“I smile, but Without Showing My Teeth”: The Lived Experience of Cleft, Lip, and Palate in Adults

Objective: To explore and describe the experience of growing up with unilateral cleft lip and palate (CLP) in adults. Design: Face-to-face interviews. Giorgi’s phenomenological method was used for analysis. Participants: Twenty-one (mean age: 40.8 years) adults treated for unilateral CLP during childhood and adolescence participated in the study. Results: Growing up with CLP meant to become aware of bodily otherness. The possible reactions from peers early in life complicated the striving for inclusion outside the close family. Being self-confident, clever in school, physically fit, and having trusted friends represented barriers against teasing and bullying. Nevertheless, the reflected image, in mirrors, windows, and photos, reminded the participants of the objectifying looks from others and often led to bodily adjustments that persisted into adulthood. The trajectory of treatment was not questioned during childhood, and the participants accepted the decisions on care made by experts and parents. Although problems related to the cleft could persist or return after the termination of ordinary treatment, a more hesitant view on the possible benefits of additional surgery was typical in adulthood. Conclusions: In retrospect, growing up with a unilateral CLP was found to have been an unquestioned part of the adult participants’ childhood, a burden that they feared would, to some extent, also be passed to their own children. However, the CLP had not prevented them from achieving goals and satisfaction in life. The occurrence of persisting psychological, functional, and esthetic challenges in adults suggests the need for an individualized, lifelong, and multidisciplinary perspective on CLP follow-up.publishedVersio

Tumor infiltration levels of CD3, Foxp3 (+) lymphocytes and CD68 macrophages at diagnosis predict 5-year disease-specific survival in patients with oropharynx squamous cell carcinoma

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (−) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (−) patients.publishedVersio

The acute phase reaction and its prognostic impact in patients with head and neck squamous cell carcinoma: Single biomarkers including c-reactive protein versus biomarker profiles

C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan–Meier analyses; three subsets could then be identified, and they differed in survival (p < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.publishedVersio

Tumor HPV status, level of regulatory T cells and macrophage infiltration predict up to 20-year non-disease-specific survival in oropharynx squamous cell carcinoma patients

Oropharynx squamous cell carcinoma (OPSCC) is of special interest because human papilloma virus (HPV) and/or smoking cause this disease. Influxes of inflammatory cells into such tumors are known to vary with prognoses. Aims: To study whether the density of tumor-infiltrating T lymphocytes and tumor-infiltrating macrophages predicted general 20-year overall survival (OS), as well as OS with only disease-specific survival (DSS) patients included. Methods: Biopsies from patients treated for OPSCC (n = 180) were stained by immunohistochemistry and the tumor cell macrophage (CD68), pan T lymphocytes (CD3), and regulatory T lymphocytes (Foxp3) densities were determined. The HE-determined percentage of matured tumor cells and the rate of invasion were calculated, and stromal desmoplasia were performed. Tumor HPV presence was studied by PCR. Twenty-year OS and five-year DSS patients were determined. Results: Tumor HPV status strongly predicted survival. High tumor infiltration of CD3, Foxp3 and CD68-positive cells predicted better twenty-year OS, with and without HPV stratification. Foxp3 and CD68 levels predicted OS, and 20-year among DSS patients, primarily among HPV(+) patients. Tumor HE-derived variables did not predict such survival. Conclusions: Tumor HPV status, level of Foxp3 tumor-infiltrating lymphocytes and CD68 tumor-infiltrating macrophages predicted up to 20-year OS of both all patients and disease-specific survived patients.publishedVersio

MicroRNA-138 abates fibroblast motility with effect on invasion of adjacent cancer cells

Background: Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells. Methods: Expression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion. Results: Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts’ motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway. Conclusions: Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.publishedVersio

Forbedringsseminar som metode for å styrke sykepleiestudenters kompetanse innen forbedringsarbeid og fremme pasientsikkerhet innen legemiddelhåndtering

AbstractQuality improvement seminar as a method to improve nursing students&rsquo; competence in the field of quality improvement and as a method to promote patient safety in medication managementQuality improvement projects between academia and clinical practice are in demand. The aim of this project was to develop and test an improvement method which could be implemented in a busy clinical hospital environment. An action research inspired approach was used. The action consisted of a quality improvement seminar where nursing students, teachers and nurses from clinical wards analyzed six case reports related to adverse events in medication management. Questionnaires determining the competence of nursing students related to improvement in medication management were used in a pretest - posttest study. Findings showed a significant improvement both in knowledge about the quality improvement process (p = 0.001) and about adverse events of medication (p = 0.005). On a scale from 0 (not suited) to 7 (particularly well suited), students scored 6.0 related to learning outcome of the quality improvement seminar. Quality improvement seminars seem to be effective for stimulating reflection on adverse events related to medication management.&nbsp

N-substituted benzamides inhibit NFκB activation and induce apoptosis by separate mechanisms

Benzamides have been in clinical use for many years in treatment against various disorders. A recent application is that as a sensitizer for radio- or chemotherapies. We have here analysed the mechanism of action of N-substituted benzamides using an in vitro system. We found that while procainamide was biologically inert in our system, the addition of a chloride in the 3′ position of the benzamide ring created a compound (declopramide) that induced rapid apoptosis. Furthermore, declopramide also inhibited NFκB activation by inhibition of IκBβ breakdown. An acetylated variant of declopramide, N-acetyl declopramide, showed no effect with regard to rapid apoptosis induction but was a potent inhibitor of NFκB activation. In fact, the addition of an acetyl group to procainamide in the 4′ position was sufficient to convert this biologically inactive substance to a potent inhibitor of NFκB activation. These findings suggest two potential mechanisms, induction of early apoptosis and inhibition of NFκB mediated salvage from apoptosis, for the biological effect of N-substituted benzamides as radio- and chemo-sensitizers. In addition it suggests that N-substituted benzamides are potential candidates for the development of anti-inflammatory compounds using NFκB as a drug target. © 1999 Cancer Research Campaig

