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Biomedical subjects

I A Sutherland

Publications and source records attributed to I A Sutherland.

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

Transport of isometamidium (Samorin) by drug-resistant and drug-sensitive Trypanosoma congolense.

The uptake kinetics of a 14C-labelled trypanocidal compound isometamidium chloride (Samorin, RMB Animal Health Ltd, UK) was measured in drug-resistant and drug-sensitive Trypanosoma congolense. It was established that drug uptake was significantly more rapid and quantitatively greater in drug-sensitive parasites. There was clear evidence that drug uptake in both the resistant and sensitive trypanosomes was by a specific, receptor-mediated process. This specific drug transport was energy-dependent, being sensitive to metabolic inhibition with SHAM/glycerol. Significant differences in drug transport were observed which could be correlated with resistance to isometamidium. The optimal pH for drug accumulation was lowered in the resistant trypanosomes; this finding, along with an observed change in specificity for the related compound homidium bromide, suggested that the specific receptor for isometamidium is altered in the resistant trypanosomes, possibly resulting in a reduction in drug uptake. In addition to these alterations in drug uptake, efflux of isometamidium also appears to occur in the resistant trypanosomes. Both a reduction in incubation temperature and metabolic inhibition increased the level of trypanosome-associated isometamidium in the resistant parasites. This was in contrast to observations using drug-sensitive parasites. Furthermore, the addition of calcium flux-modulating agents to the incubation medium also resulted in an increase in accumulation by the resistant parasites.

Animals↗
PubMed1992

Kinetic modelling of isometamidium chloride (Samorin) uptake by Trypanosoma congolense.

Clones of Trypanosoma congolense which express resistance to the widely used trypanocide isometamidium chloride accumulate less of the drug than clones which are sensitive to drug treatment. A mathematical model has been developed which was able to predict theoretical lines representing the uptake kinetics in trypanosomes which were sensitive to isometamidium, as well as for resistant trypanosomes in which reduced accumulation was a result of either reduced uptake or enhanced efflux of the drug. Data from drug uptake experiments were then fitted to these theoretical lines. While the value for drug efflux could not be separated from the dissociation constant of the trypanosomes for isometamidium, it was demonstrated that reduced accumulation is not a result of reduced uptake of isometamidium by drug-resistant trypanosomes.

Animals↗
PubMed1992

A single-blind, randomized study to compare the efficacy of two ear drop preparations ('Audax' and 'Cerumol') in the softening of ear wax.

A parallel group, single-blind, randomized study was carried out in a general practice to compare the effectiveness and tolerability of two ear drop preparations ('Audax' and 'Cerumol') in the softening of ear wax in 50 adult patients with impacted or hardened ear wax. Assessments were made on entry of the amount, colour and consistency of the ear wax, symptoms, and objective hearing. Patients were then allocated at random to receive one or other preparation and instructed to use the drops, morning and evening, for 4 days after which they were reassessed. Details were recorded of any side-effects or discomfort caused by the study medication and both physician and patients were asked to give their overall opinion of treatment efficacy. Both treatments were shown to be effective in the softening of ear wax and were well tolerated, there being no significant difference between the two groups in these parameters. However, patients who had abnormal hearing before treatment had a significantly greater improvement in objective hearing after treatment with 'Audax' ear drops compared to those patients treated with 'Cerumol' ear drops. There were no between-treatment differences in either either the physician's or patient's overall assessments of effectiveness.

Adolescent↗
PubMed1991

Therapeutic and prophylactic activity of isometamidium chloride against a tsetse-transmitted drug-resistant clone of Trypanosoma congolense in Boran cattle.

An investigation was conducted on the therapeutic and prophylactic activity of isometamidium chloride (SamorinR) in Boran (Bos indicus) cattle against a Trypanosoma congolense clone, IL 3270. This clone was derived, without drug selection, from a stock originally isolated in Burkina Faso and has previously been shown to be resistant to isometamidium in both cattle and mice using an infection and treatment regimen. A group of 5 cattle were treated intramuscularly with 1.0 mg kg-1 isometamidium chloride and 28 days later challenged with Glossina morsitans centralis infected with T. congolense IL 3270. All 5 cattle and 17 untreated cattle challenged on the same day became parasitaemic by day 16 post challenge, indicating that prophylaxis did not extend to 28 days post treatment. The cattle were then treated with isometamidium chloride at one of the following doses and by different routes of administration; 1.0 or 2.0 mg kg-1 intramuscularly, 0.25, 0.5, 0.75 or 1.0 mg kg-1 intravenously. Infections relapsed in all cattle at an interval of 12-21 days following treatment, with the exception of those treated with 2.0 mg kg-1 intramuscularly in which the development of relapse infections was delayed. Similar studies were also conducted with a highly sensitive clone of T. congolense, IL 1180. Infections in cattle with this clone were eliminated by intravenous treatment with 0.25 mg kg-1 isometamidium chloride or intramuscular treatment with 0.5 mg kg-1 isometamidium chloride. Thus, although intravenous administration of isometamidium eliminated a fully sensitive infection, treatment by this route appeared not to enhance the therapeutic efficacy of the drug in the treatment of a T. congolense clone which expresses a high level of resistance.

