Release of cortical catecholamines by visual stimulation requires activity in thalamocortical afferents of monkey and cat

Catecholamine (CA) release was measured in vivo in the monkey and cat visual cortices electrochemically. Stereate-modified, graphite-paste electrodes were used to monitor changes in norepinephrine and dopamine release. Micromolar changes in CA concentration were obtained by stimulation of the eye with nonspecific (strobe) or specific (oriented bars, radial gratings) stimuli. CA release depended on which eye was illuminated. Electrodes passed tangentially through the striate area recorded release following visual stimulation of one eye or the other in succession, and the shift in eye dominance occurred at about 500 microns intervals. The magnitude of CA release was highly correlated with the ocular dominance of neuronal activity measured with tungsten microelectrodes. Light-stimulated release was not recorded in monkey area V2, V4, or somatosensory area 1, but was recorded in cat V2, suggesting that the presence of LGN afferents is associated with CA release. Results are discussed in terms of the role of geniculate activity and the specific role of CAs in cortical information processing.     

Does the Amygdala Mediate Anesthetic-induced Amnesia?: Basolateral Amygdala Lesions Block Sevoflurane-induced Amnesia

Background: Amnesia for aversive events caused by benzodiazepines or propofol depends on the basolateral amygdala (BLA). Whether the amnesia of volatile anesthesia is also mediated through the BLA is unknown. If so, a general principle of anesthetic-induced amnesia may be emerging. Here, using an inhibitory avoidance paradigm, the authors determine whether BLA lesions prevent sevoflurane-induced amnesia.

Methods: Male Sprague-Dawley rats were separated into two groups: sham-operated controls (n = 22) and rats given bilateral N-methyl-d-aspartate lesions of the BLA (n = 32). After a 1-week recovery, the rats were randomly assigned to be trained during either air or sevoflurane (0.3% inspired, 0.14 minimum alveolar concentration) exposure. Animals learned to remain in the starting safe compartment of a step-through inhibitory avoidance apparatus for 100 consecutive seconds by administering foot shock (0.3 mA) whenever they entered an adjacent shock compartment. Memory was assessed at 24 h. Longer latencies to enter the shock compartment at 24 h imply better memory.

Results: Sham-air (n = 10) animals had a robust memory, with a median retention latency of 507 s (interquartile range, 270-600 s). Sham-sevoflurane (n = 6) animals were amnesic, with a latency of 52 s (27-120 s) (P < 0.01, vs. sham-air). Both the air-exposed (n = 5) and the sevoflurane-exposed (n = 8) animals with BLA lesions showed robust memory, with latencies of 350 s (300-590 s) and 378 s (363-488 s), respectively. The latencies for both did not differ from the performance of the sham-air group and were significantly greater than the latency of the sham-sevoflurane group (both P < 0.01).     

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.     

Lesions of the basolateral amygdala complex block propofol-induced amnesia for inhibitory avoidance learning in rats

BACKGROUND: As the unitary theory of anesthesia gives way to the "multiple sites, multiple mechanisms" concept, the sites involved in mediating the components of anesthesia must be identified. In the current study, we test the hypothesis that the basolateral amygdala complex (BLAC) is a brain site involved with mediating propofol-induced amnesia. METHODS: Male Sprague-Dawley rats were divided into two groups, sham-operated control animals and rats given bilateral excitotoxic N-methyl-D-aspartate lesions of the BLAC. For each group, animals were given intraperitoneal saline or propofol (25 mg/kg) 5 min before inhibitory avoidance learning. Rats were given a foot shock (0.4 mA) upon entering the dark side of a two-sided apparatus. Rats could escape additional shock by returning to and staying in the light side. Training ended after shock avoidance for greater than 60 s. Memory was tested at 24 h. Longer latencies to enter the dark side 24 h after training imply better memory. RESULTS: Sham-saline-treated animals had a robust memory latency (median latency [interquartile range] = 300 [163-567] s). Sham-propofo-treated animals exhibited a significant anterograde amnesia (latency = 63 [14-111] s) (P < 0.05 vs. sham-saline-treated animal). Both the saline-injected and propofol-injected animals with BLAC lesions showed robust memory (latency = 300 [264-485] and 323 [143480] s, respectively). These latencies did not differ from performance in the sham-saline-treated group and were significantly higher than the latency of the sham-propofol-treated group (both P < 0.05). CONCLUSIONS: Discrete BLAC lesions blocked the amnestic effect of propofol. BLAC activity appears to be a requirement for propofol-induced amnesia. This finding suggests that the BLAC is a key brain site mediating anesthetic-induced amnesia.     

