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Biomedical subjects

G J Wilson

Publications and source records attributed to G J Wilson.

At least 37 records · Page 2Linked to original sources

Eliminating arterial pulsatile strain by external banding induces medial but not neointimal atrophy and apoptosis in the rabbit.

We have examined the role of vessel pulsation and wall tension on remodeling and intimal proliferation in the rabbit infrarenal abdominal aorta. A rigid perivascular polyethylene cuff was used to reduce vessel systolic diameter by 25%, producing a region of reduced circumferential strain. At 6 weeks postoperatively, reduced circumferential strain caused medial atrophy, with 45% reduction of medial area and 30% loss of medial smooth muscle cells. Apoptotic cell death was indicated by DNA fragmentation, propidium iodide staining, and cell morphology. Cuffing the aorta after balloon denudation produced medial atrophy but did not inhibit neointimal growth. At 1 week postoperatively, intimal thickness was slightly decreased in regions with reduced strain; however, intimal thickening in regions of reduced strain was not different from control segments at 3 weeks postoperatively (intimal area was 0.37 +/- 0.05 mm2 with reduced strain and 0.50 +/- 0.08 for controls, mean +/- SEM). We conclude that circumferential strain is a major factor controlling medial structure and cell number, whereas growth of the neointima after injury is not significantly affected by either reduced strain or extensive medial cell death. Vessel cuffing represents a new model of blood vessel remodeling in vivo that involves extensive smooth muscle cell apoptosis.

Animals↗

Brain damage and myocardial dysfunction: protective effects of magnesium in the newborn pig.

BACKGROUND: Brain damage is associated with myocardial dysfunction resulting from excessive release of endogenous catecholamines and Ca2+ overload. Magnesium ion, a natural Ca2+ blocker, has recently been recognized as a myoprotective agent. METHODS: Myocardial function was assessed in 3- to 7-day-old piglets from pressure-volume data (obtained by the conductance catheter/micromanometer technique) before and for 4 hours after ligation of the aortic arch vessels and was correlated with ultrastructural changes. Group a (n = 6) received MgSO4 immediately after induction of brain damage for 4 hours, whereas group b (n = 6) did not receive MgSO4 and served as control. RESULTS: In both groups after induction of brain damage, there was a significant (p < 0.05) increase in end-systolic elastance and preload-recruitable stroke work that persisted for 1 hour. However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in both variables in group b (end-systolic elastance, 74% +/- 5% and 59% +/- 6%, respectively, and preload-recruitable stroke work, 77% +/- 4% and 64% +/- 3%, respectively, compared with baseline), and in group a, the values returned to baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15 minutes after induction of brain damage and remained significantly (p < 0.05) higher for 4 hours versus no significant change in group a. Plasma levels of epinephrine and norepinephrine were similar in the groups before and after brain damage. Electron microscopic study showed severe ultrastructural changes in group b and significantly milder changes in group a. CONCLUSIONS: We conclude that MgSO4 may protect the neonatal myocardium when administered immediately after brain damage.

Adrenergic Agonists↗

Hypersensitivity myocarditis caused by an allergic reaction to cefaclor.

An adolescent girl was seen with acute heart failure 6 days after the onset of a viral illness and otitis media treated with cefaclor. An endomyocardial biopsy specimen revealed active myocarditis with an eosinophilic infiltrate typical of hypersensitivity myocarditis. The patient showed dramatic improvement within 48 hours after withdrawal of the drug and administration of corticosteroids and immunoglobulin.

Biopsy↗

Stretch-shorten cycle compared with isometric preload: contributions to enhanced muscular performance.

To isolate any difference muscular contraction history may have on concentric work output, 40 trained male subjects performed three separate isokinetic concentric squats that involved differing contraction histories, 1) a concentric-only (CO) squat, 2) a concentric squat preceded by an isometric preload (IS), and 3) a stretch-shorten cycle (SSC) squat. Over the first 300 ms of the concentric movement, work output for both the SSC and IS conditions was significantly greater (154.8 +/- 39.8 and 147.9 +/- 34.7 J, respectively; P < 0.001) compared with the CO squat (129.7 +/- 34.4 J). In addition, work output after the SSC test over the first 300 ms was also significantly larger than that for the corresponding period after the IS protocol (P < 0.05). There was no difference in normalized, integrated electromyogram among any of the conditions. It was concluded that concentric performance enhancement derived from a preceding stretch of the muscle-tendon complex was largely due to the attainment of a higher active muscle state before the start of the concentric movement. However, it was also hypothesized that contractile element potentiation was a significant contributor to stretch-induced muscular performance under these conditions.

