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Biomedical subjects

M J Davis

Publications and source records attributed to M J Davis.

At least 91 records · Page 5Linked to original sources
PubMed1993

A disease activity index: its use in clinical trials and disease assessment in patients with rheumatoid arthritis.

Measuring disease activity is important in the assessment of patients with rheumatoid arthritis (RA). The value of composite indices in determining activity is discussed. A validated index, the Stoke index, has been used in clinical trials of combination therapy in patients with RA, both to evaluate efficacy and to stratify response to single-agent therapy before randomization to combination treatment. Disease activity determines the use of disease-modifying antirheumatic drugs. Should these drugs be used in mild RA when disease activity is low? Results of a study comparing hydroxychloroquine with placebo in this situation suggest that they should. Finally, the outcome of suppressing disease activity over a 5- to 10-year period is unknown. Measured either radiologically or functionally, preliminary data suggest that the lower the mean disease activity over time, the more favorable the outcome.

Antirheumatic Agents↗
PubMed1993

Suspected cutaneous drug toxicity in rheumatoid arthritis--an evaluation.

Cutaneous toxicity from drugs used to treat RA is a major perceived problem. Over a 2-yr period we have prospectively reviewed 114 patients with a suspected adverse cutaneous reaction to anti-rheumatic drugs. In 71 (62%), the rash was thought to be unrelated to drug therapy. This group included 10 in whom the rash had resolved before review (usually < 1 week), 38 with a rash related to their rheumatoid disease and 23 with eruptions unrelated to either drugs or arthritis. Forty-three (38%) patients had rashes thought to be related to their drug therapy. Gold therapy (both oral and intramuscular) was implicated most frequently (31 patients). However, the majority of these (23) had a pityriasiform/discoid eczematous eruption that responded to potent topical steroids occasionally with a reduction in gold dosage. In this sample it was possible to continue drug therapy in 82% of patients with what were initially thought to be cutaneous adverse drug reactions. Careful evaluation should allow a majority of patients to continue drug therapy from which they are often gaining benefit.

Anti-Inflammatory Agents↗
PubMed1993

Undesirable mode switching with a dual chamber rate responsive pacemaker.

The Telectronics 1250 Meta MV DDDR pacemaker is a new device featuring automatic mode switching from DDDR to VVIR pacing in the event of an atrial arrhythmia. Although mode switching is a valuable feature, sinus tachycardia can cause an undesirable mode switch to occur. Of 24 implants at this institution, 11 have been for an AV conduction disorder. Eight of these 11 patients were specifically evaluated for undesirable mode switching. During exercise testing and/or Holter monitoring, mode switching was repeatedly seen in seven of the eight at low levels of exercise. Factors precipitating mode switching were a low rate response factor, low upper rate setting, long base postventricular atrial refractory period (PVARP) and a long AV delay. During Holter monitoring, patients spent up to 50% of the time in VVIR pacing as opposed to DDDR pacing. It is concluded that patients with intact sinus node function are at risk of undesirable mode switching and should probably be programmed to the DDD mode unless there is a specific indication for DDDR pacing. If the DDDR mode is chosen, careful selection of the aforementioned pacing parameters is required.

Adult↗
PubMed1993

Spontaneous contractions of isolated bat wing venules are inhibited by luminal flow.

The hypothesis that spontaneous contractions of bat wing venules could be modulated by luminal flow was tested. Single venules (114 +/- 5 microns diam) from the wings of anesthetized pallid bats were dissected, cannulated, and pressurized in vitro. A dual reservoir system was used to independently control luminal pressure and flow. In the absence of flow, and with pressure set to 10 cmH2O, all venules contracted spontaneously at rates between 20 and 40 cycles/min. Pressure elevation over the range of 3-10 cmH2O caused a rapid increase in contraction frequency and decrease in amplitude; pressure reduction caused a rapid decrease in contraction frequency and increase in amplitude. In contrast, initiation of flow resulted in a delayed and gradual reduction of contraction amplitude and/or frequency (sometimes to zero). The net effect of flow was to increase mean diameter and decrease the product of frequency x cross-sectional area. Flow-induced inhibition of venular contraction was eliminated by endothelial denudation but persisted in the presence of NG-monomethyl-L-arginine (10(-4) M) or indomethacin (10(-5) M) in concentrations that blocked the effects of exogenously applied ATP or arachidonic acid, respectively. The flow-induced venular response also persisted in the presence of superoxide dismutase (55 U/ml). Denuded venules responded to flow when placed downstream (i.e., perfused in series) from venules with intact endothelium. These results indicate that luminal flow can modulate the contractile function of bat wing venules via release of a transferable substance from the endothelium. The exact nature of the substance is not yet known but it does not appear to be classical endothelium-derived relaxing factor, a prostaglandin, or an oxygen radical.

