T-cell development and function--a down under experience.
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Biomedical subjects
Publications and source records attributed to R Boyd.
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Witnessed resuscitation is the process of active 'medical' resuscitation in the presence of family members. Witnessed resuscitation though not as yet wide spread in practice is becoming established. Early reports of programs designed to promote such a process first appeared in the early 1980s. More recent work appears to show both public support and a desire for inclusion in the resuscitation process. Some research has been produced that indicates both satisfaction and psychological benefit for those relatives enabled to witness. Limited work only, exists pertaining to the effects on health care providers and these reports currently do not show any significant deleterious effects. Approval of witnessed resuscitation programs is not universal amongst all groups of health care workers. Concerns about the ethics of witnessed resuscitation and its medico-legal implications have been raised. The quality of the initial witnessed resuscitation reports is however variable and there is a great need for further work to validate the initial findings particularly in the areas of psychological stressors in staff and risk management implications.
Postoperative pain in children with spastic cerebral palsy (CP) is often attributed to muscle spasm and is difficult to manage using opiates and benzodiazepines. Adductor-release surgery to treat or prevent hip dislocation in children with spastic CP is frequently performed and is often accompanied by severe postoperative pain and spasm. A double-blinded, randomized, placebo-controlled clinical trial of 16 patients (mean age 4.7 years) with a mainly spastic type of CP (either diplegic or quadriplegic in distribution) was used to test the hypothesis that a significant proportion of postoperative pain is secondary to muscle spasm and, therefore, might be reduced by a preoperative chemodenervation of the target surgical muscle by intramuscular injection of botulinum toxin A (BTX/A). Compared with the placebo, BTX/A was found to be associated with a reduction in mean pain scores of 74% (P<0.003), a reduction in mean analgesic requirements of approximately 50% (P<0.005), and a reduction in mean length of hospital admission of 33% (P<0.003). It was concluded that an important component of postoperative pain in the patient population is due to muscle spasm and this can be managed effectively by preoperative injection with BTX/A. These findings may have implications for the management of pain secondary to muscle spasm in other clinical settings.
OBJECTIVE: To examine secondary conditions and their relationship to life satisfaction in women with physical disabilities. DESIGN: Survey research. SETTING: Metropolitan Philadelphia. PARTICIPANTS: Women aged 18 to 65 years with self-reported functional limitations associated with neurologic, neuromuscular, brain, sensory, arthritic, spinal cord, orthopedic, or other chronic conditions. MAIN OUTCOME MEASURES: Secondary conditions, health status, functional status, and life satisfaction. RESULTS: In the past year, an average of 12 +/- 6.1 (SD) secondary conditions were experienced. Fatigue, mobility, physical deconditioning, spasticity, and joint pain were reported most frequently, followed by depression, chronic pain, access problems, weight problems, and isolation. In comparing women with multiple sclerosis (MS) and those with other disabling conditions, women with MS had higher secondary conditions problem index (SCPI) scores for bladder, bowel, and sexual dysfunction than women in the mixed disability group. Other secondary conditions with the highest SCPI scores remained similar. Self-reported emotional health status and SCPI scores were the only significant predictors of life satisfaction. CONCLUSION: Secondary conditions influence health status and quality of life for women with physical disabilities. Despite differences among disability groups in terms of the type of secondary conditions, common secondary conditions experienced by most women may be amenable to non-disability-specific health promotion programs.
