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PubMed1976

Botulinum antitoxins and antibacterial IgM and IgG antibodies in sera of persons immunized with botulinum polytoxoid combined with cholera vaccine. I. Response to botulinum toxoid.

Two groups of subjects were immunized with combined vaccine containing aluminum hydroxide-adsorbed botulinum toxoids, types A, B, and E, and 4 mld of formaldehyde-inactivated V. cholerae Inaba and Ogawa organisms. The first group included laboratory workers who were previously immunized against cholera and had professional contact with botulinum toxins and viable V. cholerae organisms. The second group included young men who were never vaccinated against botulism or cholera. The three-dose immunization schedule with combined vaccine resulted in clear-cut antitoxin response; after the third dose, the A, B, and E antitoxin level ranged from 0-2 to 10 IU/ml. Immunity against botulinum toxins lasted at least one year. Distribution of the antitoxins among IgM and IgG globulin classes resembled that in the case of response to other toxoids; 21 days after the third immunization antitoxin activity was found in IgG globulins.

Adult↗
PubMedDate not supplied

[Change in biogenic amine metabolism in botulin poisoning].

An increase in content of serotonin, histamine, the elevated histaminase activity in tissues and an increase in excretion of 5-hydroxyindolylacetic acid with urine were observed in experimental botulism, accompanied by paresis of sceletal muscles. As the paralysis progressed content of histamine gradually decreased in nervous tissue but it remained to be increased in the internal tissues although the histaminase activity was high. At the same time, content of serotonin was maintained at an increased level in the nervous tissue, but it was normalized in several internal organs. Excretion of 5-hydroxyindolylacetic acid with urine was decreased. LD50 of botulinic toxin was titrated in mice, which were simultaneously administered with preparations increasing or decreasing the synthesis and the activity of biogenic amines. The data obtained suggest that the impairments in metabolism of biogenic amines could be important for development of the intoxication.

Amine Oxidase (Copper-Containing)↗
PubMed1993

Botulinum toxin. From poison to medicine.

Although thousands of people in the world each year continue to be poisoned with botulinum toxin-food-borne, infantile, or wound botulism-the neurotoxin is now sufficiently understood to allow it to be used as a medicinal agent to paralyze specific muscles, giving temporary symptomatic relief from a variety of dystonic neurologic disorders. I review some of the epidemiologic, clinical, and pathophysiologic aspects of botulinum toxin and how the neurotoxin may act as a poison or a medicine.

Botulinum Toxins↗
PubMed1993

Paralytic syndrome attributed to lasalocid residues in a commercial ration fed to dogs.

Lasalocid, accidently introduced into a commercial dog food, was found to be the cause of neuromuscular toxicosis in 10 dogs. Toxicosis was confirmed in 4 principal dogs. The history, clinical signs, and pattern of onset of lasalocid-induced toxicosis in the 14 dogs were similar to those reported for botulism. The signs, which were related to a generalized lower motor neuron deficit, were generally different from ionophore-induced toxicosis reported in other species. Supportive therapy and close monitoring were sufficient to bring about a gradual improvement in all of the dogs, despite the severity of clinical signs.

Animal Feed↗
PubMedDate not supplied

[Role of hypoxia factor in changes of ionic composition of blood and muscle tissue in experimental botulinum poisoning].

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.

Animals↗
PubMed1997

Ecosystem health as a clinical rotation for senior students in Canadian veterinary schools.

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.

Agriculture↗
PubMedDate not supplied

[Detection of Clostridium botulinum spores in honey].

A total of 177 honey samples were examined for Clostridium botulinum, 68 of which were from commercial origin, 8 from small rural producers for family consumption, and the remaining 6 from fractionizing centers in Mendoza and San Luis provinces in Argentina. C. botulinum type A was detected in two samples of rural producer origin (1.1%) by the centrifugation-dilution method. The strain was recovered from one of the samples, obtaining a spore count of 55/g of honey. Even though the positive percentage was lower than that found in other countries, honey consumption by children under one year old should be avoided in order to prevent infant botulism.

Argentina↗
PubMed1997

Effect of calcium addition and acidification on the quality characteristics of canned okra (Hibiscus esculentus L).

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.

Acetic Acid↗
PubMed1990

Acute autonomic neuropathy. Two cases and a clinical review.

Acute autonomic neuropathy is an uncommon syndrome, usually affecting healthy young people. Presentation is often dramatic and initial misdiagnosis is common. We describe two young women with acute autonomic neuropathy who presented with gastrointestinal involvement heralding widespread dysautonomia and review 26 additional cases of acute autonomic neuropathy from the English language literature. Acute autonomic neuropathy can be primarily cholinergic without orthostatic hypotension (26%) or pandysautonomic (74%) involving sympathetic adrenergic functions. Onset has been temporally related to viral syndromes in 20% of cases, with autonomic deficits usually evolving over 1 to 3 weeks. Gastroparesis (69%) and syncope (12%) are frequent presenting complaints. Spinal fluid protein levels are often (75%) elevated in pandysautonomic subtypes. Prolonged and incomplete recovery is the rule (60%), with persistent gastroparesis and orthostatic hypotension. Other specific diseases that occasionally mimic acute autonomic neuropathy include botulism, porphyria, amyloidosis, and paracarcinomatous neuropathies. Acute autonomic neuropathy shares several clinical features with acute idiopathic polyneuropathy (Guillain-Barré syndrome), suggesting an immune-mediated pathogenesis.

