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R Brooks

Publications and source records attributed to R Brooks.

At least 19 recordsLinked to original sources
PubMed1998

The double-stranded RNA-binding domains of Xenopus laevis ADAR1 exhibit different RNA-binding behaviors.

We have cloned cDNAs encoding two versions of Xenopus double-stranded RNA adenosine deaminase (ADAR1). Like ADAR1 proteins from other species Xenopus ADAR1 contains three double-stranded RNA-binding domains (dsRBDs) which are most likely required for substrate binding and recognition of this RNA-editing enzyme. Analysis of mammalian ADAR1 identified the third dsRBD in this enzyme as most important for RNA binding. Here we analyzed the three dsRBDs of Xenopus ADAR1 for their in vitro RNA-binding behavior using two different assays. Northwestern assays identified the second dsRBD in the Xenopus protein as most important for RNA binding while in-solution assays demonstrated the importance of the third dsRBD for RNA binding. The differences between these two assays are discussed and we suggest that both the second and third dsRBD of Xenopus ADAR1 are important for RNA binding in vivo. We show further that all three dsRBDs can contribute to a cooperative binding effect.

Adenosine Deaminase↗
PubMed1998

The role of bradykinin in the regulation of blood flow to hindlimb muscle groups of the anaesthetized cat.

1. Male cats were anaesthetized with alphaxalone-alphadolone and breathed spontaneously following tracheotomy, Using coloured microspheres, muscle blood flow was measured at rest and during two periods of contraction elicited by simultaneous stimulation of the left sciatic and femoral nerves at 3 Hz for 10 min. In one group, the hindlimb blood flow was allowed to increase during muscle contraction and in another group the perfusion of the hindlimb was limited by a stenosis on the left external iliac artery. 2. In the absence of flow restriction, soleus muscle blood flow increased from 18.9 +/- 3.8 to 30.4 +/- 3.3 ml min-1 (100 g tissue)-1 (n = 6; P < 0.02) and gastrocnemius muscle blood flow increased from 24.8 +/- 5.9 to 61.6 +/- 12.8 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) during contraction. The bradykinin (BK) antagonists HOE 140 (1 mg kg-1, i.v.) did not affect the response in either the soleus (37.7 +/- 7.3 ml min-1 (100 g tissue)-1; n = 6; n.s.) or the gastrocnemius (62.9 +/- 7.9 ml min-1 (100 g tissue)-1; n = 6; n.s.) muscles. 3. In the stenosis group, soleus muscle blood flow increased from 9.8 +/- 2.3 to 22.9 +/- 4.9 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) and gastrocnemius muscle blood flow increased from 15.8 +/ 3.4 to 36.4 +/- 5.5 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) during contraction. Following administration of HOE 140, functional hyperaemia in the soleus muscle was unaffected (blood flow, 17.8 +/- 2.2 ml min-1 (100 g tissue)-1, n = 6; n.s.) white blood flow in the gastrocnemius muscle was reduced to 21.8 +/- 6.0 ml min-1 (100 g tissue)-1 (n = 6; P < 0.05). 4. The results show that BK does not contribute ot functional hyperaemia associated with twitch contraction at 3 Hz when blood flow is unrestricted, but may contribute up to 40% of the vasodilation of predominantly glycolytic muscle groups such as the gastrocnemius when flow is restricted. BK plays no role in hyperaemia associated with twitch contraction of oxidative muscle groups such as the soleus.

Anesthesia↗
PubMed1998

Infant feeding practices in Barbados predict later growth.

This longitudinal study was designed to examine reciprocal relationships between feeding practices and infant growth over the first 6 mo of life. The following three hypotheses were tested: 1) early feeding practices predict later infant growth; 2) early infant growth predicts later feeding practices; and 3) these relationships occur after controlling for related background variables. The sample included 226 healthy, well-nourished infants born at the Queen Elizabeth Hospital, Bridgetown, Barbados. Assessments were made at birth, 7 wk, and 3 and 6 mo of age. Factor analysis of a feeding practices questionnaire for those mothers who attended all three postnatal visits yielded five uncorrelated factors. Three of these factors, preference for breast-feeding, feeding intensity and feeding difficulty, declined with infant age. Two of these factors, father helps and relatives help, increased with infant age. Several background variables, including maternal age, anthropometry and reproductive history, and reliance on outside sources of information were correlated with infant growth. Multivariate analyses confirmed all three hypotheses. The group of feeding practices (particularly the preference for breast-feeding) at 7 wk predicted increases in infant lengths at subsequent ages. Conversely, infant weights at 3 and 6 mo predicted subsequent feeding practices, especially feeding intensity. These reciprocal relationships remained even after statistically controlling for the influence of the background variables. Implications for public policy include the need for comprehensive programs advocating breast-feeding and supporting the general health of mothers and infants.

