Botulin

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 delayed for microbiological testing.

Comp Biochem Physiol A Mol Integr Physiol, 2001 Feb, 128(2), 233 - 9
Neuropathogenic properties of Argas (Persicargas) walkerae larval homogenates; Maritz C et al.; Several tick species have been demonstrated, described, or suspected to cause paralysis in their host during the repletion process, presumably by impairing neurotransmission . The resulting polyneuropathy gradually spreads to the upper limbs causing incoordination and ends in respiratory failure . This form of paralysis is commonly confused with Guillain-Barre syndrome, botulism and myasthenia gravis and although the clinical symptoms of these diseases are similar, it is not clear whether the pathogenesis is also the same . During this study we investigated the mechanism of paralysis by the tick Argas (Persicargas) walkerae by determining the effect of larval homogenates on both potassium-stimulated (calcium-dependent) and veratridine-stimulated (external calcium-independent) release of {3H}glycine from crude rat brain synaptosomes . The results indicated that larval homogenates inhibited both processes . These findings are reconcilable with the results obtained for two other paralysis-causing tick species, Ixodes holocyclus and Dermacentor andersoni, which were indicated to cause paralysis by decreasing the synthesis or release of acetylcholine at the neuromuscular junction.

Cell Mol Life Sci, 1999 Oct 1, 56(1-2), 47 - 61
Botulinum toxin as a carrier for oral vaccines; Simpson LL et al.; Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid paralysis . To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events . During the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the lumen of the gut to the general circulation . During the second, circulating toxin binds to peripheral cholinergic nerve endings, it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis . Although botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning . This is due to the fact that the dose of toxin that produces flaccid paralysis-and potentially death-is less than the dose needed to evoke an antibody response . In the recent past, the techniques of molecular biology have been used to generate an expression product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability to evoke an immune response, but has lost the ability to produce neurotoxicity . This modified toxin may have two clinical applications . The expression product itself may have utility as an oral vaccine against botulism . Beyond this, the modified toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines . Both potential applications could lead to the expression of oral vaccines in common foods.

Muscle Nerve Suppl, 2000, 9, S53 - 62
Acute care pediatric electromyography; Jones HR Jr et al.; The recognition of uncommon pediatric motor unit disorders or unusual clinical presentations of common illnesses, such as Guillain-Barre syndrome (GBS), have increased the need for electromyography (EMG) in childhood critical care units . There are two different clinical sets, one appropriate to newborns and infants and the other to older children . Some illnesses that present as an acute floppy infant are not found in the differential diagnosis of motor unit disorders in the older child or adult . These include spinal muscular atrophy, postvaccine poliomyelitis, intrauterine GBS, infantile botulism, and severe myopathies, such as myotonia dystrophy, and some glycogen storage diseases . An appreciation of the neurophysiological maturational norms is essential to an effective pediatric EMG consultation for children ages 0-3 years . Additionally, the neuromuscular complications of extended intubation and sepsis in children are gaining broader recognition . An increased dialogue between clinical neurophysiologists and pediatric neurologists and intensivists in both neonatal and pediatric intensive care units is essential .

J Paediatr Child Health, 2000 Dec, 36(6), 596 - 7
A taste of honey; McMaster P et al.; Infantile botulism classically presents with a triad of clinical features: Bulbar palsies (slow/absent pupil response) Alert Absent fever Other common features are: Constipation, ptosis and poor feeding The diagnosis is a clinical one, confirmed by EMG and by testing stool for the organism, C . botulinum, or its toxin . Parents should be advised not to dip pacifiers in honey . In future Botulinum Immune Globulin may be available and should be considered if further trials are published showing benefit . Nosocomial infections, such as RSV, are important and should be carefully avoided, particularly in patients recovering from botulism.

Przegl Epidemiol, 2000, 54(1-2), 115 - 21
{Botulism in 1998}; Przybylska A; Total 93 cases of botulism were registered in Poland in 1998 . The morbidity amounted 0.24/100,000 . In the rural regions were registered 61 (morbidity 0.41), and in the urban regions 32 (morbidity 0.13) cases . The morbidity of men (0.34) outnumbered the morbidity of women (0.15) . In 1998 there were 57 outbreaks of one person noted, 8 outbreaks of two people, 4 of three people and 2 of four people . Among the vehicles of the botulinum toxin dishes from meat remained on the first position (50.5% of the cases) and in these numbers prevailed weeks of home production (18.3%) . In 1998 were noted 4 deaths from botulism . In this number were 4 men (46, 57, 74 and 78 years old).

Przegl Epidemiol, 2000, 54(1-2), 103 - 14
{Foodborne infections and intoxications in 1998}; Przybylska A; In total were registered 30,515 cases of bacterial foodborne infections and intoxications (salmonelloses of animal source, staphylococcal, botulism, other bacterial and caused by undetermined agents) in 1998 . Morbidity amounted 78.9/100,000 . In 399 outbreaks of collective illnesses (4 people and more) 8225 cases were registered altogether . S . Enteritidis caused 92.5% cases in outbreaks . The main vehicle of foodborne infections and intoxications in outbreaks was food prepared from raw materials of animal source, which caused 86.8% cases in outbreaks . Dishes from eggs brought about 45.5% of these cases . Among the places of the ready made food production, private homes prevailed (58.1% of the whole amount of outbreaks) . Seven epidemics numbering above 100 cases each were registered in 1998.

J Med Assoc Thai, 2000 Sep, 83(9), 1021 - 5
Foodborne botulism outbreaks following consumption of home-canned bamboo shoots in Northern Thailand; Swaddiwudhipong W et al.; We report epidemiological investigations of 2 outbreaks of foodborne botulism following consumption of home-canned bamboo shoots in northern Thailand . The first outbreak affecting 4 female and 2 male cases occurred in Mae Sot District, Tak Province, in December 1997 . All 6 cases were hospitalized, 4 of whom required mechanical ventilation . All cases experienced neurological features and 4 had gastrointestinal symptoms . One case died, giving a case-fatality rate of 16.7 per cent . A case-control study revealed a significant association (p < 0.01) between the disease and consumption of home-canned bamboo shoots purchased from the same foodshop in the village . The second outbreak of a similar clinical syndrome occurred in Thawangpha District, Nan Province, in April 1998 . A total of 13 cases were identified, 9 (69.2%) of whom were female . Nine cases (69.2%) were hospitalized, 4 (30.8%) of whom required mechanical ventilation . Two early hospitalized cases died due to ventilatory failure, giving a case-fatality rate of 15.4 per cent . A case-control study indicated that home-canned bamboo shoots prepared by a local foodshop served as the vehicle for the disease transmission . One bamboo shoot specimen from one affected house was positive for botulinum toxin type A by enzyme-linked immunosorbent assay and mouse antitoxin bioassay . Improper home-canning procedures for bamboo shoot preservation were similarly detected in both outbreaks although performed by different merchants . Prompt recognition and treatment of the disease are essential in reducing the fatality rate . Safe home-canning procedures should be widely distributed and instructed to persons who perform bamboo shoot preservation for sale.

Pediatr Neurol, 2000 Oct, 23(4), 338 - 9
Biphasic course of infant botulism; Ravid S et al.; The syndrome of infant botulism, characterized by constipation, poor feeding, hypotonia, poor head control, and bulbar involvement, is typically a monophasic disease . We describe a 7-month-old infant with a recurrence of illness 13 days after resolution of the presenting signs . The source of infection was unknown and the only potential risk factors were exclusive breastfeeding and decreased bowel movements, which by themselves cannot explain the recurrence . Although treatment with botulism immunoglobulin is now suggested for the acute phase of infantile botulism, its use for recurrence is controversial.

Clin Infect Dis, 2000 Oct, 31(4), 1018 - 24 Epub 2000 Oct 25.
Wound botulism in California, 1951-1998: recent epidemic in heroin injectors; Werner SB et al.; California has reported most of the world's wound botulism (WB) cases and nearly three-fourths of the cases reported in the United States . We reviewed the clinical, epidemiologic, and laboratory features of WB . From the first case in 1951, through 1998, a total of 127 cases were identified-93 in the last 5 years . The dramatic increase has been due to an epidemic (of WB) in people who inject black tar heroin . Whereas early cases of WB occurred after gross trauma, all but 1 of the last 102 cases occurred in drug users, primarily those who inject drugs subcutaneously ("skin poppers") . Cases are occurring disproportionately in Hispanics and women . Misdiagnosis and diagnostic delays of up to 64 days have occurred . This unprecedented, ongoing epidemic is now being reported in other states . We discuss the clinical and laboratory features that distinguish botulism from conditions that can mimic it, the relative yield of various diagnostic laboratory tests for botulism, and its treatment.

Clin Microbiol Rev, 2000 Oct, 13(4), 602 - 14
Passive immunity in prevention and treatment of infectious diseases; Keller MA et al.; Antibodies have been used for over a century in the prevention and treatment of infectious disease . They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia . Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism . High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections) . Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections . Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants . The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.

J Infect Dis, 2000 Nov, 182(5), 1503 - 10 Epub 2000 Sep 27.
Infectious disease morbidity in the US region bordering Mexico, 1990-1998; Doyle TJ et al.; The United States and Mexico share an international boundary approximately 3000 km long . This border separates 2 nations with great differences in health status . The objective of this study was to assess morbidity due to infectious diseases in the US region bordering Mexico . The incidence between 1990 and 1998 of 22 nationally notifiable infectious diseases was compared between border and nonborder regions . Disease rates, reflected as rate ratios, were higher in the border region for botulism, brucellosis, diphtheria, hepatitis A, measles, mumps, rabies, rubella, salmonellosis, and shigellosis than in either of 2 nonborder comparison regions . These data indicate that incidence rates for a variety of infectious diseases of public health importance are significantly higher in the United States along the Mexican border than in nonborder regions . These results suggest that an inadequate public health infrastructure may contribute to excess morbidity due to infectious diseases in the border region.

Rev Neurol, 2000 Aug 1-15, 31(3), 252 - 62
{Neonatal hypotonia}; Erazo-Torricelli R; INTRODUCTION: Neonatal hypotonia is a condition which appears to expand continually . Since the 1980s new clinical disorders, such as mitochondriopathies, peroxisomal diseases, disorders of the beta-oxidation of fatty acids, congenital myasthenic syndromes and botulism in infants have been described . At the same time, considerable progress has been made in the understanding of congenital myopathies, congenital muscular dystrophy and neonatal myotonic dystrophy . In this review we describe the most relevant conditions in which hypotonia is seen, and give guidelines for orientation in the study of newborn babies with this condition . We emphasize the importance of a clinical approach based on the family history (myotonic dystrophy, transitory neonatal myasthenia), the prenatal history (fetal movements, polyhydramnios) and neurological examination (facial diplegia, lingual fasciculations, arthrogryposis, respiratory difficulty) which permits early completion of studies, including muscle biopsy--very useful in the neonatal period--and genetic analysis . This allows the prognosis of the condition to be established early so that timely and effective genetic counselling may be given to the parents, avoiding recurrence of the serious morbi-mortality of many of these conditions.

MMWR Morb Mortal Wkly Rep, 2000 Sep 1, 49(34), 778 - 80
Foodborne botulism from eating home-pickled eggs--Illinois, 1997; Anaerobic infections in children; Georgetown University School of Medicine, Washington, DC, USAAnaerobic bacteria commonly cause infection in children . Anaerobes are the most predominant components of the normal human skin and mucous membrane bacterial flora, and are therefore a common cause of bacterial infections of endogenous origin . 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 . Anaerobic bacteria 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 directing adequate therapy against these organisms may lead to clinical failures . Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens . Treatment of anaerobic infection is complicated by the slow growth of these organisms, by their polymicrobial nature, and by the growing resistance of anaerobic bacteria to antimicrobials . Antimicrobial therapy is often the only form of therapy required, whereas in other cases it is an important adjunct to a surgical approach . Because anaerobic bacteria generally are recovered mixed with aerobic organisms, the choice of appropriate antimicrobial agents should provide for adequate coverage of both types of pathogens.

Paediatr Drugs, 2000 Mar-Apr, 2(2), 91 - 100
The role of drug treatment in children with strabismus and amblyopia; Chatzistefanou KI et al.; Strabismus, or misalignment of the eyes, is a common ophthalmic problem in childhood, affecting 2 to 5% of the preschool population . Amblyopia is an important cause of visual morbidity frequently associated with strabismus, and both conditions should be treated simultaneously . Pharmacological means for treating strabismus and amblyopia can be divided into 3 categories: paralytic agents (botulinum toxin) used directly on the extraocular muscles to affect eye movements; autonomic agents (atropine, miotics) used topically to manipulate the refractive status of the eye and thereby affect alignment, focus and amblyopia; and centrally acting agents, including levodopa and citicoline, which affect the central visual system abnormalities in amblyopia . Botulinum toxin, the paralytic agent that causes the clinical symptoms of botulism poisoning, can be injected in minute quantities to achieve controlled paralysis of the extraocular muscles . Although the role of botulinum toxin is established in adults with paralytic strabismus, its usefulness in the treatment of comitant childhood strabismus (primary esotropia and exotropia) is not universally accepted . Botulinum injections tend to be more effective with smaller degrees of strabismus, in patients with good binocular fusion, and in managing overcorrections or undercorrections after traditional muscle surgery . Inadvertent ptosis and paralysis of adjacent muscles, unpredictable responses and technical constraints of the injections limit its use in children . Miotic therapy, by altering the refractive state of the treated eye, offers an alternative to optical correction with bifocals in treating esotropia due to excessive accommodative convergence . It is also effective in treating residual esotropia following surgery . The ease of use of glasses restricts the wide application of miotics in these common strabismus syndromes . Atropine, an anticholinergic agent, paralyses the ability of the eye to focus or accommodate . In amblyopia therapy, atropine is used to blur vision in the non-amblyopic eye and offers a useful alternative to traditional occlusion therapy with patching, especially in older children who are not compliant with patching . The neurotransmitter precursor levodopa and the related compound citicoline have been demonstrated to improve vision in amblyopic eyes . The therapeutic role of these centrally acting agents in the clinical management of amblyopia remains unproven.

Nat Struct Biol, 2000 Aug, 7(8), 617 - 9
Intimate details of the most poisonous poison; Singh BR; Crystal structures of type B botulinum neurotoxin, determined under conditions relevant to the extracellular binding and intracellular substrate cleavage steps of its toxic action, reveal that minimal structural changes occur upon binding a ganglioside or after substrate cleavage . The unique structure of this toxin provides information for developing preventive measures against botulism.

Semin Pediatr Neurol, 2000 Jun, 7(2), 91 - 102
Guillain-Barré syndrome: perspectives with infants and children; Jones HR Jr; An acute flaccid paraparesis or ascending quadriparesis in an infant or child constitutes a very important pediatric neurology emergency . The Guillain-Barre syndrome (GBS) is the most frequent cause . This is primarily an autoimmune, post-infectious, demyelinating, peripheral nervous system process . A small percentage of children develop a primary axonal process not unlike that identified more commonly in China . Because of the potential for acute respiratory compromise, any child suspected of having GBS needs immediate hospitalization . The major considerations in differential diagnosis include transverse myelitis, toxic neuropathies, tick paralysis, infantile botulism, myasthenia gravis, and dermatomyositis . On occasion, some younger children present with an acute severe pain syndrome that may mask as a pseudo-encephalopathy . Another clinical variant is the Miller-Fisher syndrome characterized by ataxia, ophthalmoparesis, and areflexia . This is associated with a high frequency of the anti-GQ-1-b antibodies . Although most children with GBS have a relatively benign clinical course, some become very ill and require intubation with intensive care monitoring . Immunomodulating treatment should be used for any child who loses the ability to walk . To date, no well-controlled study has been completed analyzing the relative merits of the two most commonly used therapies, namely plasmapheresis or intravenously administered immunoglobulin.

