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C Brophy

Publications and source records attributed to C Brophy.

At least 19 recordsLinked to original sources
PubMed2000

Vascular smooth muscle mechanics in isolated perfused segments of carotid arteries.

BACKGROUND: We hypothesized that smooth muscle contraction and relaxation responses in a muscle bath (isometric tension) would be different than responses of intact vessels (isotonic tension). METHODS: Bovine carotid artery contractile responses to the catecholamine, norepinephrine, and smooth muscle relaxant, 3-isobutyl-1-methylxanthine, were examined in strips of vessels in a muscle bath and in intact whole vessels in an isolated perfused whole-vessel perfusion apparatus. RESULTS: The maximal tension in the muscle bath depended on the length of the strip. The responses of whole vessels to increasing pressure was curvilinear. The maximal decrease in vessel diameter in intact vessels in response to the catecholamine and norepinephrine occurred at low intraluminal pressures. The dose-response curve to norepinephrine was shifted to the left in intact vessels compared with strips of vessels in the muscle bath, which suggests that whole vessels were more sensitive to norepinephrine. The maximal increase in diameter to increasing intraluminal pressure occurred in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, which suggests that there was significant intrinsic tone in the vascular smooth muscle. CONCLUSIONS: These results suggest that there are differences in the contractile properties of the vascular smooth muscle that are related to the ex vivo system used to examine smooth muscle responses. Responses obtained in isolated perfused whole vessels may more closely approximate in vivo responses.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Early experience with infectious complications of percutaneous femoral artery closure devices.

Percutaneous femoral artery closure devices are being used routinely after cardiac catheterizations. The use of these devices has been advocated to decrease length of stay, promote early ambulation, and prevent bleeding. We reviewed the use of these devices in our institution and report three cases of infectious complications (two pseudoaneurysms and one infected hematoma). Reports of infected pseudoaneurysms after cardiac catheterization before the implementation of these devices are rare. The use of these devices may be associated with an increased incidence of infected femoral pseudo-aneurysms.

Aneurysm, False↗
PubMed2000

Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins.

Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.

Animals↗
PubMed2000

Enhanced arterial contractile responses in diabetic hypercholesterolemic pig carotid arteries.

BACKGROUND: Two of the common risk factors for atherosclerosis are diabetes and hypercholesterolemia. AIMS: The purpose of this investigation was to determine the independent and combined effects of experimental diabetes (DM) and hypercholesterolemia (HC) on vasomotor responses. METHODS: Yorkshire pigs were rendered hypercholesterolemic, diabetic, hypercholesterolemic/diabetic, or maintained as control. Dose dependent physiologic responses of the carotid artery smooth muscle to serotonin, sodium nitroprusside and phorbol ester were determined in a muscle bath. RESULTS: Vascular smooth muscle from the DM and HC/DM pigs showed enhanced contractile responses to serotonin. The HC pigs showed diminished contractile responses to serotonin. The DM smooth muscles had enhanced contractile responses to phorbol dibutyrate. There were no differences in endothelial-independent relaxation responses to sodium nitroprusside. CONCLUSIONS: This study demonstrates that diabetes enhances smooth muscle contractile responses in the presence and absence of hypercholesterolemia.

Animals↗
PubMed1999

Recanalization of an occluded popliteal artery following posterior knee dislocation.

Posterior knee dislocation results in popliteal artery injury in up to one-third of cases. Prompt recognition and treatment of arterial injury is essential for limb salvage. We report a case of complete occlusion of the popliteal artery following posterior knee dislocation treated with saphenous vein bypass without exclusion of the injured arterial segment. Follow-up duplex scanning demonstrated a patent vein graft and a patent ipsilateral popliteal artery. This report suggests that, in some instances, a traumatically occluded popliteal artery may recanalize, and that revascularization with a bypass graft may be the preferred method of repair, particularly in young patients.

Child↗
PubMed1998

How long should Atrovent be given in acute asthma?

