Israel Medical Association Journal

Background: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated.

Objectives: To analyze demographic, clinical and laboratory data of AGEP[1] cases in Israel, based on the RegisCAR study, a multinational European study.

Methods: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system.

Results: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10–60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs.

Conclusions: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, unique findings consisting of marked female predominance, seasonality and a profile of culprit drugs were noted.

7.4.10.6.04

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: 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.
 

Background: As the shortcomings of the Bentall operation and its variants in the Marfan syndrome have become apparent, the recent cusp-sparing techniques (remodeling or reimplantation) bear promise of better mid-term and long-term outcomes.

Objective: To examine the results of aortic root surgery in patients with Marfan syndrome.

Methods: During the period March 1994 to September 2007, 220 patients underwent aortic valve-sparing surgery; 20 were Marfan patients (group 1) who were compared with another 20 Marfan patients undergoing composite aortic root replacement (group 2). Fourteen patients had aortic dissection and 26 had thoracic aortic aneurysm. There were 31 males and 9 females with a mean age of 37.9 ± 13.8 years. In group 1, reimplantation was used in 13 patients, remodeling in 4, and aortic valve repair with sinotubular junction replacement in 3. In group 2, a mechanical valve conduit was used. Mean logistic Euroscore was 12.27 ± 14.6% for the whole group, five of whom were emergent cases

Results: Group 2 had more previous cardiac procedures compared to group 1 (9 vs. 2, P = 0.03) and shorter cross-clamp time (122 ± 27.1 vs. 153.9 ± 23.7 minutes, P = 0.0004). Overall mortality was 10%. Early mortality was 10% in group 2 and 5% in group 1(NS). Mean follow-up time was 25 months for group 2 and 53 months for group 1. Three patients were reoperated; all had undergone the remodeling. Five year freedom from reoperation and death was 86% and 90% in group 2 and 70% and 95% in group 1 (P = 0.6, P = 0.6), respectively.

Conclusions: Late survival of patients with Marfan syndrome was similar in both groups. Root reconstruction tends towards a higher incidence of late reoperations if the remodeling technique is used. We now prefer to use the reimplantation technique.
 

Management of asthma is currently based on symptoms (in children, usually a second-hand report from parents) and lung function measurements. Inhaled steroids, targeted at controlling airway inflammation, are the mainstay of asthma management. Due to possible side effects they should be used at the lowest possible doses while asthma is adequately controlled. Fractional exhaled nitric oxide is a simple non-invasive method to assess inflammation in asthma and its role in asthma management is increasing in popularity. The present review summarizes recent research on the use of FeNO[1] in monitoring airway inflammation and optimizing asthma management. The addition of FeNO measurements to the conventional assessment of asthma control appears promising. The practicability of including this measuring method into everyday clinical practice is currently being evaluated.

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: 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: With the development of computer technology and the high-tech electronic industry over the past 30 years, the technological age is flourishing. New technologies are continually being introduced, but questions regarding the economic viability of these technologies should be addressed.

Objectives: To identify the medical technologies that are currently in use in different rehabilitation medicine settings in Israel

Methods: The TECHNO-R 2005 survey was conducted in two phases. Beginning in 2004, the first survey used a questionnaire with open questions relating to the different technologies in clinical use, including questions on their purpose, who operates the device (technician, physiotherapist, occupational therapist, physician, etc.), and a description of the treated patients. This questionnaire was sent to 31 rehabilitation medicine facilities in Israel. Due to difficulties in comprehension of the term “technology,” a second revised standardized questionnaire with closed-ended questions specifying diverse technologies was introduced in 2005. The responder had to mark from a list of 15 different medical technologies which were in use in his or her facility, as well as their purpose, who operates the device, and a description of the treated patients.

Results: Transcutaneous electrical nerve stimulation, the TILT bed, continuous passive movement, and therapeutic ultrasound were the most widely used technologies in rehabilitation medicine facilities. Monitoring of the sitting position in the wheelchair, at the bottom of the list, was found to be the least used technology (with 15.4% occurrence). Most of the technologies are used primarily for treatment purposes and to a lesser degree for diagnosis and research.

Conclusions: Our study poses a fundamental semantic and conceptual question regarding what kind of technologies are or should be part of the standard equipment of any accredited rehabilitation medicine facility for assessment, treatment and/or research. For this purpose, additional data are needed.
 

Background: Burns are a major public health problem, with long hospitalization stay in both intensive care units and general wards. In Israel about 5% of all hospitalized injuries are burn injuries. There are no long-term epidemiological studies on burn injuries in adults in Israel.

Objectives: To identify risk factors for burn injuries and provide a starting point for the establishment of an effective prevention plan.

Methods: We analyzed the demographic, etiologic and clinical data of 5000 burn patients admitted to the five major hospitals with burn units in Israel during a 7 year period (1997–2003). Data were obtained from the records of the Israeli National Trauma Registry. The differences between various groups were evaluated using the chi-square test.

Results: Male gender was twice as frequent as female gender in burn patients (68.0% vs. 31.9%), and Jewish ethnicity was more common than non-Jewish (62.3% vs. 36.8%). Second and third-degree burns with body surface areas less than 10% constituted the largest group (around 50%). The largest age group was 0–1 years, constituting 22.2% of the cases. Inhalation injury was uncommon (1.9%). The most common etiologies were hot liquids (45.8%) and open fire (27.5%). Children less than 10 years old were burnt mainly by hot liquids while the main cause of burns for adults > 20 years old was an open flame. The majority of burns occurred at home (58%); around 15% were work related. The mean duration of hospitalization was 13.7 days (SD 17.7); 15.5% were in an intensive care unit with a mean duration of 12.1 days (SD 17.1). Surgical procedures became more common during the period of the study (from 13.4% in 1998 to 26.59% in 2002, average 19.8%). The mortality rate was 4.4%. We found a strong correlation between burn degree and total body surface area and mortality (0.25% mortality for 2nd to 3rd-degree burns with less than 10% TBSA[1], 5.4% for 2nd to 3rd-degree burns with 20–39% TBSA, and 96.6% for burns > 90% TBSA). The worst prognosis was for those over the age of 70 (mortality rate 35.3%) and the best prognosis was for the 0–1 year group (survival rate 99.6%).

Conclusions: The groups at highest risk were children 0–1 years old, males and non-Jews (the incidence rate among non-Jews was 1.5 times higher than their share in the general population). Those with the highest mortality rate were victims of burns > 90% TBSA and patients older than 70. Most burns occurred at home.

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.