Correlation of pre-treatment transurethral resection and prognosis in patients with stage C carcinoma of the prostate treated with definitive radiotherapy--RTOG experience

Four hundred and ninety-four patients with clinical Stage C carcinoma of the prostate, who were entered onto a phase III RTOG study, have been analyzed as to the potential effect of the pre-treatment transurethral resection (TUR) of the tumor. Treatment consisted of definitive irradiation to the prostate (6500-7000 cGy) and regional lymphatics (4500-5000 cGy). A total of 202 patients underwent pre-treatment TUR. This population was compared with the remaining 292 patients as to the rate of locoregional failure, incidence of distant metastases, disease-free survival, and survival. The TUR population fared significantly worse for all four end-points. To account for uneven distribution of recognized prognostic factors the results were then adjusted using stratified Mantel-Haenszel tests. The stratification process resulted in a reduced level of significance in the differences between the two populations. However, a trend toward a higher incidence of distant metastases could be observed within most strata. The trend was most pronounced in subpopulations characterized by Gleason score 6-7 and normal serum acid phosphatase (SAP). For the population characterized by Gleason score 6-10 and normal SAP, the differences in the incidence of distant metastases retained statistical significance. Whether these findings are secondary to tumor dissemination during TUR or are due to incompletely identified selection biases remains to be demonstrated in future (prospective) studies.     

Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice

The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure.     

Comparison of respiratory inductive plethysmography versus head-out plethysmography for anesthetized nonhuman primates in an animal biosafety level 4 facility

For inhalational studies and aerosol exposures to viruses, head-out plethysmography acquisition has been traditionally used for the determination of estimated inhaled dose in anesthetized nonhuman primates prior to or during an aerosol exposure. A pressure drop across a pneumotachograph is measured within a sealed chamber during inspiration/exhalation of the nonhuman primate, generating respiratory values and breathing frequencies. Due to the fluctuation of depth of anesthesia, pre-exposure respiratory values can be variable, leading to less precise and accurate dosing calculations downstream. Although an anesthesia infusion pump may help stabilize the depth of sedation, pumps are difficult to use within a sealed head-out plethysmography chamber. Real-time, head-out plethysmography acquisition could increase precision and accuracy of the measurements, but the bulky equipment needed for head-out plethysmography precludes real-time use inside a Class III biological safety cabinet, where most aerosol exposures occur. However, the respiratory inductive plethysmography (RIP) acquisition method measures the same respiratory parameters by detecting movement of the chest and abdomen during breathing using two elastic bands within the Class III biological safety cabinet. As respiratory values are relayed to a computer for software integration and analysis real-time, adjustment of aerosol exposure duration is based on the depth of sedation of the animal. The objective of this study was to compare values obtained using two methodologies (pre-exposure head-out plethysmography and real-time RIP). Transitioning to RIP technology with real-time acquisition provides more consistent, precise, and accurate aerosol dosing by reducing reported errors in respiratory values from anesthesia variability when using pre-exposure head-out plethysmography acquisition.     

The Effects of Feedback Sensory Modality, Feedback Information Content, and Sex on Short-Term Biofeedback Training of Three Responses

In three factorial experiments, auditory vs visual vs tactile feedback, analog feedback vs analog feedback which was anchored, and sex, were varied to assess the effects of these variables on performance in short-term biofeedback training of heart rate reduction, hand temperature increase, and forehead muscle tension reduction. A total of 108 subjects served in the study. Moderate but reliable changes were found during the course of the training session for all three physiological responses. The ability to reduce heart rate in a single training session did not appear to be a function of any of the variables manipulated in this study, but rather could be attributed to adaptation. In both muscle tension and temperature training, however, there were significant interactions between sex and sensory modality of the feedback stimulus and, in the case of muscle tension training, between information content of the feedback signal and sex. The overall pattern of results indicated that performance during biofeedback training is a complicated function of sex and the type of signal used to provide feedback, and that this function is not constant across physiological response systems.     

