Ori Lev PhD and Bracha Rager-Zisman PhD
Emerging and re-emerging infections cause huge concern among public health workers and international and national bodies such as the World Health Organization (WHO) and the U.S. National Institutes of Health (NIH). Indeed, scientists around the world express the view that despite the danger, research on these emerging virulent pathogens is crucial and must continue. While most of the studies underway are targeted at improving and protecting public health, some studies bear potentially serious risks resulting from misuse. These studies are defined as dual-use research (DUR) of concern, where it is not evident that the benefits outweigh the risks. The H5N1 controversy has pushed various governments to institute new policies to govern such research. We describe the regulations that govern this emerging field of research in the United States and Israel, two countries that have taken leading stands on these issues. We suggest that the existing policies are able to mitigate many of the risks that this research encapsulates, yet more work is required – especially on the global level.
Yedidia Bentur MD, Yael Lurie MD, Alfred Cahana MD, Nona Kovler MD, Anna Bloom-Krasik MD, Bella Gurevych MD and Wendy Klein-Schwartz PharmD MPH
Background: The Israel National Poison Information Center (IPIC), Rambam Health Care Campus, provides 24 hour telephone consultations in clinical toxicology as well as drug and teratogen information. It participates in research, teaching and regulatory activities, and also provides laboratory services.
Objectives: To report data on the epidemiology of poisonings and poison exposures in Israel.
Methods: We made computerized queries and descriptive analyses of the medical records database of the IPIC during 2012.
Results: A total of 31,519 poison exposure cases were recorded, a 157.6% increase compared with 1995. Children < 6 years of age were involved in 43.1% of cases; 74.0% of calls were made by the public and 23.7% by physicians; 74.8% of exposures were unintentional and 9.1% intentional. Chemicals were involved in 35.8% of all cases (single and multiple substances), pharmaceuticals in 48.8%, bites and stings in 3.8%, and plants and mushrooms in 1.6%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.4%. Substances most frequently involved in moderate/major exposures were corrosives, insecticides and snake venom. Four fatalities were recorded; all were intentional exposures in adults (corrosive, medications, energy drink).
Conclusions: Poison exposures and poisonings have increased significantly and have contributed substantial to morbidity and mortality in Israel. The IPIC database is a valuable national resource for the collection and monitoring of poisoning exposure cases. It can be used as a real-time surveillance system for the benefit of public health. It is recommended that reporting to the IPIC become mandatory and its activities be adequately supported by national resources.
Alex Margulis MD, Ehud Alperson and Allan Billig MD
Background: Cleft lip repair with the Millard technique has undergone many modifications throughout the years, yet analysis of the successes of these various methods is still lacking.
Objectives: To make a quantitative evaluation of the outcomes obtained after unilateral cleft lip surgical repair using the Kernahan and Bauer technique with primary rhinoplasty.
Methods: Five anatomical parameters for evaluating upper lip and nostril symmetry were compared between the cleft and the normal side at least 1 year post-surgery in 23 children who underwent unilateral cleft lip repair with this particular technique.
Results: Surgical success (defined as a 10% or less deviation between the cleft and contralateral side) was achieved for four of the five parameters: distance between oral commissure and peak of cupid’s bow, nasal sill width, distance between peak and lowest point of Cupid’s bow, and vertical distance between the highest point of the philtral column and lowest point of the upper lip. Surgical success was not achieved for the last parameter, namely, length of philtral column.
Conclusions: Unilateral cleft lip repair using the Kernahan and Bauer technique with primary cleft rhinoplasty is mostly successful when aiming to achieve symmetry between the cleft and the normal side of the upper lip. Success was elusive in achieving symmetry between the philtral columns, despite an overall average difference of only 1.2 mm.
Joseph Menczer MD, Letizia Schreiber MD, Esther Berger PhD, Erez Ben-Shem MD, Abraham Golan MD FRCOG and Tally Levy MD
Background: Elevated serum levels of the epithelial marker CA125 are occasionally observed in leiomyosarcoma (LMS) patients.
Objectives: To assess the immunohistochemical expression of this marker in the tissue of LMS.
Methods: The consecutive unselected records of all patients with LMS diagnosed during the period 1995–2012 were located and abstracted. After verification of the diagnosis, 4 µm unstained slides were prepared from each case for immunohistochemical staining for CA125. Sections of ovarian carcinoma known to express CA125 were used as positive controls.
Results: We located 17 LMS patients from the period under study. Bleeding was the presenting symptom in 9 patients; the diagnosis was established prior to treatment in 11 patients. The tumor was in an advanced stage in 6 patients, and in 7 unstaged patients it was grossly confined to the uterus. Ten patients died within 14 months after the diagnosis. Serum CA125 levels prior to treatment were assessed in only 8 patients and were above normal limits (> 35 U/ml) in 3 of them. Two of the three with elevated serum levels were in stage III, and the third was an unstaged apparent stage I patient. None of the LMS tissue specimens demonstrated immunohistochemical expression of CA125.
Conclusions: CA125 was not immunohistochemically expressed in the tissue of any LMS tumors examined by us. The origin of elevated serum CA125 in some of these tumors is therefore not in its tissue and remains unknown.
