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Biomedical subjects

G Hicks

Publications and source records attributed to G Hicks.

At least 19 recordsLinked to original sources
PubMed2006

Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension.

Tegaserod is a 5-HT(4) receptor partial agonist approved for the treatment of irritable bowel syndrome in women with constipation and in both men and women with chronic constipation. The efficacy of tegaserod is based on the importance of 5-HT(4) receptors regulating intestinal peristalsis and secretion, and possibly visceral sensory pathways. Our aim was to investigate the effect of tegaserod on colorectal sensitivity using models of normal and exaggerated responsiveness to colorectal distension (CRD). The visceromotor responses (VMR) to CRD at graded pressures (0-60 mmHg) were measured by the number of reflex abdominal contractions. Acute colorectal hypersensitivity was induced by intracolonic infusion of dilute acetic acid. Chronic hypersensitivity was observed in rats following spontaneous resolution of trinitrobenzenesulfonic acid-induced colitis. Rats with normosensitive colons served as controls. Tegaserod (0.1-10 mg kg(-1)) caused dose-dependent reduction of the VMR to CRD in control rats and in those with colonic hypersensitivity. 5-HT(4) antagonists reversed the effects of tegaserod in rats with normosensitive colons, and partially inhibited effects in rats with colonic hypersensitivity. Central administration of tegaserod had no inhibitory effect. These results support the assumption that colonic hypersensitivity could be normalized by tegaserod acting, at least in part, through peripheral 5-HT(4) receptors.

Acetic Acid↗
PubMed2004

Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children.

BACKGROUND: Anti-leukotrienes agents are currently being studied as alternative first line agents to inhaled corticosteroids in mild to moderate chronic asthma. OBJECTIVES: To compare the safety and efficacy of anti-leukotriene agents with inhaled glucocorticoids (ICS) and to determine the dose-equivalence of anti-leukotrienes to daily dose of ICS. SEARCH STRATEGY: We searched MEDLINE (1966 to Aug 2003), EMBASE (1980 to Aug 2003), CINAHL (1982 to Aug 2003), the Cochrane Airways Group trials register, and the Cochrane Central Register of Controlled Trials (August 2003), abstract books, and reference lists of review articles and trials. We contacted colleagues and international headquarters of anti-leukotrienes producers. SELECTION CRITERIA: Randomised controlled trials that compared anti-leukotrienes with inhaled corticosteroids during a minimal 30-day intervention period in asthmatic patients aged 2 years and older. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality or trials and extracted trial data. The primary outcome was the rate of exacerbations requiring systemic corticosteroids. Secondary outcomes included lung function, indices of chronic asthma control, adverse effects and withdrawal rates. MAIN RESULTS: 27 trials (including 1 trial testing two protocols) met the inclusion criteria; 13 were of high methodological quality; 20 are published in full-text. All trials pertained to patients with mild to moderate persistent asthma. Only 3 trials focused on children and adolescents. Trial duration varied from 4 to 37 weeks. In most trials, daily dose of ICS was 400 mcg of beclomethasone or equivalent. Patients treated with anti-leukotrienes were 65% more likely to suffer an exacerbation requiring systemic steroids [Relative Risk 1.65; 95% Confidence Interval (CI) 1.36 to 2.00]. Twenty six (95% CI: 17 to 47) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra exacerbation. Significant differences favouring ICS were noted in secondary outcomes where()the improvement in FEV(1) reached 130 mL [13 trials; 95% CI: 50, 140 mL ]. Other significant benefits of ICS were seen for symptoms, nocturnal awakenings, rescue medication use, symptom-free days, and quality of life. Anti-leukotriene therapy was associated with 160% increased risk of withdrawals due to poor asthma control. Twenty nine (95% CI 20 to 48) patients must be treated with anti-leukotrienes instead of inhaled corticosteroids to cause one extra withdrawal due to poor control. Risk of side effects was not different between groups. REVIEWERS' CONCLUSIONS: Inhaled steroids at a dose of 400 mcg/day of beclomethasone or equivalent are more effective than anti-leukotriene agents given in the usual licensed doses. The exact dose-equivalence of anti-leukotriene agents in mcg of ICS remains to be determined. Inhaled glucocorticoids should remain the first line monotherapy for persistent asthma.

