Tobramycin Serum Concentrations After Aerosol and Oral Administration in Cystic Fibrosis

We sought to describe tobramycin absorption after aerosol administration to cystic fibrosis (CF) subjects. Serum tobramycin concentrations were determined by modification of the radioimmuno-assay (RIA) technique, lowering the limit of detection from 1.0 &mgr;g ml(minus sign1) to 0.05 &mgr;g ml(minus sign1). In 37 studies, after aerosol delivery of 666 plus minus 195 mg to the airway of 24 patients, in which 222 samples were assayed, only 1 serum sample contained tobramycin at a concentration greater than 1.0 &mgr;g ml(minus sign1). Twenty-six of the 37 studies permitted estimation of pharmacokinetic parameters of tobramycin. The serum clearance of tobramycin following aerosol adminstration is 39.13 plus minus 0.393 L h(minus sign1) (mean plus minus standard error of the mean), with an elimination half-life of 3.072 plus minus 0.194 h. The half-life was significantly longer than that found after intravenous adminstration. The elimination rate constant (K(e)) was calculated to be 0.234 plus minus 0.002 h(minus sign1). Estimated total-body clearance in which systemic absorption was determined from sputum and urinary recovery of tobramycin was 0.094 plus minus 0.002 1 hr(minus sign1) kg(minus sign1). We also studied tobramycin absorption in six CF subjects after ingestion of a 80-mg m(minus sign2) dose, to gain insight into the tobramycin levels observed after swallowing an aerosol. Four out of the six subjects had measurable serum tobramycin concentration after ingestion. The serum concentration-time curve mirrored what was seen after aerosol administration. We concluded that tobramycin has poor systemic absorption in CF subjects after aerosol administration. Tobramycin in serum after aerosol administration is in part due to the gastrointestinal absorption of swallowed drug, as well as absorption from lower respiratory tract.     

Plasma kinetics of aclacinomycin A and its major metabolites in man

Summary The plasma pharmacokinetics of the antineoplastic anthracycline antibiotic aclacinomycin A (Acm) and its metabolites were studied in 12 patients treated with 60–120 mg/m² during a phase I clinical trial. Total plasma drug fluorescence initially declined very rapidly, but from 2 to 24 h after injection, fluorescence rose progressively to intensities greater than those measured 1 min after Acm injection. Plasma total drug fluorescence slowly declined from 24 to 72 hours after Acm administration. These events reflected the rapid disappearance of Acm and the subsequent appearance of two highly fluorescent metabolites. One metabolite co-chromatographed with and had a fluorescence spectrum identical to known metabolite F₁ (bisanhydroaklavinone). The other metabolite did not co-chromatograph with any previously described Acm metabolite. This metabolite had a fluorescence spectrum unlike any previously described Acm metabolite and was not altered by treatment for 60 min with 0.2N HCl at 100°C or by treatment for 24h at 37°C with bacterial -glucuronidase or limpet aryl sulfatase.Abbreviations used Acm aclacinomycin A - Dnr daunorubicin - Ard adriamycin - TLC thin layer chromatography - MLAB on-line modeling laboratory, Division of Computer Resources and Technology, National Institutes of Health - CxT concentration times time - C_p plasma concentration - t Time after administration of drug - R_f relative retardation factor - HPLC high performance liquid chromatography     

Understanding the role of COVID-19–related workplace stress and institutional betrayal on mental health in nurses: Some heroes wear scrubs

This study examined the association of three specific COVID-19–related workplace stressors (percentage of nursing work with COVID-positive [COVID+] patients, number of COVID-19–related patient deaths witnessed, and living separately from family for safety) and their associations with posttraumatic stress symptoms (PTSS) and symptoms of major depressive disorder (MDD) and generalized anxiety disorder (GAD) among 391 nurses (93.6% White, 93.4% utilize she/her pronouns). Cross-sectional data were collected via an online survey. Institutional betrayal (i.e., the perception that an institution failed to protect a member who depends on and trusts it) was examined as a moderator of these associations. Although institutional betrayal was not a significant moderator in the three individual models, it held small-to-medium–sized positive main effects with PTSS and symptoms of GAD and MDD in both the individual and combined models. In the individual models, the percentage of nursing work with COVID+ patients was significantly positively associated with all three mental health conditions, f² = .019–.195, whereas it only showed a significant effect with PTSS in the combined model, f² = .138. Living separately from family was significantly positively associated with PTSS and MDD symptoms in both the individual, f² = .037 and .015, respectively, and combined models, f² = .025 and .013, respectively. Number of patient deaths held a significant positive association with PTSS alone, f² = .022, in the individual model only. The findings are discussed in light of ways in which health care settings can better support and prioritize mental health among nursing staff.     

A Neuropsychological Perspective on Abstract Word Representation: From Theory to Treatment of Acquired Language Disorders

Natural languages are rife with words that describe feelings, introspective states, and social constructs (e.g., liberty, persuasion) that cannot be directly observed through the senses. Effective communication demands linguistic competence with such abstract words. In clinical neurological settings, abstract words are especially vulnerable to the effects of stroke and neurodegenerative conditions such as Alzheimer’s disease. A parallel literature in cognitive neuroscience suggests that abstract and concrete words are at least partially neuroanatomically dissociable. Much remains to be learned about the nature of lexical-semantic deficits of abstract words and how best to promote their recovery. Here, we review contemporary theoretical approaches to abstract-concrete word representation with an aim toward contextualizing patient-based dissociations for abstract words. We then describe a burgeoning treatment approach for targeting abstract words and suggest a number of potential strategies for future interventions. We argue that a deeper understanding of is essential for informing language rehabilitation.