Predictors of psychiatric comorbidity in cancer patients at the time of their discharge from the hospital

Purpose

A cancer diagnosis can have a substantial impact on one’s mental health. The present study investigated the prevalence and predictors of psychiatric comorbidities in cancer patients at the time of their discharge from the hospital.

Methods

Psychiatric comorbidities were assessed shortly before hospital discharge and half a year after hospitalization using a structured clinical interview (SCID), based on the diagnostic and statistical manual of mental disorders (DSM-IV). Frequencies at both time points were estimated using percentages and corresponding 95% confidence intervals. Predictors of mental disorders were identified using binary logistic regression models.

Results

At time of hospital discharge, 39 out of 334 patients (12%) were diagnosed with a psychiatric comorbidity, and 15 (7%) were diagnosed half a year later. Among the diagnoses, adjustment disorders (3%) were most frequent at the time of hospital release, while major depression (3%) was the most frequent 6 months later. Having a mental disorder was associated with unemployment (odds ratio (OR) 3.4, confidence interval (CI) 1.1–10.9, p = 0.04). There was no evidence that school education (OR 2.0, CI 0.4–9.0, p = 0.38), higher education (OR 0.7, CI 0.2–2.4, p = 0.60), income (OR 1.0, CI 1.0–1.0, p = 0.06), tumor stage (OR 1.1, CI 0.4–3.2, p = 0.85), type of disease (OR 0.6, CI 0.2–2.1, p = 0.47), pain (OR 1.0, CI 1.0–1.0, p = 0.15), fatigue (OR 1.0, CI 1.0–1.0, p = 0.77), or physical functioning (OR 1.0, CI 1.0–1.0, p = 0.54) were related to the presence of a psychiatric comorbidity.

Conclusions

Unemployment was associated with at least a threefold increased risk of mental disorder, which highlights the need for special attention to be given to this subgroup of cancer patients.

     

Social withdrawal after laryngectomy

This investigation focuses on the psychosocial concomitants of a laryngectomy. Semistructured interviews were conducted with 218 laryngectomized patients. Standardised questionnaires were used to assess patients’ social activity (FPAL, EORTC QLQ-C30), intelligibility of speech (PLTT, FPAL), mental well-being (HADS), and perceived stigmatisation (FPAL). More than 40% of the patients withdrew from conversation. Only one-third of all patients regularly took part in social activities. About 87% perceived stigmatisation because of their changed voice and more than 50% felt embarrassed because of their tracheostoma. Almost one-third of the patients had increased anxiety and depression scores. Moderate objective speech intelligibility was found, though patients were not particularly satisfied with their voice. Social activity emerged to be independent from age, gender, treatment variables, and stage of disease. Multivariate analysis resulted in two independent factors representing two patterns of social withdrawal. On the one hand, there was withdrawal from conversation accompanied by increased depression and poor speech intelligibility. On the other hand, there were reduced social activities accompanied by increased anxiety and perceived stigmatisation.     

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

Objectives

Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs.

Material and methods

To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA.

Results

CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier.

Conclusions

CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly.

Clinical relevance

Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.

     

Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

Volume dynamics in migrating epithelial cells measured with atomic force microscopy

Migration of transformed renal epithelial cells (transformed Madin-Darby canine kidney cells, MDCK-F cells) relies on the activity of a Ca(2+)-sensitive K+ channel (IK channel) that is more active at the rear end of these cells. We have postulated that intermittent IK channel activity induces local cell shrinkage at the rear end of migrating MDCK-F cells and thereby supports the cytoskeletal mechanisms of migration. However, due to the complex morphology of MDCK-F cells we have not yet been able to measure volume changes directly. The aim of the present study was to devise a new technique employing atomic force microscopy (AFM) to measure the volume of MDCK-F cells in their physiological environment and to demonstrate its dependence on IK channel activity. The spatial (x, y' and z) co-ordinates of each pixel of the three-dimensional image of MDCK-F cells allow calculation of the volume of the column "underneath" a given pixel. Thus, total cell volume is the sum of all pixel-defined columns. The mean volume of 17 MDCK-F cells was 2500+/-300 fl. Blockade of the IK channel with the specific inhibitor charybdotoxin (CTX) increased cell volume by 17+/-4%; activation of IK by elevating the intracellular [Ca2+] with the Ca2+ ionophore ionomycin decreased cell volume by 19+/-3%. Subtraction images (experimental minus control) reveal that swelling and shrinkage occur predominantly at the rear end of MDCK-F cells. In summary, our experiments show that AFM allows the measurement not only of total cell volume of living cells in their physiological environment but also the tracing of local effects induced by the polarized distribution of K+ channel activity.     

Nuclear pore function viewed with atomic force microscopy

In this review we focus on studies using atomic force microscopy (AFM) to describe the function of nuclear pore complexes (NPC). After a short introduction of AFM we follow the route of cargo molecules from the cytosol into the nucleus. AFM visualizes cargo before translocation into the nucleoplasm, cargo docking at the cytoplasmic NPC surface, cargo passing through the NPC and changes in NPC conformation in response to ATP, Calcium and pH. We discuss AFM experiments on nuclear envelopes on the basis of previous data obtained with more conventional techniques such as electron microscopy, confocal microscopy and other imaging techniques. Finally we draw attention to the recently developed nuclear hourglass technique that serves as a new electrophysiological approach to studying the structure-function relationship of NPC in combination with AFM at a molecular level.