J Voice, 1999 Dec, 13(4), 612 - 7 Treatment of laryngeal contact ulcers and granulomas: a 12-year retrospective analysis; Emami AJ et al.; Multiple etiological factors including gastroesophageal reflux, hyperfunctional voice use, and endotracheal intubation have been implicated in the development of posterior laryngeal ulcers and granulomas . The optimal approach to treatment of these lesions remains controversial . The mainstay of treatment at Vancouver General Hospital has been aggressive medical management of gastroesophageal reflux, with complimentary voice therapy offered to patients suspected of having significant hyperfunctional phonation . The authors reserve Botulinum toxin injection or surgical excision for patients who fail initial therapy . They conducted a retrospective analysis of their voice clinic records from 1985-1997 to examine the efficacy of this approach . They identified 76 patients with the diagnosis of contact ulcer or granuloma . Fifty-two patients had follow-up data available for review . Ninety-four percent of patients were treated nonsurgically: 35 patients were treated solely by dietary and medical therapy to control gastroesophageal reflux, 10 patients were treated by a combination of medical gastroesophageal reflux control and voice therapy, 3 patients had Botox injections, 2 patients had surgical excision of granuloma, 1 patient had a Kenalog injection, and 1 patient underwent laparoscopic fundoplication . Overall, 77% of patients had complete resolution, whereas 11% had partial resolution and another 11% had no significant improvement . The data supports control of gastroesophageal reflux as a central component in treatment of posterior laryngeal ulcers and granulomas. Curr Opin Ophthalmol, 1999 Oct, 10(5), 362 - 7 Aesthetic periocular surgery including brow, midface, and upper face; Tayani R et al.; Because of the rapid evolution and wide scope of cosmetic surgery in this decade we focus on some of the newer techniques used by oculoplastic surgeons for the rejuvenation of the periorbital area . These procedures may be used alone or as adjuncts to more established plastic surgery techniques . We discuss the role of botulinum toxin in the treatment of facial furrows, new techniques in forehead and brow suspension, the suborbicularis oculi fat suspension, and the role of chemical peels in the periorbital area, upper face, and forehead . All four of these techniques are important in addressing facial rhytids in the periorbital region . It is important to realize that in modern-day cosmetic surgery the best results are achieved using a multidimensional approach incorporating surgical procedures together with nonsurgical techniques or minimally invasive procedures. Neuroscience, 2000, 95(1), 227 - 34 Multiple types of calcium channels mediate transmitter release during functional recovery of botulinum toxin type A-poisoned mouse motor nerve terminals; Santafe MM et al.; The involvement of different types of voltage-dependent calcium channels in nerve-evoked release of neurotransmitter was studied during recovery from neuromuscular paralysis produced by botulinum toxin type A intoxication . For this purpose, a single subcutaneous injection of botulinum toxin (1 IU; DL50) on to the surface of the mouse levator auris longus muscle was performed . The muscles were removed at several time-points after injection (i.e . at one, two, three, four, five, six and 12 weeks) . Using electrophysiological techniques, we studied the effect of different types of calcium channel blockers (nitrendipine, omega-conotoxin-GVIA and omega-agatoxin-IVA) on the quantal content of synaptic transmission elicited by nerve stimulation . Morphological analysis using the conventional silver impregnation technique was also made . During the first four weeks after intoxication, sprouts were found at 80% of motor nerve terminals, while at 12 weeks their number was decreased and the nerve terminals were enlarged . The L-type channel blocker nitrendipine (1 microM) inhibited neurotransmitter release by 80% and 30% at two and five weeks, respectively, while no effects were found at later times . The N-type channel blocker omega-conotoxin-GVIA (1 microM) inhibited neurotransmitter release by 50-70% in muscles studied at two to six weeks, respectively, and had no effect 12 weeks after intoxication . The P-type channel blocker omega-agatoxin-IVA (100 nM) strongly reduced nerve-evoked transmitter release (>90%) at all the time-points studied . Identified motor nerve terminals were also sensitive to both nitrendipine and omega-conotoxin-GVIA . This study shows that multiple voltage-dependent calcium channels were coupled to transmitter release during the period of sprouting and consolidation, suggesting that they may be involved in the nerve ending functional recovery process. Dev Biol Stand, 1999, 100, 75 - 82 Alternatives to the use of animals for bacterial toxins and antitoxins; Sesardic D; The potency of several novel botulinum toxin-derived biological therapeutic products now in routine medical use is determined exclusively by in vivo methods . In addition, large numbers of animals continue to be used for the potency and safety testing of therapeutic antitoxins and toxoid vaccines . There is thus an increasing need to develop acceptable alternative assays for toxicity testing of clostridia neurotoxins which could be applied to different toxin derived therapeutic agents, including vaccines . Scientific advances in the understanding of the mode of action of clostridial neurotoxins have now provided the basis for improving conventional testing procedures. Ann Fr Anesth Reanim, 1999 Nov, 18(9), 987 - 90 {Respiratory failure caused by megaesophagus and tracheomalacia}; Galan G et al.; We report a case of acute respiratory failure in an 83-year-old woman suffering from a megaoesophagus compressing the posterior tracheal wall . Naso-oesophageal aspiration did not allow tracheal extubation because of associated tracheomalacia . Treatment included tracheostomy and decrease of cardial tonus by administration of botulinic toxin, after weaning from mechanical ventilation. J Child Neurol, 1999 Dec, 14(12), 781 - 6 Treatment of childhood myoclonus with botulinum toxin type A; Awaad Y et al.; Because of inadequate response to or intolerable side effects of oral medication, nine patients with segmental, generalized, and focal myoclonus were treated with intramuscular botulinum toxin type A . All patients were evaluated with neuroimaging, routine and limb-monitored electroencephalography, electromyography, evoked potentials and appropriate biochemical studies . Patients were aged 2 to 22 years, with duration of myoclonus from 1 month to 10 years . Multiple medication trials included antiepileptic drugs, benzodiazepines, tryptophan, L-dopa/carbidopa, baclofen, and dantrolene . Patients were injected with botulinum toxin in their affected area with electromyographic guidance to affected muscles with different doses (8 to 20 units/kg), except two patients who were injected with 32 and 45 units/kg, respectively, at 4- to 8-month intervals . One patient did not complete botulinum toxin treatment because of subjective weakness, although there were virtually no side effects reported in patients completing therapy . Patients reported a dramatic reduction in painful myoclonus . In addition, patients exhibited improved functional skills, as demonstrated by markedly improved use of affected extremities and improvements in ambulation . One patient, who was nonambulatory prior to treatment, was able to walk afterward . Long-term benefits could be related to higher dosage used or negative feedback effect. J Protein Chem, 1999 Aug, 18(6), 701 - 7 Calcein permeability of liposomes mediated by type A botulinum neurotoxin and its light and heavy chains; Fu FN et al.; The mode of botulinum neurotoxin action involves binding of its heavy chain for internalization into the presynaptic end of a nerve cell through endocytosis . The low-pH conditions of endosomes trigger translocation of the light chain across the endosomal membrane to the cytosol, where the light chain cleaves specific target proteins involved in the docking and fusion of synaptic vesicles for acetylcholine release . In an effort to model the interaction of botulinum neurotoxin and its subunit chains with lipid bilayer at low pH during the translocation process, we have examined type A botulinum neurotoxin-mediated calcein release from asolectin liposomes . At equimolar concentration (0.1 microM), the neurotoxin and its heavy and light chains evoked 23%, 58%, and 28% calcein release, respectively . Calcein release was observed only when the cis-side (the side to which neurotoxin samples were added) pH was lowered to 4 . Calcein release activity of the heavy chain was mostly blocked (76%) by a polyclonal antibody raised against the neurotoxin . Additionally, two peptide-specific polyclonal antibodies derived from the N-terminal and C-terminal halves of the heavy chain were also able to block the calcein release activity by 15-20% . In summary, these results suggest that calcein release from liposomes is specifically mediated by the heavy chain, and the light chain also integrates into the membrane . Implications of these results for the molecular mode of neurotoxin light-chain translocation across the endosomal membrane are discussed. Eur Neurol, 2000, 43(1), 9 - 12 Low-dose treatment of cervical dystonia, blepharospasm and facial hemispasm with albumin-diluted botulinum toxin type A under EMG guidance . An open label study; Rollnik JD et al.; Several studies support the hypothesis that low-dose botulinum toxin treatment may be as beneficial as high-dose regimen . Therefore, we studied 115 patients (aged 27-84; mean 58.0, SD = 12.9 years; 68% females, 32% males) suffering from cervical dystonia (n = 66), blepharospasm (n = 28), and facial hemispasm (n = 21) over a period of 2 years in an open label, non-controlled pilot study . Patients received low-dose treatment with botulinum toxin type A (Dysport((R))) . The toxin was diluted in 20 ml of 0.1% albumin solution to arrive at a concentration of 25 MU/ml and injected under EMG control . Patients responded to the treatment about 1 week after injection (mean 7.3 days, SD = 4.6) . The mean duration of beneficial effects was 11.7 weeks (SD = 5.6) . Patients evaluated the clinical global improvement on a scale ranging from 0 to 4 . For the whole population, the mean was 2.7 points (SD = 1.1) . In none of the subjects could antibodies to botulinum toxin type A be detected, and only a few side effects were observed . In conclusion, low-dose therapy with botulinum toxin A merits further controlled studies . Am J Gastroenterol, 1999 Dec, 94(12), 3434 - 9 Long-term efficacy of Botulinum toxin in classical achalasia: a prospective study; Kolbasnik J et al.; OBJECTIVE: We sought to examine the long-term efficacy of intrasphincteric Botulinum toxin A injection in a prospective cohort study of 30 patients with achalasia . METHODS: Thirty patients with classical achalasia were treated with intrasphincteric Botulinum toxin A injection . Follow-up consisted of clinical assessment, symptom scoring, and postinjection manometry . RESULTS: Symptomatic improvement for >3 months was seen in 23 of 30 patients (77%) . Of the 23 initial responders, seven (30%) experienced a sustained symptomatic response after a single Botulinum toxin injection (mean follow-up, 21 months) . The remaining 16 initial responders (70%) eventually relapsed (mean initial response, 11 months) . Nine received a 2nd Botulinum toxin injection, and seven experienced an ongoing response (mean duration, 9 months); two patients eventually required a 3rd injection with good effect (mean duration, 22 months) . The remaining seven patients who relapsed after Botulinum toxin opted for pneumatic dilation or surgical myotomy . Five of the seven patients who had no initial response received a 2nd injection but again did not respond . A residual lower esophageal sphincter pressure <18 mm Hg after the first Botulinum toxin injection predicted a good response to Botulinum therapy (single or multiple injections, p < 0.002, positive predictive value = 0.71, negative predictive value = 1.0) . Neither initial nor sustained response to Botulinum toxin could be predicted based on gender, age, duration of illness, previous pneumatic dilation, or esophageal motility before treatment . CONCLUSIONS: We found that 77% of patients with classical achalasia experienced a good symptomatic response after Botulinum toxin and 30% of initial responders achieve sustained symptomatic relief after a single treatment with Botulinum toxin . The initial responders who relapsed did well with subsequent Botulinum toxin A . Lack of an initial symptomatic response and residual lower esophageal sphincter pressure > or =18 mm Hg after Botulinum toxin are associated with a poor response. Ann Otol Rhinol Laryngol, 1999 Dec, 108(12), 1140 - 5 Laryngeal chemodenervation: effects of injection site, dose, and volume; Lee P et al.; A canine model was used to measure changes in laryngeal adductory pressure (LAP) following injections of vecuronium bromide, a short-acting neuromuscular blocking agent . At a constant volume, LAP was inversely related to the dose (and concentration) of vecuronium injected . At a constant dose (0.05 mg), LAP did not vary significantly over a wide range of injection volumes, from 0.05 to 0.50 mL . At a constant dose and volume, the site of injection was varied among the anterior, middle, and posterior vocal fold, the interarytenoid region, and the anterior contralateral vocal fold . Reduction in LAP was greatest (p<.05) for the posterior vocal fold injection site (78% reduction); less reduction was seen for the middle (54%) and anterior (52%) vocal fold and interarytenoid (43%) injection sites . These results have implications for laryngeal botulinum toxin injections, which are discussed. J Cell Biol, 1999 Dec 13, 147(6), 1249 - 60 Botulinum neurotoxin A blocks synaptic vesicle exocytosis but not endocytosis at the nerve terminal; Neale EA et al.; The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis . Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis . We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis . In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K(+)-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins . In marked contrast, K(+) depolarization, in the presence of Ca(2+), triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A-blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles . These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca(2+) is required for synaptic vesicle membrane retrieval. Am J Physiol, 1999 Dec, 277(6 Pt 2), H2222 - 32 Caveolae require intact VAMP for targeted transport in vascular endothelium; McIntosh DP et al.; Caveolae appear to function in vesicular trafficking of specific molecular cargo into and across vascular endothelial and other cells . They contain the molecular machinery for docking and fusion, similar to other vesicular trafficking systems, yet the mechanisms mediating ligand internalization and targeted intracellular transport by caveolae remain unclear . Using immunoelectron microscopy, we show that caveolae in the microvascular endothelium of rat lung express vesicle-associated membrane protein (VAMP)-2 (also called synaptobrevin) on their cytoplasmic surface . Immunofluorescence studies of cholera toxin B (CTB)-FITC internalization in toxin-treated cells demonstrate that intact VAMP-2 is necessary for the efficient trafficking of caveolar ligands . The CTB subunit binds preferentially to GM1 in caveolae, and N-ethylmaleimide treatment drastically inhibits the intracellular accumulation of CTB . The cleavage of caveolar VAMP-2 with VAMP-specific neurotoxins (botulinum D and F but not A) significantly inhibits CTB endocytosis and targeted intracellular accumulation in cultured endothelial cells . This impairment of caveolae-mediated trafficking provides evidence that caveolae require intact VAMP-2 for efficient targeted delivery via vesicle docking with target organelles. Protein Expr Purif, 1999 Dec, 17(3), 339 - 44 High-level expression, purification, and characterization of recombinant type A botulinum neurotoxin light chain; Li L et al.; Botulinum neurotoxin light chain (BoNT LC, 50 kDa) is responsible for the zinc endopeptidase activity specific for proteins of neuroexocytosis apparatus . We describe the expression of recombinant type A BoNT LC in Escherichia coli as well as the purification and characterization of the recombinant protein . A high level of expression of BoNT/A LC was obtained by an extended postinduction time of 15 h at 30 degrees C . Recombinant BoNT/A LC was isolated from an Ni(2+) column . Due to its high pI ( approximately 8.7), purification was achieved by a single step of passing the protein through anion-exchange chromatography at pH 8.0 without the need of elution . The purified recombinant BoNT/A LC retained proteolytic activity and had a secondary structure similar to that of native LC determined by CD measurement . Neurology, 1999 Dec 10, 53(9), 2102 - 7 Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up; Tan EK et al.; OBJECTIVE: To study the safety and efficacy of botulinum toxin A (BTX) in patients with oromandibular dystonia (OMD) and to compare the treatment results of the various subtypes of OMD . BACKGROUND: OMD is one of the most challenging forms of dystonia to treat . Pharmacologic therapies are generally not effective, and there are no surgical alternatives . METHODS: Of 202 patients diagnosed clinically to have OMD in a movement disorders clinic over a period of 10 years, 162 patients satisfied the study inclusion criteria . The masseters and submentalis complex were the only two muscle groups injected with BTX in this group of patients . RESULTS: The mean age was 57.9+/-15.3 years and the mean follow-up period was 4.4+/-3.8 years . More than half the patients had jaw-closing (JC) dystonia . A total of 2,529 BTX treatments were administered into the masseter muscles, submentalis complex, or both during a total of 1,213 treatment visits . The mean doses of BTX (per side) were 54.2+/-15.2 U for the masseters and 28.6+/-16.7 U for the submentalis complex . The mean total duration of response was 16.4+/-7.1 weeks . The mean global effect of BTX was 3.1+/-1.0 (range, 0 to 4, where 4 equals the complete abolition of the dystonia), with the JC dystonia patients responding best . Fifty-one patients (31.5%) reported adverse effects with BTX in at least one visit . Complications such as dysphagia and dysarthria were reported in 135 (11.1%) of all treatment visits . CONCLUSIONS: BTX is a safe and effective long-term treatment for OMD . JC dystonia responds better than jaw-opening or mixed dystonias, and the treatment of the latter types of OMD are more likely associated with dysphagia and dysarthria . Jaw-opening dystonia can be treated successfully by injecting the submentalis complex. Ophthalmology, 1999 Dec, 106(12), 2322 - 4 Successful treatment of crocodile tears by injection of botulinum toxin into the lacrimal gland: a case report; Riemann R et al.; OBJECTIVE: Pathologic lacrimation (crocodile tears) is a rare but stigmatizing symptom after facial nerve paralysis . The aim of this pilot study was to examine whether botulinum toxin injection into the lacrimal gland is effective in reducing pathologic tear secretion . DESIGN: Case report . INTERVENTION: One patient who had crocodile tears after a zoster oticus infection received a botulinum toxin injection (2.5 mouse units) into the lacrimal gland . TESTING: Before injection, 1 week, 1 month, and 6 months after injection, patient's lacrimation was assessed by a Schirmer test . RESULTS: The lacrimation of the injected eye was reduced after 1 week and equal after 1 month when compared to the healthy side . After 6 months, hyperlacrimation reoccurred . No side effects were observed . CONCLUSION: Intraglandular injection of botulinum toxin into the lacrimal gland may serve as a sufficient therapy for crocodile tears. Aviat Space Environ Med, 1999 Dec, 70(12), 1235 - 7 Dystonia, botulinum neurotoxin, and the aviator; Feinberg MJ; Dystonia is both a symptom and the name for group of illnesses called the dystonias . The physical manifestation consists of sustained, involuntary contractions of the muscles in one or more parts of the body, resulting in twisting or distortion of that part of the body . For focal dystonias including torticollis, blepharospasm and spasmodic dysphonia, botulinum toxin injections have become the treatment of choice because of the ability of this toxin to sufficiently weaken the muscle to reduce the spasm but not so much as to cause paralysis . This paper involves the fate of four airmen all afflicted with a form of dystonia who had been reviewed in the Aeromedical Certification Division of the FAA Civil Aeromedical Institute. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S35 - 8 Protection against botulinum toxins provided by passive immunization with botulinum human immune globulin: evaluation using an inhalation model; Gelzleichter TR et al.; Pentavalent botulinum toxoid adsorbed (ABCDE) vaccine is intended to protect military personnel from battlefield exposures to botulinum serotypes A-E . To determine the neutralizing antibody levels in serum that are indicative of protection against aerosolized botulinum toxins, a guinea pig model of passive antibody transfer was developed . Botulinum immune globulin (BIG), derived from plasma of vaccinated volunteers, was administered to guinea pigs by intraperitoneal injection to attain neutralizing antibody levels in serum of ca . 0.25 U ml(-1) . Control groups were treated with vaccinia immune globulin (VIG), with dosages normalized to antibody content . Neutralizing antibody levels were determined by a mouse bioassay . Twenty-four hours after BIG treatment, animals were challenged with lethal levels (target of 25 x LCt(50)) of botulinum toxins by an inhalation route . Protection was defined as 80% or greater survival for BIG-treated animals . If protective, additional groups were treated with progressively smaller BIG dosages (75% decreases per iteration) and challenged with 25 x LCt(50) until protection was no longer afforded . Greater than 80% survival was observed at target levels of 0.25 U ml(-1) for all five serotypes . Breakthrough mortality (>20%) was observed at test levels of 0.05, 0 . 004, 0.015, 0.014 and 0.003 U ml(-1) for serotypes A-E, respectively . These results, along with neutralizing antibody measurements from clinical trials, can be used to predict human efficacy following vaccination with pentavalent botulinum toxoid adsorbed (ABCDE) vaccine. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S27 - 8 Phospholipaise A2 and arachidonic acid-mediated mechanism of neuroexocytosis: a possible target of botidinum neurotoxin A other then SNAP-25; Ray P et al.; The vesicular neuroexocytosis process consists of two important steps: fusion of transmitter-loaded vesicles at release sites on the presynaptic nerve terminal membrane; followed by the release of transmitter molecules into the synaptic cleft . We previously reported that in nerve growth factor (NGF)-differentiated PC12 cells, arachidonic acid (AA) release is associated with acetylcholine (ACh) release, botulinum neurotoxin A (BoNT/A) inhibits both processes and AA itself or a phospholipase A(2) (PLA(2)) activator can cause ACh release in BoNT/A-poisoned cells in which SNAP-25 has supposedly been hydrolyzed . In the present study, we examined the roles of two endogenous intraterminal components in neuroexocytosis: the membrane fusogenic agent AA; and the vesicle fusion protein SNAP-25 . A PLA(2) activator, mastoparan, was used to induce the release of AA and ACh from NGF-differentiated PC12 cells . Release depended upon the mastoparan concentration, as well as Ca(2+) influx via the neuronal-type voltage-sensitive Ca(2+) channels . Release of ACh followed a rise in intracellular free Ca(2+) concentration; the increased Ca(2+) activated PLA(2) and, thereby, increased the AA level . Scanning and transmission electron microscopy confirmed that mastoparan-induced ACh and AA release were not due to simple diffusion through damaged plasma membranes . Treatment of PC12 cells with appropriate antisense oligonucleotides blocked SNAP-25 expression, as judged by Western blot protein analysis with a specific monoclonal antibody . Despite apparent elimination of SNAP-25, treatment of differentiated PC12 cells with mastoparan and high (80 mM) K(+) induced ACh exocytosis . The results support the conclusion that PLA(2) and AA have important roles in neuroexocytosis that are independent of SNAP-25 . Both PLA(2) and AA have been shown to be involved in actin cytoskeletal organization related to vesicle fusion and exocytosis . This mechanism may be an alternative target of BoNT/A other than SNAP-25. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S23 - 6 Peptides that mimic the carboxy-terminal domain of SNAP-25 block acetylcholine release at an Aplysia synapse; Apland JP et al.; Botulinum neurotoxin serotypes A and E (BoNT/A and BoNT/E) block neurotransmitter release, presumably by cleaving SNAP-25, a protein involved in docking of synaptic vesicles with the presynaptic plasma membrane . Three excitation-secretion uncoupling peptides (ESUPs), which mimic the carboxy-terminal domain of SNAP-25 and span or adjoin the cleavage sites for BoNT/A and BoNT/E, also inhibit transmitter release from permeabilized bovine chromaffin cells . In this study, these peptides were tested for effects on acetylcholine (ACh) release at an identified cholinergic synapse in isolated buccal ganglia of Aplysia californica . The presynaptic neuron was stimulated electrically to elicit action potentials . The postsynaptic neuron was voltage-clamped, and evoked inhibitory postsynaptic currents (IPSCs) were recorded . The ESUPs were pressure-injected into the presynaptic neuron, and their effects on the amplitude of the IPSCs were studied . Acetylcholine release from presynaptic cells, as measured by IPSC amplitudes, was gradually inhibited by the ESUPs . All three peptides caused ca . 40% reduction in IPSC amplitude in 2 h . Random-sequence peptides of the same amino acid composition had no effect . Injection of BoNT/E, in contrast, caused ca . 50% reduction in IPSC amplitude in 30 min and almost complete inhibition in 2 h . These results are the first demonstration that ESUPs block neuronal cholinergic synaptic transmission . They are consistent with the concept that ESUPs compete with the intact SNAP-25 for binding with other fusion proteins, thus inhibiting stimulus-evoked exocytosis of neurotransmitter. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S19 - 22 Buforin I, a natural peptide, inhibits botulinum neurotoxin B activity in vitro; Garcia GE et al.; Botulinum neurotoxin B (BoNT/B) serotype specifically cleaves between the amino acids glutamine and phenylalanine (Q and F bond) in position 76-77 of synaptobrevin (VAMP2) . We evaluated peptides that contain the QF cleavage site but are not identical in primary structure to the VAMP2 sequence surrounding the QF site for both inhibition of BoNT/B proteolytic activity and as substrates for BoNT/B . A reverse-phase high-performance liquid chromatography (RP-HPLC) method was used to measure digested peptides . A dose as high as 600 microM of substance P, and 11-amino acid peptide containing the QF bond, was neither a substrate nor inhibitor of BoNT/B in our assay, suggesting that more than the QF bond is required to be recognized by BoNT/B . Buforin I (B-I, QF site 24-25) is 39 amino acids in length, and sequence comparison of B-I and VAMP2 indicated a similarity of 18% for conserved amino acids around the QF site . Furthermore, computer-aided secondary structure computations predict alpha-helical structures flanking the QF site for VAMP2 and for the upstream sequence of B-I . Although predictions for the downstream sequence give nearly equal tendencies for alpha-helical and beta-sheet structures, Yi et al . showed that the downstream sequence is likely to be the alpha-helix based on their examination of buforin II (B-II, a 21-amino acid subset of B-I (16-36)), which includes the QF site and the downstream sequence of B-I . Buforin I was found not to be a substrate for BoNT/B; however, B-I dose dependently and competitively inhibited BoNT/B activity, yielding IC(50) = 1 x 10(-6) M . In contrast, B-II was not a substrate for BoNT/B and exhibited only 25% of the B-I inhibition of BoNT/B . Two additional B-I deletion peptides were tested for inhibition of BoNT/B proteolysis: peptide 36 (36 mer; containing B-I amino acids 1-36) and peptide 24 (24 mer; B-I amino acids 16-39) . Peptide 24 had a similar inhibitory effect to B-II (ca . 