Stimulus range influences intensity and hedonic ratings of flavour

Five concentrations of an artificial orange drink were presented for sensory evaluation in three overlapping concentration ranges. Three sensory panels, each of 30 subjects, rated the concentrations for intensity of flavour (intensity scale), relation to ideal flavour intensity (ideal-point scale), and pleasantness (hedonic scale). Except for the two extreme concentrations, neither of which was presented in more than one range, in all three response tasks the mean rating for a given concentration varied with the concentration range in which it was presented. However, the mean ratings showed good correspondence across response tasks (e.g. the concentration perceived as "moderately sweet" on the intensity scale was perceived as "just right" on the ideal-point scale and of maximal pleasantness on the hedonic scale), suggesting a link between the intensity and hedonic dimensions of sensory experience.     

Arsenic uptake,cytotoxicity and detoxification studied in mammalian cells in culture

The cytotoxicity of trivalent and pentavalent inorganic arsenic salts was determined in mouse fibroblasts in vitro. Concentrations of As (III) in the M range led to a reduction of proliferation and viability with a concomitant increase in LDH release and stimulation of lactic acid production. Similar effects were noted with approximately 10-fold greater molar concentrations of As(V). Cells pretreated with a low As(III) concentration are less sensitive to toxic doses of As(III) or As(V).Uptake of As(III) by the fibroblasts is greater than that of As(V). Both forms of inorganic arsenic are converted intracellularly to monomethylarsonic (MMA) and dimethylarsinic (DMA) acids, which are then released into the culture medium. In As-pretreated cells, which are more resistant to As toxicity, biotransformation of inorganic arsenic to MMA and DMA is increased.     

Mediated smoking cessation programs in the Stanford five-city project

Two mediated smoking cessation programs were subjected to a field evaluation. The Quit Kit is a printed self-help package, and "Calling It Quits" consists of five segments which were aired on the local television news. A sample of 239 persons requested the Quit Kit and were followed. At the 2-month and 12-month follow-ups, respectively, 13.6% and 17.9% of those surveyed reported abstinence. Results indicate the potential of mediated interventions.     

Pharmacokinetics of tolfenamic acid in patients with cirrhosis of the liver

Summary Six patients with alcoholic cirrhosis of the liver received 100 mg tolfenamic acid p.o. and i.v. The disposition of tolfenamic acid could be described by a two-compartment open body model, with a mean central compartment volume of 8.71, and a -phase volume of 251. The elimination rate constant k_e averaged 1.13 h^–1 and the half-life of the -phase was 1.73 h; the mean total plasma clearance was 159 ml/min. These pharmacokinetic parameters differed only slightly from those in two groups of healthy volunteers studied previously; k_e was significantly reduced by about 30% in the patients but none of the other parameters differed significantly. There was good correlation between individual elimination rate constants or plasma clearances with the liver function tests, serum albumin and P-coagulation factors. Oral absorption was good and bioavailability of about 100% was shown by comparison of the areas under the plasma concentration — time curves after i.v. and p.o. administration. Metabolism was qualitatively and quantitatively very similar to previous observations in healthy volunteers. There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis.     

Cholinergic control of gastric acid secretion

Summary In the perfused stomach preparation of the anaesthetized rat the cholinergic agonists acetylcholine (ACh) and bethanechol stimulated gastric acid secretion. Both agonists produced similar maximal acid output (70 mol/15 min) when infused intravenously. However, bethanechol was more potent, eliciting half maximal stimulation at 1.98 mol/kg/h. Secretory responses to either agonist were antagonized in a dose related fashion by blockade of muscarinic receptors with atropine. In contrast, inhibition of nicotinic receptors with hexamethonium produced a striking potentiation of ACh stimulated secretion whilst the bethanechol elicited secretion remained unaffected. In the presence of full nicotinic receptor blockade the ACh response curve was shifted to the left sixfold, half maximal stimulation being produced at 1.79 mol/kg/h. Cimetidine partially inhibited the secretory responses elicited by either ACh or bethanechol while blockade of adrenoceptors ( and ) did not affect acid output induced by cholinergic agonists. Secretion elicited by ACh is interpreted as being the composite effect of prosecretory action and an inhibitory mechanism due to the activation of nicotinic receptors. Hexamethonium, through nicotinic receptor blockade, inhibits the restricting mechanism and thus reveals the full stimulatory action of ACh.     

Desensitization to substance P following intrathecal injection

Summary The intrathecal injection of substance P (SP) (2.5–15 g) has been shown to produce hyperalgesia in the rat tail flick test. Repeated injection of SP (7.5 or 15 g) or pretreatment with two of these doses produces desensitization to this hyperalgesic response. Desensitization is doserelated with respect to degree and duration. This phenomenon is relatively specific because the hyperalgesic response to methysergide, a serotonin receptor antagonist, is unaffected, while that produced by phentolamine, an adrenergic receptor antagonist, is much less affected than that of SP. Pretreatment with a desensitizing regimen of SP potentiates the antinociceptive effect of morphine and baclofen when they are tested immediately after the regimen but if a 30 min delay is permitted, an inhibition of their effects is observed. These results support the notion that the spinal antinociceptive effect of morphine and baclofen is due to an interaction with SP mechanisms in the spinal cord, the nature of which may be more complex than is presently understood. Desensitization produces no change in baseline responsiveness in the tail flick test. This suggests that the hyperalgesic response to SP is due either to an action at a site other than the primary afferent synapse, or if it is at this site either compensatory mechanisms occur or SP is not the primary determinant of tail flick latency but may play a modulatory role.     

