Neutron-rich isotopes 54-57Ti.
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Biomedical subjects
Publications and source records attributed to M Robinson.
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The role of MHC class II in the presentation of Heligmosomoides polygyrus antigens has been investigated, using a number of T cell hybridomas produced in A and E positive and negative mice. By using fixed and irradiated antigen presenting cells (APC), further evidence has emerged, to support earlier data, that there can be differential processing requirements during the presentation of H. polygyrus antigens by A and E molecules. In concordance with these earlier observations, this work provides further evidence than individual T cells can respond to antigen when presented by more than one MHC molecule. Previously, this evidence has been restricted to individual MHC molecules of the same haplotype, but these data show that H. polygyrus produces antigens which can be presented by both syngeneic and allogeneic MHC molecules. These antigens do not appear to be synonymous with the previously described H. polygyrus superantigen, as presentation is restricted to specific MHC haplotypes. It is proposed that H. polygyrus may produce these antigenic molecules as part of its strategy to manipulate the host immune system.
The sensory neurons of the vestibular and nodose ganglia of the chicken embryo have nearby and distant targets, respectively. In vitro studies have shown that these neurons survive independently of neurotrophins when their axons are growing to their targets and become dependent on brain-derived neurotrophic factor (BDNF) for survival when their axons reach the vicinity of their targets. Although the timing of BDNF dependence is principally controlled by an intrinsic timing mechanism in the neurons, the onset of dependence can be accelerated by BDNF exposure toward the end of the phase of neurotrophin independence. We have used quantitative reverse transcription/polymerase chain reaction to study the expression of transcripts coding for BDNF and the catalytic isoform of its receptor tyrosine kinase, TrkB, in these neurons and their targets at different stages of development. We show that the peripheral and central target tissues of these neurons express BDNF mRNA prior to the arrival of sensory axons. Vestibular neurons express trkB mRNA before nodose neurons, which accords with the earlier response of vestibular neurons to BDNF. In culture, early nodose neurons start expressing trkB mRNA after 36 h incubation, which is 36 h before these neurons become dependent on BDNF for survival. Although BDNF does not affect the timing and level of trkB mRNA expression during the first 48 h in vitro, it increases the level of trkB mRNA after this time. The timing of BDNF-induced elevation of trkB mRNA correlates with the period during which BDNF exposure accelerates the onset of BDNF dependence in nodose neurons. These results suggest that the timing of BDNF dependence in developing sensory neurons is due in part to expression of catalytic TrkB and demonstrate that a BDNF autocrine loop is not required for the survival of sensory neurons during the earliest stages of their development.
In patients with cystic fibrosis (CF), dehydration of airway secretions leads to a decrease in mucociliary clearance (MCC). We examined the acute effect of MCC of a single administration by aerosolization of hypertonic saline (7%) (HS), amiloride (0.3% in 0.12% NaCl) (AML) and a combination of AML and HS (AML + HS) in 12 patients with CF using a radioaerosol technique. Isotonic saline [0.9%] (IS) was used as a control solution. As both the AML and HS solutions induced cough in some patients, the last nine patients studied also underwent a cough clearance day. This was to eliminate the possible confounding effect of cough on MCC measurement. Patients ranged from 18 to 28 yr (mean +/- SD, 22 +/- 3) with an FEV1 of 27 to 112% predicted (61 +/- 30%). Following deposition of the radioaerosol, baseline clearance was assessed for 30 min. This was followed by a 30-min intervention period. Assessment of post-intervention clearance for a further 30 min was then performed. Comparison of the amount of radioaerosol cleared from the right lung was made at 60 min (%C60) and 90 min (%C90) using repeated measures ANOVA. The percent cleared at 60 and 90 min was significantly increased with HS (%C60 = 26.5%, %C90 = 29.4%) and the combination of AML + HS (%C60 = 23.1%, %C90 = 27.4%) compared with both IS (%C60 = 14.7%, %C90 = 17.5%) and COUGH (%C60 = 18.0%, %C90 = 19.5%), p < 0.01. Inhalation of hypertonic saline is a potentially useful treatment in patients with cystic fibrosis.
