Search PubMed⌕ Search

Biomedical subjects

M J Wall

Publications and source records attributed to M J Wall.

At least 55 records · Page 3Linked to original sources

A role for potassium currents in the generation of the swimming motor pattern of Xenopus embryos.

1. To assess the role that K+ currents play in the production of the swimming motor pattern in the Xenopus embryo, we have used low doses of the K+ channel blockers, 3,4-diaminopyridine (3,4-DAP; 25-100 microM) and tetraethylammonium (TEA; 500 microM), to reduce K+ currents and investigated the effects on motor output. 2. To confirm that 3,4-DAP and TEA block K+ currents and characterize their actions, we made whole-cell voltage-clamp recordings from acutely isolated spinal neurons. Both 25-100 microM 3,4-DAP and 100-500 microM TEA blocked the sustained K+ current in a dose-dependent manner. 3. Because TEA can block acetylcholine nicotinic receptors on autonomic ganglia, and nicotinic acetylcholine receptors have recently been shown to be present on Xenopus spinal neurons, we have tested both 3,4-DAP and TEA for antagonist action against the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP). Although 500 microM TEA blocked the DMPP-induced depolarization, 25 microM 3,4-DAP did not. 4. In the intact embryo, application of 25-100 microM 3,4-DAP or 500 microM TEA disrupted both the left and right alternation of ventral root discharge and the motor pattern recorded intracellularly from spinal neurons during swimming. Both blockers allowed the firing of an extra action potential at midcycle, which led to a number of different patterns. These patterns were categorized as follows: type A, cycles with midcycle action potentials; type B, the simultaneous firing of neurons on both sides of the cord; and type C, in which one side was active, whereas the other side was inhibited. In both 3,4-DAP and TEA these abnormalities tended to occur at the beginning of swimming episodes. Both blockers also caused a significant increase in the cycle period. Because both 3,4-DAP and TEA produced very similar affects to the motor pattern, we conclude that the perturbations are probably a result of reducing K+ current amplitude. 5. To investigate whether 3,4-DAP and TEA were producing disruptions in the motor pattern by increasing synaptic drive through the broadening of action potentials, we made measurements of spike width, tonic depolarization, and midcycle inhibitory postsynaptic potential (IPSP) amplitude during swimming. Both 3,4-DAP and TEA caused significant but modest spike broadening (20.8 and 29.8%, respectively); however, their effects on tonic depolarization were inconsistent although both blockers increased midcycle IPSP amplitude. 6. To test whether a reduction in K+ currents could plausibly produce the specific motor pattern perturbations that were seen, we have made computer simulations of simplified spinal networks.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord.

Activation of GABAB receptors in the Xenopus embryo, a simple vertebrate, causes presynaptic inhibition of transmitter release from glycinergic spinal neurons and an increase in action potential threshold. To investigate the underlying mechanisms of GABAB receptor action, we have made whole-cell voltage-clamp recordings from acutely isolated Xenopus embryo spinal neurons. The GABAB receptor agonist baclofen caused a reversible reduction in the amplitude of Ca2+ currents. This reduction of Ca2+ currents appeared to be voltage dependent as it was removed at very positive potentials. Since the specific GABAB antagonists CGP35348, phaclofen, and 2-hydroxysaclofen all blocked the reduction in Ca2+ currents, we concluded that the modulation of the Ca2+ current was mediated by GABAB receptors. We have investigated the pharmacological identity of the Ca2+ current modulated by baclofen using the selective blocker omega-conotoxin, fraction GVIA (omega-CgTX). omega-CgTX selectively blocked voltage-gated Ca2+ currents without affecting the voltage-gated Na+ current. omega-CgTX substantially occluded the action of baclofen, suggesting that GABAB receptors modulate an omega-CgTX-sensitive Ca2+ current. Since GABAB receptors mediate presynaptic inhibition, we have studied the involvement of the omega-CgTX-sensitive Ca2+ current in synaptic transmission in the intact spinal cord. Inhibitory interneuron axons were stimulated to evoke monosynaptic IPSPs in motoneurons, and recorded intracellularly. Since omega-CgTX blocked inhibitory transmission, we concluded that the omega-CgTX-sensitive Ca2+ current plays an essential role in transmitter release. If modulation of this current were to occur in nerve terminals, it could contribute to the GABAB receptor-mediated presynaptic inhibition of transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Planned reoperation for trauma: a two year experience with 124 consecutive patients.

Planned reoperation is a new approach to severe truncal trauma. A review of 124 patients treated over two years was undertaken. Penetrating injuries predominated (78%) involving primarily the abdomen or abdomen and chest. An abbreviated procedure was performed when direct hemostasis was impossible (102 patients), abrupt termination was required (56 patients), or the abdomen or chest could not be closed (20 patients). The techniques employed included packing, rapid skin closure, gastrointestinal interruption, rapid vascular control, temporary urinary diversion, stapled lung resection, and plastic bag closure. Seventy-three patients survived to undergo 101 operations. The first reoperation was planned in 52 patients and unplanned (either for bleeding or for abdominal compartment syndrome) in 21 patients. There were 14 missed injuries. The overall mortality rate was 58%. Survival was significantly better when the decision to abruptly terminate the initial procedure was made early and in patients undergoing planned reoperation. Wider adoption and better definition of the indications will result in more effective use of this approach.