Cyclic GMP and acid production in isolated gastric cells of the rat

Summary Just as cAMP is regarded as an intracellular mediator of histamine, so has cGMP been connected with cholinergic stimulation of gastric acid secretion. The object of the present investigation was to study the possible role of cellular cGMP on ¹⁴C-aminopyrine uptake, an indirect measure of parietal cell H⁺-production, by using mixtures of isolated rat gastric cells and fractions with different parietal cell content. Cellular cAMP and cGMP. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) enhanced the cAMP and cGMP of gastric cells in a time- and concentration-dependent manner, by 98 and 124% (1 mmol/l) and was included in all further studies. In parietal cell enriched fractions, histamine elevated cAMP by 109% (100 mol/l) without changing cGMP while carbachol did not influence either nucleotide. Various thiols and nitrogen compounds strongly enhanced cellular cGMP, e. g. hydroxylamine and l-cysteine (1 mmol/l) by 527 and 656%, whereas changes in cAMP were minimal. The hydroxylamine response occurred in parietal cell depleted and enriched fractions. ¹⁴ C-aminopyrine (AP) uptake. IBMX alone reduced the basal AP uptake, potentiated the effect of histamine and inhibited the effect of carbachol, which alone stimulated basal accumulation by 302%. The most efficacious stimulant of parietal cell H⁺-production was dibutyryl cAMP (582%, 100 mol/l), whereas dibutyryl cGMP was without effect. However, this latter compound (1 mmol/l) reduced AP accumulation due to dibutyryl cAMP almost completely. Thiols and nitrogen compounds all more or less reduced AP uptake.The data contraindicate the theory of a second messenger function for cGMP in cholinergic acid stimulation of the rat stomach. They show, that an increase in cGMP is associated with low H⁺-production, even if cAMP levels are raised above their resting state. Thus, the results suggest that cGMP rather mediates inhibition of acid secretion, possibly by counteracting the messenger function of cAMP.This study was supported by the Deutsche Forschungsgemeinschaft     

Measurement of 5-HIAA levels in ventricular CSF (by LCEC) and in striatum (byin vivo voltammetry) during pharmacological modifications of serotonin metabolism in the rat

Summary The relationship between the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the CSF and in the striatum has been evaluated in the rat by measuring the levels of this metabolite in ventricular CSF (by liquid chromatography coupled with electrochemical detection) and in the striatal extracellular fluid (byin vivo voltammetry) after administration of inhibitors of serotonin synthesis or degradation. Pargyline, NSD 1015 and-propyldopacetamide all caused an exponential decline of 5-HIAA in both CSF and striatum. For a given drug, the rate constants for 5-HIAA disappearance were identical in the CSF and in the striatal extracellular fluid. These results confirm the view that CSF 5-HIAA may serve as a good index of brain serotonin turnover.     

The effect of cost containment on the practice of cardiology: predictions

When health care cost containment is tied to unit pricing, the system may become price-driven rather than care-driven. Although the incentives engendered by unit pricing may not necessarily result in practices detrimental to the young or the patient with relatively pure disease, the potential for adverse effects on the elderly, the poor and the chronically ill is real. Hospitals will soon emphasize quick turnover, efficiency and intensive care. Diagnostic evaluations and chronic disease care will be moved out of hospitals into physician owned-and-operated facilities and out-of-hospital settings, respectively. The health care system will fractionate, and quality control will require restructuring to achieve the present level of quality assurance. Cardiologists, as well as other physicians, will need to alter their teaching style and teaching locations. Better methods for predicting outcomes will need to be developed; we will no longer have the safety net of following a patient closely and altering management plans according to the patient's response. Cost containment may occur under diagnosis related groups, preferred provider organizations, health maintenance organizations and other prepaid or "capped" systems. There are, however, many issues relative to cost versus quality that need to be resolved if severe detrimental effects on care are to be avoided.     

Qualitative and quantitative evaluation of the exercise electrocardiogram in assessing the degree of coronary heart disease

Exercise-induced changes in the ST segments of the electrocardiogram were compared with the results of coronary arteriography in 73 consecutive patients referred for preoperative evaluation of coronary artery disease. Eighteen patients had single-, 25 double-, and 30 triple-vessel disease. Thirteen were taking digitalis alone, 28 were taking beta blockers alone, 21 had beta blockers and digitalis and 11 had no cardiac drugs. Exercise induced elevation of the ST segment in 11 patients, all with a predominant lesion in the left anterior descending coronary artery. ST depression with an upsloping ST segment was observed in patients with one-, two-, and three-vessel disease and it was the most common type of ST change in patients with single-vessel disease. Horizontal ST depression was most common in two-vessel disease and downsloping ST segment in three-vessel disease. There was a good correlation between the number of stenosed vessels and ST changes caused by exercise, expressed as the sum of ST segment displacements in twelve leads recorded immediately after the end of exercise (sigma/ST/) or as ST depression per unit increase in heart rate during exercise ("m" (ST/HR]. The latter was obtained by linear regression of ST displacement and heart rate measured at three or four different workloads in the lead with the greatest displacement of the ST segment. The mean values of sigma/ST/ were 0.58 +- 0.030 mV in single-vessel, 0.97 +- 0.41 mV in double-vessel and 1.58 +- 0. 46 mV in triple-vessel disease. The mean values of "m" (ST/HR) were 0.0024 +- 0.0013 mV X min-1 X beat-1 in single-vessel, 0.0042 +- 0.0012 in double-vessel, and 0.0078 +- 0.0033 in triple-vessel disease. These differences were highly significant (p less than 0.01 - 0.001) and there was only minimal overlap between the single- and triple-vessel groups. Digitalis caused a slight (statistically nonsignificant) increase in sigma/ST/ but not in "m" (ST/HR).