Search PubMed⌕ Search

Biomedical subjects

M J Davis

Publications and source records attributed to M J Davis.

At least 109 records · Page 6Linked to original sources
PubMed1992

Stretch-induced increases in intracellular calcium of isolated vascular smooth muscle cells.

Vascular smooth muscle responds to stretch with an increase in active force development. To investigate the role of Ca2+ in this response, we used the fluorescent dye fura-2 to quantitate changes in cytosolic Ca2+ in single, vascular smooth muscle cells during rapid stretch. Cells were enzymatically dispersed from pig coronary arteries, loaded with fura-2/AM, and studied using a digital-imaging microscope. Stretch of individual cells was accomplished by attachment with suction to two patch-type micropipettes to apply force to the ends of the cell. Stretch induced the release of Ca2+ from intracellular stores as well Ca2+ influx across the plasma membrane. In physiological saline solution containing 1.5 mM Ca2+, intracellular calcium increased with cell stretch in a sigmoidal fashion. This relationship was shifted upward in 10 mM Ca2+ bath solution and abolished after several minutes in Ca(2+)-free solution. The dihydropyridine Ca2+ channel blocker nifedipine, in doses sufficient to completely block inward Ca2+ current, produced only a partial block of the sustained stretch-induced intracellular Ca2+ response. It is concluded that in isolated pig coronary arterial smooth muscle cells, stretch-induced Ca2+ influx occurs in part via a nifedipine-resistant pathway, which may be a stretch-activated cation channel.

Animals↗
PubMed1992

Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine.

The goals of this study were 1) to quantitate the effects of atherosclerosis on physiological and pharmacological endothelium-dependent vasoactive responses in coronary arterioles downstream from arterial lesions and 2) to determine if administration of L-arginine, the precursor for endothelium-derived was induced in pigs, and vasomotor responses of isolated, cannulated coronary arterioles (30-70 microns in diameter) were assessed by measuring diameter changes in vitro. To assess pharmacological alterations of endothelium-dependent responses, dose-response curves were constructed to ADP, serotonin, and histamine. To assess physiological alterations in endothelial function, different flow rates were established across the vessel. Arteriolar diameters were measured in vessels from normal and atherosclerotic pigs under control conditions, after administration of L-arginine, and after endothelial denudation. In arterioles from normal pigs, administration of serotonin, histamine, or ADP produced dose-dependent vasodilation, which was abolished by endothelial denudation. In arterioles from atherosclerotic pigs, administration of histamine, serotonin, and ADP produced dilation at only the highest doses (10(-6)-10(-7) M), and the extent of dilation was only 20-30% of that observed in arterioles from normal pigs. Initiation of flow also produced vasodilation in arterioles from normal pigs that was completely abolished after endothelial denudation. In arterioles from atherosclerotic pigs, flow-induced responses were absent. These abnormal physiological and pharmacological responses (i.e., blunted vasodilation to pharmacological stimulation and to flow) were restored after administration of L-arginine for 40 minutes. The vascular responses after administration of L-arginine were not different from those observed under control conditions in arterioles from normal pigs. In addition, L-arginine did not restore vasodilation to the endothelium-dependent agonists in denuded segments. From these data in arterioles downstream from atherosclerotic lesions, we conclude that 1) the ED50 and maximal responses of endothelium-dependent vasodilation to ADP, histamine, and serotonin are attenuated; 2) the physiological response to flow, that is, flow-mediated endothelium-dependent vasodilation, is absent; and 3) the abnormality in arteriolar responsiveness during large vessel disease involves an impairment of the synthesis and/or release of endothelium-derived relaxing factor.

Animals↗
PubMed1992

Rheumatoid arthritis: an association with pemphigus foliaceous.

We have observed a high incidence of pemphigus foliaceous, in the absence of therapy with penicillamine, within a small population of patients with rheumatoid arthritis. We suggest that penicillamine as well as inducing autoimmune disease might exacerbate subclinical pemphigus foliaceous in this group, accounting for those few patients whose skin disease fails to resolve following drug withdrawal. Pemphigus and rheumatoid arthritis have both been associated with HLA DR4, which was present in all three of our patients who were tested.

Adult↗
PubMed1991

Should disease-modifying agents be used in mild rheumatoid arthritis?

