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Biomedical subjects

Lawrence B Cohen

Publications and source records attributed to Lawrence B Cohen.

At least 19 recordsLinked to original sources

Temporal dynamics and latency patterns of receptor neuron input to the olfactory bulb.

Odorants are first represented in the brain by distributed patterns of activity in the olfactory bulb (OB). Although neurons downstream of sensory inputs respond to odorants with temporally structured activity, sensory inputs to glomeruli are typically described as static maps. Here, we imaged the temporal dynamics of receptor neuron input to the OB with a calcium-sensitive dye in the olfactory receptor nerve terminals in anesthetized mice. We found that diverse, glomerulus- and odorant-dependent temporal dynamics are present even at this initial input stage. Instantaneous spatial patterns of receptor input to glomeruli changed both within and between respiration cycles. Glomerular odorant responses differed in amplitude, latency, rise time, and degree of modulation by sniffing in an odorant-specific manner. Pattern dynamics within the first respiration cycle recurred in a similar manner during consecutive cycles. When sniff rate was increased artificially, pattern dynamics were preserved in the first sniff but were attenuated during subsequent sniffs. Temporal response properties were consistent across individuals on a coarse regional scale and on a fine scale of individual glomeruli. Latency and magnitude of glomerular inputs were only weakly correlated and might therefore convey independent odorant information. These data demonstrate that glomerular maps of primary sensory input to the OB are temporally dynamic. These dynamics may contribute to the representation of odorant information and affect information processing in the central olfactory system of rodents.

Animals↗

Efficiency of an endoscopy suite in a teaching hospital: delays, prolonged procedures, and hospital waiting times.

BACKGROUND: Increased demand for screening colonoscopy necessitates improved efficiency in endoscopy units, especially more efficient use of existing resources. The purpose of this study was to assess the efficiency of the endoscopy unit of a large tertiary care teaching hospital. OBJECTIVE: To assess the efficiency of the endoscopy unit in a large tertiary care teaching hospital. DESIGN: Prospective study from May 16 to September 5, 2003. SETTING: Endoscopy unit of a 650-bed acute care teaching hospital. PATIENTS: Inpatient and outpatient procedures. MAIN OUTCOME MEASUREMENTS: Time elapsed between endoscopic procedures; the duration of the procedures; procedure delays (>15 minutes between procedures) and the reasons for them. RESULTS: The research assistant observed 675 endoscopic procedures done for 625 patients (207 inpatients [33%]). The most common procedure was colonoscopy (42.1%), followed by EGD (36.0%). Overall, procedures for 193 (30.9%) of the 625 patients were delayed (>15 minutes between procedures), 70.5% (136/193) because the physician was not available to start the procedure. The time elapsed between procedures was longer than 30 minutes for 47 of the 193 delayed procedures (24.4%). The duration of procedures was prolonged for about 22% (130/593) of procedures. CONCLUSIONS: Physician unavailability contributed to considerable delays in endoscopic procedures. Strategies to reduce procedure delays could have a favorable impact on the volume of procedures performed in the unit, thereby improving the use of existing resources. We encourage other groups to assess the efficiency of their hospital-based endoscopy units.

Canada↗

Sedation in endoscopic practice.

Sedation impacts every aspect of endoscopy practice--the quality fo the examination, the satisfaction of endoscopist and of patient, the efficiency and cost of delivering services, and the compliance of patients with surveillance guidelines. New sedation agents and improved patient-monitoring and drug-delivery technologies are challenging traditional practices. Increasing demand for endoscopic services, shrinking reimbursements, and competing diagnostic technologies are prompting recognition that new approaches to sedation can improve practice efficiency and patient outcome. This article discusses new developments in endoscopic sedation and their implications for practice management.

Anesthesiology↗

Endoscopic sedation in the United States: results from a nationwide survey.

OBJECTIVES: The introduction of new sedative agents as well as a desire for improved patient satisfaction and greater efficiency has changed the practice of endoscopic sedation. This survey was designed to provide national and regional data on endoscopic sedation and monitoring practices within the United States. METHODS: A 22-item survey regarding current practices of endoscopy and sedation was mailed to 5,000 American College of Gastroenterology physician members nationwide. RESULTS: A total of 1,353 questionnaires (27.1%) were returned. Respondents performed an average of 12.3 esophagogastroduodenoscopies (EGDs) and 22.3 colonoscopies per wk. Endoscopic procedures were performed within a hospital setting (55.2) more often than at an ambulatory center (35.8%) or private office (8.8%). The vast majority of EGDs and colonoscopies (>98%) were performed with endoscopic sedation. Almost three quarters (74.3%) of the respondents used a narcotic and benzodiazepine for sedation, while propofol was preferred by 25.7%. Sedation practices varied considerably within different geographic regions of the United States. Respondents routinely monitored vital signs and pulse oximetry (99.2% and 98.6%, respectively), and supplemental oxygen was administered to all patients during EGD by 72.7% of endoscopists. Endoscopist satisfaction with sedation was greater among those using propofol than conventional sedation (10 vs 8, p < 0.0001). CONCLUSIONS: During the past 15 yr, the volume of procedures performed by endoscopists in the United States has increased two- to fourfold. Propofol is currently being used for sedation in approximately one quarter of all endoscopies in the United States. The findings from this survey may help in the formulation of updated policies and practice guidelines pertaining to endoscopic sedation.

