Specific binding and laterality of human extrastriatal dopamine D2/D3 receptors in late onset type 1 alcoholic patients

Late onset type 1 alcoholism has been suggested to be associated with decreased dopaminergic transmission. Our hypothesis was that late onset type 1 alcoholics have also abnormal extrastriatal dopamine D(2)/D(3) receptor distribution. We performed binding, heterogeneity and laterality analysis of extrastriatal and striatal dopamine D(2)/D(3) receptors in nine late onset male alcoholics and in 12 age-matched healthy males. A radioligand, [(123)I]epidepride was used in high resolution single-photon emission tomography (SPET). Specific binding of epidepride in the left temporal pole was significantly (P<0.05) lower in type 1 alcoholics (0.74+/-0.14 ml/ml) than in controls (0.89+/-0.14 ml/ml). In alcoholics, there was no normal left-to-right asymmetry of the temporal cortical heterogeneity of epidepride distribution observed in control males (0.89+/-0.19 vs. 1.10+/-0.19; P<0.05). The results suggest that the specific binding of dopamine D(2)/D(3) receptors in late type 1 alcoholics is decreased and its laterality in the temporal brain is altered from normal.     

Dopamine transporter and D2-receptor density in late-onset alcoholism

Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is relevant to study both postsynaptic D₂-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D₂-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality disorder (ASPD), and nine healthy controls. Methods: [¹²³I]PE2I and [¹²³I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D₂-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent alcohol abuse. Received: 22 March 1999 / Final version: 25 June 1999     

Increased whole blood chemiluminescence in patients with Shwachman syndrome: therapy trial with thiamine and α-tocopherol

Neutrophils purified from peripheral blood of patients with the Shwachman syndrome show enhanced chemiluminescence (CL) and depressed chemotaxis. Here we present data showing that the increased CL response can be demonstrated by using a whole blood CL assay. This assay is well-suited for studies in infants, because the blood sample volumes needed are small. Increase in CL was most distinct in the initial (1 min) activation induced by N-formyl-methionyl-leucyl-phenylalanine. The 1-min response is considered to derive from extracellular production of oxygen radicals. Such an extracellular oxygen radical production may render the patients susceptible to undue oxidant stress. We therefore treated the patients with two antioxidants, thiamine and -tocopherol, for 3 months. This supplementation, however, failed to exert any significant effect on either whole blood CL or migration of the patients' neutrophils under agarose.     

Low cdc27 and high securin expression predict short survival for breast cancer patients

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase–anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow‐up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti‐mitotic drug development.     

The holistic approach to rehabilitation: A commentary

Abstract

Maria Pachalska's approach to aphasia rehabilitation is from a holistic perspective. Traditionally, aphasia therapists have tried to promote communicative ability using several methods. Pachalska has combined the most important approaches and created a model which she calls the Complex Aphasia Rehabilitation Model (CARM). She offers this model as an example of a holistic approach to aphasia rehabilitation. It stresses the importance of taking into account both psychological and social factors in aphasia rehabilitation.     

Patient participation in pro re nata medication in psychiatric inpatient settings: An integrative review

Pro re nata (PRN) medication is widely used and studied in psychiatric care, but our knowledge about patient participation in its administration is fragmented. The aim of this integrative review was to describe and synthesize previous knowledge of patient participation in PRN in psychiatric inpatient settings. We conducted both electronic and manual searches, using the CINAHL, Scopus, PsycINFO, and PubMed databases, and eight scientific journals. Searches were limited to the English language, to the years 2006–2016, and to selected papers using inclusion, exclusion, and quality criteria. We identified 16 relevant papers, and these showed that patient participation included patient‐related starting points, including the patients’ willingness to participate and their knowledge of the medication. The patients’ participation in PRN practices was demonstrated by the opportunity to request PRN and to refuse any PRN that was offered. Patient participation was shown to be linked to certain situations where PRN was recommended. The role that the professionals played in patient participation included interacting with patients, providing counselling and alternatives for PRN. Our results also revealed that coercion was used administering PRN. The existing literature exposed challenges that need to be addressed if patient participation in the use of PRN medication is to be effectively achieved in psychiatric inpatient settings. Equal partnerships between patients, nurses, and physicians are an essential part of this process, and further research into PRN medication is urgently needed, particularly studies that focus on patients’ experiences.     

A Case of Abnormal Lymphatic-Like Differentiation and Endothelial Progenitor Cell Activation in Neovascularization Associated with Hemi-Retinal Vein Occlusion

PurposePathological vascular differentiation in retinal vein occlusion (RVO)-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease.MethodsVitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC) adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), and prospero-related homeobox protein 1 (Prox-1). Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67) and expression of the stem cell marker CD117.ResultsThe specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity.ConclusionsIntraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.Key Words: Hemi-retinal vein occlusion, Endothelial progenitor cell, Platelet endothelial cell adhesion molecule 1, Podoplanin, Prospero-related homeobox gene 1, Lymphatic endothelial cell, Lymphatic vessel endothelial hyaluronan receptor 1, Immunohistochemistry, Proliferative diabetic retinopathy, Vascular endothelial stem cell     

Activated protein C and inflammation in human myocardium after heart surgery

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.