Prostate specific antigen for early detection of prostate cancer: longitudinal study

Objective To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results

Preparo da veia safena na cirurgia de revascularização miocárdica: uma nova técnica -no touch- que mantém a parede da veia íntegra e proporciona uma alta perviabilidade imediata

BACKGROUND: The technique of harvesting the saphenous vein (SV) for coronary artery bypass grafting (CABG) influences the fate of vein grafts. A new no touch (NT) technique of SV preparation was developed where the vein is harvested with a pedicle of surrounding tissue, which protects the vein from spasms therefore obviating the need for distension. METHOD: A prospective randomized study in 156 patients who underwent CABG was performed comparing three SV harvesting techniques. The techniques were conventional (c) (adventitial stripping of the vein, manual distention and storing in saline solution); Intermediate (I) (after adventitial stripping, the vein was left in situ, covered with a papaverine-soaked compress, and stored in heparinized blood); and no touch (SV dissected with its surrounding tissue was left in situ, covered with a saline-soaked compress and stored in heparinized blood). A morphological study of the endothelium was preformed using scanning electronic microscopy and an angiographic assessment of the vein graft patency was performed at 18 months mean follow-up time. Also an immunohistochemistry assessment was performed to identify the enzyme, nitric oxide synthase (NOS) in the vein wall. RESULTS: The preservation of the endothelial cell integrity was greater with the no touch technique than with the other procedures. At angiographic follow up, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I. The immunohistochemistry assessment revealed NOS in all three layers of the vein wall that was prepared by the no touch technique. However, a great reduction of this enzyme in veins treated by the conventional technique was observed. CONCLUSION: The endothelial integrity and NOS activity were better preserved when using the no touch technique for vein graft harvesting. The vasorelaxation and thrombo-resistant activities of nitric oxide (NO) may be responsible for the reduced of vasospasms and improved patency rate. Furthermore, the mechanical properties provided by the cushion of surrounding tissue in graft harvested by NT technique may contribute to the observed high patency rate.OBJETIVO: O objetivo deste trabalho é apresentar uma nova técnica no touch de preparo da veia safena e sua importância clínica. Esta nova técnica consiste na retirada da veia safena do seu leito, juntamente com um pedículo de tecido adiposo, protegendo a veia contra espasmos e, conseqüentemente, da necessidade de distendê-la durante a operação. MÉTODO: O estudo foi realizado em dois tempos: 1) Inicialmente, foi realizado um estudo prospectivo e randomizado, envolvendo 156 pacientes que foram submetidos à operação de revascularização miocárdica. Neste estudo nós comparamos a técnica no touch (NT) com duas outras: a convencional (C) e a intermediária (I). Foi feita uma avaliação detalhada da morfologia endotelial, utilizando a microscopia eletrônica, enquanto que a perviabilidade das pontes foi determinada com um exame angiográfico executado num período médio de 18 meses após a operação. 2) Finalmente, a enzima óxido nítrico síntase (NOS) foi identificada com ajuda do estudo imunohistoquímico e também pela localização auto-radiográfica de (3H)-L- Nitro-Arginina (NOARG). RESULTADOS: A avaliação morfológica mostrou integridade endotelial de 97% nas veias que foram tratadas pela técnica NT; enquanto quase metade da superfície endotelial das veias tratadas pelas outras duas técnicas exibiu ausência de células endoteliais. O exame angiográfico revelou perviabilidade de 95,4% para as pontes do grupo NT, 88,9% para as pontes do grupo (C) e 86,2% para as pontes do grupo (I). O estudo imunohistoquímico revelou a presença de NOS nas três camadas que compõem a parede da veia quando, as mesmas, foram tratadas pela técnica NT. Por outro lado, foi observada uma elevada redução desta enzima nas veias que foram tratadas pela técnica (C). A análise auto-radiográfica confirmou os resultados imunohistoquímicos. CONCLUSÃO: A integridade endotelial e a atividade da enzima óxido nítrico síntase foram melhor mantidas com o uso da técnica NT no preparo da veia safena. A atividade vasodilatadora e bloqueadora da agregação plaquetária causada pelo óxido nítrico (NO) pode ser a responsável pela proteção da veia contra o espasmo, como também pela alta perviabilidade imediata da mesma. Além disso, as propriedades mecânicas providas pelo tecido gorduroso em volta da veia, contribuíram para o melhor resultado desta nova técnica.University Hospital of Örebro Cardiothoracic Surgery DivisionUniversity Hospital Royal Free College Medical School Molecular Pathology and Biochemical DivisionHospital do Servidor Público EstadualUNIFESP Paulista Medical School Cardiothoracic Surgery DivisionHospital Oswaldo Cruz Cardiothoracic Surgery DivisionUNIFESP, Paulista Medical School Cardiothoracic Surgery DivisionSciEL

A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets. In healthy nonhuman primates, HMB-001 prolonged the half-life of endogenous FVIIa, resulting in its accumulation. Mouse bleeding studies confirmed antibody-mediated potentiation of FVIIa hemostatic activity by TLT-1 targeting. In ex vivo models of GT, HMB-001 localized FVIIa on activated platelets and potentiated fibrin-dependent platelet aggregation. Taken together, these results indicate that HMB-001 has the potential to offer subcutaneous prophylactic treatment to prevent bleeds in people with GT and other inherited bleeding disorders, with a low-frequency dosing regimen

