FEBS Lett, 2003 Dec 4, 555(2), 375 - 9 Antagonism of botulinum toxin type A-induced cleavage of SNAP-25 in rat cerebral synaptosome by toosendanin; Zhou JY et al.; Toosendanin (TSN), a triterpenoid derivative extracted from Chinese traditional medicine, has been demonstrated to be an effective cure for experimental botulism . This study is designed to explore its antibotulismic mechanism by Western blotting . The results showed that TSN incubation did not change the electrophoresis pattern and the amounts of synaptosomal-associated protein of 25 kDa (SNAP-25), syntaxin and synaptobrevin/vesicle-associated membrane protein in rat cerebral synaptosomes, but made the synaptosomes completely resistant to botulinum neurotoxin A (BoNT/A)-mediated cleavage of SNAP-25 . After binding of BoNT/A to synaptosomes, TSN still partially antagonized the toxin-mediated cleavage of SNAP-25 . However, TSN-incubated synaptosomal membrane fraction did not resist the cleavage of SNAP-25 by the light chain of BoNT/A . It is suggested that the antibotulismic effect of TSN results from blocking the toxin's approach to its enzymatic substrate. Anal Bioanal Chem, 2004 Jan, 378(1), 68 - 75 Epub 2003 Nov 13. Ganglioside-liposome immunoassay for the detection of botulinum toxin; Ahn-Yoon S et al.; A rapid and highly sensitive receptor immunoassay for botulinum toxin (BT) has been developed using ganglioside-incorporated liposomes . Botulism outbreaks are relatively rare, but their results can be very severe, usually leading to death from respiratory failure . To exert their toxicity, the biological toxins must first bind to receptors on the cell surface, and the trisialoganglioside GT1b has been identified as the cell receptor for BT . Therefore, in this study, GT1b was used to prepare the ganglioside-liposomes by spontaneous insertion into the phospholipid bilayer . In a sandwich-based, hybrid receptor immunoassay, BT is detected as a colored band on a nitrocellulose membrane strip, where BT bound to the GT1b-liposomes are captured by anti-BT antibodies immobilized in a band across the strip . The intensity of the colored band can be visually estimated, or measured by densitometry using computer software . The limit of detection (LOD) for BT in the lateral-flow assay system was 15 pg mL(-1), which is comparable to the limits of detection achieved with the most sensitive assays previously reported . However, this rapid assay can be completed in less than 20 min . These results demonstrate that the sandwich assay using GT1b-liposomes for detection of BT is rapid and very sensitive, suggesting the possibility for detecting BT in field screening, simply and reliably, without the need for complex instrumentation. Eur J Clin Microbiol Infect Dis, 2003 Dec, 22(12), 749 - 52 Epub 2003 Nov 06. Nine cases of foodborne botulism type B in France and literature review; Abgueguen P et al.; Presented here is an outbreak of nine cases of type B botulism that occurred in France in 2000 followed by a review of the relevant literature . The outbreak resulted from the consumption of home-canned asparagus and required the intubation of six patients . Despite complications, all patients recovered completely . Specific antitoxin treatment was not administered because it is no longer manufactured in France . The literature review covers the epidemiologic data reported from Europe and the USA to date and an assessment of the treatment options for botulism . The usefulness of establishing a European network to provide access to botulism antitoxins is discussed . Although their efficacy is not unanimously accepted, they remain the only specific treatment now known. J Med Chem, 2003 Oct 23, 46(22), 4648 - 56 Development of potent inhibitors of botulinum neurotoxin type B; Anne C et al.; Botulinum neurotoxins are the most potent toxins known to date . They are zinc-metalloproteases able to cleave selectively an essential component of neurotransmitter exocytosis, causing the syndrome of botulism characterized by a flaccid paralysis . There is a great interest in designing antagonists of the action of these toxins . One way is to inhibit their catalytic activity . In this study, we report the design of such inhibitors directed toward BoNT/B . A study of the S(1) subsite specificity, using several beta-amino thiols, has shown that this subsite prefers a p-carboxybenzyl moiety . The specificity of the S(1)' and S(2)' subsites was studied using two libraries of pseudotripeptides containing the S(1) synthon derived from the best beta-amino thiol tested . Finally, a selection of various non natural amino acids for the recognition of the "prime" domain led to the most potent inhibitor of BoNT/B described to date with a K(i) value of 20 nM. Rev Neurol, 2003 Sep 1-15, 37(5), 444 - 6 {Iatrogenic botulism: a complication to be taken into account in the treatment of child spasticity}; Beseler-Soto B et al.; INTRODUCTION: During the last decades the use of botulinum toxin for management of muscular disorders and spasticity associated to cerebral palsy has become a widespread practice . CASE REPORT: A 6-years female suffering of cerebral palsy secondary to a partial agenesis of the corpus callosum who was receiving bolulinum toxin since October 2001 . One week after the last dose (Dysport 46 U/kg/dose) she started high grade fever, malaise, food refusal, choking, constipation, eyelid ptosis, absence of deep tendon reflexes, and abundant mucous discharge . Such features were so progressively severe that ventilatory support became mandatory . After a previous dose five months before, she developed similar features but they were less severe and thought to be related to a respiratory infection . CONCLUSIONS: At the present, there are two forms of botulinum toxin commercially available: the British brand Dysport and the American brand Botox . Bio equivalences are 1 U Botox to 2 or 6 U Dysport . Dosing (U/kg per session) has been established as follows: 5 U for Botox, 35 U for Dysport . Safety limits are a wide range with a therapeutic toxic index rate of 1:10 . Generalized side effects after diffusion to blood of locally injected botulinum toxin are rare. J Vet Intern Med, 2003 Sep-Oct, 17(5), 708 - 12 Mechanical ventilation in foals with botulism: 9 cases (1989-2002); Wilkins PA et al.; "Shaker foal" disease, toxicoinfectious botulism of foals, was 1st described as a clinical entity in 1967 . The reported mortality rate was 90%, with death occurring within 24-72 hours of the onset of the characteristic clinical signs . The mortality rate decreased when equine-origin botulism antitoxin became available; however, a certain percentage of foals continued to die of respiratory failure . Mechanical ventilation is an important part of the treatment of infant botulism and is essential to the survival of many affected infants . We report a retrospective study of 9 foals with toxicoinfectious botulism where early mechanical ventilation was employed as part of the treatment . Foals receiving mechanical ventilation were progressively acidemic and had increased PaCO2 tensions before mechanical ventilation . These arterial blood gas abnormalities were ameliorated with mechanical ventilation . One foal was euthanized for economic reasons; survival in treated foals was 87.5% . Mechanical ventilation of foals with botulism and respiratory failure appears to be an effective therapy. J Vet Intern Med, 2003 Sep-Oct, 17(5), 702 - 7 Botulism in foals less than 6 months of age: 30 cases (1989-2002); Wilkins PA et al.; Botulism has been recognized as a clinical entity in foals since the 1960s . Also known as "Shaker foal" disease, the toxicoinfectious form of botulism affects foals, with the highest incidence in the United States seen in Kentucky and the mid-Atlantic region . The disease is characterized by progressive muscular weakness caused by the action of botulism neurotoxin at cholinergic neuromuscular junctions . Increased number of episodes and duration of recumbency, muscular trembling, and dysphagia are seen in affected foals . Left untreated, the disease can be rapidly fatal, with death occuring secondary to respiratory muscle paralysis within 24 to 72 hours of the onset of clinical signs . Very mildly affected foals can survive with minimal treatment Despite advances made in treatment of these foals, including administration of botulism antitoxin early in the course of the disease, there is still an impression that the disease carries a high mortality rate . The purpose of this study was to evaluate outcome in 30 foals <6 months of age diagnosed with botulism between 1989 and 2002 at the George D . Widener Large Animal Hospital, New Bolton Center . Two foals were euthanized for economic reasons early in the disease course, and I died while being treated . Survival of treated cases was greater than 96% . Approximately 50% of the cases required oxygen therapy, whereas 30% required mechanical ventilation . All foals, excepting 1 mildly affected foal, received botulism antitoxin . Mean duration of hospitalization was 14 days . With appropriate treatment, foals with botulism have a high survival rate. Bioorg Med Chem, 2003 Oct 15, 11(21), 4655 - 60 Thio-derived disulfides as potent inhibitors of botulinum neurotoxin type B: implications for zinc interaction; Anne C et al.; Botulinum neurotoxin type B causes the inhibition of acetylcholine release at the neuromuscular junction resulting in a flaccid paralysis designated botulism . This occurs through the cleavage of synaptobrevin, an intracellular critical component of neurotransmitter exocytosis, by the zinc-metallopeptidase activity of the smallest subunit of the toxin . Blocking the proteolytic activity may present an attractive approach to treat botulism as to date there is no efficient specific drug therapy available . We have therefore recently described a series of beta-amino-thiol derived pseudotripeptides able of inhibiting the toxin at low (10(-8) M) concentration . In this study, binding characteristics of the protein's active site are explored through various structural modifications of the thiol functionality which was supposed to be a key structural constituent for effective zinc-ion chelation . Surprisingly, sulfanyl-derivatives such as symmetric disulfides were shown to be better inhibitors than their thiol-counterparts, the most potent compound displaying a Ki value of 3.4 nM. J Cell Biol, 2003 Sep 29, 162(7), 1293 - 303 Epub 2003 Sep 22. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells; Dong M et al.; Botulinum neurotoxins (BoNTs) cause botulism by entering neurons and cleaving proteins that mediate neurotransmitter release; disruption of exocytosis results in paralysis and death . The receptors for BoNTs are thought to be composed of both proteins and gangliosides; however, protein components that mediate toxin entry have not been identified . Using gain-of-function and loss-of-function approaches, we report here that the secretory vesicle proteins, synaptotagmins (syts) I and II, mediate the entry of BoNT/B (but not BoNT/A or E) into PC12 cells . Further, we demonstrate that BoNT/B entry into PC12 cells and rat diaphragm motor nerve terminals was activity dependent and can be blocked using fragments of syt II that contain the BoNT/B-binding domain . Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice . These findings establish that syts I and II can function as protein receptors for BoNT/B. MMWR Morb Mortal Wkly Rep, 2003 Sep 19, 52(37), 885 - 6 Wound botulism among black tar heroin users--Washington, 2003; Centers for Disease Control and Prevention (CDC); During August 22-26, 2003, four injection-drug users (IDUs) in Yakima County, Washington, sought medical care at the same hospital with complaints of several days of weakness, drooping eyelids, blurred vision, and difficulty speaking and swallowing . All four were regular, nonintravenous injectors of black tar heroin (BTH), and one also snorted BTH . This report summarizes the investigation of these cases, which implicated wound botulism (WB) as the cause of illness. Trends Microbiol, 2003 Sep, 11(9), 431 - 7 The journey of tetanus and botulinum neurotoxins in neurons; Lalli G et al.; Anaerobic bacteria of the genus Clostridia are a major threat to human and animal health, being responsible for pathologies ranging from food poisoning to gas gangrene . In each of these, the production of sophisticated exotoxins is the main cause of disease . The most powerful clostridial toxins are tetanus and botulinum neurotoxins, the causative agents of tetanus and botulism . They are structurally organized into three domains endowed with distinct functions: high affinity binding to neurons, membrane translocation and specific cleavage of proteins controlling neuroexocytosis . Recent discoveries regarding the mechanism of membrane recruitment and sorting of these neurotoxins within neurons make them ideal tools to uncover essential aspects of neuronal physiology in health and disease. Przegl Epidemiol, 2003, 57(1), 99 - 105 {Botulism in Poland in 2001}; Przybylska A; A total of 66 cases of botulism (foodborne) were registered in Poland in 2001, with corresponding incidence 0.17 per 100,000 population . The majority of cases (77.3%) were registered in rural areas . Incidence in these areas was 0.35 and in urban areas--0.06 . In 2001 there were 41 outbreaks of one person noted, 4 outbreaks of two people, 4 outbreaks of three, and 1 outbreak of four people . Meat dishes were the main vehicle of botulinum toxin (32 cases; 48.5%) . Out of them, home made conserves (bottling jars) prepared from pork meat prevailed (25.8% of the total) . Home made sausages were associated with 12.1% cases, commercial canned fish--with 10.6% and other dishes from fish--with 12.1% . Two deaths from foodborne botulism were registered in Poland in 2001. J Biotechnol, 2003 Aug 15, 103(3), 257 - 71 Identifying and modulating disulfide formation in the biopharmaceutical production of a recombinant protein vaccine candidate; Bouvier A et al.; Structural conversion of the serotype A recombinant botulinum neurotoxin heavy chain fragment (rBoNTA(Hc)) produced intracellularly in Pichia pastoris yeast was observed and characterized during purification development efforts . A pH screening study captured the transformation stages of the original recovered species into its derived counterpart and a number of analytical tools such as peptide mapping by LC/MS confirmed the formation of a disulfide bond, especially in samples of neutral to basic pH . A cation exchange chromatographic method proved useful in following the incidence of the reaction in various rBoNTA(Hc) samples . The disulfide formation kinetics were characterized using a one-quarter quadratic factorial design, following the investigation and development of controlled oxidation conditions using cysteine and cystamine as the redox pair . Temperature, pH and concentration of the redox pair had a significant effect on the yield and rate of the disulfide formation . This controlled reaction was eventually introduced as a functional unit operation in the purification process . The summation of preliminary scale-up and potency data showed scalability and robustness in the production of an active disulfide-bonded form of a recombinant botulism vaccine candidate . The presence of the disulfide bond did not effect the vaccine potency and it enhanced the molecule's thermal stability. Vaccine, 2003 Jul 28, 21(24), 3413 - 21 Immunization of pregnant women: reproductive, medical and societal risks; Brent RL; Establishing successful vaccine programs for pregnant women would be the quintessence of preventive medicine when you realize the preventive potential for reproductive problems of many of the new and old vaccines . The development of vaccines to prevent maternal, fetal and newborn disease is actually in its infancy . The risks and benefits are discussed in detail as well as the most appropriate and inappropriate time to immunize women of reproductive age and pregnant women . The great majority of risks are theoretical, but the problem is that birth defects and other developmental and reproductive problems are in the group of "diseases of affliction" which means that there are tremendous emotional upheavals in families affected with serious reproductive problems . The failures in reproduction are so common that immunization of a pregnant women has potential deleterious consequences . A consortium of government, academia and industry must work together and an appeal to the more responsible members of the law profession to solve the problem of non-meritorious litigation has be in place before manufacturers of vaccines will be willing to initiate the development of new vaccines . The potential for reducing the incidence of birth defects, prematurity and neonatal infectious disease exists, but it will be difficult to initiate these programs because vaccine makers may be unwilling to assume an additional burden of negligence litigation . Certainly, it is clear that we could provide a safe vaccine for Group B streptococcus and infant botulism that would be of immediate benefit and the potential for reducing other diseases is realistic . This is not going to be an easy task. J Am Dent Assoc, 2003 Jun, 134(6), 745 - 52 Bioterrorism and catastrophe response: a quick-reference guide to resources; Han SZ et al.; 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. An Sist Sanit Navar, 2003, 26 Suppl 1, 243 - 63 {Poisoning by foodstuffs, plants and mushrooms}; Pinillos MA et al.; Food poisoning is defined as poisoning caused by any foodstuff or alimentary product that causes poisoning because it contains toxic substances, germs, metals, additives, hormones, etc . It forms an important part of Clinical Toxicology, although in the majority of statistics, alimentary toxic infections provoked by bacteria, protozoa and viruses are not classified as poisonings, since they are caused by germs, and are classified as infections . Reference is made within this subject to all types of pathologies due to food, with special emphasis given to botulism . The clinical picture of botulism is discussed in its different clinical forms, but above all in its adult form which is contracted through the consumption of undercooked or badly preserved foods; poisoning by fish and seafood . Also described are the toxicological pictures that can be caused by the consumption of plants containing toxic substances, framed by the different symptomologies they produce; finally, poisonings by mushrooms are set out according to the period of incubation and possible confusions. Phys Med Rehabil Clin N Am, 2003 May, 14(2), 185 - 206 Repetitive nerve stimulation and exercise testing; Shapiro BE et al.; Repetitive nerve stimulation and exercise testing are useful in the evaluation of patients with suspected disorders of the NMJ and muscle membrane excitability when performed with close attention to technical factors . They can be very helpful in the diagnosis of myasthenia gravis . Lambert-Eaton myasthenic syndrome, and botulism, as well as rare disorders of skeletal muscle membrane excitability, including paramyotonia congenita, myotonia congenita, myotonic dystrophy, and the periodic paralyses. J Urban Health, 2003 Jun, 80(2 Suppl 1), i97 - 106 Syndromic surveillance using automated collection of computerized discharge diagnoses; Lober WB et al.; The Syndromic Surveillance Information Collection (SSIC) system aims to facilitate early detection of bioterrorism attacks (with such agents as anthrax, brucellosis, plague, Q fever, tularemia, smallpox, viral encephalitides, hemorrhagic fever, botulism toxins, staphylococcal enterotoxin B, etc.) and early detection of naturally occurring disease outbreaks, including large foodborne disease outbreaks, emerging infections, and pandemic influenza . This is accomplished using automated data collection of visit-level discharge diagnoses from heterogeneous clinical information systems, integrating those data into a common XML (Extensible Markup Language) form, and monitoring the results to detect unusual patterns of illness in the population . The system, operational since January 2001, collects, integrates, and displays data from three emergency department and urgent care (ED/UC) departments and nine primary care clinics by automatically mining data from the information systems of those facilities . With continued development, this system will constitute the foundation of a population-based surveillance system that will facilitate targeted investigation of clinical syndromes under surveillance and allow early detection of unusual clusters of illness compatible with bioterrorism or disease outbreaks. Clin Infect Dis, 2003 Jun 1, 36(11), 1458 - 73 Epub 2003 May 22. Bioterrorism web site resources for infectious disease clinicians and epidemiologists; Ferguson NE et al.; Finding bioterrorism-related information on the World Wide Web can be laborious . We hope to help readers find such information more easily by summarizing essential information in a consistent framework . A panel of 7 Centers for Disease Control and Prevention reviewers identified Web sites and evaluated them for sponsorship, mission, content usefulness, online ease of use, and adherence to commonly accepted quality criteria . Of >100 potential sites identified, 81 were chosen for target content of interest, and 43 were selected for inclusion . The results were classified into general purpose/portal sites; biological agent information; laboratory, infection control, epidemiology, and mental health information; and emergency contact sources, news and updates, event preparedness resources, information for first-responder settings, clinical and public education materials, and research resources . Agents covered included anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fever. Am Fam Physician, 2003 May 1, 67(9), 1927 - 34 Recognition and management of bioterrorism infections; O'Brien KK et al.; Recent events have demonstrated that bioterrorists have the ability to disseminate biologic agents in the United States and cause widespread social panic . Family physicians would play a key role in the initial recognition of a potential bioterrorism attack . Familiarity with the infectious agents of highest priority can expedite diagnosis and initial management, and lead to a successful public health response to such an attack . High-priority infectious agents include anthrax, smallpox, plague, tularemia, botulism, and viral hemorrhagic fever . Anthrax and smallpox must be distinguished from such common infections as influenza and varicella . Anthrax treatment is stratified into postexposure prophylaxis and treatment of confirmed cutaneous, intestinal, or inhalation anthrax . Disease prevention by vaccination and isolation of affected persons is key in preventing widespread smallpox infection . Many resources are available to physicians when a bioterrorism attack is suspected, including local public health agencies and the Centers for Disease Control and Prevention. Emerg Infect Dis, 2003 May, 9(5), 556 - 64 Endemic, notifiable bioterrorism-related diseases, United States, 1992-1999; Chang MH et al.; 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. Plasmid, 2003 Mar, 49(2), 93 - 105 Mobile genetic elements and bacterial toxinoses: the superantigen-encoding pathogenicity islands of Staphylococcus aureus; Novick RP; It is a remarkable observation that virtually all bacterial toxins associated with specific clinical conditions (toxinoses) are encoded by mobile (and therefore variable) genetic elements . Remarkably, these rarely, if ever, carry determinants of antibiotic resistance . Examples are the toxins responsible for diphtheria, anthrax, tetanus, botulism, cholera, toxic shock, scarlet fever, exfoliative dermatitis, food poisoning, travelers' diarrhea, shigella dysentery, necrotizing pneumonia, and others . A recently discovered example of this phenomenon is the family of related staphylococcal pathogenicity islands encoding superantigens (SAgs) . These are 15-20kb elements that occupy constant positions in the chromosomes of toxigenic strains, and are characterized by certain phage-related features, namely genes encoding integrases, helicases, and terminases, and the presence of flanking direct repeats . The prototype, SaPI1 of Staphylococcus aureus, encodes TSST-1 plus two newly described SAgs, SEK