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Biomedical subjects

E M Thomas

Publications and source records attributed to E M Thomas.

At least 37 records · Page 2Linked to original sources

Effect of ovariectomy and estradiol on unity of female rat circadian rhythms.

Sixteen rats were ovariectomized and given either a 1-cm implant of crystalline estradiol-17 beta (eight rats) or an empty implant (eight rats). A further six rats were sham ovariectomized and given empty implants, and eight rats were left unoperated. The rats were exposed to 70 days of constant dim light (LL) with a maximum illumination level of 20 lx, and circadian running and drinking rhythms were monitored. In LL, both the running and drinking activity rhythms of the ovariectomized, blank-implanted rats became markedly disrupted, whereas unoperated and sham-operated rats maintained unified rhythms. Estradiol-implanted rats developed fewer rhythm desynchronies, and the majority displayed a single band of free-running activity. Rather than being arrhythmic, the activity of the LL-exposed ovariectomized rats appeared to contain several free-running components. Thus these data are consistent with the concept of a multioscillatory basis to the circadian system and support a role for the ovary and its hormone estradiol in the maintenance of coherence between component oscillators.

Activity Cycles↗

Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients.

The incidence of venous thromboembolism after elective knee surgery has previously been studied almost exclusively in patients receiving total knee replacements, in whom the risk of a deep vein thrombosis is approximately 60%. We report the results of ipsilateral ascending venography in 312 patients undergoing a wide variety of elective knee operations under tourniquet ischaemia, none of whom received any specific prophylaxis against thromboembolism. Total knee replacement was confirmed to carry a high risk with ipsilateral deep vein thrombosis in 56.4% and symptomatic pulmonary embolism in 1.9%. By contrast, arthroscopy was associated with a low incidence of venous thrombosis (4.2%). Meniscectomy, arthrotomy, patellectomy, synovectomy and arthrodesis were all high-risk procedures, particularly in patients over 40 years of age, and were associated with deep vein thrombosis rates of 25% to 67%. On the basis of these findings, we advise prophylaxis against venous thromboembolism in all patients over 40 years of age undergoing elective knee surgery other than arthroscopy.

Adult↗

Use and abuse of performance indicators.

An audit was performed by this department after allegations by the regional health authority of low productivity. It was found that the health authority had underestimated the number of operations performed in 1983 by only 5%, but an inexact classification and grading of operations had led to errors in the performance indicators of 19.8% for the "weighted number of operations" and 34.5% for the "number of major operations per consultant." When the throughput of orthopaedic departments in districts was compared by the regional health authority it was found that such errors in performance indicators had been further compounded by the inconsistent use of population data and incorrect data on medical staffing. Medical practitioners and the health authorities are alerted to this amplification of inaccurate data. Other methods for assessing trauma and orthopaedic surgery are proposed, such as a simplification of the Office of Population Censuses and Surveys classification of surgical operations, grading operations based on time spent in the operating theatre, and provision of computer programs to code for diagnosis and operation when writing discharge summaries.

Catchment Area, Health↗

Use of an intraruminal soluble glass bolus containing melatonin for early lamb production.

The use of melatonin to advance the onset of seasonal oestrus is potentially useful for early lamb production. A number of delivery systems for melatonin have been developed and this study evaluates an intraruminal soluble glass bolus under field conditions. Anoestrous, non-lactating mule and Dorset cross mule ewes were treated in late June with two types of bolus of different solubilities (melatonin 1, 'slow release' and melatonin 2, 'extra slow release'). Rams were introduced in mid-August for a target lambing pattern in mid-January. The percentage pregnancy/lambing rates were 80/78, 97/92 and 100/100 in the control, melatonin 1 and melatonin 2 groups, respectively. The number of lambs born per ewe put to the ram was significantly increased by treatment with melatonin 2 (P less than 0.05) from 1.17 to 1.64 in the mule ewes and 1.64 to 1.72 in the Dorset cross mule ewes. The melatonin containing soluble glass bolus is a novel and convenient method of reducing the number of barren ewes in an early lambing flock.

Animals↗

Melatonin administration entrains female rat activity rhythms in constant darkness but not in constant light.

In female rats the luteinizing hormone (LH) is timed by the circadian system and is followed by a display of intense, estrogen-induced running behavior. This proestrous running on the night of ovulation can be used as a marker of the estrous cycle. Entrainment of the mammalian circadian system by exogenous melatonin (MT) has been demonstrated only in the activity rhythms of male rats. The present experiments were designed to study the effect of daily MT injections on activity rhythms and proestrous running of female rats in 1) continuous dim white light (LL) and 2) continuous darkness (DD). In LL, MT injections (50 micrograms/kg or 1 mg/kg) had no discernible effect on activity rhythms. In DD, four of the six MT-treated rats (100 micrograms/kg) entrained to the injection, and a fifth animal showed phase advances in its activity rhythm when onset of activity passed through injection time. The sixth animal was not injected with MT at activity onset time. None of the six control animals showed either effect. MT had no effect on the length of the estrous cycle. Thus MT injections can entrain circadian rhythms of activity and proestrous running in female rats in DD but not in LL.