Ventilatory mechanics were measured at rest and during steady-state (25%, 50%, 75%) and maximal exercise (W-Max) on a cycle-ergometer in eight adult patients (FEV1 22 to 114% of predicted) with cystic fibrosis (CF). Tidal flow-volume loops were measured at rest and during exercise and placed within the maximal pre- and postexercise flow-volume loops, based on measured end-expiratory lung volume (EELV). The degree of flow limitation was expressed as the percentage of the tidal flow-volume loop that met the expiratory boundary of the maximal loop (TFVL%). Pressure-volume relationships were assessed by measurement of transpulmonary pressure (PTP). Peak inspiratory PTP was compared with maximal inspiratory pressures at rest and during exercise (Pcap(i)) at the equivalent lung volume. The maximal effective expiratory pressure (Pmax(e)) was determined using the orifice technique. Three patients with milder disease (FEV1 114, 98, 89% of predicted) did not show any flow limitation at rest or 50% W-Max but two did show some flow limitation at W-Max (0, 3, 23 TFVL%) with a decrease in EELV (-400, -200, -300 ml). There was considerable reserve for inspiratory and expiratory pressure generation at W-Max. Flow limitation was noted at rest in three patients and at 50% W-Max in the five patients with more severe airways obstruction. The increased flow was achieved by an increase in EELV in all five patients (+400, +430, +330, +150, +700 ml at W-Max). Pcap(i) was reached in two patients (-28, -36 cm H2O), while Pmax(e) was exceeded by four patients suggesting inefficient pressure generation. Expiratory flow limitation, hyperinflation, and pressure swings approaching capacity severely compromised the capacity to generate ventilation in some patients with CF.
With increasing numbers of elderly people, and the escalating costs of health care, screening becomes increasingly important for identifying those older people with social health care needs who appear in their primary care physicians' offices. Many people are not aware of available social services. Families with serious social problems are not finding the help they need. The aim of this study was to develop and refine a questionnaire as a screening tool to identify elderly outpatients in primary care settings who are at high risk for psychological, social or environmental needs. This study identified those ten factors at each site which were most indicative that further intervention was needed. There were consistencies among the coordinators across sites in terms of what factors triggered intervention. Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) were more likely to be predictive of the coordinator's intervention than were other factors.
Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but toxicity, at the higher doses, was evident by: 1) losses in body weight gain and organ weights, 2) reductions in food and water consumption, and 3) in the hematological and microscopic examinations in both study periods. Significant decreases in erythrocyte count, hemoglobin, and hematocrit levels were found in the high dose level in males after 10 and 90 days. Dose-related increases in kidney and liver weights were observed in both sexes at 25 mg/kg-day in the 90-day study and in various organs for both 19 and 46 mg/kg-day in the 10-day study. Histopathological examination identified the forestomach as the primary target organ for both sexes and in both studies with significant dose-related increases in mucosal hyperplasia (acanthosis) and hyperkeratosis. Based on the data presented, a lowest observable adverse effect level (LOAEL) for oral exposure of Sprague-Dawley rats to epichlorohydrin is 3 mg/kg-day for 10 days and 1 mg/kg-day is suggested as the no observed adverse effect level (NOAEL) for a 90 day oral exposure. These conclusions were the same whether the lesions were analyzed for each sex individually or whether the data in each study was pooled.