Dissociable brain activation responses to 5-Hz electrical pain stimulation: a high-field functional magnetic resonance imaging study

BACKGROUND: To elucidate neural correlates associated with processing of tonic aching pain, the authors used high-field (3-T) functional magnetic resonance imaging with a blocked parametric study design and characterized regional brain responses to electrical stimulation according to stimulus intensity-response functions. METHODS: Pain was induced in six male volunteers using a 5-Hz electrical stimulus applied to the right index finger. Scanning sequences involved different levels of stimulation corresponding to tingling sensation (P1), mild pain (P2), or high pain (P3). Common effects across subjects were sought using a conjunction analyses approach, as implemented in statistical parametric mapping (SPM-99). RESULTS: The contralateral posterior/mid insula and contralateral primary somatosensory cortex were most associated with encoding stimulus intensity because they showed a positive linear relation between blood oxygenation level-dependent signal responses and increasing stimulation intensity (P1 < P2 < P3). The contralateral secondary somatosensory cortex demonstrated a response function most consistent with a role in pain intensity encoding because it had no significant response during the innocuous condition (P1) but proportionally increased activity with increasingly painful stimulus intensities (0 < P2 < P3). Finally, a portion of the anterior cingulate cortex (area 24) and supplementary motor area 6 demonstrated a high pain-specific response (P3). CONCLUSIONS: The use of response function modeling, conjunction analysis, and high-field imaging reveals dissociable regional responses to a tonic aching electrical pain. Most specifically, the primary somatosensory cortex and insula seem to encode stimulus intensity information, whereas the secondary somatosensory cortex encodes pain intensity information. The cingulate findings are consistent with its proposed role in processing affective-motivational aspects of pain.     

Memory Enhancing Effect of Low-dose Sevoflurane Does Not Occur in Basolateral Amygdala-lesioned Rats

Background: Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought.

Methods: First, the memory-enhancing potential of various anesthetics was determined. Rats underwent single-trial inhibitory avoidance training (0.3 mA shock/1 s) during exposure to air, 0.11% sevoflurane, 0.10% halothane, 0.77% desflurane, or 0.12% isoflurane. Memory was assessed at 24 h. Second, the BLA contribution to sevoflurane memory enhancement was determined. Rats received bilateral excitotoxic N-methyl-d-aspartate (12.5 mg in 0.2 [mu]l per BLA) lesions of the BLA 1 week before training. Memory of lesioned and control rats was compared 24 h after training in air or sevoflurane.

Results: Sevoflurane exposure during training significantly enhanced 24-h retention performance for both nonoperated and sham-operated rats (P < 0.005 for both vs. their respective controls). Halothane, but not desflurane or isoflurane, also enhanced retention performance (P < 0.05). However, halothane-induced hyperalgesia during learning clouds interpreting enhanced retention performance solely as a memory consolidation effect. BLA lesions significantly reduced and equalized retention performance for both sevoflurane- and air-exposed animals. Lesions blocked memory enhancement without also causing a generalized inability to learn, because additional training revealed essentially normal task acquisition and 24-h memory.     

Management of space problems in the primary and mixed dentitions.