Acute Disease↗
PubMed1982

The diagnostic value of electromyography in infantile hypotonia.

There is controversy over the usefulness of electromyography (EMG) in the examination of hypotonic infants with suspected neuromuscular disease. We compared the initial EMG findings of 51 such children under 1 year of age with their final clinical diagnoses determined by independent means. The EMG predicted the final diagnosis in 82% of infants less than 4 months of age and 85% of those over 4 months of age. Botulism was correctly identified by EMG in nine of 11 cases. The EMG diagnosis was identical to that obtained by muscle biopsy in 64% of cases in which biopsy was done, and diagnosis obtained by the two methods were inconsistent in only 14%. Electromyography is a sensitive and noninvasive diagnostic tool for the diagnosis of neuromuscular disease in infantile hypotonia.

Electromyography↗
PubMed1983

Clostridium difficile cytotoxin in a pediatric population.

Assays for cytotoxin of Clostridium difficile were performed on stool samples submitted to the laboratory for routine microbiologic study. Cytotoxin was recovered from 8.6% of 208 pediatric patients studied. Cytotoxin was identified significantly more often in younger patients (median age, 11 months) and in those with hospital-associated illness (17%) and antibiotic-associated illness (18%). Hospitalization and antibiotic use were significant independent risk factors. Clinical diagnoses in patients with C difficile cytotoxin included classic pseudomembranous colitis, acute self-resolving diarrheal syndrome, chronic diarrhea with failure to thrive, infant botulism, and asymptomatic carriage.

Adolescent↗
PubMed1996

Necrotizing soft-tissue infections.

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.

Adult↗
PubMed1996

Productive and non-productive binding of botulinum neurotoxin A to motor nerve endings are distinguished by its heavy chain.

Botulinum neurotoxin type A, a di-chain protein produced by Clostridium botulinum and responsible for botulism, blocks acetylcholine release from peripheral nerves by binding to the terminals, undergoing internalization and proteolyzing a protein essential for exocytosis. As butolinum neurotoxin is being used clinically for the treatment of dystonias and certain spasticities, deciphering the details of its specific targeting to cholinergic nerve endings has assumed great importance. Thus, interaction of butolinum neurotoxin type A with murine motor nerve terminals-a prime target in vivo-was investigated. Autoradiographic analysis revealed saturable, high-affinity interaction of radioiodinated toxin (0.4 nM) with two ecto-acceptor types, distinguished by an excess of the toxin's heavy chain which prevented only a fraction of this binding. Botulinum neurotoxin was also biotinylated through its free sulfhydryl groups, known not to be essential for neurotoxicity. Similar binding of this active derivative was, likewise, partially blocked by heavy chain, confirming the above results. This binding that is resistant to heavy chain equates to botulinum neurotoxin interacting with productive ecto-acceptors, leading to delivery to its cytosolic site of action, because heavy chain proved unable to antagonize toxin-induced neuromuscular paralysis. In contrast, it is deduced that botulinum neurotoxin bound to heavy chain-susceptible sites has a different fate, presumably due to trafficking via another route, and thus would be inefficient in causing neuroparalysis.

Animals↗
PubMed1997

Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome.

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.

Adolescent↗
PubMed1999

Comparison of in vivo and in vitro mouse bioassays for botulinum toxin antagonists.

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.

Animals↗
PubMed2000

Acute care pediatric electromyography.

The recognition of uncommon pediatric motor unit disorders or unusual clinical presentations of common illnesses, such as Guillain-Barré 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.

Acute Disease↗
PubMed1991

From conjecture and refutation to the documentation of occupational diseases in Taiwan.

The documentation of occupational diseases in a developing country like Taiwan is a challenge to an occupational physician. For lack of a system including material safety data sheet (MSDS), workers are usually not aware of what chemicals they are exposed to. Since many occupational diseases have long latencies and do not show any specific symptoms and signs, recognition and identification of the occupational origin are often very difficult. Using databases which provide a relatively complete list of industrial chemicals and a set of specific signs and/or symptoms, combined with the epidemiologic approach of conjectures and refutations--i.e., considering and ruling out all possible alternative explanations--we have documented eight kinds of occupational diseases and an outbreak of botulism. We recommend that a similar approach be applied to any other country with a similar situation, and that a system involving an identification sheet (e.g., MSDS) for each chemical be advocated and implemented in such countries as one means to enable prompt recognition and prevention of occupational diseases.

Acute Disease↗
PubMed2005

Partial protection against Botulinum B neurotoxin-induced blocking of exocytosis by a potent inhibitor of its metallopeptidase activity.

Clostridium botulinum neurotoxins (BoNTs) cause botulism, which is characterized by a flaccid paralysis, through inhibition of acetylcholine release by peripheral cholinergic nerve terminals. This is due to the zinc metallopeptidase activity of the neurotoxin, cleaving one component (synaptobrevin for BoNT/B) of the exocytosis machinery. Yet, there are no specific agents able to control the peptidase-related effects of BoNT/B. We recently developed the first compounds to inhibit this enzymatic activity in the nanomolar range. Here we report that two of our best inhibitors prevent the BoNT/B-induced cleavage of native synaptobrevin on synaptic vesicles, and partially inhibit the suppression of [3H]noradrenaline release from synaptosomes that is caused by BoNT/B. These results were obtained at micromolar concentrations, consistent with the measured inhibitory potency of these inhibitors on the native toxin. These compounds provide a new way to possibly prevent and/or to control the neurotoxin effects of botulinum.

Animals↗