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S Harding

Publications and source records attributed to S Harding.

At least 91 records · Page 5Linked to original sources
PubMed1994

The reduction in alcohol drinking by peripherally injected angiotensin II is selectively mediated by the AT1 receptor subtype.

We investigated which of the two angiotensin (ANG) receptor subtypes mediates the reduction in alcohol intake produced by peripheral injections of ANG II. Adult male Wistar rats were trained to self-administer alcohol (6% w/v) using a procedure that, by limiting access to a brief daily availability period (40 min), fosters a bout pattern of alcohol drinking and a pharmacodynamic effect. Water was continuously available. Once intake stabilized, groups received daily injections either 200 micrograms/kg ANG II SC or the control vehicle saline immediately prior to alcohol availability. Alcohol consumption was attenuated and water intake elevated in the groups receiving ANG II and was unaffected by the vehicle injections. Following this, different groups were pretreated with ascending doses (0.25, 0.5, 1.0 mg/kg) of either PD123319, the selective AT2 receptor antagonist, Sar1,Thr8-ANG II (0.25 mg/kg), the nonselective ANG II antagonist, or DuP753 (0.25, 0.5, 1.0 mg/kg), the selective AT1 receptor antagonist. Control groups received antagonist pretreatment followed by the ANG II vehicle. Neither PD123319, DuP753, or Sar1, Thr8-ANG II had any effect of their own on alcohol or water intake. Pretreatment with PD123319 did not alter the suppressive effect of ANG II on alcohol intake. DuP753 produced a dose-dependent attenuation in the suppressive effect of ANG II on alcohol intake and antagonized the dipsogenic effect of ANG II on water intake. The effect of Sar1,Thr8-ANG II was similar to that of DuP753. These findings suggest that the reduction in alcohol intake produced by ANG II is mediated through the AT1 receptor subtype.

Alcohol Drinking↗
PubMed1994

Social patterning of medical mortality in youth and early adulthood.

It has been suggested that socio-economic gradients in health reduce or disappear during youth, to be re-created during early adulthood through a process of health-related social mobility. The present analysis tests this hypothesis in relation to 'medical mortality', using a data set which is free of numerator-denominator bias. The sample consists of the appropriate age groups in the OPCS Longitudinal Study; 62,647 males and 59,644 females aged 0-14 at the 1971 census. 'Medical mortality' during 1971-1985, calculated as standardised mortality ratios, is analysed by parental social class, housing tenure and car access in 1971. 'Medical mortality' during 1981-1985 is analysed by own social class in 1981. The results suggest that 'medical mortality' is inversely related to social advantage at ages of death 0-9 years, that this gradient flattens or disappears at ages 10-14 and that it re-emerges at ages 15-29. Within the present analysis this apparent re-emergence could not have been due to health-related social mobility. It is concluded that the apparent absence of socio-economic gradients in 'medical mortality' during youth may be an artefact of the high levels of health enjoyed by this age group and its consequent low levels of non-accidental death.

Adolescent↗
PubMed1994

Distribution of unlinked receptor sites for transposed Ac elements from the bz-m2(Ac) allele in maize.

We have shown before that the Ac element from the maize bz-m2(Ac) allele, located in the short arm of chromosome 9 (9S), transposes preferentially to sites that are linked to the bz donor locus. Yet, about half of the Ac transpositions recovered from bz-m2(Ac) are in receptor sites not linked to the donor locus. In this study, we have analyzed the distribution of those unlinked receptor sites. Thirty-seven transposed Ac (trAc) elements that recombined independently of the bz locus were mapped using a set of wx reciprocal translocations. We found that the distribution of unlinked receptor sites for trAs was not random. Ten trAcs mapped to 9L, i.e., Ac had transposed to sites physically, if not genetically, linked to the donor site. Among chromosomes other than 9, the Ac element of bz-m2(Ac) appeared to have transposed preferentially to certain chromosomes, such as 5 and 7, but infrequently to others, such as 1, the longest chromosome in the maize genome. The seven trAc elements in chromosome 5 were mapped relative to markers in 5S and 5L and localized to both arms of 5. We also investigated the transposition of Ac to the homolog of the donor chromosome. We found that Ac rarely transposes from bz-m2(Ac) to the homologous chromosome 9. The clustering of Ac receptor sites around the donor locus has been taken to mean that a physical association between the donor site and nearby receptor sites occurs during transposition. The preferential occurrence of 9L among chromosomes harboring unlinked receptor sites would be expected according to this model, since sites in 9L would tend to be physically closer to 9S than sites in other chromosomes. The nonrandom pattern seen among the remaining chromosomes could reflect an underlying nuclear architecture, i.e., an ordering of the chromosomes in the interphase nucleus, as suggested from previous cytological observations.

Alleles↗
PubMed1993

Thromboembolism coincident with tourniquet deflation during total knee arthroplasty.

Despite prophylactic therapy, pulmonary embolism remains the leading cause of perioperative mortality in patients undergoing total knee arthroplasty (TKA). We used transoesophageal echocardiography to monitor 29 consecutive patients during TKA. Showers of substantial amounts of echogenic material, lasting for 3-15 min, were visible in the right atrium and ventricle within 10-15 s of tourniquet deflation in all patients. A 3 x 6 mm fresh thrombus was aspirated from the central circulation of one patient. Another patient, who had had a Greenfield filter placed for previous thromboembolism, showed very little echogenic material after tourniquet deflation. The composition and importance of these echogenic emboli remain uncertain.

Adult↗
PubMed1993

Bradykinin suppresses alcohol intake and plays a role in the suppression produced by an ACE inhibitor.

The possible role of the endogenous kinins in the control of alcohol intake was assessed in two experiments. In Experiment 1, naive rats, maintained on ad lib food and water, were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal (IP) injections of captopril (20 mg/kg) significantly reduced alcohol intake, while pretreatment with subcutaneous (SC) injections of the bradykinin antagonist [D-Phe7]-bradykinin (100-300 micrograms/kg) attenuated the suppressive effect of captopril on alcohol intake. The saline vehicle or the bradykinin antagonist alone did not alter alcohol intake. In Experiment 2, bradykinin was administered daily at 100, 200, and 400 micrograms/kg doses SC either alone or in combination with captopril 10 mg/kg IP. Neither bradykinin nor captopril by themselves changed alcohol or water intake. Bradykinin combined with captopril stimulated water intake and reduced alcohol intake by up to 70%. This effect was not due to drug-induced changes in the pharmacokinetics of alcohol. The angiotensin II receptor antagonist [Sar1,Thr8]-angiotensin II at 250 and 500 micrograms/kg SC attenuated the stimulation of water intake but not the reduction in alcohol intake. It is suggested that by inhibiting kininase II, ACE inhibitors extend the duration of action of bradykinin and thereby unmask a potent inhibition of alcohol intake mediated by kinins--an effect that is dissociable from the accompanying stimulation of water intake. Taken together, these results point to an involvement of the kinin system in the regulation of alcohol intake and in particular to a role of bradykinin in the suppressive effect of ACE inhibitors on alcohol intake.

Alcohol Deterrents↗
PubMed1993

Captopril and hydrochlorothiazide (Capozide) combine to enhance the reduction in voluntary alcohol intake in rats.

The effect of Capozide, the combination of captopril with a hydrochlorothiazide diuretic, on voluntary alcohol intake was assessed in two experiments. In experiment 1 naive rats who were maintained on ad libitum food and water were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal injections of captopril (10 mg/kg) reduced alcohol intake, but the combination of captopril (5 and 10 mg/kg) and hydrochlorothiazide (2.5, 5, and 10 mg/kg) enhanced the reduction in intake. In experiment 2, captopril alone, hydrochlorothiazide alone, and the combination of captopril and hydrochlorothiazide were again administered daily in the limited access procedure. Captopril (10 mg/kg) again reduced alcohol intake as did all three doses of hydrochlorothiazide (2.5, 5, and 10 mg/kg). Compared with the individual effects of captopril and hydrochlorothiazide, Capozide exerted a supra-additive reduction in alcohol intake. These effects were not due to drug-induced changes in the pharmacokinetics of alcohol. Taken together these results demonstrate an enhanced potency of Capozide in suppressing alcohol intake and invite their testing in a population of hypertensive alcoholics and alcohol abusers.

Alcohol Drinking↗
PubMed1993

Reduction of ethanol intake by aerosol inhalation of a beta-adrenergic agonist: new route--new treatment approach?

The quick, convenient, unobtrusive administration of a low dose of a drug that effectively reduces alcohol intake could be a useful adjunct to any program that aims to treat alcohol abuse. This study evaluates the ability of isoproterenol, a drug that has previously been shown to reduce ethanol intake, to exercise this action when administered as a metered aerosol mist. Rats were trained to self-administer ethanol using a procedure that limits access to a brief daily availability period. Once intake stabilized, animals were given isoproterenol by metered aerosol inhalation just before ethanol availability. A custom-designed helmet attached to a commercially available mistometer was used to deliver the drug. Isoproterenol produced a dose-dependent reduction in ethanol intake and an increase in water intake replicating the effects of parenterally administered isoproterenol on ethanol and water consumption. These findings demonstrate that the administration of isoproterenol in inhaled aerosol form can effectively reduce voluntary ethanol consumption in rats. The administration of pharmacologically active antialcohol agents via the inhalation route may be useful in the symptomatic treatment of alcohol abuse in humans.

Administration, Inhalation↗
PubMed1991

A prospective study of oral Nadolol in the management of patients with newly diagnosed chronic simple glaucoma.

Thirty patients with newly diagnosed chronic open angle glaucoma were initially treated with once daily oral Nadolol at a dose of 20 mg. This was increased to 40 mg where control was considered inadequate. Topical therapy was then added as necessary if control was still not maintained. Significant decreases in intra-ocular pressure (IOP) were achieved with a dose of 20 mg, but there was no significant further reduction when the dose was increased to 40 mg. One patient was controlled throughout the study period with 40 mg Nadolol daily and 4% Pilocarpine four times daily. At best, only temporary control was achieved in the remaining 29 patients. Intra-ocular pressures were measured 24 hours after the previous dose of Nadolol in 13 patients who were controlled for a minimum of 1 month on Nadolol alone and then again 3 hours after their normal dose. Control of IOP was lost in all patients at 24 hours pre-dose but was regained by 3 hours post-dose. Four patients were withdrawn because of mild side effects attributable to the beta-blocking action of Nadolol. The treatment regime used in this study was ineffective at controlling the IOP in the group of patients studied. A once daily regime of Nadolol does not control IOP over a full 24 hours.

Administration, Oral↗
PubMed1991

Doubled-masked three-period crossover investigation of metipranolol in control of raised intraocular pressure.

Metipranolol is a non-cardioselective beta adrenergic blocking drug used in the treatment of glaucoma. 56 patients with intraocular pressure between 30-49 mm hg were randomised to one of six treatment regimens for a 12 week period. Each patient received each concentration for 4 weeks and intraocular pressures were checked every two weeks. Using a worst and an average eye approach, mean initial intra-ocular pressures were 35.8 and 35.0 mm hg respectively. The mean fall in intra-ocular pressure after 4 weeks treatment ranged from 12.8 (0.1%) to 14.1 mm hg (0.6%) for average eyes (n = 56), and from 13.4 to 16.7 mm hg for worst eyes. These differences were not statistically significant (p greater than 0.05-p greater than 0.5). Increasing the concentration had no significant effect on pressure. Reducing the concentration had no effect except in patients who changed from 0.6% to 0.1%, when there was a mean rise of approximately 2 mm hg, p less than 0.02. The incidence of stinging varied from 19% of attendances on 0.1%, to 63% on 0.6%. We recommend the use of the 0.1% strength since all three significantly lower intra-ocular pressure but the higher concentrations are more expensive, cause more stinging, and are no better at lowering intra-ocular pressure.

Adult↗
PubMed1990

Inheritance and effect on ripening of antisense polygalacturonase genes in transgenic tomatoes.

The role of the cell wall hydrolase polygalacturonase (PG) during fruit ripening was investigated using novel mutant tomato lines in which expression of the PG gene has been down regulated by antisense RNA. Tomato plants were transformed with chimaeric genes designed to express anti-PG RNA constitutively. Thirteen transformed lines were obtained of which five were analysed in detail. All contained a single PG antisense gene, the expression of which led to a reduction in PG enzyme activity in ripe fruit to between 5% and 50% that of normal. One line, GR16, showed a reduction to 10% of normal PG activity. The reduction in activity segregated with the PG antisense gene in selfed progeny of GR16. Plants homozygous for the antisense gene showed a reduction of PG enzyme expression of greater than 99%. The PG antisense gene was inherited stably through two generations. In tomato fruit with a residual 1% PG enzyme activity pectin depolymerisation was inhibited, indicating that PG is involved in pectin degradation in vivo. Other ripening parameters, such as ethylene production, lycopene accumulation, polyuronide solubilisation, and invertase activity, together with pectinesterase activity were not affected by the expression of the antisense gene.

Food Technology↗
PubMed1990

Intracerebroventricular morphine enhances alcohol consumption by rats.

Previous experiments have shown that systemically administered low doses of opioid agonists increase subsequent alcohol consumption by rats. In this experiment, 10 micrograms of morphine were infused intracerebroventricularly (ICV) in free-feeding rats, daily for 6 days, 30 min prior to one-hour access to a 12% alcohol solution. Alcohol consumption was significantly increased in the morphine-treated group compared to that of a saline-treated control group, confirming that the locus of the effect is within the central nervous system.

Alcohol Drinking↗
PubMed1990

A comparison of different methods for calculating overall risk scores from risk factors ascertained in a computerized obstetric information system.

Current obstetric risk-scoring systems depend upon simple addition of weighted or unweighted risk factors. In this study a population of 994 pregnant women (470 primiparae; 524 multiparae) has been examined in order to compare the use of weighted and unweighted risk scores, together with Bayes theorem, in estimating an overall risk score from the presence of individual risk factors. The findings have been related to fetal outcome in these pregnancies and expressed as receiver-operating characteristic (ROC) curves for different cutoff levels between normal and abnormal. In primiparae, the use of weighted risk factors, with or without Bayes theorem, was clearly superior to the use of unweighted factors. In multiparae there was only a marginal difference between the three approaches. The increasing use of computerised information system in antenatal care should make calculation of risk scores for every pregnant woman a practical option.

Adolescent↗
PubMed1990

[Effect on atrioventricular conduction of a new calcium antagonist: lacidipine. Evaluation by the Holter method].

The modification of AV conduction induced by 4 mg b.i.d. of lacidipine (L), a new calcium antagonist, was assessed by studying the changes in ventricular rhythm in 10 patients with stable chronic atrial fibrillation (mean age 71 +/- 15) by daily Holter recordings. The study was single blind versus placebo (P), nifedipine (N) 10 mg b.i.d. and for five patients diltiazem (D) 120 mg b.i.d. Five or seven consecutive 24 hours Holter were recorded in the following order: P, P, N or L, P, N or L, D, D. For each hour, an RR histogram was drawn and the 10 per cent and 90 per cent values of the cumulative cycle length curve were computed, as were the total number of QRS, and the mean value of RR intervals. The correlation coefficient between the number of QRS from the same hour on different days, the Student t test between the mean hourly RR interval values and the comparison between the histograms did not demonstrate a significant difference between the placebo, the nifedipine and the lacidipine periods. The only significant changes were induced by diltiazem (p less than 0.01), with a significant prolongation of the RR intervals. This suggests that lacidipine, like nifedipine, has no effect on AV conduction.

Aged↗
PubMed1989

Alcohol consumption following bidirectional shifts in body weight in rats.

Weight restriction has frequently been used to induce consumption of pharmacologically significant amounts of alcohol by rats. When previously weight-restricted rats are fed ad lib., however, their alcohol consumption is substantially reduced. This could occur because weight restriction per se causes increased alcohol consumption, or because the stimulus conditions (in this case, largely interoceptive) that were originally associated with drinking have changed, resulting in a stimulus generalization decrement. The present experiment was designed to discriminate between these two possibilities. Two groups of animals, one at free-feeding weight (FFW) and one at 80% FFW were initially trained to drink alcohol in a limited access paradigm. Each group was then divided into two, such that one half remained at its original weight and the other was gradually shifted to the reverse feeding condition in a double cross-over design. When alcohol consumption was again stable the experimental groups were returned to their original weights. If the weight restriction hypothesis were true, animals should drink more when weight-reduced and less when at FFW. According to the stimulus generalization decrement hypothesis, drinking should decrease with any shift from their initial weight. The direction of the results was such as to support the weight restriction hypothesis, but the magnitude of the changes was greater than would be expected on the basis of the respective control groups, and the effects were often transient. In these ways the results more closely resembled positive and negative contrast effects that have traditionally been described following shifts in amount of reinforcement. Possible mechanisms and the importance of an animal's history as a determinant of alcohol consumption are discussed.

Alcohol Drinking↗
PubMed1989

The relationship of conjunctival and arterial blood gas oxygen measurements.

Conjunctival oxymetry (CjO2) measures peripheral tissue oxygen at the conjunctival level. CjO2 changes can indicate pulmonary or circulatory conditions leading to shock. Literature review does not define 'normal' CjO2/ABG PaO2 ratios. We designed a study to measure these ratios. Twenty-two healthy patients undergoing cardiac catheterization had simultaneous PcjO2 and PaO2 measurements completed. The range of conjunctival oxygen measurements was from 34 to 68 mmHg with a mean of 50.5 mmHg. The PaO2 readings ranged from 65 to 93 mmHg with a mean of 77.1 mmHg. The average PcjO2/PaO2 ratio was 0.656 with a range of 0.47-0.93. Thus the PcjO2 is on average 66% of the arterial blood gas PaO2. This ratio of 0.66 can serve as a base for further clinical studies in which PcjO2 is looked at in patients with pulmonary or circulatory illnesses or injuries.

Adult↗
PubMed1988

Use of conjunctival oxygen monitoring in cardiac patients in the emergency unit.

Conjunctival oxygen monitoring (PcjO2) measures conjunctival tissue organ. It has proved useful in helping to evaluate hypovolemic multiple trauma patients, carotid artery surgery patients, as well as others. Little has been written about its use during medical resuscitations. This report reviews its accident and emergency department use in 13 cardiac arrest/life-threatening cardiac dysrhythmia patients. Nine patients expired and four patients survived. Accident and emergency department PcjO2 values in the group which expired averaged 6.3. Those patients who survived averaged 35.4. Subjects who maintained PcjO2 values below 20 did not survive. Furthermore, PcjO2 values taken within the first 8 min of accident and emergency department resuscitation appear to indicate outcome. Conjunctival oxygen monitoring may be useful in monitoring critically ill cardiac patients in the accident and emergency department.

Arrhythmias, Cardiac↗
PubMed1984

Training increases [3H]fucose incorporation in chick brain only if followed by memory storage.

Incorporation of [3H]fucose into glycoproteins is increased in the forebrain base and anterior forebrain roof of day-old chicks following passive avoidance training. In chicks trained but rendered apparently amnestic by immediate transcranial electroshock, the increased incorporation by comparison with untrained-shocked birds was abolished. If the electroshock was delayed by 10 min, the chicks showed recall for the task and fucose incorporation was increased by comparison with untrained but shocked or trained and immediate-shocked birds. We conclude that the increased incorporation of [3H]fucose is not a result of any concomitant of training but is directly associated with engram formation.

Amnesia↗