Search PubMed⌕ Search

Biomedical subjects

S Harding

Publications and source records attributed to S Harding.

At least 73 records · Page 4Linked to original sources
PubMed1996

Characterization of the decline in alcohol consumption by aminopeptidase inhibition.

Bestatin, an aminopeptidase inhibitor, prolongs the action of angiotensin and enkephalin. Previous studies have shown that bestatin can reduce alcohol intake in heterogeneous as well as genetically selected alcohol preferring 'P' rats, but more detailed studies of the characteristics of this effect have not yet been done. In experiment 1, daily injections of 10, 20 or 40 mg/kg bestatin for 12 days produced a uniform reduction in alcohol intake (approximately 40%) which did not recover following suspension of bestatin, but did recover following a 7 day period of morphine-stimulated alcohol drinking. In experiment 2, the lower end of the dose range was explored (2.5, 5, 10 mg/kg) and a dose-dependent effect was observed with a threshold dose of 5 mg/kg. Again, alcohol drinking did not recover following suspension of the 10 mg/kg dose of bestatin. Using a limited access procedure, bestatin reduced the intake of a preferred sodium chloride solution but not an avidly-consumed glucose solution indicating that while bestatin's effect was selective, it was not specific to alcohol. In the final experiment, the role of angiotensin and enkephalin was explored by pretreating animals with losartan (5, 10, 20 mg/kg), an angiotensin receptor blocker and naltrexone, (0.25, 0.5, 1 mg/kg) an opiate receptor blocker. Both agents produced significant but rather small attenuations in bestatin's effect suggesting that other factors are involved in its action. These findings further characterize the inhibitory effect of bestatin on alcohol intake in rodents. In addition, the novel finding of a carry-over inhibition of alcohol intake in the bestatin-free period adds further impetus to the recommendation that this drug, which has been safely used in humans, might be examined as a possible therapeutic agent for alcohol abuse.

Alcohol Drinking↗
PubMed1996

Patterns of mortality in second generation Irish living in England and Wales: longitudinal study.

OBJECTIVE: To examine the mortality of second generation Irish living in England and Wales. DESIGN: Longitudinal study of 1% of the population of England and Wales (longitudinal study by the Office of Population Censuses and Surveys (now the Office for National Statistics)) followed up from 1971 to 1989. SUBJECTS: 3075 men and 3233 women aged 15 and over in 1971. MAIN OUTCOME MEASURES: Age and sex specific standardised mortality ratios for all causes, cancers, coronary heart disease, cerebrovascular diseases, respiratory diseases, and injuries and poisonings. Deaths were also analysed by socioeconomic indicators. RESULTS: 786 deaths were traced to men and 762 to women. At working ages (men, aged 15-64; women, 15-59) the mortality of men (standardised mortality ratio 126) and women (129) was significantly higher than that of all men and all women. At ages 15-44, relative disadvantages were even greater both for men (145) and for women (164). Mortality was raised for most major causes of death. Significant excess mortality from cancers was seen for men of working age (132) and for women aged 60 and over (122). At working ages mortality of the second generation Irish in every social class and in the categories of car access and housing tenure was higher than that of all men and all women in the corresponding categories. Adjusting for these socioeconomic indicators did not explain the excess mortality. CONCLUSION: Mortality of second generation Irish men and women was higher than that of all men and all women and for most major causes of death. While socioeconomic factors remain important, cultural and lifestyle factors are likely to contribute to this adverse mortality.

Adolescent↗
PubMed1996

Neurotensin attenuates the reduction in alcohol drinking produced by angiotensin II.

Neurotensin enhances some of the behavioral effects of alcohol including motor impairment, narcosis, hypothermia and also interacts with some of the physiological actions of angiotensin (ANG) II including aldosterone release and increased blood pressure. ANG II injections also produce a dose-dependent antagonist reversible reduction in alcohol drinking. The present study is the first to examine the interaction between neurotensin and angiotensin in the behavioral context of oral alcohol self-administration. Adult male Wistar rats acquired alcohol drinking (6% w/v) using the limited access procedure which makes alcohol available for 40 min every day. When intake stabilized ANG II (400 micrograms/kg per day) or vehicle were administered subcutaneously (SC) just prior to alcohol availability but only the group receiving ANG II showed a marked reduction in alcohol intake. Following this the groups were pretreated sc with either vehicle or ascending doses of neurotensin (5, 10, 20 micrograms/kg) followed by either ANG II or vehicle. Control groups received either two vehicle injections or vehicle and neurotensin injection. Neurotensin alone did not affect alcohol intake at any of the doses tested but did attenuate, in a dose-dependent fashion, the reduction in alcohol intake produced by ANG II. These results demonstrate neurotensin's ability to alter the behavioral effect of ANG II on alcohol intake.

Alcohol Drinking↗
PubMed1996

A controlled clinical trial for stuttering in persons aged 9 to 14 years.

This paper presents the results of a controlled trial of child stuttering treatment. The aim of the study was, first, to compare the effectiveness of three viable treatments, and, second, to compare these three treatments to a no-treatment control composed of children who stuttered of a similar age and sex ratio who were on treatment waiting lists. The three treatments investigated included intensive smooth speech, intensive electromyography feedback, and home-based smooth speech. The children/adolescents were assessed across three speaking contexts on measures of percentage syllables stuttered (% SS) and syllables spoken per minute (SPM) and outcomes were assessed 12 months later. Repeated measures analyses of variance demonstrated significant differences between the control group and all three treatment groups across time on conversations in the clinic, on the telephone, and at home (although home measures were not taken for the intensive smooth speech group). Although the controls' stuttering did not change across time, the treatment groups' stuttering was decreased to very low levels posttreatment (less than 1% syllables stuttered on average), with mean improvement in stuttering frequency of at least 85% to 90% across all assessment contexts. Stuttering did not increase significantly up to 3 months and one year posttreatment in the experimental groups, although levels did rise across time (less than 3% syllables stuttered on average). Speech naturalness results showed increasing naturalness across time as rated by the clinician and parent. This was not the case for the controls. The children were also less anxious across time following treatment. The results suggest that all three treatments for children aged 9-14 who stutter were very successful in the long term for over 70% of the group, though the EMG feedback and home-based treatments were superior when percentages falling below a cutoff point (2%SS) were used to discriminate between groups. Implications for child/adolescent treatment in the community are discussed. Long-term outcomes will be assessed up to 5 years after the treatment.

Adolescent↗
PubMed1996

Relaxation: with or without imagery?

Although the benefits of relaxation are widely recognized, clinicians need to remain cognizant of its possible adverse effects. Equally, some people with mental illness may experience an exacerbation of their symptoms with the injudicious use of relaxation techniques that use imagery. This paper explores two conditions where vivid, often emotionally charged, images are problematic: (i) post traumatic stress disorder; and (ii) hallucinoses. Individuals who have these disorders may have difficulty controlling shifts between these internal and external events, or difficulty even recognising events as internal rather than external. Employing a relaxation technique that encourages imagery is likely to produce a stronger reaction because the impact of the imagery is increased by relaxation. This would result in an increase in arousal, the antithesis of relaxation. This paper suggests that relaxation techniques that avoid imagery or consider the patient's experience would be less likely to provoke unwanted reactions.

Arousal↗
PubMed1996

Effect of bestatin, an aminopeptidase inhibitor, on alcohol intake in alcohol-preferring P rats.

Bestatin is an aminopeptidase and enkephalinase inhibitor that elevates the levels of angiotensin II and angiotensin III. Although it has been used for years in the treatment of various forms of cancer, its application as an antialcohol drug has not been explored, despite its ability to stimulate angiotensin activity. The present study assesses the ability of bestatin to reduce chronic alcohol consumption in the genetically selected high alcohol-consuming P rats. Two groups of P rats were given 24-hr access to food, water, and 10% (v/v) alcohol. After a baseline period, half the rats received the saline vehicle and the other half ascending doses of bestatin (2.5, 10, 20, and 30 mg/kg, bid). Each dose was administered for a minimum of 7 days. Bestatin had little effect on water intake or weight gain, but did produce a dose-dependent reduction in alcohol intake that averaged 33% and was sustained over the course of the 1-month period of administration. Years of experience with bestatin have shown it to be safe and free of major side effects. The present findings suggest that bestatin (Ubenimex) might also be useful in the treatment of alcohol abuse in humans.

Alcohol Deterrents↗
PubMed1996

Angiotensin II and contraction of isolated myocytes from human, guinea pig, and infarcted rat hearts.

The effects of angiotensin II on myocardial contractility were assessed in isolated cardiac myocyte preparations, using video microscopy with a computerized edge-detection system. Angiotensin II (1 nM-10 microM) did not affect the contraction of rat (n = 10), guinea pig (n = 11), or human ventricular myocytes (n = 8) or of human atrial myocytes (n = 12). Isoproterenol or raised extracellular calcium increased the contraction amplitude of the cardiac myocytes to a maximum of between 150 and 560% above basal, and there were corresponding increases in the velocities of contraction and relaxation. In rat and guinea pig ventricular myocytes 1 microM angiotensin II did not affect the inotropic response to isoproterenol. Seven days after left coronary artery ligation in seven rats, the basal contraction amplitude was reduced in myocytes from the infarcted region (4.0 +/- 1.9%) compared with the noninfarcted region (5.0 +/- 2.8%, P = 0.03) and with myocytes from six sham-operated hearts (5.0 +/- 2.8%, P = 0.03). There was a switch in myosin isoform expression from the V1 to the V3 isoform in myocytes from both the infarcted and noninfarcted regions. Angiotensin II (1 nM-10 microM) had no significant effect on the contraction characteristics of myocytes from the infarcted rat hearts. In conclusion, angiotensin II had no significant inotropic effect on isolated cardiac myocyte preparations from guinea pig ventricle, normal and infarcted rat ventricle, human ventricle, and human atrium.

Adult↗
PubMed1996

Sources and uses of data on cancer among ethnic groups.

This paper identifies the data sources available in OPCS on cancer among ethnic groups, shows some of the findings of previous analyses and outlines the potential for further analyses and data collection. The main source of data comes from the registration of deaths in which country of birth of the decreased is recorded. Other sources of data include the General Household Survey (GHS) which enables analyses of risk factors such as smoking, alcohol and contraception. Data on cancer incidence among ethnic groups is currently limited. However in the future, both the Longitudinal Study and cancer registration data should provide measures of cancer incidence among ethnic groups.

Adult↗
PubMed1996

Initial results of the Osteo Ti implant system in general dental practice.

It is the purpose of this paper to present the preliminary results of 370 consecutively placed Osieo-Ti implants. Two stage screw form endosseous implants ranging in length from 7mm to 20mm in one mm increments were used. Four diameters of implant 2.75mm, 3.00mm, 3.75mm and 4.50mm were used to engage the maximum available width of bone. The larger, 3.75mm and 4.50mm diameter, implants were made from commercially pure titanium and the two smaller diameter, 2.75mm and 3.00mm, implants were manufactured from titanium alloy. The overall success rate for 370 exposed functioning Osteo-Ti implants was 98.6%.

Alveolar Bone Loss↗
PubMed1995

Mycobacterium tuberculosis chaperonin 10 forms stable tetrameric and heptameric structures. Implications for its diverse biological activities.

The chaperonin activity of sequence-related chaperonin 10 proteins requires their aggregation into heptameric structures. We describe size-exclusion chromatography and ultracentrifugation studies that reveal that while Escherichia coli chaperonin 10 exists as a heptamer, the Mycobacterium tuberculosis chaperonin 10 is tetrameric in dilute solutions and in whole M. tuberculosis lysate. At high protein concentration and in the presence of saturating amounts of divalent ions, the protein is heptameric. Human chaperonin 10 is predominantly heptameric, although smaller oligomers were detected. These differences in structural assembly between species may explain differences in biological activity such as antigenicity. Using C-terminal and N-terminal fragments, sequence 1-25 was identified as indispensable for aggregation. CD spectroscopy studies revealed that (i) a minimum at 202-204 nm correlates with aggregation and characterizes not only the spectrum of the mycobacterial protein, but also those of E. coli and human chaperonin 10 proteins; (ii) the interactions between subunits are of the hydrophobic type; and (iii) the anti-parallel beta-pleated sheet is the main secondary structure element of subunits in both tetrameric and heptameric proteins.

Amino Acid Sequence↗
PubMed1995

Intracerebroventricularly infused angiotensin II or III do not alter voluntary alcohol intake in rats.

Subcutaneous injections of angiotensin (ANG) II or III in the periphery reduce alcohol intake and raise water intake. These peptides do not cross the blood-brain barrier and cannot reach the angiotensin receptor-rich sites surrounding the lateral and third ventricles. To examine the effect on alcohol intake of ANG II and III at these ventricular sites, groups of rats were first trained to drink alcohol using a limited access procedure, then surgically prepared with chronic indwelling lateral or third ventricular cannulae, and then reoffered daily 40-min access to alcohol. Neither ANG II (25-200 ng) nor ANG III (25-100 ng) had any effect on alcohol consumption at either of the two ventricular sites. Water consumption was significantly enhanced by both peptides at both sites and could be attenuated by prior treatment with the ANG II antagonist Sar1Thr8-ANG II. The SC administration of ANG II was able to produce a significant reduction in alcohol drinking. These findings demonstrate that ICV administered ANG II or ANG III do not modulate alcohol drinking and that changes in alcohol intake do not result from the thirst promoted by ANG II. Sites in the periphery may be more involved in the interaction between angiotensin and alcohol consumption.

