Interprofessional education on complex patients in nursing homes: a focus group study.

BACKGROUND: An ageing population leads up to increasing multi-morbidity and polypharmacy. This demands a comprehensive and interprofessional approach in meeting patients' complex needs. This study describes graduate students' experiences of working practice based in interprofessional teams with complex patients' care needs in nursing homes. METHOD: Students from advanced geriatric nursing, clinical nutrition, dentistry, medicine and pharmacy at the University of Oslo in Norway were assigned to groups to examine and develop a care plan for a nursing home patient during a course. Focus groups were used, 21 graduate students participating in four groups. Data were collected during spring 2018, were inductively analysed according to a thematic analysis method (Systematic Text Condensation). An analytical framework of co-ordination practices was applied to get an in-depth understanding of the data. RESULTS: Three themes were identified: 1) Complex patients as learning opportunities- an eye-opener for future interprofessional collaboration 2) A cobweb of relations, and 3) Structural facilitators for new collective knowledge. Graduate university students experienced interprofessional education (IPE) on complex patients in nursing homes as a comprehensive learning arena. Overall, different co-ordination practices for work organization among the students were identified. CONCLUSIONS: IPE in nursing homes facilitated the students' scope from a fragmented approach of the patients towards a relational and collaborative practice that can improve patient care and strengthen understanding of IPE. The study also demonstrated the need for preparatory teamwork training to gain maximum benefit from the experience. Something that can be organized by the education institutions in the form of a stepwise learning module and as an online pre-training course in interprofessional teamwork. Further, focusing on the need for well thought through processes of the activity by the institutions and the timing the practice component in students' curricula. This could ensure that IPE is experienced more efficient by the students.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

Generation and evaluation of a monoclonal antibody, designated MAdL, as a new specific marker for adenocarcinomas of the lung.

BACKGROUND: Different therapy regimens in non-small-cell lung cancer (NSCLC) are of rising clinical importance, and therefore a clear-cut subdifferentiation is mandatory. The common immunohistochemical markers available today are well applicable for subdifferentiation, but a fraction of indistinct cases still remains, demanding upgrades of the panel by new markers. METHODS: We report here the generation and evaluation of a new monoclonal antibody carrying the MAdL designation, which was raised against primary isolated human alveolar epithelial cells type 2. RESULTS: Upon screening, one clone (MAdL) was identified as a marker for alveolar epithelial cell type II, alveolar macrophages and adenocarcinomas of the lung. In a large-scale study, this antibody, with an optimised staining procedure for formalin-fixed tissues, was then evaluated together with the established markers thyroid transcription factor-1, surfactant protein-A, pro-surfactant protein-B and napsin A in a series of 362 lung cancer specimens. The MAdL displays a high specificity (>99%) for adenocarcinomas of the lung, together with a sensitivity of 76.5%, and is capable of delivering independent additional diagnostic information to the established markers. CONCLUSION: We conclude that MAdL is a new specific marker for adenocarcinomas of the lung, which helps to clarify subdifferentiation in a considerable portion of NSCLCs.

[Diagnostics for fungal infections of the lungs]. / Diagnostik von Pilzinfektionen der Lunge.

Recognition of and therapy for fungal infections of the lungs still presents problems even for the experienced clinician. The distinction between invasive mycoses of the lungs and fungal colonisations that do not require therapy is cinically difficult and can often not be made satisfactorily even with advanced microbiological diagnostics. One must differentiate between a primary, often locally limited, endemic pulmonary mycosis and a pulmonary mycosis against the background of a locally or systemically compromised immune system. Patients at risk include those with advanced HIV infections, patients under long-term antibiotic therapy as well as oncological and multimorbid patients. The pulmonary manifestation of a mycosis may not only be the starting point for a systemic dissemination but can also arise in the course of hematogenous spread of the infection. The latter can appear, for example, as an invasive pulmonary aspergillosis in immunesuppressed patients. Thus, early clinical, radiological and biological confirmation of the diagnosis is essential in order to avoid the possible complications of pulmonary mycosis.

