Showing papers by "Cardiff University published in 1982"

A model of the nerve impulse using two first-order differential equations

Abstract: The Hodgkin–Huxley model1 of the nerve impulse consists of four coupled nonlinear differential equations, six functions and seven constants. Because of the complexity of these equations and the necessity for numerical solution, it is difficult to use them in simulations of interactions in small neural networks. Thus, it would be useful to have a second-order differential equation which predicted correctly properties such as the frequency–current relationship. Fitzhugh2 introduced a second-order model of the nerve impulse, but his equations predict an action potential duration which is similar to the inter-spike interval3 and they do not give a reasonable frequency–current relationship. To develop a second-order model having few parameters but which does not have these disadvantages, we have generalized the second-order Fitzhugh equations2, and based the form of the functions in the new equations on voltage-clamp data obtained from a snail neurone. We report here an unexpected property of the resulting equations—the x and y null clines in the phase plane lie close together when the phase point is on the recovery side of the phase plane. The resulting slow movement along the phase path gives a long inter-spike interval, a property not shown clearly by previous models2,4. The model also predicts the linearity of the frequency–current relationship, and may be useful for studying detailed interactions in networks containing small numbers of neurones.

Steroids in Saliva for Assessing Endocrine Function

Abstract: SOME difficulties in clinical studies of endocrine function based on plasma sampling regimens include time-consuming venipuncture and measurement of the “total” rather than the “free” biologically active fraction in plasma. Simple methods for determining plasma free steroids have not yet been developed, and most current procedures involve technically demanding ultrafiltration or equilibrium dialysis. In this context measurement of steroids in saliva is attractive. Steroid concentrations in saliva are independent of flow rate and reflect those in the free fraction in plasma. Recent improvements in immunoassay techniques have allowed development of simple, high output assays for salivary steroids which are well suited for routine use. Since saliva samples can be collected at frequent intervals by both adults and children, they facilitate short term dynamic tests, pharmacokinetic analyses, and studies of chronobiological changes. Problems of viscosity, which restrict processing of freshly collected saliva, m...

Dynamic analysis of an inventory and order based production control system

Abstract: In an inventory and order based production control system (IOBPCS), there are three fundamental system parameters. One of these, the production delay time, is beyond the control of the IOBPCS designer. Indeed, the production delay may be highly variable with time due to a variety of problems commonly found in manufacturing industry. This uncertainty must be countered by the proper use of a feedback loop which detects and operates on inventory deviations. The IOBPCS designer is thus left with the forward path demand averaging time and feedback path gain to adjust, as best he can. This paper studies the ability of the IOBPCS to recover from shock demands, and to protect the manufacturing process from random variations in consumption. It is shown that the feedback path is of fundamental importance in good control, and that adequate performance cannot be obtained by feedforward alone. Dynamic recovery is examined graphically by separately identifying the feedforward and feedback components. Random di...

An improved radioreceptor assay for tsh receptor antibodies

Abstract: An improved receptor assay for TSH receptor antibodies is described in which detergent-solubilized TSH receptors and 125I-labelled TSH are used. Normal human serum and immunoglobulin concentrates from normal serum showed little effect on the interaction between labelled TSH and detergent-solubilized receptors whereas immunoglobulin concentrates from some Graves sera caused marked inhibition of TSH binding. Precipitation with polyethylene glycol was the most convenient way of preparing immunoglobulin concentrates and using this technique the assay could be completed in a few hours. The coefficient of inter assay variation at 51% inhibition of labelled TSH binding was 3.7% and analysis of serum samples from patients with Graves' disease (n = 42), Hashimoto's disease (n = 26), multinodular goitre (n = 9), rheumatoid arthritis (n = 10) and normal donors (n = 35) suggested that the assay could detect TSH receptor antibodies in about 80% of patients (treated and untreated) with Graves' disease.