Br Med Bull, 2000, 56(1), 133 - 41
Economic aspects of food-borne outbreaks and their control; Roberts JA; This paper begins with a discussion of the definition of an outbreak . It considers the portion of outbreaks in the general pattern of food-borne infectious disease . The methods used to identify outbreaks are described and the importance of the potential benefits and the economic impact of outbreak recognition and control and are discussed . The paper concludes by illustrating the economic impact of intervention using three infectious diseases botulism, Salmonella and Escherichia coli O157 as case studies of outbreaks.

Muscle Nerve, 2000 Jul, 23(7), 1137 - 44
AAEM case report 16 . Botulism . American Association of Electrodiagnostic Medicine; Maselli RA et al.; Early diagnosis of botulism is essential for effective treatment . Electrophysiologic testing can be of major help to establish a prompt diagnosis, but the classic electrodiagnostic features of botulism are often elusive . Decrement or increment of compound muscle action potential (CMAP) amplitudes to slow or fast rates of nerve stimulation are often unimpressive or totally absent . Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit potentials in affected muscles are found more frequently but they are less specific . In general, the electrophysiologic findings taken together suggest involvement of the motor nerve terminal, which should raise the possibility of botulism . The case reported here illustrates a common clinical presentation of botulism . This study emphasizes realistic expectations of the electrodiagnostic testing, the differential diagnosis, and the potential pitfalls often encountered in the interpretation of the electrophysiologic data .

Semin Neurol, 2000, 20(1), 7 - 20
Ocular aspects of myasthenia gravis; Barton JJ et al.; Ocular myasthenia gravis is a not uncommon autoimmune disorder causing diplopia, ptosis, and weakness of lid closure . The predilection of myasthenia for the ocular muscles may be related to differences between limb and extraocular muscles in either physiological function or antigenicity . Clinically, ocular myasthenia can mimic any form of pupil-sparing ocular motility disorder . Dynamic abnormalities of myasthenic eye movements may reflect the primary hallmarks of the disease, which are fatigability and variability in strength, or secondary adaptive effects by the central nervous system . Tests to confirm the diagnosis include edrophonium challenge, repetitive nerve stimulation, single-fiber electromyography (EMG) of the frontalis, and assays for antibody directed against the acetylcholine receptor: all are less sensitive for ocular myasthenia than for generalized myasthenia . There is a higher incidence of other autoimmune conditions in myasthenia, notably thymoma and thyroid dysfunction . The differential diagnosis includes other diseases of the neuromuscular junction, such as Lambert-Eaton syndrome and botulism . Treatment consists of symptomatic use of acetylcholinesterase inhibitors and immunosuppression with steroids or azathioprine . Between 50 and 70% of patients with ocular myasthenia will eventually develop generalized disease: there is some retrospective data that steroids or azathioprine may reduce this by about 75% . The role of thymectomy in ocular myasthenia remains unclear.

Biochimie, 2000 May, 82(5), 427 - 46
How botulinum and tetanus neurotoxins block neurotransmitter release; Humeau Y et al.; Botulinum neurotoxins (BoNT, serotypes A-G) and tetanus neurotoxin (TeNT) are bacterial proteins that comprise a light chain (M(r) approximately 50) disulfide linked to a heavy chain (M(r) approximately 100) . By inhibiting neurotransmitter release at distinct synapses, these toxins cause two severe neuroparalytic diseases, tetanus and botulism . The cellular and molecular modes of action of these toxins have almost been deciphered . After binding to specific membrane acceptors, BoNTs and TeNT are internalized via endocytosis into nerve terminals . Subsequently, their light chain (a zinc-dependent endopeptidase) is translocated into the cytosolic compartment where it cleaves one of three essential proteins involved in the exocytotic machinery: vesicle associated membrane protein (also termed synaptobrevin), syntaxin, and synaptosomal associated protein of 25 kDa . The aim of this review is to explain how the proteolytic attack at specific sites of the targets for BoNTs and TeNT induces perturbations of the fusogenic SNARE complex dynamics and how these alterations can account for the inhibition of spontaneous and evoked quantal neurotransmitter release by the neurotoxins.

Vet Hum Toxicol . 2000 Jun;42(3):163.
Botulism-like syndrome after injections of botulinum toxin; Cobb DB et al.; Botulinum type A toxin (BTA) is an orphan drug used to treat several disorders of muscle spasticity . We report the first known case of systemic botulism-like syndrome induced by BTA therapy which resulted in respiratory arrest . Clinicians should be aware that systemic effects may occur with localized BTA therapy and may be life-threatening.

J Vet Diagn Invest, 2000 May, 12(3), 204 - 9
Type C botulism in dairy cattle from feed contaminated with a dead cat; Galey FD et al.; Four hundred twenty-seven of 441 adult Holstein dairy cattle from a 1,200-cow dairy died over a 1-week period during early spring 1998 . Affected animals were from 4 late lactation pens, one of which included the bull string . Signs included weakness, recumbency, watery diarrhea, and death . Eighty animals from the 4 pens were dead approximately 8 hours after the first ill cows were noted . Affected cows would collapse on stimulation and extend all 4 limbs with moderate rigidity . Several lacked lingual tonus and had abdominal breathing patterns . The animals had been fed a load of total mixed ration that included a rotten bale of oat hay containing a dead cat . No common toxicants were identified, and pathologic examination revealed no consistent lesions . Testing of tissue from the cat carcass found in the feed sample using mouse protection bioassay identified the presence of type C botulinum toxin . Samples of feed, tissue from affected animals, cat tissue from feed, milk, and serum were also tested using an enzyme-linked immunosorbent assay (ELISA) specific for type C botulinum . Two samples of rumen contents were tested and found to be positive for botulism by ELISA, and 1 of 3 liver samples had a weak positive finding . No botulinum toxin was found in milk or sera using the ELISA.

J Clin Anesth, 2000 Feb, 12(1), 80 - 2
Cardiac arrest due to succinylcholine-induced hyperkalemia in a patient with wound botulism; Chakravarty EF et al.; Cardiac arrest due to hyperkalemia is a known complication of succinylcholine administration in patients with neuromuscular disease, extensive burns, and prolonged immobility . We report a case of hyperkalemic cardiac arrest following the administration of succinylcholine in a patient suffering from wound botulism.

Lakartidningen, 2000 Mar 22, 97(12), 1427 - 8, 1431-2
{The men of the Andrée expedition probably died of botulism . A new hypothesis explains these mysterious deaths}; Personne M; The last camp of the three members of the 1897 Swedish Andree balloon expedition to the North Pole was found in Svalbard in 1930 . The human remains and the paraphernalia of the expedition including diaries were brought to Sweden and are presently housed in a museum . The cause of the deaths has never been determined, but several hypotheses have been put forward over the years . Trichinosis, scurvy, and poisoning by carbon-monoxide, vitamin-A or lead are some of them . In this article it is argued that botulism is a plausible explanation which is in better accord with known facts.

J Toxicol Clin Toxicol, 2000, 38(1), 21 - 8
Inadequate stocking of antidotes in Taiwan: is it a serious problem?
Ong HC, Yang CC, Deng JF.
OBJECTIVE: Insufficient hospital stock of a variety of poisoning antidotes is a worldwide problem . In an attempt to establish an antidote storage and distribution system for the response of the various poisoning accidents, we conducted a nationwide survey to characterize the current availability of selected antidotes and their anticipated need in Taiwan . MATERIALS AND METHODS: A questionnaire was mailed to 834 hospitals to gather information on the availability, anticipated need, and preferred purchase policy of 20 selected antidotes . A survey on the availability of cyanide antidote in 523 cyanide-handling facilities and their neighboring hospitals was also conducted . RESULTS: Hospitals of different size and service levels had a statistically significant difference in response rates . Except for pyridoxine, the availability and anticipated need for antidotes also varied significantly among different hospital groups . We found that physostigmine, cyanide antidote kit, BAL, EDTA, methylene blue, Vipera Russell formosensis antivenin, and botulism antitoxin were not available in most (>90%) hospitals . Interestingly, these antidotes are also among the most needed antidotes . Most hospitals preferred a government-ordered purchase of antidotes . In the survey of cyanide-processing facilities, a response rate of 24.1% was obtained and only 9.3% of these 107 facilities that both replied to the questionnaire and continued handling cyanide products had stocked cyanide antidote . It is noteworthy that cyanide antidote was also frequently lacking in the neighboring hospitals . CONCLUSIONS: The appropriate storage of antidotes in hospitals or workplaces in rural areas is instrumental in the timely treatment of certain poisonings, while nationwide unavailability is the critical problem . Raising awareness of the importance of antidotes by education, regular review of antidote storage, distribution plans, and appropriate legislation might provide solutions.

Eur J Epidemiol, 1999 Nov, 15(10), 917 - 22
Botulism surveillance in Italy: 1992-1996; Squarcione S et al.; Though a relatively rare disease, botulism can be a serious problem of public health, particularly when connected with the consumption of industrial canned food; moreover, in the last years the shortage of botulism antitoxin has caused some concern in the Public Health Authorities . This work presents the results of a five-year surveillance of botulism in Italy, with the distribution of the cases by Regions (first level administrative units which, in Italy, have administrative and legislative competencies in the sanitary field) and by vehicle of transmission . All the relevant and confirmed botulism outbreaks that occurred in the period under consideration are described.

Childs Nerv Syst, 2000 Feb, 16(2), 84 - 6
Electrophysiological studies of a child with presumed botulism; Hatanaka T et al.; Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2' was reduced during recovery . These findings suggest a conduction block of the facial nerves . Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission . Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism . A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.

J Biomed Sci, 2000 Jan-Feb, 7(1), 51 - 7
DNA vaccination using the fragment C of botulinum neurotoxin type A provided protective immunity in mice; Shyu RH et al.; Botulinum neurotoxin (BoNT) is one of the most toxic substances known to produce severe neuromuscular paralysis . The currently used vaccine is prepared mainly from biohazardous toxins . Thus, we studied an alternative method and demonstrated that DNA immunization provided sufficient protection against botulism in a murine model . A plasmid of pBoNT/A-Hc, which encodes the fragment C gene of type A botulinum neurotoxin, was constructed and fused with an Igkappa leader sequence under the control of a human cytomegalovirus promoter . After 10 cycles of DNA inoculation with this plasmid, mice survived lethal doses of type A botulinum neurotoxin challenges . Immunized mice also elicited cross-protection to the challenges of type E botulinum neurotoxin . This is the first study demonstrating the potential use of DNA vaccination for botulinum neurotoxins .

Arch Phys Med Rehabil, 2000 Jan, 81(1), 122 - 6
Serum positive botulism with neuropathic features; Chang VH et al.; A 32-year-old man presented with multiple cranial neuropathies and his serum was positive for botulism type B . However, serial electrodiagnostic studies were consistent with a primarily neuropathic process, such as Fisher syndrome, rather than a neuromuscular junction disorder . Electrodiagnostic study findings in patients with presumed neuromuscular junction disorders may mimic findings suggestive of a neuropathic process, or the bioassay for botulism may be falsely positive in patients with Fisher Syndrome.

J Biol Chem, 1999 Dec 24, 274(52), 36897 - 904
Rescue of exocytosis in botulinum toxin A-poisoned chromaffin cells by expression of cleavage-resistant SNAP-25 . Identification of the minimal essential C-terminal residues; O'Sullivan GA et al.; Botulinum neurotoxin (BoNT) types A and B selectively block exocytosis by cleavage of SNAP-25 and synaptobrevin, respectively; in humans, many months are required for full recovery from the resultant neuromuscular paralysis . To decipher the molecular basis for such prolonged poisoning, intoxication in adreno-chromaffin cells was monitored over 2 months . Exocytosis from BoNT/B-treated cells resumed after 56 days because of the appearance of intact synaptobrevin . However, inhibition continued in BoNT/A-treated cells, throughout the same interval, with a continued predominance of cleaved SNAP-25-(1-197) over the intact protein . When recovery from poisoning was attempted by transfection of the latter cells with the gene encoding full-length SNAP-25-(1-206), no restoration of exocytosis ensued even after 3 weeks . To ascertain if this failure was because of the persistence of the toxin's protease activity, the cells were transfected with BoNT/A-resistant SNAP-25 constructs; importantly, exocytosis was rescued . C-terminal truncation of the toxin-insensitive SNAP-25 revealed that residues 1-201, 1-202, 1-203 afforded a significant return of exocytosis, unlike shorter forms 1-197, -198, -199, or -200; accordingly, mutants M202A or L203A of full-length SNAP-25 rescued secretion . These findings give insights into the C-terminal functional domain of SNAP-25, demonstrate the longevity of BoNT/A protease, and provide the prospect of a therapy for botulism.

J Appl Toxicol, 1999 Dec, 19 Suppl 1, S29 - 33
Comparison of in vivo and in vitro mouse bioassays for botulinum toxin antagonists; Sheridan RE et al.; Measurements of the efficacy of novel botulinum toxin antagonists can be based on classical bioassays of toxin concentration . However, the relative sensitivities of in vivo and in vitro assays to the effects of antagonists are not necessarily correlated with the sensitivities of the assays to toxin . Comparisons of the sensitivity of an in vitro mouse muscle contraction assay with an in vivo mouse survival assay indicated that the in vivo assay was more sensitive to botulinum toxin serotype A by more than one order of magnitude at equivalent molar concentrations . However, in studies of toxin neutralization with equine antisera, the in vitro muscle assay was more than three times more sensitive to the presence of antisera than the equivalent mouse survival assay . For the development of new drugs to treat botulism, antagonist sensitivity is a primary consideration in determining relative efficacy during structure-activity studies . Thus, in studies of toxin antagonists, the in vitro assay appears to be superior for initial testing.

Vet Clin North Am Equine Pract, 1999 Dec, 15(3), 589 - 602
Therapeutics of musculoskeletal disease in the horse; Kollias-Baker C; Therapeutic medications play a crucial role in the successful therapy of many musculoskeletal diseases that occur in horses . For example, appropriate antibiotic therapy is extremely important in the treatment of diseases caused by infections with microorganisms such as botulism, tetanus, osteomyelitis, and muscle abscesses . In addition, numerous prescription medications and nutritional supplements are available for the treatment of osteoarthritis in horses . Many of these agents currently on the market fall into a new class of drugs called SADMO agents . Unfortunately, the efficacy and mechanism(s) of action for many of these agents have not been well defined . There does exist a fair amount of data indicating that the parenterally administered compounds HA and PSGAGs, commonly used to treat osteoarthritis, can decrease the severity of clinical signs and perhaps slow the progression of disease . Although there are fewer data available to support the efficacy of orally administered SADMO agents, these compounds are used commonly by lay people as osteoarthritis therapies . Finally, pharmaceutical agents such as acetozolamide can play an important role in the management of the inherited HYPP condition in horses.

J Neurochem, 1999 Dec, 73(6), 2424 - 33
Botulinum neurotoxin E-insensitive mutants of SNAP-25 fail to bind VAMP but support exocytosis; Washbourne P et al.; Neurotransmitter release from synaptic vesicles is mediated by complex machinery, which includes the v- and t-SNAP receptors (SNAREs), vesicle-associated membrane protein (VAMP), synaptotagmin, syntaxin, and synaptosome-associated protein of 25 kDa (SNAP-25) . They are essential for neurotransmitter exocytosis because they are the proteolytic substrates of the clostridial neurotoxins tetanus neurotoxin and botulinum neurotoxins (BoNTs), which cause tetanus and botulism, respectively . Specifically, SNAP-25 is cleaved by both BoNT/A and E at separate sites within the COOH-terminus . We now demonstrate, using toxin-insensitive mutants of SNAP-25, that these two toxins differ in their specificity for the cleavage site . Following modification within the COOH-terminus, the mutants completely resistant to BoNT/E do not bind VAMP but were still able to form a sodium dodecyl sulfate-resistant complex with VAMP and syntaxin . Furthermore, these mutants retain function in vivo, conferring BoNT/E-resistant exocytosis to transfected PC12 cells . These data provide information on structural requirements within the C-terminal domain of SNAP-25 for its function in exocytosis and raise doubts about the significance of in vitro binary interactions for the in vivo functions of synaptic protein complexes.