Tumors in the lung--morphologic features and the challenge of integrating biomarker signatures into diagnostics.

In the last decade, pathologic approaches concerning diagnosis and treatment of lung carcinomas have increasingly moved towards the implementation of molecular methods into the process of decision. In this study, an overview is given referring to the variety of tumors in the lung including common primary lung neoplasms and secondary tumors, and a modus operandi is presented which integrates immunology as well as molecular pathology within the process of finding correct diagnoses. Besides the conventional and approved methods and techniques leading to appropriate treatment including so-called targeted therapies, pathologist's work meanwhile depends on both histologic and molecular results. Since molecular techniques have increasingly entered the field of routine diagnostics, challenges and possibilities have changed and are still rapidly developing. The proceeding integration of molecular-biologic investigations into the process of diagnosing has changed the nature of diagnostics and will continuously grow in the near future. Only by obtaining a proper diagnosis, the optimal treatment of a patient can be assured, whereupon the knowledge of gene mutations and/or altered protein expression is crucial. By identifying those novel molecular target structures, the therapeutic spectrum is tremendously enlarged and will finally improve the patient's prognosis by personalized targeted therapies.

Expression analysis of EML4 in normal lung tissue and non-small cell lung cancer (NSCLC) in the absence and presence of chemotherapeutics.

Despite considerable progress in the development of individualized targeted therapies of tumor diseases, identification of additional reliable target molecules is still mandatory. One of the most recent targets is microtubule-associated human EML4 generating a fusion-type oncogene with ALK demonstrating marked transforming activity in lung cancer. Since EML4 is a poorly characterized protein with regard to expression, function and regulation in human tissue, specimens of human tumor and tumor-free tissues obtained from patients with NSCLC were analyzed to determine the cellular localization. All tissue samples have been previously fixed with the novel HOPE-technique and paraffin embedded. Determination of both gene expression and protein levels of EML4 were performed using RT-PCR, in situ hybridization as well as immunohistochemistry, respectively. In human NSCLC tissue samples, possible regulation of EML4 transcription upon chemotherapy with combinations of most established cytotoxic drugs for NSCLC treatment was also studied employing the recently established ex vivo tissue culture model STST. In normal lung, both marked mRNA and protein levels of EML4 were localized in alveolar macrophages. In contrast, lung tumor tissues always showed consistent transcriptional expression in situ and by RT-PCR. Stimulation of NSCLC tissues with chemotherapeutics revealed heterogeneous effects on EML4 mRNA levels. Based on its expression patterns in both tumor-free lung and NSCLC tissues, human EML4 is likely to be closely associated with processes involved in local inflammation of the lung as well as with tumor behavior. Thus, our results suggest that EML4 may have the potential as a therapeutic target molecule in NSCLC chemotherapy.

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

BACKGROUND: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). METHODS: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). RESULTS: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). CONCLUSIONS: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

DNA bending by Cro protein in specific and nonspecific complexes: implications for protein site recognition and specificity.

Scanning force microscopy was used to resolve lambda Cro protein when bound as a single dimer or multiple dimers to its three operator (OR) sites. The bend angles induced by binding of Cro to specific and nonspecific sites were determined and are 69 degrees +/- 11 degrees for specific and 62 degrees +/- 23 degrees for nonspecific complexes. Bending of the nonspecific sites is advantageous for a protein such as Cro that bends its specific site, because it increases the binding specificity of the protein and it can be used by the protein to sample contacts required for the recognition of its target sequence. It is proposed here that bending of nonspecific DNA may be a general property among DNA binding proteins that bend their specific sites.

[Favorable response of pulmonary rheumatoid nodule to Rituximab]. / Gutes Ansprechen eines pulmonalen Rheumaknoten auf Rituximab.

