PubMed Health⌕ Search

Biomedical subjects

A J Levi

Publications and source records attributed to A J Levi.

At least 19 recordsLinked to original sources
PubMed1992

Contractile properties of ventricular myocytes isolated from spontaneously hypertensive rat.

OBJECTIVE: To determine whether there are any differences in contractile properties of individual cardiac myocytes isolated from the spontaneously hypertensive rat (SHR) in comparison with its normotensive control--the Wistar-Kyoto (WKY) rat. DESIGN: The effects of cardiac hypertrophy upon individual myocytes from SHR have not been studied previously. Isolated cardiac myocytes do not suffer from a number of problems inherent in experiments on multicellular preparations. METHODS: Seven SHR and eight WKY animals were studied. Age-matched animals were compared at 60 and 100 days old. Ventricular myocytes were isolated enzymatically. Myocyte length and width was measured. The cells were stimulated with extracellular electrodes and contraction was measured optically. The effects of altering stimulus rate and extracellular calcium concentration upon contraction were studied. RESULTS: SHR myocytes were found to be significantly wider than WKY myocytes. The contraction (i.e. unloaded cell shortening) of SHR myocytes at stimulation rate of 0.3, 1, 2 and 3 Hz was significantly increased. The time-course of contraction was altered, with SHR myocytes having an increased maximal velocity of shortening and relaxation. The response to changes in bathing calcium was similar in both strains. CONCLUSIONS: Individual cardiac myocytes isolated from SHR have an increased contraction. This indicates that cardiac hypertrophy, at least in the early stages, is a protective adaptation allowing the heart to overcome the increased afterload resulting from hypertension.

Animals↗
PubMed1992

Intestinal permeability in patients with Crohn's disease and their first degree relatives.

It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's disease (n = 28) and 32 first degree relatives from 11 families underwent a polyethylene glycol 400 (PEG400) intestinal permeability test and a hyperosmotic (1500 mosmol/l) absorption/permeability test using 3-0-methyl-D-glucose, D-xylose, L-rhamnose, lactulose, and 51chromium labelled ethylenediamine-tetraacetate. The five hour urine excretion of polyethylene glycol 400 did not differ significantly between controls (n = 25) and first degree relatives, 25.5 (3.3)% v 24.6% (4)% (mean(SD)) p greater than 0.1, respectively. Patients with small bowel involvement excreted significantly less (p less than 0.01) polyethylene glycol 400 (16.3 (4.6)% than controls while those with Crohn's colitis did not (26.4 (3.9)% p greater than 0.1). The permeation of the monosaccharides in patients with Crohn's disease and their first degree relatives did not differ from normal subjects. The permeation of lactulose and 51chromium ethylenediaminetetraacetate was not significantly altered in first degree relatives but was significantly increased in the patients, as was the lactulose/L-rhamnose urine excretion ratio which is a specific measure of small intestinal permeability. These studies show normal absorption and permeability in first degree relatives of patients with Crohn's disease. A genetically determined abnormality of intestinal permeability is not likely to be an important aetiological factor in Crohn's disease.

Adolescent↗
PubMed1991

The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease.

This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% +/- 0.6% (mean +/- SE); normal, less than 3.0%] and by high fecal excretion of 111In-labeled leukocytes (14.2% +/- 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% +/- 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% +/- 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

Acute Disease↗
PubMed1991

The role of intracellular sodium in the control of cardiac contraction.

Intracellular sodium was estimated in ventricular myocytes using the new Na-sensitive fluorescent indicator SBFI. Membrane potential and contraction were also measured simultaneously. Using an in situ calibration method, we found that intracellular sodium activity (aiNa) was 2.9 mM in quiescent rabbit cells. When the digitalis analogue strophanthidin inhibited the Na-K pump of myocytes with action potentials (APs), changes of contraction and aiNa were dissociated in time. There was also marked hysteresis between contraction and aiNa. When strophanthidin was applied to the same myocytes under voltage-clamp conditions, temporal dissociation between contraction and aiNa was dramatically reduced. This suggests that much of the dissociation and hysteresis was due the change in AP shape with strophanthidin. A small amount of residual hysteresis still existed even with voltage-clamp, and this persisted when the pump was blocked by removal of external potassium as an alternative method. We suggest that a gradient of sodium concentration from the subsarcolemmal space to the bulk cytoplasm might be responsible for hysteresis. Whereas SBFI probably signals the average Na level of the cytoplasm, subsarcolemmal Na may control Ca influx and contraction via Na-Ca exchange.

Action Potentials↗
PubMed1991

Undershoots of intracellular sodium and the strength of contraction when the sodium-potassium pump of isolated sheep Purkinje fibres is reactivated by potassium.