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BACKGROUND: Twenty-four-hour ambulatory pH studies have traditionally been performed with placement of the pH electrodes proximal to the lower esophageal sphincter (LES). More recently, simultaneous gastric and esophageal pH monitoring studies have been performed to allow the simultaneous assessment and correlation of esophageal and gastric pH. OBJECTIVES: The purpose of this study was to determine if pH probe placement across the LES increases esophageal acid exposure either in asymptomatic, healthy volunteers or in symptomatic patients with a documented history of erosive esophagitis. METHODS: Ten healthy volunteers (five female, five male; mean age 27 yr) and 13 patients with endoscopically confirmed erosive esophagitis (seven female, six male; mean age 35 yr) were randomly assigned, in cross-over fashion, into two protocols. The first protocol required placement of a dual antimony pH electrode catheter (2.1-mm outside diameter) across the LES with pH electrodes positioned 5 cm above and 10 cm below the manometrically identified LES. The second protocol required catheter placement 5 cm and 20 cm above the LES. Twenty-four-hour pH monitoring was performed on all subjects. Healthy volunteers were permitted an unrestricted diet and were studied in an out-patient setting. Symptomatic patients were assessed in an inpatient setting on a standardized diet with a refluxogenic dinner meal. RESULTS: The total number of reflux episodes, number of reflux episodes greater than 5 min, and the fraction of time that pH was less than 4 were evaluated over the total 24-h time period in the upright and supine positions. Nonparametric paired tests including a Wilcoxon signed rank test and a Robust analysis were used for statistical assessment. There was no significant increase in gastroesophageal reflux observed with placement of the pH probe across the LES either in the asymptomatic healthy volunteers or in patients with documented erosive esophagitis. Neither upright nor supine esophageal acid exposures were modified by catheter placement. CONCLUSIONS: Our study results indicate that placement of a 2.1-mm diameter pH probe across the LES does not induce reflux in asymptomatic healthy volunteers or in patients with GERD. Dual site ambulatory pH monitoring with trans-sphincteric pH catheter placement is a valid diagnostic technique that can be applied clinically when required.
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Persons of African descent living in the Western hemisphere, including African Americans, have the highest prevalence of hypertension in the world. Debate continues as to whether it is their African ancestry or the Western environment that is more important in increasing the prevalence of hypertension in the African Diaspora above that of indigenous Africans as well as of fellow inhabitants in the Western hemisphere. Current data support that hypertension in African Americans, like that in other population groups, arises from the interaction of environmental factors with a susceptible physiology that is determined in part by genetic factors. Dietary sodium chloride (NaCl) is an important environmental factor, and the inability to prevent blood pressure from increasing to hypertensive levels in response to the comparatively high NaCl content of Western diets characterizes the majority of hypertensive African Americans. Studies discussed herein suggest a strong genetic component for the physiology of "salt sensitivity." Phenotypes that are indicative of this sensitivity are more common in African Americans than in Americans of European descent and in hypertensive African Americans compared with normotensive African Americans. Further studies are needed to more clearly define these genetic markers that determine salt sensitivity.
In this pilot study, data held by the Registrar of Births, Deaths and Marriages was linked to the Patient Master Index at St Vincent's Hospital Melbourne in order to identify early post discharge deaths, and inpatient records were linked with the Victorian Inpatient Minimum Database. Between July 1991 and December 1993 there were 831 deaths within 28 days of discharge. Injuries and poisoning were the commonest cause of death in younger patients who had attended the emergency department. These were responsible for 64% of deaths under the age of 40 years. There were deaths from cardiovascular disease which had been unrecognised during the hospital stay. There is also the need to identify in hospital those at risk of suicide. Amongst inpatients who were discharged home or transferred, the risk of death was greatest in the days immediately following discharge. Policies relating to the transfer of patients need to be reviewed as the study found that 30% of patients who had been transferred to long term care facilities died within four days. In conclusion, linking mortality and morbidity data can highlight areas of hospital care where there is the potential to prevent premature death, and improve management. The outcome of coronial investigations should be transmitted to hospitals for quality assurance purposes.
