Dev Biol (Basel), 2002, 111, 321 - 6 Novel in vitro functional assays for the determination of anthrax toxin components; Hallis B et al.; The characterisation and evaluation of the UK licensed human anthrax vaccine depends on several in vivo tests that determine its safety and potency . Assays for the determination of functionally active and/or immunoreactive toxin components and S-layer proteins have been developed and applied to the characterisation of anthrax vaccine . These technologies may support production of consistent and effective vaccines, and may ultimately reduce the requirements for in vivo testing. J Biol Chem, 2003 Jul 11, 278(28), 25990 - 7 Epub 2003 Apr 03. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough; Soelaiman S et al.; Edema factor (EF) and CyaA are adenylyl cyclase toxins secreted by pathogenic bacteria that cause anthrax and whooping cough, respectively . Using the structure of the catalytic site of EF, we screened a data base of commercially available, small molecular weight chemicals for those that could specifically inhibit adenylyl cyclase activity of EF . From 24 compounds tested, we have identified one quinazoline compound, ethyl 5-aminopyrazolo{1,5-a}quinazoline-3-carboxylate, that specifically inhibits adenylyl cyclase activity of EF and CyaA with approximately 20 microm Ki . This compound neither affects the activity of host resident adenylyl cyclases type I, II, and V nor exhibits promiscuous inhibition . The compound is a competitive inhibitor, consistent with the prediction that it binds to the adenine portion of the ATP binding site on EF . EF is activated by the host calcium sensor, calmodulin . Surface plasmon resonance spectroscopic analysis shows that this compound does not affect the binding of calmodulin to EF . This compound is dissimilar from a previously described, non-nucleoside inhibitor of host adenylyl cyclase . It may serve as a lead to design antitoxins to address the role of adenylyl cyclase toxins in bacterial pathogenesis and to fight against anthrax and whooping cough. J Occup Environ Med, 2003 Mar, 45(3), 222 - 33 Analysis of adverse events after anthrax immunization in US Army medical personnel; Wasserman GM et al.; A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively . Active surveillance showed that localized reactions were common and occurred more often in women than men . Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction . Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals . Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization. Rev Neurol (Paris), 2003 Feb, 159(2), 162 - 4 {Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome}; Gherardi RK; Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001 . Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries . The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients . One third of patients develop an autoimmune disease, such as multiple sclerosis . Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis . Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy . Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid . Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile . It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome . Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms . Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome . Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome . Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis . Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome . Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant . If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide. Ann Emerg Med, 2003 Apr, 41(4), 447 - 52 Syndromic analysis of computerized emergency department patients' chief complaints: an opportunity for bioterrorism and influenza surveillance; Irvin CB et al.; STUDY OBJECTIVE: Emergency department computerized triage logs might be useful for automated ED surveillance and potentially for early identification of bioterrorism events . We describe a Web-based surveillance program and its feasibility for surveillance . METHODS: A Web-based surveillance program that receives computerized chief complaint data daily from a large academic urban teaching hospital and performs syndromic analysis on these data was developed . On the basis of preset limits, the Web-based surveillance program sends an alert e-mail message when the syndromic analysis reveals an increase in the number of patients in predefined symptom groups . The feasibility of this system was tested by using historical data during an influenza outbreak (December 1999 to January 2000) and applying the anthrax symptom group . RESULTS: The Web-based surveillance program identified the influenza outbreak in the first week . CONCLUSION: Computerized triage logs might be a feasible method for bioterrorism and influenza surveillance . The Web-based nature of the surveillance program creates the opportunity for other hospitals to contribute data, potentially resulting in an automated network of ED computerized triage log surveillance. Ann Emerg Med, 2003 Apr, 41(4), 441 - 6 Medical counterbioterrorism: the response to provide anthrax prophylaxis to New York City US Postal Service employees; Partridge R et al.; STUDY OBJECTIVE: We describe and analyze a recent rapid deployment of disaster medical assistance teams and other government agencies to provide medical screening and anthrax prophylaxis to New York City US Postal Service employees potentially exposed to letters contaminated with anthrax spores . METHODS: A description of the response effort is presented . Data were collected on standardized forms and included the numbers of postal employees screened and offered antibiotic prophylaxis, as well as the numbers of patients seen per worker hour by various medical professionals . RESULTS: One hundred members of 5 disaster medical assistance teams and other health professionals were deployed to New York City within 18 hours of activation . Over a 68-hour period, 7,076 patients were evaluated, representing all postal employees in the 6 major postal facilities in New York believed to be at risk for anthrax exposure . Of the total, 2,452 patients were seen during the first 24 hours, 3,875 during the second 24 hours, and the remaining 749 during the last 20 hours of operations . An average of 161 employees were screened per hour . The antibiotic most commonly dispensed was ciprofloxacin, followed by doxycycline and amoxicillin . CONCLUSION: The deployment of disaster medical assistance teams and other agencies to New York City to provide prophylaxis against inhalation anthrax to US Postal Service employees provides lessons for a rapid, efficient, and effective response to acts of bioterrorism . This deployment might also serve as a scaleable model for future events requiring medical prophylaxis. Proc Natl Acad Sci U S A, 2003 Apr 1, 100(7), 4346 - 51 Epub 2003 Mar 21. Emergency response to an anthrax attack; Wein LM et al.; We developed a mathematical model to compare various emergency responses in the event of an airborne anthrax attack . The system consists of an atmospheric dispersion model, an age-dependent dose-response model, a disease progression model, and a set of spatially distributed two-stage queueing systems consisting of antibiotic distribution and hospital care . Our results underscore the need for the extremely aggressive and timely use of oral antibiotics by all asymptomatics in the exposure region, distributed either preattack or by nonprofessionals postattack, and the creation of surge capacity for supportive hospital care via expanded training of nonemergency care workers at the local level and the use of federal and military resources and nationwide medical volunteers . The use of prioritization (based on disease stage andor age) at both queues, and the development and deployment of modestly rapid and sensitive biosensors, while helpful, produce only second-order improvements. J Ethnopharmacol, 2003 Apr, 85(2-3), 269 - 77 Medicinal use and social status of the soap berry endod (Phytolacca dodecandra) in Ethiopia; Esser KB et al.; Berries from Phytolacca dodecandra L'Herit . (endod in Amharic) offer a readily available molluscicide to control schistosomiasis . Parts of the endod plant have been used as a detergent and as traditional medicine for centuries in Ethiopia . An interview survey was performed in the highlands of Ethiopia to provide information on the distribution of the plant, people's traditional use of it, their perception of the plant, and the potential for increased production and use of endod as a soap for indirect control of schistosomiasis . People of all ages report that they are familiar with the plant and its detergent and medicinal uses . The plant is largely disappearing from unprotected areas due to land clearing . Younger people appear to use endod as a soap whenever it is available . Older women prefer commercial soap and consider endod to be associated with poor people . Common medicinal uses include treatment of skin itching (ringworm), abortion, gonorrhea, leeches, intestinal worms, anthrax and rabies . Two thirds of the people express interest in cultivating endod for personal use if supplied with rooted cuttings . Increased cultivation of endod and use of berries for washing might be possible if information about schistosomiasis and its control is disseminated among people . Preference for commercial soap and lack of land for cultivation are major obstacles for increasing the availability and use of endod. Vaccine, 2003 Apr 2, 21(15), 1620 - 8 Comprehensive systematic surveillance for adverse effects of anthrax vaccine adsorbed, US Armed Forces, 1998-2000; Lange JL et al.; Routine vaccinations of US military personnel with Anthrax Vaccine Adsorbed began in 1998 . To systematically identify clinical diagnoses reported more frequently after vaccination than before, all military personnel were retrospectively assigned to pre- or post-vaccination cohorts . Cohort assignments were based on vaccination statuses each day of the 3-year surveillance period . For each cohort, rates of hospitalizations and ambulatory visits for 843 specific diagnoses were calculated using data in a public health surveillance system . Compared to the pre-vaccination cohort, the post-vaccination cohort had statistically higher rates of hospitalizations for 17 diagnoses, of ambulatory visits for 34 diagnoses, and in both clinical settings for one diagnosis (malaria) . After accounting for systematic differences in coding/reporting and residual confounding, the number and nature of clinical diagnoses more frequent after anthrax vaccination than before were consistent with expectations due to random variation . This surveillance suggests that Anthrax Vaccine Adsorbed has few, if any, clinically significant adverse effects. East Afr Med J, 2002 Jul, 79(7), 364 - 7 Anthrax revisited; Bhatt KM et al.; BACKGROUND: Anthrax is an ancient disease affecting animals and humans . Sporadic cases of anthrax and small epidemics have been seen from time to time in different parts of the world and in Africa . However many clinicians are not very familiar with the various presentations and management of anthrax . It is relevant for the health care workers to re-familiarise themselves with all aspects of anthrax, with the impending threat of bioterrorism . OBJECTIVE: To familiarise healthcare workers on all aspects of anthrax . STUDY SELECTION: To describe epidemiology pathogenesis, clinical features, management and prevention of anthrax including measures to take when weapons grade anthrax is suspected . DATA SYNTHESIS: Three forms of the disease are recognised, cutaneous, inhalational and intestinal . Cutaneous anthrax is the most common form . Inhalation anthrax is the most severe form of anthrax . The treatment of anthrax in most cases is penicillin, however with the threat of bioterrorism, intentional releases of anthrax spores in the environment has caused much concern . Weapons grade anthrax of more virulent strain and resistant to commonly used antibiotics is possible . CONCLUSION: In view of the different clinical presentations and outcomes it is important that health care workers re-familiarise themselves with the disease and in the event of bioterrorism are able to take appropriate measures. Euro Surveill, 2002 May, 7(5), 78 - 84 Roles and functions of a European Union Public Health Centre for Communicable Diseases and other threats to health; Van Loock F et al.; An