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Biomedical subjects

Mark Stewart

Publications and source records attributed to Mark Stewart.

At least 19 recordsLinked to original sources

Repeatable focal seizure suppression: a rat preparation to study consequences of seizure activity based on urethane anesthesia and reversible carotid artery occlusion.

Seizures can be associated with serious systemic complications (even death) due to autonomic nervous system or respiratory dysfunction. Clinical and laboratory studies examining the relationship between seizures and autonomic dysfunction have not resolved important questions, such as whether autonomic changes result primarily from muscle activation or from limbic cortical seizure activity, because correlational studies are limited by opportunities to observe seizures and study seizure spread. We describe a rat preparation that will greatly facilitate such studies. First, we show that systemic kainic acid in urethane anesthetized animals causes a period of status epilepticus as it does in ketamine/xylazine anesthetized or awake animals, but with a critical distinction: limbic cortical seizures occur without neocortical involvement. No paralytic agents are necessary to keep animals "safely" in a stereotaxic frame because there are not motor convulsions, yet animals continue to breathe on their own. Second, we describe the construction of a simple device to permit remote reversible unilateral or bilateral common carotid artery occlusion, and show that seizure activity in dorsal hippocampal regions can be unilaterally or bilaterally suppressed during periods of occlusion. Using this preparation, we found an increase in vagus nerve activity and a decrease in mean arterial pressure during suppression of right dorsal hippocampal seizures. By contrast, suppression of left dorsal hippocampal seizures caused no changes in vagus nerve activity and a small increase in mean arterial pressure. This preparation will be invaluable for defining the dynamic interactions of limbic brain regions and the interactions of limbic brain regions with autonomic brain regions.

Anesthetics, Intravenous↗

Continuous stimulation of transected distal nerves fails to prolong action potential propagation.

Wallerian degeneration of the distal portion of a cut nerve is considered irreversible. A possible reason for degeneration is lack of axon stimulation in the distal, cut nerves. We hypothesized greater rates of stimulation of distal nerve stumps would prolong time to action potential propagation failure, and uncut nerves would not be damaged by implanted nerve stimulators. We also hypothesized that action potentials measured from the body of the sciatic nerve would show similar response as motor-evoked potentials measured in the muscles innervated by branches of the sciatic nerve. We implanted a nerve stimulator onto distal cut sciatic nerves of rats and recorded motor-evoked potentials. Three groups were stimulated at 1 Hz (once per second), 0.1 Hz (once per 10 seconds), and 0.01 Hz (once per 100 seconds) respectively. Motor-evoked potentials progressively declined after nerve transection, failing faster at 1 Hz (26.8 hours +/- 108 minutes) and 0.1 Hz (22 hours +/- 66 minutes) compared with stimulation at 0.01 Hz (36.75 hours +/- 83 minutes). Intact axons were not damaged by implanted nerve stimulators. Action potentials recorded directly from nerves were equivalent to motor- evoked potentials. Failure of motor-evoked potential transmission in a transected nerve is accelerated by a greater rate of continuous stimulation of the distal stump.

Action Potentials↗

Doctor, doctor.

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Animals↗

Computer simulation of epilepsy: implications for seizure spread and behavioral dysfunction.

Hippocampal area CA3 has been one of the most intensively studied brain regions for computer models of epileptiform activity. As physiological studies begin to extend outward to other hippocampal and parahippocampal areas, we must extend these models to understand more complex circuitry containing diverse elements. Study of subiculum is of particular interest in this context, as it is a structure of intermediate complexity, with an inchoate columnar and laminar organization. In addition to helping us understand seizures, modeling of these structures will also help us understand the genesis of physiological activity patterns that are below threshold for seizure generation. Such modeling can also serve as a basis for speculation regarding the nonictal behavioral consequences of epilepsy.

Behavior↗

Mesenteric inflammatory veno-occlusive disease as a cause of acute abdomen: report of five cases.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare but increasingly recognized cause of intestinal ischemia. It can be defined as phlebitis or venulitis affecting either the bowel or mesentery, without any evidence of coexisting arterial inflammatory involvement or an obvious predisposing cause. We report the clinicopathological characteristics of five patients who, after presenting with an acute abdomen, underwent exploratory laparotomy and resection of ischemic bowel. The distinctive histopathological characteristics of MIVOD were identified in all five patients. We review the literature on this under-reported condition.

