Disease management without disease managers.
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Asthma↗
Biomedical subjects
A Lewis
Publications and source records attributed to A Lewis.
Outbreak of Salmonella indiana associated with egg mayonnaise sandwiches at an acute NHS hospital.
An outbreak of Salmonella indiana infection in December 2000 affected 17 staff, relatives and patients at an acute NHS Hospital in Swansea. Epidemiological investigation identified egg mayonnaise sandwiches as the vehicle of infection. It was not possible to definitively determine the source of the infection or how the prepared sandwiches became contaminated. The most likely explanation was a pasteurisation failure of a batch of the egg roll used to make these sandwiches. Sandwiches are the most frequently identified vehicle of infection in foodborne outbreaks of salmonella infection in hospitals in England and Wales. The process of sandwich preparation has inherent risks because it involves considerable handling of food, which is consumed without further cooking. Care is required in all stages of preparation including the sourcing of materials used to produce the sandwiches. NHS Trusts should review their Hazard Analysis Critical Control Point plans for sandwich production.
Case-Control Studies↗
The use of human hematopoietic growth factors (rhGM-CSF and rhEPO) as a supportive therapy for FIV-infected cats.
Recombinant human GM-CSF (rhGM-CSF) and erythropoietin (rhEPO) were tested on chronically FIV-infected laboratory cats and uninfected specific-pathogen-free (SPF) cats. In Study 1, a total of eight cats (four cats per group of either infected or uninfected cats) received subcutaneous injection (twice a day) for 2 weeks with 5 microg/kg of rhGM-CSF, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. Four of eight rhGM-CSF-treated cats (two cats each from infected and uninfected groups) developed elevated WBC counts which peaked at Days 5-8 of treatment when compared to placebo-treated cats. The elevated WBC counts were attributed to the increase in either neutrophils, lymphocytes, eosinophils, monocytes, or their combinations. The RBC counts, platelet counts, and blood chemistry were not significantly affected by the treatment. Anti-rhGM-CSF antibodies were detected in six of eight rhGM-CSF-treated cats by Day 35 post-first treatment. All rhGM-CSF-treated infected cats but no placebo-treated infected cats had 1-2 log increase in FIV load in the PBMC during the treatment. In vitro studies suggest that rhGM-CSF has an effect on FIV replication in T cells but not in alveolar macrophages. Five of eight rhGM-CSF-treated cats had low-grade fever at 3-6 days of treatment. In Study 2, four cats per group of either infected or uninfected cats were treated (subcutaneously once a day) three times a week for 2 weeks with 100U/kg of rhEPO and monitored as before, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. All rhEPO-treated cats had a gradual increase in RBC, Hgb, and PCV counts which peaked at 2-4 weeks post-first rhEPO treatment, whereas none of the placebo-treated cats had significant increase in these parameters. The rhEPO-treated cats also developed elevated WBC counts consisting of either elevated neutrophils, lymphocytes, or their combination by 4 weeks post-first treatment but there was no statistical difference between rhEPO-treated and placebo-treated groups. None of the cats developed anti-rhEPO antibodies and no remarkable changes in blood chemistry, clinical signs, and FIV loads or FIV antibody titers were observed. Overall, rhEPO can be used safely on FIV-infected cats but the use of rhGM-CSF on FIV-infected cats should be performed with discretion.
Anemia↗
In vivo gene transfer by low-volume jet injection.
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Adenocarcinoma↗
O(2) sensing by airway chemoreceptor-derived cells. Protein kinase c activation reveals functional evidence for involvement of NADPH oxidase.
Accumulating evidence suggests that neuroepithelial bodies are airway O(2) sensors. Recently, we have established the H-146 small cell lung carcinoma line as a suitable model to study the biochemical basis of neuroepithelial body cell chemotransduction. Here we explore the possibility that hypoxic modulation of K(+) channels is intimately linked to activity of NADPH oxidase. Graded hypoxia caused graded inhibition of whole cell K(+) currents, which correlated well with membrane depolarization. Pretreatment with the phorbol ester, 12-O-tetradecanoyl (TPA), inhibited K(+) currents at all potentials. Although 4alpha-phorbol 12,13-didecanoate and TPA in the presence of bisindolylmaleimide were also able to depress K(+) currents, only TPA could significantly ameliorate hypoxic depression of these currents. Thus, protein kinase C (PKC) activation modulates the sensitivity of these cells to changes in pO(2). Furthermore, because the addition of H(2)O(2), a downstream product of NADPH oxidase, could only activate K(+) currents during hypoxia (when endogenous H(2)O(2) production is suppressed), it appears likely that PKC modulates the affinity of NADPH oxidase for O(2) potentially via phosphorylation of the p47(phox) subunit, which is present in these cells. These data show that PKC is an important regulator of the O(2)-transduction pathway and suggests that NADPH oxidase represents a significant component of the airway O(2) sensor.
