Transplantectomy today: indications and complications

Analysis of the indications for transplantectomy and its complications over a 12-year period. Over a total of 159 failure grafts, we performed 53 transplantectomies (33.3%). The percentage of complications was 16.9%. Three patients died (5.6%) during the more or less immediate post-operative period. In our experience, consistent and prolonged maintenance of immunosuppression should avoid the need for transplantectomy in a high percentage of grafts. Only 15 transplantectomies were made on 104 failure grafts after 6 months (14.4%). Our short but successful experience with embolization of 2 rejected grafts confirms the validity of this conservative alternative versus conventional surgical transplantectomy in selected cases.     

General review of recent activities in acoustic emission technology in Italy

This paper describes the present situation in Italy in the field of Acoustic Emission researches and applications.Information on the level of instrumentation development is given. Both multichannel and multiparameter systems for large structure examination in real time and data logging systems for continuous surveillance purposes are considered.The expertise accumulated in the application of AE to pressure vessel examination during hydrotest is mentioned, this being oriented to pressure components of conventional power stations and chemical plants.Particular attention is recently paid to mechanical fatigue tests. These were conducted on intermediate PWR nuclear pressure vessel, reduced scale offshore nodes and full scale prototype aircraft.A considerable activity has been carried out on application of AE technique to the detection of fluid leakages in power plant components. Both intrusive and non-intrusive methods have been considered. Many boilers and pre-heaters of thermal power plants have been instrumented for an on-line AE monitoring during operation. The problem of the loose part monitoring has been also considered.Several basic researches for material characterization by AE have been also conducted. Different composite material, carbon and austenitic steels, metal alloys have been studied.     

Female and male emotional dependency and its implications for the therapist-client relationship.

Women and men both struggle to achieve a healthy integration of passive dependent and active autonomous strivings. However, how dependent strivings are labeled and become manifest differ for women and men. I first describe the different conceptions of male and female dependency and how such conceptions are related to sex role socialization and to societal norms and practices. I then relate these concepts to the problem of eroticism in psychotherapeutic settings and make specific recommendations for the education and training of psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurement of pulmonary resistance and dynamic compliance with airway obstruction

We compared four algorithms by using least squares regression for determination of pulmonary resistance and dynamic elastance in subjects with emphysema, normal subjects, and subjects with asthma before and after bronchoconstriction. The four methods evaluated include 1) a single resistance and elastance, 2) separate resistances and elastances for each half breath, 3) separate inspiratory and expiratory resistances with a single elastance, and 4) separate inspiratory and expiratory resistances, an expiratory volume interaction term, and a single elastance. All methods gave comparable results in normal and asthmatic subjects. We found expiratory resistance was larger than inspiratory resistance in normal and asthmatic subjects during control conditions, but inspiratory resistance was higher than expiratory resistance in subjects who experienced severe bronchoconstriction in response to methacholine. In subjects who are flow limited, method 2 gives a higher inspiratory resistance than would be computed by assuming that the elastic pressure-volume curve passes through the zero-flow points. Methods 1 and 3 overestimate dynamic elastance and inspiratory resistance. Method 4 appears to identify flow limitation and dynamic hyperinflation and gives a good measure of inspiratory resistance and dynamic elastance.     

Quantitative molecular monitoring of HIV-1 RNA during antiretroviral therapy

Plasma HIV-1 RNA testing was used to monitor 43 HIV-1 infected patients newly placed on antiretroviral therapy or whose therapy had been recently changed. A polymerase chain reaction kit was used to measure HIV-1 RNA in clinical samples or frozen plasma. The cutoff of this test was 200 RNA copies/ml. The first group (11 patients) was stable on long-term zidovudine monotherapy when switched to stavudine. The HIV-1 RNA of three patients who had a regular decline in CD4+ T cell count did not change despite this switch, with a mean follow-up of 630 days. The HIV-1 RNA copy numbers of eight patients whose CD4+ T cell counts were stable declined an average of 0.53 log10 between days 90 and 650. The second group (14 patients) was on long-term zidovudine monotherapy and had declining CD4+ T cell counts over the past 6 months. Lamivudine was added to this regimen on day 0. HIV-1 RNA copy number decreased rapidly within 30 d, reaching -0.86 log10 on day 90, and this effect was maintained thereafter, with a mean follow-up of 161 days. There was a concomitant mean gain of +33 CD4+ T cells on day 90. The third group (nine patients) had never received anti-retroviral therapy and was given zidovudine+didanosine. HIV-1 RNA copy number decreased in all cases but one, reaching -1.31 log10 on day 150. This decrease was transient in three cases. The last group (nine patients) had also not had previous anti-retroviral therapy and was given zidovudine + didanosine + lamivudine in combination. HIV-1 RNA copy numbers declined rapidly in all cases, to below the cutoff in eight cases within a mean period of 50.5 days. The CD4+ cell counts increased by 164 cells/microliter on day 14 and by 201 cells/microliter on day 180. The response to therapy of the total population of 43 patients varied according to cases. The relative changes in p24 antigen compared to HIV-1 RNA also differed between patients. Measurement of HIV-1 viremia appears to be a valuable tool in current practice for individualizing therapy.     

Cell Therapies in Bladder Cancer Management

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.     

Detection of the First Epoxyalcohol Synthase/Allene Oxide Synthase (CYP74 Clan) in the Lancelet (Branchiostoma belcheri,Chordata)

The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity.