SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Of 60 patients with acute bilateral ophthalmoparesis, the cause was within the brainstem in 18 (pretectal infarct, phenytoin toxicity, and Wernicke's syndrome), in cranial nerves in 26 (Guillain-Barré or Fisher syndrome, tuberculous meningitis), within the cavernous sinuses in 8 (tumors or infection), and at the myoneural junction in 8 (myasthenia or botulism).
From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).
BACKGROUND: Dentists' responses to catastrophe have been redefined by bioterrorism. Informed response requires accurate information about agents and diseases that have the potential to be used as weapons. METHODS: The authors reviewed information about the most probable bioterrorist weapons (those from the Center for Disease Control and Prevention's Category A) from the World Wide Web and print journals and distilled it into a resource list that is current, relevant to dentistry and noncommercial. The Web sites cited include those sponsored by federal agencies, academic institutions and professional organizations. The articles cited include those published in English within the last six years in refereed journals that are available in most higher education institutions. RESULTS: The authors present the information in a table that provides a quick-reference guide to resources describing agents and diseases with the greatest potential for use as weapons: anthrax, botulism, plague, smallpox, tularemia and viral hemorrhagic fevers. This article presents Web site and journal citations for background and patient-oriented information (fact sheets), signs and symptoms, and prophylactic measures and treatment for each of the agents and diseases. The table facilitates quick access to this information, especially in an emergency. This article also points out guidelines for response should a suspected attack occur. CONCLUSIONS: Armed with information about biological weapons, dentists can provide faster diagnosis, inform their patients about risks, prophylaxis or treatment and rethink their own role in terrorism response. CLINICAL IMPLICATIONS: Fast, accurate diagnosis limits the spread of exceptionally contagious diseases. Providing accurate information to patients minimizes misinformation and the associated public fear and panic that, unchecked, could overwhelm health care systems.
Vaccination programmes are very successful as a preventive strategy against many infectious diseases which have had a major impact on human morbidity and mortality. One of these diseases, smallpox, has been eliminated as a natural infection. The recent concern about biological attacks has turned attention to the use of an immunisation programme to prevent infection with what are considered the most significant potentially harmful biowarfare pathogens. This review puts into perspective the available information on current immunisation and newer vaccine options for anthrax, smallpox, tularaemia, plague and botulism.
Since October 3, 2001, the Centers for Disease Control and Prevention and other organizations have been investigating potential bioterrorist-related anthrax cases. The pediatrician may be faced with complex issues related to diagnosis and treatment of illnesses caused by intentionally released biological agents. The agents that pose a major potential bioterrorist threat are reviewed by the clinical syndromes they produce: acute respiratory distress with fever, influenza-like illnesses, acute rash with fever, neurologic syndromes, and blistering syndromes. Specific and detailed diagnostic, treatment, and prophylaxis information is provided for anthrax, plague, tularemia, smallpox, botulism, viral hemorrhagic fevers, and other diseases. In cases of suspected bioterrorism, the pediatrician must be able to obtain diagnostic and treatment information efficiently and expeditiously. The system controlling the interaction between public and nonpublic health laboratories in suspected cases of bioterrorism is described. Finally, information regarding emergency contacts and links to educational resources is provided.
The looming threat of bioterrorism has enhanced interest in the development of vaccines against agents such as botulinum toxin. This in turn has stimulated efforts to create vaccines that are effective by the oral and inhalation routes. Recently, considerable progress has been made in creating an inhalation vaccine against botulism. This work stems from the discovery that a polypeptide that represents a third of the toxin molecule retains the ability to be adsorbed from the airway and to evoke an immune response but retains none of the adverse effects of the native toxin. Interestingly, this polypeptide can also serve as a carrier molecule in the creation of inhalation vaccines against other pathogens.
