In the authors' in vivo expiratory neuronal model, the depressive effect of sevoflurane on synaptic neurotransmission was caused by a reduction of presynaptic glutamatergic excitation and an enhancement of GABA(A)ergic inhibition. The effects on expiratory neuronal activity were similar to halothane, but sevoflurane caused a stronger depression of phrenic nerve activity than halothane.

Journal of Cutaneous PathologyDiagnostic concordance rates in the subtyping of basal cell carcinoma by different dermatopathologists Background There are numerous subtypes of basal cell carcinoma (BCC). Defining the histopathologic subtype is an essential element in patient management, but there is little known data regarding interobserver precision in subtyping BCC. Methods We studied interobserver variance between six board-certified dermatopathologists who subtyped 100 BCCs in a blinded fashion. We used kappa statistic to calculate the concordance in suggested subtype by different dermatopathologists. Provided diagnoses were then re-categorized into low-risk and high-risk phenotypes, and kappa statistic for concordance on high-risk BCC was determined. Results The overall κ statistic was 0.301, indicating fair agreement among the six observers. Superficial and fibroepithelial BCC had the highest individual kappa statistics. When subtypes were re-classified into a two-tier system of high-risk and low-risk phenotypes, there was substantial interobserver agreement on high-risk BCC with a κ statistic of 0.699. Conclusion These results suggest only fair agreement among dermatopathologists on specific BCC subtypes, but substantial agreement on superficial, fibroepithelial and high-risk BCC growth patterns. A simplified classification system comprised of superficial, fibroepithelial, nodular and infiltrative subtypes would increase interobserver precision and facilitate clinical decision-making.

Zuperku EJ, Sanchez A, Tonkovic-Capin M, Tonkovic-Capin V, Mustapic S, Stuth EA. Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations. J Neurophysiol 100: 2878 -2888, 2008. First published September 24, 2008 doi:10.1152/jn.90620.2008. Opioids depress the activity of brain stem respiratory-related neurons, but it is not resolved whether the mechanism at clinical concentrations consists of direct neuronal effects or network effects. We performed extracellular recordings of discharge activity of single respiratory neurons in the caudal ventral respiratory group of decerebrate dogs, which were premotor neurons with a likelihood of 90%. We used multibarrel glass microelectrodes, which allowed concomitant highly localized picoejection of opioid receptor agonists or antagonists onto the neuron. Picoejection of the receptor agonist [D-Ala 2 , N-Mephe 4 , gly-ol 5 ]-enkephalin (DAMGO, 1 mM) decreased the peak discharge frequency (mean Ϯ SD) of expiratory neurons to 68 Ϯ 22% (n ϭ 12), the ␦ 1 agonist D-Pen 2,5 -enkephalin (DPDPE, 1 mM) to 95 Ϯ 11% (n ϭ 15), and ␦ 2 receptor agonist [D-Ala 2 ] deltorphin-II to 86 Ϯ 17% (1 mM, n ϭ 15). The corresponding values for inspiratory neurons were: 64 Ϯ 12% (n ϭ 11), 48 Ϯ 30% (n ϭ 12), and 75 Ϯ 15% (n ϭ 11), respectively. Naloxone fully reversed these effects. Picoejection of morphine (0.01-1 mM) depressed most neurons in a concentration dependent fashion to maximally 63% (n ϭ 27). Picoejection of remifentanil (240 -480 nM) did not cause any significant depression of inspiratory (n ϭ 11) or expiratory neurons (n ϭ 9). 4. Intravenous remifentanil (0.2-0.6 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) decreased neuronal peak discharge frequency to 60 Ϯ 12% (inspiratory, n ϭ 7) and 58 Ϯ 11% (expiratory, n ϭ 11). However, local picoejection of naloxone did not reverse the neuronal depression. Our data suggest that , ␦ 1 , and ␦ 2 receptors are present on canine respiratory premotor neurons. Clinical concentrations of morphine and remifentanil caused no local depression. This lack of effect and the inability of local naloxone to reverse the neuronal depression by intravenous remifentanil suggest that clinical concentrations of opioids produce their depressive effects on mechanisms upstream from respiratory bulbospinal premotor neurons.

Halothane and sevoflurane at 1 MAC produced a small increase in overall inhibition of expiratory premotor neuronal activity. The increase in inhibition results from a marked enhancement of postsynaptic GABAA receptor function that is partially offset by a reduction in presynaptic inhibitory input by the anesthetics.

. Subtype composition and responses of respiratory neurons in the pre-Bötzinger region to pulmonary afferent inputs in dogs. J Neurophysiol 93: 2674 -2687, 2005. First published December 15, 2004 doi:10.1152/jn.01206.2003. The brain stem pre-Bötzinger complex (pre-BC) plays an important role in respiratory rhythm generation. However, it is not clear what function each subpopulation of neurons in the pre-BC serves. The purpose of the present studies was to identify neuronal subpopulations of the canine pre-BC and to characterize the neuronal responses of subpopulations to experimentally imposed changes in inspiratory (I) and expiratory (E) phase durations. Lung inflations and electrical stimulation of the cervical vagus nerve were used to produce changes in respiratory phase timing via the Hering-Breuer reflex. Multibarrel micropipettes were used to record neuronal activity and for pressure microejection in decerebrate, paralyzed, ventilated dogs. The pre-BC region was functionally identified by eliciting tachypneic phrenic neural responses to localized microejections of DL-homocysteic acid. Antidromic stimulation and spike-triggered averaging techniques were used to identify bulbospinal and cranial motoneurons, respectively. The results indicate that the canine pre-BC region consists of a heterogeneous mixture of propriobulbar I and E neuron subpopulations. The neuronal responses to ipsi-, contra-, and bilateral pulmonary afferent inputs indicated that I and E neurons with decrementing patterns were the only neurons with responses consistently related to phase duration. Late-I neurons were excited, but most other types of I neurons were inhibited or unresponsive. E neurons with augmenting or parabolic discharge patters were inhibited by ipsilateral inputs but excited by contra-and bilateral inputs. Late-E neurons were more frequently encountered and were inhibited by ipsi-and bilateral inputs, but excited by contralateral inputs. The results suggest that only a limited number of neuron subpopulations may be involved in rhythmogenesis, whereas many neuron types may be involved in motor pattern generation.