and SEL . Other members of the family encode enterotoxins B (SaPI3) and C (SaPI4), plus at least two other SAgs each . SaPI1 and SaPI2, also encoding TSST-1, are excised and induced to replicate by certain staphylococcal phages, and are then encapsidated at high efficiency into phage-like infectious particles with heads about 1/3 the size of the helper phage heads, commensurate with the sizes of the respective genomes . This results in transfer frequencies of the order of 10(8)/ml, and is presumably responsible for the spread of these elements as well as for their acquisition in the first place . In the absence of a helper phage, these two islands are highly stable; neither excision, loss, or transfer occurs at detectable frequency . Several general implications of this phenomenon will be discussed . One is that the determinants of these toxins have been imported from other species and therefore are not components of the basic genome of the extant producing organisms . This raises the question of the biological (adaptive?) roles of these toxins . Another is that the toxin-carrying units can spread among different (though probably related) species . An interesting question is that of the biological basis for the separation of toxin and resistance determinants. Eur Neurol, 2003, 49(3), 151 - 3 Early antitoxin treatment in wound botulism results in better outcome; Chang GY et al.; Wound botulism in 7 heroin 'skin poppers' produced ophthalmoplegia and descending paralysis . Rapid recovery occurred in 2 who received the antitoxin within the fourth day of symptom onset . A poor outcome was seen in 4 who received the antitoxin after the eighth day of symptoms and 1 who did not receive the antitoxin . Early antitoxin administration is important in achieving a favorable outcome . Euro Surveill, 1999 Jan, 4(1), 7 - 9 Classic and emergent forms of botulism: the current status in Italy; Aureli P et al.; Botulism is a rare, severe, neuroparalytic disease . Four forms of botulism are described in humans: foodborne botulism and the more recently described wound botulism, infant botulism, and infant-like botulism . The two last forms are sometimes grouped un Euro Surveill, 1999 Jan, 4(1), 2 - 7 Botulism in the European Union; Therre H; Botulinum toxin was first described as a potent neurotoxin in the late eighteenth century . Currently three main distinct clinical and epidemiological botulism syndromes are described - foodborne botulism, which results from the ingestion of food contamina Euro Surveill . 1999 Jan;4(1):1. Rare diseases deserve attention; Salmaso S; In August, Eurosurveillance published reports of two outbreaks of trichinellosis detected in 1998 in France and Italy and linked with horse meat imported from Yugoslavia . This issue, otherwise dedicated to botulism, includes a report of a third one . Repor Euro Surveill, 1999 Jun, 4(6), 69 - 72 Surveillance of foodborne botulism in Poland: 1960-1998; Galazka A et al.; Human foodborne botulism, in contrast to the other two forms of botulism (wound and infant botulism), is an intoxication that results when preformed botulinum toxin is ingested . Sporadic cases and family and general outbreaks occur when food products are MMWR Morb Mortal Wkly Rep, 2003 Jan 17, 52(2), 21 - 4 Infant botulism--New York City, 2001-2002; {Clinical and epidemiological analysis of patients with botulism hospitalized at the Department of Infectious Disease et al.; Bielec D, Semczuk G, Lis J, Firych J, Modrzewska R, Janowski R. Katedra i Klinika Chorob Zakaznych Akademii Medycznej w LublinieIn the paper we presented results of clinical and epidemiological analysis of 32 patients with botulism hospitalized at the Department of Infectious Diseases, Medical University of Lublin in 1990-2000 . In the studied group, the relationships between botulism incidence and sex and place of residence were not significant . The incubation period ranged from 7 hours to 5 days (average 36 hrs) . The clinical manifestations of botulism were typical in all cases . In one female patient the course of disease was complicated . She developed right-sided bronchopneumonia and left-sided purulent parotitis . The type B botulinum toxin occurred more frequently than the other types and the cases without serological confirmation (Chi 2 = 6.125 p = 0.01) . It was found in serum of 23 patients (in 2 cases together with the type A toxin) . The type E toxin was found in serum of one patient . The presence of toxin in serum was not detected in 8 patients . In all patients trivalent (types A, B and E) equine antitoxin was administered . The dose ranged from 50 to 150 cm3 . Symptomatic treatment was given in all cases . Nobody required mechanical ventilation . The duration of hospitalization ranged from 5 to 28 days (average 16.6 days) . A few patients complained of long-lasting blurred vision or dry mouth. Bull Soc Pathol Exot, 2002 Nov, 95(4), 272 - 5 {Botulism in Casablanca . (11 cases)}; Ouagari Z et al.; Botulism is a rare but severe disease . Whereas until 1980, only one case of botulism had been reported in our department, in 1999, a real botulism epidemic took place in Morocco . To our knowledge, it's the first outbreak of that kind in Morocco . We report here an epidemiologic and descriptive study of 11 patients suffering from botulism, admitted at the Infectious Diseases department and in the Medical Intensive Care Unit of Ibn Rochd University Hospital, from August, the 10th to October, the 1st, 1999 . Clinical diagnosis of botulism was made, at the admission, on ocular signs (diplopia, ptosis), swallowing troubles and/or muscle weakness . There was no fever, no trouble of conscience and normal reflexes, at the early stage of the disease . The average age of patients was of 23.9 years +/- 12.07 . Three patients were first admitted in the Medical Intensive Care Unit . The period before symptom appearance varied between 7 and 96 hours . Dysphagia sore throat, dry mouth and dysphonia were always found in all patients, with normal conscience . The fever was noted in 3 cases, polypnea in 3 cases leading to respiratory assistance in 2 cases . Neurologic findings were dominated by ptosis and hypotonia . The search of botulism toxin B in blood was positive in 6 cases . The electromyography showed clear signs of botulism . The evolution was favourable in 10 cases . Respiratory complications were found in 2 cases and infectious complications in 4 cases . One patient died . The period of hospitalization varied between 10 to 24 days with an average stay of 15.8 days . Eating "mortadella" has been noticed in 7 patients) and investigations permitted to identify the factory of "mortadella" as well as the toxin's type B responsible for these poisoning . It appears clearly that it is important to reinforce hygiene controls . Physicians and specialists in public health must be aware of the severity of this illness, knowing that the recovery is shortened when the treatment is administered on an early stage of the disease. Infect Immun, 2003 Mar, 71(3), 1147 - 54 Inhalational poisoning by botulinum toxin and inhalation vaccination with its heavy-chain component; Park JB et al.; Botulinum toxin is the etiologic agent responsible for the disease botulism, which is characterized by peripheral neuromuscular blockade . Botulism is ordinarily encountered as a form of oral poisoning . The toxin is absorbed from the lumen of the gut to reach the general circulation and is then distributed to peripheral cholinergic nerve endings . However, there is a widespread presumption that botulinum toxin can also act as an inhalation poison, which would require that it be absorbed from the airway . Experiments have been done to show that both pure toxin and progenitor toxin (a complex with auxiliary proteins) are inhalation poisons . Interestingly, the data indicate that auxiliary proteins are not necessary to protect the toxin or to facilitate its absorption . When studied on rat primary alveolar epithelial cells or on immortalized human pulmonary adenocarcinoma (Calu-3) cells, botulinum toxin displayed both specific binding and transcytosis . The rate of transport was greater in the apical-to-basolateral direction than in the basolateral-to-apical direction . Transcytosis was energy dependent, and it was blocked by serotype-specific antibody . The results demonstrated that the holotoxin was not essential for the process of binding and transcytosis . Both in vivo and in vitro experiments showed that the heavy-chain component of the toxin was transported across epithelial monolayers, which indicates that the structural determinants governing binding and transcytosis are found in this fragment . The heavy chain was not toxic, and therefore it was tested for utility as an inhalation vaccine against the parent molecule . This fragment was shown to evoke complete protection against toxin doses of at least 10(4) times the 50% lethal dose. Rev Neurol, 2003 Jan 1-15, 36, 93 - 6 {The most common dysautonomias}; Kaufmann H; Aims . To review the classification and the clinical and pathological characteristics of the most common dysautonomias . Method . Primary dysautonomia includes neurodegenerative diseases of unknown causes that are characterised by the intracytoplasmic accumulations of alpha synuclein that manifest with four different phenotypes: pure autonomic failure, Parkinson s disease, dementia with Lewy bodies and multiple system atrophy . Of the secondary dysautonomias, diabetes mellitus is the most common cause of autonomic neuropathy in developed countries . Familiar dysautonomia is a recessive autosomic disease; the gene responsible for it has been located in the long arm of chromosome 9 (9q31) . Paraneoplasic dysautonomia is associated with cancer of the lungs, the pancreas, Hodgkin s disease and testicular cancer . In Lambert Eaton myasthenic syndrome and in botulism the release of acetylcholine is deficient in both the somatic and the autonomic neurons . There are other diseases that affect autonomic cholinergic neurotransmission without bringing about any disorders in neuromuscular transmission . Chagas disease affects the neurons of the parasympathetic ganglion and produces megaesophagus, megacolon and myocardiopathy . Dopamine beta hydroxylase enzyme deficiency is a congenital disease characterised by the failure to convert dopamine into noradrenaline which results in orthostatic hypotension . Conclusions . Dysautonomias can be classified, according to their aetiology, as primary or secondary; according to the deficient neurotransmitter, as cholinergic, adrenergic and mixed (pan dysautonomia) or, according to the anatomical distribution of the neurons that are affected, as central and peripheral. Tidsskr Nor Laegeforen, 2002 Dec 10, 122(30), 2860 - 2 {Botulism in Osterdalen in 1831}; Schjonsby HP; The earliest report we have had of an outbreak of botulism in Norway is from 1934, of five cases caused by contaminated salted and dried ham . All patients survived . This paper describes an early outbreak of botulism in the county of Hedmark in 1831 on the basis of a previously unknown report to the county governor from district public health officer Peter Heiberg (1778-1849) . Two cases were reported, one of them fatal . The contaminated food was salted and fermented trout or char. J Paediatr Child Health, 2003 Jan-Feb, 39(1), 22 - 6 Acute flaccid paralysis in Australian children; Morris AM et al.; OBJECTIVES: To describe the epidemiology and causes of acute flaccid paralysis (AFP) in Australian children, and the clinical features of the two most common causes of AFP, Guillain-Barre syndrome and transverse myelitis . METHODS: Monthly active surveillance for AFP was carried out through the Australian Paediatric Surveillance Unit, with AFP defined as 'acute onset of flaccid paralysis in one or more limbs or of bulbar paralysis in any child less than 15 years of age' . RESULTS: Between March 1995 and December 1999, 143 cases of AFP were reported (approximately 0.8 per 100000 children < 15 years of age per annum) . The age range was 2 months-14 years and 59% were boys . Out of these children, 137 (96%) were hospitalized and 47 required intensive care . No case of wild or vaccine-associated