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Biomedical subjects

J V Jones

Publications and source records attributed to J V Jones.

At least 55 records · Page 3Linked to original sources
PubMed1992

Antiphospholipid antibodies: new perspectives on antigenic specificity.

Antiphospholipid antibodies (aPL) are found in up to 60% of patients with systemic lupus erythematosus (SLE), and appear to predispose to a number of complications of the disease. We purified IgG from patients with SLE and the antiphospholipid antibody syndrome (APS) who have high levels of aPL and used this IgG in a modified ELISA where we excluded any source of cofactor in the assay. We showed that for 10 of the 11 patients, IgG bound strongly to cardiolipin only in the presence of the cofactor, which was present in fetal calf serum, normal human serum (NHS), and in the infranatant lipoprotein fractions obtained by flotation ultracentrifugation of NHS. We then purified beta 2 glycoprotein I (beta 2GPI) from NHS and showed that for 9 of the 11 samples of IgG, beta 2GPI was as effective, or more effective, than NHS as a source of cofactor. When beta 2GPI was coated on ELISA plate and used as an antigen we found little or no reactivity of patient sera or IgG, suggesting that beta 2GPI alone is not antigenic in our system. Three possible explanations could be put forward to explain the behavior of cardiolipin and beta 2GPI, neither of which is antigenic alone.

Antibodies, Antiphospholipid↗
PubMed1992

Antiphospholipid antibodies require beta 2-glycoprotein I (apolipoprotein H) as cofactor.

IgG was isolated from 9 patients with high levels of anticardiolipin antibodies (aCL). The standard ELISA was modified, using gelatin to postcoat ELISA plates and as diluent. Under these conditions, 8/9 samples of IgG bound to cardiolipin only in the presence of a cofactor, found in fetal calf serum and normal human serum (NHS). beta 2-glycoprotein I (apolipoprotein H) was at least as effective as NHS as a cofactor for 7/9 IgG samples. Our studies confirm that for some aCL detected in conventional assays, the antibody will react with cardiolipin only if beta 2-glycoprotein I is present.

Antibodies, Antiphospholipid↗
PubMed1992

Cognitive impairment in patients with systemic lupus erythematosus.

Seventy unselected patients with systemic lupus erythematosus (SLE) were studied to determine the prevalence of cognitive impairment and the association with other clinical variables. Twenty-five patients with rheumatoid arthritis (RA) and 23 healthy subjects were used as controls. All patients were evaluated with a battery of standardized neuropsychological tests to determine ability in 8 areas of cognitive function. Clinically overt neuropsychiatric (NP) SLE, cumulative disease manifestations and concurrent medications were documented. In patients with SLE, generalized disease activity was expressed using the SLE disease activity index. Cognitive impairment was identified in 15/70 (21%) patients with SLE, 1/25 (4%) patients with RA and in 1/23 (4%) healthy subjects (p = 0.042). The prevalence was higher in patients with active NP-SLE at the time of assessment (2/5, 40%) compared to patients with inactive NP-SLE (2/10, 20%) but was also increased in those patients who had never had known clinical NP-SLE (11/55, 20%). A history of serositis (p = 0.015), active SLE (p = 0.064) and corticosteroid use (p = 0.027) at the time of assessment were more common in patients with cognitive impairment. The results suggest that cognitive impairment is increased in patients with SLE. It may occur independently of clinically overt NP-SLE and is more common in patients with active disease who are receiving corticosteroids.

Adult↗
PubMed1991

Plasmapheresis and subsequent pulse cyclophosphamide versus pulse cyclophosphamide alone in severe lupus: design of the LPSG trial. Lupus Plasmapheresis Study Group (LPSG).

A group of clinics are collaborating in the Lupus Plasmapheresis Study Group (LPSG) to investigate whether repeated plasmapheresis prior to pulse cyclophosphamide improves the therapeutical results in severe systemic lupus erythematosus (SLE). The underlying rationale is the hypothesis that plasmapheresis 1) eliminates pathogenic autoantibodies and immune complexes and 2) induces compensatory lymphocyte activation via feedback mechanisms between circulating antibodies and their respective clones ("antibody rebound"). It should be possible to utilize this enhanced activity for increased clonal deletion if pulse cyclophosphamide is applied shortly after plasmapheresis. Accordingly, in a randomized study, the LPSG will be comparing the repeated application of pulse cyclophosphamide alone with a treatment involving repeated plasmapheresis prior to the cyclophosphamide pulses in severe SLE. A third arm of the study will be gathering experience with a more intensified procedure. This overview summarizes the most important details of the planned study.