4-Aminopyridine↗
The effect of serum iron concentration on iron secretion into mouse milk.
1. The concentration of iron in mouse milk is approximately 3 times that of the serum. Although there is clear evidence for the presence of the transferrin receptor in the rodent mammary gland, the precise mechanisms of iron transfer into milk are not known. 2. Milk iron was linearly related to the serum iron:transferrin ratio in lactating mice whose serum iron ranged from 8 to 66 microM. 3. Increasing the iron binding capacity of the milk by 340 microM by targeting the lactoferrin transgene to the mammary gland did not alter the relation between milk iron and the serum iron:transferrin ratio. 4. The steady-state distribution ratio of 125I-transferrin between plasma and milk was about 0.2, indicating that transcytosed transferrin contributed a maximum of 6% of the milk iron. 5. Fluorescently labelled transferrin incubated with the in situ gland localized mainly near the basal surface of the mammary alveolar cells. 6. These experiments provide evidence that the initial and rate-limiting step in the transfer of iron into milk is binding to a basal transferrin receptor. 7. A theoretical model of the relation between milk and serum iron suggests that the affinity of apotransferrin for the basal recycling system may be higher than observed in many other cell types.
Animals↗
Electrical stimulation of neonatal cardiac myocytes activates the NFAT3 and GATA4 pathways and up-regulates the adenylosuccinate synthetase 1 gene.
Electrically stimulated pacing of cultured cardiomyocytes serves as an experimentally convenient and physiologically relevant in vitro model of cardiac hypertrophy. Electrical pacing triggers a signaling cascade that results in the activation of the muscle-specific Adss1 gene and the repression of the nonmuscle Adss2 isoform. Activation of the Adss1 gene involves the calcineurin-mediated dephosphorylation of NFAT3, allowing its translocation to the nucleus, where it can directly participate in Adss1 gene activation. Mutational studies show that an NFAT binding site located in the Adss1 5'-flanking region is essential for this activation. Electrical pacing also results in the increased synthesis of GATA4, another critical cardiac transcription factor required for Adss1 gene expression. MEF2C also produces transactivation of the Adss1 gene reporter in control and paced cardiac myocytes. Using the Adss1 gene as a model, these studies are the first to demonstrate that electrical pacing activates the calcineurin/NFAT3 and GATA4 pathways as a means of regulating cardiac gene expression.
Adenylosuccinate Synthase↗
3D MR imaging of coronary arteriovenous fistulas.
Coronary arteriovenous fistula are uncommon if not rare, but represent the most prevalent hemodynamically significant congenital malformations of the coronary arterial circulation. The goal of this report is to evaluate the use of 3D volume rendering from transaxial breathhold coronary MR angiograms to visualize coronary arteriovenous fistulas. Coronary MR angiography offers a new non-invasive technique that accurately defines the anatomy of these malformations, setting the stage for surgical intervention.
Adult↗
GFP is a selective non-linear optical sensor of electrophysiological processes in Caenorhabditis elegans.
Electrophysiology of the nematode Caenorhabditis elegans has the potential to bridge the wealth of information on the molecular biology and anatomy of this organism with the responses of selected cells and cellular neural networks associated with a behavioral response. In this paper we report that the nonlinear optical phenomenon of second harmonic generation (SHG) can be detected using green fluorescent protein (GFP) chimeras expressed in selected cells of living animals. Alterations in the SHG signal as a result of receptor ligand interactions and mechanical stimulation of the mechanosensory cells indicate that this signal is very sensitive to membrane potential. The results suggest that this approach to membrane potential measurements in C. elegans and in other biological systems could effectively couple data on selective locations within specific cells with functional responses that are associated with behavioral and sensory processes.
Animals↗
The effect of food on the bioavailability of oral gemifloxacin in healthy volunteers.
