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Graefe's Archive for Clinical and Experimental Ophthalmology - To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with...  相似文献   
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Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.  相似文献   

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Introduction Amisulpride is a substituted benzamide that, at low doses, selectively blocks D2 and D3 presynaptic dopamine receptors, enhancing dopaminergic transmission in frontal cortex and limbic areas. Many clinical studies versus placebo, tricyclic antidepressants and selective serotonin reuptake inhibitors showed amisulpride antidepressant effect, supporting its safety and rapid onset of action. In oncological population, depression is quite frequent and difficult to treat because of the particular sensitivity of cancer patients to the antidepressants’ side effects. Goals of work The aims of this study were to evaluate efficacy, safety and tolerability of low doses of amisulpride (50 mg) in oncological, depressed patients during chemotheraphy. Materials and methods One hundred six consecutive cancer outpatients with depressive symptoms were treated in a prospective, intention to treat, 4-week study, and were evaluated in single-blind with Montgomery Asberg rating scale for depression (MADRS), clinical global impression (CGI) and dosage record treatment emergent symptom scale (DOTES) to assess side effects of treatment. Main results After 4 weeks of treatment, scores of MADRS and CGI significantly improved (p < 0.002; p < 0.001, respectively), with a reduction of depressive symptoms concerning both emotional (such as apparent sadness, reported sadness, inner tension, etc.) and physical cluster (such as lack of appetite, reduction in weight, tiredness and insomnia) with good tolerability (only two patients dropped out). Conclusions This study is the first trial on the use of amisulpride in a cohort of oncological, depressed patients during chemotherapy. Amisulpride demonstrated high efficacy and safety. Controlled studies are needed to confirm these preliminary data.  相似文献   
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Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.  相似文献   
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OBJECTIVE: To evaluate the dynamics of bacterial contamination of healthcare workers' (HCWs) hands during neonatal care. SETTING: The 20-bed neonatal unit of a large acute care teaching hospital in Geneva, Switzerland. METHODS: Structured observation sessions were conducted. A sequence of care began when the HCW performed hand hygiene and ended when the activity changed or hand hygiene was performed again. Alcohol-based handrub was the standard procedure for hand hygiene. An imprint of the five fingertips of the dominant hand was obtained before and after hand hygiene and at the end of a sequence of care. Regression methods were used to model the final bacterial count according to the type and duration of care and the use of gloves. RESULTS: One hundred forty-nine sequences of care were observed. Commensal skin flora comprised 72.4% of all culture-positive specimens (n = 360). Other microorganisms identified were Enterobacteriaceae (n = 55, 13.8%); Staphylococcus aureus (n = 10, 2.5%); and fungi (n = 7, 1.8%). Skin contact, respiratory care, and diaper change were independently associated with an increased bacterial count; the use of gloves did not fully protect HCWs' hands from bacterial contamination. CONCLUSIONS: These data confirm that hands become progressively contaminated with commensal flora and potential pathogens during neonatal care, and identify activities at higher risk for hand contamination. They also reinforce the need for hand hygiene after a sequence of care, before starting a different task, and after glove removal.  相似文献   
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Benzo[a]pyrene diol epoxide adducts with hemoglobin (Hb) weremeasured to detect human exposure to environmental benzo[a]pyrenefrom traffic exhaust. Benzo[a]pyrene tetrahydrotetrols (BPTs)released from Hb after acid hydrolysis were quantitated by gaschromatography-mass spectrometry after immunoaffinity chromatography.Fifty three newspaper vendors were enrolled. The median adductconcentration was 0.3 fmol BPTs/mg Hb in high density traffic-exposedvendors and  相似文献   
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