Adult↗

Interglomerular center-surround inhibition shapes odorant-evoked input to the mouse olfactory bulb in vivo.

Mouse olfactory receptor proteins have relatively broad odorant tuning profiles, so single odorants typically activate a substantial subset of glomeruli in the main olfactory bulb, resulting in stereotyped odorant- and concentration-dependent glomerular input maps. One of the functions of the olfactory bulb may be to reduce the extent of this rather widespread activation before transmitting the information to higher olfactory centers. Two circuits have been studied in vitro that could perform center-surround inhibition in the olfactory bulb, one circuit acting between glomeruli, the other through the classical reciprocal synapses between the lateral dendrites of mitral cells and the dendrites of granule cells. One unanswered question from these in vitro measurements was how these circuits would affect the response to odorants in vivo. We made measurements of the odorant-evoked increase in calcium concentration in the olfactory receptor neuron terminals in the anesthetized mouse to evaluate the role of presynaptic inhibition in reshaping the input to the olfactory bulb. We compared the glomerular responses in 2- to 4-wk-old mice before and after suppressing presynaptic inhibition onto the receptor neuron terminals with the GABAB antagonist, CGP46381. We find that the input maps are modified by an apparent center-surround inhibition: strongly activated glomeruli appear to suppress the release from receptor neurons terminating in surrounding glomeruli. This form of lateral inhibition has the effect of increasing the contrast of the sensory input map.

Afferent Pathways↗

Synthesis, spectra, delivery and potentiometric responses of new styryl dyes with extended spectral ranges.

Styryl dyes have been among the most widely used probes for mapping membrane potential changes in excitable cells. However, their utility has been somewhat limited because their excitation wavelengths have been restricted to the 450-550 nm range. Longer wavelength probes can minimize interference from endogenous chromophores and, because of decreased light scattering, improve recording from deep within tissue. In this paper we report on our efforts to develop new potentiometric styryl dyes that have excitation wavelengths ranging above 700 nm and emission spectra out to 900 nm. We have prepared and characterized dyes based on 47 variants of the styryl chromophores. Voltage-dependent spectral changes have been recorded for these dyes in a model lipid bilayer and from lobster nerves. The voltage sensitivities of the fluorescence of many of these new potentiometric indicators are as good as those of the widely used ANEP series of probes. In addition, because some of the dyes are often poorly water soluble, we have developed cyclodextrin complexes of the dyes to serve as efficient delivery vehicles. These dyes promise to enable new experimental paradigms for in vivo imaging of membrane potential.

Action Potentials↗

Oscillations in the olfactory bulb carry information about odorant history.

While odorant-evoked oscillations in the vertebrate olfactory bulb have been studied extensively, information about their possible cognitive role has been missing. Using voltage-sensitive dye imaging, we show that repeated odorant presentations with interstimulus intervals of 2-12 s had dramatic and diverse effects on the three oscillations that occur in the turtle olfactory bulb. Two of the oscillations are strikingly depressed in response to the second stimulation even of a new odorant was presented. The third oscillation is enhanced if the odorant is the same but suppressed if the odorant is new. The effects suggest that the oscillations carry information about odorant novelty and consistency.

Animals↗

Imaging brain activity with voltage- and calcium-sensitive dyes.

This paper presents three examples of imaging brain activity with voltage- or calcium-sensitive dyes and then discusses the methodological aspects of the measurements that are needed to achieve an optimal signal-to-noise ratio. Internally injected voltage-sensitive dye can be used to monitor membrane potential in the dendrites of invertebrate and vertebrate neurons in in vitro preparations. Both invertebrate and vertebrate ganglia can be bathed in voltage-sensitive dyes to stain all of the cell bodies in the preparation. These dyes can then be used to follow the spike activity of many neurons simultaneously while the preparations are generating behaviors. Calcium-sensitive dyes that are internalized into olfactory receptor neurons in the nose will, after several days, be transported to the nerve terminals of these cells in the olfactory bulb. There they can be used to measure the input from the nose to the bulb. Three kinds of noise are discussed. a. Shot noise from the random emission of photons from the preparation. b. Vibrational noise from external sources. c. Noise that occurs in the absence of light, the dark noise. Three different parts of the light measuring apparatus are discussed: the light sources, the optics, and the cameras. The major effort presently underway to improve the usefulness of optical recordings of brain activity are to find methods for staining individual cell types in the brain. Most of these efforts center around fluorescent protein sensors of activity.