The effect of food on the bioavailability of gemifloxacin was investigated at two doses (320 and 640 mg) in healthy male and female volunteers. A total of 21 subjects entered the open label, four-period crossover study. Each subject received single oral doses of 320 and 640 mg in the fasted state and after a high fat meal, on separate dosing occasions in a randomised fashion. There was on average, a 3% (95% CI (0.88, 1.07)) and 12% (95% CI (0.79, 0.97)) reduction in AUC and a 12% (95% CI (0.76, 1.02) and 14% (0.75, 1.00) reduction in Cmax after the 320- and 640-mg doses, respectively. The results indicate a minor effect of food on bioavailability of gemifloxacin (320 and 640 mg). Such a reduction in systemic exposure would be considered to be not clinically relevant. Tmax data were inconclusive but indicated a possible slight delay in Tmax of, on average, 0.75 and 0.21 h after the 320- and 640-mg doses, respectively. Delays of this magnitude in reaching maximum concentrations are unlikely to be of clinical importance for an antibiotic drug. Both 320 and 640 mg gemifloxacin were well tolerated in fed and fasted states by healthy volunteers. It can be concluded therefore, that gemifloxacin can be taken with and without food.
Adult↗
The effect of ferrous sulphate and sucralfate on the bioavailability of oral gemifloxacin in healthy volunteers.
Sucralfate is a cytoprotectant with antacid properties and ferrous sulphate is commonly prescribed for iron-deficiency anaemia. This open, randomized, single-dose, five-way crossover study investigated the effect of sucralfate and ferrous sulphate on the bioavailability of gemifloxacin, a novel fluoroquinolone antimicrobial. Twenty-seven healthy male volunteers received gemifloxacin, 320 mg p.o., alone, 3 h after sucralfate (2 g) or ferrous sulphate (325 mg), or 2 h before sucralfate or ferrous sulphate. Each subject received all five dosing regimens in random order with at least 6 days between regimens. Plasma samples collected up to 48 h after dosing with gemifloxacin, were assayed for gemifloxacin to determine pharmacokinetic parameters. Administration of gemifloxacin 3 h after sucralfate produced a marked decrease of 53% in the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-infinity), and a decrease of 69% in the maximal plasma concentration (Cmax). Administration of gemifloxacin 3 h after ferrous sulphate resulted in only a modest reduction of 11% in AUC0-infinity and of 20% in Cmax, which was not considered to be clinically significant. In contrast, at the doses used neither sucralfate nor ferrous sulphate altered gemifloxacin bioavailability when it was administered 2 h before either of these agents. Gemifloxacin was well tolerated in all the regimens. The results of this study support the dosing recommendation that gemifloxacin can be safely administered at least 2 h before sucralfate or ferrous sulphate, or at least 3 h after ferrous sulphate.
Adolescent↗
An educational intervention for front-line health professionals in the assessment and management of suicidal patients (The STORM Project).
BACKGROUND: Suicide prevention is a health priority in many countries. Improved management of suicide risk may improve suicide prevention. This study aimed to assess the feasibility of health district-wide training in the assessment and management of people at risk of suicide; and to assess the impact of training on assessment and management skills. METHODS: Staff in three health care settings, namely primary care, accident and emergency departments and mental health services (N = 359), were offered suicide risk management training in a district-wide programme, using a flexible 'facilitator' approach. The main outcomes were the rate of attendance at training, and changes in suicide risk assessment and management skills following training. RESULTS: It was possible to deliver training to 167 health professionals (47 % of those eligible) during a 6 month training period. This included 95 primary care staff (39%), 21 accident and emergency staff(42%) and 51 mental health staff (78%). Of these, 103 (69%) attended all training. A volunteer sample of 28 staff who underwent training showed improvements in skills in the assessment and management of suicide risk. Satisfaction with training was high. The expected costs of district-wide training, if it were able to produce a 2.5% reduction in the suicide rate, would be 99,747 pound sterling per suicide prevented and 3,391 pound sterling per life year gained. CONCLUSIONS: Training in the assessment and management of suicide risk can be delivered to approximately half the targeted staff in primary care, accident and emergency departments and mental health services. The current training package can improve skills and is well accepted. If it were to produce a modest fall in the suicide rate, such training would be cost-effective. However, a future training programme should develop a broader training package to reach those who will not attend.
Adult↗
Epidemiological features of and public health response to a St. Louis encephalitis epidemic in Florida, 1990-1.