BACKGROUND: In acute asthma the optimal duration of treatment with combination beta agonist and anticholinergic nebuliser solutions is unknown; most studies have investigated single doses or treatment for up to 12 hours. To determine whether longer treatment with ipratropium bromide might aid recovery a study was undertaken in 106 patients with acute asthma. METHODS: A double blind, randomised, placebo controlled, three group study was performed with all patients receiving ipratropium for 12 hours and salbutamol for 60 hours after admission (both nebulised four hourly), systemic steroids and, if necessary, theophylline. At 12 hours ipratropium was stopped in group I (n = 35) but was continued in the other two groups, and at 36 hours ipratropium was also stopped in group II (n = 35) while patients in group III (n = 36) continued with ipratropium for 60 hours. Spirometric tests were performed before and after salbutamol, and again 30 and 60 minutes after ipratropium or placebo at 12, 36 and 60 hours. Peak flow rates (PEFR) were measured before and after each nebulisation. RESULTS: There were no differences between the groups in PEFR on admission (group I: 214 l/min, group II: 198 l/min, group III: 221 l/min), or mean forced expiratory volume in one second (FEV1) at 12 hours (group I: 1.81, group II: 2.01, group III: 2.21), 36 hours (group I: 2.11, group II: 2.31, group III: 2.41), or at 60 hours (group I: 2.21, group II: 2.31, group III 2.51). Despite this, median time to discharge was significantly higher for patients in group I (5.4 days) than for those in groups II (4.1 days) and III (4.0 days). CONCLUSIONS: Combination nebulised therapy can be continued beyond 12 hours and up to 36 hours after admission with improved recovery time. Lung function testing may not reflect the full benefit of treatment.

Acute Disease↗
PubMed1998

Thrombin-induced vasospasm: cellular signaling mechanisms.

BACKGROUND: In the setting of arterial injury, thrombin contributes to the hemostatic process by activating the coagulation cascade and platelets. We hypothesized that thrombin also contributes to hemostasis by inducing vasospasm. The purpose of this investigation was to characterize the cellular signaling mechanisms that modulate thrombin-induced vascular smooth muscle contractions. METHODS: Contractile responses of intact bovine carotid artery smooth muscles were determined in a muscle bath. Contractile responses were correlated with phosphorylation events as determined with whole cell phosphorylation and two-dimensional gel electrophoresis and with immunoblotting of glycerol-urea or two-dimensional gels. RESULTS: Thrombin (1 to 1000 units/ml) induced sustained vascular smooth muscle contractions of similar magnitude as the potent contractile agonist, endothelin. Thrombin-induced contractions were associated with increases in the phosphorylation of the myosin light chains (MLC20) and in the tyrosine phosphorylation of mitogen-activated protein kinase. CONCLUSIONS: These data suggest that thrombin is a potent physiologic contractile agonist that may modulate some forms of vasospasm. Thrombin-induced contractions are associated with the activation of two cellular signaling pathways, the myosin light chain kinase and the mitogen-activated protein kinase pathways.

Animals↗
PubMed1997

Exposure of endothelial cells to cyclic strain induces elevations of cytosolic Ca2+ concentration through mobilization of intracellular and extracellular pools.

We have previously reported that exposure of endothelial cells to cyclic strain elicited a rapid but transient generation of inositol 1,4,5-trisphosphate (IP3), which reached a peak 10 s after the initiation of cyclic deformation. To address the effect of cyclic strain on intracellular Ca2+ concentration ([Ca2+]i) and its temporal relationship to IP3 generation, confluent bovine aortic endothelial cells were grown on flexible membranes, loaded with aequorin and the membranes placed in a custom-designed flow-through chamber. The chamber was housed inside a photomultiplier tube, and vacuum was utilized to deform the membranes. Our results indicate that the initiation of 10% average strain induced a rapid increase in [Ca2+]i which contained two distinct components: a large initial peak 12 s after the initiation of stretch which closely followed the IP3 peak, and a subsequent lower but sustained phase. Pretreatment with 5 microM GdCl3 for 10 min or nominally Ca2+-free medium (CFM) for 3 min reduced the magnitude of the initial rise and abolished the sustained phase. Repetitive 10% average strain at a frequency of 60 cycles/min also elicited a single IP3 peak at 10 s. However, there was also a large initial [Ca2+]i peak followed by multiple smaller transient [Ca2+]i elevations. Preincubation with 5 microM GdCl3 or CFM diminished the initial [Ca2+]i transient and markedly inhibited the late-phase component. Preincubation with 25 microM 2,5-di-(t-butyl)-1,4-benzohydroquinone (BHQ) attenuated the initial [Ca2+]i transient. Cyclic-strain-mediated IP3 formation in confluent endothelial cells at 10 s, however, was not modified by pretreatment with 25 microM BHQ, 500 microM NiCl2, 10 nM charybdotoxin, 5 microM GdCl3 or CFM. We conclude that in endothelial cells exposed to cyclic strain, Ca2+ enters the cytosol from intracellular and extracellular pools but IP3 formation is not dependent on Ca2+ entry via the plasma membrane.

Animals↗
PubMed1997

The impact of balloon embolectomy on the function and morphology of the endothelium.

