Otolaryngol Clin North Am, 1991 Oct, 24(5), 1227 - 37 Treatment options in spasmodic dysphonia; Miller RH et al.; Options in the treatment of spasmodic dysphonia include surgical interruption of the recurrent laryngeal nerve, anterior laryngoplasty, voice therapy, and Botulinum toxin injection . Although none of these treatments is ideal, Botulinum toxin injection appears to have the greatest potential to benefit the greatest number of patients. Jpn Circ J, 1991 Oct, 55(10), 1036 - 43 Small GTP-binding proteins in bovine aortic smooth muscle; Kawahara Y et al.; In bovine aortic smooth muscle, GTP-binding activity was equally distributed in the membrane and cytosol fractions . The most abundant GTP-binding proteins (G proteins) in each fraction were purified to near homogeneity and characterized . The most abundant G protein in the membrane fraction had a Mr value of about 22,000 (m22K G) as estimated on sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE) . m22K G and the human platelet smg p21, a ras p21 like G protein having the same effector domain as ras p21s, were eluted at the same retention time on C4 reversed-phase high performance liquid chromatography (HPLC) . Moreover, m22K G was specifically recognized by an anti-smg p21 polyclonal antibody . m22K G was phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein . The most abundant G protein in the cytosol fraction had a Mr value of about 21,000 (c21K G) as estimated on SDS-PAGE . c21K G was ADP-ribosylated by botulinum ADP-ribosyltransferase and about 0.4 mol of ADP-ribose was maximally incorporated into 1 mol of c21K G . c21K G and the bovine brain rhoA p21, another ras p21 like G protein, were eluted at the same retention time on C4 reversed-phase HPLC and migrated at the same position on two-dimensional gel electrophoresis . These results indicate that the major G proteins in the membrane and cytosol fractions of bovine aortic smooth muscle are smg p21 and rhoA p21, respectively . Possible roles of these G proteins in vascular smooth muscle are discussed. Naunyn Schmiedebergs Arch Pharmacol, 1991 Oct, 344(4), 387 - 95 Distinct targets for tetanus and botulinum A neurotoxins within the signal transducing pathway in chromaffin cells; Marxen P et al.; Tetanus and botulinum A neurotoxins inhibited exocytosis evoked by various secretagogues in intact and permeabilized chromaffin cells . The block of exocytosis in intact chromaffin cells due to botulinum A neurotoxin could partially be overcome by enhancing nicotine- and veratridine-induced stimulation, whereas the block due to tetanus toxin persisted under the same conditions . The receptor-mediated restoration of 3H-noradrenaline release was specific for nicotinic stimulation, because exocytosis did not occur during muscarinic stimulation . Depolarization of intact chromaffin cells with increasing concentration of K+ failed to restore exocytosis that had been blocked by either toxin . When chromaffin cells, treated with tetanus or botulinum A neurotoxins, were exposed to the Ca2(+)-ionophore A 23187 or permeabilized by staphylococcal alpha-toxin, Ca2(+)-stimulated exocytosis was also inhibited . The inhibition was unaffected by increasing concentrations of free Ca2+ . Activation of proteinkinase C and of G-proteins by phorbolester and GMPPNHP, respectively, increased Ca2(+)-induced exocytosis in control cells as well as in cells treated with tetanus and botulinum A neurotoxins . The block, however, could not be relieved by these manipulations, and it could not be relieved by activating the cGMP or cAMP pathways with analoga of cyclic nucleotides, phosphodiesterases inhibitors, and forskolin either . It is concluded that nicotine and veratridine trigger a mechanism within the sequence of events leading to exocytosis that is located beyond the increase in intracellular Ca2(+)-concentration . This pathway may not be affected by botulinum A neurotoxin . The target of tetanus toxin is probably located even closer to the fusion process, i.e . beyond the step upon which botulinum A neurotoxin acts. Biochem J, 1991 Oct 1, 279 ( Pt 1), 43 - 8 Redistribution of 23 kDa tubulovesicle-associated GTP-binding proteins during parietal cell stimulation; Basson MD et al.; Small GTP-binding proteins are important regulators of intracellular traffic . The presence of several small GTP-binding proteins was documented in subfractions of rabbit parietal cells . Upon maximal stimulation of the cells with a combination of histamine and forskolin, one 23 kDa GTP-binding band was observed to decrease in a 50,000 g membrane fraction while increasing in 4000 g membranes . The 23 kDa band resolved into one major and two minor species on two-dimensional gels . GTP-binding species of 23 kDa, 24 kDa and 25 kDa were present in purified preparations of tubulovesicles . The three isoelectric species of the 23 kDa proteins observed in parietal cell 50,000 g microsomes were enriched in tubulovesicle preparations . None of the tubulovesicle-associated GTP-binding proteins were substrates for ADP-ribosylation by a preparation of botulinum D toxin . These results indicate that tubulovesicles contain discrete small GTP-binding proteins which redistribute during parietal cell stimulation. Am J Physiol, 1991 Oct, 261(4 Suppl), 118 - 22 Two types of G proteins involved in regulation of phosphoinositide turnover in pulmonary endothelial cells; Tkachuk VA et al.; The involvement of G proteins in hormonal regulation of phospholipase C in bovine pulmonary arterial endothelial cells and human umbilical vein endothelial cells has been investigated . Histamine and bradykinin stimulated phosphoinositol (PI) turnover in a dose-dependent manner, and phorbol-myristate-acetate inhibited hormone-dependent activation of PI turnover, indicating a feedback control of this process . Activation of PI turnover by histamine and bradykinin is guanine nucleotide-dependent . Stimulation of the endothelial cell G proteins by guanosine 5'-O-(3-thiotriphosphate) leads to the potentiation of hormone-induced activation of PI turnover, whereas guanosine 5'-O-(2-thiodiphosphate), which inactivates G proteins, blocks the hormone-dependent PI turnover . Pertussis toxin blocked the histamine-dependent stimulation but did not affect the bradykinin-dependent stimulation of phospholipase C . By contrast, botulinum toxin (C2 + C3 components) blocked the bradykinin-dependent stimulation of phospholipase C but did not affect the histamine-dependent stimulation of this enzyme . These data suggest that at least two different G proteins are involved in hormone-dependent stimulation of phospholipase C in endothelial cells. Mol Pharmacol, 1991 Oct, 40(4), 563 - 71 Inhibition of cytoskeletal rearrangement by botulinum C2 toxin amplifies ligand-evoked lipid mediator generation in human neutrophils; Grimminger F et al.; Botulinum C2 toxin, a binary toxin that ADP-ribosylates nonmuscle G-actin, was used as a selective tool to evaluate the role of actin-dependent cytoskeletal rearrangement in ligand-evoked lipid mediator generation . Human neutrophils (PMN) were preincubated with varying concentrations of the toxin for 30 min . Lipoxygenase products of arachidonic acid were measured by chromatographic techniques in the presence of exogenous arachidonic acid to probe PMN 5-lipoxygenase activity . Formation of platelet-activating factor (PAF) was assayed by the bioincorporation of {3H}acetate . Stimulation was performed with the soluble chemotactic ligands formyl-methionyl-leucyl-phenylalanine (FMLP) and PAF, as well as opsonized zymosan . PMN pretreatment with C2 toxin in the range between 200/400 and 800/1600 ng/ml C2I/II caused a dose-dependent suppression of the basal F-actin content and of stimulus-induced actin assembly . Phosphoinositide hydrolysis (measured as liberated inositol phosphates) and PAF generation in response to FMLP and exogenous PAF were markedly increased at these toxin doses . Minor C2 toxin concentrations (range, approximately 25/50 to 200/400 ng/ml C2I/II) were sufficient to amplify stimulus-induced formation of leukotriene B4 and its omega-oxidation products, nonenzymatic hydrolysis products of leukotriene A4, and 5-hydroxyeicosatetraenoic acid (5-HETE) . With increasing toxin doses, leukotriene generation declined and 5-HETE became the predominant metabolite . In contrast to the soluble ligands, the zymosan-effected generation of PAF and leukotrienes was dose-dependently inhibited by C2 toxin concentrations of greater than 200/400 ng/ml, paralleled by a loss of motile and phagocytotic functions in these cells . We conclude that selective inhibition of actin assembly amplifies PAF and 5-lipoxygenase product formation in response to soluble chemoattractants with distinct dose dependences . The augmentation of PAF generation may be linked to amplified second messenger levels at higher doses of C2 toxin, whereas the sensitivity of the 5-lipoxygenase metabolism to low concentrations may indicate toxin effect on a small, functionally specified, actin pool . The present data support an important role of cytoskeletal rearrangement in temporal and/or spatial limitation of chemoattractant-evoked PMN activation. Tidsskr Nor Laegeforen, 1991 Sep 10, 111(21), 2637 - 9 {Treatment of focal dystonia with botulinum toxin}; Gjerstad L et al.; Focal dystonia and hemifacial spasms are difficult to treat . Medication and surgery may suppress the dystonic movements but the improvement is not satisfactory . The present article reviews use of Botulinum toxin in cases of focal dystonia . Injections of very small doses of Botulinum A toxin into the affected muscles is a new and efficient therapy for patients with focal dystonia . The toxin acts by inhibiting the release of acetylcholine from the nerve terminal, leading to a localized paralysis of the treated muscle . The effect is temporary and gradually diminishes, but the treatment can be repeated . The use of Botulinum toxin must be applied on the basis of a thorough knowledge of its effect and possible side effects. J Neurol Neurosurg Psychiatry, 1991 Sep, 54(9), 813 - 6 A double blind trial of botulinum toxin "A" in torticollis, with one year follow up; Moore AP et al.; A double blind placebo controlled crossover trial was performed of botulinum toxin "A" in 20 patients with spasmodic torticollis . There was a statistically significant benefit for those treated with toxin; 12 on toxin improved objectively, compared with four on placebo (p less than 0.04) . After a follow up period of one year, 16 still seemed to benefit from repeated toxin injections . The main side effect was dysphagia, which appeared to be dose related in individual patients. Laryngoscope, 1991 Sep, 101(9), 960 - 4 Quantifying the spread of botulinum toxin through muscle fascia; Shaari CM et al.; Botulinum toxin was recently approved for treating several head and neck dystonias . Paralysis of neighboring muscles is the major complication of its use . Spread of toxin from the injected muscle has been suggested as an etiology . This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis . Botulinum toxin (0.2 to 10 U) was placed onto the fascia of rat tibialis anterior (TA) muscles (n = 6) . Toxin was also placed on dose-matched muscles that had their fascia surgically removed (n = 6) . Twenty-four hours later, the nerve to the tibialis anterior was electrically stimulated to deplete the muscle fibers of glycogen . Toxin-paralyzed fibers retained their glycogen and appeared purple on periodic acid-Schiff (PAS) stain . Botulinum toxin easily passed through muscle fascia even at subclinical doses . The presence of fascia reduced the spread of botulinum toxin by 23% . These results suggest that spread of botulinum toxin can be prevented only by delivering small doses to the center of a target muscle. J Neurochem, 1991 Sep, 57(3), 1024 - 32 Binding of botulinum and tetanus neurotoxins to ganglioside GT1b and derivatives thereof; Schengrund CL et al.; The ability of fragments derived from botulinum neurotoxin (BTx) serotype A to bind to GT1b-coated plastic wells was investigated and compared with the binding characteristics of the parent approximately 150-kDa protein . Although the approximately 50-kDa light chain of BTxA had a marginal binding capacity, the predominant adherence to GT1b-coated wells was exhibited by the approximately 50-kDa carboxy-terminal half of the approximately 100-kDa heavy chain of BTxA; the amino-terminal half of the heavy chain lacked the ability to bind . Binding to GT1b by BTxA and its fragments was compared with that of tetanus neurotoxin (TTx) and the carboxy-terminal half of its heavy chain . Binding of BTxA and the C-terminal half of the heavy chain was optimal in buffers of low ionic strength (mu less than or equal to 0.04 and 0.06, respectively), whereas the heavy chain bound GT1b best at mu greater than or equal to 0.10 . TTx and the approximately 50-kDa C-terminal half of its approximately 100-kDa heavy chain bound GT1b at ionic strengths similar to those of BTxA . Comparison of the binding of BTx serotypes A, B, and E to GT1b (using conditions that were found to be optimal for binding by BTxA) indicated differences in the interaction of the three serotypes with GT1b . Compared with BTxA, adherence to GT1b by serotypes B and E was reduced by approximately 60 and approximately 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Klin Oczna, 1991 Sep, 93(9), 264 - 5 {Injection of botulinum toxin into the oculomotor muscles in disorders of ocular motility}; Glasner L et al.; Injections of botulinum toxin into the oculomotor muscles was used in incorrectible diplopia, ocular torticollis, Duane's syndrome and congenital nystagmus . Favourable results were obtained and the sole complications which could be observed were a transitory ptosis and subconjunctival haemorrhages . Frequently 2 to 3 injections were sufficient for a permanent effect. J