Combined Modality Therapy↗
PubMed1991

Effect of different levels of briefly sustained ventricular pressure on arrhythmia in the isolated working rat heart.

1. The effect of different levels of ventricular pressure upon the prevalence of ventricular arrhythmias has been studied in 42 rat hearts by using the isolated working heart model. 2. The results have shown that there is an increased prevalence of arrhythmia at the highest levels of pressure tested in hearts from both normal and hypertensive rats. In hearts from normal rats total ectopic counts were 304 at 140 mmHg and 150 at 60 mmHg (P less than 0.05). In hearts from hypertensive rats total ectopic counts were 4217 at 180 mmHg and 2179 at 100 mmHg (P less than 0.05). 3. Hearts from hypertensive rats demonstrated significantly more ectopic activity than hearts from normal rats at all test pressures. Median values for ectopic counts for each study period were 68 in hearts from hypertensive rats and seven in hearts from normotensive rats (P less than 0.001). 4. There was evidence that the increased arrhythmia observed was not due to ischaemia or fatigue, and it seems likely that these effects of raised pressure are due to its effect on ventricular wall stress. The differences between various pressures were relatively small, but do suggest that a sustained increase in ventricular wall stress is arrhythmogenic. 5. This small arrhythmogenic effect over the relatively short period of these studies may be of much greater significance when considered in the context of the prolonged periods for which the diseased heart may be subjected to raised wall stress.

Animals↗
PubMed1991

Attenuation of nitrate effect during an intermittent treatment regimen and the time course of nitrate tolerance.

The long-term efficacy of transdermal nitrate therapy, in particular the ability of a single patch to provide 24 h prophylaxis against angina, has been questioned. Two mechanisms have been suggested for this loss of effect: the development of pharmacological tolerance, and premature patch exhaustion. This study was designed to investigate this problem, and in particular to investigate the time course of treatment failure. It comprised a randomized, double-blind, cross-over comparison of transdermal glyceryl trinitrate and matching placebo transdermal patches. Significant treatment effects were demonstrated by several criteria for 8 h of continuous therapy, with some limited effect persisting for 15 h. Loss of effect began to develop very soon after treatment was initiated and progressed in a steady, linear fashion so that there was virtually no treatment effect after 24 h. In contrast, during intermittent therapy, treatment effects were maintained on the second day following a nitrate-free interval. Significant benefit was demonstrated for up to 32 h (i.e. 8 h of treatment on day 2). Both nitrate-free intervals (12 and 16 h) seemed to be equally effective in maintaining efficacy after 3 h of treatment on the second day, although this was still somewhat attenuated compared with day 1. These results confirm that loss of therapeutic efficacy of transdermal nitrate is due to the development of tolerance and not premature patch exhaustion. In contrast to previous studies, however, they suggest that tolerance can only partly be reversed by intermittent therapy and also that the onset of tolerance is so rapid that it is well established in less than a day's treatment.

Administration, Cutaneous↗
PubMed1991

Anti-arrhythmic properties of the alpha-adrenoceptor blocking drug indoramin.

1. The anti-arrhythmic properties of the alpha-adrenoceptor blocking drug indoramin were compared with the effect of disopyramide and placebo in a randomised, single-blind, cross-over study. Two doses of indoramin were tested, 25 mg and 50 mg and the dose of disopyramide was 150 mg. All treatments were administered three times daily. 2. Forty patients with benign ventricular arrhythmia were studied. 3. Assessment was by 24 h ambulatory electrocardiography at entry and at the end of each 2 week treatment period. 4. Indoramin was found to have a significant anti-arrhythmic effect compared with placebo, but only at the higher dose tested. 5. The anti-arrhythmic effect was less than that achieved with disopyramide. 6. The mechanism for this anti-arrhythmic effect is unknown but these results suggest that alpha-adrenoceptor blockade may merit further attention as an anti-arrhythmic treatment.

Adrenergic alpha-Antagonists↗
PubMed1991

Response to sulfasalazine in rheumatoid arthritis: life table analysis of a 5-year followup.

Eighty-six patients with rheumatoid arthritis treated with sulfasalazine were followed for 5 years, or until treatment was discontinued. At the end of 5 years, there was a 22% probability of successfully continuing treatment. Most adverse effects developed in the first 3 months of treatment. In 38 patients treatment was discontinued because of inefficacy. In 18 of these, a brief period of improvement was followed by clinical relapse. Twenty were regarded as having no useful response to sulfasalazine. The treatment continuation rate of 22% at 5 years is in marked contrast to the pessimistic longterm evaluations of second line drugs that have recently been reported.

Adolescent↗
PubMed1991

Strength and function in the normal and rheumatoid hand.