Adult↗

Absorption, distribution, metabolism, and excretion of atevirdine in the rat.

Atevirdine mesylate (U-87201E) is a highly specific nonnucleoside inhibitor of human immunodeficiency virus type 1 reverse transcriptase. The absorption, metabolism, and excretion of atevirdine were investigated in male and female Sprague-Dawley rats after oral administration of nonradiolabeled atevirdine mesylate at doses of 20 mg/kg/day or 200 mg/kg/day for 8 days, with [14C]atevirdine mesylate single doses of 10 mg/kg or 100 mg/kg on study days 1 and 10. The distribution of [14C]atevirdine mesylate was also evaluated by whole-body autoradiography in male and female Sprague-Dawley, pregnant Sprague-Dawley, and male Long-Evans rats after a single 10 mg/kg oral dose. Plasma levels of atevirdine and its N-desethyl and O-desmethyl metabolites were determined by high-performance liquid chromatography (HPLC) with ultraviolet detection, urine and feces were profiled for atevirdine and metabolites by HPLC with radiochemical detection, major metabolites in urine were isolated and identified by nuclear magnetic resonance and mass spectrometry, and minor urinary metabolites were identified by liquid chromatography/mass spectrometry. Atevirdine was rapidly absorbed. The pharmacokinetics of atevirdine were nonlinear. Gender differences in the pharmacokinetics and metabolism of atevirdine were observed, consistent with the involvement of cytochrome P450 3A. Atevirdine effectively crossed the blood-brain barrier and had a high rate of maternal-fetal transfer. At the low doses, <2% of the dose was excreted as unchanged parent drug, while atevirdine constituted 9%-25% of the dose at the high doses. The metabolism of atevirdine was extensive in the rat and involved N-deethylation, O-demethylation, hydroxylation at the C-6 position of the indole ring, and hydroxylation of the pyridine ring.

Animals↗

A new self-expanding lined stent-graft in the dog ureter: radiological, gross, histopathological and scanning electron microscopic findings.

Recurrent or intractable ureteral strictures pose a significant problem for the practicing urologist. Metallic stents have been used sparingly for this problem with varying success. We investigated the use of a stent-graft consisting of a metal stent lined with a porous biocompatible polymer to determine if the liner would prevent urothelial ingrowth. One ureter of each of 11 dogs was treated with either a metallic woven stent or stent-graft inserted retrograde via a midline cystotomy. Six bare wire stents (controls) and five lined with a new, porous, biocompatible, polycarbonate elastomer liner (Corethane) were placed. The animals were followed radiographically with intravenous urography (IVP) at 6 weeks and just prior to sacrifice (12 to 22 weeks). Gross, histological, and electron microscopic analyses were performed. The results demonstrate that all of the bare metal stented animals developed moderate to severe hydroureteronephrosis with significant urothelial hyperplasia and ingrowth through the spaces between the metal wires. The animals implanted with lined stents showed one instance of mild hydroureteronephrosis (observed radiographically but not grossly at time of sacrifice) and virtually no papillary in-growths of urothelium through the stent interstices. This obstructive phenomenon was prevented by the porous polymer lining. There was no evidence of biodegradation of the liner on scanning electron microscopy. Based upon these findings, the marriage of a biocompatible polymer which provokes minimal tissue reaction, and metallic stents which provide tremendous strength, seems to offer significant advantages when placed into the urinary tract to maintain ureteral luminal patency.

Animals↗

Correlations between peak power output, muscular strength and cycle time trial performance in triathletes.

OBJECTIVE: To examine the relationship between the peak power output (Wmax), peak oxygen uptake (VO2peak), lower limb muscular strength and cycling time (CT) during a short course triathlon race. EXPERIMENTAL DESIGN: The study involved a cross-sectional analysis involving both physiological and biomechanical variables. SETTING: Testing was performed at the exercise physiology and biomechanics laboratory, School of Exercise Science and Sport Management, Southern Cross University, Lismore, Australia. PARTICIPANTS: Ten male triathletes who had been endurance cycle training for a minimum of 12 months prior to the commencement of the study. MEASURES: Subjects completed a maximal incremental cycle test as well as a series of muscular function tests including a 6-s cycle test, a concentric isoinertial squat jump as well as an isokinetic leg extension test performed at velocities of 60 degrees (s-1, 120 degrees (s-1 and 180 degrees.s-1. In addition, each subject also participated in a triathlon race of distance 1.5 km swim, 40 km cycle and 10 km run. RESULTS: A significant correlation existed between CT and absolute VO2 peak and Wmax. However, no significant correlations were found between the results of the muscular function tests and the incremental cycle test as well, as CT during the triathlon race. CONCLUSIONS: Wmax and WDmax are useful variables in assessing cycle performance in triathletes. However, the importance of muscular strength of the lower limbs may be minimal in overall cycle performance during a short course triathlon race.