Action Potentials↗

Enteryx implantation for GERD: expanded multicenter trial results and interim postapproval follow-up to 24 months.

BACKGROUND: Enteryx implantation in the esophagus is an alternative therapy for patients with proton pump inhibitor (PPI) dependent GERD. Although this treatment resulted in highly significant improvement at 6 and 12 months, longer follow-up is needed to more fully assess the durability of these positive effects. METHODS: An open-label, international clinical trial was conducted in 144 PPI-dependent patients with GERD with follow-up at 6 and 12 months. In addition, the durability and the safety of the treatment were assessed for 24 months in 64 patients enrolled in a postapproval study. The primary study outcome measure was usage of PPI. Secondary outcomes in the multicenter trial were GERD health-related quality of life (GERD-HRQL) symptom score and esophageal acid exposure. RESULTS: At 12 months, PPI use was reduced > or =50% in 84%: 95% confidence interval (CI) [76%, 90%] and was eliminated in 73%: 95% CI[64%, 81%] of evaluable patients (intent-to-treat analysis 78%: 95% CI[70%, 84%] and 68%: 95% CI[60%, 76%], respectively). A GERD-HRQL < or =11 was attained in 78%: 95% CI[69%, 85%] of evaluable patients. Esophageal acid exposure (total time pH <4) was reduced by 31%: 95% CI[17%, 43%]. At 24 months, a > or =50% or greater reduction in PPI use was achieved in 72%: 95% CI[59%, 82%] and PPI use was eliminated in 67%: 95% CI[54%, 78%] of patients. CONCLUSIONS: This investigation provides evidence for sustained effectiveness and safety of implantation of Enteryx in the esophagus in PPI-dependent patients with GERD.

Belgium↗

Cutaneous nocardiosis complicating management of Crohn's disease with infliximab and prednisone.

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that is efficacious in treating Crohn's disease. However, its immunomodulatory properties increase susceptibility to opportunistic infections. We present a case of cutaneous Nocardia infection in a patient who was taking infliximab for Crohn's disease. The case illustrates the challenges in the diagnosis and management of this disease and serves as a reminder of the complications associated with the use of immunomodulatory agents.

Anti-Bacterial Agents↗

Moderate level sedation during endoscopy: a prospective study using low-dose propofol, meperidine/fentanyl, and midazolam.

BACKGROUND: Propofol provides several benefits over benzodiazepine and narcotic agents as a sedative medication for endoscopic procedures, including faster recovery and improved patient satisfaction. However, its use generally has been limited to anesthesiologists because of the risks associated with deep sedation. METHODS: One hundred patients undergoing colonoscopy or EGD were sedated with low-dose propofol, midazolam, and fentanyl (or meperidine). Depth of sedation was assessed at 2-minute intervals by an independent observer by using the American Society of Anesthesiologists criteria. Recovery time was determined by using paired neuropsychometric tests. A post-procedure satisfaction survey and 24-hour follow-up questionnaires were administered. RESULTS: For colonoscopy and EGD, respectively, the mean propofol dose was 98 mg and 79 mg, the mean midazolam dose was 0.9 mg and 0.8 mg, the mean fentanyl dose was 69 mcg and 63 mcg, and the mean meperidine dose was 42 mg (for both procedures). There were 628 assessments of the level of sedation performed during 74 colonoscopies and 101 assessments during 26 EGDs. The level of sedation was minimal in 77%, moderate in 21%, and deep in 2% of assessments. Nine of the 13 episodes of deep sedation were recorded during colonoscopy and 4 during EGD. In no instance was more than a single assessment of deep sedation recorded during one procedure. Ninety-eight percent of patients were satisfied with the sedation, and 71% returned to their usual activities within 2 hours of discharge. There was no serious adverse event. CONCLUSIONS: Endoscopic sedation with low-dose propofol, a narcotic agent, and midazolam produces a moderate level of sedation. The quality of sedation and measures of recovery are comparable with the results reported with standard-dose propofol.

Adult↗

Propofol for endoscopic sedation: A protocol for safe and effective administration by the gastroenterologist.