J Wildl Dis, 1999 Oct, 35(4), 710 - 5
Immunization of ducks for type C botulism; Martinez R et al.; A single subcutaneous immunization with a vaccine used for protecting ranch mink (Mustela vison) against type C botulism reduced morbidity and mortality in mallard (Anas platyrhynchos) and northern pintail (Anas acuta) ducks challenged with approximately 4.5 x 10(4) and 2.25 x 10(4) mouse lethal doses (MLD50), respectively, of botulinum toxin at 10 and 15 days post-immunization (pi) . There was no significant protection at 5 days pi . Protection persisted in mallards for 90 days pi . To simulate use of vaccine as a part of treatment of sick birds in the field, mallards were exposed to toxin and, when clinical signs were evident, each bird was treated by intraperitoneal injection of type C botulinum antitoxin and one-half of the birds were immunized . Immunization had no significant effect on recovery from intoxication . At 10 days posttreatment, all birds were challenged with toxin . Clinical signs and mortality were significantly less frequent among immunized birds than among non-immunized birds after the second exposure . Immunization might be useful as part of the treatment regimen in botulism outbreaks.

Acta Paediatr Suppl, 1999 Aug, 88(430), 42 - 6
Human milk and host defence: immediate and long-term effects; Hanson LA; Convincing studies demonstrate significant protection during breastfeeding against diarrhoea, respiratory tract infections, otitis media, bacteraemia, bacterial meningitis, botulism, urinary tract infections and necrotizing enterocolitis . There is also good evidence for enhanced protection for years after the termination of breastfeeding against Haemophilus influenzae type b infections, otitis media, diarrhoea, respiratory tract infections and wheezing bronchitis . In some reports breastfeeding has also improved vaccine responses . Several studies show that milk may actively stimulate the immune system of the offspring via transfer of anti-idiotypic antibodies and lymphocytes . This may explain why breastfeeding diminishes the risk of developing coeliac disease . Some investigations suggest that there may also be a similar effect on allergic diseases and autoimmune diseases, as well as inflammatory bowel diseases and certain tumours . This needs to be confirmed.

Muscle Nerve, 1999 Dec, 22(12), 1698 - 703
Stimulation single-fiber EMG in infant botulism; Chaudhry V et al.; The principal electrodiagnostic feature of infant botulism, an incremental response on high rates of repetitive nerve stimulation, has variable sensitivity and may not always be useful as a diagnostic test given the vagaries of test timing and severity of illness . We report the use of stimulation single fiber EMG (S-SFEMG) in making this clinical diagnosis . Four infants between 1 and 5 months of age presented with rapidly progressive bulbar and limb weakness, internal and external ophthalmoplegia, areflexia, and compromised ventilation . Incremental response with high-rate repetitive nerve stimulation and a typical clinical course for infant botulism confirmed the diagnosis in all; stool toxin studies were positive for type B botulinum in 2 of the 3 cases in which they were obtained . S-SFEMG was performed by surface stimulation of median and ulnar nerves and recording with a single fiber needle in the thenar, hypothenar, or first dorsal interosseous muscles . A total of eight single fiber recordings were studied at rates of 2, 5, 10, and 20 Hz . All single fibers studies showed an improvement with higher rates of stimulation, beginning at 10 Hz and peaking at 20 Hz . Compared to baseline study at 2 Hz (100%), the mean percent changes in jitter at 5, 10, and 20 Hz were 109, 60, and 47, respectively . This is the first report of the usefulness of S-SFEMG in the diagnosis of infant botulism .

Alaska Med, 1999 Apr-Jun, 41(2), 35 - 43
Emerging infectious diseases in Alaska and the Arctic: a review and a strategy for the 21st century; Butler JC et al.; Emergence of new, previously unknown, and drug-resistant infectious diseases pose a major threat to global health . The emergence of infectious diseases in Alaska and the Arctic parallels the resurgence of infectious diseases worldwide . The Centers for Disease Control and Prevention has developed a strategy to revitalize the capacity to protect the public from emerging infectious diseases by improving four major public health activities: surveillance and response, applied research, infrastructure and training, and prevention and control . The plan targets high-priority emerging infectious disease problems and particular groups of people at increased risk . These target areas encompass a number of diseases of special concern in Alaska, such as drug-resistant Streptococcus pneumoniae infections, foodborne botulism, alveolar hydatid disease, viral hepatitis, Helicobacter pylori infections, Haemophilus influenzae type b bacteremia and meningitis, and infections of immunocompromised persons, pregnant women and newborns, and tourists . To address these and other emerging infectious disease issues, including the threat of bioterrorism in Alaska and the Arctic, future issues of Alaska Medicine will include updates on specific emerging infectious diseases for health care providers, clinical laboratory workers, and community public health professionals who form the front lines for recognizing, treating, and preventing emerging infectious diseases.

J Cell Sci, 1999 Aug, 112 ( Pt 16), 2715 - 24
Functional characterisation of tetanus and botulinum neurotoxins binding domains; Lalli G et al.; Tetanus and botulinum neurotoxins constitute a family of bacterial protein toxins responsible for two deadly syndromes in humans (tetanus and botulism, respectively) . They bind with high affinity to neurons wherein they cause a complete inhibition of evoked neurotransmitter release . Here we report on the cloning, expression and use of the recombinant fragments of the heavy chains of tetanus neurotoxin and botulinum neurotoxin serotypes A, B and E as tools to study the neurospecific binding of the holotoxins . We found that the recombinant 50 kDa carboxy-terminal domains of tetanus and botulinum neurotoxins alone are responsible for the specific binding and internalisation into spinal cord cells in culture . Moreover, we provide evidence that the recombinant fragments block the internalization of the parental holotoxins in a dose-dependent manner, as determined by following the neurotoxin-dependent cleavage of their targets VAMP/synaptobrevin and SNAP-25 . In addition, the recombinant binding fragments cause a significant delay in the paralysis induced by the corresponding holotoxin on the mouse phrenic nerve-hemidiaphragm preparation . Taken together, these results show that the carboxy-terminal domain of tetanus and botulinum neurotoxins is necessary and sufficient for the binding and internalisation of these proteins in neurons and open the possibility to use them as tools for the functional characterisation of the intracellular transport of clostridial neurotoxins.

Przegl Epidemiol, 1999, 53(1-2), 115 - 20
{Botulism in 1997}; Przybylska A; In 1997 81 cases of botulism in Poland were registered . The morbidity amounted 0.21/100,000 . In the rural regions were registered 55, and in urban regions 26 cases . The morbidity in the rural regions amounted 0.37, and in urban regions 0.13 . The morbidity of men (0.23) outnumbered the morbidity of women (0.19) . In 1997 there were 8 outbreaks of two people noted, 2 outbreaks of three people and 2 of four people . Among the vehicles of the botulinum toxin dishes from meat remained on the first position (65.4% of cases), and in these numbers prevailed wecks of home production (19.8%) . No deaths caused by botulinum toxin were noted in 1997.

Przegl Epidemiol, 1999, 53(1-2), 103 - 14
{Foodborne infections and food poisoning in 1997}; Przybylska A; In total were registered 27,922 cases of foodborne infections and intoxications in 1997 (salmonelloses of animal source, staphylococcal, botulism, other bacterial and caused by undetermined agents) . Morbidity amounted 72.7/100,000 . In 274 outbreaks of collective illnesses (4 people and more) 4,817 cases were registered altogether . Salmonella enteritidis caused 95.5% causes in outbreaks . The main vehicle of foodborne infections and intoxications in outbreaks was food prepared from raw materials of animal source, which caused 91.2% cases in outbreaks, in which dishes from eggs brought about 47.4% of these cases . Among the places of the ready made food production, private homes prevailed (57.9% of the whole amount of outbreaks) . There epidemics numbering above 100 cases each were registered in 1997.

Eur J Anaesthesiol, 1999 May, 16(5), 346 - 9
Botulism with respiratory insufficiency requiring extra corporeal carbon dioxide removal; Buchmann T et al.; Despite a low incidence of botulism in the industrialized world some cases occasionally occur in Germany after eating contaminated food . Because botulism is rarely seen, most physicians are unfamiliar with its early recognition and treatment . However, immediate intensive care treatment is important . We report the case of a previously healthy 54-year-old female who developed signs of botulism after eating vacuum packed smoked fish and developed severe respiratory insufficiency with difficult carbon dioxide elimination in the days following.

MMWR Morb Mortal Wkly Rep, 1999 Jun 4, 48(21), 437 - 9
Foodborne botulism associated with home-canned bamboo shoots--Thailand, 1998; Generalised muscular weakness after botulinum toxin injections for dystonia: a report of three cases; Department of Clinical Neurology, Institute of Neurology, University College, London, Queen Square, London, UKThree patients are reported on who developed transient generalised weakness after receiving therapeutic doses of botulinum toxin for cervical dystonia (one case) and symptomatic hemidystonia (two cases) respectively . Clinical and electrophysiological findings were in keeping with mild botulism . All patients had received previous botulinum toxin injections without side effects and one patient continued injections without recurrence of generalised weakness . The cause is most likely presynaptic inhibition due to systemic spread of the toxin . Patients with symptomatic dystonia may be more likely to have this side effect and botulinum toxin injections in these patients should be carried out cautiously.

Can J Neurol Sci, 1999 May, 26(2), 123 - 6
Botulism: heart rate variation, sympathetic skin responses, and plasma norepinephrine; Chen JT et al.; BACKGROUND: Botulism may involve the autonomic nervous system . METHODS: We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine . RESULTS: Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole . Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 +/- 1.2% vs . 20.9 +/- 2.0%, p = 0.0018) and during deep breathing (4.3 +/- 2.3% vs . 29.7 +/- 2.6%, p = 0.0018) . The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 +/- 10.1 pg/ml vs . 257.5 +/- 65.8 pg/ml, p = 0.0018; standing 40.3 +/- 13.1 pg/ml vs . 498.5 +/- 85.6 pg/ml, p = 0.0018) . The heart rate variation and sympathetic skin response was greatly improved 6 months after onset . CONCLUSIONS: Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

Int J Fertil Womens Med, 1999 Mar-Apr, 44(2), 83 - 95
A lifetime of healthy skin: implications for women; Bergfeld WF; During her lifetime, a woman faces the possibility of seeking dermatological assistance for a myriad of conditions, including acne, rosacea, striae, photodamage, and skin cancers . It is important for clinicians and patients to be aware of the symptoms of these conditions as well as the most beneficial approaches for prevention, diagnosis, treatment, and management . The life expectancy of women has increased and predictions for the year 2050 estimate the average age at 81 years . This will place women at greater risk for dermatological problems, especially photodamage and skin cancer . In addition, various ethnic groups may manifest these conditions differently . Although acne is most prevalent among teenaged males, most can expect clearing by age 25 . Females may continue to experience acne into the adult years, sometimes beyond the age of 40 . Although it is not a life-threatening disease, acne may have psychosocial and quality-of-life consequences . Treatments for acne can be topical or systemic, and include retinoids, antibiotics, benzoyl peroxide, azelaic acid, and hormonal therapy . Rosacea is more common in women (especially during menopause) than in men . It is a chronic condition that can cause complications, including telangiectasia, conjunctivitis, and blepharitis . Although there is no cure, rosacea can be managed and controlled with medication . Topical antibiotics, such as metronidazole, and systemic antibiotics, such as tetracycline, clarithromycin, and doxycycline, are used to manage rosacea . Striae, or stretch marks, occur most frequently in pregnant women, adolescents experiencing growth spurts, weight lifters, and the obese . Although not a health threat, they can be psychologically distressing . There are not many treatment options for striae, but topical tretinoin and the pulsed dye laser offer promising results . Intrinsic, or normal, aging of the skin results from the process of chronological aging . Photodamage is skin damage caused by chronic exposure to ultraviolet (UV) light . It is the leading cause of extrinsic aging, or alterations of the skin due to environmental exposure . Estimates indicate that almost half of a person's UV exposure occurs by age 18 . Photoaging causes numerous histologic, physiologic, and clinical changes; it also increases the risk for skin cancer . Photodamage can be prevented through the use of sun screens, protective clothing, and avoidance of the sun during peak intensity time . The only product approved by the FDA for the treatment of photodamage (fine wrinkles, mottled hyperpigmentation, and skin roughness), topical tretinoin emollient cream, may help prevent additional photoaging when it is used to treat existing photoaging . Other management options for photodamaged skin include alpha-hydroxy acids, antioxidants, antiandrogens, moisturizers, and exfoliants . In patients with excessive manifestations of photodamage, surgical management may be needed, including dermabrasion, chemical peels, soft tissue augmentation, laser resurfacing, botulism toxin, and Gortex threads . Clinicians must educate their patients about the most appropriate skin care regimen as well as approaches for preventing and treating common afflictions . In this way, women will have the best opportunity for having and maintaining healthy skin.

Berl Munch Tierarztl Wochenschr, 1999 Apr, 112(4), 139 - 45
{Botulism--a forgotten disease?}; Bohnel H; The laboratory diagnosis of C . botulinum is described for cattle and horses in the years 1995-1998 . Out of 122 cases 66 were positive . All types of toxins were identified; in cattle mainly types C and D . In 9 cases typing was not conclusive . The results of an enquiry of afflicated animal owners showed, that modern agricultural technology has an important impact on toxinogenesis in feed stuff . Possibilities to prevent the disease and to reduce economic losses are discussed; a solution cannot be presented.

Philos Trans R Soc Lond B Biol Sci, 1999 Feb 28, 354(1381), 259 - 68
Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses; Pellizzari R et al.; The clostridial neurotoxins responsible for tetanus and botulism are proteins consisting of three domains endowed with different functions: neurospecific binding, membrane translocation and proteolysis for specific components of the neuroexocytosis apparatus . Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized and transported retroaxonally to the spinal cord . The spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory interneurons . In contrast, the seven serotypes of botulinum neurotoxins (BoNTs) act at the periphery by inducing a flaccid paralysis due to the inhibition of acetylcholine release at the neuromuscular junction . TeNT and BoNT serotypes B, D, F and G cleave specifically at single but different peptide bonds, of the vesicle associated membrane protein (VAMP) synaptobrevin, a membrane protein of small synaptic vesicles (SSVs) . BoNT types A, C and E cleave SNAP-25 at different sites located within the carboxyl-terminus, while BoNT type C additionally cleaves syntaxin . The remarkable specificity of BoNTs is exploited in the treatment of human diseases characterized by a hyperfunction of cholinergic terminals.

Eur J Neurol, 1999 Jan, 6(1), 91 - 3
Botulism: a case associated with pyramidal signs; Santini M et al.; Botulism is a widespread neuroparalytic disease that may be confused with other neurological disorders . As it is potentially lethal, clinicians are required to be aware of its diagnosis and management . We report a case of botulism complicated by pyramidal signs in a 35-year-old woman . Clinical aspects, differential diagnoses and therapeutic problems are discussed .

J Child Neurol, 1999 Mar, 14(3), 156 - 8
Infantile botulism: pitfalls in electrodiagnosis; Sheth RD et al.; Botulism in infants, unless recognized early, is associated with high mortality and morbidity . The diagnosis is suspected when infants present with sudden onset of weakness, respiratory failure, and constipation and is confirmed by demonstration of botulinum toxin in stool several weeks later . Electrodiagnosis allows quick and reliable confirmation of botulism . Low-amplitude compound muscle action potentials, tetanic or post-tetanic facilitation, and the absence of post-tetanic exhaustion support the diagnosis . Two infants with confirmed botulism did not exhibit the characteristic electrodiagnostic features, demonstrating the pitfalls in electrodiagnosis of infantile botulism.