Adenosine Triphosphate↗
PubMed1993

Myogenic response gradient in an arteriolar network.

Experiments were conducted to test the hypothesis that a longitudinal gradient in myogenic responsiveness exists within an arteriolar network. Single arterioles were dissected from the hamster cheek pouch, cannulated with micropipettes, and transferred to an inverted microscope for in vitro study. Pressure-diameter relationships of five branching orders of arterial vessels were measured in the presence of spontaneous vascular tone and after elimination of tone with a Ca(2+)-free solution containing nitroprusside. At luminal pressures matching those found in vivo, the diameters of the vessels with spontaneous tone were as follows: small arteries, 81 microns; first-order arterioles, 52 microns; second-order arterioles, 32 microns; third-order arterioles, 24 microns; and fourth-order arterioles, 11 microns. All branching orders of vessels exhibited true myogenic responses as indicated by negative slopes of their pressure-diameter relationships. Each vascular branching order exhibited its maximum myogenic responsiveness at a pressure near or just slightly higher than its normal pressure as measured in vivo. Relative myogenic responsiveness increased with decreasing vessel size down to the level of the second- and third-order arterioles, whereas fourth-order arterioles were substantially less responsive than third-order arterioles. A compilation of data from numerous in vivo and in vitro studies suggests that the same myogenic response pattern may be found in other vascular beds.

Animals↗
PubMed1993

Coronary venular responses to flow and pressure.

In previous studies, we demonstrated that both endothelium-dependent flow-induced vasodilation and endothelium-independent myogenic responses occur in porcine coronary arterioles. However, it was not established whether these responses are present in the coronary venular microcirculation. The aim of this study was to test the hypotheses that 1) coronary venules, like arterioles, exhibit flow-induced dilation and myogenic responsiveness, and 2) venular flow-induced dilation is endothelium-dependent and is mediated by the release of a nitrovasodilator. Experiments were performed in porcine subepicardial coronary venules, 80-120 microns in diameter, by using cannulated isolated vessel techniques to allow intraluminal pressure and flow to be independently controlled. Flow was initiated by simultaneously moving two perfusion reservoirs connected to the cannulating pipettes in equal amounts but in opposite directions. In the absence of flow, i.e., zero pressure gradient (delta P) between the two reservoirs, venules developed spontaneous tone to 75-80% of maximum diameter at 10 cm H2O intraluminal pressure. Venules gradually dilated in response to stepwise increases in flow (i.e., delta P). The threshold for the flow-induced dilation occurred at delta P = 1 cm H2O (flow = 3.5 nl/sec), and the maximal response (dilation to 93 +/- 2% of maximum diameter) occurred when delta P was elevated to > or = 6 cm H2O (flow = 21 nl/sec at delta P = 6 cm H2O). Flow-induced dilation was abolished after the endothelium was damaged by perfusion of an air bolus through the lumen. Vasoconstriction was observed when denuded venules were subjected to relatively high luminal flows (> or = 21 nl/sec).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Rifampicin in early rheumatoid arthritis.

Sixteen patients with definite or classical Rheumatoid Arthritis (RA) of less than twelve months duration were recruited into a randomised, open twelve month study comparing Rifampicin 600 mg daily (9 patients) with Hydroxychloroquine (HCQ) 400 mg daily (7 patients). Ten patients completed twelve months of treatment (4 Rifampicin, 6 HCQ). Five patients were withdrawn from the study due to lack of efficacy (1 HCQ, 4 on Rifampicin). One further patient on rifampicin was withdrawn due to development of abnormal liver function tests. Significant improvement (p < 0.03) was noted in the Stoke Index (SI) at six and twelve months in the HCQ group which was not seen in the rifampicin group. In both groups there was no significant improvement in the single variables (Ritchie index, morning stiffness, grip strength, synovitis score, ESR, CRP). The results fail to confirm that Rifampicin may be useful in the treatment of RA in early stages of disease.

Adult↗
PubMed1993

Endothelial regulation of coronary microvascular tone under physiological and pathophysiological conditions.