Behav Ther Exp Psychiatry, 1991 Sep, 22(3), 221 - 3 Meige's disease misdiagnosed as anxiety disorder; Cairns SL et al.; A woman in her late 40s with a 5 year history of anxiety was treated with relaxation training and cognitive restructuring . Her anxiety was manifested by facial twitching, hand fidgeting, vocal tremor, loss of self-esteem, and depression . Therapy seemed to reduce motor symptoms and improve her self-esteem, confidence, and mood . Six months after the start of therapy the client was found to have Meige's Disease . Following treatment with botulinum toxin, motor symptoms disappeared . This case highlights the need for psychotherapists to be more aware of neurological and medical problems which may mimic psychological ones. Arch Neurobiol (Madr), 1991 Sep-Oct, 54(5), 210 - 7 {Focal dystonias and facial hemispasm: treatment with botulinum A toxin}; Astarloa R et al.; We report the results of the treatment of 80 patients with various idiopathic focal dystonia and essential hemifacial spasm with Botulinum A toxin . A statistically significant improvement was obtained in our 34 patients with blepharospasm, 19 patients with hemifacial spasm, 59% of 22 patients with cervical dystonia and 60% of 5 patients with hand dystonia . Mean duration of the benefit of each injection was 15.3, 16.3, 7.6 and 8.7 weeks respectively . Adverse effects were local and transient . We concluded that botulinum A toxin is a safe and effective therapy for patients with focal dystonia and hemifacial spasm. Arch Neurobiol (Madr), 1991 Sep-Oct, 54(5), 206 - 9 {Treatment with botulinum toxin in blepharospasm}; Grandas F; Blepharospasm is a cranial dystonia characterized by forceful spasms of the orbicularis oculi muscle which may lead to functional blindness in approximately two-thirds of patients . Botulinum toxin injection is a simple procedure, very effective and with little morbidity . It is considered as the treatment of choice for patients with disabling blepharospasm. Arch Neurobiol (Madr), 1991 Sep-Oct, 54(5), 198 - 205 {Advances in the treatment of the dystonias}; Gimenez-Roldan S; Except in Wilson's disease, few secondary dystonias are susceptible to benefit from an aetiological treatment . The somatic distribution of dystonia often determines the therapeutic strategy . Thus, stereotactic surgery may be the treatment of choice for hemidystonia while anticholinergic medication may alleviate generalized dystonia, particularly in childhood . Finally, local infiltrations of botulinum toxin are particularly useful for various forms of local and segmental dystonia . Certain subsyndromes as myoclonic dystonia, levodopa sensitive dystonia and paroxysmal choreoathetosis may benefit from relatively specific treatment strategies. Ann Ophthalmol, 1991 Sep, 23(9), 326 - 33 A five-year analysis of botulinum toxin type A injections: some unusual features; Balkan RJ et al.; We analyzed patients treated during the past five years with botulinum toxin type A for strabismus and blepharospasm, reviewed our successes, failures, and unusual cases, and drew conclusions based on these treatments . Thirty-seven percent of the strabismus patients were cured, but many patients who were outside the strict definitions, still believed that they were significantly improved . A prominent feature in the treatment of strabismus was variability . Frequently, patients expected to do poorly had encouraging results . One permanent overcorrection occurred, and it converted an esotopic patient into an exotropic one with diplopia . This has persisted for 2.5 years and is the longest reported overcorrection to our knowledge . Our results indicate that larger doses of botulinum toxin produce longer spasm-free intervals in the treatment of blepharospasm . One patient receiving injections for her blepharospasm discovered that its cause was her sedative medication . This is the first reported case of a benzodiazepine inducing blepharospasm to our knowledge. Neuron, 1991 Sep, 7(3), 421 - 7 TTX-sensitive and TTX-insensitive sodium channel mRNA transcripts are independently regulated in adult skeletal muscle after denervation; Yang JS et al.; The expression of mRNA encoding the TTX-sensitive (SkM1) and TTX-insensitive (SkM2) voltage-dependent sodium channels in adult skeletal muscle is independently regulated . In normal skeletal muscle, only the SkM1 message is expressed and the level varies with muscle fiber type . After surgical denervation, the steady-state SkM1 mRNA level declines transiently, but returns to control levels within 5 days . Expression of SkM2 transcripts is markedly activated, reaching a peak 3 days after axotomy and then declining to a maintained level at approximately 30% of peak . Chemical denervation with botulinum toxin results in higher levels of SkM2 mRNA, which by 7 days posttreatment are 7-fold greater than levels in paired axotomized muscles . SkM2 expression subsequently declines as functional reinnervation appears . Quantal acetylcholine release appears to play a major role in suppression of SkM2 expression in adult innervated or reinnervated muscle, whereas nonquantal factors in toxin-treated, but not axotomized, muscle may sustain high level SkM2 mRNA expression. J Pharmacol Exp Ther, 1991 Sep, 258(3), 830 - 6 Lectins from Triticum vulgaris and Limax flavus are universal antagonists of botulinum neurotoxin and tetanus toxin; Bakry N et al.; Lectins from Anguilla anguilla, Artocarpus integrifolia, Canavalia ensiformis, Datora stramonium, Glycine max, Limax flavus, Ricinus communis and Triticum vulgaris were tested for their abilities to antagonize the binding of botulinum neurotoxin and tetanus toxin to rat brain membranes and to antagonize the ability of these toxins to block neuromuscular transmission in mouse phrenic nerve-hemidiaphragm preparations . Lectins from Limax flavus and Triticum vulgaris, both of which have affinity for sialic acid, were antagonists of the various serotypes of botulinum neurotoxin and tetanus toxin . When tested against the high affinity binding site for botulinum neurotoxin type B, the lectin from Limax flavus had a Ki of 3.1 x 10(-7) M and the lectin from Triticum vulgaris had a Ki of 3.75 x 10(-7) M . When tested against the high affinity binding site for tetanus toxin, the lectins from Limax flavus and Triticum vulgaris had Ki values of 1.5 x 10(-7) and 1 x 10(-6) M, respectively . In all cases the lectins behaved as competitive antagonists . In reverse experiments, neither botulinum toxin nor tetanus toxin was a very effective antagonist of lectin binding to brain membranes . Studies on isolated neuromuscular preparations showed that the lectin from Triticum vulgaris did not affect transmission at concentrations of 10(-6) to 10(-3) M, but at a concentration of 3 x 10(-5) M the lectin produced highly statistically significant antagonism of the neuromuscular blocking properties of botulinum neurotoxin types A, B, C, D, E and F as well as tetanus toxin . The lectin did not antagonize beta-bungarotoxin.(ABSTRACT TRUNCATED AT 250 WORDS) J Immunol, 1991 Aug 15, 147(4), 1139 - 46 Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes; Melamed I et al.; The mechanisms responsible for initiating the conversion of globular to filamentous actin (assembly) after stimulation of B lymphocytes and the role of these cytoskeletal changes in cell activation are incompletely understood . We investigated the molecular basis of the signals leading to actin polymerization and concentrated on the involvement of guanosine triphosphate (GTP)-binding regulatory proteins, and protein kinase C (PKC) . In addition, we related these early events to later events in B-cell activation, including cell proliferation . Cross-linking the Ag receptor with Staphylococcus aureus Cowan I (SAC) or anti-IgM antibodies, or stimulation of PKC with phorbol ester induced a time- and concentration-dependent increase in the filamentous actin content of B cells . Inhibition or depletion of PKC resulted in decreased actin assembly induced by anti-IgM, SAC, and PMA, suggesting that the signal for polymerization is generated distally to PKC activation . Pertussis toxin pretreatment inhibited the responses to anti-IgM and SAC but not PMA, and direct stimulation of permeabilized cells with GTP gamma S induced microfilament assembly, indicating the involvement of a GTP-binding protein for receptor-mediated events . Disruption of actin polymerization with botulinum C2 toxin or cytochalasin D inhibited the assembly of actin and {3H}TdR incorporation induced by all stimuli . We conclude that human B cell activation by receptor-mediated stimuli results in actin polymerization by signaling pathways coupled to GTP-binding proteins . These changes in the cytoskeleton may be involved in the transduction of messages leading to responses such as proliferation in B lymphocytes. Hosp Pract (Off Ed), 1991 Aug 15, 26(8), 35, 38, 41 - 2 Botulinum toxin A therapy in dystonia; Adler CH; Local injections can decrease posturing and pain in 70% to 90% of patients for up to eight months . Responses can be extended with further injections. Br J Ophthalmol, 1991 Aug, 75(8), 487 - 90 Surgical management of essential blepharospasm; Bates AK et al.; We have reviewed the surgical management of essential blepharospasm over the last 15 years, comparing the results from facial nerve avulsion with those from orbicularis muscle stripping . After facial nerve avulsion 50% of patients remained free of troublesome spasm for 15 months after surgery, but only 25% remained so for more than two years . Following orbicularis oculi myectomy 50% of patients were free of troublesome spasms for 30 months after surgery and 55% of patients had relief from spasm for more than two years . Secondary effects of the two procedures are compared and are found to be fewer after orbicularis myectomy . There were no major complications after either form of surgery . Botulinum toxin is the treatment of first choice for this condition . If this becomes ineffective or inconvenient, surgical treatment is warranted and should not be deferred for fear of severe side effects of treatment, since these are rare . Protractor myectomy gives longer relief from blepharospasm than facial nerve avulsion and has fewer complications . However, it is technically difficult, time consuming, and has greater peroperative morbidity . Facial nerve avulsion may therefore still have a role in selected patients. Neurology, 1991 Aug, 41(8), 1185 - 8 Botulinum toxin treatment of tremors; Jankovic J et al.; We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1) . The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years . During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both . The average peak effect for all patients was rated as 3.0 (0 to 4 scale) . Thirty-five (67%) patients improved (peak effect greater than or equal to 1) . The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks . Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%) . Six (60%) patients with hand tremor had transient focal weakness . EMG recordings showed decreased amplitude of EMG bursts after Botox treatment . The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed. Laryngoscope, 1991 Aug, 101(8), 911 - 4 A method for the treatment of abductor spasmodic dysphonia with botulinum toxin injections: a preliminary report; Rontal M et al.; A preliminary technical report of the effective treatment of abductor spasmodic dysphonia with botulinum toxin is presented . Our technique attempts to place the toxin close to the posterior cricoarytenoid muscle to allow diffusion of the material to the PCA . Our pilot study demonstrates that botulinum toxin is an effective approach for reducing or eliminating the abductor glottal spasms during phonation and, thereby, providing functional speech communication. J Pharmacol Exp Ther, 1991 Aug, 258(2), 613 - 9 Tetanus toxin and neuronal membranes: the relationship between binding and toxicity; Bakry N et al.; Tetanus toxin labeled by the Bolton-Hunter technique possesses high specific activity and retains substantial biological activity . This material can be used to characterize tetanus toxin binding to receptors in brain membrane preparations . In experiments aimed at measuring the absorption of labeled toxin, the displacement of labeled toxin by unlabeled toxin and the on-rate and off-rate constants, the data revealed two binding sites . The high affinity site had a Kd of 0.033 to 0.070 nM and a Bmax of 0.26 to 0.4 pmol/mg of protein; the low affinity site had a Kd of 0.89 to 6.9 nM and a Bmax of 1.55 to 3.0 pmol/mg of protein . The binding of tetanus toxin to brain membranes was enhanced greatly by low pH and ionic strength . Similarly to tetanus toxin, botulinum neurotoxin could be labeled by the Bolton-Hunter technique, and its binding to brain membranes was also enhanced by low pH and ionic strength . In studies with a neutralizing monoclonal antibody against tetanus toxin, the antigen-antibody interaction was not significantly altered by media with low ionic strength and pH . On the other hand, the ability of the antibody to block toxin binding to brain membranes was reduced substantially in nonphysiologic media . In a bioassay aimed at determining the effect of pH and tonicity on tissue association by toxin, low pH and ionic strength did not enhance toxicity . The biological activity of tetanus toxin was unaffected and that of botulinum neurotoxin was greatly diminished . The present findings confirm the widely reported observation that low pH and ionic strength promote tissue association by tetanus toxin, but they challenge the premise that this binding is relevant to the normal process of cell poisoning. Neurology, 1991 Jul, 41(7), 1088 - 91 Cervical dystonia: clinical findings and associated movement disorders; Jankovic J et al.; We studied 300 patients, 61% women, with mean age 49.7 years and mean duration