Int J Circumpolar Health, 1998, 57 Suppl 1, 228 - 34
Primer on food-borne pathogens for subsistence food handlers; Himelbloom BH; Subsistence food preparations may lead to human illnesses caused by pathogenic bacteria and viruses . Little is known about the incidence of food-borne illnesses other than botulism in circumpolar indigenous populations . Lack of documentation for other pathogens may be related to the sparsely populated communities involved, limited laboratory analysis, and non-lethality to healthy individuals . This overview covers the major food-borne pathogens, their sources, transmission, growth parameters, and prevention . Examples of indigenous peoples' food preparations that may be susceptible to pathogenic bacterial growth and toxin formation are described.

Toxicol Lett, 1998 Dec 28, 102-103, 191 - 7
In vitro biological activity and toxicity of tetanus and botulinum neurotoxins; Pellizzari R et al.; Tetanus and botulinum neurotoxins are the most potent toxins known and cause tetanus and botulism, respectively . They are zinc-endopeptidases acting in the cytosol, where they cleave SNARE proteins . Here, we report on the assay of their metalloproteolytic activity in vitro on recombinant SNARE proteins . We also describe the assay of their activity in nerve cells in culture using antibodies specific for the SNARE proteins . Together with recent reports from other laboratories, these results show that the toxicity of these powerful neurotoxins can be appropriately assayed in vitro, thus reducing considerably the number of animals currently used in the evaluation of the toxicity of tetanus toxoid vaccine and of the botulinum neurotoxins to be used for human therapy.

Tidsskr Nor Laegeforen, 1998 Nov 20, 118(28), 4366 - 7
{Botulism after intake of half-fermented fish}; Jensen T et al.; From 1975 to 1997, 21 cases of foodborn botulism have been reported in Norway . Half-fermented fish is the major cause . We describe one patient with botulism following intake of home-prepared half-fermented fish . Seven people had eaten fish from the same bucket, but only two developed symptoms . The fish was initially stored at 13 degrees C; this probably explains why toxin developed . Type E toxin in moderate concentrations was found in fish samples . The patient was treated with specific antitoxin and made a gradual recovery . He returned to work after eight months.

Tidsskr Nor Laegeforen, 1998 Nov 20, 118(28), 4363 - 5
{Clinical wound botulism in injecting drug addicts}; Jensen T et al.; Wound botulism among drug abusers was first described in the USA in 1982 . From 1988 to 1995, 46 laboratory confirmed cases were reported in California . The condition occurred for the first time in Norway in 1997 when three cases of suspected wound botulism among drug users who injected heroin subcutaneously or intramuscularly were reported . Two of these cases are presented here with neurophysiological findings and differential diagnosis.

Rev Laryngol Otol Rhinol (Bord), 1998, 119(4), 261 - 4
{Bilateral laryngeal movement disorder and synkinesia: value of botulism toxin . Apropos of a case}; Marie JP et al.; Several years after a subtotal thyroidectomy complicated by bilateral vocal cord paralysis, the patient presented with progressive dyspnea due to laryngeal synkinesis . The impairement of the ventilation status, in spite of laser arytenoidectomy, followed by contralateral posterior transverse cordotomy, suggested a botulinum toxin injection in the intrinsic adductor laryngeal muscles . The rapid improvement in ventilation without phonatory impairement is discussed in the following report.

Muscle Nerve Suppl, 1997, 6, S129 - 45
Botulinum toxin: historical perspective and potential new indications; Jankovic J et al.; Botulinum toxin (BTX), a purified form of the neurotoxin responsible for botulism, is used worldwide for the treatment of abnormal muscle contractions . The ability of BTX to block acetylcholine release in a long-lasting but reversible fashion with few side effects has made it an important tool in a wide variety of neuromuscular disorders, including the dystonias, tremor, tics, and spasticity . There are seven antigenically distinct toxins . BTX-A has been in clinical use for almost two decades, with an outstanding efficacy and safety profile . Clinical effects are often seen within 1 week of injection, and benefits typically last from 3-6 months . Patient selection and the proper choice of dose and administration site are the most important determinants of a favorable response to BTX treatment.

Med Klin (Munich), 1998 Sep 15, 93(9), 533 - 40
{Autonomic disorders in polyneuropathies}; Hilz MJ et al.; BACKGROUND: Many polyneuropathies manifest autonomic disturbances . Diabetic neuropathy, the most frequent neuropathy in the western world, serves as model of the symptomatology of autonomic disturbances . DIABETIC NEUROPATHY: Clinical symptoms comprise pupillary and cardiovascular dysfunction such as orthostatic hypotonia and syncopes, thermoregulatory, gastrointestinal symptoms, disturbances in urogenital and respiratory function and unawareness of hypoglycemia . OTHER NEUROPATHIES: This article also describes autonomic symptoms in alcoholic neuropathy, in Guillain-Barre syndrome, in paraneoplastic polyneuropathies, in toxic neuropathies, in acute and subacute autonomic neuropathy, in amyloidosis, in porphyria, in familiar dysautonomia, in HIV infection and in botulism.

Nat Struct Biol, 1998 Oct, 5(10), 898 - 902
Crystal structure of botulinum neurotoxin type A and implications for toxicity; Lacy DB et al.; Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a potential biological weapon and an effective therapeutic drug for involuntary muscle disorders . The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined at 3.3 A resolution . The structure reveals that the translocation domain contains a central pair of alpha-helices 105 A long and a approximately 50 residue loop or belt that wraps around the catalytic domain . This belt partially occludes a large channel leading to a buried, negative active site--a feature that calls for radically different inhibitor design strategies from those currently used . The fold of the translocation domain suggests a mechanism of pore formation different from other toxins . Lastly, the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.

Neurology, 1998 Oct, 51(4), 1093 - 9
Clinical evidence of extraocular muscle fiber-type specificity of botulinum toxin; Stahl JS et al.; OBJECTIVE: To compare the effects of botulinum toxin on static and dynamic aspects of eye movements, and thereby elucidate the mechanisms of its action on eye muscles . BACKGROUND: Laboratory evidence indicates that static alignment and saccades are subserved by different extraocular muscle fiber types, and botulinum toxin may cause specific dysfunction of the fibers controlling static alignment . Diplopia is a well-known side effect of periorbital botulinum toxin injections in humans, and may be a clinical correlate of the laboratory findings . METHODS: Search coil recording of eye movements was performed in one patient with systemic botulism, and in three patients with diplopia following periorbital injection of botulinum toxin A . RESULTS: In the patient with acute botulism, eye movement alignment, range, and saccadic velocity profiles were abnormal . In three patients with iatrogenic diplopia, static alignment was abnormal but movement range and saccadic velocities were within normal limits . Edrophonium improved the range of movements and saccadic velocities in the patient with systemic botulism but was ineffective in reversing ocular misalignment in the one iatrogenic patient to whom it was administered . CONCLUSIONS: Precise alignment is subserved by orbital singly innervated muscle fibers, and the effects of botulinum toxin are greatest on these fibers . This predilection is apparent when the toxin dose is very small, as must have been the case in our patients with iatrogenic diplopia . The lack of a response to edrophonium probably reflects structural damage to muscle fibers . In contrast, larger doses of toxin produce an acute dysfunction of all extraocular muscle fiber types, which is responsive to edrophonium and consequently reflects partial blockade at the neuromuscular junction.

Int J Food Microbiol, 1998 Aug 18, 43(1-2), 1 - 5
Type E botulism associated with vacuum-packaged hot-smoked whitefish; Korkeala H et al.; On January 16, 1997 two Germans got botulism after eating hot-smoked Canadian whitefish produced in Finland . The serum sample of one of the patients contained 6 MLD/ml of botulinum toxin . The type of toxin was identified as E by the toxin neutralization test and the botulinum neurotoxin type E (BoNT/E) gene was also amplified from the serum by polymerase chain reaction (PCR), but C . botulinum could not be isolated from the positive serum sample . The remains of the hot-smoked whitefish eaten by the patients contained botulinum toxin detected by the mouse bioassay and the BoNT/E gene as determined by PCR . C . botulinum was isolated from the fish sample and it was confirmed to be type E by the mouse bioassay and by PCR . Eleven other fish samples from the same lot did not contain botulinum toxin nor any BoNT gene . The incriminated food was processed on the 9th and 10th of January, 1997 from frozen whitefish imported to Finland from Canada . The pulsed-field gel electrophoretic pattern of the isolated C . botulinum strain resembled a reference strain of North American origin . It did not match any C . botulinum strains isolated from the Baltic sea-bottom or from the fish caught in the area indicating that the fish was contaminated by C . botulinum in Canada . The conditions resulting in toxin production could not be identified . The safety problems associated with vacuum-packaged hot-smoked fish seem to be of utmost concern and the product is one of the most important botulism food vehicles processed on an industrial scale . Temperature monitoring and the use of time-temperature indicators are to be recommended in order to ensure adequate storage temperature from processing through to consumption . Allowing the use of nitrate and nitrite together with sufficiently high NaC1 concentration in this particular product should also be considered.

C R Seances Soc Biol Fil, 1998, 192(3), 485 - 502
{Implications of bacterial protein toxins in infectious and food-borne diseases}; Alouf J; Among the 315 protein toxins elicited by gram positive and gram negative bacteria so far characterized, about 50 toxins are currently considered as totally or partially, responsible of the pathological manifestations and/or lethality resulting from host infection or intoxication (contaminated food) by relevant toxinogenic bacteria . A certain number of criteria are required for the assessment of indisputable involvement of a toxin or an array of toxins (from the same bacteria) in infectious diseases: 1) The bacterial microorganism clearly identified as the pathogenic agent of the disease produces component(s) considered as toxin(s); 2) The administration to appropriate animal(s) of the toxin(s) separated from the relevant bacteria or produced by genetic engineering from a heterologous tox+ recombinant bacterial strain produces symptoms and pathophysiological disorders that mimic those observed in the natural disease or at least those elicited in experimental animals by the cognate toxin-producing bacteria; 3) The in vitro incubation of the isolated toxin(s) with appropriate animal organs, tissues or cells elicits certain pathophysiological, biochemical or metabolic manifestions observed in the host infected with the relevant toxinogenic bacteria; 4) Toxin concentration in the organism of the host infected by the toxinogenic bacteria should be compatible with the characteristics of the relevant disease . The toxins of pathogenic interest exhibit a variety of effects in bacterial diseases . Bacteria that colonize a wound or mucosal surface but do not invade target cells can produce toxins that act locally or enter the bloodstream and attack internal organs (e.g . Corynebacterium diphtheriae, Vibrio cholerae, ...) . Bacteria growing in a wound can produce toxins that destroy host tissue and kill phagocytes in the immediate vicinity of the bacteria, thus facilitating bacterial growth and spread . On the basis of the above mentioned criteria, the following bacterial diseases among many others are toxin-associated (toxinoses): diphtheria, tetanus, botulism, whooping cough, diarrhea, bloody diarrhea, hemolytic uremic syndrome, cholera, scarlet fever, toxic shock syndrome, gas gangrene, B . fragilis diarrhea, anthrax, pseudomembranous colitis.

Lijec Vjesn, 1998 May, 120(5), 131 - 7
{Membrane metalloendopeptidase (CD10/CALLA): distribution, physiologic and pathophysiologic functions and its inhibitors}; Stanovic S et al.; Membrane metalloendopeptidase EC 3.4.24.11 (Enkephalinase, neutral endopeptidase, NEP) is a cellular ectoenzyme, immunophenotypically identified as the leukocyte cluster of differentiation CD10 or CALLA (common acute lymphoblastic leukemia antigen) . Immunological, biochemical and molecular biology techniques have identified tis cell membrane feature in various organs: brain, cardiovascular system, lung, placenta, kidney etc . The CD10 immunophenotype is a common feature of lymphoblasts in acute lymphoid leukemia not expressing the T- or B-markers . The enzymatic activity of CD10/NEP possibly influences normal lymphocyte ontogeny by proteolytic cleavage of the regulatory peptides . The substrates of CD10/NEP in the kidneys are (see the list of abbreviations) ANP, adrenomedullin and PAMP; in the brain, the substrates are enkephalins and oxytocin; in the lung, bombesin, BLP, GRP, neuromedin C, substance P and neurokinin A; in the cardiovascular system, angiotenisin II, bradykinin and CGRP; in the gut, VIP; on the neutrophil membrane, fMLP etc . Some substrates are not strictly tissue-specific, e.g . substance P . Preclinical and clinical trials explore possibilities of therapeutic application of the inhibitors of neutral endopeptidase, such as thiorphan in the management of pain, diarrhoea, depression, arterial hypertension and asthma . Other possibilities of application include the treatment of hyalinomembranous disease and prevention of neurotoxicosis in tetanus and botulism.

J Protein Chem, 1998 Jul, 17(5), 453 - 62
Production of an expression system for a synaptobrevin fragment to monitor cleavage by botulinum neurotoxin B; Nowakowski JL et al.; Recombinant DNA techniques were used to develop an expression system for a 51-amino acid peptide fragment that encompasses residues 44-94 of human synaptobrevin 2 . This protein is associated with secretory vesicles of nerve terminals and is a substrate for four of the seven serotypes of botulinum neurotoxin (BoNT) . The DNA for the recombinant peptide was amplified by the polymerase chain reaction and cloned into the pTrxFus vector . The resulting synaptobrevin peptide was expressed as a thioredoxin fusion protein in E . coli and released into the medium by osmotic lysis . The 18.7-kDa thioredoxin-synaptobrevin protein, designated as TSB-51, is intended for use in a cell-free assay to test potential inhibitors of BoNT/B-mediated proteolysis of synaptobrevin with the ultimate aim of developing clinically effective therapeutic agents to counteract botulism . Incubation of TSB-51 with the purified light chain of BoNT/B resulted in proteolysis which was evident within 30 min and increased with time until completion (approximately 4 hr) . Cleavage of TSB-51 appeared to be at the appropriate BoNT/B cleavage site as indicated by a reduced intensity of the 18.7-kDa band and the appearance of a band at 16.4 kDa on Tris-tricene polyacrylamide gradient gels . The concentration of free Zn2+ had a significant effect on the cleavage rate; low Zn2+ concentrations stimulated substrate cleavage, whereas high concentrations were inhibitory . Cleavage was not significantly depressed by the naturally occurring metalloprotease inhibitor phosphoramidon when tested at concentrations up to 5 mM . TSB-51 appears to be a useful substrate for studying BoNT/B and is expected to aid in the discovery of effective BoNT inhibitors.

J Neuroimmunol, 1998 Jun 1, 86(1), 74 - 9
Is IgG anti-GT1a antibody associated with pharyngeal-cervical-brachial weakness or oropharyngeal palsy in Guillain-Barré syndrome?
Koga M, Yuki N, Ariga T, Morimatsu M, Hirata K.
The pharyngeal-cervical-brachial variant (PCB) of Guillain-Barre syndrome (GBS) has clinical features similar to those of botulism and diphtheria . Mizoguchi et al . (1994) {Mizoguchi, K., Hase, A., Obi, T., Matsuoka, H., Takatsu, M., Nishimura, Y., Irie, F., Seyama, Y., Hirabayashi, Y., 1994 . Two species of antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial variant of Guillain-Barre syndrome . J . Neurol . Neurosurg . Psychiatry 57, 1121-1123} reported a patient with PCB-like symptoms who had serum IgG anti-GT1a antibodies which did not cross-react with GQ1b . We assumed that PCB is associated with anti-GT1a antibodies that do not have reactivity to GQ1b and made a serological study of a PCB patient . We searched for PCB patients prospectively and found one with PCB . This patient had IgG anti-GT1a antibodies which were not absorbed with GQ1b in an absorption study, whereas IgG anti-GT1a antibodies from Fisher's syndrome patients were . The frequency of positive IgG anti-GT1a antibody did not differ in patients with and without bulbar palsy . Our findings indicate that IgG anti-GT1a antibodies which do not cross-react with GQ1b are specifically detectable in PCB and can be used as a diagnostic marker of PCB.