The interaction of motivational elements- how officials gets motivated in a public department

Det har sedan lång tid tillbaka funnits en löneskillnad mellan den privata och offentliga sektorn, där den offentliga sektorn har befunnit sig på en lägre lönenivå. Denna skillnad är något som faller sig naturligt och som medarbetarna har lärt sig acceptera. Vad är det då som gör att medarbetarna börjar jobba inom offentlig sektor och vad är det som gör dem motiverade till att stanna kvar när det finns en tydlig skillnad i löneutvecklingen. När då gränszonen nås och de monetära medlen inte är disponibla kan det då finnas andra element som kan fungera som kompensation för att motivera medarbetarna.Syftet med denna uppsats är att undersöka om det finns en växelverkan mellan inre och yttre motivationsfaktorer. Samt om det är möjligt att upprätthålla en tillräckligt hög motivation med hjälp av inre motivationsfaktorer för att kompensera avsaknaden av yttre motivationsfaktorer. Vi har genom en fallstudie vid en offentlig avdelning utrett vad som motiverar medarbetarna, för att på så sätt kunna identifiera olika motivationselement som kan finnas på avdelningen. Vi har arbetat fram en modell med underliggande element som ska underlätta analysen av empirin. Analysen och resultat visar att det finns en växelverkan, där vissa element är mer betydelsefulla och kan kompensera upp varandras brister

Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma

BACKGROUND: High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses. METHODS: We used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects. RESULTS: We found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment. CONCLUSION: We highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment

The no-touch vein graft for coronary artery bypass surgery preserves the left ventricular ejection fraction at 16 years postoperatively : long-term data from a longitudinal randomised trial

OBJECTIVES: To assess the left ventricular heart function and the clinical outcome 16 years after coronary artery bypass surgery. DESIGN: In a randomised trial, the no-touch (NT) vein graft in coronary artery bypass surgery has shown a superior patency rate, a slower progression of atherosclerosis and better clinical outcome compared to the conventional (C) vein graft at 8.5 years. All patients at mean time 16 years were offered an echocardiographic and clinical examination. RESULTS: In the NT-group 34 patients and in the C-group 31 patients underwent an echocardiography examination. A significantly better left ventricle ejection fraction was seen in the NT-group compared to the C-group (57.9% vs 49.4%; p=0.011). The size of the left atrium in NT was 21.7 cm(2) compared to 23.9 cm(2) in C; p=0.034. No patient in NT had atrial fibrillation compared to five patients in C (p=0.021). Patients with a brain natriuretic peptide value (BNP) ≥150 was 30% in NT compared to 38% in C. Total mortality was 25% in NT vs 27% in C. Cardiac-related deaths were 8% and 12% in NT and C respectively. CONCLUSIONS: The NT vein graft preserves the left ventricular ejection fraction after 16 years. A smaller left atrium, a lower BNP and no atrial fibrillation indicates an improved diastolic left ventricular function in the NT-group. TRIAL REGISTRATION: The study is registered with clinicaltrials.gov (NCT01686100) and The Research and Development registry in Sweden (no. 102841)

A study of possible associations between single nucleotide polymorphisms in the estrogen receptor 2 gene and female sexual desire

INTRODUCTION: Female sexual desire and arousal problems have been shown to have a heritable component of moderate size. Previous molecular genetic studies on sexual desire have mainly focused on genes associated with neurotransmitters such as dopamine and serotonin. Nevertheless, there is reason to believe that hormones with more specific functions concerning sexuality could have an impact on sexual desire and arousal. AIM: The aim of the present study was to investigate the possible effects of 17 single nucleotide polymorphisms (SNPs) located in estrogen receptor genes on female sexual desire and subjective and genital arousal (lubrication). Based on previous research, we hypothesized that ESR1 and ESR2 are relevant genes that contribute to female sexual desire and arousal. MAIN OUTCOME MEASURES: The desire, arousal, and lubrication subdomains of the Female Sexual Function Index self-report questionnaire were used. METHODS: The present study involved 2,448 female twins and their sisters aged 18-49 who had submitted saliva samples for genotyping. The participants were a subset from a large-scale, population-based sample. RESULTS: We found nominally significant main effects on sexual desire for three ESR2 -linked SNPs when controlled for anxiety, suggesting that individuals homozygous for the G allele of the rs1271572 SNP, and the A allele of the rs4986938 and rs928554 SNPs had lower levels of sexual desire. The rs4986938 SNP also had a nominally significant effect on lubrication. No effects for any of the SNPs on subjective arousal could be detected. CONCLUSIONS: The number of nominally significant results for SNPs in the ESR2 gene before correcting for multiple testing suggests that further studies on the possible influence of this gene on interindividual variation in female sexual functioning are warranted. In contrast, no support for an involvement of ESR1 was obtained. Our results should be interpreted with caution until replicated in independent, large samples. Gunst A, Jern P, Westberg L, Johansson A, Salo B, Burri A, Spector T, Eriksson E, Sandnabba NK, and Santtila P. A study of possible associations between single nucleotide polymorphisms in the estrogen receptor 2 gene and female sexual desire