Verocytotoxigenic Escherichia coli infection in dairy farm families.
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Biomedical subjects
Publications and source records attributed to J Wilson.
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Memory T cell responses are frequently highly restricted in terms of receptor usage. How and when such clonotypic dominance is established remains poorly understood. Here we have investigated the evolution of the T cell responses to an epitope from Epstein-Barr virus (EBV), (FLRGRAYGL), by analyzing TCR use of clones specific for this epitope, derived from peripheral blood mononuclear cells taken from individuals early during primary EBV infection and up to 3 years later. We show that, in a given individual, particular T cell clonotypes are selected early during the primary response to this epitope and that the same clonotypes dominate the late memory response. In one individual direct analysis of HLA-B8-restricted FLRGRAYGL-specific T cells, isolated from peripheral blood lymphocytes taken during primary EBV infection using a tetrameric MHC-peptide complex, confirmed the early selection of the dominant clonotypes.
OBJECTIVE: To determine the clinical and immunogenetic features of systemic sclerosis (SSc) patients with anti-Th/To autoantibodies. METHODS: HLA class II alleles were determined by DNA oligotyping in a large group of SSc patients with anticentromere antibodies (ACA), anti-topoisomerase I (anti-topo I), and anti-Th/To autoantibodies. RESULTS: Clinical features of the 28 anti-Th/To-positive SSc patients were similar to those observed in the 56 ACA-positive SSc patients, except for a decreased frequency of gastrointestinal involvement in anti-Th/To-positive patients. Immunogenetic analysis revealed a significant increase in the frequency of HLA-DR11 in the anti-Th/To-positive and the anti-topo I-positive patients. The anti-Th/To-positive patients also had a significant reduction in the frequency of HLA-DR7, similar to that seen in ACA-positive SSc patients. CONCLUSION: Despite clinical and immunogenetic similarities with both the ACA- and anti-topo I-positive patients, anti-Th/To-positive SSc patients present a characteristic pattern of clinical and immunogenetic features that may have implications regarding etiology, pathogenesis, and treatment.
The human zeta-globin gene is expressed in a tissue- and developmental-specific pattern, with expression confined to primitive erythroid cells of the embryonic yolk sac blood islands. Transgenic mouse studies have shown that the proximal zeta-globin promoter contains sequences that contribute to the stage-specificity of expression, but no systematic functional studies of the cis elements in the proximal zeta-globin promoter have been reported. In this paper, we show that a number of conserved sequence elements in the zeta-globin promoter are important for promoter activity in transiently transfected K562 erythroleukemia cells, which constitutively express zeta-globin. These include a GATA site at -105, a CCACC site at -93, a CCAAT box at -65, and a TATA box at -29. A highly conserved CCTCC sequence at -78 is not important for zeta-globin promoter activity in this system. Mutations at these sites do not result in increased promoter activity in OCIM1 cells, an erythroid line that does not express zeta-globin, suggesting none of these sites is a developmental silencer. Electrophoretic mobility shift assays show that K562 and OCIM1 nuclear extracts contain DNA-binding activities that interact with the -105 GATA, -65 CCAAT, and -29 TATA sites. In addition K562 cells, but not OCIM1 cells, have an activity that binds the -93 CCACC site. GATA-1 interacts with the GATA site. The K562 CCACC-binding protein is distinct from Sp1, Sp2, Sp3, Sp4, EKLF, and BKLF. A specific -65 CCAAT-binding activity is present in K562 and OCIM1 nuclear extracts that is distinct from other CCAAT-binding proteins including CBF/NF-Y, C/EBP, NF-1, and CP2. Thus, we have identified two novel factors that may contribute to the tissue or developmental stage-specific expression of zeta-globin.
The effects of the CCK(B) antagonists, CAM1028 and CI988 and a CCK(A) antagonist, CAM1481, were studied on the anxiety-related behaviour produced by withdrawal from chronic ethanol treatment, using the elevated plus maze. Cessation of chronic ethanol administration produced a profile, in both mice and rats, consistent with increase in anxiety-related behaviour. In mice, SC administration of CAM1028 or CI988 reduced the decrease in the time spent on the open arms, the number of entries into these arms and the increases in the latencies to first open arm entry, after withdrawal from the ethanol treatment. The increases in stretched attend postures and head dips from the closed arms and the central square seen during the withdrawal phase, were also decreased by the CCK(B) antagonists, but the decreases in the number of rears and in general activity were unaffected. The doses of CAM1028 and CI988 tested were 0.1 and 1 mg/kg; for some of the withdrawal-induced changes in behaviour only the 1 mg/kg dose was effective. In contrast, the CCK(A) antagonist, CAM1481, at the same doses, had little effect on the anxiety-related behaviour produced by withdrawal from chronic ethanol treatment, although it did decrease the changes in the number of rears and the head dipping behaviour. In rats, the majority of the changes produced by withdrawal from chronic ethanol treatment were decreased by CAM1028 at 1 mg/kg, although the decreases in open arm entries, rearing behaviour and in overall activity were unaffected. CAM1028, CI988 and CAM1481 had no effects on the behaviour of control mice or rats in the plus-maze. The results show that CCK(B) antagonists were effective in decreasing the majority of the anxiogenic effects of withdrawal from chronic ethanol treatment.