J Infect Dis, 1998 Jul, 178(1), 172 - 7
A large outbreak of botulism: the hazardous baked potato; Angulo FJ et al.; In April 1994, the largest outbreak of botulism in the United States since 1978 occurred in El Paso, Texas . Thirty persons were affected; 4 required mechanical ventilation . All ate food from a Greek restaurant . The attack rate among persons who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among persons who did not eat the dip (relative risk {RR} = 13.8; 95% confidence interval {CI}, 7.6-25.1) . The attack rate among persons who ate an eggplant-based dip was 67% (6/9) compared with 13% (241189) among persons who did not (RR = 5.2; 95% CI, 2.9-9.5) . Botulism toxin type A was detected from patients and in both dips . Toxin formation resulted from holding aluminum foil-wrapped baked potatoes at room temperature, apparently for several days, before they were used in the dips . Consumers should be informed of the potential hazards caused by holding foil-wrapped potatoes at ambient temperatures after cooking.

Arch Phys Med Rehabil, 1998 May, 79(5), 589 - 90
An aggressive approach to limb dystonia: a case report; Moberg-Wolff EA; A 15-year-old boy presented with a severe fluctuating foot and ankle dystonia resulting from a basal ganglia insult at the age of 4 . This followed an embolic event related to an undiagnosed prolapsed mitral valve . Functionally, the patient was ambulatory with rocker bottom crutches and an ankle-foot orthosis, but there were periods of up to a year when pain and increased dystonic deformity required him to use a wheelchair . A new orthotic was made nearly every month because the orthotist could find no material that would withstand his tone without breaking, yet he could not ambulate without one . Multiple interventions, including biofeedback, contrast baths, stretching and strengthening, oral lioresal (Baclofen), diazepam (Valium), benztropine mesylate (Cogentin), carbidopa-levodopa (Sinemet), carbamazepine (Tegretol), and injections of botulism toxin (BOTOX) were tried, all with minimal effects . Amputation was recommended, based on anatomic and functional considerations . The patient and his family adjusted well to this decision, although not all orthopedists and therapists adjusted easily to the choice . The patient is now functionally independent with a prosthesis and has a normal teenage lifestyle for the first time.

Biochemistry, 1998 Apr 14, 37(15), 5267 - 78
Role of zinc in the structure and toxic activity of botulinum neurotoxin; Fu FN et al.; Zn2+-protease activity of botulinum neurotoxin causes the blockage of neurotransmitter release resulting in botulism disease . We have investigated the role of Zn2+ in the biological activity of type A botulinum neurotoxin by removing the bound Zn2+ by EDTA treatment, followed by monitoring its structure in terms of secondary and tertiary folding (second derivative UV, FT-IR, and circular dichroism spectroscopy) and function in terms of its effect on the release of norepinephrine from PC12 cells . The single Zn2+ bound to each neurotoxin molecule was reversibly removed by EDTA treatment, whereas the biological activity of the neurotoxin was irreversibly lost . Based on the Amide III IR spectral analysis, the alpha-helical content of neurotoxin increased from 29% to 42% upon removal of Zn2+, which reverted to 31% upon treatment with 1:5 molar excess of exogenous Zn2+ . Second derivative UV spectroscopy revealed no change in surface topography of Tyr residues with removal of Zn2+ . However, near-UV circular dichroism signals suggested significant alterations in the topography of Phe and Tyr residues that could be buried in the protein matrix . Thermal unfolding experiments suggested that removal of Zn2+ results in the formation of the molten globule-like structure of type A botulinum neurotoxin . Tertiary structural changes introduced by Zn2+ removal were irreversible, which correlated well with the irreversibility of the biological activity of the neurotoxin . On the basis of these results, we suggest that Zn2+ plays a significant structural role in addition to its catalytic role in Zn2+-protease activity of type A botulinum neurotoxin.

Rev Sci Tech, 1997 Dec, 16(3), 770 - 5
National surveillance of poultry diseases in Lebanon; Barbour EK et al.; From 1992 to mid-1996, a national survey of poultry diseases in Lebanon was conducted . This surveillance included meat breeder, layer breeder, commercial layer and chicken broiler flocks . The history, signs, lesions and laboratory tests of poultry were used in the diagnosis of prevalent poultry diseases . Culture techniques were used to screen for bacterial diseases; serological techniques and, to a lesser extent, culture techniques were used to diagnose viral diseases; and both serological and culture techniques were used to diagnose Mycoplasma infections . The outbreaks of diseases detected in broiler breeder flocks and the number of such flocks experiencing these diseases were as follows: femoral head necrosis (6), egg-drop syndrome (3), reovirus-associated malabsorption syndrome (3), synovitis (Mycoplasma synoviae infection) (7), swollen head syndrome (SHS) (3), tenosynovitis (viral arthritis) (1), lymphoid leukosis (3), avian encephalomyelitis (1), fowl pox (1) and aortic rupture (1) . The disease outbreaks detected in layer breeders were as follows: SHS (2), bumble foot (2), egg-drop syndrome (3) and avian infectious bronchitis (IB) (1) . The disease outbreaks detected in commercial layer flocks were as follows: egg-drop syndrome (5), avian infectious laryngotracheitis (2), avian IB (nephrogenic strain) (1), malabsorption (1), avian tuberculosis (Mycobacterium avium) (1), Marek's disease (1), fowl pox (1), Salmonella enterica subsp . enterica Enteritidis infection (1), salpingitis (1) and Heterakis gallinae infestation (1) . The disease outbreaks detected in broiler flocks were as follows: colibacillosis (40), infectious bursal disease (Gumboro disease) (15), malabsorption syndrome (8), avian infectious laryngotracheitis (8), paratyphoids (salmonellosis) (7), femoral head necrosis (8), SHS (6), avian mycoplasmosis (Mycoplasma gallisepticum infection) (6), synovitis (7), avian IB (6), botulism (1), avian encephalomyelitis (1) and gangrenous dermatitis (1) . Diseases which occurred and which were reported for the first time in Lebanon were as follows: bumble foot, femoral head necrosis, avian IB (nephrogenic strain), malabsorption syndrome and SHS . This surveillance helped to establish baseline data concerning the predominant poultry diseases in Lebanon . Such information is a prerequisite for future regional and international collaboration to identify the source of the aetiological agents and to control their spread to neighbouring countries.

J Neurol Sci, 1998, 156(1), 96 - 8
Transient tonic pupils in botulism type B; Monaco S et al.; We report a 29-year-old woman who developed unilateral unreactive mydriasis and cycloplegia after 5 days of persistent constipation . During the next hours the patient complained of dry mouth and difficulties in swallowing food; iris and ciliary muscle palsies spread over the second eye . Ocular motility was normal and there were no clinical signs of neuromuscular involvement . Conventional electromyography and evoked muscle action potentials following repetitive nerve stimulation were normal; single-fiber electromyography showed normal jitter and absence of blocking . The diagnosis of botulism was considered as most likely, and the patient was given botulinum antitoxin . The post-treatment course was characterized by bilateral tonic pupillary reaction to near, sectoral iris contractions to light and pupillary constriction to 2 mm in 40 min following topical instillation of 0.1% pilocarpine . Ocular manifestations completely disappeared within 5 weeks . Botulism type B toxin was demonstrated in the pretreatment stool of the patient but not the serum.

Tijdschr Diergeneeskd, 1997 Jul 15-Aug 1, 122(14-15), 402 - 7
{Experiences of a veterinary meat inspector . II}; Smit MP; A number of unusual or repeat inspections are described . These inspections took place in relation to investigations for the presence of agents that slow bacterial growth (New Netherlands Kidney Test), condemnation of the animal/carcass for more than one reason, investigations to detect the presence of hormones and beta-antagonists, severe abscesses in the spleen, absence of the entire carcass, special emergency slaughter, deep cuts in the kidney, and botulism . Emphasis is placed on the importance of veterinary meat inspectors being closely involved in the rejection or condemnation of animals for slaughter.

Can J Neurol Sci, 1998 Feb, 25(1), S36 - 9
Methods of testing neuromuscular transmission in the intensive care unit; Grand'Maison F; All disorders of neuromuscular transmission (NMT) may cause ventilatory failure, albeit rarely . Respiratory muscle weakness is occasionally the presenting feature of myasthenia gravis (MG), the Lambert-Eaton myasthenic syndrome (LEMS), hypermagnesemia and botulism . Chronic MG, congenital myasthenic syndromes and LEMS may be acutely exacerbated by various intercurrent conditions and by drugs which interfere with NMT . Finally, in the ICU, difficulty in weaning from the ventilator may be caused by prolonged use of neuromuscular blocking agents . Electrophysiological studies of NMT disorders in the intensive care unit have rarely been reported . Nevertheless, the available data indicates that the electrodiagnosis of severe NMT disorders can be misleading . With severe NMT defects, the electrophysiological distinction between post-synaptic and pre-synaptic disorders is blurred and the differential diagnosis with myopathies may be difficult . A clinically suspected NMT disorder should therefore not be ruled out when electrodiagnosis fails to demonstrate the expected abnormalities.

Arch Latinoam Nutr, 1997 Mar, 47(1), 62 - 5
Effect of calcium addition and acidification on the quality characteristics of canned okra (Hibiscus esculentus L); Nogueira JN et al.; A study was conducted on calcium chloride treatments of canned okra acidified by adding either acetic, citric, lactic, malic or tartaric acids or by lactic fermentation . The quality of the processed okra was determined by physical, chemical, microbiological and sensory analyses after a two month storage period at room temperature . The results indicated the possibility of processing high quality canned okra by small canneries, with low cost equipment and low energy requirements . The acidification procedures ensure minimal risk of botulism.

Emerg Infect Dis, 1997 Oct-Dec, 3(4), 523 - 8
Maximizing the usefulness of food microbiology research; Roberts TA; Funding for food microbiology research often follows disease outbreaks: botulism from vacuum-packed white-fish chubs, listeriosis from soft cheeses, or illness due to Salmonella Enteritidis or Escherichia coli . As a consequence of research, detection, identification, and subtyping methods improve, and more is learned about pathogenicity and virulence . Research also explores the organisms' capacity to multiply or survive in food and to be killed by established or novel processes . However, rarely is there a critical overview of progress or trustworthy statements of generally agreed-on facts . That information is not maintained in a form that can readily be used by regulatory departments and the food industry to ensure a safe food supply . A centralized system is urgently needed that is accessible electronically and carries information in a standardized format on the essential properties of the organisms, including pathogenicity, methods of detection, enumeration and identification, alternative prevention and control methods, and growth and survival characteristics.

J Clin Apheresis, 1997, 12(3), 116 - 21
Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome; Mahalati K et al.; Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX) . According to the North American Acute GBS PEX study there is a 50% or more reduction in the recovery time if PEX is initiated early in the course of the disease . Demyelinating antibodies are usually IgM . IgA antibodies require prolonged PEX . Patients with predominant IgG antibodies have chronic inflammatory demyelinating polyneuropathy (CIDP), which requires an even longer course of PEX, over weeks to months or years . We reviewed records of 73 patients with the initial diagnosis of GBS treated with PEX . Among these patients, 55 had classic GBS, three had the Miller-Fisher variant, two had CIDP, and 13 had demyelinating-like polyneuropathies associated with other conditions including malignancy, vaccine-related myelitis, steroid-induced myopathy, polymyositis, botulism, gram-negative sepsis, Sjogren's, and AIDS . Hughes grading system was used . Patients were graded 3 to 5, with grade 3 patients being unable to walk 5 m without support, grade 4 patients being bed or chair bound, and grade 5 patients being ventilator dependent . Of 60 unassociated (GBS) demyelinating cases receiving a mean of 6.5 PEX procedures, 13 (21%) were intubated early in the treatment, with four (6%) remaining ventilator dependent post-PEX . Of 51 non-intubated patients, 15 became ambulatory post-PEX . Patients with the Miller-Fisher variant showed improvement within 6 hours of PEX initiation . We did not investigate correlation of GBS with infection; however, we did observe a rise in CMV titer among 15% of the 58 patients with acute GBS . Considering our results we believe that intensive PEX on a daily basis for a few days is necessary for severely affected individuals . We advise five to nine procedures at consultation unless early, rapid recovery occurs.

Early Hum Dev, 1997 Oct 29, 49 Suppl, S105 - 20
Does breast feeding protect against non-gastric infections?
Golding J, Emmett PM, Rogers IS.
There is convincing evidence that breast-feeding is protective against gastro-enteritis and diarrhoea, but for other infections the situation is less clear cut . There is evidence that breast-fed infants are at increased risk of one infection (infant botulism) . They are probably not significantly protected from upper respiratory tract infections (other than otitis media.), but they may be at a decreased risk of lower respiratory tract infections, particularly those associated with respiratory syncytial virus . There is strong evidence that Haemophilus influenzae B infection is more likely in the bottle-fed infant, and consistent evidence of protection of young children from chronic otitis media with prolonged breast-feeding.

Muscle Nerve, 1997 Oct, 20(10), 1284 - 95
Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study; Maselli RA et al.; Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness . Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases . Muscle biopsies showed variable signs of neurogenic atrophy . In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder . Mechanical ventilation was required in 5 patients . Half of the patients were treated with polyvalent antitoxiin . Prognosis was favorable, though recovery was slow . In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism . High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.

Neurophysiol Clin, 1997 Jun, 27(3), 220 - 6
{Importance of electromyography in the diagnosis of botulism}; Zouari N et al.; Botulism is a cause of neuromuscular transmission impairment . We report here an electrophysiological study of the neuromuscular junction in a patient presenting with botulism . Repetitive stimulation of a motor nerve showed a characteristic triad, indicating presynaptic block of neuromuscular transmission: the muscle action potential amplitude was low; repetitive high frequency stimulation (20 Hz) induced a more than 100% increment in the amplitude; low frequency repetitive stimulation (3 Hz) induced a more than 10% decrement in the amplitude . Progressive clinical improvement spontaneously occurred and the electrophysiological control recording that was done 1 month later was normal . Botulism toxin reduces acetylcholine quanta released in the autonomic and neuromuscular junction, causing presynaptic block . Electrophysiological recordings associated with clinical data contributed more to the diagnosis of botulism than serological analysis, which remained negative in this patients.

C R Seances Soc Biol Fil, 1997, 191(3), 433 - 50
{Action mechanisms of botulinum neurotoxins and tetanus neurotoxins}; Deloye F et al.; Tetanus (TeNT) neurotoxin and botulinum (BoNT, serotypes A-G) neurotoxins are di-chain bacterial proteins of MW-150 kDa which are also termed as clostridial neurotoxins . They are the only causative agents of two severe neuroparalytic diseases, namely tetanus and botulism . The peripheral muscle spasms which characterise tetanus are due to a blockade of inhibitory (GABAergic and glycinergic) synapses in the central nervous system leading to a motor neurones desinhibition . In contrast, botulism symptoms are only peripheral . They are consequent to a near irreversible and highly selective inhibition of acetyl-choline release at the motor nerve endings innervating skeletal muscles . During the past decade, the cellular and molecular modes of action of clostridial neurotoxins has been near completely elucidated . After a binding step of the neurotoxins to specific membrane acceptors located only on nerve terminals, BoNTs and TeNT are internalized into neurons . Inside their target neurones, the intracellularly active moiety (their light chain) is translocated from the endosomal compartment to the cytosol . The neurotoxins' light chains are zinc-dependent (endopeptidases which are specific for one among three synaptic proteins (VAMP/synaptobrevin, syntaxin or SNAP-25) implicated in neurotransmitter exocytosis . The presence of distinct targets for BoNTs and TeNT correlates well with the observed quantal alterations of neurotransmitter release which characterize certain toxin serotypes . In addition, evidence for a second, non-proteolytic, inhibitory mechanism of action has been provided recently . Most likely, this additional blocking action involves the activation of neurone transglutaminases . Due to their specific action on key proteins of the exocytosis apparatus, clostridial neurotoxins are now widely used as molecular tools to study exocytosis.