international consensus has been reached that a European Union (EU) Technical Coordination Structure (TCS) for communicable diseases is needed to improve Europe s future response to international communicable disease threats within and beyond its boundaries . After the American events of September 11 2001 and the deliberate releases of anthrax, the EU created a Health Security Committee, adopted a civil protection decision, and established for 18 months a team to develop responses for deliberate releases of biological and chemical agents . These two initiatives, the network s approach and health security work, must converge into a single stream addressing health protection for the people of Europe . They could be combined into a European Centre for Communicable Diseases that is planned to become active by 2005. Prehospital Disaster Med, 2002 Jul-Sep, 17(3), 119 - 25 Instrument development and evaluation of domestic preparedness training for first responders; Beaton RD et al.; INTRODUCTION: In the wake of domestic terrorists attacks on 11 September 2001 and subsequent bioterrorist events employing anthrax, there no longer can be any debate about the potential for attacks employing Nuclear, Biological, or Chemical (NBC)/Weapons of Mass Destruction (WMD) . As one way of acknowledging this long-standing threat and, in a concerted effort to mitigate the effects of possible future domestic NBC/WMD terrorist attacks, the US Department of Defense (DOD) and other US governmental agencies already had mounted an effort to provide Domestic Preparedness Training for First Responders in urban centers throughout the USA . METHODS: A paper and pencil questionnaire specifically designed to evaluate the effectiveness of Domestic Preparedness Training for Emergency First Responders has been developed . An earlier version of this instrument was piloted with a convenience sample of firefighters and paramedics (n = 78) in a northwest state . Based on replies to the pilot questionnaire, a pool of 27 items based on the objectives and content of the NBC/WMD Domestic Preparedness Awareness and Operations courses (plus additional background and appraised competency items) were selected for inclusion in a Domestic Preparedness Questionnaire (DPQ) . RESULTS: This paper first describes the essential psychometric properties of the DPQ based on replies from baseline and follow-up samples (n = 206 and n = 246 respectively) of urban firefighters and paramedics employed by a metropolitan city in a northwest state . The DPQ was employed to evaluate the outcomes of Domestic Preparedness training provided to a sample of urban fire-service personnel . The DPQ documented significant improvements in a group of "DP trained"-urban firefighters (n = 80) both in their awareness and operations content knowledge as well as in their perceived competencies to respond to acts of biological, chemical, or nuclear terrorism "in their own community" at four months post-training . A comparison group of "Not DP-trained" firefighters (n = 78) showed no statistically significant changes on these DPQ indices, suggesting that the documented improvements in the "DP-trained" firefighters on the DPQ were not due to "test reactivity" or to "historical" factors . CONCLUSION: The findings suggest that the DPQ has adequate inter-item and test-retest reliability, possesses concurrent validity, and appears to be a sensitive measure of the Domestic Preparedness Training provided for urban firefighter and paramedic First Responders. Account Res, 2002 Apr-Jun, 9(2), 93 - 103 Informed consent and investigational new drug abuses in the U.S . military; Cummings ML; Objective: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND) . Design: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, legal pleadings, and protocols for specific investigational drugs . Results: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs . However, the waiver approval was conditional, and the FDA insisted on several safeguards . Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War . The FDA cited the military for significant deviations from the originally approved protocols . Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical . In addition, there was a gross lack of documentation and no monitoring of adverse reactions . The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy . The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations . There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine . In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules . There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered unethical . Conclusions: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections . The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner . In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent. Vaccine, 2003 Mar 28, 21(13-14), 1348 - 54 Adverse medical events in British service personnel following anthrax vaccination; Enstone JE et al.; The safety of the UK anthrax vaccine in British service personnel was evaluated by a retrospective cohort study of randomly selected personnel from five Royal Air Force bases by investigating adverse medical events and consultation rates for a period before and after vaccination . Vaccination acceptance rate varied from 27 to 89% (P=0.0001) . In the vaccinated cohort 11.1% (n=368) reported side-effects . The number of consultations in the year prior to vaccination (P=0.04) and RAF base (P=0.0085) were associated with side-effects . Only the RAF base remained a statistically significant factor (P=0.007) after adjusting for other factors . The anthrax vaccine resulted in mild side-effects in 11%, and no serious side-effects were observed . Acceptors of vaccine did not have significantly more medical consultations following vaccination than their unvaccinated counterparts. Antiviral Res, 2003 Jan, 57(1-2), 7 - 12 Smallpox: a potential agent of bioterrorism; Whitley RJ; The events of 11 September 2001, in New York City, and subsequent identification of anthrax in the United States Postal System, have generated a new sense of awareness for the potential of biological terrorism, if not warfare . Among those agents identified by the Centers for Disease Control and Prevention as 'Class A Bioterrorist Threats', smallpox is among the most dangerous . The ease of transmission of this agent, the lack of immunity in the population at large to this agent, and rapidity of its spread, if released, all generate significant concern for its deployment . A vaccine directed against smallpox is available but it is also associated with significant adverse events-some of which are life-threatening . Further, no antiviral drug has proven efficacious for therapy of human disease, although one licensed drug, cidofovir, does have in vitro activity . Regardless, heightened awareness should lead to the development of a vaccine without significant adverse events and safe and efficacious antiviral drugs . The availability of a vaccine and antiviral drugs that are safe would significantly remove any major threat of smallpox deployment by a terrorist. Microbes Infect, 2003 Jan, 5(1), 69 - 74 Robert Koch; Munch R; This article traces the origins of bacteriological research, with particular attention to the role of Robert Koch, and his postulates, on infectious agents . By chronologically following Koch's work on anthrax, germ photography and tuberculosis, it shows how the visual representation of germs transformed laboratory research in medical science. Schweiz Arch Tierheilkd, 2003 Jan, 145(1), 7 - 16 {Sacer ignis, quam pustulam vocant pastores: anthrax--cultural historical traces of a zoonosis}; Eitel J; The knowledge of anthrax as a disease and its importance as a zoonosis in the Greco-Roman world is revealed through a selection of classical texts and mythological sources, taking into account evidence of reworking and reuse of these texts up until the nineteenth century . The numerous names given to the disease throughout history and their linguistic origins will also be examined in this paper . The narrative of the epizoonoses in Noricum in Virgil's Georgics; taken by several to represent a description of an anthrax epidemic, and which had a great influence in written works on veterinary medicine up until the discovery of bacteria, will be given particular attention . The crucial term is "Sacer Ignis", synonymous for several different human and animal diseases through time . This term will be analysed in terms of linguistic origin and the changes in meaning it acquired throughout the centuries. Am J Clin Pathol, 2003 Feb, 119(2), 292 - 7 Effects of sterilizing gamma irradiation on bloodspot newborn screening tests and whole blood cyclosporine and tacrolimus measurements; Stickle DF et al.; Sterilizing irradiation of the US mail has been proposed as a method to prevent delivery of viable anthrax spores . Because newborn screening samples (bloodspots) and cyclosporine and tacrolimus specimens (whole blood) are delivered routinely through the mail, we studied whether sterilizing gamma irradiation could affect these test results . Specimens were exposed to 18 kGy gamma irradiation (100 hours x 18,000 rad/h), a "kill dose" for Bacillus pumilus spore strips . Irradiation had no significant effect on whole blood cyclosporine or tacrolimus results, but it had a degradative effect on bloodspot phenylalanine, hemoglobins, biotinidase, galactose-1-phosphate uridyltransferase, thyroxine, and thyrotropin . Such irradiation potentially could cause false-negative results for the detection of phenylketonuria and likely would lead to an increase in secondary testing for hemoglobin variants, but it is unlikely to lead to false-negative or false-positive results for the remaining newborn screening tests . These experiments cannot rule out possible greater effects by larger doses or other types of irradiation. Curr Med Chem, 2003 Jan, 10(1), 21 - 39 Biological activity and synthetic metodologies for the preparation of fluoroquinolones, a class of potent antibacterial agents; Da Silva AD et al.; In this present review we report different synthetic methodologies for the preparation of fluoroquinolones and their biological properties . The appearance of the fluoroquinolones, a new class of antibacterial agents (based on nalidixic acid, 4-quinolone-3-carboxylates), in early 1980's, gave a new impulse for the international competition to synthesize more effective drugs . Fluoroquinolones have a broad spectrum of activity against Gram-positive, Gram-negative and mycobacterial organisms as well as anaerobes . The fluoroquinolone ciprofloxacin hydrochloride is an important bioterrorist weapon and also an antibiotic used to treat bacterial infection in many different parts of the body, approved for use in patients who have been exposed to the inhaled form of anthrax. J Cell Biol, 2003 Feb 3, 160(3), 295 - 6 Anthrax toxin rafts into cells; Kurzchalia T; Anthrax toxin binds to a plasma membrane receptor and after endocytosis exerts its deadly effects on the cell . Until now, however, the mechanism of initial toxin uptake was unknown . In this issue, Abrami et al . (2003) demonstrate that toxin oligomerization clusters the anthrax receptor into lipid rafts and this complex is internalized via the clathrin-dependent pathway. Am J Emerg Med, 2003 Jan, 21(1), 77 - 9 Meeting the challenge of bioterrorism: lessons learned from West Nile virus and anthrax; Crupi RS et al.; Hospital emergency departments (EDs) and ambulatory clinics may be the first to recognize illness related to a bioterrorist event . Every health-care institution must develop a weapons-of-mass- destruction (WMD) preparedness plan as part of its all-hazards disaster planning . As part of an all-hazards disaster plan, WMD preparedness should use the incident-command model to insure the required chain of command for effectively coordinating activities between hospital departments and external agencies . Preparedness for bioterrorism poses unique challenges . In the event of a biological attack, the hospital infection control staff and administration must already have in place the means to communicate with local and state public health agencies, the Centers for Disease Control and Prevention (CDC), local law-enforcement agencies, and the Federal Bureau of Investigation (FBI) . Local and regional planners must consider how to coordinate the responses of emergency medical services (EMS), police, and fire departments with healthcare providers and the news media . Most hospitals are ill equipped to deal with a catastrophic event caused by WMD . The burden of responding to such events will fall initially on ED physicians and staff members . The severity of such an incident might be mitigated with careful planning, training and education . The responses of one hospital network to the outbreak of West Nile virus and, more recently, to the threat of anthrax, are presented as guides for bioterrorism preparedness . J Cell Biol, 2003 Feb 3, 160(3), 321 - 8 Epub 2003 Jan 27. Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process; Abrami L et al.; The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm . Here, we report that clustering of the anthrax toxin receptor (ATR) with heptameric PA or with an antibody sandwich causes its association to specialized cholesterol and glycosphingolipid-rich microdomains of the plasma membrane (lipid rafts) . We find that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger efficient internalization and allow delivery of LF to the cytoplasm . Importantly, altering raft integrity using drugs prevented LF delivery and cleavage of cytosolic MAPK kinases, suggesting that lipid rafts could be therapeutic targets for drugs against anthrax . Moreover, we show that internalization of PA is dynamin and Eps15 dependent, indicating that the clathrin-dependent pathway is the major route of anthrax toxin entry into the cell . The present work illustrates that although the physiological role of the ATR is unknown, its trafficking properties, i.e., slow endocytosis as a monomer and rapid clathrin-mediated uptake on clustering, make it an ideal anthrax toxin receptor. Ann Pharmacother, 2003 Feb, 37(2), 297 - 300 Figs--the earliest known ancient drug for cutaneous anthrax; Ben-Noun LL; BACKGROUND: Anthrax is an often fatal bacterial infection, occurring in cutaneous, inhalational, gastrointestinal, and meningeal forms . Evaluation of anthrax treatment from ancient history may help healthcare providers to handle this serious disease more efficiently . OBJECTIVE: To evaluate the biblical descriptions of anthrax, focusing on its therapy in ancient times . STUDY SELECTION: All biblical texts associated with anthrax were examined and passages relating to this disease were studied closely . DATA SYNTHESIS: Biblical passages such as: "Take a cluster of figs . And they took and laid it on the boil {anthrax}, and he recovered," and "Let them take a cluster of figs, and lay it upon the boil {anthrax}, and he shall recover," convincingly indicate that figs have healing properties in cutaneous anthrax lesions . CONCLUSIONS: On the basis of this study, the National Institutes of Health together with the pharmaceutical industry may consider to work on isolation of compounds from fig plants to develop products against cutaneous and possibly other forms of anthrax once screening tests are completed. BMC Med Inform Decis Mak . 2003 Jan 23;3(1):2. Time series modeling for syndromic surveillance; Reis BY et al.; BACKGROUND: Emergency department (ED) based syndromic surveillance systems identify abnormally high visit rates that may be an early signal of a bioterrorist attack . For example, an anthrax outbreak might first be detectable as an unusual increase in the number of patients reporting to the ED with respiratory symptoms . Reliably identifying these abnormal visit patterns requires a good understanding of the normal patterns of healthcare usage . Unfortunately, systematic methods for determining the expected number of (ED) visits on a particular day have not yet been well established . We present here a generalized methodology for developing models of expected ED visit rates . METHODS: Using time-series methods, we developed robust models of ED utilization for the purpose of defining expected visit rates . The models were based on nearly a decade of historical data at a major metropolitan academic, tertiary care pediatric emergency department . The historical data were fit using trimmed-mean seasonal models, and additional models were fit with autoregressive integrated moving average (ARIMA) residuals to account for recent trends in the data . The detection capabilities of the model were tested with simulated outbreaks . RESULTS: Models were built both for overall visits and for respiratory-related visits, classified according to the chief complaint recorded at the beginning of each visit . The mean absolute percentage error of the ARIMA models was 9.37% for overall visits and 27.54% for respiratory visits . A simple detection system based on the ARIMA model of overall visits was able to detect 7-day-long simulated outbreaks of 30 visits per day with 100% sensitivity and 97% specificity . Sensitivity decreased with outbreak size, dropping to 94% for outbreaks of 20 visits per day, and 57% for 10 visits per day, all while maintaining a 97% benchmark specificity . CONCLUSIONS: Time series methods applied to historical ED utilization data are an important tool for syndromic surveillance . Accurate forecasting of emergency department total utilization as well as the rates of particular syndromes is possible . The multiple models in the system account for both long-term and recent trends, and an integrated alarms strategy combining these two perspectives may provide a more complete picture to public health authorities . The systematic methodology described here can be generalized to other healthcare settings to develop automated surveillance systems capable of detecting anomalies in disease patterns and healthcare utilization. Eur J Biochem, 2003 Feb, 270(3), 404 - 14 Novel aspects of calmodulin target recognition and activation; Vetter SW et al.; Several crystal and NMR structures of calmodulin (CaM) in complex with fragments derived from CaM-regulated proteins have been reported recently and reveal novel ways for CaM to interact with its targets . This review will discuss and compare features of the interaction between CaM and its target domains derived from the plasma membrane Ca2+-pump, the Ca2+-activated K+-channel, the Ca2+/CaM-dependent kinase kinase and the anthrax exotoxin . Unexpected aspects of CaM/target interaction observed in these complexes include: (a) binding of the Ca2+-pump domain to only the C-terminal part of CaM (b) dimer formation with fragments of the K+-channel (c) insertion of CaM between two domains of the anthrax exotoxin (d) binding of Ca2+ ions to only one EF-hand pair and (e) binding of CaM in an extended conformation to some of its targets . The mode of interaction between CaM and these targets differs from binding conformations previously observed between CaM and peptides derived from myosin light chain kinase (MLCK) and CaM-dependent kinase IIalpha (CaMKIIalpha) . In the latter complexes, CaM engulfs the CaM-binding domain peptide with its two Ca2+-binding lobes and forms a compact, ellipsoid-like complex . In the early 1990s, a model for the activation of CaM-regulated proteins was developed based on this observation and postulated activation through the displacement of an autoinhibitory or regulatory domain from the target protein upon binding of CaM . The novel structures of CaM-target complexes discussed here demonstrate that this mechanism of activation may be less general than previously believed and seems to be not valid for the anthrax exotoxin, the CaM-regulated K+-channel and possibly also not for the Ca2+-pump. Clin Infect Dis, 2003 Feb 1, 36(3), 328 - 36 Epub 2003 Jan 20. Clinical features that discriminate inhalational anthrax from other acute respiratory illnesses; Kuehnert MJ et al.; Inhalational anthrax (IA) is a rapidly progressive disease that frequently results in sepsis and death, and prompt recognition is critical . To distinguish IA from other causes of acute respiratory illness, patients who had IA were compared with patients in an ambulatory clinic who had influenza-like illness (ILI) and with hospitalized patients who had community-acquired pneumonia (CAP) at the initial health care visit . Compared with patients who had ILI, patients who had IA were more likely to have tachycardia, high hematocrit, and low albumin and sodium levels and were less likely to have myalgias, headache, and nasal symptoms . Scoring systems were devised to compare IA with ILI or CAP on the basis of strength of association . For ILI, a score of > or =4 captured all 11 patients with IA and excluded 664 (96.1%) of 691 patients with ILI . Compared with patients who had CAP, patients with IA were more likely to have nausea or vomiting, tachycardia, high transaminase levels, low sodium levels, and normal white blood cell counts . For CAP, a score of > or =3 captured 9 (81.8%) of 11 patients with IA and excluded 528 (81.2%) of 650 patients with CAP . In conclusion, selected clinical features of patients with IA differ from those of patients with ILI and are more similar to those of patients with CAP. Mod Healthc, 2002 Dec 23-30, 32(51), 22 - 4 Year in review 2002; Moon S; The year opened on a somber note, with the nation still struggling to cope with the aftermath of the Sept . 11, 2001, attacks and subsequent anthrax scare . The healthcare industry was scrambling to be ready for any future attacks and pondering the best preparedness measures . Meanwhile, compliance and quality of care simmered on the back burner, along with soaring malpractice insurance costs and growing budget deficits in the states . And debate over provider reimbursement rates, staffing shortages and more double-digit increases in the cost of healthcare coverage also made headlines. Proc Natl Acad Sci U S A, 2003 Jan 21, 100(2), 657 - 62 Epub 2003 Jan 13. Potent antitumor activity of a urokinase-activated engineered anthrax toxin; Liu S et al.; The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy . We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity . Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage . Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice . In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice . Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase . The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors . This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation . The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent. Gesundheitswesen, 2002 Dec, 64(12), 689 - 91 {Consequences and challenges due to bioterrorist attacks}; Kurth R; Ever since the terrorist attacks of 11 September 2001 and the cases of inhalational anthrax and other types of anthrax caused by attacks with anthrax spores, responsible authorities and experts must reckon with bioterrorist attacks conducted with much greater criminal "drive" and greater financial resources than had been imagined so far . This consideration triggered cautionary measures in Germany and Europe as briefly summarised here . For more detailed information please refer to internet and see the references given below. Qual Manag Health Care, 2002 Spring, 10(3), 31 - 9 Anthrax attacks and practice patterns: a learning opportunity for health care systems; Jones JW et al.; Sudden and unexpected events directly influencing clinical practice patterns are uncommon . After the first report of bioterrorism-related anthrax, the authors studied retrospectively 13 months of anthrax-related antibiotic prescription rates for Veterans Affairs outpatients in one urban area where no cases of anthrax were reported . During the 26 days after the first anthrax report, the rate of acute respiratory illnesses treated with fluoroquinolones was 62.8 per 10,000 outpatient visits, an increase of 41 percent over the rate of 44.4 observed approximately one year earlier (p = 0.058) . Acute sociopolitical events such as bioterrorist attacks present a unique opportunity to investigate changes in health care. J Community Health Nurs, 2002 Winter, 19(4), 203 - 11 Bioterrorism preparedness for local health departments; Morse A; Bioterrorism preparedness has not traditionally been an everyday concern of local public health departments . The likely first responders to a biological bioterrorism event will be local public health personnel . The events of September 11, 2001, and the anthrax crisis that followed tested the capabilities of the public health system and demonstrated its fragility . Little federal funding has trickled down to local health departments, and they have not been included in planning or training for bioterrorism preparedness . Now local health departments must develop detailed bioterrorism response plans . Effective plans will involve internal assessment of strengths and weaknesses and strategizing with other local community agencies . Our health department is a suburban county agency that serves a population of over 250,000 . We have started this self-assessment and planning process . This bioterrorism guide has provided some structure for us and may be helpful for other local health departments as they begin this process. Semin Pediatr Infect Dis, 2002 Oct, 13(4), 289 - 99 Robert Koch: Nobel laureate and controversial figure in tuberculin research; Ligon BL; Tuberculosis has been a major cause of death for centuries . Likewise, anthrax has posed a deadly threat to both farm animals and humans and today poses a threat as a weapon of biological warfare . Cholera, which wreaked havoc in the East and threatened to enter Europe, also posed a deadly threat . The causes of these diseases remained mysteries for centuries . Nobel laureate Robert Koch (1843-1910), often called the founder of medical bacteriology, is credited with discovering the tubercle bacillus, Mycobacterium tuberculosis; with demonstrating for the first time in history the life cycle of the anthrax bacillus under controlled in vitro conditions; and with identifying Vibrio cholorae as the cause of cholera . In later life, he also was at the center of several controversies . This article provides a brief summary of Koch's exploration into bacteriology and, especially, his experience with tuberculosis and the controversies that developed in the latter part of his life, as well as his childhood and early adult years and the development of his now well-known "postulates." EMBO J, 2002 Dec 16, 21(24), 6721 - 32 Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins; Shen Y et al.; Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively . Using spectroscopic, enzyme kinetic and surface plasmon resonance spectroscopy analyses, we show that low Ca(2+) concentrations increase the affinity of CaM for EF and CyaA causing their activation, but higher Ca(2+) concentrations directly inhibit catalysis . Both events occur in a physiologically relevant range of Ca(2+) concentrations . Despite the similarity in Ca(2+) sensitivity, EF and CyaA have substantial differences in CaM binding and activation . CyaA has 100-fold higher affinity for CaM than EF . CaM has N- and C-terminal globular domains, each binding two Ca(2+) ions . CyaA can be fully activated by CaM mutants with one defective C-terminal Ca(2+)-binding site or by either terminal domain of CaM while EF cannot . EF consists of a catalytic core and a helical domain, and both are required for CaM activation of EF . Mutations that decrease the interaction of the helical domain with the catalytic core create an enzyme with higher sensitivity to Ca(2+)-CaM activation . However, CyaA is fully activated by CaM without the domain corresponding to the helical domain of EF. Biochem Biophys Res Commun, 2003 Jan 3, 300(1), 61 - 4 Exchange characteristics of calcium ions bound to anthrax protective antigen; Gao-Sheridan S et al.; Protective antigen (PA), the receptor-binding moiety of anthrax toxin, contains two calcium atoms buried within domain 1(') (amino acid residues 168-258) . We showed that these ions are stably bound and exchange with free 45Ca(2+) only slowly (t(1/2) approximately 4.0 h) . Dissociation is the rate-limiting step . PA(63), the heptameric prepore form of PA, showed a slightly higher exchange rate than the monomeric intact protein . Exchange by this form was retarded by binding of the enzymatic moieties of the toxin, but was unaffected by reducing the pH to 5.0, a condition known to trigger conversion of the prepore to the pore form . These results are consistent with the hypothesis that bound Ca(2+) within PA plays primarily a structural role, maintaining domain 1(') in a conformation that allows PA(63) to oligomerize and bind the enzymatic moieties of the toxin. J Biol Chem, 2003 Feb 14, 278(7), 5227 - 34 Epub 2002 Dec 04. Cell surface tumor endothelium marker 8 cytoplasmic tail-independent anthrax toxin binding, proteolytic processing, oligomer formation, and internalization; Liu S et al.; The interaction of anthrax toxin protective antigen (PA) and target cells was assessed, and the importance of the cytosolic domain of tumor endothelium marker 8 (TEM8) in its function as a cellular receptor for PA was evaluated . PA binding and proteolytic processing on the Chinese hamster ovary cell surface occurred rapidly, with both processes nearly reaching steady state in 5 min . Remarkably, the resulting PA63 fragment was present on the cell surface only as an oligomer, and furthermore, the oligomer was the only PA species internalized, suggesting that oligomerization of PA63 triggers receptor-mediated endocytosis . Following internalization, the PA63 oligomer was rapidly and irreversibly transformed to an SDS/heat-resistant form, in a process requiring an acidic compartment . This conformational change was functionally correlated with membrane insertion, channel formation, and translocation of lethal factor into the cytosol . To explore the role of the TEM8 cytosolic tail, a series of truncated TEM8 mutants was transfected into a PA receptor-deficient Chinese hamster ovary cell line . Interestingly, all of the cytosolic tail truncated TEM8 mutants functioned as PA receptors, as determined by PA binding, processing, oligomer formation, and translocation of an lethal factor fusion toxin into the cytosol . Moreover, cells transfected with a TEM8 construct truncated before the predicted transmembrane domain failed to bind PA, demonstrating that residues 321-343 are needed for cell surface anchoring . Further evidence that the cytosolic domain plays no essential role in anthrax toxin action was obtained by showing that TEM8 anchored by a glycosylphosphatidylinositol tail also functioned as a PA receptor. Proc AMIA Symp . 2002;:365-91. National Pharmaceutical Stockpile drill analysis using XML data collection on wireless Java phones; Karras BT et al.; This study describes an informatics effort to track subjects through a National Pharmaceutical Stockpile (NPS) distribution drill . The drill took place in Seattle on 1/24/2002 . Washington and the State Department of Health are among the first in the nation to stage a NPS drill testing the distribution of medications to mock patients, thereby testing the treatment capacity of the plan given a post-anthrax exposure scenario . The goal of the Public Health Informatics Group at the University of Washington was to use informatics approaches to monitor subject numbers and elapsed time . This study compares accuracy of time measurements using a mobile phone Java application to traditional paper recording in a live drill of the NPS . Pearson correlation = 1.0 in 2 of 3 stations . Differences in last station measurements can be explained by delay in recording of the exit time . We discuss development of the application itself and lessons learned . (MeSH Bioterrorism, Informatics, Public Health) Hong Kong Med J, 2002 Dec, 8(6), 440 - 6 Hospital preparedness for chemical and biological incidents in Hong Kong; Chan JT et al.; The risk of mass exposure to toxic substances has increased steadily during the twentieth century due to the expansion of industry and the deliberate development and use of agents of chemical warfare . Although Hong Kong is considered a relatively safe place, hoax anthrax attacks have occurred since 17 October 2001 . People who have been seriously injured by hazardous materials have a greater chance of recovery without complications when appropriate emergency treatments are provided . Recognition and identification of hazardous materials, assessment of the conditions, decontamination, and protection of staff and facilities are important elements in the formulation of a contingency plan . The objective of this article is to outline the efforts of the Hong Kong Hospital Authority in formulating a hospital response to incidents involving hazardous materials. Vaccine, 2002 Dec 13, 21(3-4), 211 - 20 Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells transduced with replication-defective recombinant adenovirus; Matsui M et al.; We studied the potential of dendritic cells (DCs) in priming hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTLs) in mice . Recombinant adenovirus expressing HCV core (Adex1SR3ST) was employed to express core in DCs . Core-specific CTLs are effectively elicited by injecting Adex1SR3ST-transduced DCs, whereas injection of Adex1SR3ST does not result in effective priming . Further, Adex1SR3ST-transduced DCs more efficiently prime core-specific CTLs than Adex1SR3ST-transduced macrophages, or DCs treated with an anthrax toxin fusion protein reported previously . Upon challenge with recombinant HCV-core-expressing vaccinia virus, vaccinia titers are significantly reduced in mice immunized with Adex1SR3ST-transduced DCs . Thus, adenovirus-transduced DCs may be a promising candidate for a CTL-based vaccine against HCV. Health Aff (Millwood), 2002 Nov-Dec, 21(6), 117 - 30 Public health and national security: the critical role of increased federal support; Frist B; Protecting the public's health historically has been a state and local responsibility . However, the growing threat of bioterrorism has highlighted the importance of a strong public health infrastructure to the nation's homeland security and has focused increased attention on the preparedness of the public health system . As a result, federal public health funding has increased exponentially since the anthrax attacks of late 2001, and Congress has passed sweeping new federal legislation intended to strengthen the nation's public health system . This heightened level of federal interest and support should yield important public health benefits . Most recognize that after years of neglect the public health infrastructure cannot be rebuilt overnight . As we implement a comprehensive strategy to increase the capabilities and capacity of our nation's public health system, it is essential to address a series of important policy questions, including the appropriate level of ongoing public health investments from local, state, and federal sources. Health Aff (Millwood), 2002 Nov-Dec, 21(6), 106 - 16 Dealing with the dangers of fear: the role of risk communication; Gray GM et al.; Among the many lessons of the homeland terrorist attacks of 2001 was that fear has powerful public health implications . People chose to drive instead of flying, thereby raising their risk of injury or death . Thousands took broad-spectrum antibiotics to prevent possible anthrax infections, thereby accelerating antimicrobial resistance . Such potentially harmful actions were taken by people seeking a sense of safety because they were afraid . This essay argues for greater emphasis on risk communication to help people keep their fears in perspective . Effective communication, not only through what the government says but implicit in the actions it takes, empowers people to make wiser choices in their own lives, and to support wise choices by society in applying limited resources to maximize public and environmental health. Vet Clin North Am Food Anim Pract, 2002 Nov, 18(3), 379 - 87, v Maintaining a vigilance for foreign animal diseases; Waldrup KA et al.; The incursion of foot-and-mouth disease (FMD) into the United Kingdom in February 2001 served as a wakeup call for North American agriculture . As the livestock health crisis in the United Kingdom progressed, it became increasingly evident that the United States, Canada, and Mexico were also susceptible to an incursion of a foreign animal disease . The terrorist attacks of September 11, 2001, and the subsequent anthrax mailings reaffirmed the fact that the United States is vulnerable to an infectious assault, regardless of whether it is intentional or accidental. J Med Microbiol, 2002 Oct, 51(10), 821 - 31 In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody; Welkos S et al.; Antibodies (Abs) to the protective antigen (PA) component of the anthrax toxins have anti-spore as well as anti-toxin activities . Anti-PA antisera and purified anti-PA Abs enhance the phagocytosis by murine-derived macrophages (MQs) of spores of the Ames and Sterne strains and retard the germination of extracellular spores in vitro . The fate after phagocytosis of untreated and anti-PA-treated spores was further studied in culture medium that supported phagocytosis without stimulating spore germination (Dulbecco's minimal essential medium with horse serum 10%) . The spores germinated within cells of primary peritoneal murine MQs (C3H/HeN) and MQs of the RAW264.7 MQ-like cell line; germination was associated with a rapid decline in spore viability . Exposure of MQs to inhibitors of phago-endosomal acidification (bafilomycin A and chloroquine) reduced the efficiency of MQ killing and allowed outgrowth and replication of the organisms . Treatment of spores with anti-PA Abs stimulated their phagocytosis and was associated with enhanced MQ killing of the spores . The enhanced killing of spores correlated with the greater extent of germination of anti-PA-treated spores after phagocytosis . A PA null mutant of the Ames strain exhibited none of the effects associated with anti-PA Ab treatment ofthe parental strain . Thus, the anti-PA Ab-specific immunity induced by vaccines has anti-spore activities and its role in impeding the early stages of infection with Bacillusanthracis needs to be assessed. Dis Mon, 2002 Aug, 48(8), 493 - 564 Biological terrorism: understanding the threat, preparation, and medical response; Franz DR et al.; The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago . Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all . The "anthrax letters" and the resulting deaths from inhalation anthrax have changed that perception . The national, state, and local governments in the United States are preparing for what is now called "not if, but when and how extensive" biological terrorism . In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray . Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack . As individual health care providers, we must add the exotic agents to our diagnostic differentials . Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism . Above all, we must all educate ourselves . If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon . A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of the disease, no matter what the cause of the disease. Cell Cycle, 2002 Jan, 1(1), 10 - 5 Anthrax, MEK and cancer; Bodart JF et al.; The MEK family of protein kinases plays key roles in regulating cellular responses to mitogens as well as environmental stress . Inappropriate activation of these kinases contributes to tumorigenesis . In contrast, anthrax lethal factor, the principal virulence factor of anthrax toxin, has been demonstrated to selectively inactivate MEKs . In this article we will discuss recent advances in our understanding of molecular aspects of the pathogenesis of anthrax, emphasizing the potential role of MEK signalling in this disease, and outline novel strategies to use anthrax lethal toxin in the treatment of cancer. Tijdschr Diergeneeskd, 2002 Oct 15, 127(20), 616 - 9 {Bioterrorism: the role of veterinarians in detection and prevention}; de Balogh KK et al.; The fear of terrorist attacks has increased since the events of 11 September 2001 in New York . In the weeks following the terrorist attack, letters containing anthrax spores were received at various locations in the USA . This shows that bioterrorism is possible and that is necessary to be prepared for the potential release of biological agents . Such agents can be distributed not only via the air and drinking water but also via household pets . The aim of terrorist attacks, namely, the disruption of society and daily life, can be achieved in three ways, ways which are of importance to practising veterinarians, namely, via pets, via contamination of pet foods of animal origin, and by the spread of infectious animal diseases that have far-reaching economic consequences . These ways are discussed in this article, together with possible ways in which veterinarians can act to diminish the consequences of such an event. Physician Exec, 2002 Sep-Oct, 28(5), 64 - 6 Smallpox vaccine policy: the national debate; Benjamin GC; As a result of the 2001 anthrax attacks, the U.S . government is trying to forge a plan to handle something much worse: an outbreak of smallpox due to terrorist activity . Here's a look at where the debate stands today. Online J Issues Nurs . 2002;7(3):5. Public health nursing practice: aftermath of September 11, 2001; Berkowitz B; America's experience on September 11, 2001, forms the backdrop of this review of the public health nursing role in bioterrorism preparedness . The risks and challenges to the public health infrastructure are reviewed in order to place bioterrorism preparedness in a public health context . A review of the literature provides background material on the extent to which public health has evolved in planning for a bioterrorism event . The skills and competencies that will prepare public health nurses in their planning for and response to threats of bioterrorism are addressed . Anthrax is used as an example to illustrate how public health nursing can assist in a bioterrorism response. Emerg Infect Dis, 2002 Oct, 8(10), 1160 - 2 Epidemic anthrax in the eighteenth century, the Americas; Morens DM; Anthrax has been described as a veterinary disease of minor importance to clinical medicine, causing occasional occupational infections in single cases or clusters . Its potential for rapid and widespread epidemic transmission under natural circumstances has not been widely appreciated . A little-known 1770 epidemic that killed 15,000 people in Saint-Domingue (modern Haiti) was probably intestinal anthrax . The epidemic spread rapidly throughout the colony in association with consumption of uncooked beef . Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural circumstances . Historical information may not only provide important clues about epidemic development but may also raise awareness about bioterrorism potential. Emerg Infect Dis, 2002 Oct, 8(10), 1096 - 102 Laboratory response to anthrax bioterrorism, New York City, 2001; Heller MB et al.; In October 2001, the greater New York City Metropolitan Area was the scene of a bioterrorism attack . The scale of the public response to this attack was not foreseen and threatened to overwhelm the Bioterrorism Response Laboratory's (BTRL) ability to process and test environmental samples . In a joint effort with the Centers for Disease Control and Prevention and the cooperation of the Department of Defense, a massive effort was launched to maintain and sustain the laboratory response and return test results in a timely fashion . This effort was largely successful . The development and expansion of the facility are described, as are the special needs of a BTRL . The establishment of a Laboratory Bioterrorism Command Center and protocols for sample intake, processing, reporting, security, testing, staffing, and and quality control are also described. Emerg Infect Dis, 2002 Oct, 8(10), 1093 - 5 Coordinated response to reports of possible anthrax contamination, Idaho, 2001; Tengelsen L et al.; In 2001, the intentional release of anthrax spores in the eastern United States increased concern about exposure to anthrax nationwide, and residents of Idaho sought assistance . Response from state and local agencies was required, increasing the strain on epidemiologists, laboratorians, and communications personnel . In late 2001, Idaho's public health communications system handled 133 calls about suspicious powders . For each call, a multiagency bridge call was established, and participants (public health officials, epidemiologists, police, Federal Bureau of Investigation personnel, hazardous materials officials, and others) determined which samples would be tested by the state public health laboratory . A triage system for calls helped relieve the burden on public safety and health systems. Harv Bus Rev, 2002 Oct, 80(10), 80 - 9, 129 Open-market innovation; Rigby D et al.; Companies in many industries are feeling immense pressure to improve their ability to innovate . Even in these tough economic times, executives have pushed innovation initiatives to the top of their priority lists, but they know that the best ideas aren't always coming out of their own R&D labs . That's why a growing number of companies are exploring the idea of open-market innovation--an approach that uses tools such as licensing, joint ventures, and strategic alliances to bring the benefits of free trade to the flow of new ideas . For instance, when faced with the unanticipated anthrax scare last fall, Pitney Bowes had nothing in its R&D pipeline to help its customers combat the deadly spores . So it sought help from outside innovators to come up with scanning and imaging technologies that could alert its customers to tainted letters and packages . And Dow Chemical and Cargill jointly produced a new form of plastic derived from plant starches--a breakthrough product that neither company could have created on its own . In this article, Bain consultants Darrell Rigby and Chris Zook describe the advantages and disadvantages of open-market innovation and the ways some companies are using it to gain competitive advantage . By importing ideas from the outside, the authors say, companies can collect more and better ideas from different kinds of experts . Creative types within a company will stick around longer if they know their ideas will eventually find a home--as internal R&D projects or as concepts licensed to outside buyers . Exporting ideas also gives companies a way to measure an innovation's real value . However, the authors warn against entering into open-market innovation without properly structuring deals: Xerox and TRW virtually gave away their innovations and had to stand by while other companies capitalized on them. Ann N Y Acad Sci, 2002 Oct, 969, 245 - 50 Emergency response planning for anthrax outbreaks in bison herds of northern Canada: a balance between policy and science; Nishi JS et al.; Anthrax outbreaks in northern Canada have implications for ongoing recovery efforts for the threatened wood bison and may pose a health risk to humans, other wildlife, and domestic livestock . RWED and WBNP maintain Anthrax Emergency Response Plans (AERPs) for their respective jurisdictions . An AERP is a pre-planned logistical framework for responding effectively and rapidly to an outbreak so as to minimize spread of the disease, reduce environmental load of spores available for future outbreaks, and minimize risk to public health . In this paper, we describe the main components of an AERP and outline areas for future research. Br J Anaesth, 2002 Aug, 89(2), 306 - 24 Chemical and biological weapons . Implications for anaesthesia and intensive care; White SM; In the wake of recent atrocities there has been renewed apprehension regarding the possibility of chemical and biological weapon (CBW) deployment by terrorists . Despite various international agreements that proscribe their use, certain states continue to develop chemical and biological weapons of mass destruction . Of greater concern, recent historical examples support the prospect that state-independent organizations have the capability to produce such weapons . Indeed, the deliberate deployment of anthrax has claimed several lives in the USA since September 11, 2001 . In the event of a significant CBW attack, medical services would be stretched . However, victim survival may be improved by the prompt, coordinated response of military and civil authorities, in conjunction with appropriate medical care . In comparison with most other specialties, anaesthetists have the professional academic background in physiology and pharmacology to be able to understand the nature of the injuries caused by CBWs . Anaesthetists, therefore, play a vital role both in the initial resuscitation of casualties and in their continued treatment in an intensive care setting . This article assesses the current risk of CBW deployment by terrorists, considers factors which would affect the severity of an attack, and discusses the pathophysiology of those CBWs most likely to be used . The specific roles of the anaesthetist and intensivist in treatment are highlighted. Biochem Biophys Res Commun, 2002 Oct 11, 297(5), 1121 - 7 Delivery of nucleic acid into mammalian cells by anthrax toxin; Gaur R et al.; Gene delivery vehicles based on receptor-mediated endocytosis offer an attractive long-term solution as they might overcome the limitations of toxicity and cargo capacity inherent to many viral gene delivery systems . The protective antigen component of anthrax toxin bind to specific receptors and deliver lethal factor or edema factor into the cytosol of mammalian cells . The N-terminal 254 amino acids of LF (LF(1-254)) binds to PA and, when fused to heterologous proteins, delivers such proteins into the cytosol . However, so far no attempt has been made to use the anthrax toxin system for the intracellular delivery of DNA . In the present study, LF(1-254) of anthrax toxin was fused to the DNA-binding domain of GAL4 protein . The fusion protein (LF(254)-GAL4DBD) showed both PA binding as well as DNA-binding activity in solution . The complex of fusion protein with plasmid DNA containing a reporter gene (luciferase or green fluorescent protein) along with PA delivered plasmid DNA into the cytosol of COS-1 cells . These results suggest that anthrax toxin components can be used as a non-viral system for the efficient delivery of DNA into the cytosol of mammalian cells. J Fam Pract, 2002 Sep, 51(9), 745 - 50 On the front lines: family physicians' preparedness for bioterrorism; Chen FM et al.; OBJECTIVE: The events of September 11, 2001, and the nation's recent experience with anthrax assaults made bioterrorism preparedness a national priority . Because primary care physicians are among the sentinel responders to bioterrorist attacks, we sought to determine family physicians' beliefs about their preparedness for such an attack . STUDY DESIGN: In October 2001 we conducted a national survey of 976 family physicians randomly selected from the American Academy of Family Physicians' active membership directory . POPULATION: 614 (63%) family physicians responded to the survey . OUTCOMES MEASURED: Physicians' self-reported ability to "know what to do as a doctor in the event of a suspected bioterrorist attack, recognize signs and symptoms of an illness due to bioterrorism, and know where to call to report a suspected bioterrorist attack." RESULTS: Ninety-five percent of physicians agreed that a bioterrorist attack is a real threat within the United States . However, only 27% of family physicians believed that the US health care system could respond effectively to a bioterrorist attack; fewer (17%) thought that their local medical communities could respond effectively . Twenty-six percent of physicians reported that they would know what to do as a doctor in the event of a bioterrorist attack . Only 18% had previous training in bioterrorism preparedness . In a multivariate analysis, physicians reported that preparedness for a bioterrorist attack was significantly associated with previous bioterrorism preparedness training (OR 3.9 {95% CI 2.4-6.3}) and knowing how to obtain information in the event of a bioterrorist attack (OR 6.4 {95% CI 3.9-10.6}) . CONCLUSIONS: Only one quarter of family physicians felt prepared to respond to a bioterrorist event . However, training in bioterrorism preparedness was significantly associated with physicians' perceived ability to respond effectively to an attack . Primary care physicians need more training in bioterrorism preparedness and easy access to public health and medical information in the event of a bioterrorist attack. Vet Hum Toxicol, 2002 Oct, 44(5), 291 - 2 Believe it or not--silver still poisons! Hori K, Martin TG, Rainey P, Robertson WO. For centuries, silver has been endowed with therapeutic benefits . It is still used today as a "caustic" for superficial bleeding . Within 7days, we had 3 cases of "argyria" and then 2 more over the next month . The first 2 cases involved a husband and wife with a 3-y exposure to naturopathic hydrolyzed silver treatment . The third casewas a 37-y-old male in a state psychiatric facility noted to have darkly "discolored" skin probable obtained from herbal tea . The last 2 cases were a married couple into herbal medications who developed bluish discoloration of face and hands . Current cases due to "alternative medicine" may get worse as rumor reveals its popularity as prophylaxis against anthrax . The skin's grayish discoloration, made worse by sunlight, may persist for life. Nat Rev Mol Cell Biol, 2002 Oct, 3(10), 753 - 66 Furin at the cutting edge: from protein traffic to embryogenesis and disease; Thomas G; Furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway . But the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever . This review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo. Psychol Rep, 2002 Aug, 91(1), 187 - 91 Comments on the Institute of Medicine's 2002 report on the safety of anthrax vaccine; Schumm WR et al.; In April 2002, the prestigious Institute of Medicine of the National Academy of Sciences issued a final report on the safety and effectiveness of the anthrax vaccine currently in use by the United States military . It concluded that the present vaccine was completely safe and effective, but ignored evidence of several recent research studies from three different nations that have implicated vaccines, often including anthrax vaccine, in the epidemiology of Gulf War illnesses . Omissions and limitations of that report are discussed. Med Parazitol (Mosk), 2002 Jul-Sep, (3), 13 - 6 {Infection and invasion of humans in the Yamal Peninsula}; Fattakhov RG et al.; The helminthic fauna of vertebrates in the Yamal peninsula consists of 61 species: of them 2 species are monogenic, 6 are trematodes, 29 are cestodes, and 24 are nematodes . Twelve species of the 4 are antroponoses and 8 are zoonoses which may parasite on human beings . Human infection with some zoonoses is due to local habits of eating raw or undercooked meat of wild animals, domestic deers, and fish . These helminthic diseases include trichinosis, taeniasis, opisthorchiasis, diphyllobothriasis . On contacting with dogs and Arctic foxes, the population is infected with echinococciasis, alveococciasis, toxoplasmosis . The foci of brucellosis, anthrax, tularemia, leptospirosis, rickettsioses, rabies, and toxoplasmosis were notified in the Yamal peninsula . Intensive migration of the population contributes to the importation of new species of causative agents to the peninsula and to the deterioration of the situation of endemic invasions and infections . Thus, in-depth study of parasitic and natural focus-related diseases in this region becomes partially urgent now. J Am Pharm Assoc (Wash), 2002 Sep-Oct, 42(5 Suppl 1), S50 - 1 Disaster planning and emergency preparedness: lessons learned; Babb J et al.; Following the terrorist attacks of September 11, 2001, the federal response plan was activated immediately, with most efforts focused on helping recovery workers at Ground Zero in New York City . Comprehensive pharmacy services were critical in protecting the health of those potentially exposed to anthrax at U.S . Postal Service facilities and the U.S . Capitol . Responding to anthrax attacks taught many valuable lessons to emergency workers on how to manage a bioterrorist attack . Because of its central place in the life of many American communities, pharmacy is a natural and important ally of public health. Biochem Biophys Res Commun, 2002 Sep 27, 297(3), 506 - 9 Delayed treatment with doxycycline has limited effect on anthrax infection in BLK57/B6 mice; Kalns J et al.; Blk57/B6 mice were infected with LD90 dose of Sterne strain anthrax spores subcutaneously and then treated with doxycycline . Doxycycline at a dose of 1.5mg/kg, by intra-peritoneal injection, protected mice from death when given at the same time as spores . When doxycycline administration was delayed 4h survival is 90% . Delay of 24h increased survival time but had no impact on eventual mortality . When doxycycline was delayed 48h, mortality and time to death were comparable to sham injection . Peritoneal macrophages harvested from Blk57/B6 mice were examined for response to anthrax lethal toxin and are shown to be deficient in their ability to produce TNF-alpha and have increased expression of IL-6 compared to RAW 264.7 murine macrophage cell line . These findings suggest that antibiotic therapy has limited effects following lethal anthrax spore challenge, even when the host is of a phenotype that does not produce TNF-alpha in response to anthrax lethal toxin exposure. Scand J Infect Dis, 2002, 34(8), 627 - 8 A case of anthrax meningitis; Albayrak F et al.; Meningeal anthrax is a very rare complication of the cutaneous, respiratory and gastrointestinal form of anthrax infection . Anthrax bacilli, most commonly enter the body via the skin, and the organism then disseminates to the central nervous system via the hematogenous or lymphatic routes leading to fatal bacterial meningitis, even with intensive antibacterial therapy. Clin Infect Dis, 2002 Oct 1, 35(7), 851 - 8 Epub 2002 Aug 30. Management of anthrax; Bartlett JG et al.; From 3 October 2001 through 16 November 2001, in the United States, there were 18 confirmed cases of inhalational and cutaneous anthrax, an additional 4 suspected cases of cutaneous anthrax, and 5 deaths due to inhalational anthrax . Although the number of cases was relatively small, this experience brought bioterrorism and its potential to sharp focus as thousands of people began receiving prophylactic antibiotics after possible exposure to anthrax spores . These events have resulted in a substantial impact on the health care system, including the rewriting of pneumonia guidelines, new emphasis on identification of microbial etiology, substantial infusion of funds for bioterrorism-related research, and a sudden mandate for regional disaster and public health planning . This article provides clinicians with clinically relevant information about the diagnosis and management of anthrax. Risk Anal, 2002 Aug, 22(4), 655 - 64 Risk analysis and risk management in an uncertain world; Kunreuther H; The tragic attacks of September 11 and the bioterrorist threats with respect to anthrax that followed have raised a set of issues regarding how we deal with events where there is considerable ambiguity and uncertainty about the likelihood of their occurrence and their potential consequences . This paper discusses how one can link the tools of risk assessment and our knowledge of risk perception to develop risk management options for dealing with extreme events . In particular, it suggests ways that the members of the Society for Risk Analysis can apply their expertise and talent to the risks associated with terrorism and discusses the changing roles of the public and private sectors in dealing with extreme events. Curr Top Microbiol Immunol, 2002, 271, 61 - 85 Structure and function of anthrax toxin; Lacy DB et al.; Anthrax toxin is a binary A-B toxin comprised of protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF) . In the presence of a host cell-surface receptor, PA can mediate the delivery of EF and LF from the extracellular milieu into the host cell cytosol to effect toxicity . In this delivery, PA undergoes multiple structural changes--from a monomer to a heptameric prepore to a membrane-spanning heptameric pore . The catalytic factors also undergo dramatic structural changes as they unfold to allow for their translocation across the endosomal membrane and refold to preserve their catalytic activity within the cytosol . In addition to these gross structural changes, the intoxication mechanism depends on the ability of PA to form specific interactions with the host cell receptor, EF, and LF . This chapter presents a review of experiments probing these structural interactions and rearrangements in the hopes of gaining a molecular understanding of toxin action. Curr Top Microbiol Immunol, 2002, 271, 1 - 19 Introduction: anthrax history, disease and ecology; Turnbull PC; The familiarity with the ancient disease anthrax from the second millennium B.C . through the second millennium A.D . is reviewed, providing the backdrop to the modern understanding of this disease as covered in the remainder of the volume . By means of an overview of the aetiology, ecology, epidemiology, clinical manifestations, pathology and bacteriology of the naturally acquired disease, this opening chapter also lays down the groundwork for the subsequent state-of-the-art chapters. Med Sci Monit, 2002 Sep, 8(9), CS73 - 6 GI anthrax: report of one case confirmed with autopsy; Mansour-Ghanaei F et al.; BACKGROUND: Bacillus Anthraces is a non-motile, rod like, gram-positive and aerobic bacillus that produces central oval-shaped spores and characterized by rough, irregular and often comma-shaped colonies in blood agar . About 95% of human anthrax is cutaneous and 5% respiratory . GI anthrax, a very rare type, has been reported in less than 1% of all cases . We thus report a case of GI anthrax with autopsy