We have recorded changes of membrane current, intracellular Na+ activity (aiNa), intracellular pH (pHi) and the strength of contraction in voltage-clamped sheep Purkinje fibres during and after inhibition of the Na(+)-K+ pump. The pump was inhibited by the removal of K+ from the bathing solution and this resulted in a rise in aiNa. On return of K+ to the bathing medium to reactivate the Na(+)-K+ pump there was a fall of aiNa to below its control value after which aiNa slowly returned to its control value over the next 20 min. This 'undershoot' of aiNa was seen in 69% of contracting fibres and 78% of quiescent fibres, and the mean (+/- S.D.) values of the undershoot in contracting and quiescent fibres were 0.66 +/- 0.15 and 0.9 +/- 0.35 mM, respectively. The undershoot of aiNa was observed regardless of whether the Na(+)-K+ pump was reactivated with Rb+ or K+. It was not voltage dependent over the potential range studied (-95 to -45 mV) and was not accompanied by a change of intracellular pH. The undershoot of aiNa could be the result of a long-lasting increase in Na+ efflux or a long-lasting decrease in Na+ influx. Zero [K+]o resulted in the loss of one Na+ current, the pacemaker current i(f), but when K+ was returned to the bathing medium i(f) recovered rapidly and is therefore unlikely to be responsible for the long-lasting undershoot of aiNa. This conclusion was confirmed by the use of Cs+: although Cs+ blocked i(f), it did not block the undershoot of aiNa. The undershoot of aiNa was accompanied by (and, via Na(+)-Ca2+ exchange, was presumably the cause of) an undershoot of the force of contraction. Undershoots are not only seen after reactivation of the Na(+)-K+ pump: in a variety of different preparations, similar undershoots in aiNa and twitch force have been reported after a decrease in the frequency of stimulation. The undershoot of aiNa may be the result of novel feedback mechanism for the control of aiNa: the control of Na+ influx by aiNa.

Animals↗
PubMed1991

The effect of strophanthidin on action potential, calcium current and contraction in isolated guinea-pig ventricular myocytes.

1. A method is described for producing high yields of calcium-tolerant ventricular myocytes from guinea-pig hearts (73.4% rod-shaped cells, n = 19). Their action potential (AP) and membrane currents were recorded using conventional microelectrodes and cell shortening was measured optically using a linear photodiode array. 2. The sensitivity of the guinea-pig Na(+)-K+ pump to strophanthidin (a rapidly acting digitalis analogue) was determined by measuring the inhibition of outward pump current by different doses. The pump was found to have a dissociation constant (KD) for strophanthidin of 1.11 x 10(-5) M, and 5 x 10(-4) M-strophanthidin inhibited the pump maximally. 3. Exposure to strophanthidin resulted in an initial lengthening followed by a shortening of the AP, and an increased contraction. Initial AP lengthening was associated with a more positive AP plateau which became more negative as the AP shortened. 4. There was a reversible reduction of Ca2+ current (ICa) during exposure to strophanthidin. ICa changed reciprocally with contraction and with a similar time course. 5. Strophanthidin exposure caused a reduction of ICa at all activating voltages, suggesting that it resulted in a reduction of Ca2+ conductance with little change of its voltage dependence. 6. The role of an increase of intracellular calcium (Cai2+) was investigated by impaling myocytes with microelectrodes containing BAPTA 1,2-bis (2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid, a calcium chelator) to increase Cai2+ buffering. Strophanthidin still shortened the AP when BAPTA was present, suggesting that a rise of Cai2+ is not a major cause of AP shortening. 7. Although AP shortening was little affected, the decline of ICa with strophanthidin was markedly reduced when BAPTA was present, suggesting that a rise of Cai2+ was the cause of the ICa decline with strophanthidin. 8. When barium ions carried the current through Ca2+ channels, strophanthidin did not reduce Ca2+ channel current, suggesting that this compound does not have a direct inhibitory effect on the channel. 9. The results suggest that strophanthidin causes a reduction of ICa by increasing Cai2+, via the mechanism of Cai(2+)-dependent inactivation of ICa. The reduction of ICa at least partially explains the AP shortening and more negative plateau with strophanthidin. 10. The shortening of the AP, more negative plateau and reduced ICa have negative inotropic effects which oppose the direct positive inotropic effect of strophanthidin.

Action Potentials↗
PubMed1991

Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man.

Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during drug absorption, a systemic effect after absorption, and a local effect of the drug excreted in bile, but the relative contribution made by these factors is unknown. We assessed the effect of indomethacin and nabumetone on intestinal permeability. The principal active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, is not subject to appreciable enterohepatic recirculation. Twelve volunteers were studied before and after one week's ingestion of indomethacin (150 mg/day) and nabumetone (1 g/day) with a combined absorption/permeability test. Neither drug had a significant effect on the permeation of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Indomethacin increased the permeation of radioactive 51chromium ethylenediaminetetra-acetic acid (51Cr EDTA) significantly from baseline (mean (SEM) 0.63 (0.09)% v 1.20 (0.14)%, p less than 0.01) but nabumetone did not (0.70 (0.10)% p greater than 0.1). These results were supported by the 51Cr EDTA/L-rhamnose urine excretion ratios, which reflect changes in intestinal permeability. They suggest that NSAIDs increase intestinal permeability during absorption or after biliary excretion and that the systemic effect is of minor importance.

Adult↗
PubMed1991

Elemental diet in the management of Crohn's disease during pregnancy.