Animals↗
PubMed1991

Development of an enzyme-linked immunosorbent assay for the detection and measurement of the trypanocidal drug isometamidium chloride in cattle.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure accurately levels of the trypanocidal drug isometamidium in the serum of treated cattle. The assay requires only 5 microliters of test serum, is sensitive to a level of 0.5 pg ml-1 and is highly specific. Cross reactivity does not occur with the two other widely used trypanocidal drugs diminazene aceturate and homidium bromide. Serum drug levels are detectable for up to six months in cattle after a single dose of 1 mg kg-1 intramuscularly, the maximum period under field conditions for which effective prophylaxis can be maintained against tsetse challenge. Application of the assay will aid the rationalisation of treatment campaigns and assist in assessing the occurrence of drug-resistant trypanosome populations.

Animals↗
PubMed1991

Effect of isometamidium on Trypanosoma congolense infectivity.

Isometamidium chloride (Samorin, RMB, England) is a widely used and highly effective trypanocide for the treatment of bovine trypanosomiases. However, the appearance of isometamidium-resistant populations of T. congolense in Africa makes it necessary to develop methods for the rapid and reliable detection of drug resistance in the laboratory. Currently available tests are time-consuming and/or expensive. In the present study, the short-term in vitro incubation of trypanosomes in a range of isometamidium concentrations and the infectivity of the parasites in mice has been assessed. A series of T. congolense isolates were used which were known to differ in their in vivo sensitivity to the drug. The results showed a close correlation between the known level of resistance and the capability of trypanosomes to remain infective after incubation in isometamidium. Thus isolates displaying a high level of resistance in vivo remained infective following incubation in higher concentrations of drug. This assay may provide a simple and reliable method for detecting drug resistance in T. congolense.

Animals↗
PubMed1991

Reduced accumulation of isometamidium by drug-resistant Trypanosoma congolense.

The accumulation of the trypanocide isometamidium chloride (Samorin, RMB Animal Health Ltd., UK) by a range of clones of Trypanosoma congolense with varying sensitivity to the drug, was measured by methods based on the fluorescence of isometamidium. Fluorescence microscopy and flow cytometry showed a reduction in drug accumulation by resistant clones. Fluorescence spectrophotometry demonstrated an inverse correlation between the intensity of cell-associated fluorescence and the level of resistance of the clones expressed in vivo. The addition of the metabolic inhibitor SHAM/glycerol to the incubation medium resulted in a reduction of this apparent difference in drug accumulation between the clones; those clones which were sensitive to isometamidium showed a reduction in fluorescence while a percentage increase in fluorescence was observed as clones became more resistant to the trypanocide. These observations may be of value for the in vitro detection of resistant T. congolense populations and may also be used to estimate the mean level of resistance in a given sample. The results also imply that decreased accumulation of isometamidium by drug-resistant clones of the parasite may be responsible for the reduction in sensitivity.

Animals↗
PubMed1990

Assessment of cardiotocographs.

In recent years advances in medical electronic equipment for monitoring, diagnosis and treatment of patients have led to a large increase in the number and variety of instrumentation available to the medical profession. There is a considerable amount of duplication of equipment and in the absence of readily available information buyers are unlikely to make informed decisions about the ideal instrument for their particular circumstances. One method of increasing the users' awareness is a comparative, independent assessment of equipment, with the results disseminated to the interested parties. This paper describes the essential qualities of cardiotocographs: how they are assessed as part of the UK Department of Health's evaluation programme and the measures to inform users of the latest evaluation information.

Cardiotocography↗
PubMed1990

A larval paralysis assay for the detection of thiabendazole resistance in trichostrongyles.

Infective-stage larvae of trichostrongyle nematodes, either resistant or susceptible to thiabendazole (TBZ), were incubated in eserine, an acetylcholinesterase inhibitor. Paralysis occurred in larvae treated with eserine but significant differences were observed in the percentage of larva immobilized between TBZ-resistant and TBZ-susceptible strains of the nematodes. These differences are probably related to the presence of higher levels of acetylcholinesterase in the TBZ-resistant strains than in the susceptible strains. This could be used as a rapid and inexpensive method of detecting resistance to TBZ in trichostrongyles.

Animals↗
PubMed1990

Head-to-cervix forces and their relationship to the outcome of labor.

The force (as distinct from pressure) between the fetal head and the maternal cervix during labor was measured for the first time in an attempt to improve the intrapartum prediction of progress in labor. The 50th percentile of the variables active pressure and active force and the mean uterine activity integral were compared with the cervical dilatation rate and delivery mode in 31 women. The 50th percentile of active force had the highest correlation with the cervical dilatation rate (r = 0.54) (50th percentile of active pressure, r = 0.43; mean uterine activity integral, r = 0.40). The 50th percentile of active force was significantly higher in women who achieved a vaginal delivery (mean +/- SD 45 +/- 21.2 g wt) than in those who underwent cesarean delivery for failure to progress (16.5 +/- 9 g wt). The 50th percentile of active force discriminated among modes of delivery as effectively as did the cervical dilatation rate. These results support the hypothesis that head-to-cervix force measurements may have clinical value in the management of labor.