findings . CASE REPORT: A 15-year-old young adult man was admitted to our hospital with history of fever, abdominal pain and bloody diarrhea from 48 hours after ingestion of half-cooked sheep's meat . In endoscopic exam of upper GI tract, the esophagus had been filled with fresh blood without any varices, stomach showed evidence of hemorrhage and had multiple erosion but no ulceration of duodenum . Penicillin G 24,000,000 U/day IV was started but unfortunately severe upper and lower GI hemorrhage developed, leading to hypotension and death . In autopsy, ascites, paraaortic and mesenteric lymphadenopathy was accident with some of them being hemorrhagic . The spleen was slightly enlarged with hemorrhagic congestion in some parts of it . In the blood sample drawn from the spleen, the filamentous bacillus was successfully found . CONCLUSIONS: Because of the fatal nature of the disease and the similarity of the signs and symptoms to the other gastrointestinal diseases, we should consider it as one of the probable differential diagnosis in the patients with upper and lower gastrointestinal bleeding with fever esp . in the endemic areas. Med Confl Surviv, 2002 Jul-Sep, 18(3), 271 - 82 A short history of biological warfare; Metcalfe N; Biological weapons have been used in war from the start of recorded history . This article reviews the history of the subject, including the outbreak of the Black Death and the use of smallpox against American Indians . The new science of microbiology was misused from soon after its start and, despite the 1925 Geneva Protocol, the Japanese experimented extensively on prisoners in China . The Allies carried out extensive research during the Second World War, notably the United Kingdom into anthrax on Gruinard Island and the United States into a variety of agents . Despite the 1972 Biological Weapons Convention (BWC), a major programme continued in the former Soviet Union (leading to an accidental outbreak of anthrax) . Most recently Iraq was revealed as having an extensive programme, with weaponization of large amounts of various agents, and several terrorists groups have attempted to use biological agents as weapons . Modern developments in biotechnology could lead to even more serious developments, and effective preventive measures, including strengthening of the BWC, are imperative. J Trop Pediatr, 2002 Aug, 48(4), 225 - 6 Cutaneous anthrax: an endemic outbreak in south India; Vijaikumar M et al.; Although human anthrax has become rare, endemic outbreaks still occur in tropical countries, parts of South America and Europe . We report 23 cases of cutaneous anthrax due to an endemic outbreak of animal and human anthrax in South India . These patients were admitted to our hospital between July 1998 and July 2001 . Children outnumbered adults and most of them had lesions on the exposed sites . The majority of patients reported the death of infected animals in the neighbourhood without any direct contact with dead animals . Hence, vector borne transmission was suspected in most of the cases . Diagnosis was confirmed by the presence of a typical ulcer with eschar, Gram-stained smears from ulcers and epidemiological evidence . Except for one fatal case, all patients responded to treatment. Clin Microbiol Infect, 2002 Aug, 8(8), 510 - 21 A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000; Grunow R et al.; The events of 11 September and the subsequent anthrax outbreaks in the USA have opened the world's eyes to the threat posed by terrorist groups, criminal organizations and lone operators who will stop at nothing to achieve their goals . The open or covert use of pathogens and toxins as biological warfare agents can no longer be ruled out . Against this background, the appearance of an unusual disease must be studied in order to clarify whether it is a natural or artificially caused occurrence . This issue was recently raised in discussions with local representatives and relief organizations during a tularemia epidemic in Kosovo from October 1999 to May 2000 . This paper will present a procedure which attempts to use certain criteria to identify or rule out the use of biological warfare agents in the event of an unusual outbreak of disease . Data and findings gathered by routine epidemiologic and microbiological studies often provide only an indirect answer to this problem . For this reason, various criteria were formulated and points allocated to represent their importance, allowing us to deduce in a semiquantitative manner the degree of possibility of an artificial genesis of outbreaks . The significance and characterization of each criterion are discussed . An analysis of the tularemia epidemic in Kosovo based on the procedure described here indicates that a deliberate release of the causative agent of tularemia, Francisella tularensis, as a biological warfare agent is doubtful . In this paper, an approach is described to discriminate between the intentional use of biological warfare agents and natural outbreaks of infectious diseases . The developed model is flexible and considers the political, military and social analysis of the crisis-afflicted region, the specific features of the pathogen, and the epidemiologic and clinical characteristics of the epidemic. Clin Microbiol Infect, 2002 Aug, 8(8), 489 - 503 Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room; Cunha BA; Bioterrorism has become a potential diagnostic consideration in infectious diseases . This article reviews the clinical presentation and differential diagnosis of potential bioterrorist agents when first presenting to the hospital in the emergency room setting . The characteristic clinical features of inhalation anthrax, tularemic pneumonia, plague pneumonia, including laboratory and radiographic finding, are discussed . Ebola vieus and smallpox are also discussed as potential bioterrorist-transmitted infections from the clinical and epidemiologic standpoint . In addition to the clinical features of the infectious diseases mentioned, the article discusses the infectious disease control and epidemiologic implications of these agents when employed as bioterrorist agents . The review concludes with suggestions for postexposure prophylaxis and therapy. Vaccine, 2002 May 31, 20 Suppl 3, S48 - 50 Aluminum-containing vaccine associated adverse events: role of route of administration and gender; Pittman PR; Anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that is administered as six subcutaneous (s.q.) doses over 18 months . It is the only aluminum hydroxide licensed for s.q . administration . To optimize the vaccination schedule and route of administration, a prospective pilot study comparing the use of fewer doses administered intramuscularly (i.m.) as well as s.q . with the licensed schedule and route was performed . Data from that study on injection site reactions were extracted for this report . Erythema and induration occurred more commonly when the vaccine was administered s.q . compared to i.m . (P < 0.0001, P = 0.002, respectively) . S.q . nodules were found only among the s.q . group (P < 0.0001) . Erythema, induration and s.q . nodules were more common in women compared with men (P < 0.001) after the first s.q . dose of AVA dose . Reaction rates decreased when the interval between the first two doses of AVA was increased from 2 to 4 weeks. Infect Immun, 2002 Sep, 70(9), 4997 - 5007 Anthrax edema toxin requires influx of calcium for inducing cyclic AMP toxicity in target cells; Kumar P et al.; The anthrax edema toxin comprises two proteins: protective antigen and edema factor . Anthrax protective antigen binds to the receptors on the surface of target cells and facilitates the entry of edema factor into these target cells . Edema factor (EF) is an adenylate cyclase that catalyzes the synthesis of cyclic AMP (cAMP) in the cytosol of the host cells . In this study, we examined the requirement of extracellular calcium for anthrax edema toxin-induced toxicity in host cells . The cAMP response generated by edema toxin was analyzed in a variety of cells, including CHO, macrophage-like RAW264.7, human neutrophils, and human lymphocytes . Our investigations reveal that after EF reaches the cell cytosol, a rapid influx of calcium is triggered in the host cell that has a pivotal role in determining the cAMP response of the affected cells . Although the cAMP response generated by edema toxin in different cell types varied in intensity and in the time of initiation, the influx of calcium invariably preceded cAMP accumulation . Agents that blocked the uptake of calcium also inhibited edema toxin-induced accumulation of cAMP in the host cells . This is the first report that demonstrates that edema toxin induces accumulation of cAMP in lymphocytes . By accumulating cAMP, a potent inhibitor of immune cell function, edema toxin may actually be poisoning the immune system and thus facilitating the survival of the bacteria in the host. Neurology, 2002 Aug 13, 59(3), 327 - 34 Anthrax meningoencephalitis; Lanska DJ; OBJECTIVE: To review reported cases of anthrax meningoencephalitis and describe the clinical findings, diagnostic test results, treatment, and outcome over the past 50 years . METHODS: Retrospective review of English language articles published since Haight's (1952) review . RESULTS: Thirty-four core articles were identified, describing 70 patients with cutaneous (29%), gastrointestinal (17%), inhalational (39%), and unknown (16%) sources of infection . Clinical signs on presentation included fever, malaise, meningeal signs, hyperreflexia, and delirium, stupor, or coma . CSF analyses demonstrated hemorrhagic meningitis, with positive Gram's stains and CSF cultures . Many patients presented in extremis following a prodromal period of 1 to 6 days, and 75% died within 24 hours of presentation . Despite aggressive treatment in many cases, only 6% (4 of 70) survived, none of whom had pulmonary anthrax . Surviving patients generally had a cutaneous portal of entry, were younger, and had less severely abnormal initial CSF results than patients who died . Most of the survivors recovered fully . Pathologic findings included hemorrhagic meningitis, multifocal subarachnoid and intraparenchymal hemorrhages, vasculitis, and cerebral edema . CONCLUSIONS: Anthrax meningoencephalitis has a high case-fatality rate, even with aggressive antibiotic treatment and supportive therapy . Hemorrhagic meningitis should raise suspicion of anthrax infection, particularly if gram-positive rods are demonstrated on Gram's stain . Anthrax meningoencephalitis can develop from any primary focus, but survival appears to be most likely if meningoencephalitis develops from cutaneous anthrax . Treatment of surviving patients was generally begun before signs and symptoms of meningoencephalitis were present. Chest, 2002 Aug, 122(2), 741 - 5 Hypersensitivity pneumonitis following anthrax vaccination; Timmer SJ et al.; A case of hypersensitivity pneumonitis (HP) following anthrax vaccination is described . The patient is a 39-year-old, previously healthy man on active duty in the US Marine Corps, in whom a urticaral skin rash and progressive dyspnea on exertion developed following subcutaneous anthrax vaccination . A diagnosis of bronchiolitis obliterans with organizing pneumonia was made from transbronchial lung biopsy samples after evaluation excluded multiple infectious and collagen vascular etiologies . This appears to be the first recorded case of HP following an anthrax vaccination; however, a case report of pulmonary and cutaneous vasculitis following hepatitis B vaccination has been reported in the literature and is reviewed. Harefuah, 2002 May, 141 Spec No, 4 - 6, 124 {Characteristics of anthrax: its description and biblical name--Shehin}; Ben-Noun L; The illness known as Anthrax is very rare in the west . In developing countries relatively significant numbers of cases are found, particularly in animals . However, biological terrorist acts could cause it to spread . In Hebrew, the illness is now called Gahelet or Gameret . The purpose of this paper is to examine whether the illness is described in the Bible, and if so, to present that description and provide a broader survey of the features of this illness . The word Gahelet appears in the Bible, but not indicating a disease, while the source of Gameret is in the Talmud . In the Bible, Shehin is mentioned as the sixth of the ten plagues in Egypt, and also as the disease that affected Job . The natural course of the condition, as described in the Bible, matches the clinical symptoms of Anthrax, as we know it today . The Hebrew Language Academy is therefore advised to adopt the findings of this paper, and confirm the name of the illness in Israel--Shehin. Harefuah . 