Botulinum neurotoxin is the neuromuscular poison that is responsible for the fatal disease botulism. This toxin is also a valued therapeutic agent in the treatment of an increasing number of neuromuscular disorders. Unfortunately, in the wrong hands, botulinum neurotoxin is also a deadly biological "weapon. The diverse health consequences of botulinum neurotoxin combined with the increased threat of bioterrorism underscore the profound importance of understanding exactly how this toxin exerts its effects on the clinically relevant mammalian target site, the neuromuscular junction. Despite the fact that a great deal has been learned about the cellular actions of botulinum neurotoxin during the past three decades, questions still remain. For example, what protein or proteins mediate transport of the toxin into the cholinergic nerve terminal? What factors control the duration of toxin action in the nerve terminal? Until recently, scholarly pursuit of such questions was technically challenging in neuromuscular tissues. Recent advancements in biotechnology have now made it feasible to pursue these important issues at the neuromuscular junction and to correlate biochemical studies in nontarget tissues with clinically relevant functional outcomes. This narrative reviews our current understanding of the actions of botulinum neurotoxin at the neuromuscular junction, presents recent findings from our own work in neuromuscular tissues, and encourages future studies regarding botulinum neurotoxin at its target site.
OBJECTIVE: The purpose of this study was to investigate whether this semiquantitative measurement of the motor end-plate acetylcholine receptors (AChRs) can be used to confirm the diagnosis of myasthenia gravis (MG), and in particular ocular MG. METHODS: Motor point biopsies were performed from the biceps brachii muscles. Measurement of AChRs was made in peroxidase-labeled alpha-bungarotoxin stained muscle specimens. PATIENTS: Twenty patients with ocular MG, 37 with generalized MG, 5 with Lambert-Eaton myasthenic syndrome, 3 with botulism, 8 with amyotrophic lateral sclerosis, and 8 controls were included in this study. RESULTS: AChRs were decreased in all patients with generalized MG and in 80% of ocular MG including patients without detectable circulating anti-AChR antibodies, as compared with the control subjects. CONCLUSION: This method is useful to confirm the diagnosis of MG, in particular ocular MG without detectable anti-AChR antibodies.
We encountered three patients (Patient I: 39-year-old man, Patient II: 34-year-old woman, and Patient III: 5-year-old girl) with acute methyl bromide poisoning, which had occurred as a result of exposure to the gas that leaked from methyl bromide cans stored in a warehouse of a seedling farm. Since all three patients exhibited almost the same initial symptoms, i.e., severe vomiting, tonic convulsions and clouding of consciousness, botulism was suspected at first. However, subsequent inquiry revealed that 27 cans of methyl bromide had been stored in the building that the patients lived in, and that the cans had been damaged a few days before the onset of the patients' illness by a thrashing machine that was being moved by them to another location. Inspection revealed that all the cans of methyl bromide had passed the expiry date and were corroded. Even though none of the cans had been used, three cans with a capacity of 750 g were found to be empty. Plasma bromide ion concentrations were determined to be high (72.9 microg/ml, 67.8 microg/ml and 91.5 microg/ml; normal level, < 5 microg/ml), and acute methyl bromide poisoning was diagnosed 8 days after admission of the patients to the hospital. Hemodialysis (peritoneal lavage in the case of the child) was performed immediately, after which the plasma bromide ion concentrations returned to normal and the general condition of the patients gradually improved.
