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Lawrence B Cohen

Publications and source records attributed to Lawrence B Cohen.

22 records · Page 2Linked to original sources

Endoscopic implantation of enteryx for treatment of GERD: 12-month results of a prospective, multicenter trial.

OBJECTIVES: This study aimed to assess the efficacy and safety of endoscopically implanting a nonresorbable biocompatible polymer (Enteryx) in the distal esophagus and proximal gastric cardia for the treatment of gastroesophageal reflux disease (GERD). METHODS: In a prospective, multicenter, international trial, 85 well-controlled GERD patients who were receiving chronic proton pump inhibitor (PPI) therapy underwent Enteryx implantation under fluoroscopic visualization, without general anesthesia. After the procedure, patients were discharged within approximately 2-4 h. Patients were judged to be treatment responders if after implantation they reduced PPI dosage by >/=50%. Follow-up evaluations were conducted at 1, 3, 6, and 12 months and included medication usage, symptoms, quality of life, endoscopy, pH monitoring, manometry, and documentation of adverse events. RESULTS: At 12 months, 80.3% (95% CI = 69.9%-88.3%) of 81 evaluable patients were treatment responders. Of the responders, 87.7% completely discontinued PPIs, and 12.3% reduced PPI dosage by >/=50%. Treatment response was more likely in patients with residual implant volume of >/=5 mL (p = 0.027). Other patient and treatment variables were not predictive. Both GERD heartburn and regurgitation symptom scores significantly improved at 12 months compared with baseline (p < 0.001). There were significant reductions in median supine, upright, and total percent time of esophageal exposure to pH <4. Endoscopically assessed esophagitis grades were unchanged. No serious adverse events were encountered. Transient retrosternal chest pain was experienced by 91.8% of patients. This pain was seldom severe and was typically successfully managed with prescription pain medication. CONCLUSIONS: Enteryx implantation allows most patients to discontinue PPI therapy, improves their symptoms, and reduces esophageal acid exposure. The effects of implantation are long-lasting, and morbidity is transient and minimal. The procedure requires basic endoscopic skills and seems to provide a useful option in the effective clinical management of GERD.

Adult↗

Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb.

We compared odorant-evoked patterns of receptor neuron input to the mouse olfactory bulb, imaged with a calcium-sensitive dye, with those of intrinsic optical signals imaged from the same preparations. Both methods yielded patterns of glomerular activity that showed a strong concentration dependence, a loosely organized chemotopy, and involved widely distributed glomeruli. Presynaptic calcium and intrinsic signals showed similar odorant concentration thresholds. Intrinsic signal foci were larger than their corresponding calcium signals, and input to multiple adjacent glomeruli often appeared as a single intrinsic focus. Nonetheless, at near-threshold concentrations, the correspondence between the glomerular calcium and intrinsic signals averaged 75%, with a 71% correspondence between the most strongly activated glomeruli. The correspondence between strongly activated glomeruli decreased as odorant concentration increased, dropping to 51% at 5- to 15-fold higher concentrations. Intrinsic signal foci often saturated at lower concentrations than the calcium signal, implying a smaller dynamic range, and suprathreshold concentrations could recruit strong intrinsic signals in areas showing little or no calcium signal. These differences were such that, at suprathreshold concentrations, the chemotopy of calcium and intrinsic signal response maps often differed. These results suggest that intrinsic optical signals closely reflect receptor neuron input to glomeruli at low odorant concentrations but reflect additional processes at higher concentrations (activation of second-order neurons, centrifugal input, or constraints on the coupling between neuronal activity and hemodynamic changes). Intrinsic signals that are not associated with receptor neuron input have the potential to impact the interpretation of spatial coding strategies in the olfactory bulb.

Animals↗

Presynaptic inhibition of olfactory receptor neurons in crustaceans.

Presynaptic inhibition of transmitter release from primary sensory afferents is a common strategy for regulating sensory input to the arthropod central nervous system. In the olfactory system, presynaptic inhibition of olfactory receptor neurons has been long suspected, but until recently could not be demonstrated directly because of the difficulty in recording from the afferent nerve terminals. A preparation using the isolated but intact brain of the spiny lobster in combination with voltage-sensitive dye staining has allowed stimulus-evoked responses of olfactory receptor axons to be recorded selectively with optical imaging methods. This approach has provided the first direct physiological evidence for presynaptic inhibition of olfactory receptor neurons. As in other arthropod sensory systems, the cellular mechanism underlying presynaptic afferent inhibition appears to be a reduction of action potential amplitude in the axon terminal. In the spiny lobster, two inhibitory transmitters, GABA and histamine, can independently mediate presynaptic inhibition. GABA- and histaminergic interneurons in the lobster olfactory lobe (the target of olfactory receptor neurons) constitute dual, functionally distinct inhibitory pathways that are likely to play different roles in regulating primary olfactory input to the CNS. Presynaptic inhibition in the vertebrate olfactory system is also mediated by dual inhibitory pathways, but via a different cellular mechanism. Thus, it is possible that presynaptic inhibition of primary olfactory afferents evolved independently in vertebrates and invertebrates to fill a common, fundamental role in processing olfactory information.

Animals↗

Distributed and concentration-invariant spatial representations of odorants by receptor neuron input to the turtle olfactory bulb.

We sought to characterize how odorants are represented at the level of afferent input to the olfactory bulb of the box turtle, a terrestrial reptile that, like mammals, detects airborne odorants. Using methods developed first in zebrafish, we selectively labeled olfactory receptor neurons with Calcium Green-1 dextran and imaged odorant-evoked input to glomeruli in vivo. Odorant representations were imaged at a glomerular level of resolution over a portion of the dorsal olfactory bulb and at a regional level of resolution over the entire dorsal surface. We report two new findings. First, even at low concentrations, odorants typically elicited input to a large fraction of all imaged glomeruli. Second, while the amplitude of the odorant-evoked input to glomeruli was concentration dependent, the relative pattern of input to the bulb changed only slightly over a concentration range of up to three log units. These results suggest the hypothesis that odorant representations in the turtle involve differential levels of input to many glomeruli, and that detecting relative patterns of distributed glomerular activation may be an important strategy for encoding odor quality independent of intensity.

Animals↗