Animals↗

Development of a novel in vitro equine anthelmintic assay.

An in vitro assay involving the use of a horse strongyle (Strongylus edentatus) and the micromotility meter has been developed to test for equine anthelmintic activity. Three commercially available equine anthelmintics (dichlorvos, ivermectin, and pyrantel pamoate) and an investigational drug (p-toluoyl chloride phenylhydrazone) were evaluated in this assay at four concentrations. After a 24-h incubation, greater than or equal to 10 micrograms/ml of all four drug treatments significantly (P less than or equal to 0.05) reduced the motility of ensheathed L-3 S. edentatus larvae, thereby indicating anthelmintic activity. Pyrantel pamoate also reduced motility at 1 microgram/ml, while the hydrazone significantly increased movement at this level. At 0.1 microgram/ml, none of the treatments significantly reduced motility; one treatment (dichlorvos) significantly increased larval motility. Incubation for 48 h resulted in significant activity (reduction in motility) at greater than or equal to 1 microgram/ml with two drugs (ivermectin, pyrantel pamoate); dichlorvos and the hydrazone reduced motility at greater than or equal to 10 micrograms/ml. None of the treatments significantly reduced motility at the lowest concentration (0.1 microgram/ml); however, at 48 h, two treatments (dichlorvos, hydrazone) significantly increased motility at the lowest concentration (0.1 microgram/ml). The in vitro S. edentatus motility assay proved to be sensitive, accurate and rapid. This assay system should be a valuable addition to tests used to identify potential equine anthelmintics, monitor helminth resistance to drugs, and perhaps define the kinetics and mode of action for drugs.

Animals↗

In vitro response of Haemonchus contortus larvae harvested during different times of the patent period to anthelmintics.

Three commercially available ruminant anthelmintics and an investigational drug were evaluated for effects on the motor function/motility of third stage (ensheathed) Haemonchus contortus. Helminth ova were collected at one, five, nine and 13 weeks during the patent period, cultured to the third larval stage and assayed for sensitivity to four different drugs. All four drugs (100 and 10 micrograms ml-1) significantly affected the motility of third stage H contortus larvae cultured from eggs passed at each of the times examined. However, the investigational drug (p-toluoyl chloride phenylhydrazone, 10 micrograms ml-1) had a significantly greater effect on the motility of larvae harvested at 13 weeks than those cultured at nine weeks (32 per cent difference). No other significant differences in the motility response during the patent period were observed.

Albendazole↗

Pharmacokinetics and effects on the renin-angiotensin system of ramipril in elderly patients.

Converting enzyme inhibitors are likely to be prescribed with increasing frequency in elderly patients. The pharmacokinetics of ramipril, a new potent long-acting non-sulphydryl converting enzyme inhibitor, and its effects on blood pressure, plasma renin activity and angiotensin II concentrations were studied in a group of 8 elderly volunteers (mean age 77, range 61 to 84). Circulating concentrations of the active diacid formed from its parent drug were consistently higher in this group despite apparently normal renal function, assessed by serum creatinine and urea concentrations, compared with younger volunteers (age range 21 to 30). The initial dose of ramipril should be lower in older subjects. The study emphasizes the importance of careful extrapolation of data obtained from young volunteers to older subjects.

Aged↗

Detecting in vitro anthelmintic effects with a micromotility meter.

An in vitro target parasite anthelmintic assay utilizing a micromotility meter has been developed and validated. Haemonchus contortus, an economically important ruminant helminth with worldwide distribution, was the parasite used in the model. Four commercially available ruminant anthelmintics (albendazole, ivermectin, levamisole hydrochloride and coumaphos) were initially evaluated at concentrations of 200, 150, 100 and 50 micrograms ml-1. All four significantly affected helminth motor activity and were active at 200 and 150 micrograms ml-1, and three of the four were active at 100 and 50 micrograms ml-1. An Upjohn compound (p-toluoyl chloride phenylhydrazone) was also assayed and was significantly active at all four levels. In a subsequent titration study, albendazole, levamisole hydrochloride, ivermectin and the hydrazone were significantly active at 100 and 10 micrograms ml-1; only levamisole hydrochloride and the hydrazone were active at 1.0 microgram ml-1. None of the drugs were active at 0.1 microgram ml-1. The data indicate that the in vitro H. contortus assay utilizing the micromotility meter is sensitive, accurate, rapid, repeatable, and inexpensive. With additional effort, this model can be extended to incorporate other target helminth parasites and stages of development. This in vitro assay system should be a valuable addition to the battery of tests used to identify anthelmintic candidates, monitor drug resistance, and define the kinetics and mode of action of drugs.

Albendazole↗

Hodgkin's disease: is there a price for successful treatment? A 25-year experience.

Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.

Antineoplastic Agents↗

Improved survival of the diabetic foot: the role of a specialized foot clinic.

