Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-seven patients entered a prospective randomized trial to assess the effect of early botulinum neurotoxin A treatment to the ipsilateral antagonist medial rectus on the ultimate recovery rate of acute unilateral sixth nerve palsy. Twenty-two patients received injections and 25 acted as controls. The overall etiologies were microvascular (72.3%), unknown (17%), multiple sclerosis (6%), and one case each of central nervous system (CNS) sarcoidosis and basilar artery ectasia. Eighty-three percent of the patients entered the trial within 2 weeks of the onset of symptoms and 95.7% within 3 weeks. The controls had a final recovery rate of 20/25 (80%), and the injected group had a final recovery rate of 19/22 (86%). No serious side effects were encountered. We conclude that there is no evidence for a prophylactic effect of botulinum toxin in the group that we have studied.
J Pediatr Ophthalmol Strabismus
PMID:Results of a prospective randomized trial of botulinum toxin therapy in acute unilateral sixth nerve palsy. 763 91

Esotropia from chronic sixth nerve palsy or paresis usually requires surgery. Chemodenervation of the antagonist medial rectus muscle, while popular for the treatment of acute sixth nerve palsies and pareses, has not been used extensively for chronic cases. In this study, 22 patients with sixth nerve palsies or partially recovered palsies of greater than 5 months duration were treated with chemodenervation. The etiologies of the sixth nerve palsies were trauma (n = 7), tumor (n = 4), infection/inflammation (n = 3), nerve compression from aneurysm or increased intracranial pressure (n = 4), congenital (n = 1), ischemia (n = 2), and idiopathic (n = 1). The mean preinjection deviation was 41 prism diopters. A total of 38 injections were administered (mean, 1.7 per patient). Each patient received an injection of 2.5 to 7.5 units (mean, 4.1) of botulinum neurotoxin A to the ipsilateral medial rectus muscle. Treatment success was assessed 6 months after the last injection. A course of chemodenervation significantly improved the alignment of 9 of the 22 patients (41%). The mean postinjection deviation was 8 delta. Seven patients (32%) had single binocular vision in primary position restored. These patients had a mean horizontal binocular field of 70 degrees (range, 40 degrees to 100 degrees). Thirteen patients (59%) had only modest improvement and required surgery. The data suggest that injection of botulinum neurotoxin A is a useful treatment for some patients with chronic sixth nerve weakness. A course of chemodenervation therapy compares less favorably with transposition surgery with concomitant neurotoxin injection for the treatment of these difficult problems.
J Pediatr Ophthalmol Strabismus
PMID:The efficacy of botulinum neurotoxin A for the treatment of complete and partially recovered chronic sixth nerve palsy. 771 9

As the diversity of clinical applications for the botulinum neurotoxin continues to grow, exciting developments are occurring in its use around the eye, where indeed its benefits were first recognized. These include use to treat strabismus, eyelid disorders and a number of other ocular conditions.
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PMID:The use of botulinum toxin in ophthalmology. 1153 May 85

More than fifty years following the discovery that botulinum neurotoxins inhibit neuromuscular transmission, these powerful poisons have become drugs with many indications. First used to treat strabismus, local injections of botulinum neurotoxin are now considered a safe and efficacious treatment for neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum neurotoxin is a treatment for diseases of the gastrointestinal tract. Botulinum neurotoxin is not only potent in blocking skeletal neuromuscular transmission, but also block cholinergic nerve endings in the autonomic nervous system. The capability to inhibit contraction of smooth muscles of the gastrointestinal tract was first suggested based on in vitro observations and later demonstrated in vivo; it has also been shown that botulinum neurotoxin does not block non adrenergic non cholinergic responses mediated by nitric oxide. This has further promoted the interest to use botulinum neurotoxin as a treatment for overactive smooth muscles and sphincters, such as the lower esophageal sphincter to treat esophageal achalasia, or the internal anal sphincter to treat anal fissure. Information on the anatomical and functional organization of innervation of the gastrointestinal tract is a prerequisite to understand many features of botulinum neurotoxin action on the gut and the effects of injections placed into specific sphincters. This review presents current data on the use of botulinum neurotoxin to treat diseases of the gastrointestinal tract and summarizes recent knowledge on the pathogenesis of disorders of the gut due to a dysfunction of the enteric nervous system.
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PMID:Gastrointestinal smooth muscles and sphincters spasms: treatment with botulinum neurotoxin. 1267 92