Abdomen, Acute↗

Endoscopic transanal rectal mucosal ablation in the surgical treatment of ulcerative colitis: preliminary results of a novel technique.

PURPOSE: We describe a new technique that endoscopically eradicates rectal stump mucosa after total colectomy for ulcerative colitis. METHODS: Seven patients (5 males; median age, 56 (range, 36-72) years) underwent attempted endoscopic transanal rectal mucosal ablation using the 28-French-gauge urologic resectoscope, either at the time of total colectomy and ileostomy for failed medical therapy (5 patients) or as an alternative to completion proctectomy (2 patients) with rectal stump discharge. All had declined restorative proctocolectomy. Clinical, endoscopic, and histologic follow-up was undertaken during a mean of 15 (range, 3-28) months. RESULTS: The operative technique evolved during these cases; mucosal ablation was successfully performed leaving a denuded muscular rectal tube in situ in six patients. Mean operative time was 45 minutes. Postoperative endoscopic surveillance has not demonstrated any viable rectal mucosa in these six patients, with only granulation tissue detected histologically. Narrowing of the rectal tube has occurred in two patients. Although all patients report insignificant rectal discharge, urinary and sexual function have remained unchanged. CONCLUSIONS: Diathermy ablation of the rectal mucosa via endoscopic transanal rectal mucosal ablation avoids the complications of pelvic dissection and might offer an effective alternative to proctectomy for ulcerative colitis.

Adult↗

Prediction of outcome after ankle fracture.

STUDY DESIGN: Prospective inception cohort study of 62 consecutive patients seen in 2 orthopaedic clinics following ankle fracture. OBJECTIVES: To investigate 4 putative predictors (age, fracture classification, acute management [surgical or nonsurgical], and ankle dorsiflexion range of motion measured at the time of cast removal) of outcome after ankle fracture and to develop simple predictive models of outcome after ankle fracture. BACKGROUND: Ankle fracture is a common condition. However, few studies have investigated factors that predict outcome after ankle fracture. METHODS AND MEASURES: Sixty-two consecutive subjects aged 17 or older with ankle fractures were recruited from 2 hospital orthopaedic clinics. Outcome measures recorded at 6 weeks and 6 months after cast removal included 2 functional questionnaires, patients' ratings of global improvement, and a measure of ankle dorsiflexion. The predictive value of 4 variables selected a priori was analyzed using bivariate and stepwise multiple linear regression. RESULTS: Ankle dorsiflexion and fracture classification predicted outcome 6 weeks and 6 months after cast removal for all outcome measures used (P < .05, r2 = 0.09-0.47). Fracture management (surgical or nonsurgical) inconsistently predicted outcome at both 6 weeks and 6 months, and age did not predict outcome at either 6 weeks or 6 months after cast removal. The predictive models explain between 19% and 58% of the variance in outcomes 6 weeks after cast removal and 19% to 52% of the variance in outcomes 6 months after cast removal. CONCLUSION: Ankle dorsiflexion measured at the time of cast removal and fracture classification are clinically significant predictors of outcome after ankle fracture; however, much unexplained variation in outcomes still exists.

Adolescent↗

Becoming a GP--a qualitative study of the career interests of medical students.

AIM: Only a minority of Australian graduates are interested in careers in general practice. The factors influencing medical students toward general practice as a career choice are poorly understood, even though this is important to the makeup of the medical workforce. METHODS: We ran 10 focus groups involving 82 first and final year medical students from three Australian medical schools in 2002, and analysed factors influencing participants' interest in working in general practice. RESULTS: About half the students were interested in general practice. Attractive factors were: the nature of the work (including its diversity), continuity of care, community context, and working conditions (including flexibility of training and work, availability of part time work and portability of qualifications). Negative factors included: the breadth of knowledge needed, boring work (in urban general practice), having to run a business, and working conditions (including relatively poor remuneration, overwork in rural general practice, and poor status of general practitioners). Some students were strongly influenced by negative attitudes of the GPs they were taught by, deciding against general practice as a career. DISCUSSION: Medical educators and GPs should be aware of this important influence.

