Intraoperative cell salvage in radical prostatectomy does not appear to increase long‐term biochemical recurrence,metastases, or mortality

BACKGROUND: Blood management strategies help to conserve allogeneic red blood cells, a finite resource. Intraoperative cell salvage (ICS) is an effective method of allogeneic avoidance. However, concerns persist about the safety of ICS in surgical oncology cases, including radical prostatectomy (RP). Previous findings do not support these concerns. We hypothesized that ICS would not increase rates of long‐term prostate cancer recurrence characterized by biochemical failure, disease dissemination, or mortality. STUDY DESIGN AND METHODS: Consecutive patients undergoing RP by a single urologist over two 3‐month periods 1 year apart were analyzed retrospectively. Patients in the first period had preoperative autologous donation (PAD) but not ICS (PAD group), whereas those in the second period had ICS only (ICS group). Variables assessed included patient demographics, prostate‐specific antigen levels at surgery and end of follow‐up, clinical stage, operative time, surgical margin status, pathologic stage and grade, Gleason score sum, length of hospital stay, biochemical recurrence, metastases, and mortality. RESULTS: A total of 116 consecutive patients were analyzed. Of these, 32 patients in the PAD group and 42 patients in the ICS group had follow‐up of at least 4.75 years. There was a significantly higher rate of biochemical failure (34.4% vs. 9.5%; p = 0.02) and metastases (12.5% vs. 0%; p = 0.03) in the PAD group versus the ICS group; there was no significant difference in mortality (9.4% vs. 0%; p = 0.08). CONCLUSION: ICS appears to be a safe and effective method of allogeneic blood conservation in patients undergoing RP. The findings suggest that there is no increased risk of biochemical failure, disease dissemination, or mortality at 5 years post‐RP as a result of ICS use.     

Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy

OBJECTIVES:

The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB.

METHODS:

We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB.

RESULTS:

The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course.

CONCLUSION:

An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.     

Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

This study investigates the participation of the endothelial factors in the α-adrenoceptor contractile responses in mesenteric resistance arteries from 15 days ouabain-treated (25 µg/kg/day) and untreated rats. Ouabain treatment increased blood pressure and heart rate without changing the contractile response to phenylephrine (3 nM–30 µM). Endothelium removal or N^G-nitro-l-arginine methyl ester (l-NAME, 100 µM), increased the responses to phenylephrine. The endothelial modulation was similar in both rat groups, but the l-NAME effects were bigger in arteries from ouabain-treated rats. However, the endothelial NOS expression and the relaxation to acetylcholine (0.1 nM–10 µM) remained unaltered after ouabain treatment. The coincubation with l-NAME and indomethacin (100 µM) leftward shifted the concentration–response curves to phenylephrine in arteries from untreated rats similarly to the displacement after incubation only with l-NAME. However, in mesenteric arteries from treated rats, the co-incubation with indomethacin and l-NAME did not alter the response to phenylephrine. The addition of the inhibitor of calcium activated potassium channels tetraethylammonium (2 mM) further leftward shifted the phenylephrine curves only in arteries from untreated rats. Cyclooxygenase-2 (COX-2) expression was greater in vessels from ouabain-treated rats. In conclusion, the chronic ouabain treatment for 15 days modified the participation of endothelial factors in response to phenylephrine in mesenteric resistance arteries, by increasing the release of NO and prostanoids and impairment the endothelium-derived hyperpolarizing factor (EDHF) release. This was accompanied by an increased COX-2 expression. Although this balance avoids changes in the phenylephrine concentration–response curves, these vascular changes might contribute to maintain the ouabain-induced hypertension.     