REASONS FOR PERFORMING STUDY: The reasons why equine grass sickness (EGS) recurs on premises are unknown and, consequently, practical methods for reducing the risk of recurrence are not available. OBJECTIVES: To identify risk factors associated with recurrence of EGS on premises and to gain possible insights into the pathogenesis of the disease. METHODS: Data on disease history and risk factors were collected by postal questionnaire from premises with EGS cases between 1st January 1997 and 31st December 2001. Data on variation in rates of recurrence of EGS for different risk factors were analysed using Poisson regression analysis. RESULTS: Of 509 premises contacted, 305 (60%) returned useable questionnaires and 100 of these (33%) were classified as 'recurrent' premises. An overall median incidence rate for EGS of 2.1 EGS incidents/100 horses/premises/year was recorded. There was an increased rate of recurrence with higher numbers of horses, presence of younger animals, stud farms and livery/riding establishments, loam and sand soils, rearing of domestic birds and mechanical droppings removal. The rate of recurrence decreased with chalk soil, cograzing ruminants, grass cutting on pastures and removal of droppings by hand. Several statistically significant interactions were identified. CONCLUSIONS: Many of the findings are consistent with the theory that EGS is a toxico-infectious form of botulism. Several of the significant factors identified may directly or indirectly relate to soil disturbance and consequent soil contamination of grass, thereby increasing the rate of exposure of grazing horses to Clostridium botulinum, which resides in soil. POTENTIAL RELEVANCE: Identification of potentially modifiable risk factors may, ideally following validation in appropriately designed, controlled and randomised intervention studies, lead to practical measures to reduce the incidence of EGS on previously affected premises.
Little information is available in the United States regarding the incidence and distribution of diseases caused by critical microbiologic agents with the potential for use in acts of terrorism. We describe disease-specific, demographic, geographic, and seasonal distribution of selected bioterrorism-related conditions (anthrax, botulism, brucellosis, cholera, plague, tularemia, and viral encephalitides) reported to the National Notifiable Diseases Surveillance System in 1992 to 1999. Tularemia and brucellosis were the most frequently reported diseases. Anthrax, plague, western equine encephalitis, and eastern equine encephalitis were rare. Higher incidence rates for cholera and plague were noted in the western United States and for tularemia in the central United States. Overall, the incidence of conditions caused by these critical agents in the United States is low. Individual case reports should be considered sentinel events. For potential bioterrorism-related conditions that are endemic and have low incidence, the use of nontraditional surveillance methods and complementary data sources may enhance our ability to rapidly detect changes in disease incidence.
The events surrounding September 11, 2001, and its aftermath have compelled the public health and medical community to face the hitherto unfamiliar reality of bioterrorism. Physicians and public health personnel are frontline soldiers in this new form of warfare. This article provides a general overview of the pathophysiology, clinical presentation, diagnosis, and management of patients infected with the 6 highest priority agents that could potentially be used in bioterrorism. The diseases discussed include anthrax, smallpox, tularemia, plague, botulism, and viral hemorrhagic fevers. Despite the unpredictable nature of bioterrorism, disaster preparedness and knowledge of essential diagnostic and epidemiological principles can contribute substantially toward combating this new threat.
The ability of automated ribotyping to differentiate between major types and individual strains of Clostridium botulinum was tested using the Qualicon Riboprinter Microbial Characterization System. Pure spores of C. botulinum type A, proteolytic type B, nonproteolytic type B, and type E strains were inoculated onto modified anaerobic egg yolk agar and incubated 24 h at 35 degrees C. Plates were rinsed with buffer (2 mM Tris + 20 mM EDTA) to remove vegetative cells that were heated for 10 min at 80 degrees C, treated with a lysing agent, and ribotyped in the Qualicon Riboprinter utilizing the enzyme EcoRI. Riboprint patterns were obtained for 30 strains of the four major types of C. botulinum most commonly involved in human foodborne botulism. Proteolytic strains yielded the best and most consistent results. Fifteen ribogroups were identified among the 31 strains tested. Interestingly, in two cases, a single ribogroup contained patterns from isolates belonging to evolutionarily distinct Clostridium lineages. This degree of differentiation between strains of C. botulinum may be useful in hazard analysis and identification, hazard analysis and critical control point monitoring and validation, environmental monitoring, and in inoculation studies.
Botulism is a deadly disease caused by ingestion of the preformed neurotoxin produced from the anaerobic spore-forming bacteria Clostridium botulinum. Botulinum neurotoxins are the most poisonous toxins known and have been a concern in the food industry for a long time. Therefore, rapid identification of botulinum neurotoxin using molecular and biochemical techniques is an essential component in the establishment of coordinated laboratory response systems and is the focus of current research and development. Because of the extreme toxicity of botulinum neurotoxin, some confirmatory testing with the mouse bioassay is still necessary, but rapid methods capable of screening large numbers of samples are also needed. This review is focused on the development of several detection methods for botulinum neurotoxins in foods.
