Adenovirus 5‐ and 35‐based immunotherapy enhances the strength but not breadth or quality of immunity during chronic SIV infection

Heterologous adenovirus‐based vectors hold promise as preventative HIV vaccines but their capacity to induce effective T‐cell immunity in established infection has not been explored. We vaccinated rhesus macaques chronically infected with SIVmac251 and undergoing antiretroviral therapy (ART) with human adenovirus serotype 5‐based vectors expressing SIV Gag, Env, and Nef with and without IL‐15 and evaluated vaccine immunogenicity. Vaccination increased Ag‐specific T cells 20‐fold but did not expand the breadth of epitopes recognized or the quality of response, as the majority of CD8⁺ and CD4⁺ T cells produced only one cytokine irrespective of vaccination. Immunization transiently restored blood CD4⁺ central memory T cells (Tcm) and boosted CD4⁺ and CD8⁺ Tcm and effector cell responses but did not prevent virus rebound upon cessation of ART. Boosting with human adenovirus serotype 35‐based vectors during a second ART cycle increased Ag‐specific T cells to 50‐fold above pre‐vaccination levels and boosted CD4⁺ Tcm numbers but did not expand the breadth or quality of immunity or control virus levels following drug discontinuation. The number of blood CD4⁺ Tcm correlated positively with complexity of T‐cell responses and negatively with virus load, suggesting that more complete restoration of this subset through vaccination would be beneficial.     

Physician‐Assisted Suicide Attitudes of Older Mexican‐American and Non‐Hispanic White Adults: Does Ethnicity Make a Difference?

Little is known about attitudes toward physician‐assisted suicide (PAS) in various ethnic groups. This study compares attitudes held by older Mexican Americans and non‐Hispanic whites and examines subject characteristics that may influence their responses. A convenience sample of 100 older Mexican Americans and 108 non‐Hispanic whites (n=208) aged 60 to 89 were recruited from four primary care community‐based practice sites in San Antonio, Texas. Interview items measured attitudes toward PAS, cognitive status, functional status, and religiosity. Older Mexican Americans (52.7%) reported stronger agreement than non‐Hispanic whites (33.7%) with PAS. Male sex (odds ratio (OR)=2.62, 95% confidence interval (CI)=1.09–6.35) predicted agreement with legalization in Mexican Americans, whereas lower religiosity scores (OR=0.84, 95% CI=0.75–0.94) were predictive of agreement in older non‐Hispanic whites. This study is the first to find positive attitudes among community‐dwelling older Mexican Americans toward PAS that are higher than those of older non‐Hispanic white adults. Sex and religious views were important determinants of positive attitudes toward PAS. Larger, more‐generalizable studies should be conducted to confirm the attitudinal patterns that have been identified in this study.     

Leitlinienkonforme Versorgung

Background

Whereas the Scottish guidelines are audited annually, nobody evaluates guideline compliance in Germany. Thus, can external quality assurance data pursuant to section 137 of the German Social Code Book V be suitable for auditing guideline compliance?

Materials and methods

From North Rhine Westphalia, a total of 48,831 cases of femoral fractures near the hip joint were evaluated. Compliance with the guidelines was determined based on preoperative hospital stay, thrombosis, and antibiotic prophylaxis. Guideline rationale was reviewed in terms of mortality and thromboembolism rate.

Results

Sixty-four percent of the interventions were performed in a timely manner. Thrombosis prophylaxis was given in 99% of cases. Antibiotics were given as a single shot. There was no connection between mortality and thromboembolism rates or time to surgery.

Conclusion[Überschrift]

Guideline compliance is similar in German and Scotland. The external quality assurance data are suitable for evaluating guideline compliance. The literature recommends a short time to surgery. Given the short observation period, it was not possible to demonstrate any improvement in outcomes.     

Gene promoter hypermethylation in ductal lavage fluid from healthy <Emphasis Type="Italic">BRCA</Emphasis>gene mutation carriers and mutation-negative controls

Introduction  

Female germline BRCA gene mutation carriers are at increased risk for developing breast cancer. The purpose of our study was to establish whether healthy BRCA mutation carriers demonstrate an increased frequency of aberrant gene promoter hypermethylation in ductal lavage (DL) fluid, compared with predictive genetic test negative controls, that might serve as a surrogate marker of BRCA1/2 mutation status and/or breast cancer risk.     

Influence des facteurs psychosociaux sur l’apparition de douleurs post-tumorectomie Une étude prospective auprès de cinquante femmes opérées d’un cancer du sein

Objective

To study the influence of psychological factors in predicting the onset of postmastectomy pain syndrome (PMPS). The objective was to evaluate the possible role of factors, such as depression and anxiety, in the appearance of PMPS.

Patients and methods

We carried out an exploratory study of fifty breast cancer patients who underwent lumpectomy, including axillary node dissection, by the same technique in the gynaecology department of CHR Orléans. These patients were evaluated before and one month after the surgical procedure. We measured depression using the Montgomery-Asberg depression rating scale, and anxiety using the Hamilton anxiety scale. At the time of the second evaluation of pain, a pain management specialist assessed the patients to establish a diagnosis of PMPS.

Results

The results showed a statistically significant difference in the preoperative level of depression and anxiety between the patients who later develop PMPS and those who do not. One month after surgery, patients experiencing pain are always more depressed and have more intense psychological and somatic anxiety compared to the others.

Conclusion

Psychological factors, such as depression and anxiety, are possible predictive factors in the onset of PMPS. Moreover, we demonstrated the role of depression and anxiety in the appearance and maintenance of pain, as previously described in the literature.     

FIBRIN CUFF LYSIS IN CHRONIC VENOUS ULCERS TREATED WITH A HYDROCOLLOID DRESSING

Background. Pericapillary fibrin cuffs (PFC) are a recognized part of the pathology of venous stasis ulcers. A hydrocolloid dressing capable of lysing wound surface fibrin was tested in venous ulcers for its capacity to lyse pericapillary fibrin below the wound surface. Methods. Tissue biopsies from the rims of 19 venous ulcers were evaluated for thickness of shallow and deep dermal PFCS before and after treatment with DuoDERM covered by Unna's boot and a compression bandage (DD+UB; n=9) versus the same treatment without the hydrocolloid dressing (UB; n=10). Frozen sections of all biopsies were stained with an immunofluorescent antibody to fibrin for rating of PFC thickness. Separate sections were stained with hematoxylin and eosin to assess capillary frequency, histopathology, and inflammation. All ratings and pathology assessments were performed blinded to treatment conditions. Results. Both deep and shallow PFCS were reduced in 89% of ulcers treated with DD+UB versus 40% of ulcers treated with UB (α < 0.04). No other significant differences in inflammation, histopathology, or capillary frequency were observed. Conclusions. Treatment with DD+UB reduced PFCS in twice the number of ulcers than UB alone in 1 week. This is the first scientific documentation that a topical wound dressing could reduce the pathophysiology associated with venous ulcers, beyond the known beneficial effect of graduated compression. Not all hydrocolloid dressings are fibrinolytic, so this effect may not generalize to other dressings.     

Unitary Current Analysis of L-type Ca2+ Channels in Human Fetal Ventricular Myocytes

INTRODUCTION: L-type calcium channels were studied in cell-attached patches from ventricular cell membranes of human fetal heart. METHODS AND RESULTS: Experiments were performed in the presence of 70 mM Ba2+ as the charge carrier at 22 degrees C to 24 degrees C. Unitary current sweeps were evoked by 300-msec depolarizing pulses to 0 mV from a holding potential of -50 mV at 0.5 Hz. Recorded currents were blocked by nisoldipine (1 microM) and stimulated by (-)Bay K 8644 (1 microM). During control, channel activity was seen in 13.9%+/-4.2% of the total 200 sweeps. Ensemble average current amplitude was 0.03+/-0.01 pA (n = 6) and average conductance was 20.4+/-0.2 pS (n = 5). Analysis of single channel kinetics showed open time and closed time histograms were best fit by one and two exponentials, respectively. Mean open time was tau(o) = 0.99+/-0.05 msec (n = 6). Mean closed time fast (tau(cf)) and slow (tau(cs)) component values were tau(cf) = 0.85+/-0.09 msec and tau(cs) = 8.0+/-0.94 msec (n = 6), respectively. With intrapipette (-)Bay K 8644 (1 microM), mean open time was best fit by two exponentials, tau(of) = 0.9+/-0.2 msec (n = 10) and tau(os) = 13.4+/-2.6 msec (n = 10); mean close time values were tau(cf) = 0.6+/-0.1 msec (n = 10) and tau(cs) = 9.8+/-1.9 msec (n = 10), respectively. With (-)Bay K 8644, channel activity was 66.5%+/-7.4%, the ensemble average current was 0.52+/-0.04 pA (n = 10) and the conductance 20.7+/-0.5 pS (n = 5). CONCLUSION: (1) the data establishes the characteristics of L-type Ca channels of human fetal hearts and their modulation by dihydropyridines; (2) the open time kinetics differ from those of avian embryonic and rat fetal hearts; and (3) the findings provide new and relevant information for understanding the physiologic behavior of unitary Ca2+ channels in the developing human heart and the baseline comparison for diseases that implicate Ca2+ channels in their etiology, such as autoimmune-associated congenital heart block.