Aging↗
PubMed1998

The relationship between a patient's spirituality and health experiences.

BACKGROUND AND OBJECTIVES: The relationship between spirituality and health is a new frontier in medicine. This study is a preliminary investigation into the relationship between a patient's experience of overall health, physical pain, and intrinsic spirituality. METHODS: We used a stratified, random sample of 462 patients at a family practice residency clinic. The Index of Core Spiritual Experiences (INSPIRIT) measured intrinsic spirituality, and Dartmouth Primary Care Cooperative Charts measured overall health and pain. Pearson correlations tested the association between health, pain, and spirituality. Patient scores on the INSPIRIT were then placed into three groups (high, medium, and low levels of intrinsic spirituality). ANOVA tested for significant differences in health and pain. RESULTS: We collected information from 442 of the patients surveyed (95%). We found significant correlation between patient health and spirituality. Significant differences were also found in both overall health and physical pain, based on the three levels of spirituality. Gender differences were only significant for overall health, not for patient pain. CONCLUSIONS: Our results suggest an association between intrinsic spirituality and a patient's experience of health and pain. Assessment of spirituality may be important for family physicians to consider as a supplement to patient interviews.

Adult↗
PubMed1997

The effects of selective cholinergic basal forebrain lesions and aging upon expectancy in the rat.

The effects of selective cholinergic cell loss within the basal forebrain (BF) were determined using a task that requires shifting of attention between two visual stimuli. Discriminability between two stimuli and response bias were determined in young and old F-344 rats given BF injections of IgG-192 saporin (100 ng). The lesion reduced ChAT activity in the frontal and parietal cortices, hippocampus, and olfactory bulbs. The lesion did not significantly alter Na+/K(+)-ATPase activity in cortex, hippocampus, or olfactory bulbs, or endogenous levels of neuropeptide Y and neurokinin B within the BF. The BF lesions impaired both stimulus discriminability and response bias in young and old rats. The BF lesions had a significantly greater effect upon stimulus discriminability and response bias in aged rats, compared to young rats, only when the stimulus duration was very brief, i.e., when the task was most difficult to solve. At longer stimulus durations, aging and lesions showed no interaction. The results suggest that the selective loss of cholinergic cells in the BF, but not normal aging, impairs the ability to discriminate between independent sensory stimuli. The loss of these cells confers a response bias in simple operant tasks involving motor responses to reward-related visual stimuli.

Acetylcholine↗
PubMed1997

Quality of life outcomes after intensive care. Comparison with a community group.

OBJECTIVE: Compare the health related quality of life of intensive care patients with a community sample. DESIGN: Self-completed questionnaire posted to a consecutive sample of 238 patients 16 months after discharge from an intensive care unit (ICU) and to a random community sample (n = 242). SETTING: The Liverpool Hospital is the main referral and teaching hospital in a community of 620,000 people. It has a ten-bed general ICU. PATIENTS AND PARTICIPANTS: All patients admitted to the ICU over 8 months with a length of stay > or = 24 h and a sample drawn from the community telephone directory. MEASUREMENTS AND MAIN RESULTS: The self completed questionnaire contained physical and psychosocial health and quality of life (QOL) scales. Analysis of variance indicated that ICU patients were more physically ill and anxiously depressed than the community sample. Sixty-three per cent of patients had not attained full health, were functionally impaired and had a poorer QOL than those patients who had returned to full health and the community. Psychosocial health (apart from anxious depression) was related to the level of perceived physical health rather than to whether or not they had been admitted to the ICU. Those subjects not in full health had poorer interpersonal relationships, less positive attitudes about life, more anxious depression and more suicidal depression. CONCLUSIONS: ICU patients following discharge have worse perceived health and more anxiety than others in the community. Sixty-three per cent of patients had a poorer QOL and functional health than those who returned to full health and those in the community.

Analysis of Variance↗
PubMed1997

Improving the performance of small incontinence pads: a study of "wet comfort".