Can Vet J, 1997 Aug, 38(8), 485 - 90
Ecosystem health as a clinical rotation for senior students in Canadian veterinary schools; Ribble C et al.; We describe 4 years of an experimental rotation in ecosystem health offered to senior veterinary students in Canada . Faculty from the 4 Canadian veterinary colleges collaborated in offering the rotation once annually at 1 of the colleges . The 1st rotation was held in Guelph in 1993, followed in successive years by rotations at Saskatoon, Saint-Hyacinthe, and Charlottetown . The rotation is a predominantly field-based experience that allows students to work with veterinary and other role models who are actively engaged in clinical research related to ecosystem health . Five specific field studies that worked particularly well during the rotations are presented . These studies involved investigating mortality in wildlife due to botulism, designing an environmental surveillance system around herds of beef cattle, using belugas to evaluate the health of the St . Lawrence River, dealing with competition for water use by aquaculture and agriculture, and exploring the role of veterinarians during major coastal oil spills . The experience has resulted in our developing the subject matter, field examples, teaching approach, and confidence necessary to make ecosystem health the focus of a productive clinical rotation for senior year veterinary students.

Acad Emerg Med, 1997 Aug, 4(8), 805 - 9
Wound botulism associated with black tar heroin; Anderson MW et al.; The incidence of wound botulism is increasing and the epidemiology of the disease is changing . The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin . This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism . In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness . For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness . This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism . To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.

Emerg Med Clin North Am, 1997 Aug, 15(3), 605 - 23
Approach to generalized weakness and peripheral neuromuscular disease; LoVecchio F et al.; A large number of intellectually engaging and potentially serious neuromuscular diseases have been presented . The emergency medicine physician must be able to recognize those entities that have the potential to clinically deterioration . The evaluation of weakness requires a comprehensive, broad-based differential that is driven by the history and physical . Diagnostic testing is determined by the clinical suspicion as is the urgency for further work-up . The following are the final diagnoses of the eight illustrative cases that were presented at the beginning of this article . Case 1 . This unfortunate woman had a metabolic myopathy that was only diagnosed after enzymatic analysis of a muscle biopsy . Her genetic defect, carnitine palmitoyltransferase deficiency, is unusual as it does not present until late in adolescence or slightly later in life . It is a defect in lipid metabolism in which long-chain fatty acids are unable to gain entrance into the mitochondrion for oxidative degradation . The defect is apparent only after prolonged exercise or fasting . In this patient, rhabddomyolysis led to acute renal failure that resolved without requiring temporary dialysis . Case 2 . This patient had an elevated CPK-MM . Her EMG showed myopathic changes and her nerve conduction studies were normal . She had a positive test for antinuclear antibodies . A biopsy of her quadriceps muscle revealed lymphocytic infiltration of the muscle fibers that showed some focal myocyte degeneration . The diagnosis of dermatomyositis was made based on the findings noted previously and the heliotrope hue of her periorbital skin . A search for an occult neoplasm was negative . She responded moderately to a course of high-dose prednisone . Case 3 . The laboratory test that confirmed this diagnosis was the potassium of 2.4 mEq/L . The remainder of the electrolytes were normal . Infusion of 20 mEq of potassium over 2 hours led to a prompt return of normal muscle strength . The final diagnosis was hypokalemic periodic paralysis . In this disease there is an inherited defect in the ability of the myocyte to maintain a normal transmembrane potential . The defect is latent until there is a precipitating factor, such as an high carbohydrate meal or prolonged immobility . There is also a form seen with thyrotoxicosis and is essentially cured when the patient becomes euthyroid . The disease is seen most frequently in Asian males, although it is reported in most ethnic groups . Prophylaxis in these patients is with acetazolamide which raises the serum potassium indirectly by causing a metabolic acidosis . Triamterene and spironolactone have also been successfully used on occasion . This patient turned out to have thyrotoxicosis as well . Case 4 . This man had both cranial motor and peripheral muscular dysfunction . There was no evidence of nonmotor cranial nerve dysfunction, nor was there evidence of any peripheral sensory deficits . The diagnosis of myasthenia gravis was established by the rapid and transient response of this patient to 2 mg of edrophonium . He was found to have antiacetylcholine receptor antibodies and was also thyrotoxic . He had a stormy course requiring intubation and prolonged ventilation . Eventually, he underwent thymectomy and is stable on pyridostigmine . Case 5 . Initially suspected to be hysteria, this patient and his relatives had botulism from home-canned peppers . The index case required prolonged intubation and ventilation . The patients were treated with polyvalent antiserum and gastric lavage to remove the residual contaminated food which was still in their stomachs due to the gastric atony seen with this disease . The botulinus toxin prevents the release of acetylcholine molecules from their storage vesicles in nerve terminals . Thus, this disease is the opposite of the cholinergic syndrome seen with organophosphate insecticide poisonings except that cognitive functioning is not impaired in botulism . Case 6 . This is a celebrated case that took a great deal of sleuthing

J Wildl Dis, 1997 Apr, 33(2), 181 - 6
Avian botulism--another perspective; Wobeser G; Waterfowl botulism is unique among intoxications because toxin produced within its victims leads to secondary poisoning of other birds . Because of this phenomenon, the epizootiology of the carcass-maggot cycle of botulism resembles that of an infectious disease and the reproductive rate (R) of the disease could be defined as the average number of secondary intoxications attributable to a single carcass introduced into a marsh . I propose that toxin production and botulism occur commonly at a low level in many marshes and that factors which influence R determine when the disease expands into a large epizootic . A model that incorporates the number of carcasses occurring in a marsh, the probability of a carcass containing spores, the probability of a carcass persisting until toxin-bearing maggots emerge, and the contact rate between live birds and toxin, may be useful for predicting the extent of secondary poisoning, for identifying questions for research, and as a theoretical basis for management.

Vet Clin North Am Equine Pract, 1997 Apr, 13(1), 107 - 28
Botulism; Whitlock RH et al.; Equine botulism is being recognized with increasing frequency by veterinarians throughout North America . Muscular weakness and dysphagia that progress during a period of 1 to 4 days, in the absence of laboratory derangements that indicate the presence of systemic disease, are suggestive of botulism . A tentative diagnosis usually is based on the presence of the following findings on physical examination: delayed pupillary light response, mydriasis, ptosis, generalized weakness, decreased tail tone, and slow prehension of feed . Definitive diagnosis requires detection of botulinum toxin in plasma, serum, gastrointestinal contents, or body tissues . Early treatment with antitoxin generally results in a favorable outcome . Botulism in foals and adult horses can be prevented by vaccination.

J Pharmacol Exp Ther, 1997 Mar, 280(3), 1489 - 98
In vitro characterization of botulinum toxin types A, C and D action on human tissues: combined electrophysiologic, pharmacologic and molecular biologic approaches; Coffield JA et al.; Human exposure to botulinum toxin typically occurs in two settings: 1) as an etiologic agent in the disease botulism and 2) as a therapeutic agent for the treatment of dystonia . Epidemiologic studies on botulism suggest that the human nervous system is susceptible to five toxin serotypes (A, B, E, F and G) and resistant to two (C and D) . In the past, these epidemiologic findings have been used as the basis for selecting serotypes that should be tested as therapeutic agents for dystonia . Epidemiologic data have been utilized because there are no studies of botulinum neurotoxin action on isolated human nerves . In the present study, electrophysiologic techniques were used to monitor toxin effects on neuromuscular transmission in surgically excised human pyramidalis muscles, ligand binding studies were done to detect and characterize toxin receptors in human nerve membrane preparations, and molecular biologic techniques were used to isolate and sequence a human gene that encodes a substrate for botulinum neurotoxin . The results demonstrated that stable resting membrane potentials (-61.5 mV; S.E.M . +/- 0.7) were maintained in individual fibers of pyramidalis muscle for up to 6 hr at 33 degrees C . The rate of spontaneous miniature endplate potentials was low in physiologic solution (0.14 sec(-1)) but increased in response to elevations in extracellular potassium concentration . In keeping with epidemiologic findings, botulinum toxin type A (10(-8) M) paralyzed transmission in human preparations (ca . 90 min) . In contrast to epidemiologic findings, serotype C (10(-8) M) also paralyzed human tissues (ca . 65 min) . Iodinated botulinum toxin displayed high-affinity binding to receptors in human nerve membrane preparations (serotype A high-affinity site: K(d) = 0.3 nM, B(max) = 0.78 pmol/mg protein; serotype C high-affinity site: K(d) = 1.96 nM, B(max) = 8.9 pmol/mg protein) . In addition, the human nervous system was found to encode polypeptides that are substrates for botulinum neurotoxin types A (synaptosomal-associated protein of M(r) 25,000) and C (syntaxin 1A) . These data have important implications bearing on: 1) the development and administration of vaccines against botulism and 2) the testing of toxin serotypes for the treatment of dystonia.

Electromyogr Clin Neurophysiol, 1996 Dec, 36(8), 477 - 80
Botulism with sensory symptoms diagnosed by neuromuscular transmission studies associated with edrophonium responsiveness; Kuruoglu R et al.; A 43-year-old female patient developed bilateral ophtalmoplegia, bulbar paresis and weakness of the respiratory and extremity muscles . Additionally she had decreased sensation on the left half of the body . Repetitive nerve stimulation (RNS) test confirmed the diagnosis of botulism and edrophonium injection caused a reduction in the decremental response . When in doubt, RNS testing can provide the definitive results in the diagnosis of botulism.

ASAIO J, 1996 Sep-Oct, 42(5), M649 - 54
Microencapsulated vaccines to provide prolonged immunity with a single administration; Whalen RL et al.; Vaccines that provide lasting immunity with a single administration of the antigen can reduce the cost of routine immunization programs while increasing their efficacy by lessening the need for patient compliance . The authors have been developing methods for using biodegradable polymer microspheres to encapsulate vaccines . These microcapsules are designed to provide timed release of the antigen on a schedule that mimics conventional booster shots . The microspheres are made from poly-DL-lactide-co-glycolide . The rate of biodegradation of this polymer is controllable by varying the molar ratio of the monomers . High performance liquid chromatography was used to measure release kinetics in vitro, and a process was developed for the encapsulation of water soluble protein antigens . This process then was used to prepare a microencapsulated vaccine for type A botulism made using a recombinant C fragment antigen . A series of 27 adult C57BL/6J mice were used to study the efficacy of this vaccine . Six mice injected with saline filled microspheres served as a control group . Plasma samples were taken weekly to measure antibody levels using enzyme linked immunosorbent assay . At 14 weeks, 21 immunized mice and six control subjects were used for an aerosol challenge test with botulinum toxin . All control subjects died within 72 hrs . Fifteen (71%) of the immunized mice survived.

Clin Infect Dis, 1996 Aug, 23(2), 337 - 40
Experience with the use of an investigational F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt; Hibbs RG et al.; During an outbreak of type E foodborne botulism in Cairo in 1991, an investigational equine F(ab')2 "despeciated" heptavalent botulism immune globulin (dBIG) was provided to the Egyptian Ministry of Health by the U.S . Army . Of 54 patients known to have been treated with antitoxins, 4 received commercially available trivalent antitoxins, 45 received dBIG, and 5 received both commercial antitoxin and dBIG . Physicians recorded side effects in 10 (22%) of 45 patients who received dBIG; in nine cases, reactions were considered "mild," and in one case they were believed to be serum sickness . In contrast, possible serum sickness during hospitalization was recorded for two of four patients who were receiving commercial antitoxins . No complications of therapy were noted for any patient who was receiving both antitoxin types . In a separate study, 31 patients were contacted about their reactions to the antitoxin by telephone after discharge from the hospital . Seven (54%) of 13 patients attributed symptoms that they experienced while they were hospitalized to receipt of dBIG, while four (44%) of nine patients who indicated that they had received commercial antitoxins and one (20%) of five who received both commercial antitoxin and dBIG reported side effects before discharge . Data on the efficacy of the antitoxins were not obtained . In our experience, equine dBIG was at least as safe as commercially available antitoxins in treating type E foodborne botulism.

Arch Surg, 1996 Aug, 131(8), 846 - 52; discussion 852-4
Necrotizing soft-tissue infections; Bosshardt TL et al.; OBJECTIVES: To evaluate the causes of necrotizing soft-tissue infections (NSTls) and to determine the outcomes of patients with NSTls . DESIGN: A restrospective survey of the causes and factors associated with the outcomes . SETTING: An urban community hospital serving an indigent population . PATIENTS: A consecutive series of patients with NTSls who were treated between December 11, 1990, and December 28, 1995 . INTERVENTIONS: Patients were treated with operative debridement, intravenous antibiotics, and supportive measures . MAIN OUTCOME MEASURES: Patient outcomes, causes, the extent of infection, the health status of the patients, causative organisms, and treatment delays . RESULTS: Forty-five patients with NSTls were identified . Twenty-eight cases (62%) have occurred since January 13, 1994 . Parenteral drug abuse, the causative event in 25 cases (56%), accounted for 21 (75%) of the 28 cases identified since January 13, 1994 . Skin flora were the primary isolates in 18 (40%) of the cases; 78% of these flora were polymicrobial . Clostridial species were isolated in 8 (18%) of the cases . The overall mortality was 27% . Survivors had less extensive infections and were more stable hemodynamically than nonsurvivors . Patients with necrosis and cellulitis greater than 250 cm2 were less likely to survive than those with less extensive infections . Logistic regression analysis identified the extents of infection, the initial blood pressure, and the initial temperature as independent predictors of outcome in this patient series . CONCLUSIONS: This is 1 of the largest reported series of patients with NSTls in which parenteral drug abuse is a prevalent causative factor . The proportion of NSTls attributable to the injection of illicit substances has increased notably in the past 2 years and has reached epidemic proportions . Survivors of NSTls had less extensive infections and were more often hemodynamically stable than nonsurvivors . Clostridial species were common in patients with NSTls related to parenteral drug abuse, underscoring the need for awareness of the potential for wound botulism in these patients.

Rev Esp Anestesiol Reanim, 1996 Jun-Jul, 43(6), 208 - 11
{Botulinum toxin: clinical uses and anesthetic implications}; Vidal-Marcos A et al.; Botulinum toxin, a neurotoxin responsible for botulism, is at present used to treat anomalous muscle contractions . Administration to children and relatively uncooperative patients requires general anesthesia, which should be selected taking into consideration the special characteristics of the surgical procedure and the possible interactions of anesthetic drugs and the toxin.

Mil Med, 1996 May, 161(5), 251 - 6
Strategies for the prevention of a successful biological warfare aerosol attack; Wiener SL; Biological warfare (BW) aerosol attacks are different from chemical attacks in that they may provide no warning/all clear signals that allow the soldier to put on or remove his M17/M40 protective mask . Methods are now being perfected to detect a BW aerosol cloud using an airborne (helicopter) pulsed laser system to scan the lower altitudes upwind from a troop concentration of corps size, and to sample and analyze the nature of the aerosol within a brief time interval . This system has certain limitations and vulnerabilities, since it is designed specifically to detect a line-type aerosol attack . Provision of, training with, and field use of a lightweight dust mist or HEPA filter respirator for each soldier is proposed for protection against undetected aerosol attacks . This particulate filter respirator would be issued in addition to the M17/M40 mask . Such a BW respirator will be able to purify the soldier's air by removing particles in the 0.3- to 15-micro m-diameter range with an efficiency of 98 to 100% . Particle size of BW aerosols is in the same range, with an optimum size for high-efficiency casualty production of 1 to 5 micro m mass median diameter . The proposed BW respirator will be lightweight; will require low inhalation pressures; will be comfortable to wear for prolonged periods; will not interfere with vision, hearing, and communication; and will not degrade overall effectiveness and performance to the degree observed with the M17/M40 masks . Such respirators would be worn as part of a contingency defense against an enemy likely to use BW agents . This respirator could be worn for prolonged periods when under threat of an undetectable BW attack during weather conditions favorable to the success of such an attack (i.e., low wind velocity and temperature inversion in the target area) . In addition, tactically important assets such as command and control centers and missile batteries can also be protected continuously by air filtration systems powered by electricity (modular collective protection equipment) . Vaccinations against anthrax, botulism, Q fever, plague, and tularemia are now available and immune protection against ricin and staphylococcal toxins appears feasible in the near future . Chemotherapy can also be provided for prophylaxis of infectious agents released on the battlefield . The vaccines and antibiotics can provide back-up protection against an unexpected BW attack during a period when the BW respirator is not in use or malfunctions due to a poor seal or filter leak . Enemy sites of biological weapon production, assembly, testing, and storage, and delivery vehicles can be targeted for destruction by bombs and/or missiles . An integrated, well-planned, BW defense with multiple components can decrease the likelihood of a successful enemy BW aerosol attack.