Four patients with Crohn's disease were treated with an elemental diet during pregnancy. Two had active disease and two also had symptoms of small intestinal obstruction. All went into a clinical remission within a few days of starting treatment. Treatment periods varied from two to four weeks, and were followed by elemental diet as a supplement to normal food in two patients. At term, all delivered a healthy infant. These patients indicate that elemental diet is a safe form of treatment for Crohn's disease during pregnancy and may be considered as an alternative to conventional drug treatments which carry a theoretical risk of teratogenesis.

Adult↗
PubMed1991

The effect of polyacrylic acid polymers on small-intestinal function and permeability changes caused by indomethacin.

Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin-induced increased intestinal permeability. Using a test solution of 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and 51Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine.

Acrylic Resins↗
PubMed1990

Ten years' experience with an elemental diet in the management of Crohn's disease.

The immediate and longterm outcome of treating patients with acute Crohn's disease with an elemental diet was studied retrospectively. Successful diet induced remission was achieved in 96 of 113 patients (85%) regardless of age, sex, site or severity of disease, or associated complications of strictures, fistula, or perianal disease. Treatment was unsuccessful in 17 patients (15%), but there were no features at the outset of treatment that distinguished these patients from those who had successful remission. The longterm outcome of treatment was assessed over a five year period by analysis of life tables and survival curves. Twenty two per cent of the patients relapsed within six months of treatment and thereafter the annual relapse rate was 8-10%. Patients with disease complicated by fistula or perianal involvement had early relapse, approaching 100% for the latter. A further retrospective comparison of longterm outcome of diet v steroid induced remissions showed no significant difference in the relapse rates between the two groups at one, three, and five years.

Adolescent↗
PubMed1990

Treatment of non-steroidal anti-inflammatory drug induced enteropathy.

Non-steroidal anti-inflammatory drug induced small intestinal inflammation may have an adverse effect on the joints of patients with rheumatoid arthritis. We therefore assessed small intestinal and joint inflammation in patients with rheumatoid arthritis before and after three to nine months' treatment with sulphasalazine (n = 40) and other second line drugs (n = 20), while keeping the dosage of non-steroidal anti-inflammatory drug at the same level. Sulphasalazine significantly decreased the mean (SD) faecal excretion of 111indium labelled leucocytes from 2.39 (2.22)% to 1.33 (1.13)% (normal less than 1%, p less than 0.01) and improved the joint inflammation as assessed by a variety of parameters. There was no significant correlation between the effects of sulphasalazine treatment on the intestine and the joints. Treatment with other second line drugs had no significant effect on the faecal excretion of 111indium (1.58 (1.04)% and 1.86 (1.51)%, respectively) but improved joint inflammation significantly. The lack of correlation between the intestinal and joint inflammation and their response to treatment suggests that the two are not causally related.

Adult↗
PubMed1979

Male infertility due to sulphasalazine.

Four young immigrants whose ulcerative colitis was controlled by sulphasalazine had oligospermia and infertility. No other cause for infertility was found in any of them nor in their wives. Findings on semen analyses rapidly improved in all patients on withdrawal of sulphasalazine, which resulted in four pregnancies in three of the wives. Reintroduction of sulphasalazine was followed by rapid deterioration in the semen of two patients. The frequency and importance of the effect of sulphasalazine on fertility requires further evaluation.

Adult↗
PubMed1979

Low frequency of chlamydial antibodies in patients with Crohn's disease and ulcerative colitis.

Serum samples from 55 patients with Crohn's disease and from 23 patients with ulcerative colitis were tested for antibodies to Chlamydia trachomatis immunotypes by a micro-immunofluorescence technique. Antibody titres of 1:8 or greater against several immunotypes were detected in 14.5% of patients with Crohn's disease and in 21.7% of those with ulcerative colitis. These figures resemble the incidence in a healthy, non-venereal-disease population. Furthermore, there was no correlation between the presence of antibody and such factors as duration of symptoms, localisation of disease, or disease activity. These findings indicate that there is no reason to believe that Crohn's disease involves chlamydiae or that examination for chlamydial antibody is helpful in diagnosis.

Adult↗
PubMed1979

Mean cell volume in a working population: the effects of age, smoking, alcohol and oral contraception.

The effects of mean cell volume (MCV) of age, smoking habit, alcohol consumption, menopausal status, and use of oral contraceptives have been studied as appropriate in 1596 white men and 892 white women in working populations in North-West London. In men, increasing age, smoking and alcohol consumption each make an independent contribution to MCV. In women, the effect of smoking is similar to that in men; the effect of alcohol is less obvious, possibly because of the low stated alcohol intake in women. The effect of alcohol on MCV in the population studied is not as marked as in hospital patients who admit to excessive alcohol consumption; this may partly be due to differences in methods of eliciting intake. There is a small increase in MCV following the menopause. Women on oral contraceptives show a rise in MCV with increasing age; this is not seen in women not on oral contraceptives. There is a strong inverse association between MCV and red blood cell count, which may be part of a mechanism to ensure constant oxygen carrying capactiy.

Adolescent↗