Qualitative angiographic and quantitative myocardial perfusion assessment using fluorescent cardiac imaging during graded coronary artery bypass stenosis

Intraoperative graft assessment in coronary artery bypass (CAB) grafting is important to avoid early graft failure. This study aimed to evaluate the accuracy of fluorescent cardiac imaging (FCI) for intraoperative qualitative angiographic and quantitative myocardial perfusion assessment during graded CAB stenosis compared to coronary angiography (CA). After CAB grafting to the left anterior descending coronary artery, graded distal bypass stenoses were created in ten pigs by 25, 50, 75, and 100% flow reduction assessed by transit-time flow measurement (TTFM). Visual angiographic assessment was performed by FCI and CA during baseline and graded bypass stenoses. Altered myocardial perfusion was assessed by quantitative intraoperative fluorescence intensity (QIFI) derived from FCI and correlated to TTFM. Patent bypass grafts and graft occlusion were visualized successfully by FCI and CA, while discrimination between various graded bypass stenosis was possible in 73.3%. The degree of CAB stenosis was overestimated in 16.7% and underestimated in 10.0% by FCI compared to CA. Graded CAB stenosis reduced regional myocardial perfusion quantified by decreased QIFI value (p?<?0.001). Mean QIFI value was 76.8 (95% CI 67.2–86.3) during baseline, 55.6 (95% CI 45.3–65.9) during 25% flow-reduction, 30.6 (95% CI 22.3–39.0) during 50% flow-reduction, 20.3 (95% CI 15.4–25.3) during 75% flow-reduction, and 0 during CAB occlusion (p?<?0.001) with a significant correlation to TTFM (r?=?0.955; p?<?0.0001). Solely visual assessment of CAB quality using FCI is limited as compared to CA. Additional QIFI assessment identified graded CAB stenosis and occlusion with a significant correlation to TTFM.     

Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES:

To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate

METHODS:

A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer''s test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872

RESULTS:

All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer''s test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression.

CONCLUSIONS:

All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment.     

Early and sustained haemodynamic improvement with levosimendan compared to intraaortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction

OBJECTIVE: To investigate the haemodynamic effects of levosimendan in patients with cardiogenic shock (CS) complicating acute myocardial infarction in comparison to the effects of intra-aortic balloon counterpulsation (IABP). METHODS: 10 patients with intractable CS under standard therapy (including the use of PCI, inotropes, and vasopressors) received i.v. infusion of levosimendan (bolus 12 microg/kg i.v., followed by continuous infusion 0.1 microg/kg/min for 24 h). Haemodynamic effects were compared to the effects of IABP-placement added to standard care in 12 patients with CS. RESULTS: Within 24 h, both levosimendan and IABP produced a significant increase in cardiac index (CI) and cardiac power index and a decrease in systemic vascular resistance (SVR) (CI [l/min/m2] baseline 1.97+/-0.15, at 24 h 2.82+/-0.22 for levosimendan; baseline 1.98+/-0.17, at 24 h 2.66+/-0.08 for IABP; SVR [dyn*s*cm-5] baseline 1353+/-106, at 24 h 846+/-69 for levosimendan; baseline 1311+/-214, at 24 h 853+/-63 for IABP, respectively). After 3 h of treatment, CI and SVR had significantly improved in patients treated with levosimendan but not in the IABP-group (CI [l/min/m2] at 3 h 2.72+/-0.28 (+38%) for levosimendan versus 2.18+/-0.15 (+10%) for IABP). CONCLUSION: Infusion of levosimendan in acute CS results in early and sustained haemodynamic improvement. Short-term haemodynamic effects compare favourably with those seen after invasive IABP placement.     

Antibody responses to the herpes simplex virus type 2 glycoprotein G in sera of human immunodeficiency virus-infected patients in Slovakia.

Thirty sera of human immunodeficiency virus-positive (HIV+) and 37 sera of HIV-negative (HIV-) individuals in Slovakia were tested for the presence of antibodies to herpes simplex virus type 2 (HSV-2) glycoprotein G (gG). A notable difference between the prevalence of HSV-2-specific antibodies in HIV+ and that in HIV- individuals was found (37% vs. 11%) confirming and extending previous reports that HSV-2 infection is an important risk factor for HIV transmission. Efforts toward the detection of HSV-2 infection and its therapy by anti-HSV drugs should be considered an important factor in decreasing the risk of contracting and spreading of HIV in Slovakia.