Adolescent↗

Differential modulation by carbachol of four separate excitatory afferent systems to the rat subiculum in vitro.

The subiculum is a limbic cortical region that receives inputs from hippocampus and other parahippocampal regions. We used horizontal brain slices to study the modulatory effects of muscarinic receptor activation on excitatory afferent systems of the subiculum. Multiple inputs are preserved in these slices. Carbachol (CCh, applied to the bath) induced a decrease in the field responses (40-50% at 50 microM; 60% at 100 microM) to CA1, presubicular (PreS), and medial entorhinal (MEC) stimulation. Subicular responses to lateral entorhinal (LEC) stimuli were not depressed. The M1 receptor antagonist pirenzepine at 1 microM was sufficient to reverse most of the CCh-induced depression of afferent excitation, but 10 microM concentrations were required to eliminate the CCh-induced firing in the isolated subiculum. A partial reversal of the CCh-induced depression of afferent excitation was achieved by the M2 receptor antagonist methoctramine (1 or 10 microM), but these concentrations did not prevent CCh-induced firing. When CA1 afferents were repetitively activated with submaximal stimuli in the presence of CCh, population excitatory postsynaptic potentials (EPSPs) showed modest summation, but every response was smaller than a corresponding events in normal media. Population spikes, particularly late spikes in a train, showed pronounced facilitation during CCh exposure. The NMDA receptor antagonist CPP (10 microM) prevented facilitation of responses to repetitive stimulation in the presence of carbachol. We conclude that CA1, PreS, and MEC afferents to the subiculum exhibit CCh sensitivity similar to that established for area CA3 afferents to CA1, and LEC afferents to subiculum exhibit CCh resistance. Our data suggest that much of the hippocampal formation circuitry is modulated by CCh and the properties of this modulation can explain some specific firing characteristics of hippocampal formation neurons in "cholinergic" versus "noncholinergic" brain states.

Acetylcholine↗

Transmembraneous irrigation of multipolar radiofrequency ablation catheters: induction of linear lesions encircling the pulmonary vein ostium without the risk of coagulum formation?

INTRODUCTION: Pulmonary vein (PV) isolation for the curative treatment of atrial fibrillation using conventional radiofrequency ablation (RF) catheters with the point by point technique is time consuming and carries a remaining risk for thrombembolic complications. AIMS OF THE STUDY: Aim of the present in vivo study was to evaluate feasibility and safety of a novel multipolar irrigated ablation catheter designed to create contiguous lesions encircling the PV ostium in a single ablation position. METHODS: The entire ablation section (tripolar, length of each electrode 22 mm, interelectrode distance 2 mm, helix radius: 9 and 10 mm) of the 7F RF catheter (Encirclr, Medtronic, MN, USA) was covered by a porous membrane (pore size 30 micron) providing continuous irrigation. The helical formed catheter was used in two different experimental settings. Initially, a thigh muscle preparation has been performed in 7 anesthetized sheep in order to evaluate the development of lesions at different power level (40-80 W) and RF duration (30-90 sec). The ablation catheter was placed at the surface of the thigh muscle in a perpendicular position (0.1 N contact pressure) and perfused with heparinized blood (250 ml/min, 37C degrees ). Irrigation was provided with a flow rate of 10 ml/min. The resulted lesion morphology was evaluated with regard to coagulum or crater formation and lesion depth and diameter. Subsequently in 9 anesthetized sheep intracardiac ablation has been achieved with 50 W and an irrigation flow of 10 ml/min. Transseptal puncture and RF ablations were guided using fluoroscopy and intracardiac echocardiography (ICE, Acuson, USA). Endpoint of the intracardiac RF applications was the reduction of local electrogram amplitude >50%. RF applications were achieved at both atrial appendages and in the orifices of the coronary sinus (CS), the vena cava inferior (VCI) and PV. Following RF ablation all animals were sacrificed and following in vivo staining (2% TTC) macroscopically and histologically investigations of the lesions were performed. RESULTS: At the thigh muscle preparation 57 RF applications have been performed. The lesion depth was homogeneous without gaps between the ablation electrodes. There was a significant increase comparing 30 with 90 sec of RF duration for 40, 50 and 60 W applications respectively: 40 W: 1.1 +/- 0.4 vs. 3.6 +/- 0.5; 50 W: 1.2 +/- 0.3 vs. 4.6 +/- 0.4 mm and 60 W: 2.6 +/- 0.6 vs. 4.8 +/- 0.5 mm. All applications with 80 W (n = 3) had to be terminated due to immediate increase of impedance >150 omega. Late impedance rises (>60 sec) without occurrence of coagulum formation have been observed in 1 out of 4 RF applications with 60 W.A total of 85 RF applications could be achieved intracardiacally in the right atrium (right atrial appendage n = 18, ostium of the coronary sinus n = 12, ostium of the inferior caval vein: n = 12) and in the left atrium (left atrial appendage: n = 15, ostium of the PV: n = 28). ICE guided positioning of the catheter and showed during all applications no coagulum formation at the electrode or impedance rise (>150 Omega). Reduction of local electrograms (>50%) were observed following 48 out 85 (56%) RF applications. The lesions showed a homogeneous depth of 4 +/- 2 mm and a width 5 +/- 2 mm at the surface. No charring or crater formation could be observed in any of the lesions. CONCLUSIONS: In the present in vivo studies it could be demonstrated that long irrigated ablation electrodes induce continuous lesions without the risk of thrombus formation at the electrode. Increase of RF duration from 30 to 90 seconds with power setting of 40-60 W, respectively, created deeper lesions without the risk of thrombus formation. Thus, the helical formed irrigated ablation catheter appears to be appropriate for simplified PV isolation.