of dystonia 7.8 years, to determine the demographic and clinical characteristics of cervical dystonia (CD) and its relationships to other movement disorders . Torticollis was present in 82%, laterocollis in 42%, retrocollis in 29%, and anterocollis in 25%; however, the majority (66%) had a combination of these abnormal postures . Scoliosis was present in 39%, local pain reported by 68%, and 32% had evidence of secondary cervical radiculopathy . In addition to CD, 16% of patients had oral dystonia, 12% mandibular dystonia, 10% hand/arm dystonia, and 10% had blepharospasm . Tremor was noted in 71% of patients; head-neck tremor was present in 60%, and tremor in other body regions was present in 32% . A family history of a movement disorder was present in 44% of the CD patients . Tardive dystonia was the cause in 6%; 11% had posttraumatic dystonia . Anticholinergic drugs provided moderate improvement in 33% of patients, but local intramuscular botulinum toxin injections relieved CD, local pain, or both in over 90% of all treated patients. Behring Inst Mitt, 1991 Jul, (89), 153 - 62 Clostridial neurotoxins: from toxins to therapeutic tools? Niemann H, Binz T, Grebenstein O, Kurazono H, Thierer J, Mochida S, Poulain B, Tauc L. Tetanus toxin and botulinum toxins are powerful neurotoxins which block neurotransmitter release through an unknown mechanism my means of their light chains . The heavy chains provide the machinery for neuroselective binding, internalization, retrograde intraaxonal transport, and translocation of the L-chains into the cytosole . We have cloned and sequenced the structural genes of tetanus toxin and of five serologically distinct botulinum toxins to identify structurally and functionally conserved subdomains . The minimum essential domains of the L-chains of tetanus and botulinum toxin type A were identified by combined in vitro transcription and microinjection of L-chain specific mRNA into identified presynaptic neurons of Aplysia californica . In addition, a nontoxic mutant of tetanus was generated by replacing histidine(237) by a proline residue . The development of nontoxic neuroselective transporter molecules carrying various marker enzymes is discussed. Surv Ophthalmol, 1991 Jul-Aug, 36(1), 28 - 46 Botulinum A toxin (Oculinum) in ophthalmology; Osako M et al.; Botulinum A toxin has been used to treat strabismus and a variety of spasmodic neuromuscular diseases . Botulinum toxin treatment of strabismus is not as definitive and stable as the traditional surgical approach, but it has been found most useful in postoperative overcorrection, small deviations, sensory deviations, and acute sixth nerve palsy . This toxin has been effective in the treatment of essential blepharospasm and hemifacial spasm, for which it produces temporary relief of symptoms . In addition, this treatment has been applied to lower lid entropion, myokymia, aberrant regeneration of the seventh nerve, lid retraction, corneal exposure, nystagmus, spasmodic torticollis, and adductor spastic dysphonia. Muscle Nerve, 1991 Jul, 14(7), 672 - 5 Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes; Lange DJ et al.; We used single fiber electromyography (SFEMG) to study 42 patients who had enrolled in a double-blind, placebo-controlled trial undertaken to assess the efficacy of botulinum toxin (BTX) injection of neck muscles to treat torticollis . SFEMG in a limb muscle was performed before treatment, 2, and 12 weeks after injection of placebo or BTX . Before treatment, the mean jitter was 26.8 microsec in patients who were to receive BTX, and 25.7 microsec in the placebo group . Two weeks after injection, mean jitter in the group receiving BTX was 43.6 microsec . In the placebo group, it was 26.5 microsec (P = less than .05) . Twelve weeks after injection, mean jitter in the BTX group was 35.5; for the placebo group it was 24.5 . Fiber density did not change in any patient during the study . There were no remote clinical effects of BTX . Injection of BTX into muscles affected with focal dystonia is a promising and safe treatment, but there are subclinical effects on uninjected muscles. Rehabil Nurs, 1991 Jul-Aug, 16(4), 184 - 8 Botulinum toxin for blepharospasm: challenges for rehabilitation nurses; Kinash RG et al.; Blepharospasm is a chronic, progressive, involuntary spasmodic closure of the eyelids associated with abnormal facial and oromandibular movements . It is a neurologic disorder whose cause is unknown and whose pathophysiology is poorly understood . Without appropriate treatment, it can result in functional blindness and other disabilities . In the last decade, botulinum toxin has been found to be effective therapy for most individuals . The drug, which is given by local injection, has a denervation effect . It relieves symptoms for several months, allowing patients to resume their former lifestyles between treatments . This new therapy modality challenges rehabilitation nurses to bridge the gap between disabled persons in the community and this new technology . Casefinding, referrals, and patient education are among the interventions that can help meet this challenge . The major purpose of this article is to inform rehabilitation nurses about how to recognize the symptoms of neurologic blepharospasm and how to intervene to prevent disabilities that could result. Clin Neuropharmacol, 1991 Jun, 14(3), 262 - 7 Electromyographic guidance of botulinum toxin treatment in cervical dystonia; Dubinsky RM et al.; We report the results of electromyographic (EMG) guidance in the treatment of cervical dystonia with botulinum toxin . Eight-four patients received a total of 225 injection sessions . Overall there was moderate objective improvement in 78.7% . The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean duration of maximum effect was 107 +/- 49 days . Complications included excessive neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions . We conclude that EMG guidance is a safe and effective method of administering botulinum toxin in the treatment of cervical dystonia. Am Fam Physician, 1991 Jun, 43(6), 2113 - 20 Facial dystonia, essential blepharospasm and hemifacial spasm; Holds JB et al.; Movement disorders, or dyskinesias, in the facial region may be categorized in several ways . Dystonic movement disorders in the cranial-cervical region, including essential blepharospasm, Meige syndrome and spasmodic torticollis, are characterized by uncontrollable squeezing movements in the face and neck . These disorders typically present in the fifth and sixth decades of life . Essential blepharospasm is particularly debilitating, as the involuntary eyelid closure that accompanies this condition may result in functional blindness with an otherwise normal visual pathway . Hemifacial spasm is an intermittent, unilateral, spasmodic contraction of the muscles innervated by the facial nerve . This disorder usually presents in the third or fourth decade and has a different underlying pathophysiology than the dystonias . Botulinum A toxin therapy has largely supplanted surgical intervention in the treatment of essential blepharospasm and hemifacial spasm. Laryngoscope, 1991 Jun, 101(6 Pt 1), 630 - 4 Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia; Troung DD et al.; The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study . Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngologist, and a neurologist . The toxin or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance . Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice . Fundamental frequency and phonation time remained unchanged . Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group . Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group . Injection with saline resulted in edema of the vocal cord in one patient . Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia. Otolaryngol Head Neck Surg, 1991 Jun, 104(6), 849 - 55 Successful treatment of selected cases of abductor spasmodic dysphonia using botulinum toxin injection; Ludlow CL et al.; Ten patients with abductor spasmodic dysphonia, who exhibited spasmodic bursts and heightened activity of the cricothyroid muscle during speech, were selected for participation . Between 5 and 20 U of botulinum toxin type A were injected into both right and left cricothyroid muscles . Six patients benefited substantially, whereas four did not . Acoustic analyses of voice patterns showed similar changes to the clinical impressions . Significant group improvements were found in sentence duration while selected patients improved in the proportion of their speech that was voiced and the duration of their voiceless consonants . Those patients with abductor spasmodic dysphonia and other muscle abnormalities in addition to the cricothyroid and with constant breathiness did not benefit. Am J Physiol, 1991 Jun, 260(6 Pt 1), L539 - 47 ADP ribosylation of type II pulmonary epithelial cell G proteins; Rybin VO et al.; Secretion of pulmonary surfactant by type II pulmonary epithelial cells (T2P) is regulated by receptor-mediated mechanisms . In other systems, coupling of receptor-linked signals to intracellular events involves guanine nucleotide-binding proteins (G proteins), but the specific role of G proteins in T2P signaling pathways is poorly defined . The present studies begin to address the role of G proteins in transmembrane signaling in these pneumocytes . Membrane preparations from purified T2Ps demonstrated ADP ribosylation of specific substrates by pertussis, cholera, and botulinum toxins (PT, CT, and BT, respectively) . Toxin-dependent T2P substrate labeling from 32P-labeled NAD was dependent on time and membrane protein concentration . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed ADP ribosylation of membrane substrates of the following molecular masses: PT, 40/41 kDa; CT, 47/51 kDa; BT, 22 kDa . BT-dependent ADP ribosylation of a 22-kDa cytosolic substrate was also observed . Pretreatment of cultured T2P with the individual toxins led to ADP ribosylation of their respective specific substrates in a time-dependent fashion . In cells pretreated with PT or CT, substrates for the complimentary toxins remained available for subsequent ADP ribosylation in vitro . This result supports the specificity of the toxin effects . Basal secretion of the major phospholipid of pulmonary surfactant, disaturated phosphatidylcholine (DSPC) was unaffected in T2P treated with PT, but was stimulated in cells exposed to CT or BT . Neither CT nor BT altered release of lactate dehydrogenase . In cells treated with AMP or with isoproterenol DSPC secretion was stimulated six- to eightfold; preexposure of the cells to CT reduced the response to either agonist by 70%.(ABSTRACT TRUNCATED AT 250 WORDS) J Biol Chem, 1991 May 25, 266(15), 9580 - 5 Heterologous combinations of heavy and light chains from botulinum neurotoxin A and tetanus toxin inhibit neurotransmitter release in Aplysia; Poulain B et al.; The neuroparalytic activities of botulinum neurotoxin type A (BoNT A), tetanus toxin (TeTx), or homologous and heterologous combinations of their constituent polypeptides were examined at cholinergic and non-cholinergic synapses of Aplysia californica . When applied extracellularly, BoNT A or a mixture of its heavy (HC) and light (LC) chains were far more potent in blocking transmitter release at cholinergic than non-cholinergic synapses . The reverse was true for TeTx or a mixture its constituent chains . Such selectivity was assigned to differences in neuronal targetting and uptake of the neurotoxins since both exhibited similar potencies when injected directly into the cell body of either cell type . When bath-applied, heterologous combinations of the toxins' HC and LC appeared as effective as the parent neurotoxins from whence each HC was derived . Moreover, targetting/internalization was attributable to the analogous N-terminal moieties, H2 and beta 2, of the HC from BoNT A and TeTx . Thus, it may be postulated that the latter regions possess two functional domains, one being distinct and responsible for the divergent neuronal specificity, whereas the other serves a common role in translocating the LC of either toxin . Also, it was shown that the C-terminal portion of the HC of TeTx is unable to play the intracellular role of its counterpart in BoNT A. Ned Tijdschr Geneeskd, 1991 May 18, 135(20), 889 - 92 {The treatment of hemifacial spasms using botulin}; Struys MA et al.; At the Academic Medical Center of the University of Amsterdam the results of treatment of hemifacial spasms (HFS) with botulinum toxin type A were evaluated in a pilot study . Five men and 21 women with HFS were treated with toxin injections . The mean age was 65 years . Most patients were referred from other centers and had been previously treated without success with various medications or with surgical treatment . Treatment took place at the outpatient department . The toxin was injected into the M . orbicularis oculi at the medial and lateral sides of the upper and lower lids . The total dose varied between 6 and 16 LD50 . Patients were reinjected on demand . All patients except for one reported satisfying improvement of their spasm . The onset of the beneficial effect was 1-2 days after the injection and the effect lasted about 3 months . All patients were re-examined 1 to 2 weeks after each treatment and showed reduction or disappearance of synkinesias . No systemic side effects occurred and local complications were mild and transient . We conclude that local injection of botulinum toxin appears to be a successful alternative in the current treatment of hemifacial spasm. J Clin Invest, 1991 May, 87(5), 1575 - 84 Adenosine diphosphate-ribosylation of G-actin by botulinum C2 toxin increases endothelial permeability in vitro; Suttorp N et al.; The endothelial cytoskeleton is believed to play an important role in the regulation of endothelial permeability . We used botulinum C2 toxin to perturb cellular actin and determined its effect on the permeability of endothelial cell monolayers derived from porcine pulmonary arteries . The substrate for botulinum C2 toxin is nonmuscle monomeric actin which becomes ADP-ribosylated . This modified actin cannot participate in actin polymerization and, in addition, acts as a capping protein . Exposure of endothelial cell monolayers to botulinum C2 toxin resulted in a dose- (3-100 ng/ml) and time-dependent (30-120 min) increase in the hydraulic conductivity and decrease in the selectivity of the cell monolayers . The effects of C2 toxin were accompanied by a time- and dose-dependent increase in ADP-ribosylatin of G-actin . G-Actin content increased and F-actin content decreased time- and dose-dependently in C2 toxin-treated endothelial cells . Phalloidin which stabilizes filamentous actin prevented the effects of botulinum C2 toxin on endothelial permeability . Botulinum C2 toxin induced interendothelial gaps . The effects occurred in the absence of overt cell damage and were not reversible within 2 h . The data suggest that the endothelial microfilament system is important for the regulation of endothelial permeability. J Med Assoc Thai, 1991 May, 74(5), 239 - 47 Writer's cramp: the experience with botulinum toxin injections in 25 patients; Poungvarin N; Twenty-five writer's cramp patients have been attending the Movement Disorder Clinic at the Division of Neurology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok during three years period (between January 1988 - January 1991) . There were 17 male subjects and the male to female sex ratio was 2.125:1 . The mean age of the patient was 36.80 (SD 10.21) years with the range of 18-60 years . The mean duration of illness of all patients was 5.88 (SD 7.14) years with the range of 1 to 30 years . Eighteen patients (72.0%) were classified as simple writer's cramp and seven patients (28.0%) were dystonic writer's cramp . The mean age of the patients of both groups was not different while the duration of illness in the dystonic group was statistically significantly longer than the simple group, i.e . 12.0 (SD 12.1) versus 3.9 (SD 3.1) years . Fourteen patients (56%) had associated pain during writing and 6 patients (24%) had hand tremor . All patients were right handed and had a history of various pharmacological treatments without any consistent benefit . They included muscle relaxants, tranquillisers, antiepileptic drugs, and betablockers . Fourteen patients from 17 available history records (82.4%) had been spending at least 4-10 hours writing each day . Twenty-one patients (84%) had botulinum toxin injections, 40-80 international mouse units were given in 2-4 divided doses over the overactive forearm muscles observed during writing without the electromyographic glidance . There was no loss to the follow-up . Fourteen of the 21 subjects (66.7%) showed definite improvement in hand writing, 4 patients (19.0%) improved minimally and 3 patients (14.3%) revealed no improvement . Arm pain in all 12 patients associated during writing was abolished after the injections . There were complications in 7 patients (33.3%) presented as transient finger drop (5 patients, 23.8%) and easily fatigued arm (2 patients, 9.5%) . These preliminary results confirm that botulinum toxin injections is a successful treatment for many patients with writer's cramp without performing complex electromyographic recordings while the patients are writing . The constraints of this treatment are its high cost (i.e . 1 vial of 100 units costs 300 US dollars) and its benefit lasts for only 4-6 months. J Biol Chem, 1991 Apr 25, 266(12), 7646 - 50 Purification of GTPase-activating protein specific for the rho gene products; Morii N et al.; A GTPase-activating protein specific for the rho gene products (rho-GAP) was purified from the cytosol of bovine adrenal gland . Purification procedures consisted of ammonium sulfate fractionation, chromatographies on columns of phenyl-Sepharose and CM-Sepharose, gel filtration on a TSK-gel G3000SW, and Mono S fast protein liquid chromatography . By these procedures the activity was purified about 36,000-fold with a recovery of 0.6% . The final preparation showed a major protein band at Mr 28,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stimulated GTP hydrolysis by the purified rho A protein in a time- and dose-dependent manner . No stimulation was found for ras p21 . The ADP-ribosylation on the rho protein by botulinum C3 exoenzyme did not affect its interaction with the purified rho-GAP. Dtsch Med Wochenschr, 1991 Apr 12, 116(15), 567 - 72 {Treatment of spasmodic torticollis with local injections of botulinum toxin A}; Erbguth F et al.; Sixty patients (30 men, 30 women, mean age 45.5 {18-71} years) with various forms of spasmodic torticollis were treated with local injections of botulinus A toxin . The results of treatment were assessed on an arbitrary scale (0-4) by the patients, by an examiner and by a neurologist who studied video recordings without knowing at what stage they had been recorded . After the first course of injections (a maximum of three injections of 10-40 ng in four weeks) 50 patients (83%) reported a better than 50% improvement; the mean score on the four point scale fell from 3.6 to 1.85 (P less than 0.001) . The severity of the disorder as judged from the video recordings fell from a mean of 3.23 to 1.71 (P less than 0.001) . The effect lasted for an average of 14 weeks . 6 patients developed mild dysphagia, in two further cases severe dysphagia occurred which lasted for up to four weeks . Twenty patients were followed up for more than one year: in nine of them the interval between courses of injections, the dose being unaltered, remained the same (12-14 weeks), but thereafter the abnormal movements returned with the same severity as before treatment . In eight patients the intervals between courses grew longer and the abnormal movements became less severe . Two patients have been symptom free for 20 and 13 months respectively, but one female patient failed to respond owing to the presence of antibodies against botulinus A toxin . The results indicate that local injection of botulinus toxin is a successful treatment for spasmodic torticollis. Can J Ophthalmol, 1991 Apr, 26(3), 148 - 51 Occult pontine glioma in a patient with hemifacial spasm; Westra I et al.; Hemifacial spasm due to an intracranial mass lesion is rare . We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years . The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation . Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion . Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma . Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours . Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm. Can J Ophthalmol, 1991 Apr, 26(3), 133 - 8 Treatment of blepharospasm and hemifacial spasm with botulinum A toxin: a Canadian multicentre study; Taylor JD et al.; Botulinum A exotoxin was recently approved for use in Canada . We describe the efficacy of botulinum toxin in the management of 235 patients with blepharospasm (mean age 64.3 years) and 130 patients with hemifacial spasm (mean age 60.4 years) treated at three Canadian ophthalmologic centres between 1984 and 1989 . A total of 98% of the patients with blepharospasm and 100% of the patients with hemifacial spasm had significant relief of their symptoms; however, 11% of the former and 2% of the latter did not respond to the usual starting concentrations of the drug and needed stronger dosages for relief . The duration of relief varied widely in both groups . Up to 7% of patients had ineffective treatments but responded to subsequent injections . Analysis of variance and linear trend statistics showed that there were no changes in the mean duration of relief over the first several treatments for individual patients in either group . Side effects were transient and included ptosis, exposure keratitis, epiphora and strabismus. Ophthalmology, 1991 Apr, 98(4), 509 - 12; discussion 512-3 Use of botulinum toxin in strabismus after retinal detachment surgery; Petitto VB et al.; Botulinum toxin was used to treat 20 patients with strabismus after retinal detachment surgery . Preinjection motility deviations ranged from 10 to 60 prism diopters (D) . Postinjection deviations ranged from 0 to 20 prism D, with 75% being 10 D or less . Eighty-five percent achieved fusion that persisted, with 73% requiring only one or two injections . Only muscles in the eye that had undergone retinal reattachment surgery were injected . The average period of follow-up was 12 months . Complications were rare and all resolved spontaneously . Botulinum toxin appears to be useful as a primary treatment modality for persistent strabismus following retinal detachment surgery, possibly obviating the need for complicated strabismus surgery. Exp Eye Res, 1991 Apr, 52(4), 445 - 9 Succinylcholine-stimulated muscle tensions following botulinum injection in the domestic cat; Dennehy PJ et al.; Succinylcholine (SCh) selectively stimulates, and can therefore selectively assay, the multiple innervated (MI) fiber system of the extraocular muscles . Since botulinum-A toxin has been observed to induce changes in eye position in humans, SCh was used to assess the effect of botulinum-A on the SCh-sensitive MI fibers of extraocular muscles . Intravenous SCh infusion (40 micrograms-1 kg-1 min-1 was performed in the anesthetized domestic cat . Thirty-eight infusions were performed in 19 normal controls, measuring the peak tensions generated in the four horizontal and four vertical rectus muscles . Succinylcholine-stimulated muscle tensions (SSMT) were then repeated in nine animals, 4 weeks and 10 weeks following injection of botulinum-A toxin into both medial rectus muscles . Mean peak SSMTs were unchanged at 4 and 10 weeks following botulinum injection when compared to controls . We propose that botulinum chemo-denervation has no acute or chronic effect on the MI SCh-sensitive muscle fibers of the medial recti of the domestic cat . This lack of effect on the postsynaptic MI fibers indirectly supports light and electron microscopic studies which show changes predominantly in the singly innervated (SI), rather than the MI fibers following botulinum injection . Mean peak SSMTs were also greater for medial and superior rectus muscles compared to lateral and inferior recti respectively, suggesting a greater number or proportion of MI fibers in medial and superior recti. Ann Otol Rhinol Laryngol, 1991 Apr, 100(4 Pt 1), 274 - 9 Recurrent laryngeal nerve section for spastic dysphonia: 5- to 14-year preliminary results in the first 300 patients; Dedo HH et al.; This presentation compares the preoperative voice recordings and the latest follow-up voice recordings, made 5 to 14 years postoperatively, of the first 300 patients with various degrees of spastic dysphonia whom we treated with recurrent laryngeal nerve (RLN) sections from 1975 to 1982 . Voice therapy was usually given afterward and in some patients, when necessary, "fine tuning" surgery was performed later . The 243 patients who could be located were asked to answer a questionnaire regarding their voice production and communication abilities, and to make a voice recording . The preoperative and long-term postoperative voice recordings were analyzed by means of perceptual voice evaluation and acoustic analysis of the voice spectra . Fifteen percent developed recurrence of mild to moderate spasticity 6 to 24 months after the RLN section . This was curable with laser vocal cord thinning via direct laryngoscopy . Eighty-two percent of patients had little or no voice spasticity 5 to 14 years after their RLN section . The experimental alternative of injecting botulin directly into the vocal cord to temporarily paralyze it is discussed. Mayo Clin Proc, 1991 Apr, 66(4), 365 - 71 Selective peripheral denervation for torticollis: preliminary results; Davis DH et al.; Herein we report the preliminary results in nine patients who have undergone selective peripheral denervation for spasmodic torticollis and have been followed up for at least 13 months . All patients had improvement immediately after surgical intervention, and the results have been maintained in five patients . In one patient who had recurrent torticollis, a second procedure in conjunction with injection of botulinum toxin has produced substantial improvement; however, follow-up was brief (6 months) . No surgical complications occurred . We believe that selective peripheral denervation is safe and that it can benefit patients with torticollis who have not responded to other types of therapy . These favorable results confirm other published reports on the efficacy of selective peripheral denervation . Long-term follow-up, however, is necessary for determining the role of this procedure in the management of torticollis. Ann Neurol, 1991 Apr, 29(4), 370 - 6 Change in pattern of muscle activity following botulinum toxin injections for torticollis; Gelb DJ et al.; Twenty patients with torticollis had electromyographic studies of their neck muscles performed before and after a series of local injections of botulinum toxin . The pattern of muscle activity changed after the injections, and this effect persisted even after head position had returned to baseline . Patients who did not experience any clinical benefit from the injections also demonstrated a change in the pattern of muscle activity . These results suggest that the underlying abnormality in torticollis usually involves a general motor program for head position, rather than the activity of individual neck muscles. Klin Monatsbl Augenheilkd, 1991 Apr, 198(4), 268 - 70 {Involuntary lid closure caused by defective healing of facial paralysis and its treatment with botulinum toxin}; Roggenkamper P et al.; Unvoluntary lidclosure with movement of the mouth is not so rare in aberrant regeneration of nerve fibers after Bell's palsy . There was no therapy until now . 