Pulmonary rheumatoid nodules can be found in over 4% of patients with rheumatoid arthritis. Diagnostically they have to be differentiated from malignant and infectious processes. The present article describes a case of pulmonary rheumatoid nodule which responded well to Rituximab therapy.

Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide.

We have examined the effects of several PGs on the synthesis and release of the atrial natriuretic peptide (ANP) in vivo and in vitro. PGF2 alpha infusion in anesthetized rats resulted in a significant increase in plasma immunoreactive (ir) ANP levels in vivo despite effecting only modest changes in hemodynamics. The PGs were also effective at promoting irANP secretion in primary cultures of neonatal rat atrial and ventricular cardiocytes. PGF2 alpha increased irANP release with half-maximal induction seen at approximately 10(-8) M; PGE2 was somewhat less effective and prostacyclin (PGI2) was without effect. The PGs also increased ANP mRNA levels in these cells, suggesting that these agents exert a major effect on the synthesis as well as the secretion of the prohormone. Transient expression analysis of atrial cells transfected with 2,500 bp of human (h) ANP 5' flanking sequence linked to a chloramphenicol acetyltransferase (CAT) reporter demonstrated that PGF2 alpha (10(-5) M) increased hANP promoter activity approximately twofold relative to the control. PGF2 alpha had no effect on the promoterless control (pSV0-lamin CAT). Treatment of cultured atriocytes with high concentrations of a cyclooxygenase inhibitor resulted in a significant suppression of ANP secretion in vitro and a truncation of the plasma ANP response to volume infusion in vivo. Taken together these studies support a role for PGs as regulators of cardiac ANP synthesis and secretion, and suggest an additional mechanism whereby eicosanoids may act to control cardiovascular and renal homeostasis.

Donor Smoking and Older Age Increases Morbidity and Mortality After Lung Transplantation.

BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking status; these were further divided into three age groups: group A: 0 to 39 years; group B: 40 to 54 years; and group C: ≥55 years. RESULTS: One hundred fifty-one donors were former or actual smokers, 175 were nonsmokers, and 128 had unknown smoking histories. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from a smoking donor. CLAD-free survival was identical in all smoking groups, and overall survival was better both for lungs from nonsmoking donors and donors with unknown smoking status compared to lungs from smoking donors. One hundred sixty-nine donors were in age group A, 203 in B, and 82 in C. Baseline forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of carbon monoxide were lowest in the groups who received lungs from donors older than 55 years. Overall survival as well as CLAD-free survival was significantly lower with donors ≥55 years. CONCLUSIONS: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking waiting list mortality into account.

The HOPE technique opens up a multitude of new possibilities in pathology.

Fixation of tissues with formalin results in well-preserved morphology but to a high degree leads to degradation of nucleic acids, which substantially constricts the spectrum of applicable molecular techniques. The novel HOPE-fixative with subsequent paraffin embedding, as an alternative to formalin, has been shown to result in a morphological preservation comparable to formalin-fixed, paraffin-embedded specimens. Due to a similar workflow like in formalin-fixation and paraffin embedding, the HOPE technique can be successfully established within any pathological institute. We have shown that DNA, RNA and proteins are protected in HOPE-fixed, paraffin-embedded tissues for at least eight years. Moreover, we described procedures which permit successful application of all common molecular techniques such as in situ hybridization targeting either DNA or RNA, immunohistochemistry without antigen retrieval and for formalin-refractory antigens, PCR, RT-PCR, Western blot, Northern blot, and transcription microarrays to HOPE-fixed, paraffin-embedded tissues. Furthermore, HOPE-fixed tissues can be used for the construction of tissue microarrays for enhanced high-throughput analyses on the molecular level. Using the HOPE technique as its crucial methodological base, ex vivo model systems could be established, e.g. for the simulation of early events in human infections and detection of chemotherapy resistances in human cancer. In addition to tissues, cell-culture preparations have been prepared utilizing the HOPE technique, which were then successfully applied to in situ hybridization targeting mRNA or immunocytochemistry with excellent preservation of morphological details. Taken together, the HOPE technique to date represents an alternative fixation that is, in contrary to other procedures, scientifically broadly analyzed. Therefore new possibilities are opened up especially within the rapidly growing field of molecular pathology.