The contribution of nucleus reticularis paragigantocellularis and nucleus raphe magnus to the analgesia produced by systemically administered morphine, investigated with the microinjection technique

Abstract: Intracerebral administration of morphine into either nucleus reticularis paragigantocellularis (NRPG) or nucleus raphe magnus (NRM) of rats produced analgesia, as measured by the tail flick test. NRPG was more sensitive to morphine and the effect was dose dependent. The narcotic antagonist naloxone blocked these analgesic effects of morphine. The effect of intracerebral injection of naloxone on the analgesia produced by systemically administered morphine was examined. Morphine was administered subcutaneously (2.86 mg/kg) and naloxone was microinjected 35 min later. Microinjection of 5 μg of naloxone into NRM was found to be more effective in reversing the analgesia produced by morphine than naloxone microinjected into more lateral sites, including NRPG. Lesions of NRPG did not attenuate the analgesia produced by systemically administered morphine, whereas lesions of NRM did attenuate this analgesia. The analgesia produced by morphine administered into NRPG was blocked by lesions of NRM. Cinanserin, a serotonergic blocker, blocked the effects of morphine microinjected into NRM but not effects of morphine injected into NRPG. Phenoxybenzamine partially blocked the effects of morphine injected into NRPG but not the effects of morphine injected into NRM. These results show that both nuclei are sensitive to morphine, exert their effects by different synaptic mechanisms and that NRPG does not make an appreciable contribution to the analgesia produced by systemically administered morphine.

Color preference, arousal, and the theory of psychological reversals

Abstract: The theory of psychological reversals asserts that there are two levels of preferred felt arousal, one high and one low. Only one of them is preferred at a given time, although discrete switches (“reversals”) occur from time to time, so that each level is preferred at different times. In order to document such changes in preferred levels of arousal, 75 subjects were asked to make color preference choices at regular intervals during their working day, some for as many as 8 days. The assumption was that different colors are arousing or relaxing, and that color choice indicates arousal preference. The typical patterns of color choices that occurred clearly displayed the expected reversal effect over time and were considerably more consistent with reversal theory than with optimal arousal theory. In a second study, 41 new subjects were asked to respond to a simple mood adjective checklist each time they made their color preference choices. The results strongly supported the association between arousal preference and color preference and also supported the reversal theory thesis that low arousal preference is associated with seriousness and planning orientation (all these characterizing the “telic state”), and that high arousal preference is associated with playfulness and spontaneity (all these characterizing the “paratelic state”). Finally, both studies showed that there is a systematic tendency for long-wavelength colors to induce feelings of high arousal and for short-wavelength colors to induce feelings of low arousal.

Epidemiology in anaesthesia ii: factors affecting mortality in hospital

Abstract: The hospital mortality following 108 878 anaesthetics in Cardiff between 1972 and 1977 has been analysed. There was a total of 2391 deaths, giving a crude mortality rate of 2 2 per 100 patients. Data are presented on several important variables that influence mortality These include age, sex, preoperative clinical assessment score, preoperanve condition, site of operation, operation, whether elective or emergency and duration of anaesthesia

The accumulation and intracellular compartmentation of cadmium, lead, zinc and calcium in two earthworm species (Dendrobaena rubida and Lumbricus rubellus) living in highly contaminated soil.

Abstract: The earthworm Lumbricus rubellus contained more Ca and Zn, and less Pb and Cd, than Dendrobaena rubida living in the same contaminated disused-mine soil. Differences in the kinetics of Ca turnover may account for some of the inter-specific differences in heavy metal burdens, although the calciferous glands do not seem to be directly involved in heavy metal excretion. A comparison of the present findings with published data indicated that the concentration of soil Ca and the bioavailability of heavy metals, both factors being allied to soil pH, are important exogenous determinants of heavy metal accumulation by different earthworm populations. Electron microprobe X-ray analysis of air-dried smears of chloragogenous tissue showed that the metals were fairly specifically compartmentalized into two distinct organelles in both worms: Ca, Pb and Zn were found (associated with P) in the chloragosomes; Cd was found (with S and probably in stoichiometric association) in a more electron-lucent vesicular component, designated the ‘cadmosome’, but which may be identical with the debris vesicles which are characteristic inclusions in conventionally-fixed chloragocytes. The in vivo incorporation of Pb by the chloragosomes of D. rubida was accompanied by the loss of Ca, Zn and P.