25% of B-I) but peptide 36 was almost 50% as potent as B-I . These findings suggest that the buforin tertiary structure is important for the inhibitory activity of these peptides for BoNT/B. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S13 - 7 Rapid microplate assay for monitoring botulinum neurotoxin B catalytic activity; Keller JE et al.; The binding activity of a rabbit polyclonal antiserum raised against a 51-residue peptide (P51) homologous to human VAMP2 (residues 44-94) was examined . Human VAMP2 is an 18-kDa protein located on the external membrane of small synaptic vesicles and is targeted by four of the seven botulinum neurotoxin (BoNT) serotypes (B, D, F and G) . The antiserum, designated anti-P51, recognized P51 but exhibited little cross-reactivity with the two cleavage products that result from BoNT/B-mediated proteolysis of P51 . The larger of these fragments, designated as P33 (residues 44-76), exhibited a weak but measurable interaction with the antiserum . The smaller cleavage product, designated as P18 (residues 77-94), was not recognized by the antiserum . Anti-P51 was used to monitor BoNT/B light chain (LC)-mediated cleavage of P51 using an indirect ELISA . The serine protease inhibitor phenylmethylsulfonyl fluoride did not inhibit BoNT/B activity, but the zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) and the elastase inhibitor 7- N -phenylcarbamoylamino-4-chloro-3-propyloxyisocoumarin (ICD 1578) produced complete blockade of BoNT/B LC action . Under ideal conditions, it will be possible to evaluate up to seven candidate anti-BoNT/B drugs in triplicate at four concentrations using a single 96-well microtiter plate . These findings indicate that the ELISA will be suitable for rapid screening of BoNT/B inhibitors. J Appl Toxicol, 1999 Dec, 19 Suppl 1, S5 - S11 Evaluation of phosphoramidon and three synthetic phosphonates for inhibition of botulinum neurotoxin B catalytic activity; Adler M et al.; Three putative metalloprotease inhibitors were synthesized and tested for their ability to inhibit the catalytic activity of botulinum neurotoxin B light chain (BoNT/B LC) . The compounds were designed to emulate the naturally occurring metalloprotease inhibitor phosphoramidon, which has been reported to be a weak antagonist of BoNT/B action . All three analogs contained the dipeptide Phe-Glu in place of Leu-Trp of phosphoramidon and possessed a phenyl, ethyl or methyl group in place of the rhamnose sugar of the parent compound . The inhibitors were evaluated in a cell-free assay based on the detection of a fluorescent product following cleavage of a 50-mer synaptobrevin peptide ({Pya(88)} S 39-88) by BoNT/B LC . This peptide corresponds to the hydrophilic core of synaptobrevin-2 and contains a fluorescent analog L-pyrenylalanine (Pya) in place of Tyr(88) . Cleavage of {Pya(88)} S 39-88 by BoNT/B LC gives rise to fragments of 38 and 12 amino acid residues . Quantification of BoNT/B-mediated substrate cleavage was achieved by separating the 12-mer fragment (FETSAAKLKRK-Pya) that contains the C-terminal fluorophore and measuring fluorescence at 377 nm . The results indicate that the phenyl-substituted synthetic compound ICD 2821 was slightly more active than phosphoramidon, but analogs with methyl or ethyl substitutions were relatively inactive . These findings suggest that phosphonate monoesters may be useful for providing insights into the structural requirement of BoNT/B protease inhibitors. Anaesthesia, 2000 Jan, 55(1), 32 - 41 Anaesthesia and pain management in cerebral palsy; Nolan J et al.; Cerebral palsy is the result of an injury to the developing brain during the antenatal, perinatal or postnatal period . Clinical manifestations relate to the area affected . Some of the conditions associated with cerebral palsy require surgical intervention . Problems during the peri-operative period may include hypothermia, nausea and vomiting and muscle spasm . Peri-operative seizure control, respiratory function and gastro-oesophageal reflux also require consideration . Intellectual disability is common and, in those affected, may range from mild to severe . These children should be handled with sensitivity as communication disorders and sensory deficits may mask mild or normal intellect . They should be accompanied by their carers at induction and in the recovery room as they usually know how best to communicate with them . Postoperative pain management and the prevention of muscle spasm is important and some of the drugs used in the management of spasm such as baclofen and botulinum toxin are discussed . Epidural analgesia is particularly valuable when major orthopaedic procedures are performed. Muscle Nerve, 2000 Jan, 23(1), 18 - 36 The utility of interference pattern analysis; Fuglsang-Frederiksen A; The interference pattern of the electrical activity of muscle can be quantified by amplitude measurements, different spike counting methods, and power spectrum analyses . Interference pattern analysis (IPA) methods are used to describe the degree of activation of different muscles, muscle fatigue, occupational work, muscles in chronic pain syndromes, disused muscle, and dystonic muscle treated with botulinum toxin . In patients with neuromuscular disorders, the turns/amplitude analysis is useful for diagnosis . High diagnostic yields can be obtained without force measurements, for example, by using the amplitude as an indicator of force (the peak ratio method) or plotting the amplitude against the turns (cloud analysis) . The diagnostic possibilities of the power spectrum analysis and the motor unit firing rate obtained by decomposition techniques are still unclear . Wien Klin Wochenschr, 1999 Oct 29, 111(20), 837 - 42 {Safety and tolerance of single-dose botulinum toxin Type A treatment in 204 patients with spasticity and localized associated symptoms . Austrian and German botulinum toxin A spasticity study group}; Wissel J et al.; High dose oral anti-spastic medication is effective in the treatment of spasticity but has the disadvantage of frequent systemic side effects such as drowsiness and general weakness . Therefore, neurolytic and chemodenervation procedures are further therapeutic options, especially in cases of local spasticity . Apart from phenol blocks with the risk of persisting painful dysesthesia, botulinum toxin type A (BtxA) appears to be a safe and effective treatment . In 204 patients (mean age, 41.5 years {range 3-91 years}) with acute (n = 29, mean duration of disease 2.9 months {range, 1-6 months}) and chronic (n = 175, mean duration of disease 111 months {range, 7-500 months}) spasticity due to stroke, traumatic brain and spinal injury and other lesions of the upper motor neuron, the effects of single-dose BtxA treatment were studied . An overall dose of 181.2 units {range, 15-600 units} of BtxA (Botox) was injected in a mean of 3.3 {1-14} muscles per patient . Results were assessed using a modified Rating of Response to BtxA (RRB, Brin et al . 1995) . The RRB includes a pre- and post BtxA assessment of the severity of spasticity-associated problems (patient's self-assessment), a rating of the current percentage of normal function in the region of the body selected for BtxA and a global rating of changes induced by BtxA . 191 (93.6%) patients demonstrated improvement over a mean of 7.7 weeks {1-36}; no deterioration was observed . Mean overall severity and function improved significantly (p < 0.001) . No systemic or severe side effects were registered . Only in 5.9% of the patients were mild (n = 10) or moderate (n = 2) reversible adverse events reported . We conclude that BtxA injections are safe and effective in the treatment of local spasticity. Mov Disord, 1999 Nov, 14(6), 1017 - 20 Combined use of type A and F botulinum toxins for blepharospasm: a double-blind controlled trial; Mezaki T et al.; Type A botulinum toxin has widened its clinical range of applications, but the risk of developing antibodies limits the repeated use of high-dose injection . To minimize the risk, mixing different types of toxin might reduce the antigenic presentation of a specific toxin and associated proteins . At the same time, inhibition of the neuromuscular release process at the multiple sites might potentiate the clinical response or the duration of action . We compared the effectiveness of a mixture of type A and type F botulinum toxins with that of type A or type F toxin alone for treating patients with blepharospasm in a double-blind study . Fifty-four patients had 10 units of toxin injection, a mixture of type A and F toxins (including 5 units of each) on one side and either type A or F toxin on the other side of the orbicularis oculi muscle . Clinical evaluation at 4 and 10 weeks after the injection revealed that the peak clinical effect at 4 weeks was similar among the three preparations . The duration of action of the mixture was intermediate between type A and type F alone, as assessed at 10 weeks, when there was a tendency of conserving the beneficial effect on one eye at the expense of that on the other . Although there was no apparent potentiation of the clinical efficacy, the combination of these different types of toxin might be used for decreasing the risk of antibody development. Mov Disord, 1999 Nov, 14(6), 994 - 9 Trick maneuvers in cervical dystonia: investigation of movement- and touch-related changes in polymyographic activity; Wissel J et al.; Antagonistic gestures or trick maneuvers are well-known clinical features to reduce or abolish dystonic posturing in cervical dystonia (CD) . The maneuvers typically consist of a finger touch to the facial skin but their physiology remains unknown . To determine the temporal profile of geste maneuver performance, 25 patients with idiopathic CD were studied by means of polymyography of six cervical muscles prior to any botulinum toxin treatment . Two piezoelectric elements fixed to a fingertip of the hand involved in the trick maneuver and to the facial target region, respectively, were used to relate the essential points of the trick maneuver time course (start of geste-arm movement, facial contact, end of contact, end of movement) to changes in polymyographic activity . Thirteen patients (52%) showed marked reductions of electromyographic (EMG) activity (> or =50% in at least one muscle) during arm movement, definitely prior to contact between fingers and facial target area; in the remaining 12 patients (48%), geste-related EMG effects were confined to facial-finger contact . These results might indicate different physiological mechanisms in clinically indistinguishable antagonistic gestures. Acta Chir Belg, 1999 Oct, 99(5), 215 - 20 Fissure-in-ano, to divide or not to divide? Brugman T, Bruyninx L, Jacquet NJ. Anal fissure is one of the most common and painful proctological pathologies affecting mainly young individuals . The physiopathology in the development of a chronic anal fissure seems to be a combination of internal anal sphincter hypertonia and poor vascularization at the posterior midline . Treatment of acute fissures is conservative with supportive therapy, leading to healing in the majority of the patients . Open or closed lateral internal sphincterotomy is the treatment of choice for chronic anal fissures . In low pressure chronic fissures, sphincterotomy should be avoided and a V-Y island advancement flap may be an alternative procedure . Sphincterotomy can induce anal incontinence, a feared complication of this technique . Recent interest has developed in chemical sphincterotomy with local botulin toxin injections or glyceryl trinitrate application . Long-term follow-up is needed to evaluate these new therapeutic options. J Cell Biol, 1999 Nov 29, 147(5), 1023 - 38 Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo; Kawano Y et al.; Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, phosphorylates myosin-binding subunit (MBS) of myosin phosphatase and thereby inactivates the phosphatase activity in vitro . Rho-kinase is thought to regulate the phosphorylation state of the substrates including myosin light chain (MLC), ERM (ezrin/radixin/moesin) family proteins and adducin by their direct phosphorylation and by the inactivation of myosin phosphatase . Here we identified the sites of phosphorylation of MBS by Rho-kinase as Thr-697, Ser-854 and several residues, and prepared antibody that specifically recognized MBS phosphorylated at Ser-854 . We found by use of this antibody that the stimulation of MDCK epithelial cells with tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF) induced the phosphorylation of MBS at Ser-854 under the conditions in which membrane ruffling and cell migration were induced . Pretreatment of the cells with Botulinum C3 ADP-ribosyltransferase (C3), which is thought to interfere with Rho functions, or Rho-kinase inhibitors inhibited the TPA- or HGF-induced MBS phosphorylation . The TPA stimulation enhanced the immunoreactivity of phosphorylated MBS in the cytoplasm and membrane ruffling area of MDCK cells . In migrating MDCK cells, phosphorylated MBS as well as phosphorylated MLC at Ser-19 were localized in the leading edge and posterior region . Phosphorylated MBS was localized on actin stress