We have reevaluated the Martin vigorimeter to measure grip strength in healthy subjects, and patients with rheumatoid arthritis (RA), and investigated the correlation of grip strength and hand function using the Jebsen hand function tests and Purdue pegboard test before and after treatment. The vigorimeter showed good test-retest reliability (r greater than 0.911) and interrater reliability (r greater than 0.915). Test-retest reliability was greater than 0.97 for the Jebsen test, and greater than 0.94 for the Purdue test in healthy individuals. Seventeen patients with RA were studied at intervals of 1 to 16 weeks. Active joint count and grip strength both improved significantly. Improvement in grip strength correlated with improvement in active joint count. Hand function tests were significantly impaired in the patients with RA.

Adolescent↗
PubMed1991

Left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) may be physiological or pathological. Only pathological LVH has been shown to be a risk factor for cardiovascular events. LVH may not be homogeneous. It seems to progress from muscle hypertrophy to eventual cell death and myocardial fibrosis. Potential for reversal of LVH may therefore depend on the stage at which it has been attempted. An interaction between LVH and serum potassium levels could have important therapeutic implications, particularly with regard to the use of thiazide diuretics as long-term treatment for hypertension.

Animals↗
PubMed1990

Systolic wall stress and ventricular arrhythmia: the role of acute change in blood pressure in the isolated working rat heart.

1. The effect of a sudden acute change in blood pressure upon arrhythmia provocation has been studied in an isolated working heart model from the Wistar-Kyoto strain of rat. Twenty-four hearts were studied. 2. They were perfused with two different, modified, Krebs-Henseleit solutions at a fixed left atrial pressure. 3. Acute changes in pressure, both increases and decreases, were arrhythmogenic. Whilst ectopic activity was more predictably produced by pressure reductions, this consisted of simple ventricular ectopics only. Pressure increases, in contrast, were capable of provoking more complex and sustained arrhythmias. 4. The effect of pressure changes were highly dependent upon electrolyte concentrations in the perfusate. Low potassium and magnesium concentrations increased the amount of arrhythmia provoked by pressure increases but tended to reduce that provoked by pressure reductions. 5. We conclude that the direct effect of an acute change in pressure upon the myocardium is arrhythmogenic. However, the myocardial response to a pressure change is interdependent upon prevailing electrolyte concentrations.

Animals↗
PubMed1990

The effect of oral dosing of xamoterol on systolic time intervals in man and xamoterol plasma concentrations in heart failure patients.

1. Six healthy male human volunteers of mean age 30.8 years (range 23-37) were given single oral doses of xamoterol (20, 50, 100 or 250 mg) and placebo with a 1 week interval between each dose. Xamoterol produced a significant decrease in systolic time intervals (QS2I, LVETI and PEPI) and a significant increase in systolic blood pressure indicating a positive inotropic effect on the heart at rest. The changes in QS2I were dose-related. Maximum decreases in QS2I were noted 1 to 2 h after dosing and were achieved with a dose of 100 mg. 2. In a second study, oral administration of xamoterol at 3 doses (100, 200 or 300 mg) and placebo were studied in 12 patients of mean age 60.4 years (range 52-73) with mild to moderate heart failure. Each dose was given twice daily for 7 days in a random order. Each dose of xamoterol produced a significant decrease in systolic time intervals indicating a positive inotropic effect on the heart at rest in patients with heart failure. It was not possible to distinguish between the effects of the three doses of xamoterol. 3. In heart failure patients, peak plasma concentrations of xamoterol occurred 1 to 2 h after dosing at all dosage levels and there was a linear relationship between dose and plasma concentration. 4. In both studies xamoterol was well tolerated and only minor adverse experiences were reported. 5. We conclude that, at rest, xamoterol has a positive inotropic effect on the heart when given orally to healthy volunteers or patients with mild to moderate heart failure.

Adult↗
PubMed1990

ACE inhibitors and the heart: hypertrophy reversal and antiarrhythmic effects.

Sudden death has been shown to be due in the majority of cases to ventricular arrhythmia. Left ventricular hypertrophy (LVH) may be implicated in the aetiology of some arrhythmia and sudden death. Recent evidence suggests that the relationship between LVH and arrhythmia may be complex and that there may be an interaction with serum potassium levels. ACE inhibitors have been shown to be anti-arrhythmic in heart failure. Although other vasodilators have been shown to be anti-arrhythmic, ACE inhibitors also raise serum potassium levels and this may therefore be of importance to their anti-arrhythmic activity. In LVH, their antiarrhythmic potential may be greatest in those who are potassium depleted.

Angiotensin-Converting Enzyme Inhibitors↗