poliomyelitis was identified . The most common causes of AFP were Guillain-Barre syndrome in 67 (47%) and transverse myelitis in 27 (19%) . Other diagnoses included acute disseminated encephalomyelitis, trauma, tick-bite paralysis and infantile botulism . CONCLUSION: The participation of paediatricians in AFP surveillance contributed to the accreditation of Australia (along with the other 36 countries of the western Pacific region) as 'polio free' by the World Health Organization in October 2000 . The surveillance also provided data on the frequency of AFP and identified Guillain-Barre syndrome and transverse myelitis as the most common diagnoses . In this large national series, many other conditions that may present as non-polio AFP were identified. Rev Inst Med Trop Sao Paulo, 2002 Nov-Dec, 44(6), 321 - 4 Botulism: a laboratory investigation on biological and food samples from cases and outbreaks in Brazil (1982-2001); Gelli DS et al.; Laboratory investigation of botulism from 1982 to 2001 confirmed the occurrence of eight positive outbreaks/cases of botulism in Brazil . From those, type A botulism was observed in seven of them . Biological material of one case (serum and feces) was positive in the first step of the bioassay, but the amount of sample was not sufficient for typification . One of the outbreaks that occurred in 2001 was negative for botulinum toxin in samples of serum, gastric washing and feces, collected eight days before the onset of the symptoms in the affected person who was clinically diagnosed as presenting the disease . Other two cases presenting compatible clinical diagnoses presented negative results . However, in those cases, the collection of samples was (1) after antiserum administration or (2) later than eight days of the onset of symptoms . Investigation was performed by mouse bioassay, as described in the Compendium of Methods for the Microbiological Examination of Foods (compiled by American Public Health Association--APHA)11, using specific antiserum from Centers for Disease Control (CDC), USA. Expert Opin Biol Ther, 2002 Dec, 2(8), 883 - 93 Vaccines for Category A bioterrorism diseases; Lutwick LI et al.; 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. Microbes Infect, 2002 Oct, 4(12), 1271 - 80 Anaerobic infections in children; Brook I; Anaerobic bacteria can cause a variety of endogenous infections in children . Because of their fastidious nature, they are difficult to isolate from infectious sites, and are often overlooked . Anaerobic infections can occur in all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues . They colonize the newborn after delivery and have been recovered from several types of neonatal infections . These include cellulitis of the site of fetal monitoring, neonatal aspiration pneumonia, bacteremia, conjunctivitis, omphalitis, and infant botulism . The lack of adequate therapy may lead to clinical failures . Their isolation requires appropriate methods of collection, transportation and cultivation of specimens . Treatment is complicated by their slow growth, their polymicrobial nature and their growing resistance to antimicrobials . Antimicrobial therapy is often the only form of therapy required, whereas in others it is an important adjunct to a surgical approach . Because anaerobes are generally recovered mixed with aerobic organisms, the choice of antimicrobial agents should provide coverage of both types of pathogens. J Neurophysiol, 2002 Dec, 88(6), 3243 - 58 Impairment of synaptic vesicle exocytosis and recycling during neuromuscular weakness produced in mice by 2,4-dithiobiuret; Xu YF et al.; Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy . DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear . The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing . We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness . Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K(+) depolarization . Terminals ranged from those with nearly normal fluorescence ("bright terminals") to terminals that were poorly labeled ("dim terminals") . Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable . A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals . Two findings suggest that posttetanic "slow endocytosis" remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles . In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block with D-tubocurarine . Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by alpha-latrotoxin . Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness . The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing. Toxicon, 2002 Dec, 40(12), 1635 - 60 Poisonous plants affecting livestock in Brazil; Tokarnia CH et al.; Plant poisoning, together with rabies and botulism, are the main causes of death in adult cattle in Brazil . Estimates indicate that about one million head of cattle die annually through plant poisoning in this country . There are approximately 75 plants of practical importance to animal husbandry that have had their toxicity confirmed by experiments with the animal species affected under natural conditions . The great majority of these plants only occur in Brazil and neighbouring countries . A few of them are forage plants that can become toxic under certain conditions . In this review the poisonous plants of interest to animal husbandry of Brazil are divided according to the clinical-pathological picture they cause in cattle; only cyanogenic plants, plants that cause nitrate/nitrite poisoning and the ones that cause oxalate poisoning, are grouped according to their toxic principles . Plants and their toxic principles, or of which possible toxic compounds have been isolated, are listed. Ann Med Interne (Paris), 2002 Sep, 153(5), 300 - 10 {Clinical and epidemiological characteristics of botulism in France}; Boyer A et al.; Botulism is still found in France . Botulism is life-threatening and may have epidemic occurrences, which justifies an epidemiological watch with systematic notification of cases . In order to complete these recent epidemiological data, older cases since 1940 have been reviewed through a survey sent to the French Ministry of Health and the Pasteur Institute (National Reference Center) . A Medline search has also been completed . In France, foodborne botulism is the main source of contamination . Type B is nearly always involved but type E botulism has been regularly reported . Fatal outcome due to botulism-induced respiratory muscle weakness can now be avoided by mechanical ventilation, leading to better prognosis . Microbiological diagnosis has been confirmed in two-thirds of the cases by isolation of toxin in the patient's serum . It is important to identify the foodstuff incriminated to prevent the development of a botulism outbreak . Foodstuffs responsible for foodborne botulism are the same since 1940 . However, the increased consumption of vacuum-packed foodstuffs might facilitate the persistence of botulism . In conclusion, this review points out the significance of epidemiological screening of foodstuffs in the alimentary chain as well as the systematic notification of botulism . The regular educational information for young physicians regarding botulism should be continued. MMWR Morb Mortal Wkly Rep, 1999 Oct 15, 48(40), 905 - 13 Safer and healthier foods. {Prevention of bioterrorism by vaccines} Levy JP. Institut Pasteur, 28, rue du Docteur-Roux, 75724 Paris, France . jplevy@pasteur.fr Prevention against the weapons of bioterrorists is limited by the multiplicity of agents that could be used . Against smallpox, stocks of the classical vaccine must be prepared, but this vaccine is dangerous and we must look for a new and safer vaccine . A vaccine against anthrax is probably possible relatively soon . One may be less optimistic concerning plague, since it is not sure that we could protect against the pulmonary plague, but research in this field is an emergency . The large number of viruses capable of inducing haemorrhagic fevers makes especially difficult the preparation of vaccines against these infections . We must also make available monoclonal antibodies that could be used as therapies against toxin, notably botulism, or against antibiotic-resistant bacteria. J Biol Chem, 2003 Jan 10, 278(2), 1363 - 71 Epub 2002 Oct 14. Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A . Basis for distinct durations of inhibition of exocytosis in central neurons; Foran PG et al.; Seven types (A-G) of botulinum neurotoxin (BoNT) target peripheral cholinergic neurons where they selectively proteolyze SNAP-25 (BoNT/A, BoNT/C1, and BoNT/E), syntaxin1 (BoNT/C1), and synaptobrevin (BoNT/B, BoNT/D, BoNT/F, and BoNT/G), SNARE proteins responsible for transmitter release, to cause neuromuscular paralysis but of different durations . BoNT/A paralysis lasts longest (4-6 months) in humans, hence its widespread clinical use for the treatment of dystonias . Molecular mechanisms underlying these distinct inhibitory patterns were deciphered in rat cerebellar neurons by quantifying the half-life of the effect of each toxin, the speed of replenishment of their substrates, and the degradation of the cleaved products, experiments not readily feasible at motor nerve endings . Correlation of target cleavage with blockade of transmitter release yielded half-lives of inhibition for BoNT/A, BoNT/C1, BoNT/B, BoNT/F, and BoNT/E (31, 25, approximately 10, approximately 2, and approximately 0.8 days, respectively), equivalent to the neuromuscular paralysis times found in mice, with recovery of release coinciding with reappearance of the intact SNAREs . A limiting factor for the short neuroparalytic durations of BoNT/F and BoNT/E is the replenishment of synaptobrevin or SNAP-25, whereas pulse labeling revealed that extended inhibition by BoNT/A, BoNT/B, or BoNT/C1 results from longevity of each protease . These novel findings could aid development of new toxin therapies for patients resistant to BoNT/A and effective treatments for human botulism. Neurochem Res, 2002 Aug, 27(7-8), 697 - 709 Complex gangliosides as autoantibody targets at the neuromuscular junction in Miller Fisher syndrome: a current perspective; O'Hanlon GM et al.; Glycosphingolipid biology has increasingly interfaced with the field of human autoimmune neuropathy over the last two decades . There are currently over 20 distinct glycolipids that have been identified as autoantibody targets in a wide range of clinical neuropathy syndromes . This review sets out the clinical and experimental background to one interesting example of anti-glycolipid antibody-associated neuropathy termed Miller Fisher syndrome . This syndrome, comprising the triad of ataxia, areflexia, and ophthalmoplegia, correlates highly with the presence of serum anti-GQ1b antibodies, arising through molecular mimicry with microbial oligosaccharides . Anti-GQ1b antibodies mediate neural injury through binding to GQ1b-enriched sites in the peripheral nervous system, including extraocular nerves . Animal experimental evidence, along with a hypothetical background, indicates the motor nerve terminal may be a key site for anti-GQ1b antibody binding with consequent defects in synaptic transmission, as occurs in botulism and other toxinopathies . Our work in recent years on this hypothesis is summarized. Przegl Epidemiol, 2002, 56(2), 305 - 10 {Botulism in Poland in 2000}; Przybylska A; A total of 72 cases of botulism were registered in Poland in 2000, with corresponding incidence 0.19 per 100,000 population . In the rural areas 56 (incidence 0.38), and in the urban areas 16 (incidence 0.07) cases were registered . In 2000, there were 46 outbreaks of one person, 7 outbreaks of two people, and 4 of three people noted . Meat dishes were the main vehicle of the botulinum toxin (41 cases; 56.9%) . Of them, prevailed homemade conserves (bottling jars) prepared from pork meat (18.1%) . Home made sausages were associated with 13.9%, canned fish with 12.5%, sausages of commercial production--with 12.5%, and dishes from poultry with 11.1% cases . Two deaths from botulism were registered in Poland in 2000. Afr Women Health, 1993 Apr-Jun, 1, 8 - 12 Why mother's milk is best; Choto RG; PIP: Breast milk substitutes made of water, porridge, or