Search PubMed⌕ Search

Biomedical subjects

Allan Gottschalk

Publications and source records attributed to Allan Gottschalk.

13 recordsLinked to original sources
PubMed2005

Effects of Kv1.1 channel glycosylation on C-type inactivation and simulated action potentials.

Kv1.1 channels are brain glycoproteins that play an important role in repolarization of action potentials. In previous work, we showed that lack of N-glycosylation, particularly lack of sialylation, of Kv1.1 affected its macroscopic gating properties and slowed activation and C-type inactivation kinetics and produced a depolarized shift in the steady-state activation curve. In our current study, we used single channel analysis to investigate voltage-independent C-type inactivation in both Kv1.1 and Kv1.1N207Q, a glycosylation mutant. Both channels underwent brief and long-lived closures, and the lifetime and frequency of the long-lived closed states were voltage-independent and similar for both channels. We found that, as in macroscopic measurements, Kv1.1N207Q exhibited a approximately 8 mV positive shift in its single channel fractional open time (fo) and a shallower fo-voltage slope compared with Kv1.1. Data suggested that C-type inactivation reflected the equilibration time with at least two slow voltage-independent long-lived closed states that followed the rapid activation process. In addition, data simulation indicated that the C-type inactivation process reflected the equilibration time between the open state and at least two long-lived closed states. Moreover, the faster macroscopic current decay in Kv1.1 mostly reflected a slower equilibration time in these channels as compared with Kv1.1N207Q. Finally, action potential simulations indicated that the N207Q mutation broaden the action potential and decreased the interspike interval. The shape of the action potential was not significantly affected by C-type inactivation, however, for a given channel, C-type inactivation increased the interspike interval. Data and simulations suggested that excitable cells could use differences in K(+) channel glycosylation degree as an additional mechanism to increase channel functional diversity which could modify cell excitability.

Action Potentials↗
PubMed2005

Impact of acute pain and its management for thoracic surgical patients.

Perioperative analgesia for thoracotomy has evolved in concert with increasing knowledge of the impact of pain on recovery, the origin of this pain, and new methods for treating it. Thoracic surgery is one of the few areas where there is more general agreement between surgeons and anesthesiologists as to the importance of aggressive pain management, often with an indwelling epidural catheter left in place until after thoracostomy tube removal. The reasons for this agreement is that it has become increasingly clear to both specialties that pain puts patients with decreased pulmonary reserve who undergo thoracotomy at greater risk for morbidity. Future studies need to examine drugs or drug combinations that can lead to further reductions in the often intense pain that patients receiving aggressive epidural analgesia still experience. Studies directed at finding interventions capable of reducing the rate of long-term postthoracotomy pain still need to be performed.

Acute Disease↗
PubMed2005

Prolonged differential wound hyperalgesia after an interval of unilateral epidural blockade during lower abdominal surgery.

We assessed postoperative pain at rest and with movement along with wound hyperalgesia in a patient who had undergone lower abdominal surgery under general anesthesia with a unilateral epidural block that persisted throughout surgery and in whom the epidural catheter was replaced immediately afterward. Pain and wound hyperalgesia were consistently greater on the "unblocked" side for the 3-wk period of observation. Thus, even imperfect intraoperative attenuation of noxious stimuli can lead to persistent reductions in postoperative pain.

Abdomen↗
PubMed2004

Multiplicative neural noise can favor an independent components representation of sensory input.

Arguments have been advanced to support the role of principal components (e.g., Karhunen-Loéve, eigenvector) and independent components transformations in early sensory processing, particularly for color and spatial vision. Although the concept of redundancy reduction has been used to justify a principal components transformation, these transformations per se do not necessarily confer benefits with respect to information transmission in information channels with additive independent identically distributed Gaussian noise. Here, it is shown that when a more realistic source of multiplicative neural noise is present in the information channel, there are quantitative benefits to a principal components or independent components representation for Gaussian and non-Gaussian inputs, respectively. Such a representation can convey a larger quantity of information despite the use of fewer spikes. The nature and extent of this benefit depend primarily on the probability distribution of the inputs and the relative power of the inputs. In the case of Gaussian input, the greater the disparity in power between dimensions, the greater the advantage of a principal components representation. For non-Gaussian input distributions with a kurtosis that is super-Gaussian, an independent components representation is similarly advantageous. This advantage holds even for input distributions with equal power since the resulting density is still rotationally asymmetric. However, sub-Gaussian input distributions can lead to situations where maximally correlated inputs are the most advantageous with respect to transmitting the greatest quantity of information with the fewest number of spikes.

Models, Neurological↗
PubMed2003

What is the role of NSAIDs in pre-emptive analgesia?

NSAIDs inhibit the cyclo-oxygenase enzymes, and decrease peripheral and central prostaglandin production. In addition to reducing the inflammation that accompanies tissue injury, decreasing prostaglandin production attenuates the response of the peripheral and central components of the nervous system to noxious stimuli. Such a reduction in the response to pain can reduce the peripheral and central sensitisation induced by noxious stimuli, and reduce the pain experienced in response to subsequent noxious stimuli. These properties would seem to make NSAIDs ideal drugs to use in a pre-emptive fashion, where analgesics are administered prior to a noxious stimulus, such as surgery, with the expectation that reduction in peripheral and central sensitisation will lead to a decrease of pain.However, the available perioperative trials of pre-emptive NSAID use have yielded modest or equivocal results, and these may be due, in part, to controversy associated with the definition of pre-emptive analgesia and how to conduct the corresponding clinical trials. Although NSAIDs may have a limited ability by themselves to induce a pre-emptive analgesic effect, the available trials suggest how the perioperative use of these drugs may be made more effective. It is expected that NSAIDs will play an increasing role in multimodal analgesia and pain relief in general.