fibers in REF52 fibroblasts . The microinjection of C3 or dominant negative Rho-kinase disrupted stress fibers and weakened the accumulation of phosphorylated MBS in REF52 cells . During cytokinesis, phosphorylated MBS, MLC and ERM family proteins accumulated at the cleavage furrow, and the phosphorylation level of MBS at Ser-854 was increased . Taken together, these results indicate that MBS is phosphorylated by Rho-kinase downstream of Rho in vivo, and suggest that myosin phosphatase and Rho-kinase spatiotemporally regulate the phosphorylation state of Rho-kinase substrates including MLC and ERM family proteins in vivo in a cooperative manner. Nat Neurosci, 1999 Dec, 2(12), 1078 - 83 Activity-dependent changes in partial VAMP complexes during neurotransmitter release; Hua SY et al.; The temporal sequence of SNARE protein interactions that cause exocytosis is unknown . Blockade of synaptic neurotransmitter release through cleavage of VAMP/synaptobrevin by tetanus toxin light chain (TeNT-LC) was accelerated by nerve stimulation . Botulinum/B neurotoxin light chain (BoNT/B-LC), which cleaves VAMP at the same site as TeNT-LC, did not require stimulation . Because TeNT-LC requires the N-terminal coil domain of VAMP for binding but BoNT/B-LC requires the C-terminal coil domain, it seems that, before nerve activity, the N-terminal domain is shielded in a protein complex, but the C-terminal domain is exposed . This N-terminal complex lasts until nerve activity occurs and may serve to cock synaptic vesicles for immediate exocytosis upon Ca2+ entry. Dig Dis Sci, 1999 Nov, 44(11), 2270 - 6 Effects of previous treatment on results of laparoscopic Heller myotomy for achalasia; Patti MG et al.; Until recently, pneumatic dilatation and intrasphincteric injection of botulinum toxin (Botox) have been used as initial treatments for achalasia, with myotomy reserved for patients with residual dysphagia . It is unknown, however, whether these nonsurgical treatments affect the performance of a subsequent myotomy . We compared the results of laparoscopic Heller myotomy and Dor fundoplication in 44 patients with achalasia who had been treated with medications (group A, 16 patients), pneumatic dilatation (group B, 18 patients), or botulinum toxin (group C, 10 patients) . The last group was further subdivided according to whether there was (C2, 4 patients) or was not (C1, 6 patients) a response to the treatment . Results for groups A, B, C1, and C2, respectively, were: anatomic planes identified at surgery (% of patients)--100%, 89%, 100%, and 25%; esophageal perforation (% of patients)--0%, 5%, 0%, and 50%; hospital stay (hrs)--26+/-8, 38+/-25, 26+/-11, and 72+/-65; and excellent/good results (% of patients)--87%, 95%, 100%, and 50% . These results show that: (1) previous pneumatic dilatation did not affect the results of myotomy; (2) in patients who did not respond to botulinum toxin, the myotomy was technically straightforward and the outcome was excellent; (3) in patients who responded to botulinum toxin, the LES muscle had become fibrotic (perforation occurred more often in this setting, and dysphagia was less predictably improved); and (4) myotomy relieved dysphagia in 91% of patients who had not been treated with botulinum toxin . These data support a strategy of reserving botulinum toxin for patients who are not candidates for pneumatic dilatation or laparoscopic Heller myotomy. Aliment Pharmacol Ther, 1999 Nov, 13(11), 1391 - 6 Review article: pharmacological options in achalasia; Bassotti G et al.; Achalasia is a common primary oesophageal motor disorder . Treatment has been based traditionally on a surgical approach; however, there is new evidence that some medical strategies may be of benefit . The purpose of the present article was to review the current medical management of achalasia . A Medline search identified original articles and reviews published in the English-language literature between 1966 and 1998 . This search has revealed that the pharmacological treatment of achalasia is limited to some subgroups of patients (for example, early stages of the disease and elderly patients), and that nitrates, nifedipine, and botulinum toxin are the best studied and most effective compounds. J Am Acad Dermatol, 1999 Dec, 41(6), 987 - 90 Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis; Heckmann M et al.; BACKGROUND: Although topical application of aluminium chloride is the most common measure against axillary sweating, severely affected patients often undergo surgical procedures that are expensive and may have considerable side effects . Recently botulinum toxin A (BT-A) has been reported as a potentially effective antihyperhidrotic agent . OBJECTIVE: Our purpose was to determine the therapeutic strength, safety, and mode of application of BT-A in severe axillary hyperhidrosis . METHODS: Intradermal injection of BT-A (Dysport) was given in an open left-versus-right side trial with each patient being his own control for initial efficacy, followed by treatment of the contralateral side . RESULTS: Seven days after initial treatment sweat production fell to below 10% of the untreated contralateral axilla as determined by gravimetry . Satisfaction was rated unanimously as "very good," the highest of 5 rankings . No side effects such as skin irritation or muscle weakness were noted in any patient . CONCLUSION: Intradermal injection of BT-A is a potent and well-accepted therapeutic option in patients with recalcitrant axillary hyperhidrosis. Gait Posture, 1999 Dec, 10(3), 206 - 10 Botulinum toxin A in hamstring spasticity; Corry IS et al.; Hamstring injection of Botulinum toxin A (BtA) may have a role in the conservative management of flexed knee gait in cerebral palsy or in simulating the effect of surgery . Ten children who were likely to require future hamstring lengthening were injected . Short term outcome was assessed by clinical examination and 3-D gait analysis . Mean popliteal angle decreased by 16 degrees and maximum knee extension in stance increased by 8 degrees, the latter relapsing by 12 weeks . Mean pelvic tilt tended to increase suggesting that isolated hamstring weakening be approached with caution . Energy cost of walking was not significantly changed in six of the ten patients . A small increase in knee extension in stance was often associated with patient satisfaction . There are theoretical grounds for expecting an associated increased longitudinal muscle growth after BtA injection. J Neurol Neurosurg Psychiatry, 1999 Dec, 67(6), 807 - 10 Disturbances of dynamic balance in phasic cervical dystonia; Muller J et al.; OBJECTIVE: To quantitatively assess control of balance under static and dynamic conditions in patients with tonic and phasic cervical dystonia . METHODS: Ten patients with purely tonic cervical dystonia with fixed postural deviation and 20 patients with cervical dystonia with phasic head movements were investigated at least 3 months after botulinum toxin injections . Seventeen age matched volunteers served as controls . Static posturography was performed on a force platform; dynamic equilibrium was studied on a stabilometer, which requires the subject to continuously adapt upright posture to an unstable tilting surface . Measurements of maximum amplitude and linear displacement of the pivot were taken with open and closed eyes . RESULTS: Sway path values in static posturography were not significantly different between patients with cervical dystonia and controls . On dynamic posturography, patients with phasic cervical dystonia showed significantly higher platform measures (maximum amplitude and linear displacement of the pivot) with eyes open and closed By contrast, none of the dynamic platform measures differed significantly between patients with tonic cervical dystonia and controls . CONCLUSIONS: Normal measures of dynamic equilibrium in tonic cervical dystonia argue against a primary abnormality of balance control in cervical dystonia . Impaired dynamic equilibrium in phasic cervical dystonia is likely to reflect a disruption of vestibular input due to repetitive, involuntary head oscillations. Can J Physiol Pharmacol, 1999 Sep, 77(9), 679 - 88 Retention of cleaved synaptosome-associated protein of 25 kDa (SNAP-25) in neuromuscular junctions: a new hypothesis to explain persistence of botulinum A poisoning; Raciborska DA et al.; Botulinum neurotoxins can block neurotransmitter release for several months . The molecular mechanism of these toxins' action is known, but the persistence of neuromuscular paralysis that they cause is unexplained . At frog neuromuscular junctions, application of botulinum toxin type A caused paralysis and reduced the C-terminus immunoreactivity of SNAP-25, but not that of the remaining N-terminus fragment . Botulinum toxin type C caused paralysis and reduced syntaxin immunoreactivity without affecting that of SNAP-25 . Co-application of botulinum A and C reduced syntaxin immunoreactivity, and that of both C and N termini of SNAP-25 . Application of hydroxylamine to de-palmitoylate SNAP-25 resulted in a slight reduction of the immunoreactivity of SNAP-25 N terminus, while it had no effect on immunoreactivity of botulinum A cleaved SNAP-25 . In contrast, application of hydroxylamine to nerve terminals where syntaxin had been cleaved by botulinum C caused a considerable reduction in SNAP-25 N-terminus immunoreactivity . Hence the retention of immunoreactive SNAP-25 at the neuromuscular junction depends on its interactions with syntaxin and plasma membrane . Persistence of cleaved SNAP-25 in nerve terminals may prevent insertion of new SNAP-25 molecules, thereby contributing to the longevity of botulinum A effects. Dev Biol Stand, 1999, 101, 267 - 76 Validation of in vitro assays for botulinum toxin: a case study; Gaines Das RE et al.; Ensuring the reliability and precision of assay results requires careful attention to assay design . In this case study we describe validation studies of an in vitro assay for botulinum neurotoxin type A based on its endopeptidase activity towards immobilised synthetic substrate . This assay, in common with many in vitro assays, is sensitive to changes in reagents and assay conditions and is time dependent . In addition, the toxin is not stable in solution . Differences in estimates of potency, resulting from positional factors, which are not significant in individual assays, are shown to be consistent and statistically significant over a longer series of assays . This study emphasizes that assay validation should not be viewed as a single step in assay development but must be considered as a continuing process if assay results are to be reliable and reproducible. Dev Biol Stand, 1999, 101, 141 - 5 Novel assays for the detection of botulinum toxins in foods; Wictome M et al.; Currently the only accepted method for the detection of botulinum neurotoxin in contaminated samples is the mouse bio-assay . Although highly sensitive this test has a number of drawbacks: it is expensive to perform, lacks specificity and involves the use of animals . With increasing resistance to such animal tests there is a need to replace the bio-assay with a reliable in vitro test . Over the past six years it has been demonstrated that all the botulinum neurotoxins act intracellularly as highly specific zinc endoproteases, cleaving proteins involved in the control of secretion of neurotransmitters . In the work described, this enzymatic activity has been utilised in assay formats for the detection in foods of neurotoxin from the serotypes involved in food-borne outbreaks in man . These assays have been shown to have a greater sensitivity, speed and specificity than the mouse bio-assay . It is envisaged that such assays will prove realistic alternatives to animal based tests. Neurology, 1999 Nov 10, 53(8), 1794 - 800 Abnormal perception of vibration-induced illusion of movement in dystonia; Rome S et al.; OBJECTIVES: To examine the illusional sensation of movement evoked by vibration of an immobilized arm . METHODS: Patients with idiopathic focal dystonia were compared with those with idiopathic PD and with patients with dystonia secondary to PD . A 100-Hz transcutaneous vibratory stimulus was applied to the biceps brachii tendon to elicit an illusional sensation of arm extension . Blindfolded patients were instructed to copy any perceived movement of the vibrated arm with the opposite (tracking) arm . By recording movement of reflective markers on the tracking arm using infrared video cameras, the change in elbow angle was quantified over 45 seconds . The effect of treatment with botulinum toxin was examined by retesting previously untreated patients after commencing therapy . These results were also compared with patients with hemifacial spasm who had ongoing treatment with botulinum toxin . RESULTS: Vibration of the biceps in dystonic patients produced a smaller sensation of arm extension than in control subjects unaffected by botulinum toxin treatment . There were no differences between the types of idiopathic focal dystonia examined, including patients with dystonia in sites other than the arm . Those with idiopathic PD and hemifacial spasm did not differ from healthy control subjects . Patients with dystonia secondary to PD showed a unilateral abnormality on the side of dystonic symptoms . CONCLUSION: Bilateral abnormal perception of the illusion of vibration-induced movement is a feature of idiopathic focal dystonia but not idiopathic PD, and is independent of treatment with botulinum toxin . Unilateral, abnormal sensorimotor integration is implicated in dystonia secondary to PD . These results may reflect abnormal sensorimotor integration of Ia afferent activity. Rev Neurol, 1999 Oct 16-31, 29(8), 700 - 3 {Vertebrobasilar abnormalities in patients with hemifacial spasm: MR-angiography findings}; Montaner J et al.; INTRODUCTION: Hemifacial spasm (HFS) is a disorder characterized by a complex of symptoms with hyperactive motor dysfunction of the facial nerve . It is indicated that HFS in the majority of cases can be caused by a blood vessel compressing the nerve adjacent to the brainstem . PATIENTS AND METHODS: We studied and treated 44 patients with HFS . Magnetic resonance imaging (MR) and MR-angiography of the brain were performed in patients with HFS to asses the presence of an artery of the vertebrobasilar system compressing the root of the facial nerve . We evaluate the response to treatment with Botulinum toxin in these cases . 