animal milk were given to babies only as a life-saving effort prior to World War II, in the event of lack of mother's milk, breast infection or the death of the mother . In the post-war era of the early 1950's, improperly constituted infant formulas became prevalent in the industrialized world to allow the release of women into the work force . Advertising and marketing techniques were also launched in Third World countries, which became easy victims of this ploy because of ignorance, poverty, and inadequate sanitation . Medical consequences include infections from contamination at the source (infantile botulism); hyponatremia, hypocalcaemia, with poor muscle, heart, and brain functioning, from over dilution with water; and infectious diarrhea, which can lead to marasmus and kwashiorkor, from mixture contaminated water . Breast milk contains colostrum, a supercharged nutrient that ensures meeting the infant's immediate energy needs as well as providing antibodies to most childhood diseases . Infant formulas cannot provide this protection . The introduction of weaning foods occurs around 5-6 months of age, when local foodstuffs rather than commercial supplements ought to be used . However, semi-literate mothers are often exposed to radio advertising about substitutes that overwhelm them . Their infants get formula diluted in unclean water and unsuitable solids too early . They will eventually live on fresh cow's milk with the attendant problems of anemia and bovine tuberculosis . Breast-feeding also provides a practical means of birth control and child spacing . The government should enact a national code on the manufacture, nutritional contents, and sale of these substitutes . Orv Hetil, 2002 Aug 18, 143(33), 1935 - 9 {Microbial warfare and bioterrorism}; Ongradi J; Infectious diseases have been used as warfares since ancient times . Since the 1920s military organizations have studied bacteria of anthrax, plague, tularemia, botulism, brucelloses, glander, Q-fever, and smallpox virus, Filo-, Arena-, Bunyaviruses causing hemorrhagic fever or Alphaviruses eliciting encephalitis . These can be dispersed by aerosol . Salmonellae, Shigellae, Vibrio cholerae, distinguished Escherichia coli strains are suitable to contaminate food, water, pharmaceutical products . Fanatical groups or terrorist individuals deploy microbe weapons . In the future, genetically engineered recombinant microbes could be used with genomes containing multiple resistance elements to antimicrobial compounds and additional virulence factors . These become resistant to all known treatment regimens, vaccination and the host immune response . Microbial terrorist attacks result in an outbrake on a restricted area with large number of casualties . The disease course is severe and unusual followed by high mortality . Identification of microbes is complicated and delayed . Most countries have neither laboratories at high biosafety level nor specially trained personnel . Physicians might misdiagnose these diseases . Health care systems with minimal elasticity face difficulties in maintaining mass quarantine . A considerable part of health care workers leave hospitals . No plan is available to stockpile medicines . Robust surveillance and laboratory systems coordinated at international level must be established . All health care personnel should be trained periodically to gain practical skills . Additional standards governing working conditions with selected microbes will be enforced by law . Related scientific data might be published with restricted access only. Nervenarzt, 2002 Jun, 73(6), 519 - 24 {Botulinum toxin--the dose controls the poison . A historical sketch}; Homann CN et al.; Botulism, a potentially lethal form of paralytic food poisoning, was described as early as 1793 . Basic research, especially in the late nineteenth and early twentieth centuries, revealed that botulism is caused by exotoxins . Further biochemical work around and after the Second World War gave insight into the molecular structure of seven different serotypes of botulinum toxin (BT/A-G) as well as into its acetylcholine blocking mode of action . In 1977, Scott treated patients with strabism by injecting minute amounts of purified BT/A . In short sequence, BT proved effective in blepharospasm, cervical dystonia, and various off-label indications . In the near future, registration of these new indications, marketing of new serotypes (BT/B), and availability of more practical antibody tests can be expected . The first applications of BT were performed by Roggenkaemper, Dressler, and Benecke in Germany and by Poewe and Auff in Austria . According to a worldwide trend, a rapid expansion regarding BT users and indications followed . Formation of BT competence centers in both countries aims at maintaining high standards in BT research and education. Dis Mon, 2002 May, 48(5), 336 - 56 Complications and adverse reactions with the use of botulinum toxin; Klein AW; Botulinum toxins are the causative agents of the severe food-borne illness botulism . With lethal doses approximating 10(-9) g/kg body weight, these neurotoxins represent some of the most toxic naturally occurring substances . Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle spasms with adverse effects being typically self-limited . This article deals with some of the complications that have occurred with these treatments . The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent treatment . Prevalence of resistance is less than 5% . Most complications associated with its aesthetic use are few and anecdotal . Nevertheless, the common problems and pitfalls associated with aesthetic treatment of the various areas of the face and neck with botulinum toxin are discussed . Also included are recommendations as to how to avoid these very undesirable, yet common, problems. Proc Natl Acad Sci U S A, 2002 Aug 20, 99(17), 11346 - 50 Epub 2002 Aug 12. Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody; Nowakowski A et al.; The botulinum neurotoxins (BoNTs) cause the paralytic human disease botulism and are one of the highest-risk threat agents for bioterrorism . To generate a pharmaceutical to prevent or treat botulism, monoclonal antibodies (mAbs) were generated by phage display and evaluated for neutralization of BoNT serotype A (BoNT/A) in vivo . Although no single mAb significantly neutralized toxin, a combination of three mAbs (oligoclonal Ab) neutralized 450,000 50% lethal doses of BoNT/A, a potency 90 times greater than human hyperimmune globulin . The potency of oligoclonal Ab was primarily due to a large increase in functional Ab binding affinity . The results indicate that the potency of the polyclonal humoral immune response can be deconvoluted to a few mAbs binding nonoverlapping epitopes, providing a route to drugs for preventing and treating botulism and diseases caused by other pathogens and biologic threat agents. Can J Vet Res, 2002 Jul, 66(3), 158 - 64 Investigation of repeated vaccination as a possible cause of glomerular disease in mink; Newman SJ et al.; The search for antigens capable of causing immune-complex-mediated glomerulonephritis continues . Modified live-virus vaccines commercially available for veterinary use are a possible source . In this study, repeated vaccination of mink with live-virus vaccines was investigated as a model for vaccine-induced glomerular injury . Three groups of 10-wk-old mink, 15 per group, were vaccinated once with 4-way vaccine against distemper, Pseudomonas aeruginosa infection, botulism and mink viral enteritis . Subsequently, all mink in each group each were vaccinated either with the 4-way vaccine, a monovalent canine distemper vaccine, or saline . Glomerular function was assessed at 2-wk intervals by determining the urinary protein:creatinine (P:C) ratio . Kidney sections taken at necropsy, 20 wk after the 1st vaccination, were examined by light and immunofluorescent microscopy for deposition of immunoglobulin and complement . There was no statistically significant difference between the treated and control groups based on average urinary P:C ratio medians . Light microscopic changes were detected in glomeruli, but Fisher's exact test showed no significant differences between any of the treatment groups . Deposition of immunoglobulin but not complement was significantly more frequent (P < 0.05) in the glomeruli of animals that received multiple injections of the 4-way vaccine than in the glomeruli of those given only the monovalent canine distemper vaccine or saline . These findings suggest that repeated vaccination may increase the glomerular deposition of immunoglobulin . Further studies are required to determine if the increased deposition of immunoglobulin contributes to the development of glomerular damage and to identify the antigens driving production of the deposited immunoglobulin. Annu Rev Microbiol, 2002, 56, 167 - 85 Epub 2002 Jan 30. Bioterriorism: from threat to reality; Atlas RM; The fears and predictions of attacks with biological weapons, which were increasing at the close of the twentieth century, were transformed into reality not long after September 11, 2001, when several anthrax-laden letters were sent through the U.S . postal system . The attack challenged our medical preparedness and scientific understanding of the epidemiology of biothreat agents . It is fortunate that this was not a massive aerosol release that could have exposed hundreds of thousands . Rapid diagnoses and medical treatments limited casualties and increased survival rates, but tragically some individuals died of inhalational anthrax . Even as physicians tested new treatment regimes and scientists employed new ways of detecting anthrax and decontaminating the mail, new predictions were made for potentially even more devastating attacks with anthrax, smallpox, plague, tularemia, botulism, or hemorrhagic fever viruses . Fear gripped the nation . Law enforcement sought to find the villain(s) who sent the anthrax letters and to deter future bioterrorist attacks . The biomedical community began to seek new ways of protecting against such future threats of bioterrorism. Mayo Clin Proc, 2002 Jul, 77(7), 661 - 72 Confronting bioterrorism: physicians on the front line; Varkey P et al.; 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. ALTEX, 2002, 19 Suppl 1, 49 - 54 {PCR and ELISA--in vitro alternatives to the mouse-bioassay for assessing the botulinum-neurotoxin-C1 production potential in environmental samples?}; Zechmeister TC et al.; Botulism is one of the most important bird diseases world-wide and is caused by the intoxication with Botulinum-Neurotoxin-C1 (BoNt-C1), which is produced by toxigenic clostridia under appropriate conditions . Avian botulism leads regularly to large losses among the migrating bird populations breeding and resting at the saltwater pools of the Austrian national park Neusiedler See-Seewinkel . Despite of its ethical dubiousness and its high technical expense the mouse-bioassay is still used as the routine standard method for the detection of BoNt-C1 . According to the 3R-concept, in vitro alternative methods for the qualitative detection of BoNt-C1 (immunostick-ELISA) and a corresponding BoNt-C1 gene fragment (nested-PCR) were established . In order to estimate the BoNt-C1 production potential the methods were tested with sediment samples from different saltwater pools subjected to cultivation conditions appropriate for in vitro BoNt-C1-production . With the mouse-bioassay, 52 out of 77 samples were found to have a positive toxin production potential . The immunostick-ELISA showed a similar sensitivity as the mouse-bioassay and exhibited a highly significant positive correlation (r=0.94; p<0.001) with the mouse-bioassay in detecting BoNt-C1 . The nested-PCR approach revealed higher numbers of positive BoNt-C1 gene fragment detections as compared to the direct toxin analysis approaches . A weak correlation (r=0.21; p=0.07) with the mouse-bioassay was discernible, no correlation was found with the immunostick-ELISA (r=0.09; p=0.46) . Obviously, the PCR approach detected the BoNt-C1 gene fragment in some of the samples where no toxin expression has occurred . Thus it is suggested that the qualitative immunostick-ELISA represents a potential in-vitro alternative to the mouse-bioassay for assessing the BoNt-C1 production potential in environmental samples . In contrast, qualitative BoNt-C1 gene fragment detection via PCR led to an overestimation of the actual toxin production potential. Med J Aust, 2002 May 6, 176(9), 431 - 3 Biological agents as weapons 1: smallpox and botulism; Whitby M et al.; 1 . Early recognition by clinicians of illnesses suggesting a biological attack is integral to the public health response . 