The aim of this study was to compare the exercise intensity and rating of perceived exertion (RPE) of a high-impact (HIP) and a low-impact (LIP) university aerobic dance session. Ten women [mean (SD) age 22.9 (2.6) years] took part in the study. An incremental treadmill test was performed by each subject to determine maximum oxygen consumption (VO2max) and maximum heart rate (HRmax). The measured VO2max [mean (SD)] was 49.0 (7.5) ml x kg(-1) x min(-1). The subjects were randomly assigned to LIP and HIP sessions (i.e. five of the subjects participated in the HIP session first, and the other five participated in the LIP session first). In a laboratory, heart rate, oxygen uptake and RPE were measured throughout each session for each subject. Expired air was collected continuously throughout the sessions using Douglas bags (ten bags over a 30-min period). The sessions consisted of 20 min of aerobic exercise (bags 1-7) followed by 5 min of local muscular endurance exercise (bags 8 and 9) and 5 min of flexibility exercises (bag 10). The mean intensity of the aerobic section of the LIP and HIP sessions was 51.6% and 64.7% VO2max, respectively. Ninety-five percent confidence intervals for the average difference between the HIP and LIP sessions demonstrate that the %VO2max was between 12% and 14% higher for the HIP session. The mean %HRmax for the LIP and HIP sessions was 71.4% and 76.7%, respectively, with the %HRmax in the HIP session being between 5.4% and 7.2% higher on average than that of the LIP session. On average, the RPE for the aerobic section of the HIP session (12.1) was consistently higher than that of the LIP session (11.1). HIP activity has the potential to maintain/improve the aerobic fitness of its participants. According to the literature, the exercise intensity elicited by LIP activity may have a limited training effect for the population utilised in this study, and for some individuals may result in detraining. Conversely, LIP activities may be an appropriate mode of exercise for overweight and unfit individuals.
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Although considerable effort has been directed toward improving the management of acute pain, ineffective pain management practices remain in many institutions across this country. While educational efforts have increased health care providers' knowledge regarding the management of pain, a concomitant change in practice has not occurred. This project was designed to examine barriers to the effective management of pain encountered in acute care settings. A repeated case study of attempts to change was conducted in six institutions located in the southeastern United States. Results identified seven major barriers to pain management: lack of knowledge, non-facilitative attitudes, inconsistent leadership, poor working relationships, cultural and religious biases, physicians' fears of legal repercussions and a lack of resources.
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Effects of the CCK(B) antagonists, CAM1028 and C1988, and the CCK(A) antagonist, CAM1481, were studied on the ethanol withdrawal syndrome. When handling-induced behavior was measured hourly for 12 h from withdrawal of ethanol, a small, but significant, protective effect was seen with 3 mg/kg CAM1028, but not with 0.3, 1, or 10 mg/kg. C1988 (0.3 1,3, or 10 mg/kg), or CAM1481 (0.1 or 1 mg/kg), had no effects. At 16 h from ethanol withdrawal, these ratings were significantly decreased by 3 mg/kg CAM1028 or C1988, but not by lower doses. At 16 h, CAM1481 had very small, but significant, protective effects. At 3 mg/kg, CAM1028, increased the latencies to audiogenic seizures, but had only small effects on convulsion incidence. CAM1481 did not alter the audiogenic convulsions. The decrease in convulsion thresholds to NMDLA, at 16 h from ethanol withdrawal, was completely prevented by CAM1028 or C1988, at 1 and at 3 mg/kg, but not by lower doses; CAM1481 had no significant effects. The results suggest change in CCK(B) receptors may be involved in the later stages of the ethanol withdrawal syndrome.
Managed care organizations are in an excellent position to implement population-based, as well as patient-centered, approaches to reduce behavioral risk factors associated with major chronic diseases. Group Health Cooperative of Puget Sound employed a population-based model for smoking that contributed to a decrease from 25% to 15.5% in smoking prevalence in 10 years among its more than 550,000 adult enrollees in western Washington. This model may have application to other arenas where health systems can support beneficial behavior change.
Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.
The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility that patterns of digit formation may relate to spermatogenesis and hormonal concentrations. This work was concerned with the ratio between the length of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in right and left hands has a sexually dimorphic pattern; in males mean 2D:4D = 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal length. The dimorphism is present from at least age 2 years and 2D:4D is probably established in utero; (ii) high 2D:4D ratio in right hands was associated with germ cell failure in men (P = 0.04); (iii) sperm number was negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men testosterone concentrations were negatively related to right hand 2D:4D and in women and men LH (right hand), oestrogen (right and left hands) and prolactin (right hand) concentrations were positively correlated with 2D:4D ratio and (v) 2D:4D ratio in right hands remained positively related to luteinizing hormone and oestrogen after controlling for sex, age, height and weight.