Tilapia (Oreochromis mossambicus) have been implicated as the source of type C toxin in avian botulism outbreaks in pelicans (Pelecanus erythrorhynchos, Pelecanus occidentalis californicus) at the Salton Sea in southern California (USA). We collected sick, dead, and healthy fish from various sites throughout the Sea during the summers of 1999 through 2001 and tested them for the presence of Clostridium botulinum type C cells by polymerase chain reaction targeting the C(1) neurotoxin gene. Four of 96 (4%), 57 of 664 (9%), and five of 355 (1%) tilapia tested were positive for C. botulinum type C toxin gene in 1999, 2000, and 2001, respectively. The total number of positive fish was significantly greater in 2000 than in 2001 (P<0.0001). No difference in numbers of positives was detected between sick and dead fish compared with live fish. In 2000, no significant relationships were revealed among the variables studied, such as location and date of collection.
In a 4-mo study (June 2004-September 2004), round gobies (Neogobius melanostomas) were dosed orally every 72 hr for up to 21 days with Clostridium botulinum neurotoxin type E (BoNT/E) at one of four doses: 0, 50, 250, and 500 mouse lethal doses (MLD). Fish were observed for changes in pigmentation and behavior for the duration of the experiment. Mortality was observed with all treatments, with the exception of the 0 MLD control. Clinical signs observed were consistent with prior research and appeared to occur in a threshold manner. The mean times to death and percent mortalities were dose dependent. Hazard ratios were determined to have a significant positive (parameter estimate = 0.03) linear relationship with dose. The hazard ratio showed that per one unit dose increase, the instantaneous probability of a fish dying increased 1.02%. Postmortem analysis of experimental fish demonstrated that 11% (3/27) of fish contained detectable BoNT/E in their visceral fraction. The other 89% tested negative for BoNT/E, despite the fact that all fish died as a result of BoNT/E exposure. Therefore, botulism should not necessarily be ruled out as the cause of a fish kill, even if the fish test negative for BoNT/E.
Conventionally raised suckling mice were given 10(7) spores of a strain of Clostridium botulinum type E. Most but not all infant mice aged 8 through 19 days at the time of administration died after developing symptoms typical of botulism. However, none of the infant mice challenged with the spores at dose levels lower than 10(6) spores/mouse developed illness.
Major human diseases caused by exotoxins produced by anaerobes include botulisms, tetanus, foodborne illness caused by enterotoxin-producing Clostridium perfringens, and diarrhea/colitis caused by toxigenic Clostridium difficile. Recently, enterotoxigenic Bacteroides fragilis (ETBF) has been recognized, that may be related to childhood diarrheal disease. Detection test of botulinal neurotoxin is hardly performed at clinical laboratories since the most reliable means of detection and identification of botulinal toxin is by using mouse toxicity and neutralization tests. Clinical laboratories should request the tests to a reference laboratory. Since tetanus is easily diagnosed clinically on the basis of its unique, recognizable sings, the bacteriological tests is not usually requested. C. perfringens foodborne illness can be confirmed by testing stool specimens or the suspect food(s) for enterotoxin by the reversed passive latex agglutination test or counting > 10 5 C. perfringens per g of suspected food or > 10 6 C. perfringens spores per g of stool. Diagnosis of C. difficile-associated diarrhea/colitis is confirmed by detection of toxins A or B of C. difficile and/or recovery of toxigenic C. difficile. Isolation of C. difficile strains or detection C. difficile-speciffic antigen from stool specimens is less diagnostic since nontoxic or toxin A positive-toxin B negative strains are prevalent in Japan. Reliable laboratory tests for ETBF-associated childhood diarrhea are not established yet although ETBF can be proved by polymerase chain reaction for detection of the enterotoxin gene.