J Emerg Med, 1996 May-Jun, 14(3), 339 - 44
A foodborne outbreak causing a cholinergic syndrome; Greenaway C et al.; We report a foodborne outbreak causing a cholinergic syndrome in three members of a family . The clinical presentation was characterized by nausea, vomiting, abdominal pain, and weakness . Physical examination revealed evidence of peripheral motor weakness and decreased level of consciousness in all three patients . Bradycardia, hypotension, and seizures occurred in two patients . Although initial therapy included administration of antitoxin for possible botulism, subsequent investigation revealed evidence of accidental organophosphate (fensulfothion) poisoning . The ubiquitous use of organophosphates as agricultural and household insecticides has ensured their continuing importance as causes of foodborne poisoning in both developed and developing countries . Physicians must remain alert to the possibility of non-bacterial causes of foodborne outbreaks in order to initiate prompt and appropriate investigations and specific therapy.

MMWR Morb Mortal Wkly Rep, 1996 Apr 26, 45(16), 325 - 6
Tick paralysis--Washington, 1995; Special challenges of maintaining wild animals in captivity in South America; Foz Tropicana, Bird Park, Parana, BrazilThe author summarises the occurrence of major diseases in wild animals maintained in captivity in South America . The epidemiology, impact and significance of the diseases are discussed, together with appropriate husbandry practices to control and prevent transmissible diseases . The following animal groups and pathologies are considered in this review: poxvirus dermatitis, gastroenteritis, pneumonia, amoebosis and coccidiosis in reptiles, management practices and diseases (including botulism, bacterial enteritis, psittacosis, aspergillosis and parasitic diseases in birds), enterocolitis, pneumonias and internal parasites in non-human primates, canine distemper, parvoviruses, babesiosis, internal and external parasites in carnivores, tuberculosis and enteritis in tapirs, haemorrhagic disease in cervids.

Przegl Epidemiol, 1996, 50(4), 443 - 5
{Co-occurring trichinellosis and sausage poisoning: report of 4 cases}; Furmaniuk J; Four cases of the coexisting trichinellosis and botulism . Four cases of the coexisting trichinellosis and botulism in an epidemia of trichinellosis are presented . Botulism varied in the clinical expressing causing diagnostic especially in an index care.

MMWR Morb Mortal Wkly Rep, 1995 Dec 8, 44(48), 889 - 92
Wound botulism--California, 1995; Expression and purification of the light chain of botulinum neurotoxin A: a single mutation abolishes its cleavage of SNAP-25 and neurotoxicity after reconstitution with the heavy chain; Department of Biochemistry, Imperial College of Science, Technology and Medicine, LondonBotulinum neurotoxin type A (BoNT/A) selectively and irreversibly inhibits acetylcholine release from peripheral nerve endings . While the toxin's heavy (H) chain contributes to neuronal binding and internalization, its light (L) chain is a Zn(2+)-dependent endoprotease that intracellularly cleaves synaptosomal-associated protein of M(r) = 25 kDa (SNAP-25) . For research and clinical exploitation of this uniquely-acting neurotoxin, recombinant wild-type L chain was produced together with a mutant in which His227 in the Zn(2+)-binding motif was substituted by Tyr . The PCR-amplified wild-type and mutant L chain genes were cloned, fused to the gene for maltose-binding protein, and expressed at high levels in Escherichia coli . The soluble fusion proteins were purified using amylose affinity chromatography, and, after factor Xa cleavage, the free L chains were isolated . The wild-type was shown to proteolyze SNAP-25 at a rate approaching that of the native chain while the mutant was inactive . Reconstitution of the pure wild-type L chain with native homogeneous H chain yielded a disulfide-linked dichain form that inhibited neuromuscular transmission in vitro and produced the symptoms of botulism in vivo . After reconstitution with the H chain, the Tyr227 mutant L chain failed to show any neuroparalytic activity in either of these assays . This methodology allows, for the first time, routine preparation of recombinant forms of the L chain that are needed to decipher the molecular details of its interaction with substrate and, thereby, assist the design of effective inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Q Rev Biophys, 1995 Nov, 28(4), 423 - 72
Structure and function of tetanus and botulinum neurotoxins; Montecucco C et al.; Tetanus and botulinum neurotoxins are produced by Clostridia and cause the neuroparalytic syndromes of tetanus and botulism . Tetanus neurotoxin acts mainly at the CNS synapse, while the seven botulinum neurotoxins act peripherally . Clostridial neurotoxins share a similar mechanism of cell intoxication: they block the release of neurotransmitters . They are composed of two disulfide-linked polypeptide chains . The larger subunit is responsible for neurospecific binding and cell penetration . Reduction releases the smaller chain in the neuronal cytosol, where it displays its zinc-endopeptidase activity specific for protein components of the neuroexocytosis apparatus . Tetanus neurotoxin and botulinum neurotoxins B, D, F and G recognize specifically VAMP/ synaptobrevin . This integral protein of the synaptic vesicle membrane is cleaved at single peptide bonds, which differ for each neurotoxin . Botulinum A, and E neurotoxins recognize and cleave specifically SNAP-25, a protein of the presynaptic membrane, at two different sites within the carboxyl-terminus . Botulinum neurotoxin type C cleaves syntaxin, another protein of the nerve plasmalemma . These results indicate that VAMP, SNAP-25 and syntaxin play a central role in neuroexocytosis . These three proteins are conserved from yeast to humans and are essential in a variety of docking and fusion events in every cell . Tetanus and botulinum neurotoxins form a new group of zinc-endopeptidases with characteristic sequence, mode of zinc coordination, mechanism of activation and target recognition . They will be of great value in the unravelling of the mechanisms of exocytosis and endocytosis, as they are in the clinical treatment of dystonias.

Schweiz Med Wochenschr, 1995 Sep 30, 125(39), 1805 - 12
{Epidemic of type B botulism: Sion, December 1993-January 1994}; Troillet N et al.; 12 cases of food-borne botulism were registered in Sion, Switzerland, between 31 December, 1993 and 12 January, 1994 . A type B toxin was isolated from the serum of one patient and from the incriminated ham . Clinical data of 10 male patients aged 21 to 54 years and some epidemiologic data are reported . The clinical course was mild to moderate with predominant autonomic and gastro-intestinal symptoms and signs: blurred vision (10 patients of 10), dry mouth with dysphagia (9/10), asthenia (7/10), diarrhea and/or constipation (7/10), nausea and vomiting (6/10), abdominal cramps (5/10), impaired sexual function (5/10), dilated pupils (4/10) . Some discomfort (mainly blurred vision, asthenia and impaired sexual function) persisted for several months in most patients . Neuromuscular involvement was never the reason for seeking medical assistance and had often disappeared at the time of the first visit . Two patients were hospitalized, one for transient ileus of unknown origin and the second (first suspected case) for monitoring and infusion of trivalent equine botulinum antitoxin . This treatment was administered on day eight after intoxication and had no effect on this patient's outcome when compared with others . No patient died . Epidemiology, diagnosis, treatment and prognosis of botulism are discussed.

Anesteziol Reanimatol, 1995 Sep-Oct, (5), 27 - 9
{Role of hypoxia factor in changes of ionic composition of blood and muscle tissue in experimental botulinum poisoning}; Morrison VV; Levels of sodium and potassium ions in muscle tissue, blood plasma and red cells were measured, and the index characterizing the capacity of tissue to accumulate cations from the environment and the discrimination coefficient were calculated in experiments on white rats subjected to experimental generalized botulinum poisoning . Late stages of botulism were found to involve a deficit of potassium and sodium ions in red cells . With the progress of intoxication, a deficit of potassium ions develops in muscle tissue and the capacity of this tissue to accumulate potassium ions from the environment declines . All these disorders are more expressed in rapidly contracting skeletal muscles . An antihypoxant gutimin reduces sodium deficit in the blood plasma and red cells and leads to normalization of potassium ion levels in muscle tissue.

Rinsho Byori, 1995 Sep, 43(9), 902 - 9
{Pathophysiology on the disorder of neuromuscular transmission defects}; Sahashi K et al.; Neuromuscular transmission defects are often puzzling but challenging diseases for the pediatric and adult neurologists . Some of these disorders entail severe or even life-threatening disability: Most are treatable, but effective therapy requires precise diagnosis sometimes difficult to make especially in congenital defects . The diagnosis rests on the combination of clinical data, the electromyogram and additional studies that may include microelectrode analysis of neuromuscular transmission, ultrastructural and cytochemical studies of neuromuscular junction (NMJ) and biochemical/molecular genetic studies on muscle specimens . Understandably, these studies often depend on the collaboration of several investigators . In each myasthenic disorder, an abnormality affects neuromuscular transmission directly or causes secondary derangements that eventually affects transmission . Namely, lesions of both the presynaptic and/or postsynaptic area manifest a variety of clinical findings . Here was discussed the pathophysiology on myasthenia gravis and Lambert-Eaton myasthenic syndrome of abnormal autoimmunity, congenital myasthenic syndromes of a chromosomal defect, and poisoning of organophosphorus, botulism and some other toxins.

Orv Hetil, 1995 Jul 9, 136(28), 1497 - 9
{Botulism in infancy}; Trethon A et al.; According to international references the publication ascertains the etiologic role of neurotoxin producing Clostridial spp., other than C . botulinum in Infant botulism . Authors report on the first Hungarian case of Infant botulism . The organism isolated -- C . barati -- is responsible only for a small proportion of published cases . Authors point out the conjunction of Infantile botulism and crib death.

J S Afr Vet Assoc, 1995 Jun, 66(2), 77 - 82
Two outbreaks of type C and type D botulism in sheep and goats in south Africa; Van der Lugt JJ et al.; Two outbreaks of botulism in sheep and goats are described; in one, 329 out of 900 sheep in a feedlot died within 9 d of the onset of the disease and in the other, 100 sheep and goats out of 330 succumbed over a period of about 3 weeks . Animals were found dead or died suddenly, without exhibiting clinical signs . Others stood with lowered heads and showed drooling of saliva or a stiff gait . Paresis and/or paralysis were frequent signs in the terminal stages of the disease . Gross lesions such as the accumulation of fluids in body cavities, pulmonary oedema, foam in the trachea, epicardial haemorrhages and congestion of the mucosa of the small intestine, suggestive of heart failure, were present in animals from both outbreaks . Botulism was confirmed via the mouse toxicity test, by the demonstration of Type C and Type D toxins in the feed and intestinal contents of sheep from the first outbreak and Type D toxin in intestinal contents of sheep from the second . The clinical signs and macropathology in the outbreaks of botulism in sheep and goats in South Africa may resemble "krimpsiekte" and cardiac glycoside and ionophore poisoning, as well as other conditions causing heart failure.

Aust Vet J, 1995 Jun, 72(6), 228 - 34
The clinical differentiation of nervous and muscular locomotor disorders of sheep in Australia; Bourke CA; Many of the nervous and muscular locomotor disorders that affect sheep throughout Australia are commonly referred to as "staggers" syndromes . The range of clinical signs displayed by sheep suffering these disorders is sufficiently diverse to enable each syndrome to be graded into one of 5 progressive clinical groups . The first group, the limb paresis syndromes, includes the primary myopathies associated with the ingestion of Ixiolaena brevicompta, Malva parviflora, and Trachymene ochracea, as well as selenium and Vitamin E disorders, Paroo virus staggers, congenital progressive muscular dystrophy, humpy back, hypocalcaemic muscle weakness, Tribulus terrestris staggers and tetanus . The second group is characterised by limb paresis with knuckling of the fetlocks, and includes the plant-associated toxicities of Romulea rosea, Stachys arvensis, Trachyandra divaricata, and Tribulus micrococcus, together with haloxon toxicity, enzootic ataxia (copper deficiency), and the probably genetic disorders of segmental axonopathy, neuroaxonal dystrophy, and degenerative thoracic myelopathy . Other locomotor disorders that fit more loosely into this group are listerial myelitis (post-dipping staggers), vitamin A deficiency, cervico-thoracic vertebral subluxation Stypandra glauca toxicity, Ipomoea spp toxicity, ivermectin toxicity, and botulism . The third group, the falling syndromes, includes the probably genetic disorders of thalamic cerebellar neuropathy, cerebellar abiotrophy, and globoid cell leucodystrophy, together with Swainsona spp toxicity . The fourth group, the falling syndromes, includes the plant associated toxicities of phalaris staggers, perennial rye grass staggers and nervous ergotism (Claviceps paspali).(ABSTRACT TRUNCATED AT 250 WORDS)

MMWR Morb Mortal Wkly Rep, 1995 Mar 24, 44(11), 200 - 2
Foodborne botulism--Oklahoma, 1994; Preventing complications in infant botulism; By recognizing early signs of complications and intervening appropriately, the nurse plays a critical role in improving outcomes for infant botulism patients . The profound impact of the disease upon the family unit may be lessened by meticulous nursing care, parental support and education.

MMWR Morb Mortal Wkly Rep, 1995 Jan 20, 44(2), 33 - 6
Type B botulism associated with roasted eggplant in oil--Italy, 1993; Botulism: the present status of the disease; Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USAThe main form of human botulism throughout the world is the classic foodborne intoxication . Would botulism is very rare, and most of the documented cases have been found in the United States . While infant botulism remains rare throughout the world, it has become the most frequent form of the disease in the United States in recent years . On very rare occasions botulism results from growth and toxin production in humans other than infants . Botulism occurs in animals with much higher frequency . The causative organisms constitute a diverse group of clostridia, resulting in nomenclature problems . Human botulism is largely limited to toxin types A, B, and E, while type C botulism predominates in avian and nonhuman mammalian species . The diagnosis of botulism is made on the basis of the neurologic signs and symptoms that it causes in humans and animals . The diagnosis is confirmed by tests that identify the toxin and toxigenic organisms in patient and food specimens . Treatment includes supportive intensive care and use of therapeutic antitoxin.

Naunyn Schmiedebergs Arch Pharmacol, 1995 Jan, 351(1), 67 - 78
Processing of tetanus and botulinum A neurotoxins in isolated chromaffin cells; Erdal E et al.; Tetanus and botulinum A neurotoxins were introduced into the cytosol of chromaffin cells by means of an electric field in which the plasma membrane is forced to form pores of approximately 1 micron at the sites facing the electrodes . As demonstrated by electron microscopy, both {125I} and gold-labelled tetanus toxin (TeTx) diffuse through these transient openings . Dichain-TeTx, with its light chain linked to the heavy chain by means of a disulfide bond, causes the block of exocytosis to develop more slowly than does the purified light chain . The disulfide bonds, which in both toxins hold the subunits together, were cleaved by the intrinsic thioredoxin-reductase system . Single chain TeTx, in which the heavy and light chains are interconnected by an additional peptide bond, was far less effective than dichain-TeTx at blocking exocytosis, which indicates that proteolysis is the rate-limiting step . The toxins were degraded further to low-molecular weight fragments which, together with intact toxins and subunits, were released by the cells . The intracellular half-life of {125I} dichain-TeTx was approximately three days . The number of light-chain molecules required to maintain exocytosis block in a single cell, as calculated by two different methods, was less than 10 . The long duration of tetanus poisoning may result from the persistence of intracellular toxin due to scarcity of free cytosolic proteases . This may also hold for the slow recovery from botulism.

