Graft versus host disease following intrauterine and exchange transfusions for rhesus haemolytic disease.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Y H Thong
Publications and source records attributed to Y H Thong.
Parental perceptions and attitudes about informed consent in clinical research involving children.
We interviewed 64 parents by questionnaire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent. The results show that only a small minority realised that drug trials are designed to assess not only efficacy but safety as well. More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks. Moreover, a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised. Even more worrisome was the small percentage of parents who realised that a signed consent form was primarily meant to protect their rights, and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time. These findings suggest that there may be significant attitudinal barriers to parental understanding of the informed consent process.
Adult↗
Parental perceptions and attitudes about informed consent in clinical research involving children.
We interviewed 64 parents by questionnaire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent. The results show that only a small minority realized that drug trials are designed to assess not only efficacy but safety as well. More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks. Moreover, a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised. Even more worrisome was the small percentage of parents who realized that a signed consent form was primarily meant to protect their rights, and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time. These findings suggest that there may be significant attitudinal barriers to parental understanding of the informed consent process.
Administration, Oral↗
Aftercare for participants in clinical research: ethical considerations in an asthma drug trial.
The issue of aftercare for participants in clinical research was explored in the context of an asthma drug trial. Although there may be financial constraints and practical difficulties with implementation, the results show that it may be feasible for clinical investigators and commercial sponsors to take on some limited responsibility for the medical care of research subjects after clinical trials. However, the ethical implications for this practice remain unclear. On the one hand, society may have a moral obligation to compensate and reward some of its members who assume the risk of research subjects for the benefit of society as a whole. On the other hand, the promise of aftercare may provide an inducement to volunteers which, under certain conditions may be considered morally wrong and scientifically unsound.
Aftercare↗
Nicotine-induced release of elastase and eicosanoids by human neutrophils.
We examined the direct effects of nicotine on a variety of neutrophil functions at concentrations achievable in lung and oral tissues from cigarette smoking. The results show dose-dependent suppression of chemotaxis and phagocytosis, and enhancement of degranulation and eicosanoid generation, but not superoxide production. Cell viability was not affected by the concentrations of nicotine used in these experiments, as shown by trypan blue dye exclusion and MTT assays. These results implicate nicotine as the ingredient in cigarette smoke responsible for inflammatory damage to lungs and oral tissues observed in cigarette smokers.
Cell Degranulation↗
Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats.
Two isoquinoline plant alkaloids, tetrandrine (1) and berbamine (2), have been evaluated for anti-inflammatory activity in an acute paw oedema assay and in adjuvant-induced arthritis in rats. 1 but not 2 suppressed the chronic inflammation in the arthritis model but neither compound was active in the acute inflammation assay. In the adjuvant-induced polyarthritis, 1 was not effective when given at the time of inoculation (Day 0), nor just before (Day 7-10) signs of arthritis were evident. However, when given on a therapeutic dose schedule (Days 10-13) or continually (Day -1 to +14) on a prophylactic schedule, signs of arthritis including weight loss due to cachexia were significantly reduced. Given orally, 1 was considerably more potent than aspirin but not gastro-irritant and may be a promising lead for the development of a safe and effective treatment of chronic inflammatory diseases.
Alkaloids↗
Immunopharmacology and toxicology of the plant flavonoid baohuoside-1 in mice.
The plant flavonoid baohuoside-1 (B-1), isolated from Epimedium davidii, was shown to suppress antibody and delayed-type hypersensitivity responses in mice in a dose-dependent fashion. By contrast, similar dosage schedules of B-1 did not significantly prolong survival of cardiac grafts. Furthermore, B-1 did not potentiate the effects of the standard anti-rejection drug cyclosporine. Assessment of the mice for appearance, behaviour, biochemistry, haematology and histology revealed no toxic effects at the dosages used in the experiments. These results indicate that the immunosuppressive properties of B-1 are confined to the antibody-mediated system, and suggest that B-1 may be of value in the treatment of chronic inflammatory and autoimmune diseases in which autoantibodies have a major role in pathogenesis.
Animals↗
Effect of berbamine on blood and bone-marrow stem cells of cyclophosphamide-treated mice.