BACKGROUND: There is increasing interest in the use of propofol, an ultrashort-acting hypnotic agent, for sedation during endoscopic examinations. A protocol was developed for administration of propofol, combined with small doses of midazolam and meperidine, for endoscopic sedation under the direction of a gastroenterologist. Initial experience with using this protocol is described. METHODS: A total of 819 consecutive endoscopic examinations under sedation with propofol, midazolam, and meperidine (or fentanyl), in adherence with the sedation protocol, were reviewed retrospectively. RESULTS: There were 638 colonoscopies and 181 EGDs; 89% of patients were classified as American Society of Anesthesiologists (ASA) class I or II. Mean dosages of medications were: propofol 63 (33.5) mg, meperidine 48 (7.2) mg, and midazolam 1 (0.12) mg. The dose of propofol was inversely correlated with age and ASA class, and positively correlated with patient weight and duration of examination. Hypotension (>20 mm Hg decline in either systolic or diastolic blood pressure) developed in 218 (27%) patients, and hypoxemia (oxygen saturation <90%) developed in 75 (9%). All episodes of hypotension and hypoxemia were transient, and no patient required administration of a pharmacologic antagonist or assisted ventilation. The average time for recovery after colonoscopy and after EGD was, respectively, 25 minutes and 28 minutes. All EGDs and 98% of colonoscopies were completed successfully. CONCLUSIONS: On the basis of this initial experience, it is believed that propofol, potentiated by small doses of midazolam and meperidine, can be safely and effectively administered under the direction of a gastroenterologist. Additional research will be necessary to determine whether propofol is superior to the current methods of sedation.

Adolescent↗

Odorant specificity of three oscillations and the DC signal in the turtle olfactory bulb.

The odour-induced population response in the in vivo turtle (Terepene sp.) olfactory bulb consists of three oscillatory components (rostral, middle and caudal) that ride on top of a DC signal. In an initial step to determine the functional role of these four signals, we compared the signals elicited by different odorants. Most experiments compared isoamyl acetate and cineole, odorants which have very different maps of input to olfactory bulb glomeruli in the turtle and a different perceptual quality for humans. We found substantial differences in the response to the two odours in the rise-time of the DC signal and in the latency of the middle oscillation. The rate of rise for cineole was twice as fast as that for isoamyl acetate. Similarly, the latency for the middle oscillation was about twice as long for isoamyl acetate as it was for cineole. On the other hand, a number of characteristics of the signals were not substantially different for the two odorants. These included the latency of the rostral and caudal oscillation, the frequency and envelope of all three oscillations and their locations and spatial extents. A smaller number of experiments were carried out with hexanone and hexanal; the oscillations elicited by these odorants did not appear to be different from those elicited by isoamyl acetate and cineole. Qualitative differences between the oscillations in the turtle and those in two invertebrate phyla suggest that different odour processing strategies may be used.

Animals↗

Endoscopic, deep mural implantation of Enteryx for the treatment of GERD: 6-month follow-up of a multicenter trial.

OBJECTIVES: This prospective, multicenter, single-arm study evaluated the safety and efficacy of the endoscopic implantation of Enteryx, a biocompatible, non-biodegradable liquid polymer for the treatment of GERD. METHODS: Eighty-five patients with heartburn symptoms responsive to proton pump inhibitor (PPI) use were enrolled. Inclusion requirements were HRQL score < or = 11 on PPI and > or = 20 off PPI, and 24-hour PH probe with > or = 5% total time at PH < or = 4. Patients with a hiatus hernia > 3 cm, grade 3 or 4 esophagitis, or esophageal motility disorder were excluded. Using a 4-mm needle tipped catheter during standard endoscopy, implants were made in 3-4 quadrants deep into the wall of the cardia. Use of PPI medications, pH-metry, manometry, GERD symptoms, and patient quality of life were assessed over a 6-month follow-up period. RESULTS: At 6 months, PPI use was eliminated in 74% and reduced by > 50% in 10% of patients. The median HRQL score improved from 24.0 pre-implant (baseline off PPIs) to 4.0 at 6 months (p < 0.001). Mean total esophageal acid exposure time was 9.5% pretherapy and 6.7% at 6 months (p < 0.001). Mean LES length increased from 2.0 cm at baseline to 3.0 cm posttherapy (p = 0.003). There were no clinically serious adverse events. Transient mild-to-moderate chest pain commonly occurred after implantation. CONCLUSIONS: The endoscopic implantation of Enteryx is a safe and effective therapy for eliminating or decreasing the need for PPI medications, improving GERD symptoms and patient quality of life, and decreasing esophageal acid exposure among patients suffering from GERD.

Biopolymers↗