PURPOSE: The wet comfort of small, disposable incontinence pads has been found to correlate strongly with overall acceptability. This study examined the relationship between pad properties (absorption capacity, strike-through, and wetback) and wet comfort. DESIGN: A group of women with light incontinence were asked to report on the wet comfort of a series of experimental pads made up to the same design geometry but in different combinations of materials. METHODS: Three different pad variants were selected, and two experiments were conducted. Experiment 1 used a single-blind design in which 20 testers were supplied with a random mix of the three unlabeled pad variants. All pads were saved for weighing and scored for overall performance, wet comfort, and absorbency. In experiment 2, subjects used each pad variant in turn for 1 week and at the end of each week compared that pad with the one used the previous week. MAIN OUTCOME MEASURES: Absorption capacity, wetback, and strike-through properties for each pad variant were measured in the laboratory setting, and wet comfort was measured by a written tool completed by participants during clinical trials. RESULTS: Data analysis from experiment 1 revealed statistically significant differences among pad variants, particularly when assessed for absorbency. Differences for wet comfort were less marked and only achieved significance when those with ratings of good or OK for wet comfort were compared with those with a score of poor. In experiment 2, no statistically significant differences were found for wet comfort. CONCLUSIONS: Overall, the improvement in wet comfort achieved by a substantial increase in absorption capacity and reduction in wetback were disappointing. The relatively small sample and the design specifications of the pad may have masked differences. Cost considerations mean that more evidence is needed to justify the inclusion of more expensive materials and production stages in the manufacture of small pads.

Adult↗
PubMed1997

Infant sensitivity to deviations in dynamic facial-vocal displays: the role of eye regard.

Do young infants appreciate the intentionality of adult interactors? In view of recent speculation that infants are innately sensitive to eye direction and that communicative intent is conveyed in part by attentional cues, the reactions of 3- and 5-month infants were compared to video episodes of normally responsive women who either appeared or did not appear to make eye contact. Across three experiments, lack of eye contact was achieved by either averting the eyes (E), averting the head and eyes (H&E), closing the eyes (ECL), or averting the head alone (H). Three-month-olds smiled less at H&E, H, and ECL, but not at E, relative to frontal faces, indicating sensitivity to head but not to eye orientation. By contrast, 5-month-olds smiled less at H&E, E, and ECL, but not at H, indicating sensitivity to both head and eye orientation. The implications of the data for mentalist views of infant social behavior are discussed.

Adult↗
PubMed1997

Effect of the potassium channel opener ZM260384 on skeletal muscle function during restricted blood flow in the anaesthetized cat.

The aim of the present experiment was to determine whether the potassium channel opener 2-(2,2-bis(difluoromethyl)-6-nitro-3,4-dihydro-2H-1, 4-benzoxazine-4-yl)pyridine-N-oxide (ZM260384) was capable of accelerating the decline in skeletal muscle function during restricted blood flow in vivo. Cats (3.0-4.5 kg body weight) were anaesthetized with alphaxalone-alphadalone and breathed spontaneously following tracheotomy. Isometric tension was measured in the extensor digitorum longus-anterior tibialis (EDL-TA) muscle group. Ischaemia was induced by perfusing the hindlimb with the animal's own blood at a rate of 12.5 ml min-1 using a roller pump and stimulating the common peroneal nerve to induce repetitive submaximal tetanic contractions in the EDL-TA. The number of stimulation voltage increments required each minute to maintain a constant level of submaximal mechanical output and the time to exhaustion were used as indices of the rate of tension decline. The rate of tension decline in the ischaemic EDL-TA in the presence of ZM260384 at 3 mg kg-1, a maximally hypotensive dose predicted to be within the dose range required to exert direct effects on skeletal muscle, was measured and compared with the rate of tension decline in the presence of ZM260384 at 0.03 mg kg-1, also maximally hypotensive dose but below the predicted dose range for skeletal muscle effects. The number of voltage increments per minute was 1.93 +/- 0.07 and 1.48 +/- 0.14 (P < 0.05) in the presence of 3 and 0.03 mg kg-1 ZM260384, respectively. Time to exhaustion was 17.5 +/- 4.2 and 7.2 +/- 0.8 min (P < 0.05) in the presence of 3 and 0.03 mg kg-1 ZM260384, respectively. Given that there was no difference between these two groups in any haemodynamic variable measured, the results of the present study suggest that ZM260384 (3 mg kg-1) increases the rate of isometric force loss in ischemic skeletal muscle in vivo.

Anesthesia↗
PubMed1996

In vivo characterisation of ZM 241385, a selective adenosine A2A receptor antagonist.

The in vivo characterisation of ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-+ ++ylamino] ethyl)phenol), a novel, non-xanthine, selective adenosine A2A antagonist is described. In anaesthetised dogs ZM 241385 (i.v.) was 140-fold more potent in attenuating vasodilator responses to exogenous adenosine in the constant flow perfused hind limb than the bradycardic effects. In pithed rats in which blood pressure was supported by angiotensin II infusion, ZM 241385 (10 mg kg-1, i.v.) did not inhibit the hypotensive or bradycardic effects of the A3/A1 receptor agonist N(6)-2-(4-amino-3-iodophenyl)ethyladenosine (APNEA). In conscious spontaneously hypertensive rats, ZM 241385 (3-10 mg kg-1, p.o.) selectively attenuated the mean arterial blood pressure response produced by exogenous adenosine. No inhibition of the bradycardic effects of adenosine was observed following these doses of ZM 241385. The results indicate that ZM 241385 can be used to evaluate the role of adenosine A2A receptors in the action of adenosine in vivo.