J Physiol Paris, 1995, 89(1), 43 - 50
The metallo-proteinase activity of tetanus and botulism neurotoxins; Rossetto O et al.; Tetanus and botulinum neurotoxins are produced by several Clostridia and cause the paralytic syndromes of tetanus and botulism by blocking neurotransmitter release at central and peripheral synapses, respectively . They consist of two disulfide-linked polypeptides: H (100 kDa) is responsible for neurospecific binding and cell penetration of L (50 kDa), a zinc-endopeptidase specific for three protein subunits of the neuroexocytosis apparatus . Tetanus neurotoxin and botulinum neurotoxin serotypes B, D, F and G cleave at single sites, which differ for each neurotoxin, VAMP/synaptobrevin, a membrane protein of the synaptic vesicles . Botulinum A and E neurotoxins cleave SNAP-25, a protein of the presynaptic membrane, at two different carboxyl-terminal peptide bonds . Serotype C cleaves specifically syntaxin, another protein of the nerve plasmalemma . The target specificity of these metallo-proteinases relies on a double recognition of their substrates based on interactions with the cleavage site and with a non-contiguous segment that contains a structural motif common to VAMP, SNAP-25 and syntaxin.

Ann Emerg Med, 1994 Dec, 24(6), 1184 - 7
Wound botulism; Burningham MD et al.; Wound botulism is a rare infectious and toxicologic complication of trauma and i.v . drug abuse . Only 39 cases have been reported in detail in the English literature . This case report describes a patient with wound botulism who presented to four medical facilities before receiving definitive diagnosis and treatment . Although his history and physical examination were consistent with wound botulism, diagnosis and therapy were delayed because this rare disease was not considered initially in the differential diagnosis . Wound botulism should be considered in trauma patients and i.v . drug abusers who present with cranial nerve palsies and descending paresis.

J Child Neurol, 1994 Oct, 9(4), 362 - 5
Electrodiagnosis of infantile botulism; Gutierrez AR et al.; Analysis of the literature on the electrophysiologic features of infantile botulism was undertaken . Small compound muscle action potential amplitude is a very sensitive feature but lacks specificity . The decremental response to 2- to 3-Hz repetitive nerve stimulation is inconsistent and not a reliable sign . Tetanic and posttetanic facilitation are highly sensitive and highly specific . Absence of posttetanic exhaustion is also highly specific for infant botulism and shared only by hypermagnesemia . We conclude that the findings of low compound muscle action potential amplitude in combination with tetanic facilitation or posttetanic facilitation and absence of posttetanic exhaustion constitute the triad on which the electrodiagnosis of infantile botulism can be supported.

J Wildl Dis, 1994 Oct, 30(4), 514 - 22
Use of sentinel mallards for epizootiologic studies of avian botulism; Rocke TE et al.; Captive-reared mallards (Anas platyrhynchos) were used as sentinels to study the epizootiology of avian botulism at the Sacramento National Wildlife Refuge, Willows, California (USA) from 1986 to 1989 . Sentinel mallards were wing-clipped, and 40 to 50 birds were confined in 1.6-ha enclosures in 11 selected wetlands (pools) . Enclosures were searched intensively three to four times weekly from July through October . Sick and dead wild and sentinel birds were collected, necropsied, and tested for type C botulism toxin . Botulism epizootics occurred in sentinel mallards in 1986, 1987, and 1989, but only a few isolated cases of botulism were detected in 1988 . In most epizootics, botulism also was detected simultaneously in wild birds using the same pool outside the enclosure . Epizootics in sentinels were initiated and perpetuated in the absence of vertebrate carcasses . A sex-specific trend in the probability of intoxication was detected, with males contracting botulism at a higher rate than females . Daily mortality rates of sentinels during botulism epizootics ranged from 0.0006 to 0.0600, with a mean of 0.0190 . These rates would result in the daily loss of 0.6 to 60 birds per thousand at risk . The use of sentinel birds provided an effective means of gathering site-specific epizootiologic data.

Semin Cell Biol, 1994 Aug, 5(4), 221 - 9
Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release; Schiavo G et al.; The clostridial neurotoxins responsible for tetanus and botulism are eight different proteins, composed of two disulfide-linked polypeptide chains . They bind specifically to the presynaptic membrane via the heavy chain, while the light chain enters the cytosol of the neurons, where it displays a zinc-endopeptidase activity directed to proteins of the neuroexocytosis apparatus . Tetanus neurotoxin and botulinum neurotoxin serotypes B, D, F and G cleave specifically and at single different peptide bonds VAMP/synaptobrevin, a component of small synaptic vesicles . In contrast, the other neurotoxins catalyze the hydrolysis of proteins of the presynaptic membrane . Serotypes A and E of botulinum neurotoxin cleave SNAP-25, at different sites located within the carboxyl-terminus, while the specific target of serotype C is syntaxin.

Mol Microbiol, 1994 Jul, 13(1), 1 - 8
Mechanism of action of tetanus and botulinum neurotoxins; Montecucco C et al.; The clostridial neurotoxins responsible for tetanus and botulism are metallo-proteases that enter nerve cells and block neurotransmitter release via zinc-dependent cleavage of protein components of the neuroexocytosis apparatus . Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction and is internalized and transported retroaxonally to the spinal cord . Whilst TeNT causes spastic paralysis by acting on the spinal inhibitory interneurons, the seven serotypes of botulinum neurotoxins (BoNT) induce a flaccid paralysis because they intoxicate the neuromuscular junction . TeNT and BoNT serotypes B, D, F and G specifically cleave VAMP/synaptobrevin, a membrane protein of small synaptic vesicles, at different single peptide bonds . Proteins of the presynaptic membrane are specifically attacked by the other BoNTs: serotypes A and E cleave SNAP-25 at two different sites located within the carboxyl terminus, whereas the specific target of serotype C is syntaxin.

Vet Hum Toxicol, 1994 Jun, 36(3), 233 - 7
Wound botulism; Mechem CC et al.; All published cases of wound botulism were reviewed to describe the epidemiology, clinical manifestations, diagnosis, and treatment of this rare infection . The MEDLINE data base of English-language literature was searched from 1966 to 1992, using the keywords "wound botulism" . Cases published during this period were identified, and the bibliographies of these articles were used to identify cases published before MEDLINE's search limit of 1966 . Because of the limited number of published cases, all were reviewed . Data related to epidemiology, clinical manifestations, diagnosis and treatment were collected on each case . When possible, cross-references from case series or reviews were used to corroborate and supplement data for a given case . There were 40 cases identified as wound botulism . The case fatality rate was 10% . The 36 survivors had significant morbidity requiring prolonged medical care . Wound botulism is a rare life-threatening complication of trauma and i.v . drug abuse . The diagnosis should be considered in any patient with either of these risk factors who develop paresis of cranial nerves and a descending pattern of weakness . Treatment, including administration of antitoxin, should be initiated prior to definitive diagnosis by microbiologic laboratory tests.

Ann N Y Acad Sci, 1994 Mar 9, 710, 65 - 75
Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus; Schiavo G et al.; Tetanus and botulinum neurotoxins bind to nerve cells, penetrate the cytosol, and block neurotransmitter release . Comparison of their amino-acid sequences shows the presence of the highly conserved His-Glu-x-x-His zinc-binding motif of zinc-endopeptidases (HExxH) . Atomic absorption measurements of clostridial neurotoxins show the presence of one atom of zinc/toxin molecule bound to the light chain . The toxin-bound zinc ion is essential for the neurotoxins inhibition of neurotransmitter release in Aplysia neurons injected with the toxins . Phosphoramidon, a very specific inhibitor of zinc-endopeptidases, blocks the intracellular activity of the clostridial neurotoxins . Highly purified preparations of the light chain of tetanus and botulinum B and F neurotoxins cleaved specifically VAMP/synaptobrevin, an integral membrane protein of small synaptic vesicles, both in vivo and in vitro . From these studies, it can be concluded that the clostridial neurotoxins responsible for tetanus and botulism block neuroexocytosis via the proteolytic cleavage of specific components of the neuroexocytotic machinery.

Heart Lung, 1994 Mar-Apr, 23(2), 164 - 8
Infant botulism; Mygrant BI et al.; Constipation in children is rarely thought of as a serious health condition . It is, however, one of the leading symptoms of the pathologic sequence in infantile botulism . The pathogenesis, common clinical manifestations, and common grounds in treatment and prognosis in infant botulism are summarized . The nursing role is presented, focusing on airway management, nutritional needs, environmental support, and parental role in an intensive care unit . An exemplar case study is presented.

Kansenshogaku Zasshi, 1994 Feb, 68(2), 259 - 62
{A case report of infant botulism without a history of honey ingestion}; Morikawa Y et al.; A 66-day-old female with infant botulism is reported . She was admitted to our hospital with respiratory failure . Laboratory examinations detected botulinal toxin type A in her feces . This was the first case with no history of honey ingestion among the 13 cases of infant botulism reported in Japan . It is possible that other cases, in which honey had not been consumed, remain undiagnosed . Further studies may be needed to clarify the factors necessary to cause infant botulism.

J Vet Diagn Invest, 1994 Jan, 6(1), 93 - 5
Type C botulism in turkeys: determination of the median toxic dose; Jeffrey JS et al.; The median toxic dose (TD50) of type C botulinum in turkeys was determined using an up-and-down method for toxicologic testing . Birds were dosed intravenously with 10, 20, or 40 mouse lethal dose per kilogram body weight (MLD/kg) of type C botulism toxin and observed for 5 days . Administration of toxin resulted in acute death, posterior paresis, or no effect, depending upon the dose . The TD50 causing posterior paresis was calculated as 25.75 MLD/kg (confidence interval = 17.08-38.82 MLD/kg) . Posterior paresis was identified as the principal sign associated with sublethal botulism toxicosis in turkeys . The resultant posterior paresis was similar to the clinical syndrome observed in an unsolved field investigation.

Eye, 1994, 8 ( Pt 6), 646 - 8
Neuro-ophthalmic findings in botulism type B; Simcock PR et al.; In June 1989, the largest recorded outbreak of food-borne botulism occurred in the United Kingdom . Twenty-seven patients were affected during the outbreak with type B botulism . A case note review of 14 patients admitted with this condition was performed and the neuro-ophthalmic findings are presented . Patients with severe disease presented with a combination of ocular and bulbar symptoms; in mild cases dysphagia was noted first and visual disturbance followed within 24 hours . Clustering of cases and bilaterality of cranial nerve signs aided in the diagnosis . Accommodative paresis and sixth cranial nerve palsy were frequent early signs . When there was respiratory paralysis and ventilatory failure, it occurred within 12 hours of the onset of a third cranial nerve palsy.

J Neurochem, 1993 Dec, 61(6), 2338 - 41
Botulinum A like type B and tetanus toxins fulfils criteria for being a zinc-dependent protease; de Paiva A et al.; Although botulinum neurotoxin (BoNT) types A and B and tetanus toxin (TeTx) are specific inhibitors of transmitter release whose light chains contain a zinc-binding motif characteristic of metalloendoproteases, only the latter two proteolyse synaptobrevin . Chelation of zinc or its readdition at high concentration hindered blockade of neuromuscular transmission by BoNT/A and B, indicating that type A also acts via a zinc-dependent mechanism . Such treatments prevented proteolysis of synaptobrevin II in rat brain synaptic vesicles by BoNT/B and TeTx but only the activity of the latter was antagonised appreciably by ASQFETS, a peptide spanning their cleavage site . The toxin's neuroparalytic activities were attenuated by phosphoramidon or captopril, inhibitors of certain zinc requiring proteases . However, these agents were ineffective in reducing the toxins' degradation of synaptobrevin except that a high concentration of captopril partially blocked the activity of TeTx but not BoNT/B, as also found for these drugs when tested on synaptosomal noradrenaline release . These various criteria establish that a zinc-dependent protease activity underlies the neurotoxicity of BoNT/A, a finding confirmed at motor nerve endings for type B and TeTx . Moreover, the low potencies of captopril and phosphoramidon in counteracting the toxins' effects necessitate the design of improved inhibitors for possible use in the clinical treatment of tetanus or botulism.

Toxicon, 1993 Dec, 31(12), 1581 - 94
Toxicology of a bovine paraplegic syndrome; Sevcik C et al.; A clinical entity named 'bovine paraplegic syndrome' ('sindrome paraplejico de los bovinos') has spread alarmingly in the cattle-growing areas of the central and eastern plains of Venezuela . It is estimated that four million cattle are bred in the area where the disease occurs . The mortality ranges from 5 to 25% of the animals at risk, mostly pregnant or lactating cows . The principal characteristic of the bovine paraplegic syndrome is ventral or sternal decubitus, in animals that make vain efforts to stand when stimulated . The diagnosis is established when all other possible causes (e.g . paralytic rabies, botulism and blood parasites such as Anaplasma marginal, Babesia bovis, B . bigemina, and Trypanosoma vivax) have been ruled out clinically and by laboratory tests . Death always occurs, usually after a few days, and there is no known treatment . In this work, we describe results that show the presence of a toxin in the cattle suffering from, or liable to suffer from the syndrome . The toxin is produced by ruminal bacteria . In squid giant axons under voltage clamp conditions, the toxin blocks the sodium current . We detected the toxin analytically by absorbance measurements at 340 nm after reacting with picrylsulfonic acid . We obtained a good separation of the toxin with isocratic high pressure liquid chromatography, using 40% methanol in water on phenylborasil columns.

FEBS Lett, 1993 Nov 29, 335(1), 99 - 103
Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds; Schiavo G et al.; SNAP-25, a membrane-associated protein of the nerve terminal, is specifically cleaved by botulinum neurotoxins serotypes A and E, which cause human and animal botulism by blocking neurotransmitter release at the neuromuscular junction . Here we show that these two metallo-endopeptidase toxins cleave SNAP-25 at two distinct carboxyl-terminal sites . Serotype A catalyses the hydrolysis of the Gln197-Arg198 peptide bond, while serotype E cleaves the Arg180-Ile181 peptide lineage . These results indicate that the carboxyl-terminal region of SNAP-25 plays a crucial role in the multi-protein complex that mediates vesicle docking and fusion at the nerve terminal.

Trends Biochem Sci, 1993 Sep, 18(9), 324 - 7
Tetanus and botulism neurotoxins: a new group of zinc proteases; Montecucco C et al.; The active forms of tetanus and botulinum neurotoxins, released from the precursor molecule by specific proteolysis and reduction, block the release of neurotransmitters via a Zn(2+)-dependent protease activity . VAMP/synaptobrevin, an integral membrane protein of the synaptic vesicles, is cleaved at a single site by tetanus and botulinum B, D and F neurotoxins . The unique sequence, mechanism of activation and site of activity of clostridial neurotoxins mark them out as an independent group of Zn(2+)-endopeptidases.

Neurol Clin, 1993 Aug, 11(3), 591 - 603
Infections other than AIDS; Richter RW; Neurologic manifestations of severe infectious complications of drug abuse and chronic alcoholism are reviewed in this article . Portals of entry from cutaneous postinjection infections and multiple vascular injection sites may lead to pyomyositis, tetanus, infective endocarditis, meningitis, brain abscesses, and vertebral osteomyelitis . Chronic intranasal abuse of cocaine may be followed by frontal osteomyelitis, botulism, brain abscess, and visual loss . Problems of hepatitis, malaria, and syphilis in drug abusers are discussed also.

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