The aim of this study was to determine the relationship between patients' perceptions of orthodontic treatment need and need as determined with professionally derived indexes, namely the dental aesthetic index and the index of orthodontic treatment need. This study was undertaken at orthodontic offices in San Francisco, Calif. The pretreatment study casts of 50 consecutive patients, presenting for orthodontic treatment, were objectively assessed with these indexes by 2 examiners trained and calibrated in their use. Patients were asked to complete a questionnaire consisting of 4 questions addressing appearance, function, speech, and treatment need, using either a 5-point Likert scale or a yes/no response. The professionally derived indexes showed that statistically significant correlations existed between the aesthetic component and dental health component (r = 0.46; P <.01), the aesthetic component and dental aesthetic index (r = 0.54; P <.01), and the dental health component and dental aesthetic index (r = 0.46; P <.01). Statistically significant correlations were also found for subjective assessments between biting/chewing and speech (r = 0.31; P <.05), between speech and the aesthetic component (r = -0.39; P <. 01) and the dental aesthetic index (r = 0.34; P <.05), and between the aesthetic component and appearance (r = -0.28; P <.05). Logistic regression analysis after dichotomization (treatment/no treatment need) confirmed that the aesthetic component was the only statistically significant factor (odds ratio, 0.57; 95% confidence limits 0.34 to 0.97).
The aim of this study was to ascertain if the presence of patients' relatives during cardiopulmonary resuscitation altered perceived symptoms of stress in accident and emergency personnel participating in resuscitation attempts. An anonymous structured questionnaire survey of all accident and emergency staff participating in non-traumatic adult cardiopulmonary resuscitation was designed to elicit symptoms of an acute stress reaction within 24 hours based on ICD-10 diagnostic criteria. One hundred and fourteen staff replies were received, a reply rate of 89%. Twenty-five replies had two or more symptoms of an acute stress reaction. The grade or role of the staff member had no influence on the presence of stress symptoms. There was no difference in rates of reporting between staff resuscitating in the presence or absence of relatives. It is concluded that the presence of relatives witnessing resuscitation attempts does not affect self-reported stress symptoms in staff participating in resuscitation attempts.
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The thymus is colonized by circulating progenitor cells that differentiate into mature T cells under the influence of the thymic microenvironment. We report here the cloning and function of the avian thymocyte Ag ChT1, a member of the Ig superfamily with one V-like and one C2-like domain. ChT1-positive embryonic bone marrow cells coexpressing c-kit give rise to mature T cells upon intrathymic cell transfer. ChT1-specific Ab inhibits T cell differentiation in embryonic thymic organ cultures and in thymocyte precursor cocultures on stromal cells. Thus, we provide clear evidence that ChT1 is a novel Ag on early T cell progenitors that plays an important role in the early stages of T cell development.
Thymopoiesis is initiated by the colonisation of the epithelial rudiment with blood-borne hemopoietic precursors. Their subsequent differentiation to the functionally mature T cell subsets is exquisitely linked to sequential interaction with a diverse array of thymic epithelial cells which form discrete microenvironments. The development and organisation of the epithelium, however, is in turn controlled by thymocyte subsets. In particular the medulla organization depends upon activating signals provided by mature thymocytes to epithelial and dendritic cells. These signals are lacking in RelB-deficient mice leading to the disorganization of the corticomedullary junction and abnormal negative selection despite normal thymocyte maturation. This thymic stromal cell architecture phenotype is found in autoimmune diseases suggesting that abnormalities in the establishment of medullary microenvironments might be linked to the development of autoimmunity.
The repeatability of energy-expenditure measurements were studied in five children and four adults without disabilities using the Cosmed K4 (high technology). The ability to detect change in measurements was compared between this instrument and the Physiological Cost Index (PCI; low technology). The results of repeatability (95% range) for oxygen cost were 13.1% in children and 13% in adults. In contrast, the SD of PCI was 6 to 72% of the mean in adults and wider in children (91%; 95% range). The validity of PCI as an outcome measure was questioned. In addition, 177 children with motor disability were prospectively studied using the Cosmed K4. Previous experience with the Cosmed K2 (intermediate technology) helped to develop a practical and repeatable protocol for testing children with disability using the Cosmed K4. The protocol commenced with 5 minutes of rest to achieve baseline values of heart rate and oxygen consumption, followed by 10 minutes of continuous walking at a self-selected speed on a 10-metre level oval walking track. The test concluded with 5 minutes of rest to monitor the return to baseline values. Ninety-one percent of the children with disability quickly reached a steady-state of oxygen consumption and carbon-dioxide production. The carbon-dioxide sensor in the Cosmed K4 has enabled a new group of severely involved children with cerebral palsy (9%) to be defined. These children have been termed 'physiologically marginal ambulators'.