Acceleration↗

Ischemic preconditioning: differences in protection and susceptibility to blockade with single-cycle versus multicycle transient ischemia.

BACKGROUND: We compared ischemic preconditioning (IP) induced with a single cycle of transient ischemia and reperfusion with that induced by multiple cycles in terms of (1) efficacy of protection against myocardial necrosis and (2) susceptibility to pharmacological blockade by inhibition of protein kinase C (PKC) or elevation of cAMP. METHODS AND RESULTS: All rabbits were subjected to 30 minutes of regional ischemia and 90 minutes of reperfusion in vivo. IP was induced with either one or three cycles of 5-minute transient ischemia and 10-minute reperfusion given before the 30-minute ischemia. Drug-treated hearts received a bolus dose of one of the following just before the 30-minute ischemia: (1) the PKC inhibitor chelerythrine (3.8 mg/kg), (2) the PKC inhibitor polymyxin B (10 mg/kg), or (3) the cAMP-increasing agent NKH477 (45 microg/kg). IP induced with either one or three cycles of transient ischemia and reperfusion significantly protected the heart against infarction, although the extent of protection was significantly greater with three-cycle IP. Chelerythrine, polymyxin B, or NKH477 alone did not alter infarct size in control hearts, nor did they increase infarct size in hearts preconditioned with three-cycle IP. In contrast, when IP was induced with only a single cycle, all three of these drugs significantly increased infarct size above that of the untreated one-cycle IP group. However, infarct size in all three of these drug-treated one-cycle IP groups was still significantly lower than that in the corresponding drug-treated controls, indicating a partial block of IP. CONCLUSIONS: Three-cycle IP provided more effective protection against myocardial necrosis than one-cycle IP and was less susceptible to blockade by inhibitors of PKC or an agent that increases cAMP levels. However, single-cycle IP was only partially blocked by either inhibition of PKC or stimulation of cAMP production. Neither activation of the PKC pathway nor reduced formation of cAMP alone fully accounted for the necrosis protection by IP even when induced with only a single cycle of transient ischemia.

Adenylyl Cyclases↗

Selective blockade of AT1 angiotensin II receptors abolishes ischemic preconditioning in isolated rabbit hearts.

The aim of the present study was to assess the participation of angiotensin II receptors in the triggering mechanism of ischemic preconditioning. Isolated buffer-perfused rabbit hearts were subjected to 40 min of regional ischemia (37 degrees C) followed by 60 min of reperfusion. Ischemic preconditioning was induced with three cycles of 5-min ischemia and 10-min reperfusion given prior to the 40-min ischemic period. Infarct size and ventricular function were assessed. Ischemic preconditioning reduced infarct size to 5.2 +/- 1.2% of the area at risk (mean +/- S.E.M., P<0.001) when compared to controls (26.4 +/- 3.0%), but did not protect against ventricular dysfunction. Activation of angiotensin II receptors with angiotensin II (100 nM) also limited infarct size (9.6 +/- 2.2%, P<O.01 v control group). Inhibition of angiotensin II receptors with [Sar1, Val5, Ala8]-angiotensin II (saralasin, 1 microM) blocked the protection of ischemic preconditioning against necrosis (29.7 +/- 3.2%) while it did not increase infarct size in saralasin-treated control hearts (31.5 +/- 3.9%). Furthermore, inhibition of the AT1 subtype of the angiotensin II receptor with losartan (20 microM), but not inhibition of the AT2 subtype with PD-123,319 ditrifluoroacetate (10 microM), abolished the infarct size-limiting effect of ischemic preconditioning. We conclude that the AT1 angiotensin II receptor participates in ischemic preconditioning. Thus, in the isolated rabbit heart, activation of AT1 receptors must occur before prolonged ischemia for ischemic preconditioning to limit infarction.