Abdominal Injuries↗

Successful roadside resuscitative thoracotomy: case report and literature review.

Patients with injuries severe enough to require cardiopulmonary resuscitation (CPR) have a dismal prognosis. Time to surgical intervention is a major determinant of outcome in moribund trauma patients who have a potential for survival. With the exception of endotracheal intubation during evacuation to surgical intervention, no other usual prehospital procedures have been validated to affect outcome in such cases of extremis. This is a report of a case in which resuscitative surgical techniques were extended successfully to the prehospital environment. The patient was a 30-year-old man in extremis after a stab wound to the left chest. Estimating a transport time of 15 minutes, a physician riding with the emergency medical service (EMS) crews elected to perform a resuscitative thoracotomy. Following digital aortic compression, the patient regained both blood pressure and consciousness by the time of arrival at the trauma center. A left lower lobectomy was then performed in the operating room. The patient recovered fully and was discharged home in 21 days, neurologically intact. Four years later, the patient was alive, healthy, and working. This report demonstrates the feasibility of prehospital thoracotomy and raises provocative issues regarding future intense surgical involvement in prehospital care.

Adult↗

Reoperation for bleeding in trauma.

OBJECTIVE: Analysis of the causes and clinical patterns of postoperative bleeding requiring reoperation in trauma patients. DESIGN AND SETTING: A case series of 166 consecutive patients treated over 7 years at a level I trauma center. PATIENTS: 136 patients (82%) sustained penetrating trauma, primarily gunshot wounds (102 patients). On admission, 85 patients (51%) were hemodynamically unstable. INTERVENTION: 196 reoperative procedures were performed to control bleeding: 136 laparotomies, 49 thoracotomies, five neck explorations, and six peripheral vascular operations. Results of nine explorations were negative. MAIN OUTCOME MEASURE: Of 157 initial attempts to affect hemostasis, 36 (23%) failed. Twenty-seven patients died of uncontrolled bleeding and 19 died despite successful hemostasis. The overall mortality rate was 28%. RESULTS: Major causes of bleeding were incomplete hemostasis (46%), missed injuries (30%), and iatrogenic complications (17%). Diffuse oozing occurred in only seven of 43 patients with abnormal coagulation. The liver (19 patients) and retroperitoneum (13 patients) were the most common sites of incomplete hemostasis. Missed injuries occurred mainly in the chest wall arteries (seven patients) and heart (six patients). Iatrogenic injuries most commonly involved the spleen (nine patients). CONCLUSIONS: The management of postoperative hemorrhage in trauma hinges on an early decision to reexplore, preoperative correction of abnormal coagulation, and knowledge of specific bleeding patterns.

Blood Coagulation Disorders↗

Innominate artery trauma: a thirty-year experience.

PURPOSE: Injury to the innominate artery may represent a zone I cervical, thoracic outlet, or intrathoracic vascular injury and poses diagnostic, exposure, and management problems for the general, vascular, and thoracic surgeon. This complex injury often becomes a new learning experience with each infrequent encounter. METHODS: Between 1960 and 1992 43 patients with innominate artery injuries were treated. Penetrating injuries were from gunshot wounds in 25, stab wounds in 7, and shotgun wounds in 2 patients. Blunt injuries accounted for seven of the patients. In 28 patients there were multiple injuries, including multiple vascular injuries. Median sternotomy was used in all planned operations in the later part of the study, and bilateral transsternal anterolateral thoracotomy was used in patients undergoing urgent or emergency center thoracotomy. RESULTS: Blunt injury resulted in tears near the aortic arch with intimal disruption. Bypass grafting without hypothermia, shunts, or systemic heparinization is now used in all patients. Thirty-two patients survived to leave the hospital with no new complications related to the procedure. Postoperative neurologic complications were associated with preexisting neurologic deficits. CONCLUSIONS: Patients with innominate artery injury and stable vital signs can usually be transported without difficulty and treated without complex perioperative adjuncts. These patients can undergo revascularization with simple vascular surgical techniques and should expect an uncomplicated postoperative course unless there has been associated central nervous system injury or related injuries leading to systemic infection. Synthetic conduits have been used with success and have not required systemic heparinization or complex temporary shunting.

Adolescent↗

GABAB receptors modulate glycinergic inhibition and spike threshold in Xenopus embryo spinal neurones.