Animals↗

Motor cortical and other cortical interneuronal networks that generate very high frequency waves.

A remarkable feature of motor cortical organization in higher mammals is that a brief electrical stimulus elicits in the pyramidal tract and corticospinal tract an unrelayed direct (D) wave followed by multiple indirect (I) waves at frequencies as high as 500-700 Hz. This review presents some conclusions regarding very high frequency synchronous activity in mammalian cortex: (1) Synchrony in repetitive I discharges is extraordinary in humans and monkeys, less in cats and still less in rats, being there represented by a delayed broad wave; such phylogenetic trends have important implications for the suitability of lower mammalian species for studies of high frequency cortical networks in the human brain; (2) The evidence from microstimulation at different cortical depths and pial cooling favors a vertically oriented chain of interneurons that centripetally excite corticospinal neurons as the basis for inter-I wave periodicity and synchrony; (3) Significantly, the I wave periodicity is conserved despite wide changes in stimulus parameters; (4) Synchronous high frequency activity similar to that of I waves can be recorded from other neocortical areas such as visual and somatosensory cortex; however, evidence is still lacking that the output neurons of these cortical regions have synchronized discharges comparable to I waves; (5) In limbic cortices, the frequency of synchronous neural activity is lower than that in motor cortex or related cortices and periodicity is not conserved with changes in stimulus parameters, indicating a lack of the neocortical interneuronal substrate in limbic cortex; (6) We propose that the very high frequency synchronous activity of motor cortical output reflects a computational function such as a "clock," quantizing times at which inputs would interact preferentially yielding synchronous output discharges. Such circuitry, if a general feature of neocortex, would facilitate rapid communication of significant computations between cortical regions.

Animals↗

Back extensor muscle endurance test scores in coal miners in Australia.