Analysis of Variance↗

Influence of load and stretch shortening cycle on the kinematics, kinetics and muscle activation that occurs during explosive upper-body movements.

Although explosive power in lower-body movements has been extensively studied, there is a paucity of research examining such movements in the upper body. This study aimed to investigate the influence of load and the stretch shortening cycle (SSC) on the kinematics, kinetics, and muscle activation that occurs during maximal effort throws. A total of 17 male subjects performed SSC and concentric only (CO) bench throws using loads of 15%, 30%, 45%, 60%, 75%, 90% and 100% of their previously determined one repetition maximum bench press. The displacement, velocity, acceleration, force and power output as well as the electromyogram (EMG) from pectoralis major, anterior deltoid, and triceps brachii were recorded for each throw. The results were compared using multivariate analysis of variance with repeated measures. A criterion alpha level of P < or = 0.05 was used. Similar force velocity power relationships were determined for this multijoint upper-body movement as has been found for isolated muscles, single joint movements, and vertical jumping. The highest power output was produced at the 30% [563 (104) W] and 45% [560 (86) W] loads during the SSC throws. Force output increased as a function of load; however, even the lighter loads resulted in considerable force due to the high accelerations produced. Average velocity, average and peak force, and average and peak power output were significantly higher for the SSC throws compared to the CO throws. However, peak velocity and height thrown were not potentiated by performing the pre-stretch because the duration and range of movement allowed the ability of the muscle to generate force at high shortening velocities to dominate the resulting throw. As such, explosive movements involving longer concentric actions than experienced during brief SSC movements may be limited by the ability of the muscle to produce force during fast contraction velocities.

Adult↗

The development of an isokinetic squat device: reliability and relationship to functional performance.

This study was performed to determine the reliability and validity of a new isokinetic squat device in comparison to knee-extension tests performed using a Cybex. Athletic male subjects (n = 29) performed a series of isokinetic squat tests at 0.4 m.s-1, knee-extension tests at 1.05, 2.09 and 3.14 rad.s-1, and a 6-s stationary cycle test which was used as the measure of functional performance. The squat tests included a purely concentric squat without pre-load, a test with pre-load and a stretch-shorten cycle test. Two trials of each test were performed on one testing occasion. Intraclass correlation co-efficients (r = 0.89-0.96) and co-efficients of variation (3.1-8.7%) were determined between trials, and these indicated that all of the tests were highly reliable. The velocity characteristics of the newly developed system demonstrated that it was an effective isokinetic device, with the mean velocity of 0.41 m.s-1 varying within narrow limits, a relatively small velocity overshoot and an isokinetic portion of movement of approximately 80%. The squat tests demonstrated a higher relationship to cycling performance (r = 0.57-0.65) as compared to the knee-extension tests (r = 0.45-0.51). This difference was amplified when a more homogeneous group of subjects was examined. Further, the squat tests were superior to the knee-extension tests in discriminating between differing levels of cycling performance ability. These differences were believed to be due to the greater specificity of the squat movement, in comparison to the knee extension, to the performance of interest.

Adolescent↗

Cardiomyopathy: a late complication of hemolytic uremic syndrome.

This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS.

Cardiomyopathies↗

Urinary continence after radical retropubic prostatectomy. Analysis and synthesis of contributing factors: a unified concept.

OBJECTIVE: To assess the effects of three types of apical dissection on urinary continence after radical retropubic prostatectomy and to evaluate possible contributing factors, e.g. preservation of the bladder neck and preprostatic sphincter, age, anastomotic strictures, previous transurethral resection and nerve-sparing surgery. PATIENTS AND METHODS: Having undergone one of three types of apical dissection, 280 patients were evaluated: in Group 1 (sphincter-damaging) 134 patients underwent the original technique of ligating and transecting the venous complex; in Group 2 (sphincter-repairing), 76 patients had the venous complex with part of striated sphincter incorporated within anastomotic suture(s); and in Group 3 (sphincter-preserving), 70 patients had the venous complex alone ligated using the 'bunching' technique of Myers. The outcome was analysed for the number becoming continent and the time to continence. RESULTS: Continence was achieved in 93% overall, with 90%, 93% and 99% achieving continence in Groups 1, 2 and 3, respectively. The mean time to continence was 68 days overall, taking 100, 52 and 30 days for the respective groups. Twenty patients (7%) did not achieve full continence; 15 had minor incontinence and five severe, with none of the latter being in Group 3. The group (preservation of external sphincter), age and freedom from development of anastomotic strictures were the most important factors both in regaining continence and decreasing the time to continence. CONCLUSIONS: Preservation of as much as possible of the normal anatomy of the sphincter mechanisms and their nerve supplies results in an excellent return to continence after radical retropubic prostatectomy.