Learner-control vs. program-control instructional multimedia: a comparison of two interactions when teaching principles of orthodontic appliances

BACKGROUND: Many studies have compared computer assisted learning (CAL) to more traditional learning formats and have shown CAL to be as effective as or superior to the alternative resources. However, there are only scarce attempts to show which style of CAL leads to the best learning outcomes in orthodontics. AIM: To compare the effectiveness of a learner-control (group A) vs. program-control (group B) multimedia learning environment courseware packages regarding knowledge, understanding and transfer of content when applied to teaching principles of orthodontic appliances to undergraduate students. METHODS: Pre- and post-test assessments of undergraduate dental students (n = 30) who either studied a learner-control multimedia learning environment courseware package (n = 15) or a program-control version (n = 15) on equivalent material of the orthodontic appliances curriculum. Both groups were evaluated by means of multiple-choice questions covering knowledge, understanding and application. A one-way ANOVA was carried out in order to check for statistical difference between the two groups. The P-value was set at 0.05. Results: There was no difference in prior knowledge between both groups at baseline. Although, both groups significantly improved their scores after having studied the course, no significant difference was found between both groups in relation to answers to questions about knowledge, understanding and application. CONCLUSIONS: In this study, the learner-control instructional multimedia program was found to be as effective as the program-control version when teaching principles of the orthodontic appliances to undergraduate students. The focus needs to be on improving the value of CAL. Comparative evaluations of how different CAL approaches compare with or complement one another are certainly needed.     

Reciprocal changes in gene expression profiles of cocultured breast epithelial cells and primary fibroblasts

The importance of epithelial‐stroma interaction in normal breast development and tumor progression has been recognized. To identify genes that were regulated by these reciprocal interactions, we cocultured a nonmalignant (MCF10A) and a breast cancer derived (MDA‐MB231) basal cell lines, with fibroblasts isolated from breast benign‐disease adjacent tissues (NAF) or with carcinoma‐associated fibroblasts (CAF), in a transwell system. Gene expression profiles of each coculture pair were compared with the correspondent monocultures, using a customized microarray. Contrariwise to large alterations in epithelial cells genomic profiles, fibroblasts were less affected. In MDA‐MB231 highly represented genes downregulated by CAF derived factors coded for proteins important for the specificity of vectorial transport between ER and golgi, possibly affecting cell polarity whereas the response of MCF10A comprised an induction of genes coding for stress responsive proteins, representing a prosurvival effect. While NAF downregulated genes encoding proteins associated to glycolipid and fatty acid biosynthesis in MDA‐MB231, potentially affecting membrane biogenesis, in MCF10A, genes critical for growth control and adhesion were altered. NAFs responded to coculture with MDA‐MB231 by a decrease in the expression of genes induced by TGFβ1 and associated to motility. However, there was little change in NAFs gene expression profile influenced by MCF10A. CAFs responded to the presence of both epithelial cells inducing genes implicated in cell proliferation. Our data indicate that interactions between breast fibroblasts and basal epithelial cells resulted in alterations in the genomic profiles of both cell types which may help to clarify some aspects of this heterotypic signaling. © 2009 UICC     

Genetic variations in human G protein-coupled receptors: Implications for drug therapy

Numerous genes encode G protein-coupled receptors (GPCRs)-a main molecular target for drug therapy. Estimates indicate that the human genome contains approximately 600 GPCR genes. This article addresses therapeutic implications of sequence variations in GPCR genes. A number of inactivating and activating receptor mutations have been shown to cause a variety of (mostly rare) genetic disorders. However, pharmacogenetic and pharmacogenomic studies on GPCRs are scarce, and therapeutic relevance of variant receptor alleles often remains unclear. Confounding factors in assessing the therapeutic relevance of variant GPCR alleles include 1) interaction of a single drug with multiple closely related receptors, 2) poorly defined binding pockets that can accommodate drug ligands in different orientations or at alternative receptor domains, 3) possibility of multiple receptor conformations with distinct functions, and 4) multiple signaling pathways engaged by a single receptor. For example, antischizophrenic drugs bind to numerous receptors, several of which might be relevant to therapeutic outcome. Without knowing accurately what role a given receptor subtype plays in clinical outcome and how a sequence variation affects drug-induced signal transduction, we cannot predict the therapeutic relevance of a receptor variant. Genome-wide association studies with single nucleotide polymorphisms could identify critical target receptors for disease susceptibility and drug efficacy or toxicity.     

Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.

Objective

The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.

Material and Methods

186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05).

Results

There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.

Conclusion

Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.