Alcohol Drinking↗
PubMed1995

Lack of evidence for a circadian rhythm of IGFBP-1 in the mother and fetus during labour.

OBJECTIVE: To determine whether the circadian rhythm of circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) is evident at the time of delivery. DESIGN: Prospective observational study in six pregnant women and cross-sectional study in 65 women at the time of delivery. SUBJECTS: Six pregnant women sampled over a period of 24 hours, 23 women sampled at the time of elective caesarean section, and 42 women sampled at the time of vaginal delivery. RESULTS: In the women sampled serially over a 24 hour period there was an obvious circadian rhythm of IGFBP-1 with a peak between 01.00 and 09.00 hours. In the women sampled at the time of delivery there was no evidence for any relationship between the time of delivery and maternal or fetal levels of IGFBP-1. CONCLUSIONS: The circadian rhythm of IGFBP-1 is not observed in women in labour. Therefore, the time of day is not an important confounding variable in studies on IGFBP-1 levels at the time of normal delivery.

Cesarean Section↗
PubMed1995

Social class differences in mortality of men: recent evidence from the OPCS Longitudinal Study. Office of Population Censuses and Surveys.

Social class differences in male mortality by age and cause of death are presented using the most recently available data (1976-89) from the OPCS Longitudinal Study. Consistent differences in mortality by social class (as defined by occupation) are found through to the late 1980s. On a scale of increasing mortality disadvantage, mortality of men in Social Class I was the lowest and mortality of men in Social Class V was the highest.

Adolescent↗
PubMed1995

Ethnic minorities. The role of health advocates in health visiting teams.

An east London project placed health advocates in health visiting teams to explore ways to deliver a better service to ethnic minority clients. Sonia Harding and Neeta Pandya report on the project, funded by London Implementation Zone monies, which resulted in recommendations for the development of the role and practice of health advocates, including independent home visiting.

Community Health Nursing↗
PubMed1994

Adrenalectomy does not modify the suppressive effect of angiotensin II on voluntary ethanol drinking in rats.

Enhancement of activity in the renin-angiotensin system reduces voluntary ethanol consumption in rats. Because angiotensin II, which is a major bioactive component of the renin-angiotensin system, stimulates the release of aldosterone, aldosterone may play a role in the reduction of ethanol intake by angiotensin II. The present study examined ethanol drinking in a group of rats that was bilaterally adrenalectomized and incapable of producing aldosterone, and in a sham group that underwent similar surgery except that the adrenal glands were left intact. Rats were maintained on ad libitum food, water and 1.5% saline solution in their home cages. Access to ethanol (6% weight/volume) was restricted to a daily 40 min period and was always offered as a choice in conjunction with water. Adrenalectomy did not alter the effect of angiotensin II on ethanol intake as subcutaneous injections of angiotensin II (400 micrograms/kg) significantly reduced ethanol intake to the same degree in both the adrenalectomized and sham groups. In the next phase, daily subcutaneous injections of aldosterone (100 micrograms/kg) reduced the home cage intake of 1.5% saline in the adrenalectomized group indicating that this dose of aldosterone was biologically active. These aldosterone injections did not affect ethanol intake in either the adrenalectomized or sham groups. Under the present conditions of testing aldosterone does not appear to play a role in the angiotensin II-induced reduction of ethanol consumption.

Adrenalectomy↗
PubMed1994

The effects of labor on maternal and fetal levels of insulin-like growth factor binding protein-1.

OBJECTIVE: Our purpose was to determine the effects of labor and fetal hypoxia on the levels of insulin-like growth factor binding protein-1 in the maternal and fetal circulation. STUDY DESIGN: Serum levels of insulin-like growth factor binding protein-1 were determined in maternal and umbilical blood at delivery in two groups. The first group included 43 vaginal deliveries and 23 elective cesarean sections. The second group consisted of 44 women; in 24 the liquor was meconium stained and in 20 it was clear. RESULTS: Levels of insulin-like growth factor binding protein-1 in the neonate were lower in deliveries occurring before onset of labor (p < 0.001), Mann-Whitney U test) and higher in cases with severe meconium staining (p = 0.01). There were no differences in maternal levels of insulin-like growth factor binding protein-1 between subjects in labor and not in labor or those with or without meconium staining. CONCLUSION: The process of labor leads to an increase in fetal levels of insulin-like growth factor binding protein-1. This increase may well be associated with the relative fetal stress that occurs during labor. This suggestion is supported by the finding of the highest levels in labors in which there was thick staining of the liquor.

Adolescent↗