Experimental pain impairs recognition memory irrespective of pain predictability.

BACKGROUND: Pain is hardwired to signal threat and tissue damage and therefore automatically attracts attention to initiate withdrawal or defensive behaviour. This well-known interruptive function of pain interferes with cognitive functioning and is modulated by bottom-up and top-down variables. Here, we applied predictable or unpredictable painful heat stimuli simultaneously to the presentation of neutral images to investigate (I) whether the predictability of pain modulated its effect on the encoding of images (episodic memory) and (II) whether subjects remember that certain images have been previously presented with pain (source memory). METHODS: Twenty-four healthy subjects performed a categorization task in which 80 images had to be categorized into living or non-living objects. We compared the processing and encoding of these images during cued and non-cued pain trials as well as cued and non-cued pain-free trials. Effects on recognition performance and source memory for pain were immediately tested using a surprise recognition task. RESULTS: Painful thermal stimulation impaired recognition accuracy (d', recollection, familiarity). This negative effect of pain was positively correlated with the individual expectation of pain interference and the attentional avoidance of pain-related words. However, the interruptive effect of pain was not modulated by the predictability of pain. Source memory for painful stimulation was at chance level, indicating that subjects did not explicitly remember that images had been paired with pain. CONCLUSIONS: Targeting negative expectations and a maladaptive attentional bias for pain-related material might help reducing frequently reported pain-induced cognitive impairments.

The promoter of the human cystic fibrosis transmembrane conductance regulator gene directing SV40 T antigen expression induces malignant proliferation of ependymal cells in transgenic mice.

Transgenic mice bearing a human cystic fibrosis transmembrane conductance regulator (CFTR) promoter-SV40 T antigen fusion transgene were generated in order to localize in vivo the potential oncogenesis linked to the tissue-specific activity of the promoter for the CFTR gene. Surprisingly, the only site of tumors resulting from expression of the reporter onc gene was ependymal cells lining the brain ventricles. SV40 T antigen expression in these cells led to a consistent pathology in the first weeks of age: ependymoma and consequent hydrocephaly. Tumor-derived cell lines were established, characterized and shown to originate from SV40 T antigen-induced ependymoma. No pathological alterations were found in other organs, such as lungs and pancreas, in which cystic fibrosis is pathologically manifest in humans. Such transgenic mice and derived cell lines may represent valid models for analysing (1) the role of SV40 T antigen in ependymoma formation and (2) CFTR function in ependymal cells.

Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group.

From December 1980 to January 1984, all patients with stage I nonseminomatous testicular cancer in Denmark entered a randomized trial comparing surveillance only with radiotherapy after orchiectomy. One hundred fifty patients were assessable for the final analysis. Relapse occurred in 23 patients in the surveillance group and in 11 patients in the radiotherapy group. Radiotherapy completely prevented retroperitoneal relapse; 14 retroperitoneal relapses occurred in the surveillance-only group. All relapsing patients in the surveillance-only group are without evidence of disease with a median observation time after chemotherapy of 67 months. Two of the patients with relapse in the radiotherapy group died with disease; the others are alive without evidence of disease, with a median observation time after relapse treatment of 72 months. In the surveillance group, four relapses occurred later than 2 years after orchiectomy; only one such late relapse occurred in the radiotherapy group. Four of the retroperitoneal relapses occurred without concomitant increase in the serum marker levels (alpha-fetoprotein [AFP] and human chorionic gonadotropin [HCG]). It is concluded that surveillance only should replace radiotherapy after orchiectomy as standard treatment for clinical stage I nonseminomatous testicular cancer. Improved methods for control of retroperitoneal relapses, especially of embryonal carcinomas, are needed.

Stress-induced birefringence in large-mode-area micro-structured optical fibers.