Surgery and postoperative radiotherapy a valid treatment for advanced oropharyngeal carcinoma

Since 1992 we have prospectively included all head and neck cancer patients in our health region in a departmental based register. Our hospital takes care of all head and neck cancer patients in our health region consisting of approximately 1 million people. In 1997, we evaluated the results of the treatment of oropharyngeal cancer in the 1992–1997 period. On the basis of this evaluation, we changed our treatment policy for tonsillar and base of tongue carcinoma. We first changed the treatment for the lesions with worst prognosis, i.e., those with T3–T4 carcinomas, from radiotherapy only, to radical surgery and postoperative radiotherapy. We have since that time increasingly also operated the smaller oropharyngeal carcinomas. The 2 years’ overall survival and disease-specific survival for all patients diagnosed in the 1992–1997 period was 56 and 63%, respectively. The results from a similar group of patients in the 6 years’ period from 2000 to 2005, after the change in treatment, have increased to 83 and 88%. When we looked at the subgroup of patients in the 2000–2005 period treated with surgery and postoperative radiotherapy, 45 out of 69 patients (65%) presenting with an oropharyngeal cancer were fit for operation. With radical surgery and postoperative radiation therapy, the 2 years overall survival is now 91%. The 2-year disease-specific survival is 96% and the locoregional control is 98%. This is a marked improvement as compared to radiotherapy alone and definitely competitive with modern radiochemotherapy

Komprimirani matriksni dvokomponentni sustavi s metoklopramid hidrokloridom

The purpose of the present investigation was to produce a quick/slow biphasic delivery system for metoclopramide hydrochloride using the superdisintegrant Ac-di-sol for the fast release layer and hydroxypropyl methylcellulose K100M and Ucarflock 302 to modulate the release of the drug. A dual component tablet made up of a sustained release and an immediate release layer was prepared by direct compression. A 32 full factorial design was applied to systematically optimize the drug release profile of the sustained release layer. The results of the full factorial design indicate that a small amount of HPMC K100M and a large amount of Ucarflock 302 favor sustained release of the metoclopramide hydrochloride vaginal dual component system. The ex vivo residence time reveals that the formulation was retained for more than 10 h. The formulation gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 h, thus solving the problem of repeated administration, especially in pregnancy.Cilj rada bila je priprava brzog/sporog bifazičnog sustava za isporuku metoklopramid hidroklorida koristeći dezintegrator Ac-di-sol za sloj koji brzo oslobađa i hidroksipropil metilcelulozu K100M i Ucarflock 302 za moduliranje oslobađanja ljekovite tvari. Dvokomponentna tableta sa slojem za usporeno i slojem za brzo oslobađanje pripravljena je metodom izravne kompresije. 32 faktorijalni dizajn primijenjen je za sistematsko optimiranje profila oslobađanja ljekovite tvari u sloju za usporeno oslobađanje. Rezultati ukazuju na to da su mala količina HPMC K100M i velika količina Ucarflock 302 bitne za usporeno oslobađanje metoklopramid hidroklorida u dvokomponentnom sustavu za vaginalnu upotrebu. Ex vivo ispitivanja pokazuju da se pripravak zadržava više od 10 h. Naglo oslobađanje lijeka omogućava brzo postizanje udarne doze, a postupno oslobađanje tijekom 12 h održavanje učinkovite koncentracije, čime se rješava problem opetovane primjene, posebno u trudnoći

Håndtering av uønskede hendelser i en sykehusavdeling. En kvalitativ studie.

Background: To ensure patient safety at hospital admissions, awareness around the use of adverse events have increased in health care. Adverse events are one tool available to the leader to work with patient safety. To avoid, that the patient is in any way is harmed during the stay in the hospital, adverse events are to be used in a systematic way, to implement change in the organization to reduce risks. Purpose: By using the experience the nurses have achieved by reporting adverse events, I wanted to investigate why the nurses reports as few events as they do. If the leaders know on what assumptions the nurses will increase the reporting of adverse events, they are able to secure a well organized structure around the reporting process. Material and method: As method I have used a focus group interview consisting of five respondents. I compared the answers in the interview with quantitative data from the system for reporting adverse events. Results: In order to increase patient safety the nurses experience reporting adverse events as important. But error reporting will only increase in an environment of safety and in a non blaming culture. There has to be a system for taking care of the individual reporting harmful errors. The nurses mean that reporting adverse events are supposed to result in organizational learning. This is only achieved if report of errors result in feedback from the leader. They must experience that reporting have some consequences in daily work. To ensure a good reporting process, the structure must be in place, both the criteria for what kind of errors you are supposed to report, and the knowledge about the use of reports in improvement work. Leaders must be engaged in using the reports and to motivate nurses to report adverse events. Conclusions: The leaders in this organization have not been enough engaged in implementing a good reporting culture. The result is that the nurses are not motivated to report adverse events, in spite of the fact that they are aware of that the reporting of adverse events would be of essence to work with patient safety