1. The actions of GABAB receptors in the generation of the neuronal pattern underlying swimming in the Xenopus embryo have been investigated using the agonist baclofen. 2. Baclofen (10-100 microM) greatly reduced the length of swimming episodes and ventral root spike amplitude in a reversible manner. These effects were blocked by CGP 35348 (200-300 microm) and hydroxysaclofen (200-300 microM). 3. Baclofen (10-100 microM) reduced the amplitude of glycinergic IPSPs in motoneurones during fictive swimming. 4. Strychnine-sensitive spontaneous miniature inhibitory postsynaptic potentials (mIPSPs) were recorded from motoneurones. While baclofen (10-100 microM) had no effect on the amplitude of the mIPSPs it greatly decreased their frequency of occurrence. 5. GABAB receptors may therefore be present on the terminals of commissural interneurones, the only glycinergic neurones in the Xenopus embryo's nervous system, and act to reduce neurotransmitter release. 6. Baclofen reduced the reliability of action potential firing in motoneurones during fictive swimming without an apparent effect on excitation. 7. Baclofen increased the threshold to action potential firing in response to the injection of depolarizing current in motoneurones. 8. The current-voltage relationships of motoneurones were investigated. Baclofen (10-100 microM) did not change the resting membrane potential, slope conductance or the membrane rectification.

Action Potentials↗

Coronary artery endarterectomy: a method of myocardial preservation.

The lack of acceptable coronary arteries for grafting often causes the cardiac surgeon considerable problems in treating patients with severe coronary artery disease. By combining the standard approach of coronary bypass surgery with coronary endarterectomy and with retrograde coronary sinus cardioplegia perfusion, we can achieve a longer ischemic period and can flush the debris from the coronary arteries in a retrograde fashion. Using this approach, we managed 72 patients with near inoperable coronary artery disease. One third of these patients required endarterectomy of more than one vessel. A higher than expected number of patients had diabetes mellitus. The left coronary artery system required endarterectomy in almost 60% of patients, much higher than percentages reported in other series of patients. The mortality rate in our patients who underwent the left system endarterectomy was 5.7%. Endarterectomy must be considered an adjunct in the management of high-risk patients with severe coronary artery disease.

Aged↗

Emergency center thoracotomy: impact of prehospital resuscitation.

Emergency center thoracotomy was performed at our facility on 389 patients from 1984 through 1989. There were no patients excluded from the study, and survival for all patients was 8.3% with survival rates of 15.2% and 7.3% for stab and gunshot wounds, respectively. Emergency center thoracotomy was performed on 42 patients suffering from isolated extrathoracic injuries with 7% survival. There were no survivors of blunt trauma in this study. Fifty-three percent of the patients arrived with cardiopulmonary resuscitation (CPR) in progress. The average time of prehospital CPR for survivors was 5.1 minutes compared with 9.1 minutes for nonsurvivors. Of the survivors, prehospital endotracheal intubation prolonged successful toleration of CPR to 9.4 minutes compared with 4.2 minutes for nonintubated surviving patients (p less than 0.001). Emergency center thoracotomy is useful in the resuscitation of victims dying of penetrating truncal trauma. Prehospital endotracheal intubation significantly lengthened the time of successful CPR.

Adolescent↗

Specific motor abilities associated with speech fluency in Down's syndrome.

Eight adult male stutterers with Down's syndrome (DS) were compared with a matched group of fluent speakers with DS on verbal and manual motor production tasks at two levels of complexity. The simpler tasks involved diadochokinetic rate (syllable repetition) and finger tapping; the more complex tasks involved the imitation of sentences and placing pegs in the grooved pegboard. On both verbal and manual tasks, stutterers were faster on the simpler but slower on the more complex tasks than were the fluent speakers. The findings suggest that stutterers with DS have a different motor organization than fluent speakers with DS.

Adult↗

A review of linguistic factors associated with early childhood stuttering.

This paper summarizes recent thinking on several aspects of early childhood stuttering. The concept of fluency is examined, and a review of research that traces the acquisition of fluency in young children and its relationship to language acquisition is presented. Other topics considered are the relationship of normal childhood nonfluencies to early stuttering, stuttering as it relates to language acquisition, and psycholinguistic influences on stuttering in young children.

Adolescent↗

The effect of short chain fatty acids on transmural electrical potential across rat small intestine in vivo.

Short chain fatty acids suddenly produce a phasic increase in transmural electrical potential difference (PD) when placed in the lumen of rat small intestine in vivo. With concentrations of propionate ranging from 50 muM to 1000 muM the amplitude of the response in jejunum is about 5.5 mV. The concentration giving half this effect is about 20 muM. With 10 mM propionate the duration of the response is 3-5 min; after this, PD again equals the control value and the gut is refractory to further additions. Removing propionate from the mucosal surface produces no change in PD, but does restore responsiveness to subsequent exposure to short chain fatty acids. This effect is independent of a variety of other alterations in PD such as those caused by sugars, amino acids, bile salts, theophylline, prostaglandins, and ATP. Mechanism and significance of this surprisingly sensitive response remain obscure.

Animals↗