PURPOSE: Intravascular interventions such as balloon embolectomy lead to endothelial injury. The extent and functional consequences of this endothelial injury are not known. METHODS: Segments of bovine carotid artery were equilibrated in a vasomotor perfusion apparatus (VPA). Smooth muscle function was determined by the contractile responses to 10(-5) M norepinephrine (NE). Endothelial function was evaluated by the extent of vasorelaxation to the subsequent addition of 10(-5) M acetylcholine (ACh). To determine the pattern of injury throughout the length of the vessel, strips of artery from along the vessel length were also evaluated in a muscle bath. Morphology was examined by scanning electron microscopy (SEM). RESULTS: No significant differences were noted in the contractile response to NE after embolectomy. Balloon embolectomy significantly decreased the relaxation response to ACh from 97 +/- 1% before embolectomy to 89 +/- 1% after embolectomy (n = 5 vessels, P < 0.01, ANOVA). In the muscle bath, the vasorelaxation of strips precontracted with NE was variable throughout the length of the vessel suggesting that endothelial injury was diffuse. The relaxation response to ACh was inhibited by L-NMMA. SEM revealed patchy areas of endothelial denudation. CONCLUSION: Embolectomy produces no change in smooth muscle function and partial injury to the endothelium in intact vessels. However, there remains sufficient endothelial function after balloon embolectomy to produce NO-dependent vasorelaxation and modulate vasomotor tone.

Acetylcholine↗
PubMed1995

Non-invasive impedance analysis: a new non-invasive test for graft surveillance.

Detection of failing grafts with early reoperation is clearly associated with better long-term patency than intervention after graft failure. Duplex ultrasonography is more accurate than ankle:brachial index for graft surveillance, but is expensive, time consuming and technically demanding. Non-invasive estimation of graft impedance is now possible. The present study was undertaken to evaluate the utility of non-invasive impedance in detecting the failing vein graft. Sixty-nine grafts in 51 patients were followed over a period of 12 months (April 1992-March 1993). High risk infrainguinal arterial vein bypass patients were entered into a graft surveillance program. Ankle:brachial index, non-invasive impedance and duplex ultrasonography were performed upon discharge, 1 month after surgery and then at 3-monthly intervals. Non-invasive impedance was measured using a mean Doppler flow signal obtained from both upper and lower ends of the graft paired with the mean pulse volume recording obtained from the distal arterial bed. The mean pulse volume recording and flow signals were digitized by discrete Fourier transform and an impedance index generated. An impedance index > or = 0.5 was considered abnormal. Impedance results were compared with ankle:brachial index, duplex ultrasonography and angiography when appropriate, and detected 28 failing and five failed grafts. Non-invasive impedance achieved a sensitivity of 91% and a specificity of 94%. Similarly, duplex ultrasonography was 91% sensitive and 97% specific, while ankle:brachial index was 58% sensitive and 94% specific. Non-invasive impedance is a simple, inexpensive and effective test which detects the failing graft and is an appropriate first-line alternative to duplex ultrasonography for postoperative graft surveillance.

Adult↗
PubMed1995

Kinase activation and smooth muscle contraction in the presence and absence of calcium.

PURPOSE: The intracellular signalling mechanisms that modulate the sustained vascular smooth muscle contractions that occur with vasospasm are not well understood. The purpose of this investigation was to examine cell signalling mechanisms that account for sustained vascular smooth muscle contraction, independent of increases in intracellular Ca2+ concentrations ([Ca2+]i). METHODS: Fresh bovine carotid artery smooth muscles contractile responses were examined in a muscle bath. [Ca2+]i was depleted by use of the extracellular Ca2+ chelator, ethylene glycol-bis(beta-aminoethylether) N,N,N',N'-tetraacetic acid and the intracellular chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid. RESULTS: In Ca(2+)-free conditions, depolarizing the membrane with high extracellular KCI failed to elicit a contraction. In addition, in Ca(2+)-free conditions the ([Ca2+]i) was less than 10 nmol/L as determined with the Ca(2+)-indicator, Fura 2. The protein kinase C (PKC) activator, phorbol 12, 13-dibutyrate (PDBu), induced slowly developing sustained contractions in bovine carotid artery smooth muscle, and the magnitude of the contractile response to PDBu (10 nmol/L to 10 mumol/L) was the same in the presence and absence of Ca2+. PDBu induced contractions in Ca(2+)-free conditions were not inhibited by the myosin light chain kinase inhibitor, ML-9 (50 mumol/L), but were inhibited by the PKC inhibitor, staurosporine (50 nmol/L). CONCLUSIONS: These data suggest that vascular smooth muscle contractions can occur under conditions where the [Ca2+]i is low and fixed and that these contractions may be mediated by PKC.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Public procurement.

Explore the source record for details and available documents.

Contract Services↗
PubMed1992

Repetitive stimulation of phrenic nerves in myasthenia gravis.

BACKGROUND: In the investigation of patients with myasthenia gravis, repetitive supramaximal stimulation of an affected peripheral nerve is commonly performed to detect abnormal transmission at the neuromuscular junction. A study was undertaken to determine whether abnormal transmission could similarly be detected during stimulation of the phrenic nerves. METHODS: The phrenic nerves were stimulated supramaximally with surface electrodes in 13 patients with myasthenia gravis and in 16 control subjects (six control patients with diaphragmatic weakness but not with myasthenia and ten normal subjects). The amplitude of diaphragm muscle action potentials was measured with surface electrodes during phrenic nerve stimulation at frequencies of 1-5 Hz for 3-4 seconds. RESULTS: In five patients with myasthenia gravis, a significant decrement (15-43% decrease) occurred in the amplitude of diaphragm muscle action potential during stimulation at 3 Hz. When stimulation frequency was reduced to 1 Hz, diaphragm muscle action potentials returned to their original amplitude within 4-5 seconds. The decrement in the amplitude of the diaphragm muscle action potential was reduced temporarily in three of four patients after the administration of intravenous edrophonium chloride (Tensilon). There was no significant change (< 10% decrease) in the amplitude of diaphragm muscle action potentials during stimulation at increased frequencies either in the 16 control subjects or in eight of the patients with myasthenia gravis. CONCLUSION: A significant reduction in the amplitude of diaphragm muscle action potential occurred in five of 13 patients with myasthenia gravis during phrenic nerve stimulation at 3 Hz but in none of the control subjects. This may be a useful and non-invasive method for identifying patients with myasthenia gravis in whom weakness of the diaphragm is suspected.

Action Potentials↗
PubMed1991

Measurement of twitch transdiaphragmatic pressure: surface versus needle electrode stimulation.

The transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 1 Hz from surface stimulating electrodes was compared with pressures obtained from needle electrodes inserted under local anaesthesia. Surface electrodes were used to obtain diaphragmatic electromyograms and magnetometers to monitor rib cage and abdominal configuration. Twitch Pdi was recorded at functional residual capacity in three normal subjects. Mean (SD) twitch Pdi in the three subjects during stimulation with surface electrodes was 19.4 (1.8), 22.5 (1.1), and 29.3 (2.2) cm H2O compared with 12.9 (1.5), 17:4 (1.3), and 22.6 (3.0) cm H2O with needle stimulating electrodes. Thus phrenic nerve stimulation with needle electrodes was more complicated and more invasive than stimulation with surface electrodes and resulted in lower transdiaphragmatic pressures.

Adult↗
PubMed1990

Respiratory muscle function in cystic fibrosis.

Maximal static expiratory and inspiratory mouth pressures (PEmax and PImax) and quadriceps femoris muscle strength were measured in 25 patients aged 16-28 years with cystic fibrosis (mean FEV1 46% predicted). Mean (SD) PEmax was 64% (18%) predicted (below 75% predicted in 16 of the 25 patients), and PImax was 64% (24%) predicted (below 75% predicted in 14 patients). Quadriceps muscle strength was 68% (20%) predicted (below 75% predicted in 17 patients). The relatively small reduction in respiratory muscle strength in these patients was unlikely to have contributed appreciably to their respiratory problems.

Adolescent↗
PubMed1989

Twitch pressures in the assessment of diaphragm weakness.

To assess the value of phrenic nerve stimulation in the investigation of diaphragm function, transdiaphragmatic pressures were measured in 20 healthy subjects and in 15 patients with diaphragm weakness, during unilateral and bilateral transcutaneous phrenic nerve stimulation at 1 Hz at functional residual capacity (twitch Pdi). Diaphragm function was initially assessed by measuring transdiaphragmatic pressure during a voluntary manoeuvre, the maximal sniff (sniff Pdi); normal readings were confirmed in the control subjects (102-157 (normal greater than 98) cm H2O in the 10 men, 79-102 (normal greater than 70) cm H2O in the 10 women) and reduced values were found in the 15 patients with diaphragm weakness (7.5-90 cm H2O in the 13 men, 23 and 53 cm H2O in the two women). Twitch Pdi during bilateral phrenic nerve stimulation ranged from 8.8 to 33 cm H2O in the control subjects and from 3.1 to 27 cm H2O in the 10 patients in whom a measurement could be obtained. Bilateral twitch Pdi correlated with sniff Pdi both in the control subjects and in the patients with diaphragm weakness (r = 0.75). Only four patients had a bilateral twitch Pdi below the lowest value seen in the control group, including the three with the lowest sniff Pdi (3.1-8.5 cm H2O). These results indicate that transdiaphragmatic pressure recorded during bilateral phrenic nerve stimulation discriminated between control subjects and patients with known weakness of the diaphragm only when this was severe.

Adult↗