14 patients were excluded (6 patients presented HFS due to other lesions and in 8 patients the MR was not performed) . The remaining 30 patients with idiopathic HFS underwent MR/MRA (3D-FISP) and it was also performed in 14 patients with synkineses after facial palsy to be used as controls . RESULTS: The MRA documented an abnormal position of the arteries surrounding the facial nerve (ipsilaterally to HFS) in 22 patients . The compressing artery was the PICA in 3 patients (10%), the AICA in 3 patients, the vertebral artery in 7 patients and the basilar artery in 8 patients, one patient showed a combined compression by AICA and PICA . The remaining 8 patients had a normal MRI . At the control group only one patient presented an abnormal AICA and the other had a normal MRI-MRA . Patients were followed-up for 22.4 months and after Botulinum toxin treatment patients kept 4.81 months free of symptoms . CONCLUSIONS: We recommend to perform MR studies in all HFS patients to rule out a secondary cause of the disease and MRA to evaluate the underlying vertebrobasilar abnormalities if surgery is planned . Botulinum toxin is a useful treatment in these patients and only after its failure, microvascular decompression will be considered. J Neurosci, 1999 Nov 15, 19(22), 9803 - 12 Subcellular localization of tetanus neurotoxin-insensitive vesicle-associated membrane protein (VAMP)/VAMP7 in neuronal cells: evidence for a novel membrane compartment; Coco S et al.; The clostridial neurotoxin-insensitive soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors, tetanus neurotoxin-insensitive (TI)-vesicle-associated membrane protein (VAMP)/VAMP7, SNAP23, and syntaxin 3 have recently been implicated in transport of exocytotic vesicles to the apical plasma membrane of epithelial cells . This pathway had been shown previously to be insensitive to tetanus neurotoxin and botulinum neurotoxin F . TI-VAMP/VAMP7 is also a good candidate to be implicated in an exocytotic pathway involved in neurite outgrowth because tetanus neurotoxin does not inhibit this process in conditions in which it abolishes neurotransmitter release . We have now found that TI-VAMP/VAMP7 has a widespread distribution in the adult rat brain in which its localization strikingly differs from that of nerve terminal markers . TI-VAMP/VAMP7 does not enrich in synaptic vesicles nor in large dense-core granules but is associated with light membranes . In hippocampal neurons developing in vitro, TI-VAMP/VAMP7 localizes to vesicles in the axonal and dendritic outgrowths and concentrates into the leading edge of the growth cone, a region devoid of synaptobrevin 2, before synaptogenesis . After the onset of synaptogenesis, TI-VAMP/VAMP7 is found predominantly in the somatodendritic domain . In PC12 cells, TI-VAMP/VAMP7 does not colocalize with synaptobrevin 2, chromogranin B, or several markers of endocytic compartments . At the electron microscopic level, TI-VAMP/VAMP7 is mainly associated with tubules and vesicles . Altogether, these results suggest that TI-VAMP/VAMP7 defines a novel membrane compartment in neurite outgrowths and in the somatodendritic domain. Curr Opin Neurol, 1999 Aug, 12(4), 447 - 56 Botulinum toxin in motor disorders; Bentivoglio AR et al.; Advances in the clinical use of botulinum neurotoxins continue . Of interest to the neurologist is the advanced practice in the treatment of focal dystonia and the new developments on other dyskinesias and on autonomic control of smooth muscle motility . New toxin serotypes are now being tested; their availability will improve clinical practice and will possibly lead to combined treatments . Indications in spasticity and in juvenile cerebral palsy are now under scrutiny . The combination of focal chemodenervation with specific rehabilitation procedures enables new development in this field. Curr Opin Pediatr, 1999 Oct, 11(5), 396 - 401 Update on medications used to treat gastrointestinal disease in children; Evans JS et al.; Progress in the pharmacotherapy of pediatric gastrointestinal diseases continued during 1998 despite ongoing obstacles encountered by clinicians and researchers . The major change involved warnings that cisapride, a widely used prokinetic agent, could cause potentially fatal arrythmias in susceptible people . The risk for children is unclear and a consensus of prescribing guidelines is needed . Excellent pediatric-oriented reviews have been published that summarize our knowledge of proton pump inhibitors, probiotics, 5-hydroxtryptamine-3 (5-HT3) antagonists, and the treatment of gastrointestinal infections and chronic abdominal pain . Triple medication therapy for the eradication of Helicobacter pylori is now the standard of care, but the optimal combination and duration of therapy needs to be determined . Also described are interesting developments requiring further confirmation: the treatments of infectious diarrhea with zinc; achalasia and Hirschsprung's disease with botulinum toxin; weight loss with megestrol acetate; and sialorrhea with glycopyrollate. Nervenarzt, 1999 Oct, 70(10), 903 - 8 {Torticollis spasmodicus, blepharospasm and hemifacial spasm . Subjective evaluation of therapy by patients}; Birner P et al.; Injections with botulinum toxin type A (BTX) are considered the first-line treatment for spasmodic torticollis (ST), blepharospasm (BL) and hemifacial spasm (HFS) . Because BTX brings only temporary and partial relief, patients frequently try other additional therapies to minimize their symptoms . The subjective rating of all therapies ever tried by patients with ST, BL and HFS was evaluated by using a simple questionnaire . Two hundred questionnaires were considered (112 TS, 54 BL, 34 HFS) . BTX was rated subjectively the best therapy in all three diagnostic groups (median: 2 = good effect) . Despite Citalopram and physiotherapy (median: 3 = average effect), all other therapies were rated with a median of > or = 4 (= minimal effect) . Patients with ST tried 7.7, patients with BL 2.4 and patients with HFS 2.6 different types of therapy . In conclusion, BTX is the most effective treatment for patients with ST, BL and HFS, as rated subjectively . Further evaluation of therapies additional to BTX injections is recommended. Annu Rev Microbiol, 1999, 53, 551 - 75 Clostridial toxins as therapeutic agents: benefits of nature's most toxic proteins; Johnson EA; Toxins are increasingly being used as valuable tools for analysis of cellular physiology, and some are used medicinally for treatment of human diseases . In particular, botulinum toxin, the most poisonous biological substance known, is used for treatment of a myriad of human neuromuscular disorders characterized by involuntary muscle contractions . Since approval of type-A botulinum toxin by the US Food and Drug Administration in December 1989 for three disorders (strabismus, blepharospasm, and hemifacial spasm), the number of indications being treated has increased greatly to include numerous focal dystonias, spasticity, tremors, cosmetic applications, migraine and tension headaches, and other maladies . Many of these diseases were previously refractory to pharmacological and surgical treatments . The remarkable therapeutic utility of botulinum toxin lies in its ability to specifically and potently inhibit involuntary muscle activity for an extended duration . The clostridia produce more protein toxins than any other bacterial genus and are a rich reservoir of toxins for research and medicinal uses . Research is underway to use clostridial toxins or toxin domains for drug delivery, prevention of food poisoning, and the treatment of cancer and other diseases . The remarkable success of botulinum toxin as a therapeutic agent has created a new field of investigation in microbiology. Otolaryngol Head Neck Surg, 1999 Nov, 121(5), 523 - 7 Validation by magnetic resonance imaging of tympanometry for diagnosing middle ear effusion; Alper CM et al.; This study was performed to correlate tympanometric gradient with measurements of effusion quantity by use of MRI during an experimental otitis media with effusion episode in 4 cynomolgus monkeys . Paired results for the intensity values of the T(2)-weighted MRI scans and the tympanometric width measured in the right ear of all animals before and on days 15, 21, 29, and 36 after botulinum paralysis of the tensor veli palatini muscle were analyzed . All right ears showed a progressive increase during the study period in the signal intensity of the MRI . Whereas the average middle ear pressures decreased, the average tympanometric widths demonstrated a progressive increase during the course of the experimental otitis media with effusion . Significant correlations between tympanometric width and MRI measures of effusion were documented, confirming the high predictive value of the tympanometric width for diagnosing the presence and quantity of middle ear effusion. Vaccine, 1999 Nov 12, 18(7-8), 728 - 35 The immunogenicity in humans of a botulinum type F vaccine; Montgomery VA et al.; A purified monovalent botulinum type F toxoid vaccine was administered to 35 healthy adult volunteers in a phase I clinical trial . Serum samples from the vaccinated volunteers were evaluated for an antibody response at various time intervals over 1 year by mouse bioassay and ELISA . The antibody response was measured for varying doses of vaccine (2, 5, or 10 microg), and after single or multiple (two or three doses @ 10 microg) vaccinations . Six out of 15 (40%) individuals developed antibody titers after receiving a single dose . After two and three vaccinations, there was a 90% (18/20) and 100% (10/10) seroconversion rate, respectively . Eight months after initial injection, 57 and 63% of individuals were antibody positive following two or three vaccinations, respectively . Single vaccinations, at any of the tested dosages, elicited lower, if any, antibody response than did multiple vaccinations . After the third vaccination, ELISA titers positively correlated with mouse neutralization bioassay titers (r(2)=0.86). Aliment Pharmacol Ther, 1999 Oct, 13(10), 1347 - 50 Comparison of two different formulations of botulinum toxin A for the treatment of oesophageal achalasia . The Gismad Achalasia Study Group; Annese V et al.; BACKGROUND: Intrasphincteric injection of botulinum toxin has been reported as a safe and effective alternative treatment in oesophageal achalasia, especially in high-risk and elderly patients . AIM: : To compare two formulations of botulinum toxin in the management of achalasia . PATIENTS AND METHODS: We randomly compared the efficacy and safety of 100 U of Botox (Allergan, Irvine, USA) and 250 U of Dysport (Ipsen, Milan, Italy), injected through a sclerotherapy needle at the level of the lower oesophageal sphincter, in 78 consecutive patients with achalasia . Symptom score, oesophageal manometry and 24 h pH-metry were recorded (before and 1 month after therapy) . Symptom score was also obtained 6 months after treatment . RESULTS: One month after treatment, the effects of the toxin on symptoms and oesophageal tests were similar for both formulations . Lower oesophageal sphincter pressure decreased from 31 +/- 12 to 18 +/- 5 mmHg after Botox, and from 35 +/- 9 to 18 +/- 10 after Dysport . At the end of the follow-up period (6 months), symptom score decreased from 5 +/- 1.2 to 1.2 +/- 0.8 after Botox and from 5.2 +/- 1.5 to 1.5 +/- 1 after Dysport . Moreover, the percentages of patients who failed to respond to treatment (10% and 17.5%) and who relapsed during follow-up (12% and 24%) did not differ significantly . No patient complained of reflux symptoms after treatment, although abnormal acid exposure was documented in two subjects . CONCLUSIONS: Both formulations of botulinum toxin have comparable efficacy in the treatment of oesophageal achalasia, for up to 6 months of follow-up. J Thorac Cardiovasc Surg, 1999 Nov, 118(5), 916 - 23 Video-assisted surgical management of achalasia of the esophagus; Wiechmann RJ et al.; PURPOSE: Video-assisted surgical approaches to esophageal achalasia continue to be explored by many surgeons involved in the management of this motor disorder . We report our experience with thoracoscopic and laparoscopic esophagomyotomy to more clearly define the efficacy and safety of these approaches . PATIENTS: Over 73 months, 58 patients with achalasia underwent thoracoscopic myotomy (n = 19) alone or laparoscopic myotomy (n = 39) with partial fundoplication (anterior = 15; posterior = 24) . Mean age was 47.2 years and average length of symptoms was 60 months . Primary symptoms were as follows: dysphagia, 100%; pulmonary abnormalities, 22%; weight loss; 47%, and pain, 45% . Mean esophageal diameter was 6 cm and tortuosity was present in 16% (9/58) of patients . Prior management consisted of dilation (n = 47), botulinum toxin injection (n = 8), and prior myotomy (n = 1) . METHODS: In the operating room all patients underwent endoscopic examination and evacuation of retained esophageal contents . The esophagomyotomy was extended 4 cm superiorly and inferiorly to 1 cm beyond the lower esophageal sphincter . Thoracoscopic and laparoscopic procedures were completed in all patients without conversion to an open operation . Mean operative time was 183 minutes (+/-58.1) and hospital stay averaged 2.3 days (+/-0.8) . There was no operative mortality . The 1 operative complication was a perforation that was identified during the operation and repaired thoracoscopically . RESULTS: Symptoms improved in 97% of patients . Mean dysphagia scores (range 0-10) decreased from 9.8 +/- 1.6 before the operation to 2.0 +/- 1.5 after the operation (P <.001) at a mean follow-up of 6 months . Postoperative reflux symptoms developed in 5% (1/19) of the thoracoscopy group and 8% (4/39) of the laparoscopy group . Nine patients have persistent or recurrent dysphagia (16%) . Seven patients have successfully undergone Savary dilation, and 2 required esophagectomy to manage recalcitrant dysphagia . CONCLUSION: At this intermediate term analysis, video-assisted approaches for management of achalasia are a reasonable alternative to extended medical therapy or open operations. Neurology, 1999 Oct 22, 53(7), 1439 - 46 Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia; Brashear A et al.; OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD) . BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD . METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A . Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD . The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure . Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16 . RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups . The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U) . For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures . Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients . Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose . The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses . CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia. Neurology, 1999 Oct 22, 53(7), 1431 - 8 Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia; Brin MF et al.; OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD) . Background: Local intramuscular injections of BoNT are an effective therapy for CD . After repeated use, some patients become resistant to therapy . BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients . METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD . After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles . The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement . TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16 . RESULTS: A total of 77 patients participated (38 placebo, 39 active) . Improvements in severity, disability, and pain were documented in the BoNT/B-treated group . TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129) . All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001) . A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group . Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group . CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks. Endoscopy, 1999 Sep, 31(7), 517 - 21 Esophageal achalasia: intrasphincteric injection of botulinum toxin A versus balloon dilation; Muehldorfer SM et al.; BACKGROUND AND STUDY AIMS: In patients with esophageal achalasia, pneumatic dilation is the treatment of choice, but it bears the risk of perforation in about 4% of cases . A new nonsurgical method, intrasphincteric injection of botulinum toxin A, has shown promising initial results, and we thus undertook this study to compare the long-term outcome of these two methods . PATIENTS AND METHODS: In a prospective randomized study, 24 patients with definitive esophageal achalasia were divided into two equal groups and underwent either balloon dilation or injection of botulinum toxin (20 U injected into each of the four quadrants in the lower esophageal sphincter) . The outcome was assessed on the basis of a symptom score documented before treatment and at regular intervals for two and a half years thereafter . Complications associated with the two techniques were also documented . RESULTS: No relevant complication occurred in either of the treatment groups . Initially, dilation was successful in 10 of 12 patients (83%), and botulinum toxin injection in 9 of 12 patients (75%) . The symptom scores showed no significant differences between the two groups before and one month after treatment . Over the two and a half year follow-up, however, all nine successfully treated patients in the botulinum toxin group experienced recurrence of symptoms, but only four of the ten patients (40%) in the dilation group . CONCLUSIONS: The two treatment methods initially had equal success rates, but in the long term the effect of the botulinum toxin injection was statistically significantly shorter than that of balloon dilation . As fewer risks are associated with the injection treatment, studies should be undertaken either to identify patient subgroups in whom botulinum toxin can be effective long-term or to test substances with longer-lasting effects. J AAPOS, 1997 Dec, 1(4), 231 - 4 Strabismus surgery among aged medicare beneficiaries; Repka MX; OBJECTIVES: The purpose of this study was to investigate the incidence of strabismus surgery among aged patients in the United States . METHODS: The Medicare Part B claims experience (physician professional fee billing) for 1995 was reviewed for the number of times each strabismus surgical procedure recognized in Physicians' Current Procedural Terminology (CPT) was performed . To determine the indications for the procedures that were performed, a 5% sample of claims was reviewed for the pertinent International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes . RESULTS: There were 27 million aged Medicare beneficiaries eligible for Part B benefits in 1995 in a fee-for-service setting . During that year physicians reported 9497 strabismus physician services . These represented 6585 separate procedures (CPT codes 67311 to 67343) and 277 botulinum toxin (Botox) injections for strabismus (CPT 67345) performed during 1995 . Sixty-nine percent of the surgical procedures were for horizontal correction and 28% were for vertical correction . Adjustable sutures were used for only 1240 cases (1 9%) . The add-on procedural code for reoperation surgery or surgery in the presence of restriction of the extraocular muscles was used in just 930 cases (14%) . The most common diagnosis for horizontal surgery was exotropia . Paralytic strabismus and thyroid disease were identified for 17% of cases . Three percent of the diagnoses were inappropriate for the procedures performed and may have been reported in error . CONCLUSIONS: These data confirm a very low incidence of strabismus surgical procedures (2/10,000) and injections (1/100,000) among aged Medicare beneficiaries . The strabismus surgery was most often performed to repair a horizontal deviation . The adjustable suture technique was used infrequently . These data may be extrapolated into the future to aid in determining the strabismus services that will be needed early in the next century. J AAPOS, 1998 Jun, 2(3), 144 - 6 Large-angle exotropia corrected by intraoperative botulinum toxin A and monocular recession resection surgery; Owens PL et al.; PURPOSE: Surgical correction of large-angle exotropia, greater than 70 PD, traditionally requires operating on three or four horizontal muscles . However, in secondary exotropia from monocular visual loss, it is advisable to operate only on the eye with poor vision . We used intraoperative botulinum toxin as an adjunct to the monocular recession-resection procedure for large-angle sensory exotropia, therefore operating only on the visually impaired eye . METHODS: Three patients underwent monocular recession (10 mm) and resection (10 mm) along with intraoperative botulinum toxin A injection of 10 units into the recessed muscle . All had desired cosmetic repair of long-standing large-angle exotropia (range 100 to 110 PD) with amblyopia and vision worse than 20/200 in the deviated eye . RESULTS: Within 4 days after operation all patients demonstrated maximal paresis of the lateral rectus muscle . This lasted 8 to 12 weeks and resulted in stable orthotropia at 2.5 years in case 1 and stable 8 PD exotropia at 4 years in case 2 . The third case demonstrated a stable 18 PD exotropia by 7 months with a satisfactory cosmetic result . CONCLUSION: This technique provides an alternative for the surgical correction of large-angle exotropia by operating only on two horizontal muscles . In sensory exotropia it also avoids subjecting a normal eye to an operative risk. J AAPOS, 1998 Aug, 2(4), 195 - 200 Long-term results of botulinum toxin in consecutive and secondary exotropia: outcome in patients initially treated with botulinum toxin; Lawson JM et al.; INTRODUCTION: Long-term ocular alignment can be difficult to achieve in patients with consecutive and secondary (sensory) exotropia, and botulinum neurotoxin A (BTXA) is a recognized alternative to surgery in this group . PATIENTS AND METHODS: We reviewed the results of 44 patients aged 15 to 77 years (mean 31 years) who underwent their first BTXA injections from 1989 to 1990 . In 30% of cases the choice of toxin treatment was made by the patient . In the remainder BTXA was recommended by the clinician to assess the risk of postoperative diplopia . Thirty-three patients (75%) were consecutively exotropic and 68% of patients had had previous strabismus surgery . The mean preinjection deviation was 41 delta of exotropia (range 12 to 85 delta exotropia) and the minimum mean angle change after 1 injection was 27 delta (range 0 to 57 delta) . The average number of injections was 3 (range 1 to 17) . RESULTS: Of the patient group, 59% went on to strabismus surgery, 14% continued to attend for maintenance treatment, and 9% were discharged with a small, stable deviation . The remainder were either followed up elsewhere or failed to reattend . CONCLUSIONS: Botulinum toxin appears to be a satisfactory treatment for constant exotropia in patients at risk of postoperative diplopia who have undergone multiple operations but, because more than half the group went on to surgery, surgery as a first therapy may be preferable in uncomplicated cases. J AAPOS, 1999 Oct, 3(5), 272 - 4 What is the role of botulinum toxin in the treatment of dysthyroid strabismus? Gair EJ, Lee JP, Khoo BK, Maurino V. BACKGROUND: Botulinum toxin A has been used in the treatment of dysthyroid strabismus primarily as a temporary measure during the active phase of the disease . We report on our experience with 65 patients . METHOD: We review the records of 65 patients with dysthyroid strabismus who were treated with botulinum toxin A at Moorfields Eye Hospital between 1984 and 1996 . CONCLUSIONS: Patients with a short duration of relatively mild dysthyroid strabismus have a chance of long-term benefit with botulinum toxin A . There is little use for botulinum toxin A in cases of severe dysthyroid disease. J AAPOS, 1999 Oct, 3(5), 269 - 71 Role of botulinum toxin A in surgically overcorrected exotropia; Dawson EL et al.; PURPOSE: The purpose of this study was to define the role of botulinum toxin type A (BTXA) in surgically overcorrected exotropia . METHODS: A retrospective review was performed using the BTXA clinic database of more than 3500 patients to identify patients with a consecutive esotropia . RESULTS: Sixty patients met the inclusion criteria; the patients' ages ranged from 5 to 80 years . Before toxin treatment, an average of 1.8 operations had been performed per patient . The mean distance deviation was 17 PD base out and near deviation was 18 PD base out . The time from the last operation to an injection of BTXA averaged 28.3 months . We divided our patient population into 2 groups: those with fusion potential and those with no expected fusion potential . Of the 36 patients with fusion potential, 15 patients achieved and maintained good ocular alignment and resolution of their diplopia with an injection of BTXA . In the 24 patients with no expected fusion potential, 4 patients (17%) achieved and maintained good alignment with an injection of BTXA . Although they were not cured, 10 additional patients chose to have repeated BTXA injections to maintain their ocular alignment, whereas only 2 patients required occlusive methods to eradicate intractable diplopia . Five patients had additional surgery, of which 3 patients obtained a functional result . CONCLUSIONS: BTXA has a role in surgically overcorrected exotropia for patients in whom a functional result may be obtained . BTXA is of less value for patients with poor binocular function . It has proved especially useful as a treatment given only once for 42% of patients who could regain high-quality stereopsis . The safety and ease of administration of this treatment add to its merit. J AAPOS, 1997 Mar, 1(1), 20 - 30 Vertical muscle transposition augmented with lateral fixation; Foster RS; INTRODUCTION: Full vertical rectus muscle transpositions have been shown to be an effective treatment for lateral rectus palsies and type I Duane syndrome . This operation is usually accompanied by mechanical or botulinum toxin treatment of one or both medial rectus muscles . This series evaluates the effect of augmenting the transposed muscles with lateral fixation sutures . METHODS: Transposition of the vertical rectus muscles to the lateral rectus muscle was performed in 23 eyes of 21 patients; transposition to the medial rectus muscle was performed in one eye of one of these 21 patients . A lateral fixation suture of 5-0 Dacron polyester filament was placed in the sclera 16 mm posterior to the limbus and adjacent to the lateral rectus muscle, incorporating one fourth of the transposed vertical rectus muscle . Of the 21 patients, five had type I Duane syndrome with a face turn and esotropia in the primary position, seven had a unilateral lateral rectus palsy, two had bilateral lateral rectus palsy, four had an ipsilateral lateral rectus palsy combined with a contralateral lateral rectus paresis (a recess resect procedure was performed on the paretic eye along with the augmented transposition on the paralyzed eye), two had gaze palsies, and one had a unilateral lateral rectus palsy with recurrent esotropia after a transposition procedure performed 16 years previously . Lateral fixation sutures alone were used in the last case listed . Postoperative diplopia-free fields were measured when possible (10 cases) . RESULTS: In most cases (19/23 eyes), alignment was achieved in the primary