in 30 young healthy soldiers serving in the Israel Defense Forces. Blood samples were drawn for lead, zinc protoporphyrin, iron, hemoglobin and ferritin prior to and after a 6 week period of intensive target practice in indoor firing ranges.

Results: After a 6 week period of exposure to lead dust, a mean blood lead level increase (P < 0.0001) and a mean iron (P < 0.0005) and mean ferritin (P < 0.0625) decrease occurred simultaneously. We found a trend for inverse correlation between pre-exposure low ferritin levels and post-exposure high blood lead levels.

Conclusions: The decrease in iron and ferritin levels after short-term lead exposure can be attributed to competition between iron and lead absorption via divalent metal transport 1, suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come readily to every physician's mind when treating patients with a potential risk for each problem separately.
 

Capsule endoscopy was launched at the beginning of this millennium and has since become a well‑established tool for evaluating the entire small bowel for manifold pathologies. CE[1] far exceeded our early expectations by providing us with a tool to establish the correct diagnosis for such elusive gastrointestinal conditions as obscure gastrointestinal bleeding, Crohn's disease, polyposis syndrome and others. Recent evidence has shown CE to be superior to other imaging modalities – such as small bowel follow‑through X-ray, colonoscopy with ileoscopy, computerized tomographic enterography, magnetic resonance enteroclysis and push enteroscopy – for diagnosing small bowel pathologies. Since the emergence of CE, more than 500,000 capsules have been swallowed worldwide, and more than 700 peer-reviewed publications have appeared in the literature. This review summarizes the essential data that emerged from these studies.

The completion of the human genome mapping project has provided the necessary backdrop for the development of high throughput array technologies. In contrast to the reductionist approach to studying the role of a particular molecule in a specific pathway, these technologies enable us to conduct a comprehensive survey of various molecular profiles across different cells types and individuals, placing us one step closer to understanding integrative regulatory networks and the workings of the cell as a whole.