OBJECTIVES: This study was designed to compare lansoprazole 30 mg, lansoprazole 15 mg, omeprazole 20 mg, and placebo in the treatment of erosive reflux esophagitis. METHODS: In a double-blind, multicenter study, 1284 patients with endoscopically diagnosed erosive reflux esophagitis were randomized to received lansoprazole 30 mg (n = 422), lansoprazole 15 mg (n = 218), omeprazole 20 mg (n = 431), or placebo (n = 213) once daily for 8 wk. At 2, 4, 6, and 8 wk, healing was evaluated endoscopically. Patients kept daily diaries of symptoms. RESULTS: Healing rates at 2, 4, 6, and 8 wk were 65.3%, 83.3%, 89.4%, and 90.0%, respectively, for lansoprazole 30 mg; 56.3%, 74.6%, 80.3%, and 78.8% for lansoprazole 15 mg; 60.9%, 82.0%, 89.7%, and 90.7% for omeprazole 20 mg; and 23.9%, 32.8%, 36.6%, and 40.0% for placebo (all active treatments higher than placebo, p < 0.001). Healing rates with lansoprazole 30 mg were significantly higher than with lansoprazole 15 mg at all time points (p < 0.05). Healing rates with omeprazole 20 mg were significantly higher than with lansoprazole 15 mg at 4, 6, and 8 wk and were similar to those with lansoprazole 30 mg. Based on patient diaries, lansoprazole 30 mg produced better symptomatic relief than lansoprazole 15 mg or omeprazole 20 mg, primarily early in the treatment course. CONCLUSIONS: Both lansoprazole 30 mg and omeprazole 20 mg were more effective than lansoprazole 15 mg in esophageal mucosal healing. Compared with omeprazole 20 mg, lansoprazole 30 mg was as safe, was similarly effective with respect to esophageal healing, and provided superior symptomatic relief, primarily early in treatment. Lansoprazole 30 mg provided greater symptomatic relief than lansoprazole 15 mg.
Irritable bowel syndrome (IBS), is characterized by gastrointestinal hyperalgesia. In this study we investigated mucosal application of dyclonine on urge to defecate and pain threshold in volunteers and IBS patients (n = 10). Either saline or dyclonine (40 ml enema) was administered 10 minutes prior to rectosigmoid distension or cutaneous cold water pressor test. In IBS patients and volunteers no differences in cutaneous pain thresholds were noted. However, IBS patients had a lower pain threshold in the rectosigmoid than volunteers. In volunteers there was a significant difference between the threshold for urge to defecate and the threshold for rectosigmoid pain that was not apparent in IBS patients. Dyclonine administered directly into the rectosigmoid did not alter urge to defecate or pain threshold induced by distension in volunteers or IBS patients. These data suggest that the origin of pain perception is localized in deeper structures within the wall of the rectosigmoid colon.
The miswak chewing stick is an oral hygiene device used by the majority of people in Arab Gulf countries. Despite its widespread use, few studies demonstrated its benefits or applications as an alternative and convenient means for cleansing the teeth. This paper will examine the unique properties of the miswak chewing stick and its proper use.
Studies of cell lines and some cultured neurons have demonstrated potential cross-talk between neurotrophins and their receptors; high concentrations of neurotrophins can exhibit either agonist or antagonistic actions on heterologous neurotrophin receptors. We have studied neurotrophin discrimination among the sensory neurons of the embryonic chicken trigeminal system. We show that nerve growth factor (NGF) at a concentration that is six orders of magnitude greater than that required to promote the survival of NGF-dependent dorsomedial trigeminal ganglion (DMTG) neurons has no effect on the survival of brain-derived neurotrophic factor (BDNF)-dependent trigeminal mesencephalic nucleus (TMN) neurons and does not affect the dose-response relationship of these neurons to BDNF. A similar high level of neurotrophin-3 neither promotes the survival of BDNF-dependent ventrolateral trigeminal ganglion neurons nor affects the dose response of these neurons to BDNF. High levels of BDNF have a negligible effect on the survival of mid-embryonic DMTG neurons. These results show that some neurons are able to discriminate completely between neurotrophins at very high concentrations, indicating that neurotrophin responses can be far more highly specific than previously appreciated.