Bacterial DNA activates human neutrophils by a CpG-independent pathway

Bacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and dendritic cells in a CpG-dependent manner. In this work we demonstrate that bacterial DNA, but not mammalian DNA, induces human neutrophil activation as assessed by L-selectin shedding, CD11b upregulation, and stimulation of cellular shape change, IL-8 secretion, and cell migration. Induction of these responses is not dependent on the presence of unmethylated CpG motifs, as neutrophil stimulatory properties were neither modified by CpG-methylation of bacterial DNA nor reproduced by oligonucleotides bearing CpG motifs. We found that human neutrophils express Toll-like receptor (TLR) 9 mRNA. However, as expected for a CpG-independent mechanism, activation does not involve a TLR9-dependent signaling pathway; neutrophil stimulation was not prevented by immobilization of bacterial DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of note, both single-stranded and double-stranded DNA were able to induce activation, suggesting that neutrophils might be activated by bacterial DNA at inflammatory foci even in the absence of conditions required to induce DNA denaturation. Our findings provide the first evidence that neutrophils might be alerted to the presence of invading bacteria through recognition of its DNA via a novel mechanism not involving CpG motifs.     

COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology - Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK...     

Identifying the minimal important difference in patient-reported outcome measures in the field of people with severe mental illness: a pre–post-analysis of the Illness Management and Recovery Programme

Quality of Life Research - Complementary interventions for persons with severe mental illness (SMI) focus on both personal recovery and illness self-management. This paper aimed to identify the...     

Allergy to pine nuts in a bird fancier

A patient is described with the bird-egg syndrome who experienced an anaphylactic reaction after eating some of her parrot's food (pine nuts: Pinus pinea ). Specific IgE against this nut and another pine nut ( P cembra ) was demonstrated by RAST. Cross-reactivity between these botanically related seeds was shown by RAST inhibition. Besides avian antigens, bird food antigens should be taken into consideration when symptoms of allergy occur on exposure to birds.     

Creative mathematics with clopidogrel; exaggeration of the preventive effect by manufacturer

A number of Dutch medical journals recently carried an advertisement stating that clopidogrel treatment reduced the number of ischaemic complications with 26%, compared with aspirin treatment. This is a miscalculation: the actual reduction is 0.51% in absolute rates, and 8.7% in relative terms. The error by Sanofi-Synthelabo arose by comparison of the event rates for clopidogrel (5.32%) as well as for aspirin (5.83%) with that in an imaginary placebo group (7.77%), yielding a reduction of ischaemic complications of 2.45% and 1.94% respectively; erroneous comparison of these two numbers leads to a difference of 26%.     

Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid,urinary metabolites of the fungicide captan,in rats and humans

Summary Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 g/l for THPI and 110 g/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%–2% and 3%–9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan.     

Projecting future drug expenditures--2003.

Drug expenditure projections for 2003 and factors likely to influence drug costs are discussed. The United States continues to face the challenge of increased growth in health expenditures, and drug expenditures are continuing to increase faster than the growth in total health care expenditures. These increases can be largely attributed to an increase in the average age of the U.S. population and technological advancement. On the basis of price inflation and non-price inflationary factors, including increases in volume, shifts in patient and therapeutic intensity, and expected approval of new drugs, a 10-12% increase in drug expenditures in 2003 for the inpatient setting and a 13.5-15.5% increase for ambulatory care settings are forecasted. While few new drugs are expected to greatly influence expenditures in 2003, the continued diffusion of recently approved drugs such as drotrecogin alfa and nesiritide will have a dramatic impact on total drug expenditures and must be carefully considered in the budgeting process. An agent likely to have a significant impact on HIV treatment is enfuvirtide, the first in a new class of antiretrovirals (fusion inhibitors), but its high cost ($10,000-$15,000 per year) may limit patients' access to this medication. An expanded user's guide is provided to assist the reader in appropriate application of this information in the drug budgeting process. Technological, demographic, and market-based changes and changes in public policy will continue to influence pharmaceutical expenditures in the coming year. An understanding of the overall drivers of medication expenditures and vigilance in monitoring pharmaceutical innovation are critical in the effective management of these resources.     

Patient outcomes after therapeutic interchange of dolasetron for granisetron.

The impact of using therapeutic interchange (TI) of dolasetron for granisetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) was evaluated. An outcomes evaluation was conducted in two cohorts of adult outpatients who had not previously received chemotherapy. Before the interchange, 20 patients were enrolled in a granisetron cohort, and after the interchange to dolasetron, 42 patients were matched to the initial cohort. Evaluations using the modified Functional Life Index--Emesis (MFLIE) compared changes in functional status before and after treatment. Nausea and vomiting frequency, satisfaction with antiemetics, reported adverse effects, changes in antiemetic therapy, and the use of antiemetics postchemotherapy were also evaluated. Success, defined as no vomiting and less than a 2.5-unit change in MFLIE score, was demonstrated in 45% of granisetron patients and 40% of dolasetron patients (p = 0.461). While functional status declined in both groups in response to chemotherapy, the changes in MFLIE scores did not differ between agents (-16.8 +/- 20.16 versus -19.39 +/- 26.36 in granisetron and dolasetron patients, respectively) (p = 0.650). Patients were equally satisfied with their prescribed antiemetic therapy, although less than half of patients achieved antiemetic success in the 72-hour study period. Self-reported adverse events attributed to serotonin type 3-receptor antagonist use were minimal and not significantly different between groups. The TI did not negatively affect patient outcomes and produced savings of $143,534 in the first year of the program. TI of dolasetron for granisetron for CINV did not affect functional status, nausea control, or patient satisfaction with antiemetic therapy.     

Use of qualitative and quantitative fluorescence techniques to assess dermal exposure

Fluorescent tracers provide a way of simultaneously assessing the mass of a contaminant hazardous substance on the surface of the skin of a worker and the area of skin exposed. These parameters, along with the duration of exposure and the estimated contaminant concentration in the skin contamination layer, can be used to calculate the likely uptake through the skin. Repeated assessment of the mass of tracer on a surface within a room or on the surface of the skin can also allow the net transfer of contaminant to that compartment to be estimated. Qualitative evaluation of transfer processes using fluorescent tracers can help identify important secondary sources of exposure.     

Is semi-closed endarterectomy of the superficial femoral artery combined with a short venous bypass in case of insufficient venous material an acceptable alternative for limb-threatening ischemia?

BACKGROUND: The aim of this study was to analyse the results of infragenual arterial revascularisation using semiclosed endarterectomy of the superficial femoral artery combined with a short venous bypass in patients with critical leg ischemia and insufficient venous material for a straightforward femorocrural reconstruction. METHODS: From December 1990 through December 1998 thirty patients were studied (22 males and 8 females; mean age 65 years, range 31-92 years). The mean follow-up was 26 months (range 1-96 months). Cumulative primary patency and limb salvage rates were calculated according to life-table analysis. RESULTS: The cumulative primary patency was 60.3% at 1 year and 48.4% at 3 years. The limb salvage rate was 68.6% at 1 and at 3 years. CONCLUSIONS: In patients with limb-threatening ischemia and lack of venous material for a straightforward venous femorocrural bypass, semi-closed endarterectomy of the superficial femoral artery combined with a short popliteo-crural bypass provides a good alternative.