A specialized foot clinic for diabetic patients has made a detailed analysis of the presentation of diabetic foot ulcers and from this a new, organised approach to treatment has been derived. Over three years it has achieved a high rate of ulcer healing and reduced the number of major amputations. It has brought together the skills of chiropodist, shoe-fitter, nurse, physician and surgeon to manage the distinctive lesions of the neuropathic and ischaemic diabetic foot. The neuropathic ulcer was invariably associated with callus, whereas the ischaemic ulcer presented as areas of necrosis often from localised pressure of tight shoes. Essential aspects of management are specially constructed shoes, intensive chiropody and precise antibiotic treatment. Healing was achieved in 204 out of 238 (86 per cent) neuropathic ulcers and 107 out of 148 (72 per cent) ischaemic ulcers. Relapse rate in special shoes was 26 per cent compared with 83 per cent who preferred to wear their own shoes. In the two years before the establishment of the clinic, there were 11 and 12 major amputations yearly. This rate has now been reduced to seven, seven and five amputations yearly.

Aged↗

Heparin and dihydroergotamine prophylaxis against thrombo-embolism after hip arthroplasty.

A prospective study involving 500 consecutive patients undergoing hip replacement was performed to find out whether a combination of heparin and dihydroergotamine was effective in preventing postoperative fatal and non-fatal emboli. Deep-vein thrombosis was demonstrated in 131 cases (26.2%), in 99 of whom thrombi were confined to the ipsilateral (operated) limb and in 13 to the contralateral limb; 19 patients developed bilateral thrombi. Nine patients (1.8%) died during the first four weeks after operation, before they were discharged from hospital; in one, major emboli were demonstrated in the right pulmonary artery. Three of the 500 patients developed non-fatal pulmonary emboli. Excessive bleeding occurred in 21 (4.2%) and in 19 of these prophylaxis was discontinued. Wound haematomas developed in 25 patients (5.0%); only six required evacuation but in none of these six did deep infection occur while in hospital; in three patients, however, the wound haematoma prolonged the stay in hospital. Thus the combination of heparin and dihydroergotamine proved an effective prophylaxis against pulmonary embolism in patients undergoing total hip replacement. The risk of bleeding complications is wholly acceptable when balanced against the advantages of the therapy.

Aged↗

Sympathetic innervation of the jejunal villus.

Using fluorescent histochemical methods it has been shown that the noradrenergic nerves in the jejunal villus are associated with the capillaries underlying the basolateral membrane of the epithelium. Noradrenergic fibres were also seen to lie between the epithelial basolateral membrane and the capillaries but were never observed close to the epithelium unless accompanied by an underlying capillary. The distribution of noradrenergic fibres suggests that it is unlikely that noradrenaline diffuses directly from the varicosity to the epithelial basolateral membrane. Noradrenaline may, therefore, act on the capillary itself and in some way affect fluid absorption. However, noradrenaline released adjacent to a capillary might diffuse into the capillary to be distributed at another site along its course.

Animals↗

Striatal glutamatergic function: modifications following specific lesions.

The effects of specific lesions of the striatum: (a) hemidecortication; (b) striatal injection of (+/-) ibotenate; and (c) 6-hydroxydopamine injections into the substantia nigra, were investigated on specific [3H]glutamate binding to striatal membranes. One month after decortication, there was a substantial reduction of calcium-dependent, stimulated glutamate release from striatal slices, indicating effective loss of glutamatergic fibres. Striatal glutamate binding increased by approximately 30% and this supersensitivity could be attributed solely to an increased receptor density. Ibotenate lesions which destroy target neurones for the glutamatergic fibres (sparing terminals), reduced glutamate binding in the striatum, as did nigral 6-OHDA lesions which delete striatal dopaminergic terminals. This finding supports the concept of there being glutamate receptors on pre-synaptic dopamine terminals in the striatum, involved in regulation of dopamine release. 6-OHDA lesions also result in a supersensitivity of the dopamine receptors localized on the cortico-striatal afferent terminals, as evidenced by the enhanced ability of dopamine to inhibit the K+-evoked, calcium-dependent release of endogenous striatal glutamate.

Animals↗

The noradrenergic innervation of the excretory ducts of the parotid, mandibular and sublingual glands in the rat.

The noradrenergic innervation of the excretory ducts of the parotid, mandibular and sublingual salivary glands in the rat has been examined using fluorescence histochemistry. None of the ducts were found to be innervated directly but, in the mandibular duct, innervated blood vessels are in close proximity to the epithelial cells of the duct and it is suggested that noradrenaline may diffuse from the vascular nerve endings to receptors on the epithelial cells.

Animals↗

Sites of noradrenergic innervation of the jejunal villus.

1. It has been demonstrated that the upper region of the jejunal villus is supplied with noradrenergic nerves. 2. These nerves are in close proximity to the capillary network underlying the epithelial cells and the lacteal. 3. Hitherto sympathetic innervation of the gut had not been demonstrated to extend further than the crypt region. 4. This evidence allows the proposal that the vasculature and epithelial cells may be involved in the control of absorption from the gastrointestinal tract.

Animals↗