The development and in vitro evaluation of acrylic strips and dialysis tubing for local drug delivery

Abstract: This study reports on the development of drug containing acrylic strips for delivering antimicrobial agents and compares the in vitro release pattern with dialysis tubing. Polyethylmethacrylic strips of suitable dimensions containing 10 to 50% chlorhexidine acetate, 40% metronidazole and 40% tetracycline were prepared. Daily release of the incorporated drugs into 1 ml aliquots was measured spectrophotometrically over a 14 day period. Similarly the release of chlorhexidine gluconate from various lengths of patent and heat sealed dialysis tubing was recorded for 4 days. At 30%, 40% and 50% admixtures the acrylic strips released chlorhexidine up to the 14 day period and a parallel bioassay confirmed the maintenance of antibacterial activity to this time. At the same admixture the release of metronidazole was greater than chlorhexidine and tetracycline. All drugs were released at high levels on day 1 followed by a marked fall in release by day 2 and progressive fall thereafter. The release from tubing was almost total within 24 hours and was independent of sealing the ends. The strips appear to have potential for prolonged drug delivery to periodontal pockets. Preliminary clinical use revealed no patient acceptability problems and alterations in subgingival flora were produced.

Epidemiology in anaesthesia. III: Mortality risk in patients with coexisting physical disease.

Abstract: The Cardiff Anaesthetic Record System has been used to examine the hospital mortality rates and relative risks for patients having anaesthesia who have certain preoperative conditions coexisting with their disease requiring surgery. Each preoperative condition was associated with a higher mortality rate than occurred in patients with no preoperative condition (for example ischaemic heart disease 7%, diabetes 5.7%, no preoperative condition 0 5%). Mortality was greater for emergency than for elective operations In contrast to an increasing mortality by age, the relative mortality risk decreased, suggesting that in older age groups coexisting disease may be less important than

Fission-track dating of British Ordovician and Silurian stratotypes

Abstract: Fission-track dating of zircons and apatites from tuffs and bentonites has produced the first isotopic ages for the type sections of the Ordovician and Silurian Systems. In the Ordovician the following ages have been determined: lower Arenig 493 Ma, lower Llanvirn 487 Ma, lower Llandeilo 477 Ma, upper Caradoc 463 Ma and upper Ashgill 434 Ma. In the Silurian, the following: lower Llandovery 437 Ma, lower Wenlock 422 Ma, upper Wenlock 414 Ma and Ludlow 407 Ma. The Ordovician-Silurian boundary is interpreted as occurring at about 436 Ma. Three North American Rocklandian bentonites yielded zircons whose ages average 453 Ma. This is about 10 Ma younger than supposedly correlative units in the British type sections.

Bacteria accumulate silver during leaching of sulphide ore minerals

Abstract: Silver is extremely toxic to a wide range of bacteria1–5, and has even been used in solution to control bacterial growth2. In an investigation of the oxidation of several sulphide minerals containing traces of silver by a mixed culture of Thiobadllus ferroxidans and Thiobacillus thiooxidans, it was noted that the bacteria accumulated silver. I report here that careful collection of most of the cells from such experiments yields a silver concentrate, while the silver attached to the cells remaining in contact with leach residues is readily recovered by a conventional cyanidation technique. These results suggest that the bacterial leaching of valuable and non-valuable sulphide minerals in order to release atomically bound silver, and possibly gold, may be used as part of a recovery process for these elements.

The Recognition and Interpretation of Paleokarsts: Two Examples from the Lower Carboniferous of South Wales

Abstract: Criteria for the identification and interpretation of paleokarstic surfaces in ancient carbonate sequences are discussed and two examples of such surfaces are described from the Lower Carboniferous of South Wales. One type is compared to Kavornossen karren, a type of tropical karst well developed today on Puerto Rico. The second example, a mammillated paleokarstic surface of a type common in the Lower Carboniferous, is interpreted as a deckenkarren, formed beneath a vegetation cover and similar to the Makondo karsts of South Africa. Paleokarsts can provide information on the paleoclimates, paleohydrology, and vegetation cover existing at the time of their formation.

Cyanophyte calcification and changes in ocean chemistry

Abstract: Cyanophytes range from at least 2,200 Myr (ref. 1) to the Recent, but they only produced common marine shelly fossils during the Palaeozoic and Mesozoic (570–80 Myr) (Fig. 1). This contrasts with the pattern of metazoan evolution in which rapid diversification near the Precambrian–Cambrian boundary was closely accompanied by skeletonization2 which has been retained in marine environments to the Recent. Attempts to explain this unusual geological distribution of marine calcareous cyanophytes cannot be made solely by reference to biological processes because these algae are mainly dependent on environmental conditions for their calcification3. Thus, the presence or absence of calcified cyanophytes may be a general indication of long-term changes in seawater chemistry. This likelihood has been recognized previously4 but has not been explored in any detail. Here I outline some possible explanations and suggest that cyanophyte calcification was facilitated by enhancement of marine CaCO3 precipitation rates in the late Precam-brian because of decrease in the Mg2+/Ca2+ ratio, linked to falling levels and extensive dolomite formation. Scarcity of calcareous cyanophytes in Cenozoic marine environments again implicates the Mg2+/Ca2+ ratio, inferred from ooid mineralogy to have increased in the late Mesozoic5, as a factor influencing cyanophyte calcification in the sea.