10 patients with this disease were treated with botulinum-toxin injections into the orbicularis muscle . For an average time of 11 weeks after injection there was a complete absence of synkinesis, followed by a time of 9 weeks of less complaints . Thus 2-3 injections might be sufficient treatment within a year . Complications worth mentioning, especially due to the reduced force of lidclosure, were not observed. J Neurol Neurosurg Psychiatry, 1991 Apr, 54(4), 310 - 3 Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm; Valls-Sole J et al.; Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle . It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder . We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment . Denervation signs were found with needle EMG in all treated muscles . Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections . In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections . The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm. Ophthalmology, 1991 Mar, 98(3), 357 - 66 Clinical doxorubicin chemomyectomy . An experimental treatment for benign essential blepharospasm and hemifacial spasm; Wirtschafter JD; Doxorubicin (DXR) was injected as a treatment for benign essential blepharospasm and hemifacial spasm . The other eyelids were treated concurrently with botulinum toxin (BT) . No DXR-treated eyelid has maintained 0 strength (commonly achieved with BT) . Two patients with benign essential blepharospasm and four patients with hemifacial spasm have achieved major improvement, sustained for more than 6 months . Eyelids have been swollen and inflamed for up to 3 months . No spontaneously irreversible complication has occurred . A single injection at the maximum safe dose (1 mg in the upper lid and 1.5 mg in the lower lid) has not proven sufficient to produce cure . Treatment of each lower eyelid of a muscular male with severe blepharospasm may require cumulative doses of up to 4.0 mg, delivered in three injection events separated by at least 2 months, with each injection no greater than 1.5 mg DXR per site . At the present time, there is no assurance that a permanent cure will result. Br J Ophthalmol, 1991 Mar, 75(3), 181 - 4 Pathological changes in levator palpebrae superioris muscle treated with botulinum toxin in a case of carotico-cavernous fistula; Adams GG et al.; We describe the case of a patient with carotico-cavernous fistula who had botulinum toxin A to induce a protective ptosis 4.5 days before death . The levator palpebrae superioris muscle from both sides and the superior rectus muscle from the injected side were obtained for examination . The preserved samples were stained with haematoxylin and eosin, Martius scarlet blue, Glees, S100, dehydrogenase, ATPase, and toluidine blue as well as being examined by electron microscopy . Inflammation and oedema were found that were probably due to the carotico-cavernous fistula . Axonal and some myelin sheath damage were also seen. Arch Ophthalmol, 1991 Mar, 109(3), 396 - 404 Botulinum-induced changes in monkey eyelid muscle . Comparison with changes seen in extraocular muscle; Porter JD et al.; Botulin type A was injected into the eyelids of adult monkeys, and structural alterations in the orbicularis oculi muscle were evaluated after survival times of 7 to 84 days . The most profound change seen at both the light- and electron-microscopic levels was nonselective atrophy of virtually all muscle fibers . Moreover, the botulin-induced blockade of neuromuscular transmission was nonspecific in producing alterations in the three orbicularis fiber types . Muscle structural changes appeared to be reversible, with no apparent long-term consequences . While sprouting of preterminal axons was noted in botulin-treated muscle, formation of collateral sprouts did not appear to be widespread . These changes contrast with the fiber type-specific, long-term alterations induced in extraocular muscle by botulin treatment . However, this differential response may be attributed to the very clear differences in fiber type composition and motor control mechanisms between eyelid and extraocular muscle groups . The efficacy of botulin treatments for strabismus and focal dystonia may then be directly related to both the anatomic fiber type composition and the functional properties of motor control systems of the injected muscle. Arch Ophthalmol, 1991 Mar, 109(3), 393 - 5 Histologic features of human orbicularis oculi treated with botulinum A toxin; Harris CP et al.; To evaluate muscle histologic features in humans following therapeutic botulinum toxin injections, we studied orbicularis oculi from 11 patients with blepharospasm; nine had previously received botulinum toxin injections and two had not . All muscles had comparable variability in muscle fiber diameter, with no necrosis, inflammation, denervation, or consistent alterations in muscle fiber internal architecture . Botulinum toxin produces no persistent histologic changes in human muscle fibers. Ann Acad Med Singapore, 1991 Mar, 20(2), 223 - 7 Botulinum toxin in the treatment of facial dyskinesias; Chong PN et al.; Patients with hemifacial spasm (N = 25), blepharospasm (n = 8), and benign eyelid fasciculation (n = 2) were treated with botulinum toxin injections (PHLS, Porton Down, England) . All patients reported substantial symptomatic relief . Marked improvement was seen in fifteen patients with hemifacial spasm and six patients with blepharospasm . Benign eyelid fasciculation was completely abolished . Beneficial effects was evident two to three days after injections, became maximum at one week, and remained effective for up to six months . Side effects were transitory and mild . They included periorbital edema, mild diplopia, ptosis and facial weakness . Only in two patients was ptosis unacceptable . Severity of side effects was dose-related . Reinjections had similar efficacy . Botulinum toxin therapy is a safe and effective treatment for these facial dyskinesias and should be considered a viable alternative to surgical procedures. J Neurosci, 1991 Mar, 11(3), 657 - 66 Axotomy-like changes in cat motoneuron electrical properties elicited by botulinum toxin depend on the complete elimination of neuromuscular transmission; Pinter MJ et al.; The electrical properties of cat medial gastrocnemius (MG) spinal motoneurons were studied 14-21 d following injection of type A botulinum toxin (BTX) into the MG muscle . Treated MG muscles were atrophic, displayed pronounced fibrillation activity, and were markedly but not completely paralyzed . MG motoneuron electrical properties from animals with the highest MG muscle-twitch forces (greater than 20 gm) appeared normal, while motoneuron properties from animals with the lowest MG muscle-twitch forces (less than 10 gm) exhibited axotomy-like changes, though these changes were less pronounced than after axotomy itself . No changes in the axonal conduction velocity were observed, however . Motoneuron connectivity with MG muscle fibers was determined following intracellular stimulation of MG motoneurons by averaging EMG signals from 3 or 4 pairs of recording electrodes inserted into the BTX-treated MG muscles . Normal electrical properties were observed among motoneurons in which detectable EMG activity linked to the intracellular stimulation pulse was observed . The level of this connectivity, however, indicated that a relatively small number of muscle fibers were activated by individual motoneuron action potentials . Axotomy-like changes of electrical properties were observed in MG motoneurons that could not be associated with detectable EMG activity in the BTX-treated MG muscle following repeated trials of intracellular stimulation . These results indicate that the existence of effective neuromuscular transmission at a small number of motor terminals is sufficient to prevent the appearance of axotomy-like changes in motoneuron electrical properties, and that the absence of such transmission at all motor terminals is associated with the appearance of axotomy-like changes . The results suggest that the effects of axotomy itself on motoneuron properties may be based upon the loss or elimination of a potent interaction between muscle and motoneurons normally mediated by neuromuscular transmission. J Neurochem, 1991 Mar, 56(3), 827 - 35 Microtubule-dissociating drugs and A23187 reveal differences in the inhibition of synaptosomal transmitter release by botulinum neurotoxins types A and B; Ashton AC et al.; The inhibitory effects of botulinum neurotoxins types A and B on Ca2(+)-dependent evoked release of {3H}noradrenaline from rat cerebrocortical synaptosomes were compared and their molecular basis investigated . A23187, a Ca2+ ionophore, proved more efficacious in reversing the blockade produced by type A than that by B, whereas the actions of neither were changed by increasing intraterminal cyclic GMP levels using 8-bromo-cyclic GMP of nitroprusside . Disruption of the actin-based cytoskeleton with cytochalasin D did not alter the inhibition seen subsequently with either toxin . However, prior disassembly of microtubules with colchicine, nocodazole, or griseofulvin reduced the potency of type B toxin, but not that of type A toxin; stabilization of the microtubules with taxol counteracted this effect of colchicine . Because colchicine treatment of synaptosomes did not interfere with the measurable binding of type B toxin or its apparent uptake, it appears to act intracellularly . Collectively, these data suggest that botulinum neurotoxins types A and B inactivate transmitter release by interaction at different sites in the process . Based on the consistent results observed with four different drugs known to affect selectively microtubules, their involvement in the action of the type B neurotoxin is proposed. Clin Neuropharmacol, 1991 Feb, 14(1), 62 - 77 Cognitive processes in idiopathic dystonia treated with high-dose anticholinergic therapy: implications for treatment strategies; Taylor AE et al.; Studies utilizing single doses of scopolamine have suggested a role for the cholinergic system in memory . Results are consistent in identifying a selective effect on the early encoding stage of information processing . In terms of long-term administration of anticholinergics, patients with Parkinson's disease often display memory deficits . However, underlying pathology within the forebrain cholinergic system complicates the study of treatment effects in this disorder . We therefore assessed multiple memory routines in 20 cognitively intact patients with dystonia where no such pathology has been identified . Patients were tested before and after 2-4 months of 15-74 mg of trihexyphenidyl daily . Twelve tolerated this regime . Compared to control subjects, matched for age and I.Q., only tests with a single presentation of the material to be remembered were affected at follow-up . The speed of information processing was also significantly reduced . Age was strongly related to memory performance in the patient group alone and interacted with dose and duration of treatment . Results suggest that drug-induced slowing of mentation was responsible for impaired encoding, particularly in older patients . These findings affect treatment strategies, especially now that injections of botulinum toxin have proved to be highly effective for certain forms of focal dystonia. Neurol Clin, 1991 Feb, 9(1), 205 - 24 Botulinum toxin therapy; Savino PJ et al.; Botulinum toxin therapy has emerged as a treatment modality for a variety of spastic- or contracture-related muscle diseases . Its safety has been proven for long-term use in the treatment of benign essential blepharospasm, hemifacial spasm, and certain types of strabismus . Recent approval from the Federal Drug Administration should make botulinum toxin available for use in a greater number of patients. Arch Neurol, 1991 Feb, 48(2), 221 - 3 Posttraumatic torticollis; Truong DD et al.; We report six cases of torticollis precipitated by neck trauma . The dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion, lack of improvement after sleep ("honeymoon period"), and absence of geste antagonistique . Worsening with action was not present; nor was there improvement with support as seen with idiopathic torticollis . Onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features . Anticholinergic therapy was without benefit; however, some improvement occurred with botulinum toxin injection . It is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics. Ann Otol Rhinol Laryngol, 1991 Feb, 100(2), 85 - 9 Laryngeal dystonia: a series with botulinum toxin therapy; Blitzer A et al.; Laryngeal dystonia is a syndrome characterized by action-induced, involuntary spasms of the laryngeal muscles . Most patients have involvement of the adductor laryngeal muscles producing uncontrolled spasms during phonation, and a "strain-strangle" speech pattern commonly termed "spastic dysphonia." Other patients have involvement of the abductor muscles producing "whispering dysphonia." Rare patients have paradoxical vocal cord motion during respiration with adductor spasms on inspiration . Over the past 5 years we have used botulinum toxin (BOTOX) to treat more than 200 patients with laryngeal dystonia . This group includes patients with adductor involvement (phonatory dystonia, recurrent laryngeal nerve section failure, respiratory dystonia) and those with abductor involvement (whispering dystonia) . Patients received benefit within 24 to 72 hours, with sustained improvement for 2 to 9 months with an average of 4 months . Patients improved to an average of 90% of normal function . Clinically significant adverse effects included extended breathy dysphonia and mild choking on fluids . BOTOX has become our treatment of choice for