position with the use of the augmented transposition procedure alone . On average,20 degrees of binocular fusion into the abducted field was obtained . No postoperative limitation of adduction in the transposed eye was noted . Among the patients with Duane syndrome, 80% had elimination of the face turn; one patient had 5 degrees of residual face turn . The one patient with previous transposition surgery alone had an 80% (16 PD) reduction of the recurrent esotropia after placement of lateral fixation sutures . After augmented transpositions, induced vertical deviations in the primary position were uncommon (4/20 patients) and not greater than 2 PD . Significant lid fissure changes were not seen . CONCLUSIONS: The addition of lateral fixation sutures to full vertical rectus muscle transpositions improves the tonic abducting force of the procedure for patients with lateral rectus palsy and type I Duane syndrome without compromising adduction. J Neurobiol, 1999 Nov 15, 41(3), 340 - 8 Characterization of ATP release from cultures enriched in cholinergic amacrine-like neurons; Santos PF et al.; Adenosine triphosphate (ATP) has been proposed to play a role as a neurotransmitter in the retina, but not much attention has been given to the regulation of ATP release from retinal neurons . In this work, we investigated the release of ATP from cultures enriched in amacrine-like neurons . Depolarization of the cells with KCl, or activation of alpha-amino-3-hydroxy- 5-methyl-4-isoxazole-propionate (AMPA) receptors, evoked the release of ATP, as determined by the luciferin/luciferase luminescent method . The ATP release was found to be largely Ca(2+) dependent and sensitive to the botulinum neurotoxin A, which indicates that the ATP released by cultured retinal neurons originated from an exocytotic pool . Nitrendipine and omega-Agatoxin IVA, but not by omega-Conotoxin GVIA, partially blocked the release of ATP, indicating that in these cells, the Ca(2+) influx necessary to trigger the release of ATP occurs in part through the L- and the P/Q types of voltage-sensitive Ca(2+) channels (VSCC), but not through N-type VSCC . The release of ATP increased in the presence of adenosine deaminase, or in the presence of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A(1) receptor antagonist, showing that the release is tonically inhibited by the adenosine A(1) receptors . To our knowledge, this is the first report showing the release of endogenous ATP from a retinal preparation . Biochim Biophys Acta, 1999 Oct 18, 1441(1), 1 - 3 Gangliosides are the binding substances in neural cells for tetanus and botulinum toxins in mice; Kitamura M et al.; We used the knockout mice lacking gangliosides and evaluated their response to tetanus and botulinum toxins . We found that tetanus toxin and botulinum type A or B toxin was less toxic in the knockout mice . We conclude that the toxins bind to the gangliosides on the synapses in the initial step of intoxication prior to penetration of the toxins into the neural cells. Laryngoscope, 1999 Oct, 109(10), 1589 - 93 Laryngeal contact granuloma; Wani MK et al.; OBJECTIVE: To report outcomes of treatment for laryngeal contact granuloma . STUDY DESIGN: Prospective treatment of 21 patients with laryngeal contact granulomas using proton-pump inhibitor (PPI) medication . METHODS: Patients were diagnosed and followed by office endoscopy and patient interview . RESULTS: Three patients did not tolerate PPI medication and were managed by treatment with type 2 histamine (H2) blockers . The lesion completely resolved in 14 of the 18 patients maintained on PPI medication, and significantly regressed in the other 4 . Residual granulomas were surgically excised in one patient . Lesions resolved in two patients following injection of botulinum toxin into one thyroarytenoid muscle . One patient had a residual lesion, but symptoms were controlled by medication, and he declined treatment with botulinum toxin . Of the three patients treated with H2-blocker medication, the lesion resolved in only one . CONCLUSION: PPI medication is effective in the treatment of laryngeal contact granuloma, even in the absence of identifiable symptoms of gastroesophageal reflux. J Mol Biol, 1999 Sep 3, 291(5), 1091 - 104 Sequence homology and structural analysis of the clostridial neurotoxins; Lacy DB et al.; The clostridial neurotoxins (CNTs), comprised of tetanus neurotoxin (TeNT) and the seven serotypes of botulinum neurotoxin (BoNT A-G), specifically bind to neuronal cells and disrupt neurotransmitter release by cleaving proteins involved in synaptic vesicle membrane fusion . In this study, multiple CNT sequences were analyzed within the context of the 1277 residue BoNT/A crystal structure to gain insight into the events of binding, pore formation, translocation, and catalysis that are required for toxicity . A comparison of the TeNT-binding domain structure to that of BoNT/A reveals striking differences in their surface properties . Further, the solvent accessibility of a key tryptophan in the C terminus of the BoNT/A-binding domain refines the location of the ganglioside-binding site . Data collected from a single frozen crystal of BoNT/A are included in this study, revealing slight differences in the binding domain orientation as well as density for a previously unobserved translocation domain loop . This loop and the conservation of charged residues with structural proximity to putative pore-forming sequences lend insight into the CNT mechanism of pore formation and translocation . The sequence analysis of the catalytic domain revealed an area near the active-site likely to account for specificity differences between the CNTs . It revealed also a tertiary structure, highly conserved in primary sequence, which seems critical to catalysis but is 30 A from the active-site zinc ion . This observation, along with an analysis of the 54 residue "belt" from the translocation domain are discussed with respect to the mechanism of catalysis. Neurol India, 1999 Sep, 47(3), 206 - 9 Botulinum toxin treatment of hemifacial spasm and blepharospasm: objective response evaluation; Thussu A et al.; Twenty seven patients with hemifacial spasm (HFS) and sixteen patients with blepharospasm (BS) having mean Jankovic disability rating scale score of 2.56+0.58 SD and 2.81+0.54 SD, respectively, were treated with botulinum toxin A (BTX-A) injections . The total number of injection sessions were ninety one with relief response in 98.91% . The mean improvement in function scale score was 3.78+0.64 SD and 3.29+1.07 SD respectively, in HFS and BS groups . The clinical benefit induced by botulinum toxin lasted for a mean of 4.46+3.11 SD (range 2 to 13) months in HFS group and 2.66+1.37 SD (range 1 to 6) months, in BS groups . Transient ptosis was seen in 4.39% of total ninety one injection sessions . These findings show that local botulinum toxin treatment provides effective, safe and long lasting relief of spasms. Neurosci Lett, 1999 Sep 3, 272(1), 33 - 6 Plasticity of cortical hand muscle representation in patients with hemifacial spasm; Liepert J et al.; To investigate interactions between face and hand representations in the human motor cortex, we studied patients with a hemifacial spasm before and after treatment with Botulinum toxin . Focal transcranial magnetic stimulation was used to assess the cortical motor output map of the abductor pollicis brevis muscle (APB) on both sides . Prior to therapy the representation of the APB ipsilateral to the facial muscle contractions (iAPB) was significantly smaller than on the contralateral side . Two weeks after successful therapy, the iAPB output area was significantly enlarged and expanded into the direction of the face representation . The results indicate activity dependent interactions between hand and face representations in the adult human motor cortex. Otolaryngol Head Neck Surg, 1999 Oct, 121(4), 410 - 3 Vocal fold granuloma: successful treatment with botulinum toxin; Orloff LA et al.; Vocal fold granulomas are benign but frequently recurrent lesions that can cause frustration for both the patient and the treating physician . Etiologic factors include endotracheal intubation, vocal abuse, and gastroesophageal reflux . Conventional treatment for granulomas has included medical, voice, and surgical therapy, none with uniform success . In this study 8 patients with vocal fold granulomas were treated with intralaryngeal injection of botulinum toxin . The resultant temporary paresis of the vocal folds allowed for a window of time during which the vocal process could heal and the granulomas could resolve without being exposed to ongoing intermittent contact and friction with the opposing arytenoid . Although the underlying cause of a granuloma must also be addressed, we have found that botulinum toxin can be a useful adjunct to traditional therapy and can lead to avoidance of repetitive surgical procedures. Gastrointest Endosc, 1999 Oct, 50(4), 545 - 8 Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum; Wehrmann T et al.; BACKGROUND: In some patients with pancreas divisum, obstruction to the flow of pancreatic juice into the duodenum is the presumptive cause of acute recurrent pancreatitis . However, identification of those patients who may benefit from minor papilla sphincterotomy or stent placement is difficult . METHODS: Five patients with acute recurrent pancreatitis and pancreas divisum were therefore treated by endoscopic injection of 50 units of botulinum toxin into the minor papilla in an outpatient setting . RESULTS: Botulinum toxin injection was successfully performed on six occasions in 5 patients and no adverse effects were noted . Two patients relapsed after 9 and 10 months, respectively, but had definite relief of symptoms after needle-knife sphincterotomy . One patient relapsed 7 months after botulinum toxin injection but became symptom free again after a second botulinum toxin injection . Another patient is still in clinical remission 4 months after botulinum toxin administration, and 1 patient did not respond to either botulinum toxin administration or to sphincterotomy and stent placement . CONCLUSIONS: Endoscopic injection of botulinum toxin into the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis is a safe procedure that is easy to perform and provides short-term relief in some patients . Response to botulinum toxin injection may predict whether patients with pancreas divisum and acute recurrent pancreatitis will benefit from other forms of endoscopic therapy. Gastrointest Endosc, 1999 Oct, 50(4), 492 - 8 Intrasphincteric botulinum toxin versus pneumatic dilatation for achalasia: a cost minimization analysis; Panaccione R et al.; BACKGROUND: Pneumatic dilatation or intrasphincteric botulinum toxin injection provide effective symptom relief for patients with achalasia . Although intrasphincteric botulinum toxin injection is simple and safe, its efficacy may be short-lived . Pneumatic dilatation lasts longer, but esophageal perforation is a risk . We compared treatment costs for pneumatic dilatation and intrasphincteric botulinum toxin injection using a decision analysis model to determine whether the practical advantages of intrasphincteric botulinum toxin injection outweigh the economic impact of the need for frequent re-treatment . METHODS: Probability estimates for intrasphincteric botulinum toxin injection were derived from published reports . Probability estimates for the pneumatic dilatation strategy were obtained by retrospective review of our 10-year experience using the Rigiflex dilator . Direct, "third-party payer" costs were determined in Canadian dollars . RESULTS: Intrasphincteric botulinum toxin injection was significantly more costly at $5033 compared with $3608 for the pneumatic dilatation strategy, yielding an incremental cost of $1425 over the 10-year period considered . Sensitivity analysis showed that pneumatic dilatation is less expensive across all probable ranges of costs and probability estimates . The intrasphincteric botulinum toxin injection strategy is less costly if life-expectancy is less than 2 years . CONCLUSIONS: Intrasphincteric botulinum toxin injection is more costly than pneumatic dilatation for the treatment of achalasia . The added expense of frequent re-treatment with intrasphincteric botulinum toxin injection outweighs the potential economic benefits of the safety of the procedure, unless life-expectancy is 2 years or less. Mol Cell Biochem, 1999 Aug, 198(1-2), 19 - 30 Basic fibroblast growth factor stimulates cytosolic phospholipase A2, phospholipase C-gamma1 and phospholipase D through distinguishable signaling mechanisms; Sa G et al.; Fibroblast growth factors (FGFs) stimulate proliferation, differentiation and motility of different cell types . The cellular effects of FGF are transduced by its interaction with any one of four members of a family of high affinity, cell surface FGF receptors (FGFRs) that have autophosphorylating tyrosine kinase activity . Activation of FGFR causes release of various low molecular weight signaling molecules which are required for the pleotropic effects of FGFs . We report here that basic FGF plays critical role in membrane phospholipid hydrolysis in NIH 3T3 cells that are stably transfected with FGFR1 . Upon binding to FGFR1, basic FGF stimulates cytosolic form of phospholipase A2 (cPLA2), phospholipase C-gamma1 (PLC-gamma1) and phospholipase D (PLD), the key enzymes for the production of various lipid second messengers, in a tyrosine kinase-dependent manner . In addition to tyrosine phosphorylation, cPLA2 catalytic activation requires serine phosphorylation by p42 mitogen-activated protein (MAP) kinase and possibly pertussis toxin-sensitive G-protein coupling . On the other hand, phosphatidyl inositol 4,5 bisphosphate (PIP2) hydrolysis requires direct phosphorylation at tyrosine residue of the PLC-gamma1 isozyme . The activation of PLD needs direct or indirect receptor tyrosine kinase and protein kinase C (PKC) activities . Additionally, it also requires botulinum