The bisbenzylisoquinoline alkaloid berbamine has been used in China and Japan for the therapy of leukopaenic complications of cancer. Mice treated with non-toxic doses showed significant enhancement of neutrophil and lymphocyte counts in the circulation, but a decrease in the numbers of bone marrow stem cells in a dose-dependent manner after two weeks. Similar findings were observed in cyclophosphamide-treated mice. These results indicate that berbamine acts by stimulating the maturation and release of leukocyte progenitors, and may have value in leukopaenic patients.
Alkaloids↗
Synergy between tetrandrine and FK506 in prevention of diabetes in BB rats.
Delayed administration of tetrandrine, a novel broad-spectrum anti-inflammatory agent, to BB rats at a dosage schedule of 20 mg kg-1 day-1 from 79 days of age reduced the cumulative incidence of diabetes from 73.1 to 41.7% (p < 0.01). Brief treatment with the potent immunosuppressive agent FK506 at a dosage schedule of 0.5 mg kg-1 day-1 from 79 days of age for 5 days had no significant effect on the cumulative incidence of diabetes (66.7%, p > 0.1). However, the combination of tetrandrine and FK506 in the afore-mentioned dosage schedules reduced the incidence of diabetes to only 3.6% (p < 0.001). These results suggest that the strong synergy between tetrandrine and FK506 may offer a safe and effective therapeutic strategy for the treatment of patients with recent onset or imminent IDDM.
Alkaloids↗
Comparative effects of tetrandrine and berbamine on guineapig airway microvascular leakage induced by platelet-activating factor and other allergic mediators.
The bisbenzylisoquinoline analogues, tetrandrine and berbamine, were investigated for their effects on guineapig airway microvascular leakage, an animal model of asthma and allergic inflammation. Significant inhibition of microvascular leakage by tetrandrine was observed with all four allergic mediators used in these experiments. By contrast, berbamine was able to suppress microvascular leakage induced by platelet-activating factor and bradykinin, but not by leukotriene D4 or histamine. These results indicate that tetrandrine has broad-spectrum inhibitory activity on allergic mediators, and may have value for the therapy of diseases in which these mediators have a role in pathogenesis.
Alkaloids↗
Inhibition of adherence of mucoid Pseudomonas aeruginosa by alginase, specific monoclonal antibodies, and antibiotics.
The adherence of pseudomonal species was investigated by using a newly developed radiometric dacron fiber microcolumn assay. Pseudomonas aeruginosa, P. stutzeri, and Xanthomonas maltophilia were more adherent (approximately 20%) than P. pseudomallei, P. fluorescens, and P. cepacia (approximately 10%). Mucoid strains of P. aeruginosa were consistently more adherent than nonmucoid strains (30% versus 20%). Alginase was shown to inhibit the adherence of mucoid but not nonmucoid P. aeruginosa. Monoclonal antibodies to alginate were also shown to inhibit the adherence of mucoid but not nonmucoid P. aeruginosa. In addition, antibiotics active against P. aeruginosa were shown to inhibit the adherence of both mucoid and nonmucoid strains. Furthermore, synergism between dyadic combinations of monoclonal antibodies and antibiotic (ciprofloxacin), as well as alginase and antibiotic, was also observed. These results indicate that bacterial alginate has an intrinsic role in the adherence of mucoid P. aeruginosa and may have evolved not only for protection against dehydration in the water and soil ecosystem of this bacterium, but also as a means of attaching to soil substrates in the same ecosystem to enhance survival. They also suggest that synergistic combinations of antibiotics with alginase or monoclonal antibodies to alginate may be of value in the therapy of some pseudomonal infections.
Alginates↗
Suppression of lymphocyte and neutrophil functions by Pseudomonas aeruginosa mucoid exopolysaccharide (alginate): reversal by physicochemical, alginase, and specific monoclonal antibody treatments.
The mucoid exopolysaccharide (MEP or alginate) of Pseudomonas aeruginosa is thought to be a virulence factor for this organism by virtue of its ability to suppress local host defense mechanisms. We purified MEP from clinical isolates of mucoid P. aeruginosa, subjected it to degradation by ultrasonication, heat, alkali, and alginase, and reacted it with monoclonal antibodies specific for MEP epitopes. Partial reversal or complete abrogation of the inhibitory effects of alginate on human neutrophil random migration, chemotaxis, and hexose monophosphate shunt activity and lymphocyte transformation were observed following most of these treatments. Physicochemical analysis of degraded MEP revealed a positive correlation between changes in molecular size and viscosity and loss of biological properties. The biological properties of MEP were also shown to be dependent on the structural integrity of the O-acetyl groups substituted for the mannuronic acid residues. The results show that the capacity of MEP to suppress neutrophil and lymphocyte functions is dependent on its acetyl content and the physical properties of large size and viscosity and may provide part of the explanation for the propensity of mucoid P. aeruginosa to persist in the airways of patients with cystic fibrosis. These findings highlight the important role of MEP as one of the virulence factors in the pathogenesis of inflammatory damage and subsequent pulmonary destruction in cystic fibrosis.
Alginates↗
Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor.
The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20-30 mg/kg/3 days. Both were also equipotent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis.
Alkaloids↗
Comparative effects of tetrandrine and berbamine on production of the inflammatory cytokines interleukin-1 and tumor necrosis factor.
Tetrandrine and berbamine are bisbenzylisoquinoline compounds which differ from each other in a minor way in terms of chemical structure, yet tetrandrine is 6-18 times more potent than berbamine in terms of inhibitory effects on production of interleukin-1 and tumor necrosis factor (TNF alpha) by monocytes and macrophages, and TNF beta production by lymphocytes. Moreover, tetrandrine significantly suppressed phosphoinositide turnover while berbamine did not. These findings may provide important insights into structure-activity relationships and the design of novel analogues and congeners useful in the therapy of chronic inflammatory and auto-immune diseases.
Alkaloids↗
The quality of student-tutor interactions in the clinical learning environment.
We surveyed 403 students in their clinical years for their perceptions of the quality of clinical clerkships. Between 42.6 and 67.0% of tutorials were said to contain positive factors such as a relaxed teaching atmosphere, enthusiasm, a good selection of patients and adequate preparation. Negative features in 18.2-37.2% of tutorials included unreasonable expectations, conflicting information, late arrival, early departure, failure to show up and the display of anger, a patronizing attitude, favouritism or ridicule. While two-thirds of tutors were regarded as friendly and helpful, the remaining one-third were perceived as unconcerned, discouraging, derogatory or hostile. Overall, only half the clinical tutors were rated as effective teachers; more specifically in medicine and psychiatry, less than one-third of consultants were regarded as effective teachers, as compared with some two-thirds of consultants in obstetrics and gynaecology and paediatrics who were so regarded. Almost two-thirds of the students had predominantly positive reactions to interactions with their tutors, in terms of being motivated to learn, enthused about the subject and having their self-confidence increased. Some one-quarter had negative reactions such as indifference, depression, anger, embarrassment and fearfulness. However, the impact of student-tutor interactions was mainly confined to the students' academic well-being, with little effect on their personal-social lives. Finally, one-third of students had experienced at least some form of mistreatment by their tutors, including gender, appearance, religious and racial discrimination, unfair grading and public humiliation. These findings suggest that the clinical clerkship may not be providing an optimal learning environment for medical students.
Clinical Clerkship↗
A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze.
The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding.
Child, Preschool↗
Modulation of human neutrophil adherence by oral bacteria.
Polymorphonuclear neutrophils (PMNs) comprise over 90 per cent of leukocytes in the oral cavity. Although these phagocytic cells have primary defence roles in the gingiva, their stimulation by micro-organisms may also cause substantial tissue damage due to the release of lysosomal enzymes and oxygen radicals. Adherence of PMNs to the endothelium and their subsequent diapedesis and egress to areas of infection are considered early vital events in the inflammatory process. In this study, oral bacteria were screened to determine their direct effects on PMN activation using an in vitro method of measuring PMN adherence to Dacron fibres. Most of the bacteria investigated increased PMN adherence, indicating their potential to cause tissue damage through the release of PMN lysosomal enzymes and other products. In contrast, Bacteroides species suppressed PMNs, indicating their ability to circumvent the phagocytic cells, thus gaining a potential advantage in dental colonization. The modulatory effects of oral bacteria on PMN activation may have significant roles in the immunopathogenesis of oral disease.
Aggregatibacter actinomycetemcomitans↗
The psychological profile of parents who volunteer their children for clinical research: a controlled study.
Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non-volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects.
Australia↗