Biomechanical Phenomena↗
PubMed1989

One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE: To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN: Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING: Infertility clinic. PATIENTS: 118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS: Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT: Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS: Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.

Abortion, Spontaneous↗
PubMed1989

Colorimetric assay for the detection of benzimidazole resistance in trichostrongyles.

A modified version of the aphid tile-test, which is used to detect insecticide resistance in single adult aphids that are resistant or susceptible to organophosphate or carbamate insecticides, was used to compare the levels of non-specific esterases in strains of the trichostrongyle nematodes Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis which were known to be resistant or susceptible to benzimidazole (BZ) anthelmintics. This colorimetric assay has shown that there is significantly more non-specific esterase in the infective-stage larvae of BZ-resistant strains than in susceptible strains and this may prove to be of use in the detection of resistance to benzimidazole anthelmintics.

Animals↗
PubMed1988

Validation of thermal techniques for measurement of pelvic organ blood flows in the nonpregnant sheep: comparison with transit-time ultrasonic and microsphere measurements of blood flow.

Data obtained from a thermal system capable of measuring changes in organ temperature as well as tissue thermal clearance in the uterus and vagina have been compared with blood flow measured continuously with a transit-time ultrasound volume-flow sensor placed around the common internal iliac artery and intermittently with radioactive microspheres in the chronically instrumented nonpregnant sheep. Temperature changes in both the uterus and the vagina correlated well with blood flow changes measured by both techniques after intravenous administration of estradiol or norepinephrine. Thermal clearance did not correlate well with blood flow in the vagina or uterus. These methods may have value in the investigation of blood flow patterns in various clinical situations such as the pelvic pain syndrome and early pregnancy.

Animals↗
PubMed1988

Pulsatile infusion of gonadotrophin releasing hormone (GnRH): investigative and therapeutic applications.

Normal gonadotrophin secretion, and therefore normal ovarian function, depend on delivery to the pituitary of the hypothalamic neuropeptide gonadotrophin releasing hormone (GnRH) in a pulsatile pattern. In the mid-follicular phase of the menstrual cycle, for example, discrete pulses of luteinizing hormone (LH) can be observed at approximately 90 min intervals. Many disorders of ovulation are caused by abnormalities of this natural pulsed signal. We have developed and used a small portable infusion pump to deliver GnRH to women with hypothalamic amenorrhoea; our studies, and those of other groups, have shown that successful ovulation and pregnancy result from such treatment. The results of treatment at St Mary's Hospital show that 16 women with hypogonadotrophic amenorrhoea received a total of 31 cycles of treatment with pulsatile GnRH; 25 (81%) of these cycles were ovulatory and 11 of the 14 women who were trying to conceive became pregnant. There was only one multiple pregnancy (twins).

Adult↗
PubMed1988

Detection of the fetal ECG during labour by an intrauterine probe.

The feasibility of detecting the fetal ECG (FECG) from within the uterus in labour by a technique which is non-invasive to the fetus, has been investigated. The design of a special multi-electrode flexible probe has demonstrated that the FECG can be obtained with signal amplitudes of 20-300 microV and a success rate similar to that of the scalp electrode. Under favourable conditions very large signals can be detected in utero compared to a scalp electrode, but average signal amplitudes are lower. The probe is suitable as a carrier for other sensors such as pressure and temperature transducers. Currently, simultaneous FECG and intrauterine pressure measurement using a commercially available transducer within the same probe has been achieved.

Electrocardiography↗
PubMed1988

Detection of benzimidazole resistance in trichostrongylid nematodes.

Benzimidazole anthelmintics (Box 1) have an important role in the control of economically-important nematode parasites of sheep and other ruminants. But effective control and management strategies using such compounds require a clear appraisal of the resistance or susceptibility of the target worms. Currently available tests for benzimidozole resistance in trichostrongylid nematodes tend to be costly, time-consuming and technically-demanding - as a result, attention is now turning to biochemical assays.

Journal Article↗
PubMed1987

Intravenous dihydroergotamine to relieve pelvic congestion with pain in young women.

The selective venoconstrictor dihydroergotamine (DHE) was given intravenously to 12 women with evidence of pelvic congestion. In 6 the effect of the drug on pelvic veins was observed by pelvic venography. After DHE there was a mean reduction of 35% in the diameter of the pelvic veins measured and the contrast medium cleared rapidly, with a visible reduction in pelvic congestion. In the other 6 women DHE was given during an acute attack of pelvic pain. The effect of the drug on pain relief was assessed by a single-blind crossover trial with intravenous saline as the placebo and by a visual analogue scale to assess the intensity of pain. Pain was significantly lower post-DHE 4 and 8 h and 2 and 4 days after treatment than after placebo. The results confirm a close association between demonstrable pelvic congestion and pelvic pain.

Acute Disease↗