STUDY DESIGN: A cross-sectional analytic study was conducted. OBJECTIVES: To collect normative data on back extensor endurance holding times and evaluate the discriminative validity of the Biering-Sorensen test in a group of coal miners in Australia. SUMMARY OF BACKGROUND DATA: Low back pain is a common complaint among those working in the Australian coal mining industry. One test that may be predictive of first-time episodes of low back pain is the Biering-Sorensen test of back extensor endurance strength. While this test has been evaluated in overseas sedentary populations, normative data and the discriminative ability of the test have not been evaluated with coal miners. METHODS: Eighty-eight coal miners completed a questionnaire for known risk factors for low back pain, performed the Biering-Sorensen test, and undertook a test of aerobic fitness. Data analysis was performed to describe the groups and to determine whether any significant difference existed between those with a past history of low back pain and those without. RESULTS: Significantly lower than expected holding times were found in this group of coal miners (mean 113 s). This result was significantly lower than demonstrated in previous studies (mean 138 s, t87 = 6.32, p < 0.001). When holding times for those with a past history of low back pain were compared with times for those with no history of low back pain, the difference was not statistically significant (t86 = 1.56, p = 0.12), nor was there a significant difference in fitness between those with a past history of low back pain and those without (t86 = 0.47, p = 0.64). DISCUSSION/CONCLUSIONS: Coal miners in Australia have lower than normal Biering-Sorensen holding times. This lower back holding time does not differ between coal miners with a past history of low back pain and those without.

Adult↗

Putting personality in social context: extraversion, emergent leadership, and the availability of rewards.

The present research tested relations between extraversion and emergent leadership among men in situations that differed in potential reward availability. Four-person groups of men engaged in a Leaderless Group Discussion (LGD) task and were randomly assigned to be evaluated by an attractive female observer, an attractive male observer, or not be evaluated. Evolutionary theories suggest that impressing a female evaluator in an intrasexually competitive situation should hold greater reward potential for men than impressing either a male evaluator or no evaluator. Accordingly, more extraverted men (who are more sensitive to reward cues) should display more group leadership when being evaluated by a woman than either a man or no one. Self-and peer ratings confirmed that more extraverted men were significantly more likely to emerge as leaders, but only in the female-evaluator condition. The results are discussed in terms of the interplay between personality, situational factors, and evolutionary principles.

Adolescent↗

Long-term enhancement of excitatory synaptic inputs to layer V parahippocampal neurons by low frequency stimulation in rat brain slices.

Excitatory inputs to layer V neurons of the parasubiculum and medial entorhinal cortex were examined in rat brain slices with intracellular and field potential recordings. Single extracellular stimuli to layer V evoked subthreshold excitatory postsynaptic potentials (EPSPs) or a long duration (>100 ms) depolarization that sustained high frequency firing. Repetitive stimulation at low frequencies (from 1/10 s to 1/min) induced stable long-lasting decreases in the threshold for firing in individual cells or population events, and also induced stable long-lasting increases in evoked intracellular or field response amplitudes. More stimuli were required to produce the equivalent changes in threshold and amplitude in the presence of MCPG (200 microM). Smaller changes in amplitude, but equivalent changes in threshold were elicited in the presence of CPP (10 microM), or CPPG (20 microM). No changes in threshold or amplitude were detected in the presence of CNQX (10 microM), even when used in combination with picrotoxin (100 microM). EPSP facilitation was enhanced greatly by firing in postsynaptic cells. It is suggested that stable changes in excitatory inputs to layer V parahippocampal neurons involve the activation of NMDA and metabotropic glutamate receptors, but requires AMPA receptor activation and postsynaptic cell firing.

Action Potentials↗

Results of pectoralis major transfer with fascia lata autograft augmentation for scapula winging.

Fifteen patients (9 male and 6 female) with a mean age of 32.8 years (range, 17-44 years) were examined at a mean follow-up of 64 months (range, 33-118 months) after undergoing pectoralis major transfer with a fascia lata autograft for scapular winging. Ten patients were treated as part of a worker's compensation claim. Twelve reported that they would undergo the procedure again. The mean Rowe score was 66 (range, 41-92), the mean Constant-Murley score was 74 (range, 32-95), the mean Simple Shoulder Test score was 8 of 12 positive responses, and the mean American Shoulder and Elbow Surgeons score was 63 (range, 10-87). Pain decreased in 11 patients, whereas function improved in 10 patients. According to the Rowe scoring system, the results were excellent in 2 patients, good in 5, fair in 4, and poor in 4. Better results occur in patients attaining at least 60 degrees of external rotation postoperatively. Although complete relief of pain and full function were not always achieved, most patients returned to their preoperative level of activity with minor adaptations.

Adolescent↗