Clostridium botulinum, a Gram-positive, anaerobic spore-forming bacteria, is distinguished by its significant clinical applications as well as its potential to be used as bioterror agent. Growing cells secrete botulinum neurotoxin (BoNT), the most poisonous of all known poisons. While BoNT is the causative agent of deadly neuroparalytic botulism, it also serves as a remarkably effective treatment for involuntary muscle disorders such as blepharospasm, strabismus, hemifacial spasm, certain types of spasticity in children, and other ailments. BoNT is also used in cosmetology for the treatment of glabellar lines, and is well-known as the active component of the anti-aging medications Botox and Dysport. In addition, recent reports show that botulinum neurotoxin can be used as a tool for pharmaceutical drug delivery. However, BoNT remains the deadliest of all toxins, and is viewed by biodefense researchers as a possible agent of bioterrorism (BT). Among seven serotypes, C. botulinum type A is responsible for the highest mortality rate in botulism, and thus has the greatest potential to act as biological weapon. Genome sequencing of C. botulinum type A Hall strain (ATCC 3502) is now complete, and has shown the genome size to be 3.89 Mb with a G+C content of approximately 28.2%. The bacterium harbors a 16.3 kb plasmid with a 26.8% G+C content--slightly lower than that of the chromosome. Most of the virulence factors in C. botulinum are chromosomally encoded; bioinformatic analysis of the genome sequence has shown that the plasmid does not harbor toxin genes or genes for related virulence factors. Interestingly, the plasmid does harbor genes essential to replication, including dnaE, which encodes the alpha subunit of DNA polymerase III which has close similarity with its counterpart in C. perfringens strain 13. The plasmid also contains similar genes to those that encode the ABC-type multidrug transport ATPase, and permease. The presence of ABC-type multidrug transport ATPase, and permease suggests putative involvement of efflux pumps in bacteriocin production, modification, and export in C. botulinum. The C. botulinum plasmid additionally harbors genes for LambdaBa04 prophage and site-specific recombinase that are similar to those found in the Ames strain of Bacillus anthracis; these genes and their products may play a role in genomic rearrangement. Completion of genome sequencing for C. botulinum will provide an opportunity to design genomic and proteomic-based systems for detecting different serotypes of C. botulinum strains in the environment. The completed sequence may also facilitate identification of potential virulence factors and drug targets, as well as help characterize neurotoxin-complexing proteins, their polycistronic expression, and phylogenetic relationships between different serotypes.
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PMID:Clostridium botulinum: a bug with beauty and weapon. 1583 1

Since its development for the use of blepharospasm and strabismus more than 2.5 decades ago, botulinum neurotoxin (BoNT) has become a versatile drug in various fields of medicine. It is the standard of care in different disorders such as cervical dystonia, hemifacial spasm, focal spasticity, hyperhidrosis, ophthalmological and otolaryngeal disorders. It has also found widespread use in cosmetic applications. Many other indications are currently under investigation, including gastroenterologic and urologic indications, analgesic management and migraine. This paper is an extensive review of the spectrum of BoNT clinical applications.
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PMID:Botulinum toxin: clinical use. 1687 Apr 87

Dr Alan Scott's seminal investigations in the 1970s into the use of botulinum neurotoxin for strabismus represent the pivotal moment in its clinical research. In the decades that followed, botulinum neurotoxin was increasingly studied for therapeutic and aesthetic use. Currently, several botulinum neurotoxin products are available worldwide, with only a few investigated for cosmetic applications, and only one currently approved for facial aesthetic use in the United States. Comparisons among the agents are challenging due to a limited number of controlled studies. The few comparative studies published have contributed to a better understanding of the relative efficacy and safety of these products, but factors such as a broad clinical research experience, approved indications, and pharmacologic characteristics of each agent also influence choice of therapy. Issues such as botulinum neurotoxin resistance and selection of injection sites have also emerged as considerations for treatment selection. This article provides an overview of currently available botulinum neurotoxin products, including a review of key comparative aesthetic data and a discussion of issues related to botulinum resistance and injection site selection from leading experts in the fields of dermatology and plastic surgery.
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PMID:Overview of botulinum neurotoxins. 1788 81

Since its introduction for the treatment of strabismus, botulinum toxin (BoNT) has been increasingly used in the treatment of several disorders with excessive or inappropriate muscle contractions. The therapeutic effects of BoNT occur through the temporary chemodenervation caused by the injection into the local target muscle or skin. Modulation of muscle relaxation may be achieved by varying the dose of BoNT solution injected; most adverse effects are transient. Indeed, botulinum neurotoxin has been used to selectively weaken the internal anal sphincter as a treatment for chronic anal fissure in several randomized, controlled trials and open-label studies. The use of botulinum neurotoxin seems to be an effective and safe approach for the treatment of chronic anal fissure, particularly in patients at high risk for incontinence.
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PMID:Botulinum toxin A for the treatment of chronic anal fissure. 1907 12

Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K(224)D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K(224)D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.
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PMID:Engineering botulinum neurotoxin to extend therapeutic intervention. 1948 72

Botulism is a severe neuroparalytic disease caused by toxins produced by several Clostridium species. Botulinum toxin has been of concern to the US military and its allies as a biowarfare weapon since World War II and, in more recent times, by the Centers for Disease Control and Prevention (CDC) as a potential bioterrorist threat to the public. The most effective means of defending against the toxin is by inducing a protective immune response through vaccination. Vaccination with an appropriate antigen will produce neutralizing antibodies that will bind to and clear toxin from the circulation before it can enter nerve cells and block neurotransmission. Immunity from botulism, however, has the disadvantage of precluding an individual from realizing the potential benefits of therapeutic botulinum toxin, if such a need were to arise. Botulinum toxin has been used in the treatment of numerous neuromuscular, autonomic, and sensory disorders since it was first approved for the management of strabismus and blepharospasm by the Food and Drug Administration (FDA) in 1989. Notwithstanding the value of the neurotoxin as a therapeutic drug, vaccines have been and will continue to be an important line of defense for those who work with the toxin (at-risk workers) and a select population of the military, law enforcement, and first responders. The first vaccine used to protect against botulinum neurotoxin was a chemically detoxified extract from Clostridium botulinum. A Pentavalent botulinum toxoid (PBT) vaccine in service today is administered under an Investigational New Drug (IND) application held by the CDC. Recombinant subunit vaccines are in development and a bivalent H(c) vaccine (rBV A/B (Pichia pastoris)) is presently being evaluated in a phase II clinical trial. This review focuses on botulism and the development of vaccines for its prevention.
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PMID:Botulism and vaccines for its prevention. 1983 83


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