2 . The four biological agents of most concern are smallpox virus, botulinum toxin, and anthrax and plague bacteria . 3 . Smallpox is distinguishable from chickenpox by the prominent prodromal period and lesions that develop at the same pace and, on any part of the body, appear identical to each other, evolve slowly and are peripherally distributed . 4 . The degree of protection conferred by smallpox vaccination given 20 or more years ago is unknown . 5 . Foodborne and inhalational botulism could result from deliberate release of toxin . 6 . Botulism presents with cranial nerve palsies and descending paralysis in a patient with normal conscious state and no fever. Int J Circumpolar Health, 2002 Feb, 61(1), 50 - 60 Botulism among Alaska natives in the Bristol Bay area of southwest Alaska: a survey of knowledge, attitudes, and practices related to fermented foods known to cause botulism; Chiou LA et al.; OBJECTIVES: Botulism cases due to traditional Alaska Native fermented foods occur periodically in Southwest Alaska . In this population, we conducted a survey on knowledge, attitudes, and practices related to botulism and fermented foods . METHODS: We interviewed 140 adults randomly chosen from nine villages . Data collected included fermented food consumption frequency; knowledge about the cause and symptoms of botulism; and fermented food preparation methods . RESULTS: Most respondents (81%) had eaten Alaska Native fermented foods at least once . Over 70% identified botulism as a foodborne illness, and over 87% believed eating certain Native fermented foods could cause botulism . One-third of fermented food preparers used plastic containers for fermentation . To prevent botulism, 45% vwould consider boiling fermented foods, and 65% would not eat foods fermented in plastic or glass containers . CONCLUSIONS: Despite high awareness of botulism in this population, one-third of fermented food preparers use plastic containers, a practice which may increase the risk of botulism . Misconceptions and acceptable prevention messages about botulism, such as using traditional nonplastic fermentation methods, were identified and included in an educational video. Acta Otorrinolaringol Esp, 2002 Jan, 53(1), 27 - 31 {Results of using botulism toxin in the treatment of spasmodic dysphonia}; Larrosa F et al.; Spasmodic Dysphonia (SD) is a dystonia involving laryngeal musculature thus causing a characteristic voice disorder . Two main types of SD have been described . The adductor type is the commonest and it is characterized by a strain-strangle, choked voice . The abductor type can be distinguished from the previous one by episodes of a blown and whispering voice, interrupting speech . Botulism toxin (BTX) has demonstrated to be the most effective treatment for this condition . Thirty patients diagnosed of SD (twenty-nine adductor type/one abductor type) were included . Their degree of dysphonia was evaluated using both functional and visual-analogue scales . They were treated with BTX vocal cord injections using a percutaneous technique under EMG guidance . Improvements up to a 100% of the normal vocal function were obtained, with an average of 82% in the adductor type . The adverse effects were mild and transient . Hypophonia affected 61.3% of patients lasting an average of 11.3 days . Dysphagia was reported in 44.1% of cases lasting an average of 5.8 days. Presse Med, 2002 Apr 6, 31(13), 601 - 2 {Treatment of severe botulism with 3,4-diaminopyridine}}; Dock M et al.; INTRODUCTION: The specific treatments of botulism with serotherapy and with guanidine are of debatable efficacy . We report a case of nutritional toxin B botulism successfully treated with 3,4-diaminopyridine . OBSERVATION: Following a meal, a 69 year-old woman consulted for digestive disorders followed by damage to several cranial pairs, autonomous nervous system and ventilation command, motivating mechanical ventilation on tracheal intubation . Administration of symptomatic treatment with 3,4-diaminopyridine led to progressive improvement, although the diagnosis of toxin B botulism was confirmed . COMMENTS: Administration of 3,4-diaminopyridine, the efficacy of which had been suggested by the review of experimental literature, led to rapid and clear improvement, probably due to its potentiating effect on acetylcholine release in the neuromuscular junction. Nurs Manage, 2002 Jan, 33(1), 43, 45 - 7 Bioterrorism's invisible threats: heightened awareness will help nurses identify real and suspected bioterrorism; Altman GB; Ready your nursing staff for potential bioterrorism with this review of the symptoms and treatment of anthrax, smallpox, plague, tularemia, and botulism. AAOHN J, 2002 Apr, 50(4), 174 - 81 Planning for biological disasters . Occupational health nurses as "first responders"; Salazar MK et al.; 1 . As a result of recent terrorist events, there is an immediate need for occupational nurses to review their disaster plans and to develop strategies to cope with bioterrorism in their workplaces . 2 . The Centers for Disease Control and Prevention has identified three major categories of biological weapons . Category A, which is the highest priority category (and the focus of this article), includes smallpox, anthrax, botulism, plague, tularemia, filoviruses, and adenoviruses . Dealing with bioterrorism requires occupational health nurses to be familiar with these organisms, including their pathophysiology and methods of prevention, detection, and treatment . 3 . Five principles can be used to guide responses to a biological attack . Incorporation of these principles into disaster planning will increase the effectiveness of responses to bioterrorism, if and when it occurs . Developing a plan of action before an event occurs will greatly enhance the likelihood that the repercussions of such an event are minimized. Otolaryngol Head Neck Surg, 2002 Mar, 126(3), 234 - 9 Airway complications of infant botulism: ten-year experience with 60 cases; Anderson TD et al.; OBJECTIVE: The study goal was to understand the incidence, etiology, and management of airway complications in infant botulism . METHODS: We conducted a retrospective review of the period from January 1, 1987, to December 31, 1997 . SETTING: Urban tertiary care children's hospital . RESULTS: Of 60 children with infant botulism, 37 (61.7%) required endotracheal intubation for a mean of 21 days . No patient required a tracheostomy . Airway complications (stridor, subglottic stenosis, granuloma formation) occurred in 5 (13.5%) of 37 patients, with 3 requiring surgical bronchoscopy . Of the 37 children, 14 (37.8%), including 4 with airway complications, had endotracheal tube leak pressures recorded . In 3 (50%) of 6 patients with measured leak pressures of greater than 40 cm H2O, airway complications developed . Complications did not develop in patients with leak pressures of less than 20 cm H2O . No correlation between length of intubation and complications could be established . CONCLUSION: Airway complications in infant botulism may be accompanied by high leak pressures and can be managed with endoscopic techniques . The study data suggest that leak pressures should be measured on a regular basis and maintained at less than 20 to 25 cm H2O . A prospective trial to study this issue is warranted . Tracheotomy is not routinely necessary . A high index of suspicion, early diagnosis, and prompt intervention are required for the optimal management of airway complications in infant botulism. J Cell Sci, 2002 Apr 15, 115(Pt 8), 1635 - 42 Novel syntaxin gene sequences from Giardia, Trypanosoma and algae: implications for the ancient evolution of the eukaryotic endomembrane system; Dacks JB et al.; SNAP receptors or SNARES are crucial components of the intracellular membrane system of eukaryotes . The syntaxin family of SNAREs have been shown to have roles in neurotransmission, vesicular transport, membrane fusion and even internal membrane compartment reconstruction . While syntaxins and SNAREs in general have been well characterized in mammalian and yeast models, little is known about their overall distribution across eukaryotic diversity or about the evolution of the syntaxin gene family . By combining bioinformatic, molecular biological and phylogenetic approaches, we demonstrate that various syntaxin homologs are not only present in 'eukaryotic crown taxa' but across a wide range of eukaryotic lineages . The alignment of evolutionarily diverse syntaxin paralogs shows that an isoleucine residue critical to nSec1-syntaxin complex formation and the characteristic syntaxin glutamine residue are nearly universally conserved, implying a general functional importance for these residues . Other identified functional residues involved in botulism toxicity and calcium-binding-protein interactions are also compared . The presence of Golgi-related syntaxins in the intestinal parasite Giardia intestinalis provides further evidence for a cryptic Golgi in this 'adictyosomal' taxon, and another likely case of secondary reduction in this parasite . The phylogeny of syntaxins shows a number of nested duplications, including a case of parallel evolution in the plasma membrane-associated syntaxins, and ancestral duplications in the other syntaxin paralogs . These speak to ancient events in the evolution of the syntaxin system and emphasize the universal role of the syntaxins in the eukaryotic intracellular compartment system. Pediatrics, 2002 Apr, 109(4), 685 - 92 Diagnosis and management of suspected cases of bioterrorism: a pediatric perspective; Patt HA et al.; 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. Drugs, 2002, 62(4), 705 - 22 Botulinum toxin B: a review of its therapeutic potential in the management of cervical dystonia; Figgitt DP et al.; Botulinum toxins are well known as the causative agents of human botulism food poisoning . However, in the past two decades they have become an important therapeutic mainstay in the treatment of dystonias including cervical dystonia, a neurological disorder characterised by involuntary contractions of the cervical and/or shoulder muscles . The toxins inhibit acetylcholine release from neuromuscular junctions, producing muscle weakness when injected into dystonic muscles . Data from three double-blind, randomised, placebo-controlled trials demonstrate that botulinum toxin B effectively reduces the severity, disability and pain of cervical dystonia . In two of the trials, mean Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 (primary efficacy measure) after botulinum toxin B 10 000U was reduced by 11.7 (25%) or 11 (21%) compared with baseline . These changes were significantly greater than those obtained with placebo {4.3 (10%) or 2 (4%)} and were generally similar in patients who were responsive or resistant to botulinum toxin A . Statistically significant benefits compared with placebo were also evident for a range of other efficacy parameters including TWSTRS-Severity, -Pain and -Disability subscales, patient- assessed pain and patient-/physician-assessed global improvement ratings . In another trial, the percentage of patients with botulinum toxin A-resistant or -responsive cervical dystonia who had a > or =20% improvement in the TWSTRS-Total score between baseline and week 4 was significantly higher with botulinum toxin B 2500 to 10 000U (58 to 77%) than with placebo (27%) . Overall, botulinum toxin B was generally well tolerated . The most frequently reported treatment-related adverse events were dry mouth and dysphagia . Most adverse events in patients receiving botulinum toxin B were mild or moderate; no serious adverse events or laboratory abnormalities were