Adenosine↗
PubMed1996

The yield of head-up tilt testing is not significantly increased by repeating the baseline test.

BACKGROUND AND HYPOTHESIS: Head-up tilt is widely used in evaluating patients with syncope. Data suggest that baseline tilt without isoproterenol is associated with few (< or = 10%) positive results in normals. However, there is considerable day-to-day variability in patients with syncope, resulting in low reproducibility. We hypothesized that repeating the baseline tilt would increase the total number of positive responses. METHODS: In all, 193 patients with syncope of unknown etiology prospectively underwent serial baseline tilt (Tilt-1 and Tilt-2) at 70 degrees for 25 min on two consecutive days. RESULTS: Of 193 patients, 39 (20%) had a positive Tilt-1. Of these, 19 had a positive Tilt-2, (positive concordance rate: 19/39 = 49%). Of 154 patients with a negative Tilt-1, 145 had a negative Tilt-2 (negative concordance rate: 142/151 = 94%). Only 9 of 154 patients (6%) with a negative Tilt-1 had a positive Tilt-2. Thus, the yield increased from 20% (39/193) after Tilt-1, and to 25% (48/193) after Tilt-1 plus Tilt-2, p = NS. CONCLUSIONS: (1) Reproducibility of a positive Tilt-1 is moderate. (2) Reproducibility of a negative Tilt-1 is high. (3) Repetition of tilt in patients with a negative Tilt-1 does not significantly increase the number of positive results.

Blood Pressure↗
PubMed1996

EuroQol: the current state of play.

The EuroQol Group first met in 1987 to test the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. From the outset the Group has been multi-country, multi-centre, and multi-disciplinary. The EuroQol instrument is intended to complement other forms of quality of life measures, and it has been purposefully developed to generate a cardinal index of health, thus giving it considerable potential for use in economic evaluation. Considerable effort has been invested by the Group in the development and valuation aspects of health status measurement. Earlier work was reported upon in 1990; this paper is a second 'corporate' effort detailing subsequent developments. The concepts underlying the EuroQol framework are explored with particular reference to the generic nature of the instrument. The valuation task is reviewed and some evidence on the methodological requirements for measurement is presented. A number of special issues of considerable interest and concern to the Group are discussed: the modelling of data, the duration of health states and the problems surrounding the state 'dead'. An outline of some of the applications of the EuroQol instrument is presented and a brief commentary on the Group's ongoing programme of work concludes the paper.

Cost-Benefit Analysis↗
PubMed1996

Pharmacodynamics of ZM 241385, a potent A2a adenosine receptor antagonist, after enteric administration in rat, cat and dog.

4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5] triazin-5-ylamino]ethyl)phenol (ZM 241385) is currently the most selective for the A2a adenosine receptor antagonist. This paper describes the in-vivo activity of ZM 241385 after administration by both oral and intraduodenal routes. In conscious spontaneously hypertensive rats, ZM 241385 (1-10 mg kg-1) selectively attenuated the mean arterial blood pressure response produced by exogenous adenosine (1 mg kg-1 min-1, i.v.) by up to 45% after oral administration. Activity of ZM 241385 was maintained for at least 6 h after 3 and 10 mg kg-1 (p.o.). In conscious normotensive cats, ZM 241385 attenuated the blood pressure responses to adenosine (0.6-1.0 mg kg-1, i.v.) by 94% after 10 mg kg-1 (p.o.) and by up to 74% after 0.3 mg kg-1 (i.v.). Duration of action of ZM 241385 up to 12 h (36% inhibition) was observed after 3 mg kg-1 (p.o.). In anaesthetized dogs and cats, ZM 241385, after intraduodenal administration (1-10 mg kg-1), produced a rapid (dose ratio 100-fold 15 min after administration of 10 mg kg-1 in the cat) and prolonged (dose ratio of 14 at 6 h after administration of 10 mg kg-1) attenuation of the vasodilatation responses to adenosine receptor stimulation. When administered by this route ZM 241385 was six times more potent than theophylline in the cat and at least twice as potent as theophylline in the dog. In conclusion, ZM 241385 is a potent, selective A2a adenosine receptor antagonist which is orally active, with a good duration of action by the enteric route in cat, rat and dog. It could therefore be used to evaluate the role of adenosine A2a receptors in the action of adenosine in-vivo.

Administration, Oral↗