Analgesia↗
PubMed2002

Design and impact of intraoperative pathways for head and neck resection and reconstruction.

OBJECTIVES: To describe the design and impact of 3 intraoperative pathways for the treatment of head and neck cancers; to detail the pathways schematically to illustrate projected intraoperative flow and teamwork; and to analyze impact on procedure and case lengths in each pathway and in comparison with historical prepathway average times. SETTING: Tertiary-level academic health system main operating room. PATIENTS: Twenty-one patients undergoing transcervical (TC) resection (n = 11), transmandibular (TM) resection (n = 8), or laryngopharyngectomy (LP) (n = 2) with radial forearm free-flap reconstruction for ablative or reconstructive reasons were pathway eligible. A convenience sample of 16 patients undergoing TC resection, 7 undergoing TM resection, and 7 undergoing LP prepathway is used for comparison. INTERVENTION: Our academic medical center uses 3 intraoperative clinical pathways to manage resource use and streamline care for patients. These 3 pathways were designed schematically by an interdisciplinary team. The pathways plan progression of the case by timed actions for surgical, anesthesia, and nursing teams. MAIN OUTCOME MEASURES: Procedure and case lengths. RESULTS: The TC pathway procedure and case length averaged 10.48 and 12.33 hours, respectively; TM pathway procedure and case lengths, 11.19 and 13.32 hours, respectively; and LP pathway procedure and case lengths, 12.42 and 13.83 hours, respectively. Aggregate averages were 10.93 hours and 12.85 hours for procedure and case length, respectively. The average pathway case lengths of 12.33, 13.32, and 13.83 hours compare favorably with our target times of 13, 14, and 15 hours, respectively. Environmental management, work flow, and team satisfaction anecdotally increased postpathway. CONCLUSIONS: Intraoperative pathways afford enhanced time and action efficiency to streamline care of patients undergoing head and neck procedures. Pathway implementation produced time savings. Our results suggest that implementation of such pathways will benefit similar academic medical centers seeking to improve intraoperative resource use to improve performance in the care of patients undergoing head and neck procedures.

Cervical Vertebrae↗
PubMed2002

Long-term pain and activity during recovery from major thoracotomy using thoracic epidural analgesia.

BACKGROUND: Pain following thoracotomy can persist for years with an undetermined impact on quality of life. Factors hypothesized to modulate this painful experience include analgesic regimen, gender, and type of incision. METHODS: A total of 157 generally healthy patients of both genders scheduled for segmentectomy, lobectomy, or bilobectomy through a posterolateral or muscle-sparing incision were randomly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained 4, 8, 12, 24, 36, and 48 weeks after surgery. RESULTS: Overall, there were no differences in pain scores between the control and intervention groups during hospitalization (P >or= 0.165) or after discharge (P>or= 0.098). The number of patients reporting pain 1 yr following surgery (18 of 85; 21.2%) was not significantly different (P = 0.122) from the number reporting preoperative pain (15 of 120; 12.5%). During hospitalization, women reported greater pain than men (worst pain, P= 0.007; average pain, P= 0.016). Women experienced fewer supraventricular tachydysrhythmias (P = 0.013) and were thus discharged earlier (P = 0.002). After discharge women continued to report greater discomfort than men (P <or= 0.016), but did not differ from men in their level of physical activity (P = 0.241). CONCLUSIONS: Initiation of thoracic epidural analgesia prior to incision or the use of a muscle-sparing incision did not significantly impact pain or physical activity. Although women reported significantly greater pain during hospitalization and after discharge, they experienced fewer complications, were more likely to be discharged from the hospital sooner, and were just as active after discharge as men.

Adult↗
PubMed2002

Derivation of the visual contrast response function by maximizing information rate.

A graph of neural output as a function of the logarithm of stimulus intensity often produces an S-shaped function, which is frequently modeled by the hyperbolic ratio equation. The response of neurons in early vision to stimuli of varying contrast is an important example of this. Here, the hyperbolic ratio equation with a response exponent of two is derived exactly by considering the balance between information rate and the neural costs of making that information available, where neural costs are a function of synaptic strength and spike rate. The maximal response and semisaturation constant of the neuron can be related to the stimulus ensemble and therefore shift accordingly to exhibit contrast gain control and normalization.

Contrast Sensitivity↗
PubMed2002

Current treatment options for acute pain.

The pain that accompanies surgical procedures remains prevalent and is an aspect of the perioperative experience that generates the greatest concern for patients about to undergo surgery. There is also a growing recognition of the extent that acute painful experiences can lead to longer-term painful consequences, even when tissue healing appears to be complete. The neurobiologic basis of this has been partially elucidated. The key observations are that multiple sites and multiple receptors collectively contribute, and that noxious stimuli initiate a cascade of events that sensitise the nervous system so that subsequent noxious stimuli are perceived with greater intensity and even previously non-painful stimuli can be painful. Incorporating these observations into effective perioperative regimens designed to limit acute pain and its consequences leads to a multimodal pre-emptive approach to acute pain management. Acute perioperative pain is an ideal setting for the use of pre-emptive analgesic techniques because the timing of noxious stimuli is known in advance and surgical sensitisation of the nervous system is ongoing despite adequate levels of general anaesthesia with volatile anaesthetics. The relevant neurobiology of pain, reviewed in this article, is the basis for advocating an aggressive, multimodal, pre-emptive approach to acute pain therapy throughout the entire perioperative period. A growing body of outcome studies demonstrates the long-term efficacy of this approach.

Acute Disease↗