BACKGROUND: According to the Third National Health and Nutrition Examination Survey, crowding and irregularity remain a consistent problem for children. Management of space problems continues to play an important role in a dental practice. It also represents an area of major interaction between the primary provider and the specialists. This article attempts to update clinicians on the current knowledge of space management. DESCRIPTION OF CONDITION: Proper management of space in the primary and mixed dentitions can prevent unnecessary loss in arch length. Diagnosing and treating space problems requires an understanding of the etiology of crowding and the development of the dentition to render treatment for the mild, moderate and severe crowding cases. Most crowding problems with less than 4.5 millimeters can be resolved through preservation of the leeway space, regaining space or limited expansion in the late mixed dentition. In cases with 5 to 9 mm of crowding, some can be approached with expansion after thorough diagnosis and treatment planning. Most of these cases will require extraction of permanent teeth to preserve facial esthetics and the integrity of the supporting soft tissue. Serial extraction or guidance of eruption is reserved for treatment of severe tooth-size/arch-size discrepancies. Due to variations in the timing and extraction sequence depending on the diagnosis, serial extraction should be reserved for those who can complete the treatment successfully. CLINICAL IMPLICATIONS: The recommended timing of referring patients with moderate crowding to specialists for treatment is in the late mixed-dentition stage of development. Patients with severe crowding will require earlier evaluation for serial extraction.     

Barriers to Surgical Care and Health Outcomes: A Prospective Study on the Relation Between Wealth,Sex, and Postoperative Complications in the Republic of Congo

Background

Approximately thirty percent of the global burden of disease is comprised of surgical conditions. However, five billion people lack access to surgery, with complex factors acting as barriers. We examined whether patient demographics predict barriers to care, and the relation between these factors and postoperative complications in a prospective cohort.

Methods

Participants included people presenting to a global charity in Republic of Congo with a surgical condition between August 2013 and May 2014. The outcomes were self-reported barrier to care and postoperative complications documented by medical record. Logistic regression was used to adjust for covariates.

Results

Of 1237 patients in our study, 1190 (96.2 %) experienced a barrier to care and 126 (10.2 %) experienced a postoperative complication. The most frequently reported barrier was cost (73 %), followed by lack of provider (8.2 %). Greater wealth was associated with decreased odds of cost as a barrier (OR 0.72 [0.57, 0.90]). Greater wealth (OR 1.52 [1.03, 2.25]) and rural home location (OR 3.35 [1.16, 9.62]) were associated with increased odds of no surgeon being available. Cost as a barrier (OR 2.82 [1.02, 7.77]), female sex (OR 3.45 [1.62, 7.33]), and lack of surgeon (OR 5.62 [1.68, 18.77]) were associated with increased odds of postoperative complication. Patient wealth was not associated with odds of postoperative complication.

Conclusions

Barriers to surgery were common in Republic of Congo. Patient wealth and home location may predict barriers to surgery. Addressing gender disparities, access to providers, and patient perception of barriers in addition to removal of barriers may help maximize patient health benefits.

     

Cost-Effectiveness in Global Surgery: Pearls,Pitfalls, and a Checklist

Introduction

Cost-effectiveness analysis can be a powerful policy-making tool. In the two decades since the first cost-effectiveness analyses in global surgery, the methodology has established the cost-effectiveness of many types of surgery in low- and middle-income countries (LMICs). However, with the crescendo of cost-effectiveness analyses in global surgery has come vast disparities in methodology, with only 15% of studies adhering to published guidelines. This has led to results that have varied up to 150-fold.

Methods

The theoretical basis, common pitfalls, and guidelines-based recommendations for cost-effectiveness analyses are reviewed, and a checklist to be used for cost-effectiveness analyses in global surgery is created.

Results

Common pitfalls in global surgery cost-effectiveness analyses fall into five categories: the analytic perspective, cost measurement, effectiveness measurement, probability estimation, valuation of the counterfactual, and heterogeneity and uncertainty. These are reviewed in turn, and a checklist to avoid these pitfalls is developed.

Conclusion

Cost-effectiveness analyses, when done rigorously, can be very useful for the development of efficient surgical systems in LMICs. This review highlights the common pitfalls in these analyses and methods to avoid these pitfalls.