Shay Weiss PhD, Shmuel Yitzhaki PhD and Shmuel C. Shapira MD MPH
Abstract
During recent months, the Centers for Disease Control and Prevention (CDC) announced the occurrence of three major biosafety incidents, raising serious concern about biosafety and biosecurity guideline implementation in the most prestigious agencies in the United States: the CDC, the National Institutes of Health (NIH) and the Federal Drug Administration (FDA). These lapses included: a) the mishandling of Bacillus anthracis spores potentially exposing dozens of employees to anthrax; b) the shipment of low pathogenic influenza virus unknowingly cross-contaminated with a highly pathogenic strain; and c) an inventory lapse of hundreds of samples of biological agents, including six vials of variola virus kept in a cold storage room for decades, unnoticed. In this review we present the published data on these events, report the CDC inquiry’s main findings, and discuss the key lessons to be learnt to ensure safer scientific practice in biomedical and microbiological service and research laboratories.
Avinoam Shiran MD, Eric Remer, Ihab Asmer, Basheer Karkabi MD, Eran Zittan MD, Aliza Cassel PhD, Mira Barak PhD, Orit Rozenberg PhD, Khaled Karkabi MD and Moshe Y. Flugelman MD
Abstract
Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.
Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.
Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.
Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).
Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk.
Michal M. Amitai MD, Lisa Raviv-Zilka MD, Marjorie Hertz MD, Zippora Erlich PhD, Eli Konen MD, Shomron Ben-Horin MD and Sara Apter MD
Abstract
Background: Only a few studies have compared the accuracy of magnetic resonance enterography (MRE) and computed tomography enterography (CTE) in the diagnosis of Crohn's disease and its complications.
Objectives: To compare the sensitivity of MRE and CTE analysis in their ability to detect, sign-by-sign, 10 classical imaging signs of Crohn's disease.
Methods: The study group comprised 42 biopsy-proven Crohn's disease patients who underwent both CTE and MRE within an average period of 6 weeks. Agreement between the two modalities in detecting the 10 most significant radiological signs of CD was evaluated using the Kappa index. The sensitivity of MRE and CTE was calculated using a standard of reference composed of all the findings seen by CTE and/or MRE. We analyzed MRE and CTE sensitivity separately in two groups, according to the time interval between the examinations.
Results: Agreement between CTE and MRE was more than 70% in 8 of the 10 signs: mural thickening, phlegmon, stenosis, skip lesions, mucosal stratification, fistula, abscess, and creeping fat. The Kappa level of agreement values for CTE versus MRE varied between substantial for phlegmon and skip lesions; moderate for fistula, creeping fat, abscess and mural thickening; and fair for stenosis and dilatation. CTE detected more findings than MRE, except for creeping fat and fistula. There was no significant difference in the sensitivity of CTE and MRE in the two groups defined by the time interval (time < 1.5 and time > 1.5 months) except for detection of dilatation.
Conclusions: Almost all imaging signs of Crohn's disease were detected equally well by both modalities regardless of the time interval between examinations. We therefore consider MRE to be reliable for imaging and follow-up in patients with Crohn's disease who may need recurrent imaging.
Yacov Shacham MD, Eran Leshem-Rubinow MD, Arie Steinvil MD, Gad Keren MD, Arie Roth MD and Yaron Arbel MD
Abstract
Background: In the era of primary percutaneous coronary intervention (PPCI), information on the incidence and prognostic significance of high degree atrioventricular block (AVB) in ST elevation myocardial infarction (STEMI) patients is limited.
Objectives: To assess the incidence, time of onset, predictors and prognostic significance of high degree AVB in a large cohort of consecutive STEMI patients undergoing PPCI.
Methods: We retrospectively studied 1244 consecutive STEMI patients undergoing PPCI. Patient records were reviewed for the presence of high degree AVB, its time of occurrence and relation to in-hospital complications, as well as long-term mortality over a 5 year period.
Results: High degree AVB was present in 33 patients (3.0%), in 25 (76%) of whom the conduction disorder occurred prior to PPCI. Twelve patients (36%) required temporary pacing, all prior to or during coronary intervention, and all AVB resolved spontaneously before hospital discharge. AVB was associated with a significantly higher 30 day (15 % vs. 2.0%, P = 0.001) and long-term mortality rate (30% vs. 6.0%, P < 0.001). Time of AVB had no effect on mortality. In a multivariate regression model, AVB emerged as an independent predictor for long-term mortality (hazard ratio 2.8, 95% confidence interval 1.20–6.44, P = 0.001).
Conclusions: High degree AVB remains a significant prognostic marker in STEMI patients in the PPCI era, albeit transient.
Yael Shachor-Meyouhas MD, Alla Fesenko MD, Zipi Kra-Oz PhD, Irina Zaidman MD, Moran Szwarcwort-Cohen PhD, Einat Shafran MSc and Imad Kassis MD
Abstract
Background: Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.
Objective: To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.
Methods: Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006–June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.
Results: Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.
Conclusions: HHV6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.
Naomi Nussinovitch MD PhD, Konstantin Esev MD, Merav Lidar MD, Udi Nussinovitch MD PhD and Avi Livneh MD
Abstract
Background: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF.
Objectives: To evaluate ANS function in colchicine non-responders by using the HRV tool.
Methods: The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls.
Results: No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters.
Conclusions: Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults.
Arieh Riskin MD MHA, Corina Hartman MD and Raanan Shamir MD
Abstract
Parenteral nutrition (PN) must be initiated as soon as possible after delivery in very low birth weight (VLBW) preterm infants in order to prevent postnatal growth failure and improve neurodevelopmental outcome. When administered early, high levels of parenteral amino acids (AA) are well tolerated and prevent negative nitrogen balance. Although proteins are the driving force for growth, protein synthesis is energy demanding. Intravenous lipid emulsions (ILE) constitute a good energy source because of their high energy density and provide essential fatty acids (FA) along with their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives necessary for central nervous system and retinal development. Early supply of ILE is not associated with increased morbidity. No significant differences were found between ILE based on soybean oil only and mixed ILE containing soybean oil in combination with other fat sources, except for a reduction in the incidence of sepsis with non-pure soybean ILE, and possibly less PN-associated liver disease with mixed ILE containing some fish oil. In preterm infants glucose homeostasis is still immature in the first days of life and abnormalities of glucose homeostasis are common. VLBW infants may not tolerate high levels of glucose infusion without hyperglycemia. Administering lower levels of glucose infusion as part of full early PN seems more successful than insulin at this stage. Postpartum there is a transition period when the water and electrolyte balance may be severely disturbed and should be closely monitored. Avoiding fluid overload is critical for preventing respiratory and other morbidities
Barak Benjamin MD, Roy Zaltzman MD PhD, Baruch Shpitz MD, Carlos R. Gordon MD DSc and Shmuel Avital MD
Yuval Tal MD PhD, Ido Weinberg MD MSc, Arie Ben-Yehuda MD and Mordechai Duvdevani MD
Haim Shmilovich MD, Itzhak Herz MD and Gad Keren MD
Omri Braver MD and Yosef Leibman MD
Shany Sherman MD and Eli Karniel MD
Abdulla Watad MD, Victor Belsky MD, Yehuda Shoenfeld MD FRCP MaACR and Howard Amital MD MHA
Amnon Y. Zlotnick MD ,Tamar Gaspar MD, Ronen Rubinshtein MD, David Halon MD and Amir Elami MD