OBJECTIVES: To compare two activated charcoal preparations (Carbomix and Actidose-Aqua) in terms of amount ingested and incidence of vomiting after ingestion. METHODS: Single blinded prospective randomised controlled trial. RESULTS: The mean amount of charcoal ingested was Carbomix 26.5 g, Actidose-Aqua 19.5 g. The mean difference was 7 g (95% confidence interval (CI) 1.5 to 12.4 g). The incidence of vomiting was for the Carbomix 6% and the Actidose-Aqua 8%. The mean difference in vomiting was 2% (95% CI -0.8 to 4.8) CONCLUSIONS: Carbomix administration results in an increased amount of activated charcoal ingested after oral administration. Rates of vomiting after activated charcoal administration were low when compared with previously reported rates.
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In a murine model of breast cancer, IL-12 therapy exerts potent anti-angiogenic effects which contribute to tumor regression. After 7 days of treatment, levels of tumor VEGF protein decline markedly and are undetectable at 14 days. This decline is accompanied by a fall in MMP-9 and, as the tumors regress, an increase in its natural inhibitor, TIMP-1. A cell line established from the primary tumor produced VEGF in vitro. IFN-gamma reduced tumor cell production of VEGF over a 24-hr period in vitro, suggesting that IL-12-induced IFN-gamma may be responsible for the decline in VEGF levels in vivo. There is also in vitro evidence that IL-12 regulates stromal cell interactions, leading to decreased MMP-9 and increased TIMP-1 production. Thus, we suggest that at least 2 mechanisms are involved in IL-12 regulation of angiogenesis, removing the pro-angiogenic stimulus and blocking the release and activity of MMPs.
Expression of a single Ag receptor on lymphocytes is maintained via allelic exclusion that generates cells with a clonal receptor repertoire. We show in normal mice and mice expressing functionally rearranged TCR alphabeta transgenes that allelic exclusion at the TCR alpha locus is not operational in immature thymocytes, whereas most mature T cells express a single TCRV alpha-chain. TCRV alpha allelic exclusion in mature thymocytes is regulated through a CD45 tyrosine phosphatase-mediated signal during positive selection. Using functional and genetic systems for selection of immature double TCRV alpha+ thymocytes, we show that peptide-specific ligand recognition provides the signal for allelic exclusion, i.e., mature T cells maintain expression of the ligand-specific TCRV alpha-chain, but lose the nonfunctional receptor. Whereas activation of TCRV beta-chains or CD3epsilon leads to receptor internalization, TCRV alpha ligation promotes retention of the TCR on the cell surface. Although both TCRV alpha- and TCRV beta-chains trigger phosphotyrosine signaling, only the TCRV beta-chain mediates membrane recruitment of the GTPase dynamin. These data indicate that TCRV alpha-directed signals for positive selection control allelic exclusion in T cells, and that developmental signals can select for single receptor usage.
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A cohort of ten children with X-ray negative inversion ankle injuries were studied using Magnetic Resonance Imaging. The images obtained were scored on six pathological criteria. Despite all ten having normal plain radiographs, 50 per cent were found to have direct evidence of growth plate injury. Seventy per cent of the cohort had periosteal elevation including all those with evidence of growth plate injury. This study supports previous work which suggested that children with 'X-ray' negative acute inversion ankle injuries who exhibited the clinical signs of injury to their lower fibular growth plate most probably have an undisplaced Salter-Harris Type 1 fracture of this structure, despite normal radiographs.
We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression, CIITA (for class II transactivator). Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system. Characterization of our line led to two new findings. First, a substantial number of cells can express class II molecules in the absence of CIITA, albeit at 5-fold reduced levels, most notably dendritic cells in s.c. lymph nodes; therefore, the CIITA gene cannot be an absolute 'master gene' controlling the expression of class II molecules, as had been thought. Second, in contrast to recent results on human cell lines, CIITA is not critically involved in the IFN-gamma-induced up-regulation of MHC class I genes.