toxin C-sensitive Rho-like G-protein activation . All these results suggest that the pleotropic effects of FGF are exerted through its tyrosine kinase receptors and individual effectors are activated via distinguishable signaling mechanisms according to the cell's need. Dig Dis Sci, 1999 Aug, 44(8), 1588 - 9 Repeat botulin toxin injections in anal fissure: in patients with relapse and after insufficient effect of first treatment; Jost WH et al.; Botulin toxin (BoTx) injections are an alternative treatment for uncomplicated anal fissures . Until recently, surgical management has been advocated for therapeutic failure of BoTx and recurrent fissures . In 20 patients with recurring anal fissure we examined the remission rate following a second course of botulin treatment . The dose was identical to the first treatment (5 units Botox) . In group 2, 30 patients with therapeutic failure were treated with a higher dose of botulin toxin (10 units) . In our patients with recurring fissure, 19 of 20 were pain-free within a week (95%) . After three months, 14 patients (70%) had healed fissures . In group 2, 22 of 30 patients (73%) became pain-free within the first week following the second course of treatment . Two patients (7%) suffered from transient mild incontinence . Nineteen patients (63%) showed healed fissures three months following the second BoTx treatment . BoTx remains an effective treatment in recurring anal fissure as well as in patients with therapeutic failure of prior BoTx injections. Ophthalmology, 1999 Sep, 106(9), 1727 - 30 The role of botulinum toxin A in acute-onset esotropia; Dawson EL et al.; OBJECTIVE: To establish the effectiveness of botulinum toxin A (BTXA) in the treatment of patients with acute acquired concomitant esotropia . DESIGN: Retrospective, interventional, noncomparative case series . PARTICIPANTS: Fourteen patients presenting to the Strabismus and Pediatric Service at Moorfields Eye Hospital with acute-onset esotropia over a 6-year period (1991-1997) . INTERVENTION: 2.5 units of BTXA injected into the unilateral medial rectus muscle of the deviating eye under electromyographic control . MAIN OUTCOME MEASURES: Pre- and postinjection angle of deviation, pre- and postinjection stereopsis, final level of stereopsis achieved, and whether corrective squint surgery was later required . RESULTS: Fourteen patients were identified, of whom eight were male and six female . The mean age at presentation was 5.4 years, and the average time from onset to attending the clinic was 18 weeks . The mean time from onset of acute esotropia to injection was 32.5 weeks . All patients, except one, showed considerable improvement in their manifest deviation after one injection of BTXA . Eight patients (57%) maintained high-grade stereopsis of 120 seconds of arc or better and long-term ocular alignment with toxin treatment alone . In total, 11 patients (79%) gained improved stereopsis and maintained satisfactory ocular alignment with toxin therapy and did not require squint surgery . Two patients (14%) did not maintain a stable ocular position after toxin treatment and later required squint surgery, gaining good ocular alignment and high-grade stereopsis . The one patient who did not respond to the initial BTXA injection refused all further treatment . The mean follow-up time was 22 months . CONCLUSIONS: Botulinum toxin therapy has a definite role in the treatment of children with acute-onset esotropia . It may well obviate the need for squint surgery . The safety and ease of administration of this treatment add to its merits. Neuropediatrics, 1999 Jun, 30(3), 120 - 4 Botulinum toxin A in the management of spastic gait disorders in children and young adults with cerebral palsy: a randomized, double-blind study of "high-dose" versus "low-dose" treatment; Wissel J et al.; The present study was performed to assess dose-response relationships of local botulinum toxin A (BtxA) treatment in children and teenagers with spastic gait due to cerebral palsy (CP) in a randomized, double-blind study employing a "high-dose" (200 units Botox per leg) and a "low-dose" (100 units Botox per leg) treatment arm in 33 patients with CP . Response parameters included changes in muscle tone assessed by the Ashworth scale at knee joint, range-of-motion (ROM) measurements at knee and ankle joint, objective analysis of longitudinal gait parameters as well as subjective assessments of improvement . Patients in the "high-dose" arm received 40-80 units Botox/muscle versus 20-40 units Botox/muscle in the "low-dose" group . Patients in both treatment arms showed significant improvement of Ashworth score (p<0.001) and ROM (p<0.01), while gait analysis revealed significant increase in gait velocity (p<0.01) and stride-length (p<0.001) over baseline . Subjects in the "high-dose" group showed significantly greater improvement on objective response measurements compared to "low-dose" patients . Also, children aged 7 years or less had greater functional benefit compared to the subgroup of patients older than 7 years . Incidence and severity of side-effects were similar in both treatment groups . The present study demonstrated dose-dependent functional improvement of dynamic deformities and spastic gait pattern in children and young adults with CP treated with local injections of botulinum toxin . A dose of 200 units Botox per leg distributed to 4 or 5 muscle bellies per leg is superior compared to 100 units Botox per leg without significantly affecting the risk of side-effects. Clin Neurophysiol, 1999 Sep, 110(9), 1650 - 4 Long-term botulinum toxin treatment of cervical dystonia--EMG changes in injected and noninjected muscles; Erdal J et al.; OBJECTIVE: To evaluate changes in quantitative EMG of injected and noninjected sternocleidomastoid muscles following long-term unilateral botulinum toxin treatment of cervical dystonia . METHODS: We investigated 27 patients with cervical dystonia, who received repeated unilateral botulinum toxin injections of the sternocleidomastoid muscle, with quantitative EMG at rest and at maximal voluntary contraction . The patients had on the average 7.1 botulinum toxin treatments and the follow-up period was on the average 31 months (SD 16) . RESULTS: After the first treatment, the injected sternocleidomastoid muscles showed a significant decrease in turns/s (mean 45%) and amplitude (mean 52%) at rest, and in amplitude at maximal flexion (mean 24%) and rotation (mean 39%) . Except for a reduction in turns/s at rotation (mean 19%) no further reductions in EMG parameters were seen after long-term treatment . The contralateral noninjected sternocleidomastoid muscles showed no significant change in EMG activity after the first BT treatment, but after long-term treatment a significant reduction in turns/s and amplitude at both maximal flexion (turns: mean 28%; amplitude: mean 25%) and rotation (turns/s: mean 32%; amplitude: mean 25%) were seen as compared to pretreatment values . CONCLUSION: The results indicate that there seems to be no cumulative chemodenervation by repeated botulinum toxin injections of sternocleidomastoid muscles measured by quantitative EMG . Contralateral noninjected sternocleidomastoid muscles however, seem to be affected following long-term treatment . The mechanism behind this finding is unknown. Eur J Paediatr Neurol, 1999, 3(4), 175 - 6 Botulinum toxin for amelioration of knee contracture in Duchenne muscular dystrophy; von Wendt LO et al.; An 11-year-old non-ambulant boy with Duchenne muscular dystrophy developed tightness in his left knee flexors, which caused difficulties in standing exercises . Botulinum toxin A (BTX-A) was injected into the medial and lateral hamstring muscles and the range of motion increased by 20 degrees but after 5 months, when the pharmacological effect of BTX-A had vanished, an increase of only 5 degrees in range compared with the initial finding was left . It is concluded that there may be a role for BTX-A in controlling contractures in Duchenne muscular dystrophy. Br J Plast Surg, 1999 Apr, 52(3), 230 - 1 Botulinum toxoid in the management of gustatory sweating (Frey's syndrome) after superficial parotidectomy; Birch JF et al.; Botulinum toxin has been successfully used to treat Frey's syndrome occurring in a 31-year-old patient following superficial parotidectomy for pleomorphic adenoma . An initial injection of 7.5 U (0.3 ml over 6 cm2 of cheek) resulted in 3 months' resolution of gustatory sweating and flushing and a second injection 12 months' symptomatic improvement . The symptoms recurred after further facial surgery. Ophthalmic Res, 1999, 31(6), 392 - 8 Effects of intravitreal injection of botulinum toxin on the electroretinogram of rats; Li S et al.; The retinal toxicity of botulinum toxin A (BTA) was electroretinographically studied in rats . Sixteen rats were injected intravitreally with 10 ng of BTA . A response-amplitude series was recorded before and 1, 6, 13 and 21 days after the injection of BTA . BTA did not alter the amplitude and the peak latency of the a-wave . The amplitude of the b-wave was not changed except for 2 rats, in which the b-wave was diminished . The peak latency of the b-wave was significantly prolonged after injection of 10 ng BTA (p < 0.05) . Except for these latter 2 rats, the results indicated that the dosage used therapeutically appears to have no deleterious effect on retinal integrity or function at least in the short term, but multiple injections or higher doses of BTA could alter retinal function. Gait Posture, 1999 Sep, 10(1), 1 - 9 Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy; Sutherland DH et al.; The purpose of this study was to quantify the gait of subjects receiving two injections of either botulinum A toxin or saline vehicle into the gastrocnemius muscle(s) . The study group consisted of cerebral palsy patients who walked with an equinus gait pattern . This study was a randomized, double-blinded, parallel clinical trial of 20 subjects . All were studied by gait analysis before and after the injections . There were no adverse effects . Peak ankle dorsiflexion in stance and swing significantly improved in subjects who received the drug and not in controls . Results of this double blind study give support to the short term efficacy of botulinum toxin A to improve gait in selected patients with cerebral palsy. Dermatol Surg, 1999 May, 25(5), 373 - 5; discussion 376 Raising eyebrows with botulinum toxin; Huilgol SC et al.; BACKGROUND: Brow elevation rejuvenates the facial appearance . OBJECTIVE: To determine if a significant degree of brow elevation could be achieved through selective botulinum toxin treatment of brow depressors . METHODS: Seven women aged 31-42 (mean 37) years old were treated . The distance from lowest eyebrow cilium of the eyebrow to the midpupillary point was measured before and 1 month posttreatment . Botulinum toxin was injected into the glabellar area (7-10U) and the supralateral eyebrow (0-2.5U each side), to a total dose of 10-14 U . RESULTS: Five individuals (71%) showed brow elevation of 1-3 mm with a mean elevation of 1 mm . Two individuals showed no change . Concurrent weakening of the frown response was noted in all patients . CONCLUSION: Botulinum toxin treatment of brow depressors produces a small degree of brow elevation in the majority of patients. Aliment Pharmacol Ther, 1999 Sep, 13(9), 1221 - 5 Early experience with intrasphincteric botulinum toxin in the treatment of achalasia; Greaves RR et al.; BACKGROUND: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long-lasting in the treatment of achalasia . AIM: To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia . METHODS: Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20-87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter . Patients were assessed pre-treatment and 1 month after treatment using a symptom score and oesophageal manometry . Median follow-up was 12 months (range 6-28) . RESULTS: The injection procedure was simple to perform and free of adverse effects . Although treatment had a beneficial effect on dysphagia (median pre-treatment score 3 {interquartile range 3-3}; post-treatment score 2 {0-3}: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores . Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg {21-42} pre-treatment, 28.5 {17.5-55.5} post-treatment P=0.67) . Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years . CONCLUSION: Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia. Neurol Neurochir Pol, 1999 Mar-Apr, 33(2), 351 - 7 {Spasmodic torticollis: experience of 5 years with botulinum toxin treatment}; Domzal TM; 64 cases with spasmodic torticollis were observed during 5 years and treated with botulinum toxin (BTX) . BTX was injected into dystonic muscles mostly into sternocleidomastoid then--trapezius, and splenius capitis muscle . Improvement (excellent, good and fair) was achieved in 40 patients (62%) . Lack of information about 6 patient (9%) . Injections were repeated every 3-4 months and in several cases even 1-2 during the year . After several injections atrophy and denervation potentials in EMG were observed in the majority of injected muscles . Neurotic syndromes coexisting with dystonia had worsening influence on therapeutic effects . Adverse events were observed in 5 cases . Treatment with BTX is very simple, easy, harmless and can be administered in outpatients. Neurol Neurochir Pol, 1998 Sep-Oct, 32(5), 1273 - 80 {A case of laryngeal adductor dystonia treated with transcutaneous injections of botulinum toxin}; Zielinska M et al.; We present a case of 47-year old patient with a rare form of focal dystonia restricted to laryngeal adductors with blepharospasm . Apart from typical symptoms of blepharospasm, the patient had severe problems with articulation in the form of harsh voice, frequently interrupted speech and the sound coming out with a great effort . We applied a transcutaneous botulin toxin therapy to this patient . The toxin was given into thyroarytenoid muscle in transcutaneous injections under control of