OBJECTIVE: To evaluate the authors' first 100 patients treated for achalasia by a minimally invasive approach. METHODS: Between November 1992 and February 2001, the authors performed 95 laparoscopic and 5 thoracoscopic Heller myotomies in 100 patients (age 49.5 +/- 1.5 years) with manometrically confirmed achalasia. Before presentation, 51 patients had previous dilation, 23 had been treated with botulinum toxin (Botox), and 4 had undergone prior myotomy. Laparoscopic myotomy was performed by incising the distal 4 to 6 cm of esophageal musculature and extended 1 to 2 cm onto the cardia under endoscopic guidance. Fifteen patients underwent antireflux procedures. RESULTS: There were eight intraoperative perforations and only four conversions to open surgery. Follow-up is 10.8 +/- 1 months; 75% of the patients have been followed up for at least 14 months. Outcomes assessed by patient questionnaires revealed satisfactory relief of dysphagia in 93 patients and "poor" relief in 7 patients. Postoperative heartburn symptoms were reported as "moderate to severe" in 14 patients and "none or mild" in 86 patients. Fourteen patients required postoperative procedures for continued symptoms of dysphagia after myotomy. Esophageal manometry studies revealed a decrease in lower esophageal sphincter pressure (LESP) from 37 +/- 1 mm Hg to 14 +/- 1 mm Hg. Patients with a decrease in LESP of more than 18 mm Hg and whose absolute postoperative LESP was 18 or less were more likely to have relief of dysphagia after surgery. Thirty-one patients who underwent Heller alone were studied with a 24-hour esophageal pH probe and had a median Johnson-DeMeester score of 10 (normal <22.0). Mean esophageal acid exposure time was 3 +/- 0.6% (normal 4.2%). Symptoms did not correlate with esophageal acid exposure. CONCLUSIONS: The results after minimally invasive treatment for achalasia are equivalent to historical outcomes with open techniques. Satisfactory outcomes occurred in 93% of patients. Patients whose postoperative LESP was less than 18 mm Hg reported the fewest symptoms. After myotomy, patients rarely have abnormal esophageal acid exposure, and the addition of an antireflux procedure is not required. (+info)
An intrinsic distinction in neuromuscular junction assembly and maintenance in different skeletal muscles.
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We analyzed the formation of neuromuscular junctions (NMJs) in individual muscles of the mouse embryo. Skeletal muscles can be assigned to one of two distinct classes of muscles, termed "Fast Synapsing" (FaSyn) and "Delayed Synapsing" (DeSyn) muscles, which differ significantly with respect to the initial focal clustering of postsynaptic AChRs, the timing of presynaptic maturation, and the maintenance of NMJs in young adult mice. Differences between classes were intrinsic to the muscles and manifested in the absence of innervation or agrin. Paralysis or denervation of young adult muscles resulted in disassembly of AChR clusters on DeSyn muscles, whereas those on FaSyn muscles were preserved. Our results show that postsynaptic differentiation processes intrinsic to FaSyn and DeSyn muscles influence the formation of NMJs during development and their maintenance in the adult. (+info)
Botulinum neurotoxin A activity is dependent upon the presence of specific gangliosides in neuroblastoma cells expressing synaptotagmin I.
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Botulinum neurotoxin A (BoNT/A) is the deadliest of all known biological substances. Although its toxicity makes BoNT/A a biological warfare threat, its biologic activity makes it an increasingly useful therapeutic agent for the treatment of muscular disorders. However, almost 200 years after its discovery, the neuronal cell components required for the activity of this deadly toxin have not been unequivocally identified. In this work, neuroblastoma cells expressing synaptotagmin I, a protein shown to be bound by BoNT/A, were used to determine whether specific gangliosides were necessary for BoNT/A activity as measured by synaptosomal-associated protein of 25 kDa (SNAP-25) cleavage. Ganglioside GT1b was found to support BoNT/A activity significantly more effectively than GD1a, which was far more effective than GM1 when added to ganglioside-deficient murine cholinergic Neuro 2a or to human adrenergic SK-N-SH neuroblastoma cells. Whereas both cell lines expressed synaptotagmin I, SNAP-25 cleavage was not observed in the absence of complex gangliosides. These results indicate that 1) gangliosides are required for BoNT/A activity, 2) synaptotagmin I in the absence of gangliosides does not support BoNT/A activity, and 3) Neuro 2a cells are an efficient model system for studying the biological activity of BoNT/A. (+info)
Focal lingual dystonia, urinary incontinence, and sensory deficits secondary to low voltage electrocution: case report and literature review.