The endothelium has profound potential to modulate coronary arteriolar tone under a variety of physiological and pathophysiological situations. The endothelium in coronary microvessels is responsible for producing flow-dependent vasodilation, which is mediated by nitric oxide. The endothelium, however, does not mediate the myogenic response of coronary arterioles, but production of nitric oxide nevertheless modulates myogenic responses. The endothelium also has a role in coronary alpha-adrenergic vasoconstriction, because inhibition of nitric oxide synthesis augments coronary alpha 1 and alpha 2-adrenergic vasoconstriction. Other neurohumoral substances or autocoids also have their vasodilator actions mediated through the production of nitric oxide in coronary arterioles. Specifically, serotonin, adenosine diphosphate, and histamine all have their actions transduced through the production of nitric oxide. In the pathophysiological setting with impaired endothelial function, vasodilator responses to endothelium-dependent factors are significantly attenuated, and this can be reversed by administration of L-arginine. These impaired responses may contribute to the pathogenesis of ischaemic heart disease, especially that which occurs due to microvascular spasm.

Animals↗
PubMed1993

The relationship between serial measures of disease activity and outcome in rheumatoid arthritis.

Disease activity was measured annually over a median period of 7 years (range 5-9) in a cohort of 127 patients with rheumatoid arthritis. The measurements were plotted, and the area under the resultant curve measured. The relationship of serial measures of disease activity (area under the curve) to outcome (measured radiologically, functionally and by global assessment) was investigated. A significant correlation was found between persistent disease activity and radiographic deterioration. Similar results were found for functional outcome, as measured by Steinbrocker grade, health assessment questionnaire score or global assessment (by analogue score). Single measures of disease activity did not predict outcome. Although imprecise, current methods of measuring disease activity in RA, if measured serially, are valuable in predicting outcome over a 5-10 year period.

Adrenal Cortex Hormones↗
PubMed1992

The safety and economic advantages of day case electrophysiologic studies.

Electrophysiologic Studies (EPS) have been performed as 'day case' procedures in selected patients at Royal Perth Hospital since April 1987. Previously, EPS had involved hospitalisation for two to ten days. During the 51 month period to June 1991, 484 EPS were performed in total. Of these, 153 (105 males and 48 females aged 46 +/- 31y) were day case procedures. Studies were baseline in 60 cases and included drug evaluation in 30. Sixty-one additional studies were performed solely to evaluate therapy. Twenty-one patients required cardioversion. One hundred and fifty one patients were discharged on the same day and two required prolonged observation. The financial cost savings to the hospital for day case EPS is estimated to be $115 per patient and to the community potentially a further $108 per patient. This study demonstrates that in selected patients undergoing elective EPS, day case management is a safe and economic alternative to hospital admission.

Adolescent↗
PubMed1992

Radiofrequency catheter ablation of the AV node to improve the function of an antitachycardia implantable defibrillator.

A case of coexisting atrial fibrillation and ventricular tachycardia in a patient with an implantable cardioverter defibrillator is described. Despite careful reprogramming, the device was not always able to distinguish between the two arrhythmias and continued to deliver inappropriate antitachycardia therapy including DC shocks. Attempts to pharmacologically control the atrial fibrillation were unsuccessful so radiofrequency ablation of the atrioventricular node was performed. Following successful ablation, there have been no further false detections no episodes of further ventricular tachycardia.

Aged↗
PubMed1992

Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.

In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.

Bradycardia↗
PubMed1992

Pityriasis rosea and discoid eczema: dose related reactions to treatment with gold.

Sixteen cases of either a pityriasiform or discoid eczematous rash occurring in patients with rheumatoid arthritis receiving treatment with gold (sodium aurothiomalate and auranofin) were studied. The results suggest that this is a dose related, not allergic, reaction to gold. The development of this rash is not an absolute indication to stop treatment with gold. Control can often be effected with potent topical steroids or a reduction in the dose or frequency of treatment with gold.

Arthritis, Rheumatoid↗
PubMed1992

Stretch-activated single-channel and whole cell currents in vascular smooth muscle cells.

Mechanosensitive ion channels may play a key role in transducing vascular smooth muscle (VSM) stretch into active force development. To test this hypothesis, we recorded single-channel and macroscopic currents during mechanical stimulation of enzymatically dispersed vascular smooth muscle cells. Patch pipette suction activated a nonselective cation channel that was permeable to K+, Na+, and Ca2+. Whole cell stretch was accomplished using two patch-type micropipettes attached to the cell ends with suction. Stretch elicited a sustained depolarization with a magnitude similar to that observed in pressurized arteries. Under whole cell voltage clamp, stretch activated an inward current with a reversal potential near -15 mV. In another series of experiments, whole cell stretch failed to modify the current-voltage relationship for voltage-gated calcium currents. Thus, in VSM, both single-channel and whole cell data are consistent with activation of a nonselective cation channel by stretch. This mechanism may, in part, account for pressure-induced activation of intact blood vessels.