We report on detailed numerical investigation of stress-induced birefringence in micro-structured solid-core optical fibers. The stress is induced either by external forces or stress applying parts inside the fiber. Both methods lead to different stress distributions where screening as well as enhancement effects due to the air-hole micro-structuring could be observed. Furthermore, we discuss the potential of the realization of polarization-maintaining low-nonlinearity micro-structured fibers that are suitable for applications in ultrafast optics.

Coincidence of a myeloproliferative and a lymphoproliferative disorder--a random event?

A patient with coinciding polycythemia vera and chronic lymphocytic leukemia is reported. Based on a literature review and vital statistics it is concluded that the coincidence is probably fortuitous.

The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies.

The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin properties. A recombinant form of BPI (rBPI21) has been developed and is being tested as a therapeutic agent to treat gram-negative bacterial infections and exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at other neutrophil-granule proteins may exacerbate inflammation by nonspecific effects of extracellular and cell-associated immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of gram-negative bacteria and bacterial-associated endotoxin.

Serum lipoprotein inhibitors of granulopoiesis in human bone marrow cultures.

Ammonium sulphate fractionation of human serum showed that two fractions contained an inhibitor of cluster and colony formation in agar cultures of human bone marrow cells. Further investigations demonstrated this inhibition to be caused by lipoproteins. When freshly prepared, only light density lipoproteins (LDL) were found to be inhibitory. During storage, very light density lipoproteins (VLDL) acquired inhibitory activity, while high density lipoproteins (HDL) did not show any inhibition of human bone marrow cultures. The possibility of toxic degradation of lipoproteins as an explanation for the inhibition was investigated by preincubation of human marrow cells with lipoproteins for 6 hours (37 degrees C) after storage of the lipoproteins under nitrogen (4 degrees C) for various intervals up to 48 days. Preincubation was found to be non-toxic (viable cell counts) and without colony/cluster-reducing ability for incubated marrow cells compared to controls. Addition of lipoproteins to mouse marrow cells and Ehrlich ascites tumour cells resulted in no change in colony formation by Ehrlich cells, whereas mouse marrow cells were inhibited, but to a lesser degree than human marrow cells.

Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings.

OBJECTIVE: The effects of capsaicin on sensory neurons are mediated by its interaction with a specific membrane receptor and opening of a non-selective cation channel. In the rat heart, capsaicin-sensitive nerve endings are known to be activated by oxygen radicals. We investigated the possibility that free oxygen radicals stimulate sensory nerve endings by acting upon the capsaicin receptor. METHODS: We studied the effects of capsaicin (0.16-16.0 nmol), bradykinin (0.1-10 nmol), H2O2 (1.5-30 mumol), and xanthine + xanthine oxidase (X + XO, 1 mumol + 0.03 mU) applied to the surface of the rat heart for 30 s on the activity of cardiac, capsaicin-sensitive, vagal and sympathetic afferent fibers before and after blockade of capsaicin receptors with capsazepine (200 micrograms/kg, i.v.), a specific antagonist for the capsaicin receptor. RESULTS: Application of capsaicin (0.32-16.0 nmol), H2O2 (9-30 mumol), bradykinin (1-10 nmol), and X + XO increased cardiac vagal and sympathetic afferent activity. Administration of capsazepine had no effect on the baseline activity of either vagal or sympathetic cardiac afferents, but it abolished the response of the afferent fibers to all doses of capsaicin, H2O2, and X + XO tested. Capsazepine had no effect on afferent activation by bradykinin. Administration of another capsaicin receptor blocker, ruthenium red (780 micrograms/kg, i.v.), had similar effects. CONCLUSIONS: The results of these experiments indicate that blockade of capsaicin receptors inhibits activation of vagal and sympathetic cardiac afferent fibers by free oxygen radicals. The fact that capsazepine and ruthenium red did not affect the afferent response to bradykinin suggests that this effect of the blockers was specific for capsaicin receptors. The possible functional implications of this interaction are discussed.