dystonic conditions of the larynx. Plast Reconstr Surg, 1991 Feb, 87(2), 285 - 9 Botulinum A toxin for the treatment of adult-onset spasmodic torticollis; Borodic GE et al.; Thirty-five patients with adult-onset idiopathic torticollis were treated by local injections of botulinum A toxin into dystonic cervical muscles . Substantial improvement with respect to reduction and elimination of pain was found in 81 percent, improvement in posture deformity and involuntary spasms in 70 percent, increased range of motion of the neck in 78 percent, reduction in visible sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65 percent . The syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia, head and shoulder posture, and sternocleidomastoid muscle hypertrophy . Injection strategy based on this subdivision is described. J Biol Chem, 1991 Jan 15, 266(2), 1289 - 98 Low molecular weight GTP-binding proteins in human neutrophil granule membranes; Philips MR et al.; Degranulation of neutrophils involves the differential regulation of the exocytosis of at least two populations of granules . Low molecular weight GTP-binding proteins (LMW-GBPs) have been implicated in the regulation of vesicular traffic in the secretory pathways of several types of cells . In the present study we identify distinct subsets of LMW-GBPs associated with the membranes of neutrophil-specific and azurophilic granules . Ninety-four percent of total {35S}guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding activity was equally distributed between the plasma membrane and cytosol with the remaining 6% localized in the granules . In contrast, the cytosol contained only 10% of the total GTPase activity while the specific granules accounted for 13% . {alpha-32P}GTP binding to proteins transferred to nitrocellulose revealed LMW-GBPs in all fractions except the azurophilic granules . The specific granules contained three out of four bands which were found in the plasma membrane; these ranged from 20 to 23 kDa and all were resistant to alkaline extraction . Photoaffinity labeling with {alpha-32P}8-azido-GTP in the presence of micromolar Al3+ identified proteins of 25 and 26 kDa unique to azurophilic granules; these could not be labeled with {alpha-32P}8-azido-ATP and could be extracted by acidic but not alkaline pH . Botulinum C3-mediated {32P}ADP-ribosylation identified proteins of 16, 20, and 24 kDa both in plasma membranes and those of specific granules . An anti-ras monoclonal antibody, 142-24E5, recognized a 20-kDa protein localized to the plasma and specific granule membranes which could not be extracted by alkaline pH, was not a substrate for botulinum C3 ADP-ribosyltransferase, and was translocated from specific granules to plasma membrane after exposure of neutrophils to phorbol myristate acetate . We conclude that neutrophil-specific and azurophilic granules contain distinct subsets of LMW-GBPs which are uniquely situated to regulate the differential exocytosis of these two compartments. Neurosci Lett, 1991 Jan 14, 122(1), 132 - 4 Cooperative action of the light chain of tetanus toxin and the heavy chain of botulinum toxin type A on the transmitter release of mammalian motor endplates; Weller U et al.; Purified heavy chain of botulinum toxin type A and light chain of tetanus toxin were combined to form a chimeric toxin . It was active on the mouse phrenic nerve-hemidiaphragm with a potency 6 times higher than that of native tetanus toxin . Electrophysiological data from poisoned neuromuscular junctions revealed that the pattern of nerve-evoked and spontaneous transmitter release was equivalent to that seen with tetanus toxin i.e . asynchronous release, and did not resemble that after botulinum toxin type A poisoning . We conclude that the light chain of tetanus toxin alone is responsible for the characteristic effects on spontaneous and nerve-evoked transmitter release of the native toxin and that these properties can be introduced into a new, more potent complex with the heavy chain of botulinum toxin A. Eye, 1991, 5 ( Pt 1), 45 - 7 Early botulinum toxin treatment of acute sixth nerve palsy; Murray AD; Eight patients with total sixth nerve palsy were treated with botulinum toxin injection to the antagonist non-paretic medical rectus, within eight weeks of the onset of the palsy . Within a few days seven of the eight gained fusion without the necessity of a marked head turn, and none complained of confusing reversal of diplopia . The same seven recovered full function . The mean follow-up period after the last injection was 20 months . Seven palsies were the result of head trauma and one was due to cerebro-vascular disease . This preliminary report suggests that early botulinum toxin injection of patients with recent onset sixth nerve palsy is beneficial . Although all of the patients may possibly have recovered full lateral rectus function without treatment, the aetiologies of their palsies were of the type that frequently do no resolve . A randomised double-blind study is necessary more precisely to determine the effectiveness of this form of therapy. Neuroscience, 1991, 41(1), 71 - 88 Characteristics of slow-miniature endplate currents show a subunit composition; Vautrin J et al.; The normal neuromuscular junction shows two classes of spontaneous miniature endplate potentials . These classes are based on a discontinuity in the profile of miniature endplate potential amplitude distributions . The amplitude of one class of miniature endplate potentials from a bell-shaped amplitude distribution and the remaining miniature endplate potentials compose a population which forms a left-hand skew distribution with a mode 1/7 to 1/10 that of the bell-miniature endplate potentials {Kriebel M . E . and Gross C . E . (1974) J . gen . Physiol, 64, 85-103} . Some skew-miniature endplate potentials have a slow time-to-peak and show breaks on the rising phase . Most treatments that alter the miniature endplate potential frequency change the ratio of skew-miniature endplate potentials/bell-miniature endplate potentials {Kriebel M . E . et al . (1976) J . Physiol . 262, 553-581} . The time characteristics of miniature endplate currents were readily altered in the isolated frog and mouse neuromuscular junctions with several agents known to increase the percentage of slow-miniature endplate potentials (heat, botulinum toxin, 4-aminoquinoline and increases in bath osmolarity) . The slow-miniature endplate potential amplitudes were a continuum of amplitudes from skew- to giant miniature endplate potentials . The rising phases of miniature endplate potentials were a continuum from smooth to many with breaks and offsets . In a series of sequentially recorded slow-miniature endplate currents, many had congruent rising phases of constant slope regardless of amplitude or of time-to-peak . The rising phases of congruent slow-miniature endplate currents which showed a change in slope deviated at similar amplitudes . The least value of the slope of a slow-miniature endplate current was that of the sub-miniature endplate current; and, miniature endplate currents with overall lower slope values showed a wave pattern and/or irregular breaks which suggests summation of sequentially delayed sub-miniature endplate currents . Plots of the amplitude vs time-to-peak of miniature endplate currents from identified junctions demonstrated that the normal percentage of slow-miniature endplate currents was greatly increased with the treatments used here and that the time-to-peak of giant miniature endplate currents usually was longer than that of normally occurring bell-miniature endplate currents . Giant miniature endplate currents with short time-to-peak values are probably from two miniature endplate currents occurring, by chance, almost simultaneously . During and/or after treatments, miniature endplate currents formed clusters of similar size miniature endplate currents, not randomly distributed in time, which graded from distinct miniature endplate currents to giant miniature endplate currents.(ABSTRACT TRUNCATED AT 400 WORDS) Mov Disord, 1991, 6(2), 174 - 6 Jaw dystonia triggered by biting into hard food; Lagueny A et al.; We report an unusual case of eating dystonia induced by attempts to bite into hard food and resulting in prolonged jaw opening spasms . Mastication was severely impeded . Simultaneous bilateral electromyogram (EMG) of the masticatory muscles during mastication of hard food showed an abnormal prolonged activity in the anterior digastrics with an abnormal cocontraction of these muscles during contraction of the jaw-closers and a prolonged inhibition of the jaw-closers until the hard bolus was softened . This action dystonia seems to be triggered when more than a certain pressure is exerted on the peridontal mechanoreceptors and could result from a defective central command control of their sensory inputs . Local injections of botulinum toxin had little effect. Mov Disord, 1991, 6(2), 145 - 50 Treatment of idiopathic spasmodic torticollis with botulinum toxin A: a double-blind study on twenty-three patients; Lorentz IT et al.; In a double-blind, placebo-controlled study, 23 patients suffering from intractable spasmodic torticollis (ST) were given successively either botulinum toxin A (BTA) or normal saline by intramuscular injections in the affected muscles . Evaluation was carried out by three blinded observers, using a clinical and video assessment of the severity of torticollis, employing a scoring system described by Tsui (1) . Patients were also asked to subjectively comment on changes in the amount of pain and on changes in the activities of daily living (ADL) . BTA was proven to be superior on all forms of assessment to placebo, and these results were statistically significant . Side effects mainly consisted of pain at the injection site . Tiredness occurred at equal frequency with BTA and placebo . No serious or systemic side effects were noted . Botulinum toxin is a safe, effective and relatively simple treatment for spasmodic torticollis. Toxicon, 1991, 29(2), 181 - 9 The translocation of botulinum A neurotoxin by chromaffin cells is promoted in low ionic strength solution and is insensitive to trypsin; Marxen P et al.; Botulinum A neurotoxin (BoNtx) produced a partial inhibition of carbachol induced 3H-noradrenaline (3H-NA) release from bovine adrenal chromaffin cells in monolayer culture . Each of the polysialogangliosides GD1a, GT1b and GD1b enhanced the block of exocytosis when they were applied prior to the toxin exposure . The monosialoganglioside GM1 was not effective . Chromaffin cells treated with neuraminidase lost their sensitivity to BoNtx . Application of gangliosides to these cells, however, restored their susceptibility to the toxin . Treatment of the cells with trypsin did not affect the BoNtx-blockade of 3H-NA-release . The potency of botulinum A toxin was increased in a solution of low ionic strength in which sodium chloride was replaced by sucrose . In agreement with the potency of botulinum A neurotoxin in blocking exocytosis under the various conditions, binding of 125I-botulinum A neurotoxin to chromaffin cells was enhanced in low ionic strength solution and by pretreatment of the cells with gangliosides . The binding was decreased by digestion of gangliosides with neuraminidase . It is concluded that botulinum A neurotoxin binds exclusively to polysialogangliosides which subsequently serve as carriers for the toxin . The low ionic strength may increase some physico-chemical interaction of the toxin with the polysialogangliosides. Rinsho Shinkeigaku, 1991 Jan, 31(1), 32 - 7 {Treatment of focal dystonia with botulinum toxin}; Nagamine T et al.; We have studied the effect of botulinum toxin in patients with focal dystonia, not responding sufficiently to medical therapy . Injection of 5-100 units to the muscles, selected by EMG and clinical examination, invariably resulted in reduction of muscle tonus, although to a different degree depending on the dosage . The outcome after the first trial was best when dealing with small muscles in patients with blephalospasm or Meige's syndrome . In contrast, several attempts were required for the treatment of a large muscle as in torticollis, or multiple muscles as in writers' cramps . The effect lasted 1-3 months . With precise selection of the affected muscles and careful regulation of necessary dosages, this type of therapy may contribute to the treatment of focal dystonia. Invest Radiol, 1991 Jan, 26(1), 58 - 64 Proton magnetic resonance spectroscopic studies of hypertrophied muscle . Effect of botulinum toxin treatment; Narayana PA et al.; In vivo image-guided localized proton magnetic resonance spectroscopy (MRS) studies have been performed in a patient with hypertrophied tibialis anterior (TA) muscle and following two injections of botulinum toxin into the affected muscle . Prior to treatment, lipid levels in hypertrophied muscle were found to be low compared to normal . Lipid levels were observed to approach control levels after the second injection . Three months following treatment the trend in exercise-induced changes in lipids was observed to be similar between the hypertrophied and normal TA muscle . This preliminary report demonstrates the potential clinical utility of MRS in evaluating patient response to medical treatment. Eur Neurol, 1991, 31(1), 44 - 6 Hyperkinesias after hypoglossofacial nerve anastomosis--treatment with botulinum toxin; Dressler D et al.; Hypoglossofacial nerve anastomosis is a successful method for restoration of facial nerve function . Facial hyperkinesis, however, are a common side effect of this therapy and have been a major therapeutical problem ever since . We are reporting a patient whose facial hyperkinesias responded favourably to botulinum toxin carefully injected into the most affected muscles . EMG studies are illustrating the effect of botulinum