The preservation of ultrastructure and antigenicity

Abstract: Post-fixation in osmium with complete dehydration and embedding in a tightly bonded, hydrophobic epoxide or polyester is the standard electron microscopic technique. The use of osmium ensures excellent ultrastructural detail, but impairs antigenicity and destroys enzyme activity. I t s omission, however, leads to distortion, contraction, and extraction of tissue elements, particularly if polyesters and epoxides are used (Pease, 1964). Methaerylates have been used as water-soluble, polar embedding agents with unosmicated tissue (Leduc, E.H., Bernhard W., 1967), but poor ultrastructure and retarded enzymatic or antigenic activity reduces their value. More recently the plastic 'Lowicryl K4M' (Roth e t al, 1981) has been used a t -3OOC to improve structural detail. The antigenic yield, however, is not increased, although it is claimed that the accuracy of immunolocalisation is improved. We have studied the problems of fixation and embedding in electron microscope immunocytochemistry using a versatile and sensitive immunolocalisation technique (Lasani e t al, 1980). A variety of tissues were fixed in various combinations and concentrations of glutaraldehyde, formaldehyde, and osmium, together in some instances with picric acid. Epon, HEMA, and L R White (a polar acrylic plastic) were used as embedding agents. With LR White complete or partial tissue dehydration was used. The immunolocalisation procedure was carried out on unsupported ultrathin sections on nickel grids. DAB has a high affinity for osmium, which was used, tpnly at the final stage, to increase the electron density of this immunocytochemical reaction product. Excellent antigenicity was retained after short fixation in buffered formalin-based fixatives, but ultrastructural preservation was poor. The best results were obtained when tissues were fixed for 2 3 hours in a solution of 0.1 M phosphate buffer (83 ml), 50% purified glutaraldehyde (2 ml) and picric acid (sat.aq. 15 ml) followed by embedding into LR White directly from 70% alcohol. The ultrastructure was well preserved (Plate I), particularly after perfusion-fixation, with very accurate localisation of the reaction product (Plate 2). Electron microscope immunocytochemistry involves a compromise between loss of antigenicity through fixation or antigen diffusion, and preservation of ultrastructure. Our technique uses a fixative that preserves adequate antigenicity and ultrastructure. The use of a rapid dehydration step and a polar acrylic plastic embedding agent avoids major tissue disorganisation perhaps by preserving unosmicated lipid. This simple technique allows excellent localisation of a variety of hormones and immunoglobulins; we are currently exploring i t s uses for other antigens.

Cadmium toxicity to rainbow trout, Salmo gairdneri Richardson: a study of eggs and alevins

Abstract: Cadmium toxicity to rainbow trout was evaluated at two cadmium concentrations (0.01, 0.10 mg1−1) and in water without added cadmium using eggs reared through the larval (alevin) phase to swim-up fry. Exposure to 0.1 mg Cd 1−1 promoted premature hatching, retarded growth, increased rates of mortality and the occurrence of developmental abnormalities such as spinal curvature and blood clots. Three methods of holding the eggs and alevins during the toxicity test were compared. Hatching time and success, alevin mortality, growth and development were not influenced by the method of containment but of the three methods, a subdivided perforated box system proved particularly useful for monitoring the responses of specific animals throughout the toxicity test.

Hyperpigmentation associated with oral minocycline.

Abstract: SUMMARY Two patients receiving minocycline developed blue-black pigmentation on the legs. Biopsies from the pigmented areas demonstrated granules containing iron, a pigment with staining properties similar to melanin, and a third pigment which may be a degradation product of minocycline. Electron microscopy showed that some, but not all the granules were membranebound and they were situated mainly within macrophages. Analytical electron microscopy showed that the granules contained iron, sulphur, chlorine and, in one case, calcium.