Aged↗

The ability of tests of muscular function to reflect training-induced changes in performance.

We examined the ability of isokinetic and isoinertial tests of muscular function to track training-induced changes in performance. Subjects completed the following tests before and after training: (1) two isoinertial tests using concentric and eccentric actions; (2) isokinetic knee extension at two velocities; and (3) a one-repetition maximum squat. Further, a 40 m sprint and 6 s cycle test were conducted as measures of athletic performance. The subjects were split into a weights group, which performed heavy squats, and a control group. The results showed that training significantly enhanced sprint time by 2.2%, and the improvement in cycle performance (9%) approached significance (P = 0.09). However, apart from the squat, no measure of muscular function significantly changed because of training. Furthermore, there was no relationship between the training-induced changes in performance and the training-induced changes in the isokinetic and isoinertial tests. The results suggest that tests of muscular function cannot be used to monitor training-induced changes in performance. We considered this to be due to the large degree of variance unaccounted for in the relationship between the scores on tests of muscle function and performance. Therefore, the effectiveness of training should be based on changes in performance rather than changes in test scores of muscle function.

Adult↗

Myosin head interactions in Ca2+-activated skinned rabbit skeletal muscle fibers.

Interactions between the two myosin heads were studied in skinned rabbit slow-twitch muscle fibers activated in the presence of vanadate (Vi), a phosphate analog. The strong complex between Vi, MgADP, and myosin trapped the myosin in an inactivated myosin x MgADP x Vi state. Electron paramagnetic resonance spectroscopy was used to quantitate the fraction of myosin heads trapped in the presence of a spin labeled analog of ATP (SLATP). Force was found to depend directly on the fraction of untrapped heads. At high [Vi] (low force), most untrapped heads would have a trapped partner. The equivalence of force with the proportion of untrapped heads shows that the isometric force produced by a single untrapped myosin head on a molecule with a trapped partner is equivalent to that produced by either head of a myosin molecule with neither head trapped. The actin-activated MgATPase activities of one-headed and two-headed skeletal myosin species were inhibited similarly by Vi, suggesting that trapping one head did not preclude trapping its partner. These data indicate that the two skeletal muscle myosin heads can function without interacting during maximal Ca2+-activated force generation.

Adenosine Diphosphate↗

Reovirus variants selected during persistent infections of L cells contain mutations in the viral S1 and S4 genes and are altered in viral disassembly.

Reoviruses isolated from persistently infected cultures (PI viruses) can grow in the presence of ammonium chloride, a weak base that blocks acid-dependent proteolysis of viral outer-capsid proteins during viral entry into cells. We used reassortant viruses isolated from crosses of wild-type (wt) reovirus strain, type 1 Lang, and three independent PI viruses, L/C, PI 2A1, and PI 3-1, to identify viral genes that segregate with the capacity of PI viruses to grow in cells treated with ammonium chloride. Growth of reassortant viruses in ammonium chloride-treated cells segregated with the S1 gene of L/C and the S4 gene of PI 2A1 and PI 3-1. The S1 gene encodes viral attachment protein sigma1, and the S4 gene encodes outer-capsid protein sigma3. To identify mutations in sigma3 selected during persistent reovirus infection, we determined the S4 gene nucleotide sequences of L/C, PI 2A1, PI 3-1, and four additional PI viruses. The deduced amino acid sequences of sigma3 protein of six of these PI viruses contained a tyrosine-to-histidine substitution at residue 354. To determine whether mutations selected during persistent infection alter cleavage of the viral outer capsid, the fate of viral structural proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment of virions of wt and PI viruses with chymotrypsin in vitro. Proteolysis of PI virus outer-capsid proteins sigma3 and mu1C occurred with faster kinetics than proteolysis of wt virus outer-capsid proteins. These results demonstrate that mutations in either the S1 or S4 gene alter acid-dependent disassembly of the reovirus outer capsid and suggest that increased efficiency of proteolysis of viral outer-capsid proteins is important for maintenance of persistent reovirus infections of cultured cells.

Animals↗