Maya Wertman MD, Charles Milgrom MD, Gabriel Agar MD, Yael Milgrom MD, Newton Yalom and Aharon S. Finestone MD
Background: Medical evaluation of a suspected meniscus injury begins with a history-taking and physical examination. Suspected meniscus injuries not responding to treatment are usually sent for imaging to confirm the diagnosis before arthroscopy. Tc-MDP bone single photon emission computed tomography (SPECT) scan has been suggested as an alternative to magnetic resonance imaging (MRI) in evaluating suspected knee meniscus tears.
Objectives: To examine the accuracy of knee SPECT as a tool to identify meniscus tears versus that of MRI as compared to the gold standard of arthroscopy.
Methods: The Israel Defense Forces database for 2005 through 2009 was searched according to the key words knee MRI, knee SPECT and knee arthroscopy. We identified 330 subjects who had undergone both a single knee SPECT and a single knee MRI prior to knee surgery. The medical files of 193 of the 330 subjects were randomly selected for review. A comparison was made between the preoperative SPECT and MRI studies and the arthroscopic finding. The sensitivity, specificity and accuracy were calculated.
Results: The subjects’ age was 21.3 ± 3.9. The agreement between SPECT and arthroscopy was 0.14 for the medial meniscus and 0.29 for the lateral meniscus. The agreement between MRI and arthroscopy was 0.59 for the medial meniscus and 0.69 for the lateral meniscus. SPECT scan was found to be 61% sensitive, 54% specific and 58% accurate in detecting common knee pathology, whereas MRI was found to be 95% sensitive, 67% specific and 85% accurate.
Conclusions: Knee SPECT has a lower sensitivity, specificity and accuracy than MRI in evaluating meniscal injuries and its use can result in increased unnecessary surgery.
Michael Arad MD Msc, Lorenzo Monserrat MD PhD, Shiraz Haron-Khun MSc, Jonathan G. Seidman PhD, Christine E. Seidman MD, Eloisa Arbustini MD PhD, Michael Glikson MD and Dov Freimark MD
Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.
Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.
Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.
Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.
Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.
Ran Stein MD, David Neufeld MD, Ivan Shwartz MD, Ilan Erez MD, Ilana Haas MD, Ada Magen MD, Elon Glassberg MD, Pavel Shmulevsky MD and Haim Paran MD FACS
Background: Discharge summaries after hospitalization provide the most reliable description and implications of the hospitalization. A concise discharge summary is crucial for maintaining continuity of care through the transition from inpatient to ambulatory care. Discharge summaries often lack information and are imprecise. Errors and insufficient recommendations regarding changes in the medical regimen may harm the patient’s health and may result in readmission.
Objectives: To evaluate a quality improvement model and training program for writing postoperative discharge summaries for three surgical procedures.
Methods: Medical records and surgical discharge summaries were reviewed and scored. Essential points for communication between surgeons and family physicians were included in automated forms. Staff was briefed twice regarding required summary contents with an interim evaluation. Changes in quality were evaluated.
Results: Summaries from 61 cholecystectomies, 42 hernioplasties and 45 colectomies were reviewed. The average quality score of all discharge summaries increased from 72.1 to 78.3 after the first intervention (P < 0.0005) to 81.0 following the second intervention. As the discharge summary’s quality improved, its length decreased significantly.
Conclusions: Discharge summaries lack important information and are too long. Developing a model for discharge summaries and instructing surgical staff regarding their contents resulted in measurable improvement. Frequent interventions and supervision are needed to maintain the quality of the surgical discharge summary.
Ari Zimran MD, Gheona Altarescu MD and Deborah Elstein PhD
Ricardo Silvariño MD MSc, Oscar Noboa MD and Ricard Cervera MD PhD FRCP
Basement membranes form an anatomic barrier that contains connective tissue. They are composed of type IV collagen, laminin and proteoglycans. Anti-basement membrane antibodies bind to the non-collagen site of the α3 chain of type IV collagen. A group of renal diseases, pulmonary diseases and perhaps others affecting different organs have long been associated with the presence of antibodies directed against glomerular basement membrane (GBM), alveolar basement membrane and tubular basement membrane. Goodpasture disease has a frequency of 0.5 to 1 case by million/year, and is responsible for up to 20% of crescentic glomerulonephritis in renal biopsy. It has been associated with genetic and immune abnormalities and there are usually environmental triggers preceding clinical onset. Renal disease can occur isolated or in association with pulmonary hemorrhage. In general, renal disease has a rapid progression that determines severe compromise, with rare spontaneous resolution. The diagnosis of Goodpasture disease requires the presence of the anti-GBM antibody, either in circulation or in renal tissue. The prognosis of non-treated patients is poor. The standard of care is plasma exchange combined with prednisone and cyclophosphamide. Anti-GBM antibody levels must be monitored frequently until their disappearance, and then every 6 months to confirm sustained remission in the absence of clinical signs of recurrence. Prognosis of the disease is strongly associated with its initial presentation. Survival rates are related to the degree of renal compromise at onset of the disease. Recurrence of the disease post-transplantation is low.
Eva Zold MD PhD, Edit Bodolay MD PhD, Balazs Dezső MD PhD, Györgyike Soos MD PhD, Britt Nakken PhD and Peter Szodoray MD PhD