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Electrocution injuries are well reported in review articles and cases of high voltage electrocution injury are abundant. However, reports of low voltage electrocution injury are few. A case is presented of low voltage shock from a 120 volt AC source with presentation, acute and chronic course, and a five year follow up. The patient experienced several unusual complications of low voltage electrocution: a persistent right tongue deviation, which initially presents as an isolated hypoglossal nerve palsy, but subsequently manifests as a focal lingual dystonia; total body paresthesia with urinary incontinence; and persistent sensory deficits to the face and tongue. (+info)
Local injection of botulinum toxin type A for hemifacial spasm.
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The preliminary experience of botulinum toxin treatment for hemifacial spasm is reported in this study. Five patients were treated with 10 injections of botulinum toxin in total. Botulinum toxin had a good to excellent effect in all cases. Improvement was observed 2 weeks to 1 month after the injection. The duration of improvement was 0-9 months (mean 4.2 months). The peak rank tended to decrease and the duration of improvement increased after several treatments. Hemifacial spasm caused by the anterior inferior cerebellar artery tended to subside easily. In contrast, compression by the vertebral artery was more refractory. Continuous facial spasm caused by operative trauma subsided after the injection, but paroxysmal spasm still occurred when eating or laughing. Spasm caused by trauma disappeared 4.5 months after the injection. The complications, which were facial nerve paresis in two cases (3 injections, 30%) and diplopia in one case (1 injection, 10%), were transient and subsided in 2 weeks. (+info)
Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke.
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BACKGROUND: Spasticity is a disabling complication of stroke, and it is uncertain whether intramuscular injections of botulinum toxin type A reduce disability in persons with spasticity of the wrist and fingers after a stroke. METHODS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to assess the efficacy and safety of one-time injections of botulinum toxin A (200 to 240 units) in 126 subjects with increased flexor tone in the wrist and fingers after a stroke. The primary outcome measure was self-reported disability in four areas: personal hygiene, dressing, pain, and limb position (on a four-point scale ranging from no disability to severe disability) at six weeks; at base line, each subject selected one of these areas in which there was moderate-to-severe disability as the principal target of treatment. RESULTS: Subjects who received botulinum toxin A had greater improvement in flexor tone in the wrist and fingers at all follow-up visits through 12 weeks than did subjects who received placebo (P<0.001 for all comparisons). Subjects treated with botulinum toxin A had greater improvement in the principal target of treatment at weeks 4, 6, 8, and 12 (P<0.001, P<0.001, P=0.03, and P=0.02, respectively); at week 6, 40 of the 64 subjects in the botulinum-toxin group (62 percent), as compared with 17 of the 62 in the placebo group (27 percent), reported improvement of at least one point on the Disability Assessment Scale in the principal target of treatment (P<0.001). There were no major adverse events associated with injection of botulinum toxin A. CONCLUSIONS: Intramuscular injections of botulinum toxin A reduce spasticity of the wrist and finger muscles and associated disability in patients who have had a stroke. (+info)
Complex gangliosides at the neuromuscular junction are membrane receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function.
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One specialization of vertebrate presynaptic neuronal membranes is their multifold enrichment in complex gangliosides, suggesting that these sialoglycolipids may play a major functional role in synaptic transmission. We tested this hypothesis directly by studying neuromuscular synapses of mice lacking complex gangliosides attributable to deletion of the gene coding for beta1,4 GalNAc-transferase (GM2/GD2 synthase), which catalyzes an early step in ganglioside synthesis. Our studies show that complex gangliosides are surprisingly redundant for regulated neurotransmitter release under normal physiological conditions. In contrast, we show that they are membrane receptors for both the paralytic botulinum neurotoxin type-A and human neuropathy-associated anti-ganglioside autoantibodies that arise through molecular mimicry with microbial structures. These data prove the critical importance of complex gangliosides in mediating pathophysiological events at the neuromuscular synapse. (+info)
Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog heart.
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There is no data about whether botulinum neurotoxin inhibits the parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. Therefore, we investigated whether botulinum toxin (type A) injected into the sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation of the preganglionic parasympathetic nerves in the heart of the anesthetized dog. Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation) prolonged the atrial interval but not the atrioventricular (AV) interval, and cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV intervals. After botulinum toxin (20 or 25 mouse units) was injected into the SA fat pad, it gradually inhibited the prolongation of the atrial interval evoked by SAP and CV stimulations but not the prolongation of the AV interval evoked by CV stimulation. Conditioning successive stimulation of the cervical vagus nerves accelerated the inhibition by botulinum toxin of the chronotropic response to CV stimulation. These results indicate that selective injection of botulinum toxin into the SA fat pad blocks bradycardia mediated by parasympathetic ganglionic activation in the dog heart. (+info)