2002 May;141 Spec No:21, 123. {National preparedness for biological mass casualty event: between the devil and the deep blue sea}; Eldad A; Species of plants and animals, as well as nations of human beings were extinguished throughout the prehistory and history of this planet . One of the possible explanations for this phenomenon is a large scale epidemic of viral, bacterial or fungal infections . One well-documented example was the smallpox epidemic among native Indians of South America following the European invasion . Deliberate dissemination of disease was used as a weapon during the Middle Ages when corpses of plague casualties were thrown over the walls and into the besieged towns . The Book of Kings II, of the Bible, in chapter 19 recalls the story of 185,000 soldiers of Sennacherib that died in one night, near the walls of Jerusalem . The possibility of causing mass casualty by dissemination of infectious disease has driven countries and terrorist organizations to produce and store large quantities of bacteria or viruses . The death of thousands in the USA on September 11, 2001, demonstrated that terror has no moral prohibitions, only technical limitations . Terror organizations will not hesitate to use weapons for mass destruction to kill many, and if only few will die, it will still serve the purpose of these evil organizations: to strew panic, to destroy normal life and to increase fear and instability . Any government that faces decisions about how to be better prepared against biological warfare is pushed between the devil and the deep blue sea . On the one hand: the better we will be prepared, equipped with antibiotics and vaccines--the more lives of casualties we will be able to save . Better public education will help to reduce the damage, but, on the other hand--in order to cause more people to make the effort to equip themselves or to refresh their protective kit--we will have to increase their level of concern . In order to improve the medical education of all members of the medical teams we will have to start a broad and intense campaign, thereby taking the risk of increasing stress in the public in anticipation of such an attack . The more we will encourage patients who suffer flu-like syndromes to consult their family physician, the more instances of early detection of anthrax cases we will discover . However, in so doing, we will increase the level of national stress and flood primary medicine with many thousands of patients without being able to give our general practitioners any simple and effective tool for the diagnosis of anthrax in its early stages . Between the devil of biological warfare and the deep blue sea of public reaction, a small group of decision-makers and their professional advisers is under pressure . Israel is fortunate that this is not a new problem for this group of experts . Large scale drills, thorough preparations and adequate stockpiling of everything required marks the results of this group's activities . The state of Israel is today one of the best-prepared countries for such an event. Harefuah, 2002 May, 141 Spec No, 13 - 5, 124 {Bioterrorism}; Oren M; The terror attacks of the September 11, 2001 in the U.S.A followed by the proliferation of anthrax using mail in some US cities and abroad, demonstrated the complex, devastating and harmful nature of terror activity . The use of weapons of mass destruction (WMD) in terrorist activities is a reality as is the use of biological weapons (BW) in bioterrorism . Cyberterrorism is another form of non-conventional terrorism . The health care system throughout all its different components and layers--public health, primary care, hospitals, first responders etc., must be prepared . The complete network must have a comprehensive contingency plan for any possible BW scenario . The health care system must cope successfully with the challenge of early diagnosis of extraordinary illness or outbreak of disease, having the ability to define any bioterror event and to conduct appropriate risk assessments . It is of great importance to prepare in advance a comprehensive coordinated plan with all other governmental ministries and agencies . In order to succeed it is crucial that the top decision makers--the Prime Minister and government members and top ranking officials at the Ministry of Health, be committed, and continuously proactive in the complicated and lengthy process of preparing the health care system for a bioterrorism event. Harefuah, 2002 May, 141 Spec No, 100 - 4, 119, 118 {Tetracyclines and ciprofloxacin as treatment for children and pregnant or lactating women in the era of biological terror}; Aizenstien O et al.; Many forms of bacteria, such as anthrax, can be used as biological weapons . According to the CDC guidelines, Ciprofloxacin or Doxycycline is recommended for antimicrobial prophylaxis against anthrax for 60 days . Since October 8, approximately 32,000 persons with potential exposure to anthrax have initiated antimicrobial prophylaxis, mainly with Ciprofloxacin . Children and pregnant and lactating women are likely to be among the increasing number of persons receiving Ciprofloxacin or Doxycycline as a prophylaxis regardless of the potential danger of these drugs . Once the bacteria in question are shown to be sensitive to other antibiotics, treatment should be switched to antibiotics that are commonly used in children and pregnant women . The main consideration in prescribing these antibiotics is the fear of anthrax morbidity and mortality, as opposed to the risk of antibiotic side effects . The best treatment should be provided even though it can cause side effects . This paper reviews the information about the indications, dosage and side effects of Ciprofloxacin and Doxycycline in children and pregnant women and lactating women. Biomedica, 2002 Jun, 22(2), 106 - 9 {Species of the Bacillus strain: macroscopic and microscopic morphology}; Realpe ME et al.; Between October 2001 and January 2002, the Microbiology Group of the Instituto Nacional de Salud processed 705 envelopes under suspicion of harboring anthrax spores . We present photographs of cultures and slides prepared from them of Bacillus species to be used as reference material for the accurate macroscopic and microscopic identification of the agent found in samples. AACN Clin Issues, 2002 Aug, 13(3), 452 - 69 Issues in preparedness for biologic terrorism: a perspective for critical care nursing; O'Connell KP et al.; Although the use of microorganisms as weapons is as old a practice as war itself, the sense of our collective vulnerability to these agents has seldom been as great . The events of late 2001 demonstrated that the United States is vulnerable to terrorist attack carried out by highly motivated, organized, funded, and trained individuals . It is our collective good fortune that the perpetrator of the anthrax mailings was not bent on destruction of the scale witnessed on September 11, 2001 . Because acute care and critical care nurses are on the forefront of community disease surveillance, they must be aware of the signs and symptoms of illness that may indicate that a biological attack has taken place . Many symptoms of infection or intoxication by biological warfare agents (bacterial, viral, and toxic) are nonspecific and flulike in nature, at least early in the disease process . The essential details of the presentation, diagnosis, treatment, and prophylaxis of the biological warfare agents that merit greatest concern are provided, and five biological warfare agents of particular interest are described in detail: anthrax, ricin (castor bean) toxin, smallpox, plague, and tularemia . Recommendations are given for additional Web-based resources to allow further study. Acta Medica (Hradec Kralove), 2002, 45(1), 3 - 5 Anthrax toxin characterization; Patocka J et al.; The anthrax toxin comprises three proteins . When they work together, they can kill humans, especially after spores of the bacteria have been inhaled . One anthrax protein, called protective antigen (PA), chaperones the two other toxins into human or animal cells and shields them from the body's immune system . The second, lethal factor (LF), destroys the white blood cells that hosts send in defence . The third toxin molecule, edema factor (EF), hijacks the signaling system in the body . This disrupts the energy balance of cells and leads to them accumulating fluid and complete destroy of cells. Protein Pept Lett, 2002 Feb, 9(1), 1 - 14 Peptide toxins directed at the matrix dissolution systems of cancer cells; Frankel AE et al.; Growth and spread of tumors requires a variety of membrane and extracellular proteases to modify membrane integrins, dissolve the surrounding matrix and release critical growth factors from both the tumor cell surface and surrounding structures . The two major protease systems involved in this process are the matrix metalloproteases and the serine proteases . Genes and gene products for both protease systems are overexpressed in a variety of neoplasms . Thus, these enzymes serve as excellent targets for the delivery of potent cytotoxic molecules to tumors . A number of peptide toxins have been engineered to bind to tumor cells with high levels of surface proteases and their receptors including anthrax toxins, Pseudomonas exotoxin, saporin and diphtheria toxin . These recombinant fusion proteins provide a novel class of anti-cancer agents that will enter clinical trials in the next several years. Zh Mikrobiol Epidemiol Immunobiol, 2002 May-Jun, (3), 3 - 12 {Problem of bioterrorism under modern conditions}; Vorob'ev AA et al.; It is practically impossible to discuss the problem of bioterrorism (BT) and to develop effective programs of decreasing the losses and expenses suffered by the society from the BT acts without evaluation of the threat and prognosis of consequences based on research and empiric data . Stained international situation following the act of terrorism (attack on the USA) on September 11, 2001, makes the scenarios of the bacterial weapon use (the causative agents of plague, smallpox, anthrax, etc.) by international terrorists most probable . In this connection studies on the analysis and prognostication of the consequences of BT, including mathematical and computer modelling, are necessary . The authors present the results of initiative studies on the analysis and prognostication of the consequences of the hypothetical act of BT with the use of the smallpox causative agent in a city with the population of about 1,000,000 inhabitants . The analytical prognostic studies on the operative analysis and prognostication of the consequences of the BT act with the use of the smallpox causative agent has demonstrated that the mathematical (computer) model of the epidemic outbreak of smallpox is an effective instrument of calculation studies . Prognostic evaluations of the consequences of the act of BT under the conditions of different reaction of public health services (time of detection, interventions) have been obtained with the use of modelling . In addition, the computer model is necessary for training health specialists to react adequately to the acts of BT with the use of different kinds of bacteriological weapons. Exp Mol Pathol, 2002 Aug, 73(1), 19 - 27 Antibodies to squalene in recipients of anthrax vaccine; Asa PB et al.; We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P . B . Asa et al., Exp . Mol . Pathol 68, 196-197, 2000) . The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel . Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA) . In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA . In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05) . Further analysis revealed that ASA were associated with specific lots of vaccine . The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine . Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene . Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene . ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel . Three of these individuals became ASA positive after vaccination . These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine. J Assoc Physicians India, 2002 Jul, 50, 913 - 5 Problem of timely diagnosis in anthrax meningitis; Kanungo R et al.;