Animals↗
PubMed1992

Modulation of bat wing venule contraction by transmural pressure changes.

We tested the hypothesis that the frequency and amplitude of spontaneous venular contractions in the bat wing could be modulated by changes in transmural pressure. In one series of experiments, venous pressure in the wing was elevated by pressurizing a box containing the body of the animal while the wing was exposed to atmospheric pressure. During this time, venular diameters were continuously recorded using intravital microscopic techniques while venular pressures were measured through servo-null micropipettes. In another series of experiments, single venular segments were dissected from the wing, cannulated, and pressurized in vitro. The results from both experimental protocols were qualitatively similar; alterations in venous pressure over a narrow range (+/- 5 cmH2O from control) produced substantial changes in contraction frequency and amplitude. The product of frequency and cross-sectional area was maximal over the venous pressure range between 10 and 15 cmH2O. Venules demonstrated a rate-sensitive component in their reaction to rapid pressure changes, because contraction bursts occurred immediately after positive pressure steps and quiescent periods often occurred after negative pressure steps. We conclude that venular vasomotion in the bat wing is modulated by intraluminal pressure and involves a bidirectional, rate-sensitive mechanism. In addition, comparisons with arteriolar vasomotion studies suggest that venules are more sensitive to luminal pressure changes than arterioles.

Animals↗
PubMed1992

Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles.

The purpose of this study was to test the hypothesis that endotoxemia impairs endothelium-dependent (both receptor-mediated and flow-induced) vasodilation in porcine coronary arterioles. Coronary arterioles were isolated from three groups of 4- to 8-wk old (10.3 +/- 0.8 kg) pigs: endotoxemic (E; 250 micrograms/kg endotoxin iv), control (C; equal volume of saline), and untreated pigs (UT). Subepicardial arterioles (60-120 microns) were isolated and cannulated with two micropipettes that were connected to two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O throughout the experiments. All C vessels developed spontaneous tone and exhibited flow-induced vasodilation from 65 to 95% maximal diameter. Spontaneous tone developed in only three of five arterioles from E pigs, and flow-induced vasodilation was not observed in any arteriole from E pigs. Spontaneous tone developed in all six arterioles isolated from UT pigs but disappeared in four of these vessels as a result of 1 h of in vitro incubation with endotoxin (2.5 micrograms/ml). Flow-induced vasodilation was also abolished in these vessels after 1 h of endotoxin exposure. Incubation with 3 mM L-arginine, in vitro, restored flow-induced vasodilation in E arterioles and endotoxin-treated UT arterioles. Vasoconstriction induced by acetylcholine (ACh) and vasodilation induced by nitroprusside (NP) and bradykinin (BK) were similar in arterioles from all groups. In contrast, endotoxin impairs flow-induced vasodilation of coronary arterioles. The mechanism responsible for the impairment of flow-induced vasodilation seems to reside in disruption of the L-arginine/nitric oxide pathway.

Acetylcholine↗
PubMed1992

Cellular mechanisms involved in the vascular myogenic response.

By definition, the myogenic response is the contraction of a blood vessel that occurs when intravascular pressure is elevated and, conversely, the vasodilation that follows a reduction in pressure. Over the last several decades numerous investigators have demonstrated the importance of the myogenic response in the local regulations of blood flow, capillary pressure, and in the generation of basal vascular tone. Despite the considerable information obtained from these investigations, information about the cellular mechanisms that underlie this response has been slow to accumulate. Because of the physiological significance of the myogenic response, its mechanistic basis represents an important subject for research. Currently, there are several broad hypotheses concerning the sequence of events that couple changes in intravascular pressure or stretch with alterations in vascular smooth muscle activation. These hypotheses include 1) altered membrane properties leading to activation of ion channels; 2) modulation of biochemical cell-signaling pathways within vascular smooth muscle; 3) length-dependent changes in contractile protein function; and 4) endothelial-dependent modulation of vascular smooth muscle tone. This review summarizes current work relative to each of these hypotheses and describes a possible sequence of events to account for myogenic activation of vascular smooth muscle.

Animals↗