Administration, Inhalation↗
PubMed2004

Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.

BACKGROUND: Anti-leukotriene (AL) agents are being considered as 'add-on' therapy to inhaled corticosteroids (ICS), in chronic asthma. OBJECTIVES: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). SELECTION CRITERIA: Randomised placebo-controlled trials of asthmatics aged two years and older with at least one month intervention. DATA COLLECTION AND ANALYSIS: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double). MAIN RESULTS: Of 587 citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full-text and 16 trials reported data in a way that allowed meta-analysis. In symptomatic patients, addition of licensed doses of anti-leukotrienes to ICS resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short-acting beta2-agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti-leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS-sparing studies of patients who were well controlled at baseline, addition of anti-leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD -21 mcg/d, 95%CI -65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). REVIEWERS' CONCLUSIONS: The addition of licensed doses of anti-leukotrienes to add-on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti-leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti-leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid-sparing effect cannot be quantified at present, it appears modest.

Administration, Inhalation↗
PubMed2003

Side-to-side weight-bearing asymmetry in subjects with low back pain.

The purpose of this project was to determine if subjects with low back pain (LBP) exhibit greater side-to-side weight-bearing (WB) asymmetry compared to healthy control subjects without LBP. This study utilized an observational double cohort design and consisted of 35 subjects with LBP and 31 healthy control subjects. Side-to-side WB asymmetry was calculated as the average of the absolute value of the difference between the right and left lower extremity from three trials. The percentage of the average side-to-side WB asymmetry relative to the total body weight was calculated to normalize expected differences in magnitude of asymmetry based on a subject's total body weight. An 11-point numeric pain rating scale was used to represent the subject's current level of pain. Patients with LBP demonstrated significantly greater normalized side-to-side WB asymmetry than healthy control subjects (8.8% vs. 3.6%, respectively, P<0.001). In patients with LBP, higher magnitudes of side-to-side WB asymmetry were significantly associated with increased pain (r=0.39, P=0.021). In conclusion patients with LBP exhibited increased side-to-side WB asymmetry compared to healthy control subjects without LBP. This asymmetry was associated with increased levels of pain. This finding is relevant for planning future studies that will attempt to provide evidence for the construct validity of manipulation by determining if side-to-side WB asymmetry normalizes after a manipulation intervention and if this improvement is associated with improvements in pain and function.

Adult↗
PubMed2001

Addition of anti-leukotriene agents to inhaled corticosteroids for chronic asthma.

BACKGROUND: Anti-leukotriene (AL) agents are being considered as "add-on" therapy to inhaled corticosteroids (ICS), in chronic asthma. OBJECTIVES: To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid-sparing effect of AL when added to ICS in chronic asthma. SEARCH STRATEGY: We searched Medline, Embase, Cinahl (all up to 2001), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and ATS meeting abstracts (1998-2000). SELECTION CRITERIA: Randomised placebo-controlled trials of asthmatics aged 2 years and older lasting at least one month. DATA COLLECTION AND ANALYSIS: Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well-controlled) and dose of ICS in the control group (same or double). MAIN RESULTS: Of 336 citations, 11 trials (only adults) met inclusion criteria. Six were published in full-text, eight were high quality. Daily dose of ICS was 300-2000 mcg beclomethasone-equivalent. In symptomatic adults, AL (at 2-4 times licensed dose) combined with ICS reduced the number of patients with exacerbations that required systemic corticosteroids, compared to ICS alone [Relative Risk (RR) = 0.34; 95% Confidence Interval (CI) 0.13, 0.88]. This equates to 20 patients (95% CI 1,100 patients) treated to prevent one needing systemic corticosteroids. There was no difference in side effects. No trials tested the efficacy of licensed doses of ALs as add-on to ICS. In symptomatic adults, addition of zafirlukast to ICS did not reduce the number of exacerbations requiring systemic corticosteroids, compared to doubled dose ICS [RR= 1.39; 95% CI: 0.63, 3.08)]. There were no differences in any other measure of outcome. Higher doses of zafirlukast than currently licensed were associated with increased risk of liver enzyme elevation. In ICS-sparing trials of AL agents there was no difference in ICS dose after 12-16 weeks [Weighted Mean Difference (WMD) 1.9% change; 95% CI -3.5, 7.3], and no difference in lowest tolerated dose of ICS [WMD= 44 mcg/d; 95% CI -59, 148)]. REVIEWER'S CONCLUSIONS: Used as add-on therapy to inhaled corticosteroids, high dose anti-leukotrienes reduced exacerbations, but there is no evidence to support their use at currently licensed doses. There is insufficient evidence to indicate whether they confer benefit over doubling the dose of corticosteroids. There is no evidence that they have any significant inhaled corticosteroid-sparing effect.

Administration, Inhalation↗
PubMed1998

Outcomes after severe trauma at a northern Canadian regional trauma centre.

OBJECTIVE: To evaluate outcomes of trauma patients at a northern community trauma referral centre that does not meet several of the guidelines for a trauma centre. DESIGN: A retrospective study. SETTING: Sudbury General Hospital in northern Ontario. PARTICIPANTS: All trauma patients admitted between 1991 and 1994 who had an Injury Severity Score (ISS) greater than 12. OUTCOME MEASURES: Actual survival to discharge was compared to survival predicted by TRISS analysis. Z, W and M scores were calculated by standard TRISS techniques. RESULTS: Of 526 patients with an ISS greater than 12, 416 (79%) were suitable for TRISS analysis. Of these 416 patients, 310 (74%) were men. The mean age was 39 years. Two hundred and sixty-one (63%) patients were admitted directly to the Sudbury General Hospital, whereas 155 (37%) were transferred from other hospitals. The leading causes of injury were motor vehicle-traffic accidents in 48%, motor vehicle-nontraffic in 21% and falls in 8%. Overall, there were more unexpected survivors than patients who died. The Z score for survivors was 4.95, and the W score was 5.65. CONCLUSIONS: In the setting of a geographically isolated, medium-volume trauma centre where blunt injuries predominate, excellent trauma survival can be achieved without meeting all trauma centre guidelines for staffing and facilities. Relaxing stringent requirements for the availability of physicians may facilitate surgical recruitment and retention.

Adolescent↗
PubMed1992

Use of brainstem auditory-evoked response testing to assess neurologic outcome following near drowning in children.

OBJECTIVE: To determine a correlation between serial brainstem auditory-evoked response measurements and ultimate neurologic outcome in pediatric patients who suffered a cardiac arrest resulting from a submersion accident. DESIGN: Inception cohort, prospective correlational study. SETTING: A 15-bed pediatric ICU (within a 150-bed tertiary care pediatric hospital) admitting patients of all ages except nonsurgical neonates. PATIENTS: All previously normal pediatric patients who suffered a cardiac arrest after a submersion accident. Patients evaluated: 111; patients studied: 89. METHODS: Patients received serial brainstem auditory-evoked response testing within 6 hrs of resuscitation and then once daily for up to 10 days. Brainstem auditory-evoked response measurements included wave I-V interpeak latency, wave V amplitude, and wave I/V amplitude ratio. Upon discharge, patients were evaluated and classified into one of four neurologic outcome groups: normal, handicapped, vegetative, or dead. Patients classified into the handicapped group exhibited mild neurologic deficits after discharge. Vegetative patients were noninteractive with their environment and required full-time caretaker support. Serial brainstem auditory-evoked response measurements from the four outcome groups were compared with brainstem auditory-evoked response measurements obtained from a group of 39 healthy children of comparable age. MAIN RESULTS: Patients who recovered neurologically intact manifested brainstem auditory-evoked response measurements that were similar to controls. Brainstem auditory-evoked response measurements in the handicapped outcome group were also normal after resuscitation but showed significant reduction in wave V amplitudes over the ensuing days. When compared with controls, patients with a vegetative outcome manifested abnormally prolonged wave I-V interpeak latencies, diminished wave V amplitudes, and large-wave I/V amplitude ratios following resuscitation. However, I-V interpeak latencies normalized within 24 hrs after resuscitation. I-V interpeak latencies were no different than controls until hospital day 3, at which time they became significantly prolonged. Patients who were declared brain dead or died from cardiovascular collapse exhibited very abnormal brainstem auditory-evoked response measurements on admission and until death. Wave V could not be detected on admission in 19/31 patients within this group. CONCLUSIONS: Brainstem auditory-evoked response testing is useful as an aid in the assessment of neurologic outcome following submersion-induced cardiac arrest. However, standardization of brainstem auditory-evoked response testing and production of normative data are required before this modality can be more widely studied and applied.

Analysis of Variance↗
PubMed1991

Validity and reliability of a scale to assess fatigue.

A visual analogue scale to evaluate fatigue severity (VAS-F) was developed and tested in a sample of 75 healthy individuals and a sample of 57 patients undergoing medical evaluation for sleep disorders. The scale consists of 18 items related to fatigue and energy, has simple instructions, and is completed with minimal time and effort. The VAS-F compares favorably with the Stanford Sleepiness Scale and the Profile of Mood States, and its internal consistency reliabilities are high. Healthy subjects demonstrated significant differences between their evening and morning scores on the VAS-F, while sleep-disordered patients did not.

Adult↗
PubMed1990

Comparison of perceived needs of family members between registered nurses and family members of critically ill patients in intensive care and neonatal intensive care units.

Using the Norris and Grove (1986) questionnaire of perceived needs of families of critically ill patients, 11 registered nurses working in the neonatal intensive care unit and 19 registered nurses working in the intensive care unit of two mid-northern community hospitals provided their perceptions of family needs. Their responses were compared with responses of family members of patients in the intensive care unit (n = 25) and the (n = 24). Results suggest that regardless of unit, registered nurses' perceptions of family needs are congruent. Family members collectively and by unit ranked their needs consistently higher and in some areas differently than did the registered nurses.

Adult↗
PubMed1985

Functioning of the brain-stem auditory pathway in non-retarded autistic individuals.

Functioning of auditory brain-stem pathways was examined in non-retarded autistic individuals (14-28 years of age). Functioning was assessed by recording ERPs (event-related brain potentials) generated by these auditory pathways. These ERPs were evoked by click stimuli and occurred within the first 8 msec following the onset of the click. To assess the ability of these early auditory pathways to process sensory stimuli of varying characteristics, we systematically varied click intensity, rate of stimulation, ear of stimulation, and polarity of clicks. The results show that non-retarded autistic individuals have normal functioning of the brain-stem auditory pathways which generate these ERPs: every autistic subject had normal ERPs. So, disorder in auditory brain-stem pathways which generate these ERPs is not necessary for autism to occur. The dysfunctioning neural systems directly responsible for autism in non-retarded individuals must be sought elsewhere. Ten of the autistic subjects in this study, whom we found to have normal auditory brain-stem ERPs, had previously been found to have abnormalities in longer latency cognitive ERP components (Courchesne et al. 1984, 1985). We conclude, therefore, that those abnormalities in longer latency components are not the downstream consequences of abnormalities in the structures generating the auditory brain-stem ERPs recorded in the present study.

Adolescent↗
PubMed1984

Five-year clinical experience with the Omniscience cardiac valve.

Clinical data on the Omniscience cardiac valve prosthesis (sizes 19 to 31 mm) were obtained from 326 patients (155, aortic valve replacement [AVR]; 125, mitral valve replacement [MVR]; and 46, double-valve replacement) during a five-year period (650 patient-years) with 96% accountability. Mean age was 56 +/- 12 years, and 40% (130) of the patients were 61 years old or older. Thirty-one percent (101) had prior or concomitant coronary artery bypass grafting procedures, 9% (28) had a previous malfunctioning prosthesis, and 17% (57) had other cardiac surgical procedures. Eighty percent were in New York Heart Association (NYHA) Functional Class III or IV preoperatively. Early mortality was 10% (34). Five-year actuarial thrombus-free rate is 96% for patients who underwent AVR and 95% for patients having MVR. Postoperatively, 89% (172/193) were in NYHA Class I or II, and 84% (163/193) improved by at least one Functional Class. A significantly high proportion of the postoperative hematological values fall within normal ranges: red blood cell count, 94% (176/187); hematocrit, 88% (166/188); and hemoglobin, 93% (176/190). Ninety-eight percent (287/292) are free from clinical anemia. Four of the 5 patients with clinical anemia had a preoperative history of this condition. Levels of lactic dehydrogenase in 3 patients suggested the probable presence of clinically significant hemolysis, although all 3 have normal hematological values. Actuarial five-year survival for patients who underwent AVR or MVR are similar (82% and 80%, respectively), indicating satisfactory and comparable levels of safety and performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Factors influencing thromboembolic complications in Omniscience cardiac valve patients.

Clinical data were gathered over five years (650 patient-years) for all 155 aortic valve replacement, 125 mitral valve replacement and 46 double valve replacement patients implanted with the Omniscience cardiac valve prosthesis at three North American medical cent es. Mean age was 56 +/- 12 years, 80% were preoperatively in NYHA class III or IV, and 57% had previous or concomitant cardiac surgery. Data were evaluated for the incidence of thromboembolic complications. During the late postoperative period, transient ischaemic episodes occurred in six patients (0.92% per patient-year). The five-year actuarial thrombus-free rate for serious thromboembolic complications (valve thrombosis or thromboembolism with residual effects) for aortic valve replacement patients is 96% and 95% for mitral valve replacement patients. For patients experiencing any transient or serious thromboembolic complication, 35% had a compromise of coumadin anticoagulation shortly before the thromboembolic event, 60% had a history of atrial fibrillation, and 76% a history of rheumatic heart disease. Statistically, these rates are significantly higher compared with the original valve population. The low incidence of thromboembolic complications over this five-year clinical study demonstrates a commendable degree of safety and performance for the Omniscience valve.

Actuarial Analysis↗
PubMed1982

Topographic antigenic determinants recognized by monoclonal antibodies to sperm whale myoglobin.

Monoclonal antibodies of high affinity (approximately 10(9) M-1) for sperm whale myoglobin were studied to pinpoint the antigenic determinants with which they interact. None of 6 different monoclonal antibodies tested reacted with any of the 3 CNBr cleavage fragments which encompass the whole sequence of myoglobin, an indication that they react with determinants present only on the native structure. To identify these sites, we compared the affinities of each antibody for a series of 14 mammalian myoglobins of known sequence and similar tertiary structure. Correlation of sequence differences with relative affinities allowed us, thus far, to identify critical antigenic residues recognized by 3 of the antibodies. Two of these antibodies recognize groups of residues which are far apart in primary structure but close together in the 3-dimensional structure of the native myoglobin molecule, i.e. topographic determinants. The third antibody distinguishes 140 Lys leads to Asn plus, probably, surface residues nearby. These determinants differ from previously reported antigenic sites on sperm whale myoglobin both in that they are topographic, rather than sequential, and in that almost all the critical residues recognized by these antibodies are outside the previously reported sites. Monoclonal antibodies are sensitive to subtle changes, e.g. Glu leads to Asp, in the antigenic site.

Amino Acid Sequence↗
PubMed1981

Ir genes of different high responder haplotypes for staphylococcal nuclease are not allelic.

The Ir gene controlling high responsiveness to staphylococcal nuclease in the H-2d haplotype has been mapped to the I-A subregion, in contrast to that in the H-2k and H-2a haplotypes, which maps in the I-B subregion. The nonallelic high responder genes also confer differences in fine specificity on the antibodies produced. This nonallelism of Ir genes for the same antigen in different haplotypes is consistent with Ir gene mechanisms involving associative recognition of antigen plus Ia by T lymphocytes. It further suggests that products of different subregions can perform the same function.

Alleles↗