A St. Louis encephalitis (SLE) epidemic in Florida during 25 weeks in 1990-1, resulted in 222 laboratory-diagnosed cases, an attack rate in the 28 affected counties of 2.25/100,000. Disease risk rose with advanced age, to 17.14/100,000 in persons over 80 years, and all 14 fatal cases were in persons over 55 years (median, 70 years). Community serosurveys in Indian River County, the epicenter of the outbreak (attack rate 21/100,000), showed acute asymptomatic infections in 3.6% of the persons surveyed, with higher rates in persons with outdoor occupational exposure (7.4%) and in clients of a shelter for the indigent (13.3%). A matched case-control study found that evening outdoor exposure for more than 2 h was associated with an increased risk for acquiring illness (odds ratio [OR] 4.33, 95% CI 1.23-15.21) while a number of recommended personal protective measures were protective. Four SLE patients were dually infected with Highlands J virus, the first reported cases of acute infection with this alphavirus. The case-control study provided the first evidence that a public education campaign to reduce exposure had a protective effect against acquiring the disease.
Adolescent↗
Varieties of groups and the perception of group entitativity.
Three studies examined perceptions of the entitativity of groups. In Study 1 (U.S.) and Study 2 (Poland), participants rated a sample of 40 groups on 8 properties of groups (e.g., size, duration, group member similarity) and perceived entitativity. Participants also completed a sorting task in which they sorted the groups according to their subjective perceptions of group similarity. Correlational and regression analyses were used to determine the group properties most strongly related to entitativity. Clustering and multidimensional scaling analyses in both studies identified 4 general types of groups (intimacy groups, task groups, social categories, and loose associations). In Study 3, participants rated the properties of groups to which they personally belonged. Study 3 replicated the results of Studies 1 and 2 and demonstrated that participants most strongly valued membership in groups that were perceived as high in entitativity.
Adult↗
Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.
Interleukin-1 (IL-1) is a proinflammatory cytokine that elicits its pleiotropic effects through activation of the transcription factors NF-kappaB and AP-1. Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1beta treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip-IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs). As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway.
Adaptor Proteins, Signal Transducing↗
Young school children working together: a measure of individualism/collectivism.
Co-operation and group working are key aspects of the National Curriculum, reinforced by recent moves towards redefining the primary school curriculum with a greater emphasis on 'citizenship'. There is little research on individual differences between children's preferences for group and individual working or young children's abilities to work in, and generalize from, group experiences. Furthermore, there are no reliable measures of these factors in children. The study reported in this paper was the first stage in research, the overall aim of which was to look at individual and group differences in young children working cooperatively and competitively in groups and alone. The aim of this study was to develop a new measure of individualism/collectivism and the associated factors: sociability and altruism. Some 152 children from two primary schools in England participated in this study. The mean age of the children was 5 years 5 months (range 4 years 11 months to 6 years 9 months). A new measure of individualism/collectivism based on instruments for use with adults was administered to the participating children. Two stable factors, individualism/collectivism and sociability, were identified and were both found to be reliable. The importance of the measure as a tool for use with other methods for evaluating the effectiveness of group work in classrooms is considered.
Altruism↗
Treatment of keratoderma blennorrhagicum with tazarotene gel 0.1%.
We report near clearing of keratoderma blennorrhagicum following topical application of tazarotene gel 0.1%. This is the first report detailing the use of tazarotene gel for this purpose.
Administration, Topical↗
Gastric acid suppression does not promote clostridial diarrhoea in the elderly.
Gastric acid prevents bacterial colonization of the stomach and suppression of its secretion might predispose to Clostridium difficile (CD) diarrhoea. We retrospectively studied elderly patients admitted to medical wards of an acute hospital to determine whether the incidence of CD diarrhoea was greater among those previously treated with gastric acid suppressants. From records of stool CD toxin tests undertaken in 1995 and 1996, we found 126 cases with positive results, and selected 126 controls with negative results. Information about pre-morbid illness, predisposing factors for CD and medication received in the preceding 16 weeks was obtained from case-notes. A greater number of CD positive cases had received antibiotics such as Cefuroxime, ciprofloxacin or macrolides with or without metronidazole, were more severely disabled, required assistance for feeding, or had hypoalbuminaemia before the onset of diarrhoea. A greater number of controls had received lactulose, suggesting either that its laxative effect resembled CD infection prompting frequent stool tests, or that it offered protection against CD in this group. Both groups were similar for the use of proton-pump inhibitors or H2-receptor antagonists, suggesting that susceptible elderly patients are not more likely to develop CD diarrhoea after receiving gastric acid suppression therapy.
Activities of Daily Living↗