associated with the use of botulinum toxin B and, where reported, no patients discontinued from any of the clinical trials as a result of adverse events . CONCLUSIONS: Botulinum toxin B has shown clinical efficacy in patients with cervical dystonia at doses up to 10 000U and is generally well tolerated . Its efficacy extends to patients who are resistant to botulinum toxin A . Although the potential for secondary resistance to botulinum toxin B remains unclear, it may occur less than with botulinum toxin A because methods for manufacturing commercially available botulinum toxin B do not include lyophilisation and the product does not require reconstitution before use . As injection with botulinum toxin is generally considered the treatment of choice for patients with cervical dystonia, botulinum toxin B should be considered a potential treatment option in this setting. Int J Med Microbiol, 2002 Feb, 291(6-7), 447 - 53 Lipid microdomains are involved in neurospecific binding and internalisation of clostridial neurotoxins; Herreros J et al.; The neuroparalytic syndromes of tetanus and botulism are caused by tetanus and botulinum neurotoxins, which are produced by bacteria of the genus Clostridia . These neurotoxins are structurally organised in three-domains endowed with different functions: specific interaction with the neuronal surface, membrane translocation and specific cleavage of three key components of the neurotransmitter release apparatus . Despite an identical intracellular activity, tetanus and botulinum neurotoxins are characterised by a differential intraneuronal trafficking, which is likely to be responsible for the different symptoms observed in clinical tetanus and botulism . This review aims to highlight recent discoveries on the recruitment of clostridial neurotoxins (CNTs) to the surface of neurons and neuronally-differentiated cell lines and to discuss their relevance for the internalisation and sorting of these neurotoxins. J Assoc Acad Minor Phys, 2002 Jan, 13(1), 9 - 13 Bioterrrorism: a primer for 2002; Lutwick LI et al.; The often anticipated, sometimes dismissed, threat of biological terrorism became a reality in the United States in the fall of 2001 with cases of cutaneous and inhalation anthrax . As the public health sector is rapidly focusing on enhancing awareness and preparedness, this overview is intended as a primer for clinicians . The more probable events, their most prominent characteristics, and currently available management strategies are summarized . The biowarfare characteristics of plague, tularemia and botulism are summarized . The more problematic anthrax and smallpox are presented in greater detail . Epidemiological clues to a biological attack are outlined with reference to the recent literature. Ned Tijdschr Geneeskd, 2001 Dec 29, 145(52), 2513 - 6 {Totally paralyzed or brain dead?}; van Dijk GW et al.; In two patients, men aged 23 and 42 years, a condition that mimicked brain death was observed as a consequence of rapidly progressive complete peripheral paralyses, which included the intrinsic and extrinsic eye muscles . However, the EEG revealed a waking pattern . Maximal supportive therapy was provided, which included haemodialysis for the first patient and artificial ventilation for both patients . A slow recovery was seen after four weeks . The first patient was paralyzed following the ingestion of a large quantity of ethylene glycol and the second by botulism due to the consumption of injudiciously canned food . In patients with catastrophic brain injury, the diagnosis of brain death can be confirmed by a clinical neurological examination . In considering the diagnosis 'brain death', the most important criterion is that the cause of the brain damage is established . If the cause is insufficiently, the presence of brain death should be seriously doubted, unless an isoelectric EEG is observed. Vet Clin North Am Small Anim Pract, 2002 Jan, 32(1), 189 - 206, vii Myasthenia gravis and disorders of neuromuscular transmission; Shelton GD; Myasthenia gravis is a disorder of neuromuscular transmission that occurs in congenital and acquired autoimmune forms . Acquired myasthenia gravis is probably the most common neuromuscular disorder in dogs that can be diagnosed and treated . An early, accurate diagnosis and appropriate therapy is of utmost importance to a good clinical outcome in this disorder . This article focuses on the diagnosis and treatment of acquired myasthenia gravis in dogs and cats with brief discussions of other disorders of neuromuscular transmission, including congenital myasthenia gravis, tick paralysis, botulism, and organophosphate intoxication. Eur J Emerg Med, 2001 Dec, 8(4), 295 - 300 Ciguatera poisoning: a global issue with common management problems; Ting JY et al.; Ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food-borne illness related to contaminated fish consumption . As many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the Pacific Basin, Indian Ocean and Caribbean . Isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as Europe and North America . Increase in travel between temperate countries and endemic areas and importation of susceptible fish has led to its encroachment into regions of the world where ciguatera has previously been rarely encountered . In the developed world, ciguatera poses a public health threat due to delayed or missed diagnosis . Ciguatera is frequently encountered in Australia . Sporadic cases are often misdiagnosed or not medically attended to, leading to persistent or recurrent debilitating symptoms lasting months to years . Without treatment, distinctive neurologic symptoms persist, occasionally being mistaken for multiple sclerosis . Constitutional symptoms may be misdiagnosed as chronic fatigue syndrome . A common source outbreak is easier to recognize and therefore notify to public health organizations . We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu . All responded well to intravenous mannitol . This is in contrast to a fifth patient who developed symptoms suggestive of ciguatoxicity in the same week as the index cases but actually had staphylococcal endocarditis with bacteraemia . In addition to a lack of response to mannitol, clinical and laboratory indices of sepsis were present in this patient . Apart from ciguatera, acute gastroenteritis followed by neurological symptoms may be due to paralytic or neurotoxic shellfish poisoning, scombroid and pufferfish toxicity, botulism, enterovirus 71, toxidromes and bacteraemia . Clinical aspects of ciguatera toxicity, its pathophysiology, diagnostic difficulties and epidemiology are discussed. MMWR Morb Mortal Wkly Rep, 2001 Aug 17, 50(32), 680 - 2 Botulism outbreak associated with eating fermented food--Alaska, 2001; Botulism in the horse; Department of Veterinary Sciences and Wyoming State Veterinary Laboratory, University of Wyoming, Laramie, Wyoming, USA . fgaley@uwyo.edu Botulism should be considered in cases where weakness, paralysis, or intolerance to exercise might be seen in the horse . Dysphagia may also be present, although it is not a consistent finding . Potential sources include carrion in hay, moldy or otherwise rotted vegetation or forage, birds carrying material from animal burial or other similar sites, and contaminated carcasses on-site . Horses, especially foals, may also suffer from toxicoinfectious botulism, a condition where the C . botulinum might colonize and produce toxin within the gastrointestinal tract . Wounds also may harbor the organism and otherwise promote botulism . Diagnosis of botulism is often a clinical diagnosis backed up by elimination of other possible infectious, injurious, or toxic causes of weakness of the horse . Definitive diagnosis and type identification in the laboratory are difficult and usually require a suitable sample of the source material . Treatment often is unrewarding unless a case is identified early and the proper antitoxin is readily available . Prevention involves common sense approaches to feeding and care of the horse and, where possible, judicious use of vaccination in endemic areas. Am J Health Syst Pharm, 2001 Dec 1, 58(23), 2274 - 84 Pharmacy preparedness for incidents involving weapons of mass destruction; Burda AM et al.; Recent worldwide terrorist acts and hoaxes have heightened awareness that incidents involving weapons of mass destruction (WMD) may occur in the United States . With federal funding assistance, local domestic preparedness programs have been initiated to train and equip emergency services and emergency department personnel in the management of large numbers of casualties exposed to nuclear, biological, or chemical (NBC) agents . Hospital pharmacies will be required to provide antidotes, antibiotics, antitoxins, and other pharmaceuticals in large amounts and have the capability for prompt procurement . Pharmacists should become knowledgeable in drug therapy of NBC threats with respect to nerve agents, cyanide, pulmonary irritants, radionucleotides, anthrax, botulism, and other possible WMD. Ind Health, 2001 Oct, 39(4), 353 - 8 Three cases of acute methyl bromide poisoning in a seedling farm family; Yamano Y et al.; 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. Int J Food Microbiol, 2001 Sep 28, 69(3), 183 - 90 Traditional Maori food preparation methods and food safety; Whyte R et al.; Descriptions were obtained from Maori elders knowledgeable in traditional methods for the processing of Tiroi (mussels and Puha), Kina (sea urchins), Kanga Kopiro (fermented maize) and Titi (muttonbird) . Information for a number of variations of each method was transformed into process flow charts, and these charts were analysed using a HACCP-based approach . Two of the processes (Kanga Kopiro and Titi) were found to be likely to produce safe foods as Kanga Kopiro undergoes an acid fermentation and Titi preparation involves significant cooking steps . However, the information regarding Tiroi and Kina processing did not supply the necessary data to identify definitely whether fermentations were involved, and if they were, what kind they may be . New Zealand has only experienced one outbreak of botulism, and this was associated with the consumption of Tiroi . It is, therefore, desirable to identify the processes occurring in these foods where the nature of these processes is not understood in order to facilitate their safe future production. Eur J Emerg Med, 2001 Sep, 8(3), 233 - 6 Abrupt-onset oculomotor paralysis: an endocrine emergency; Famularo G et al.; Pituitary apoplexy is a severe and potentially life-threatening condition that may be highly variable in its clinical presentation . We report a 37-year-old man presenting to the emergency department with diplopia that abruptly developed while he was eating canned and bottled food prepared at home . A computed tomography scanning revealed an isodense mass within the sellar region and, subsequently, a magnetic resonance imaging showed a pituitary apoplexy causing a compression of the right III and VI oculomotor nerves . There was no improvement with hydrocortisone therapy and the patient underwent a transsphenoidal excision of the mass with an uneventful course . Pituitary apoplexy may raise in the appropriate setting the suspicion of botulism . The abrupt-onset paralysis of oculomotor nerves has been described as the chief presenting sign of pituitary apoplexy in only few cases including this . A pathophysiology, differential diagnosis with botulism and other causes of multiple cranial nerve paralysis, and treatment are described. Przegl Epidemiol, 2001, 55(1-2), 103 - 9 {Botulism in Poland in 1999}; Przybylska A; Total 97 cases of botulism were registered in 1999 in Poland with incidence 0.25/100,000 . In the rural area were registered 61 (incidence 0.41/100,000), and in the urban regions 36 (incidence 0.15) cases . The incidence among men (0.32) outnumbered the incidence among women (0.18) . In 1999 there were 68 outbreaks of one person noted, 6 outbreaks of two people, 3 of three people and 2 of four people . Dishes from meat were the main vehicle of the botulinum toxin (58 cases; 59.8%) . In this number prevailed home made conserves (wecks) from