toxin on the facial hyperkinesias as well as on voluntary muscle activation. Wien Klin Wochenschr, 1991, 103(1), 15 - 20 {Therapeutic possibilities in spasmodic torticollis}; Wober C et al.; Spasmodic torticollis is classified as a focal dystonia . It is characterized by involuntary contractions of the muscles of the neck, with consequent deviation of the head from the correct posture . Psychological factors are recognized as important trigger and aggravating mechanisms . The various possibilities of therapeutic management (medical and surgical treatment, psychological methods and psychotherapy) are reviewed . Therapy of spasmodic torticollis should be started with methods such as biofeedback, behaviour therapy, and anticholinergic drugs . If these procedures not successful, local application of botulinum toxin offers a new and highly effective technique . Surgical treatment such as neurotomy, rhizotomy, or stereotaxic operations should be restricted to otherwise intractable cases. Mov Disord, 1991, 6(1), 55 - 9 Writer's cramp: treatment with botulinum toxin injections; Rivest J et al.; Twelve patients with writer's cramp were treated with injections of botulinum toxin . The overactive muscles were identified by clinical observation of the subjects while they were writing . Repeated injections were given at 2-week intervals until the optimal response was obtained . Eleven patients reported some benefit, which was considered by seven to be significant . Eight of the 10 patients who had pain reported moderate to significant relief . Five patients had local complications, consisting of disabling weakness of target or neighbouring muscles . These preliminary results suggest that this treatment can be successfully applied to many patients with writer's cramp without performing complex electromyographic recordings while the patients are writing. Mov Disord, 1991, 6(1), 29 - 35 Is focal hand dystonia associated with psychopathology? Grafman J, Cohen LG, Hallett M. The purpose of this study was to determine if patients with focal hand dystonia have any significant psychopathology . We studied 20 patients with hand cramps who were participating in a therapeutic trial of botulinum toxin injections . Patients were interviewed and administered the Minnesota Multiphasic Personality Inventory (MMPI) . Beck Depression Inventory, Spielberger State-Trait Anxiety Scale, a finger tapping test, and a choice serial reaction time test . Behavioral ratings were also obtained . Group statistics indicated that all personality scale scores and performances on motor tasks were within normal limits . Four out of 20 patients demonstrated mild depression . Trait anxiety scores were higher than state anxiety scores, suggesting that receiving medical treatment had a beneficial effect on mood . The number of depressive symptoms endorsed on the MMPI was correlated with reaction time speed but not finger dexterity . None of the 20 patients reported a remarkable psychiatric history . These results indicate that hand cramps are not associated with serious psychopathology. Toxicon, 1991, 29(8), 913 - 36 Cellular and molecular actions of binary toxins possessing ADP-ribosyltransferase activity; Considine RV et al.; Clostridial organisms produce a number of binary toxins . Thus far, three complete toxins (botulinum, perfringens and spiroforme) and one incomplete toxin (difficile) have been identified . In the case of complete toxins, there is a heavy chain component (Mr approximately 100,000) that binds to target cells and helps create a docking site for the light chain component (Mr approximately 50,000) . The latter is an enzyme that possesses mono(ADP-ribosyl)transferase activity . The toxins appear to proceed through a three step sequence to exert their effects, including a binding step, an internalization step and an intracellular poisoning step . The substrate for the toxins is G-actin . By virtue of ADP-ribosylating monomeric actin, the toxins prevent polymerization as well as promoting depolymerization . The most characteristic cellular effect of the toxins is alteration of the cytoskeleton, which leads directly to changes in cellular morphology and indirectly to changes in cell function (e.g . release of chemical mediators) . Binary toxins capable of modifying actin are likely to be useful tools in the study of cell biology. Acta Neuropathol (Berl), 1991, 82(2), 134 - 42 Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetylcholine; Sket D et al.; Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions . The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures . In parallel experiments, acetylcholinesterase (AChE) activity was measured and the functional state of muscles in experimental groups was determined by electrophysiological methods . The results show that pretreatment with BTx almost completely protects the muscles from DFP-induced spontaneous activity and lesions in spite of critically inhibited synaptic AChE . These results are consistent with the conclusion that the effect is not mediated by direct action of organophosphate on muscle, but by the accumulation of ACh resulting in muscle hyperactivity . Therefore, it is concluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonquantal ACh release, which is only partially affected in BTx-blocked nerve endings, seems not to be involved. J Ocul Pharmacol, 1991 Summer, 7(2), 169 - 73 Reduction of cat eye movements using retrobulbar botulinum toxin; Zimm J et al.; We studied the effects of a single retrobulbar injection of Botulinum toxin on the motility of cat eyes . Four cats were sedated and the opposite eye served as a control . Eye movements were plotted by reflecting a laser beam from a mirror fixed to the cornea . We found the mean degrees of deviation per eye per day and summarized these results as mean degrees of deviation per eye per week +/- standard deviation . Statistical analysis was accomplished using Student's t test for independent measures, since measurement of the treated eye pairs was done in a randomized manner on different test days . (table; see text) These results indicate that a single retrobulbar dose of Botulinum toxin can produce a paralysis of the ocular musculature lasting in excess of four weeks in a specific and reproducible manner . In addition, this methodology should prove useful in future experiments in which ocular motility might prove to be a technical concern. Stereotact Funct Neurosurg, 1991, 57(3), 113 - 22 Selective peripheral denervation in patients with spasmodic torticollis; Braun V et al.; The results of selective peripheral denervation of the involved muscles in 35 patients with spasmodic torticollis are reported . We modified the operation first described by Bertrand . Follow-up was 3 months to 2.5 years in 34/35 patients . 73% noticed a significant improvement or disappearance of dystonia and pain following surgery and physiotherapy for 3 months postoperatively . Selective peripheral denervation is recommended for patients with spasmodic torticollis of at least 1-2 years duration which is resistant to conservative treatment . It may also be used in patients who do not respond to injection of botulinum A toxin or who develop resistance to this kind of therapy. Arch Neurobiol (Madr), 1991, 54 Suppl 3, 44 - 51 {Focal dystonias and facial hemispasm: treatment with botulinum A toxin}; Astarloa R et al.; We report the results of the treatment of 80 patients with various idiopathic focal dystonia and essential hemifacial spasm with Botulinum A toxin . A statistically significant improvement was obtained in our 34 patients with blepharospasm, 19 patients with hemifacial spasm, 59% of 22 patients with cervical dystonia and 60% of 5 patients with hand dystonia . Mean duration of the benefit of each injection was 15.3, 16.3, 7.6 and 8.7 weeks respectively . Adverse effects were local and transient . We concluded that botulinum A toxin is a safe and effective therapy for patients with focal dystonia and hemifacial spasm. Arch Neurobiol (Madr), 1991, 54 Suppl 3, 40 - 3 {Treatment with botulinum toxin in blepharospasm}; Grandas F; Blepharospasm is a cranial dystonia characterized by forceful spasms of the orbicularis oculi muscle which may lead to functional blindness in approximately two-thirds of patients . Botulinum toxin injections is a simple procedure, very effective and with little morbidity . It is considered as the treatment of choice for patients with disabling blepharospasm. Arch Neurobiol (Madr), 1991, 54 Suppl 3, 32 - 9 {Advances in the treatment of the dystonias}; Gimenez-Roldan S; Except in Wilson's disease, few secondary dystonias are susceptible te benefit from an etiological treatment . The somatic distribution of dystonia often determines the therapeutic strategy . Thus, stereotactic surgery may be the treatment of choice for hemidystonia while anticholinergic medication may alleviate generalized dystonia, particularly in childhood . Finally, local infiltrations of botulinum toxin are particularly useful for various forms of local and segmental dystonia . Certain subsyndromes as myoclonic dystonia, levodopa sensitive dystonia and paroxysmal choreoathetosis may benefit from relatively specific treatment strategies. Acta Med Austriaca, 1991, 18(5), 125 - 9 {Botulinum toxin A in therapy of craniocervical dystonias and hemifacial spasm}; Thill R et al.; 34 patients with focal dystonias (13 with essential blepharospasm, 3 with Meige's syndrome, 2 with hemifacial spasm, 16 with spasmodic torticollis) were treated with botulinum type A toxin . 4 ng of botulinum type A toxin per eye were applied in the M . orbicularis oculi as first injection in the 18 patients without spasmodic torticollis . The 16 patients with idiopathic spasmodic torticollis received 10 ng botulinum toxin A in the contralateral M . sternocleidomastoideus as well as in the ipsilateral M . splenius capitis as first injection . The effect was monitored for a time period of at least 6 weeks by two subjective rating scores, a visual functional score and a global clinical impression score . Patients with blepharospasm showed a distinct improvement already after 4 days which lasted for 6 weeks . 75% of the patients with spasmodic torticollis experienced a moderate to distinct improvement after 4 days which remained stable for 6 weeks . A second injection was performed in 15 (7 blepharospasm, 8 spasmodic torticollis) patients 9-11 weeks later with a similar success . All observed side effects (weakness; stiffness of local muscles; feeling of dryness of eyes, unilateral ptosis) were mild and of transient nature . We suggest therefore botulinum type A toxin as treatment of first choice in focal dystonias. Ann Otolaryngol Chir Cervicofac, 1991, 108(8), 477 - 82; discussion 482-3 {Treatment of spasmodic dysphonia with botulinum toxin}; Klap P et al.; Spasmodic dysphonia is a focal laryngeal dystonia, a rare form of dystonia . Videostroboscopy, acoustic analysis, computerized voice analysis and over all electrophysiological analysis allow for the study of the different muscles involved in this dysphonia . There are two types of spasmodic dysphonia: adductor spasmodic dysphonia and abductor spasmodic dysphonia . The most efficient therapy nowadays is the injection of botulinum toxin into the thyroarytenoid muscle under fiberoptic visualization . We report 6 patient's cases of spasmodic dysphonia that we have been treating for about 2 years by direct injection of botulinum toxin in the vocal cords. Fortschr Ophthalmol, 1991, 88(4), 411 - 5 {Changes in the blink reflex in patients with essential blepharospasm and hemifacial spasm}; Roggenkamper P et al.; Electrophysiological investigations have been carried out in 46 patients with essential blepharospasm and 41 with hemifacial spasm . In both diseases reproducible pathologic alterations in the blink reflex were found . In essential blepharospasm a direct R1/R2 transition and a contralateral early component with and without direct transition into the R2C component were recorded . In patients with hemifacial spasm there was a loss of the R1 component in addition . In repeated treatments with botulinum toxin the amplitude (R1,R2) of the blink reflex was reduced in some cases, although in some cases the intensity of spasm was as high as before treatment once the effect had faded. Neuroreport, 1991 Jan, 2(1), 33 - 6 Tetanus and botulinum A toxins inhibit stimulated F-actin rearrangement in chromaffin cells; Marxen P et al.; Tetanus and botulinum A neurotoxins block exocytosis of noradrenaline in chromaffin cells . During exocytosis vesicles fuse with the plasma membrane . This requires an intact cytoskeleton . The cytoskeleton can be displayed by rhodamine-labelled phalloidin binding to F-actin . When chromaffin cells are stimulated with carbachol, F-actin forms clusters close to the plasma membrane . On withdrawal of the secretagogue the stimulated cells revert to their original appearance . The conversions, like exocytosis, depend on the presence of Ca2+, indicating the association of exocytosis with F-actin arrangement . When exocytosis is blocked in chromaffin cells by tetanus or botulinum A neurotoxins, F-actin fails to cluster during nicotinic stimulation . Thus, the toxins act somewhere between the rise in intracellular free Ca2+ and the rearrangement of F-actin. Arch Oral Biol, 1991, 36(11), 827 - 36 Ultrastructural changes in the masseter muscle of Macaca fascicularis resulting from intramuscular injections of botulinum toxin type A; Capra NF et al.; Intramuscular injections of botulinum toxin type A (Oculinum) is used to treat strabismus and focal dystonias affecting orofacial muscles . However, the toxin-induced morphological changes that underlie the therapeutic alterations of tone in the muscles of mastication have not been described . In this study, paired intramuscular injections of botulinum toxin (10 units) were made in