A 12-month double-blind controlled study comparing hydroxychloroquine 400 mg daily with placebo in 104 patients with mild RA was conducted to see whether patients with mild rheumatoid arthritis (RA) benefit from treatment with disease-modifying agents. Mild RA was defined as synovitis limited to the hands and feet, an ESR less than 30 mm/h and C-reactive protein less than 20 mg/l, a situation where accepted clinical practice is to use a non-steroidal anti-inflammatory agent alone. By 6 months, the improvement of clinical and laboratory parameters in the hydroxychloroquine treated patients was significant compared with pretreatment levels and significantly greater than the control group. This improvement was maintained at 12 months. In addition, fewer patients withdrew through lack of efficacy, eight on hydroxychloroquine versus 18 on placebo. The implications of treating this well defined group of patients is discussed.

Arthritis, Rheumatoid↗
PubMed1991

Sino-atrial arrest due to temporal lobe epilepsy.

A case of sino-atrial arrest due to temporal lobe epilepsy is described and compared with previously documented such cases in the literature. The rarity of bradycardias and sinus arrest due to arrhythmogenic seizures is discussed, as is the role of prospective ambulatory electroencephalographic and electrocardiographic studies in evaluating this association.

Adult↗
PubMed1991

Endothelial independence of myogenic response in isolated skeletal muscle arterioles.

The goal of this study was to determine whether the endothelium played a role in the myogenic response of skeletal muscle arterioles. First-order arterioles (n = 15) were isolated from the rat cremaster muscle and cannulated for in vitro study. The development of spontaneous tone reduced the diameter of the isolated arterioles from 166.7 +/- 7.6 microns to 89.2 +/- 7.2 microns. The arterioles were exposed to step changes in intraluminal pressure over a range of 10-170 cmH2O and had no flow through their lumen. The vessels exhibited active constriction to step increases or active dilation to step decreases in pressure (50-150 cmH2O). At 90 cmH2O, arterioles dilated by 89.2 +/- 6.0% in response to the endothelium-dependent vasodilator acetylcholine (10(-6) M; ACh) and 89.6 +/- 10.9% in response to endothelium-independent dilator adenosine (10(-4) M; Ado). The endothelium was physically denuded by rubbing the vessel lumen. After denudation, the arteriolar dilation to ACh was abolished, whereas the dilation to Ado was unaltered. The absence of endothelium was verified by electron microscopy. Basal tone and the response to changes in pressure were not significantly different from endothelium-intact vessels. These studies indicate that the endothelium is not responsible for myogenic activity or development of spontaneous tone in skeletal muscle arterioles.

Acetylcholine↗
PubMed1991

Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels.

Pressure-induced myogenic responses and flow-induced vasodilatory responses have been documented in coronary resistance arterioles, but the interaction of these two mechanisms and the nature of the flow-mediated response are not well understood. Experiments were designed to quantitatively study the interaction of pressure- and flow-induced responses and to characterize the nature of the substance responsible for flow-mediated dilation in isolated coronary arterioles. Subepicardial arterioles (40-80 microns) were isolated from pigs and cannulated with two glass micropipettes and then pressurized via independent reservoir systems. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions thus generating a pressure gradient (delta P) without changing the mean intraluminal pressure (IP). IP was changed by moving both reservoirs in the same direction to alter myogenic tone in the absence of flow (delta P = 0). Flow-mediated dilation competed with myogenic constriction when flow and pressure were elevated. Also, flow potentiated myogenic dilation when IP was decreased. The magnitude of flow-induced dilation was greatest at an intermediate level of vascular tone (IP = 60 cmH2O) but was attenuated at higher and lower levels of tone. In the presence of flow (delta P = 4 cmH2O), pressure-diameter relationships were shifted upward, and the magnitude of myogenic responsiveness was attenuated. Double-vessel bioassay studies indicated that a transferable substance was released from intact endothelium in response to flow. Flow-induced dilation was not affected by indomethacin but was abolished by NG-monomethyl-L-arginine or by mechanical removal of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The association and predictive value of the complex immunoglobulin A-alpha 1-antitrypsin in the development of erosions in early rheumatoid arthritis.

Immunoglobulin A-alpha 1 antitrypsin complex (IgA-AT), its constituent components and nine other clinical or laboratory variables were measured in thirty-three patients with early, non-erosive rheumatoid arthritis (RA) in order to assess their value in predicting the subsequent development of erosions. After 12 months, eighteen patients had developed erosions. Comparison of variables measured at outset between the group of patients subsequently developing erosions and those not, showed only the complex IgA-AT level to be significantly different, the mean being higher in the erosive group. In the subgroup of patients with high IgA-AT levels (greater than 3.0 arbitary units) all developed erosions. The possible therapeutic implications of these findings are discussed.

Arthritis, Rheumatoid↗
PubMed1991

Reduction of enhanced mammary carcinogenesis in LA/N-cp (corpulent) rats by energy restriction.

Restriction of energy intake significantly reduces mammary tumorigenesis in normal rats exposed to carcinogens. Genetically obese LA/N-cp (corpulent) female rats were given 7,12-dimethylbenz[a]anthracene and fed purified diets ad libitum or restricted to 60% of the ad libitum caloric intake. Phenotypically lean littermates were also fed ad libitum. Obese animals developed large mammary tumors more rapidly than genetically normal rats so that 100% of the animals had tumors in less than 16 weeks. Only 21% of the lean animals developed tumors; the energy restricted obese animals had a tumor incidence of 27%. Although obese rats fed the restricted diet weighed significantly less than those fed ad libitum, percent body fat was not reduced, indicating that lean tissue was affected more. Obese animals were markedly hyperinsulinemic (1003 +/- 193 microunits/ml) and energy restriction reduced this to 328 +/- 41; the lean animals had insulin levels of 12 +/- 2. Tumor-bearing rats had higher insulin levels than rats without tumors. These data suggest that body fatness is not directly associated with risk of carcinogenesis. Lean body mass, adipose tissue mass, and their interaction with insulin in its capacity as a growth factor rather than body fatness per se may be determinants of tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Emergency ventricular pacing using a J-electrode catheter without fluoroscopy.

The initiation of emergency ventricular pacing may be delayed by a lack of facilities for immediate fluoroscopy or staff members who are skilled in positioning a transvenous electrode catheter. Techniques have been developed to overcome these problems but have been unreliable, expensive and/or uncomfortable for patients. In each of 20 consecutive haemodynamically unstable patients (13 patients with asystole or high-grade atrioventricular block and seven patients with ventricular tachycardia), an attempt was made to pace the ventricle with a Cordis 5-FG (1.67-mm) "atrial J"-electrode catheter, which was inserted transvenously without fluoroscopic guidance. Pacing was initiated successfully in 19 cases within 40 seconds to 30 minutes (median, two minutes) of skin puncture, and in 16 cases within three minutes. Fifteen procedures were performed by operators with experience of less than 10 previous pacing catheter insertions. This study demonstrates that emergency transvenous ventricular pacing can be initiated rapidly and reliably by means of a catheter with a "J" configuration, which is inserted without the use of fluoroscopy. The method can be employed successfully by operators with little experience in pacing techniques. Standard inexpensive equipment is used; the technique is safe and well-tolerated by patients.

Adult↗
PubMed1990

Comparison of meglumine sodium diatrizoate, iopamidol, and iohexol for coronary angiography and ventriculography.

Meglumine sodium diatrizoate (Urografin), iopamidol, and iohexol were compared in a double-blind, randomized study of 287 patients undergoing elective cardiac angiography. Ninety-six patients received Urografin, 98 received iopamidol, and 92 received iohexol. The groups were similar in all respects. Variables measured before and after contrast injection were left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), systolic arterial pressure (SAP), RR, PR, and QTc intervals, QRS duration, ST segment change greater than 2 mm, arrhythmias, and symptoms. The adequacy of coronary and ventricular opacification was assessed by two experienced observers. Following left ventriculography, small rises in LVEDP occurred with iopamidol and iohexol (mean +/- SD: 18 +/- 7 to 21 +/- 7 mmHg) and a moderate fall in LVSP with Urografin (150 +/- 32 to 133 +/- 32 mmHg). Following coronary angiography there was a progressive fall in SAP (130 +/- 26 to 117 +/- 30 mmHg) and prolongation of RR intervals (900 +/- 138 to 1,266 +/- 692 msec) and QTc (440 +/- 61 to 471 +/- 73 msec) and QRS duration (87 +/- 25 to 100 +/- 27 msec) with Urografin. There was a small fall in SAP with iopamidol (138 +/- 25 to 128 +/- 27 mmHg) and prolongation of QRS duration with iohexol (85 +/- 29 to 90 +/- 24 msec). Other parameters were not significantly affected. Frequent bradyarrhythmias (sinus pause 14.5%, asystole 6%) and ST segment depression occurred following Urografin. Urografin was less well tolerated, with 10% of patients experiencing severe nausea or vomiting and 30% of patients experiencing extreme heat sensation. Differences between iohexol and iopamidol were minor.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1990

Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis.

An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.

Adult↗
PubMed1990

Exercise electrophysiology testing: the effect of exercise on the induction of ventricular arrhythmias by programmed ventricular stimulation.

In order to assess the effect of acute, reversible myocardial ischemia on the outcome of programmed ventricular stimulation (PVS), ventricular stimulation was performed at rest, during exercise, and during recovery in 10 patients with coronary artery disease. Of these ten patients, four were tested while off antiarrhythmic drugs and six were tested on antiarrhythmic drug therapy. Nine of the ten patients developed acute myocardial ischemia during exercise PVS. However, in only two of these ten patients ventricular arrhythmia could be induced by PVS, one during exercise and one during recovery.

Aged↗
PubMed1990

Primary Ewing sarcoma of rib.

Ewing sarcoma is a relatively common, highly malignant bone tumor that typically occurs in adolescents and young adults aged 10-25 years. Our archives contain 328 cases of histologically proved and radiologically correlated Ewing sarcoma collected in consultation over 40 years. From this series, we identified 34 lesions (10%) arising in ribs. Radiographically, the affected rib was predominantly lytic in most (82%) cases, but mixed lytic-sclerotic (9%) and even predominantly sclerotic (9%) patterns were also encountered. The affected rib was "expanded" in 35% of cases, although the contour change was usually mild. Abnormalities of the affected ipsilateral hemithorax varied from subtle, isolated rib involvement to solitary rib involvement accompanied by complete opacification of the hemithorax. We describe the spectrum of radiologic findings of primary Ewing sarcoma of rib, augmented where appropriate by accompanying pathologic material.

Adolescent↗
PubMed1990

Cyclooxygenase inhibition potentiates myogenic activity in skeletal muscle arterioles.

The proposition that arteriolar constriction to increased intravascular pressure is mediated through either the increased local production of an eicosanoid constrictor factor or decreased production of a dilating factor was examined. The myogenic response of arterioles was studied by enclosing anesthetized rats in an airtight Plexiglas box with the cremaster muscle exteriorized into a tissue bath containing Krebs solution. Microvascular responses were observed by video microscopy. The arteriolar response to a 20-mmHg increase in intravascular pressure was examined in the absence or presence of cyclooxygenase inhibition. In the absence of cyclooxygenase inhibition, second-order arterioles (2As) responded passively to increased pressure by distending to 107 +/- 1% of control diameter. In the presence of the indomethacin, 2As constricted to 79 +/- 5% of control. Third-order arterioles (3As) constricted to 47 +/- 8% of control without indomethacin and similarly to 33 +/- 4% with indomethacin. To test whether inhibitors of endothelium-derived relaxation factor would potentiate the myogenic response of 3As, methylene blue or gossypol was topically applied to the cremaster muscle. Neither inhibitor was found to augment the myogenic vasoconstriction; however, these inhibitors were observed to significantly reduce basal vascular tone. In comparison, the tonic local production of dilating prostaglandins appears to attenuate myogenic activity as demonstrated by the appearance of myogenic activity in the normally passive 2As when exposed to cyclooxygenase inhibitors.

Animals↗
PubMed1990

Endothelium-dependent, flow-induced dilation of isolated coronary arterioles.

Flow-mediated dilation has been documented in large conduit coronary arteries but not in coronary arterioles. The goal of this study was to determine whether this response occurs in coronary arterioles and whether it competes with myogenic constriction. Subepicardial arterioles (40-80 microns) were isolated and cannulated with two glass micropipettes connected to independent reservoir systems. During zero flow, myogenic responses were studied over the range of intraluminal pressure (IP) between 20 and 140 cmH2O. Myogenic constrictions and dilations was observed when IP was increased (greater than 60 cmH2O) and decreased (less than 60 cmH2O), respectively. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions, thus generating a pressure gradient (delta P) without changing the mean luminal pressure (range delta P = 4-60 cmH2O). Flow-induced responses were studied at low, intermediate, and high myogenic tones by setting IP at 20, 60, and 100 cmH2O, respectively. The threshold for flow-induced dilation was delta P = 4 cmH2O, and maximum dilation was observed at delta P = 20 cmH2O. Red cell velocities in isolated arterioles at delta P of 4 and 60 cmH2O were 1.2 +/- 0.2 and 15.9 +/- 1.3 mm/s, respectively, which are within the range of those reported for coronary microvessels in vivo. The magnitude of the flow-induced dilation was greatest at the intermediate tone (60 cmH2O IP) but was attenuated at lower and higher IP. After mechanical removal of the endothelium, spontaneous tone and myogenic responses were preserved, but flow-induced dilation and bradykinin-induced dilation were abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