An open study over 4 yr has been conducted to determine the efficacy of cyclical etidronate treatment in patients from the community, with osteoporosis and in those at risk who attended an osteoporosis clinic; and to clarify whether bone remodelling returns to baseline values and bone mass is maintained after completion of a 3 yr course of treatment. One hundred and fifteen female patients, with and without osteoporotic fractures (n = 62 and 53, respectively), who were unsuitable for, or declined, hormone replacement therapy, received 3 yr cyclical etidronate treatment (400 mg etidronate disodium for 14 days followed by 500 mg elemental calcium for 76 days repeated in 3-monthly cycles) and 1 yr treatment-free follow-up. There was an overall increase in lumbar spine bone density (patients without fractures 2.6%, P < 0.001; with fractures 4.3%, P < 0.01) with minimal change at the femoral neck. The serum concentration of bone formation markers (osteocalcin and bone alkaline phosphatase) fell in response to treatment to a nadir at 6/12 (75 and 83% of baseline, respectively; P < 0.001). A cohort of patients (n = 29), 14 without fractures and 15 with fractures, was studied in more detail. After completion of treatment in the following treatment-free year, there was a resurgence of bone turnover (osteocalcin and bone alkaline phosphatase 117 and 122% of baseline, respectively; P < 0.05 and P < 0.01) with some evidence of maintenance of bone mass already gained. There is no evidence of persistent suppression of bone turnover after completion of treatment.
Sinus pericranii is an anomalous extracranial vascular malformation that is in continuity with the intracranial dural venous sinuses. Five case reports, three congenital and two traumatic, are described. Clinical management, including evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by plastic surgeons will allow for earlier diagnosis and appropriate surgical management, resulting in decreased risk of complications.
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OBJECTIVE: To evaluate pain associated with chest tube insertion in a group of patients with malignant pleural effusions. DESIGN: Prospective case series. SETTING: Acute care cancer center in an academic institution. PATIENTS: Fifty-two patients with symptomatic malignant pleural effusions. Twenty-six evaluated by conventional approach to chest tube insertion (group 1), 26 evaluated after institution of a new chest tube protocol (group 2). INTERVENTIONS: A new protocol was designed to improve pain control during chest tube insertion. The protocol included improved housestaff and nursing education, premedication, proper insertion techniques, and more liberal and precise delivery of local anesthetic. OUTCOME MEASURES: Both groups were evaluated by a verbal self-report scale (1-10) to assess pain and anxiety. RESULTS: The mean pain rating in group 1 was 6.2 (+/-0.76) compared with 3.7 (+/-5.6) in group 2 (p < 0.01). In group 1, pain or anxiety was 9 or 10 in 12 of 26 on a scale of 1 to 10, compared with 2 of 26 in group 2 (p < 0.001). Anxiety rating was 4.5 (+/-0.72) in group 1 compared with 1.5 (+/-0.54) in group 2 (p < 0.01). CONCLUSIONS: Chest tube insertion was associated with an unacceptably high level of pain and anxiety in our hospital. A new protocol, including housestaff education and changes in nursing policies, technical aspects, local anesthetic dose and delivery, and pre-medication, allowed us to approach the goal of a painless chest tube insertion.
The objective of this study was to compare the single- and multiple-dose pharmacokinetics and electrocardiographic effect of a 10-mg oral dose of ebastine in elderly (ages, 65-85 years) and young (ages, 18-35 years) healthy volunteers. Thirty-seven subjects completed this randomized, double-blind, multiple-dose, placebo-controlled, parallel group study. The elderly group consisted of 18 subjects, with 13 subjects receiving 10 mg ebastine and 5 receiving matching placebo. The young group consisted of 19 subjects, with 13 subjects receiving 10 mg ebastine and 6 receiving matching placebo. On study days 1 and 3 through 10, each subject received a single 10-mg dose of ebastine or matching placebo in the morning with a standard breakfast. No drug was administered on study day 2 because of pharmacokinetic sampling. Blood samples were collected at selected times postdose on study days 1, 2, and 10. Plasma samples were analyzed for ebastine and its active metabolite, carebastine, using a validated high-performance liquid chromatography method. No plasma ebastine concentrations were detected, suggesting essentially complete metabolic conversion of ebastine to its metabolites. Analysis of variance showed no statistically significant differences between young and elderly single- and multiple-dose carebastine pharmacokinetics with respect to area under the plasma concentration-time curve, maximum concentration (Cmax ), terminal elimination rate constant, apparent oral clearance, or apparent volume of distribution. The mean time of maximum concentration value for young subjects was 1 hour longer than that for elderly subjects after single-dose administration but was comparable after multiple-dose administration. Within-group comparisons of both the young and elderly showed that pharmacokinetics between single dose and steady state were not statistically different. However, the mean steady-state carebastine Cmax values were approximately twofold greater than the mean Cmax values obtained after single-dose administration. A twofold increase in Cmax values between single-dose and steady-state administration is predicted for drugs such as carebastine, because its input interval is approximately equal to its elimination half-life. Twelve-lead electrocardiography was performed before dosing on day 1 and repeated 4 hours postdose on days 1, 5, and 10. Twenty-four hour Holter monitoring was also performed before and at the end of the study. No clinically relevant findings were found by electrocardiography or Holter monitoring between ebastine and placebo in the elderly and young subjects.