three adult monkeys (Macaca fascicularis) allowed to survive 14, 28 and 63 days . Another monkey received multiple injection-pairs over 84 days . Animals were killed by deep pentobarbital anaesthesia before transcardiac perfusion-fixation . Tissue sampled from comparable regions of the injected masseter, the uninjected masseter and an uninjected animal was processed for ultrastructural analysis . Few changes were found 14 days post-injection . However, muscle fibres showed myofibrillar dissolution, aberrations in the Z-line, and enlarged mitochondria in the region of the I-band by 28 days . In the 63-day and 84-day animals, the injected muscle was considerably smaller than the uninjected, contralateral muscle . Regions of the injected muscle contained fibres with markedly reduced cross-sectional area . Internalization of myonuclei, loss of myofibrillar organization, and helical complexes were common . Toxin-induced changes, though similar to those that follow denervation by axotomy, were not accompanied by degeneration of neuromuscular junctions . Instead, morphological evidence for axonal sprouting in the region of the neuromuscular junction, possibly contributing to functional recovery, was seen as early as 14 days in toxin-treated muscles. Eye, 1991, 5 ( Pt 4), 451 - 5 Treatment of strabismus after retinal detachment surgery with botulinum neurotoxin A; Lee J et al.; Thirty-one consecutive patients were treated with injections of Botulinum Neurotoxin A to rectus muscles for strabismus following retinal detachment surgery . In 14 cases the presenting problem was diplopia and in 17 cases the presenting problem was cosmetic appearance . A total of 67 injections was given . Twenty-seven cases had nine months or more follow-up . Of these, four of 11 cases with diplopia had fusion restored, four were shown to have no fusion potential, and three had temporary improvement only . In 16 cases with a primary cosmetic problem there was no useful effect in two, three had surgery as an alternative, three were realigned long-term, and eight had continuing maintenance therapy with toxin . Over half the series had undergone multiple detachment surgery, often for giant tears and other complex pathology. Eye, 1991, 5 ( Pt 4), 447 - 50 Binocular diplopia in unilateral aphakia: the role of botulinum toxin; Hakin KN et al.; We have treated 12 unilaterally aphakic patients, with a manifest squint and binocular diplopia, with botulinum toxin injection to the appropriate horizontal rectus muscle, in an attempt to reduce the angle of squint and thereby resolve the diplopia . In all cases a short-term reduction in the angle of squint was achieved . In nine patients, whose aphakia was corrected with a contact lens, and eight of whom had had their lenses removed because of trauma, this reduction was only temporary . In three patients, however, who had had a non-traumatic cataract removed, replaced with a posterior chamber implant, control of the deviation was maintained long after the acute effect of the toxin had disappeared, with the development of coarse binocular single vision, a fusion range, and abolition of all diplopia . The possible reasons for these different responses are discussed and it is suggested that in cases of binocular diplopia following lens extraction, botulinum toxin treatment should be considered prior to any extraocular muscle surgery, as temporary reduction of the deviation may be sufficient to allow recovery of binocular single vision. Ophthal Plast Reconstr Surg, 1991, 7(1), 54 - 60 Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy; Borodic GE et al.; Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects . All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease . A study of the innervation zone {distribution of neuromuscular junctions (NMJ)} was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery . There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining . Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid . Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm . Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods . Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse . Thus, we conclude that multiple injections are superior to the injection of a single motor point. Lakartidningen, 1990 Dec 19, 87(51-52), 4408 - 10 {Injection of botulinum toxin as a new treatment of torticollis}; Aquilonius SM et al.; Thirty patients with spasmodic torticollis were injected with Botulinum A toxin into sternomastoid and posterior neck muscles . Neurophysiological investigation showed neuromuscular transmission in the sternomastoid muscle to be impaired already within the first day after injection of 50 U toxin . Signs of denervation were discernible after seven days, and of reinnervation after two weeks . As assessed by 'blind' ratings of videotapes, 78 per cent of the patients improved, as compared with the figure of 87 per cent based on clinical evaluation . When injections were repeated every third month, there was a tendency for symptomatic effects to increase with time . Side effects were mild and transient . Thus local injections of botulinum toxin would seem to be the treatment of choice in this form of dystonia. FEBS Lett, 1990 Dec 17, 277(1-2), 171 - 4 Light chain of botulinum neurotoxin is active in mammalian motor nerve terminals when delivered via liposomes; de Paiva A et al.; Liposomal encapsulation of the individual light and heavy chain of botulinum neurotoxin A was used to investigate their intra-cellular effects on synaptic transmission at the murine neuromuscular junction . Bath-application to phrenic nerve-hemidiaphragms of liposomes containing heavy chain (up to 75 nM) caused no alteration in neurally-evoked muscle tension . In contrast, liposomes with entrapped light chain (9-20 nM final concentration) gave a pre-synaptic blockade of neuromuscular transmission that could be relieved temporarily by 4-aminopyridine, as for the dichain toxin . Any contribution from contaminating intact toxin was excluded both by the purity and minimal toxicity in mice of the light chain preparations used, and by the lack of neuromuscular paralysis seen with liposomes containing the maximum amount of native toxin that could have been present in the light chain liposomes . As bath-application of high concentrations of light chain in the absence of liposomes failed to affect neurotransmiter release, it is concluded that this chain alone can mimic the action of the whole toxin inside mammalian motor nerve endings, its predominant site of action . Thus, light chain could provide a more effective probe for an intra-cellular component concerned with Ca2(+)-dependent secretion. Am J Ophthalmol, 1990 Dec 15, 110(6), 674 - 82 Ocular movements in essential blepharospasm; Demer JL et al.; In essential blepharospasm histopathologic and electrophysiologic evidence supports the existence of lesions in proximity to brainstem nuclei controlling ocular movements . We studied horizontal ocular movements in eight patients who had been treated previously with surgery or botulinum toxin injection to control essential blepharospasm (mean age, 58 years) and compared these with seven control subjects who did not have blepharospasm (mean age, 68 years) . We examined fixation stability, saccades, the vestibulo-ocular reflex, visual enhancement and suppression of the vestibulo-ocular reflex, optokinetic nystagmus, and pursuit by using digitally sampled, direct current electro-oculography . Patients with blepharospasm exhibited no ocular movement abnormalities . Since quantitative aspects of ocular movements are sensitive to nonspecific brainstem lesions, the absence of abnormal ocular movements suggests that the lesion in blepharospasm is specifically limited to neurons regulating the facial muscles. Axone, 1990 Dec, 12(2), 40 - 3 Blepharospasm, hemifacial spasm and the nurse's role; Kinash RG et al.; Blepharospasm and hemifacial spasm are involuntary movement disorders that affect the facial muscles . They are classified as cranial dystonias . Their cause is unknown and the underlying pathophysiology is poorly understood . Both dystonias are more common in women than in men . It is the middle-aged group that is most frequently affected . Because of their high visibility, these disorders may cause considerable distress and embarrassment . Affected persons are often mistakenly considered to have psychiatric problems . In addition, both dystonias may result in severe disability . For example, the person with untreated blepharospasm may experience social isolation and functional blindness . Recently, therapy in the form of botulinum toxin became available in larger centers . Repeated injections of the toxin usually relieves symptoms and enable patients to resume a former lifestyle . Neuroscience nurses who are knowledgeable about cranial dystonias and the resources that are currently available can retard progression of disability and help restore the individual's quality of life . Informed neuroscience nurses can also play an important role in case-finding, counselling and referral . Two examples are presented in order to highlight some of the complexities inherent in the diagnosis and treatment of each type of cranial dystonia and to further clarify the nurse's role . These examples are based on the personal and professional experience of the authors. Biull Eksp Biol Med, 1990 Dec, 110(12), 637 - 8 {State of coagulation hemostasis and fibrinolysis processes in dynamics of rapidly progressing forms of botulinal intoxication}; Chesnokova NP et al.; Phase disturbances of coagulation blood potential were revealed in experiments on white rats in dynamics of rapidly progressing form of botulinic intoxication, intoxication being caused by intraperitoneal injection of type C toxin . In preclinical period of intoxication activation of procoagulant and anticoagulant parts of hemostasis system, as well as fibrinolysis system, was noted . Similar shifts were revealed in the developmental period of generalized pareses of skeletal musculature . Only in the terminal stage of intoxication insufficiency of mechanism in formation of prothrombinase activity developed by simultaneous activation of anticoagulant mechanism and fibrinolysis system. Ital J Neurol Sci, 1990 Dec, 11(6), 589 - 93 Botulinum A toxin injection in patients with blepharospasm, torticollis and hemifacial spasm; Berardelli A et al.; Botulinum A toxin was injected into the affected muscles in 20 patients with blepharospasm, 8 with torticollis and 12 with hemifacial spasm . In all cases blepharospasm and hemifacial spasm was abolished or markedly reduced . The only side effect was transient ptosis and diplopia . Patients with torticollis had a mild to moderate improvement of the dystonic posture and pain; dysphagia was the most troublesome side effect . Botulinum A toxin is an effective therapy in patients with focal dystonia and spasms. J Protein Chem, 1990 Dec, 9(6), 705 - 13 Structural analysis of botulinum neurotoxin types A and E in aqueous and nonpolar solvents by Fourier transform infrared, second derivative UV absorption, and circular dichroic spectroscopies; Singh BR et al.; Two pharmacologically similar but antigenetically distinct botulinum neurotoxins, types A and E with a 1000-fold difference in their toxicity, were examined for nonpolar solvent-induced changes in secondary structures and polypeptide foldings to understand their structural differences and their comparative responsiveness/susceptibility to solvent perturbation . Analysis of far UV circular dichroic spectra in aqueous buffer for types A and E neurotoxins yielded the following: the alpha-helix contents were 27 and 20%; the beta-sheets were 36 and 44%, the beta-turns were 6.0 and 0%, and the random coils were 31 and 36%, respectively . Fourier transform infrared spectra, obtained by using attenuated total reflection technique, indicated high content of alpha-helix and beta-pleated sheet structures for both neurotoxins as judged by strong bands at 1651 and 1633 cm-1 in the amide I frequency region and bands at 1314 and 1245 cm-1 in the amide III frequency region . The peak height ratio of 1314 and 1245 cm-1 bands, suggests that the type A neurotoxin has slightly higher alpha-helical content than the type E neurotoxin . These observations are consistent with the secondary structures estimated from far UV circular dichroic spectra . Fourier transform infrared spectra of the neurotoxins, exposed to methanol, showed sharp increases of the 1651 cm-1 band and a significant increase in the height of the 1314 cm-1 band, suggesting increases in the alpha-helical contents of the proteins . The changes were more in the type A than in the type E neurotoxin . The changes were reversible upon reexposure of the proteins to the aqueous buffer . Second derivative absorption spectroscopy demonstrated that methanol also induced changes in the degree of Tyr exposure to solvent . The results are discussed in terms of structural differences between the single and dichain neurotoxins and in terms of their mode of action. Schweiz Rundsch Med Prax, 1990 Nov 27, 79(48), 1512 - 4 {The role of botulinum toxin in the treatment of essential blepharospasm}; Safran AB; Benign essential blepharospasm is a focal dystonia consisting in involuntary closure of the eyelids . Until early 80's, therapeutic modalities included only psychotropic drugs, biofeedback and surgery, which showed limited efficiency . Recently, it has been suggested to inject botulinum toxin in affected palpebral orbicularis muscles . Used in several thousands of patients, it has been found that this procedure provides significant temporary relief from spasms of the eyelids . Local side effects are minimal, and no systemic side effects have been demonstrated in patients with blepharospasm treated with botulinum toxin. FEBS Lett, 1990 Nov 12, 274(1-2), 111 - 4 Interaction