pork meat (26.8%) . No deaths were registered in 1999. Chest, 2001 Aug, 120(2), 562 - 6 Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism; Sandrock CE et al.; STUDY OBJECTIVES: To our knowledge, the predictors of respiratory failure (RF) and long-term mechanical ventilation have not previously been examined in patients with wound botulism associated with black tar heroin use . DESIGN: Retrospective case series . SETTING: A large university hospital . PATIENTS: Twenty consecutive patients from 1991 to 1998 with a diagnosis of wound botulism associated with drug use as identified through chart records from a single institution . RESULTS: The predominant mode of drug use was subcutaneous (75%) . Fifteen of 20 patients (75%) developed RF . The clinical presentation was similar in groups with RF and without RF . Of those patients who received antitoxin within 12 h of presentation, 57% required mechanical ventilation compared to 85% of patients receiving the antitoxin after 12 h . The median durations of mechanical ventilation were 11 days for those who received antitoxin within 12 h, and 54 days for those who did not receive antitoxin within 12 h . The duration of mechanical ventilation for patients receiving antibiotics within 12 h was 35 days vs 54 days for patients receiving antibiotics after 12 h . Early tracheostomy (< 10 days after initial intubation) was associated with a shorter duration of mechanical ventilation (median, 45 days vs 60 days, respectively) . CONCLUSION: Early antitoxin administration may decrease the need for and duration of mechanical ventilation among patients with wound botulism . Early tracheostomy may be beneficial for patients with RF. Semin Cutan Med Surg, 2001 Jun, 20(2), 109 - 20 Complications and adverse reactions with the use of botulinum toxin; Klein AW; Botulinum toxins are the causative agents of the severe food-borne illness botulism . With lethal doses approximating 10(-9) g/kg body weight, these neurotoxins represent some of the most toxic naturally occurring substances . Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle spasms with adverse effects being typically self-limited . This article deals with some of the complications that have occurred with these treatments . The greatest concern with the use of BOTOX is probably the formation of blocking antibodies leading to nonresponse of subsequent treatment . Prevalence of resistance is less than 5% . Most complications associated with its aesthetic use are few and anecdotal . Nevertheless, the common problems and pitfalls associated with aesthetic treatment of the various areas of the face and neck with botulinum toxin are discussed . Also included are recommendations as to how to avoid these very undesirable, yet common, problems. Eur Urol, 2001 May, 39(5), 610 - 2 Transient paralysis of the bladder due to wound botulism; Sautter T et al.; In the last 10 years, wound botulism has increasingly been reported and nearly all of these new cases have occurred in injecting-drug abusers . After absorption into the bloodstream, botulinum toxin binds irreversibly to the presynaptic nerve endings, where it inhibits the release of acetylcholine . Diplopia, blurred vision, dysarthria, dysphagia, respiratory failure and paresis of the limbs are common symptoms of this intoxication . Surprisingly and despite the well-known blocking action of the botulinum toxin on the autonomic nerve system, little attention has been paid to changes in the lower urinary tract following acute botulinum toxin poisoning . Here we report a case of bladder paralysis following wound botulism . Early diagnosis and adequate management of bladder paralysis following botulism is mandatory to avoid urologic complications . Accordingly, the prognosis is usually favorable and the bladder recovery complete. Anaesth Intensive Care, 2001 Jun, 29(3), 297 - 300 Severe adult botulism; Mackle IJ et al.; A case of severe adult botulism with paralysis, respiratory failure and cranial nerve palsies is presented . The pathophysiology, clinical manifestations, diagnosis and treatment options for botulism are discussed. J Biol Chem, 2001 Aug 24, 276(34), 32274 - 81 Epub 2001 Jun 19. The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin; Fotinou C et al.; Tetanus toxin, a member of the family of Clostridial neurotoxins, is one of the most potent toxins known . The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the ganglioside-binding sites . The ganglioside induces cross-linking by binding to two distinct sites on the Hc molecule . The structure sheds new light on the binding of Clostridial neurotoxins to receptors on neuronal cells and provides important information relevant to the design of anti-tetanus and anti-botulism therapeutic agents. Anal Biochem, 2001 Apr 15, 291(2), 253 - 61 High-throughput fluorogenic assay for determination of botulinum type B neurotoxin protease activity; Anne C et al.; Botulinum neurotoxins are responsible for botulism, a flaccid muscular paralysis caused by inhibition of acetylcholine release at the neuromuscular junction . This occurs by cleavage of conserved proteins involved in exocytosis such as synaptobrevin by the zinc metallopeptidase activity of the light chain of some botulinum neurotoxins . Botulism, for which there is presently no therapy available, is a relatively widespread disease that may result in death . Consequently, the development of drugs able to inhibit the hydrolytic activity of these neurotoxins is of great interest . Design and screening of such inhibitors could be largely facilitated by using high-throughput assays . With this aim, a novel in vitro test for quantifying the proteolytic activity of botulinum type B neurotoxin was developed . The substrate is the 60--94 fragment of human synaptobrevin-1 which was modified by introduction of the fluorescent amino acid l-pyrenylalanine in position 74 and a p-nitrophenylalanyl residue as quenching group in position 77 . The cleavage of Syb 60-94 {Pya(74), Nop(77)} by the toxin active chain occurs selectively between residues 76 and 77 as in the case of the unmodified synaptobrevin and is directly quantified by measuring the strong fluorescence of the formed metabolite Syb 60-76 {Pya(74)} . This is the easiest, quickest, and cheapest assay described to date for measuring the proteolytic activity of botulinum type B neurotoxin . It can be easily automated for high-throughput screening . Moreover, amounts of about 3.5 pg/ml of botulinum type B neurotoxin could be detected by this method . Intern Med, 2001 May, 40(5), 376 - 81 Semiquantitative measurement of acetylcholine receptor at the motor end-plate in myasthenia gravis; Tsujihata M et al.; 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. J Emerg Med, 2001 May, 20(4), 371 - 5 Wound botulism associated with black tar heroin and lower extremity cellulitis; Mitchell PA et al.; Wound botulism is a rare and potentially fatal disease . The use of black tar heroin has spawned an increase in the incidence of the disease, with the majority of cases occurring in California . The use of botulism antitoxin and surgical debridement are recommended to decrease hospital stay . For this to be effective, the diagnosis of wound botulism first must be considered, followed by an aggressive search for any area of infection that may be debrided . This case report demonstrates several factors to consider in patients presenting with symptoms of botulism poisoning: occurrence away from the Mexico border, no obvious abscess, and the need for prolonged ventilatory support . This case report documents a prolonged hospital stay, possibly caused by delay in administration of antitoxin in a patient with cellulitis that was not considered appropriate for debridement. Eur J Clin Microbiol Infect Dis, 2001 Mar, 20(3), 192 - 5 Two cases of foodborne botulism type E and review of epidemiology in France; Boyer A et al.; In 1999, two new cases of type E botulism were observed in French hospitals . Since this type of botulism is uncommon in France, the cases prompted a national epidemiological study . Sixteen cases of type E botulism, including the two cases reported here, occurred between 1952 and 1999 . The clinical and treatment characteristics of all cases were evaluated, and the results suggest that, despite its rarity, type E botulism should be considered by clinicians in France . Changes in the eating habits of people in France, as in the rest of Europe, with the increased consumption of vacuum-packed fish from endemic areas and decreased consumption of local foodstuffs, could explain the occurrence of the most recent cases. Arch Pediatr, 2001 Mar, 8(3), 286 - 9 {Type B botulism: a family outbreak}; Lamboley G et al.; CASE REPORTS: Three cases of an outbreak of familial foodborne botulism are reported . The food incriminated could not be identified despite a careful investigation into the food history of the patients . The outcome was good following endotracheal ventilation and botulism antitoxin trivalent therapy . CONCLUSION: In France, foodborne botulism is an uncommon public health disease, and with a good prognosis when the diagnosis is promptly performed . The value of emergency electromyographic findings is emphasized, particularly when the repetitive stimulation of the motor nerve shows a presynaptic block of neuromuscular transmission . Management depends on the symptomatology, and trivalent antitoxin therapy is the only specific treatment. Croat Med J, 2001 Apr, 42(2), 130 - 4 On depleted uranium: gulf war and Balkan syndrome; Durakovic A; The complex clinical symptomatology of chronic illnesses, commonly described as Gulf War Syndrome, remains a poorly understood disease entity with diversified theories of its etiology and pathogenesis . Several causative factors have been postulated, with a particular emphasis on low level chemical warfare agents, oil fires, multiple vaccines, desert sand (Al-Eskan disease), botulism, Aspergillus flavus, Mycoplasma, aflatoxins, and others, contributing to the broad scope of clinical manifestations . Among several hundred thousand veterans deployed in the Operation Desert Storm, 15-20% have reported sick and about 25,000 died . Depleted uranium (DU), a low-level radioactive waste product of the enrichment of natural uranium with U-235 for the reactor fuel or nuclear weapons, has been considered a possible causative agent in the genesis of Gulf War Syndrome . It was used in the Gulf and Balkan wars as an armor-penetrating ammunition . In the operation Desert Storm, over 350 metric tons of DU was used, with an estimate of 3-6 million grams released in the atmosphere . Internal contamination with inhaled DU has been demonstrated by the elevated excretion of uranium isotopes in the urine of the exposed veterans 10 years after the Gulf war and causes concern because of its chemical and radiological toxicity and mutagenic and carcinogenic properties . Polarized views of different interest groups maintain an area of sustained controversy more in the environment of the public media than in the scientific community, partly for the reason of being less than sufficiently addressed by a meaningful objective interdisciplinary research. JAMA, 2001 Feb 28, 285(8), 1059 - 70 Botulinum toxin as a biological weapon: medical and public health management; Arnon SS et al.; OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population . PARTICIPANTS: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine . EVIDENCE: The primary authors (S.S.A . and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon . The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism . Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement . CONSENSUS PROCESS: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process . The working group convened to review the first draft in May 1999 . Working group members reviewed subsequent drafts and suggested additional revisions . The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members . CONCLUSIONS: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure . Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation . Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months . Treatment with antitoxin should not be del