Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is expressed in a wide variety of adenocarcinomas, and it is well recognized that cancer patients are immunologically "tolerant" to CEA. The purpose of this study was to determine whether we could break immune tolerance to CEA by vaccinating patients with a monoclonal anti-idiotype antibody that is the internal image of CEA and to determine what impact this might have on patient survival. Twenty-four patients with advanced CEA-positive colorectal cancer who failed standard therapies except for two were entered into this Phase Ib trial. One patient was considered not assessable, because on the day of entering into the study, she was diagnosed with acute myelogenous leukemia. Patients were treated with 1, 2, or 4 mg of aluminum hydroxide-precipitated 3H1 anti-idiotype antibody every other week for four injections and then monthly until tumor progression was observed. Immunological monitoring included humoral and cellular idiotypic and CEA responses, and all patients were evaluated for toxicity, response, and survival. Hyperimmune sera from 17 of 23 patients demonstrated an anti-anti-idiotypic Ab3 response, and 13 of these responses were demonstrated to be true anti-CEA responses (Ab1'). The antibody response was polyclonal, and 11 mediated antibody-dependent cellular cytotoxicity. Ten patients had idiotypic T-cell responses, and five had specific T-cell responses to CEA. None of the patients had objective clinical responses, but overall median survival for the 23 evaluable patients was 11.3 months, with 44% 1-year survival (95% confidence interval, 23-64%). Toxicity was limited to local swelling and minimal pain. Anti-idiotype monoclonal antibody 3H1 that mimics CEA was able to break immune tolerance in the majority of treated patients. Overall survival of 11.3 months was comparable to other phase II data with advanced colorectal cancer patients treated with a variety of chemotherapy agents, including irinotecan, with considerably less toxicity. Although it is not clear that the vaccine itself had an impact on survival, this should be determined in a Phase III randomized trial.     

Quantitative axial oblique contrast left ventriculography: validation of the method by demonstrating improved visualization of regional wall motion and mitral valve function with accurate volume determinations

To compare the relative merits of conventional and axial RAO/LAO angiography, we performed biplane left ventricular (LV) cineangiograms in 36 patients in both the conventional 30-degree RAO/60-degree LAO projection and in the axial 45-degree RAO/60-degree LAO/25-degree cranial projection, in random sequence. LV volumes were calculated by a computerized system utilizing modification of the area-length method. Eng-diastolic volume, end-systolic volume, and ejection fraction correlated closely between the two projections (r = 0.93, 0.95, and 0.86, respectively). The axial 60-degree LAO view projected the LV apex inferiorly, the LV outflow tract superiorly, reduced LV foreshortening, and "uncovered" the LV outflow tract in all cases. Segmental wall motion abnormalities of the ventricular septum, apex, and posterior wall were better evaluated by the axial 60-degree LAO view in patients with regional asynergy in these zones. The 45-degree RAO, compared to the 30-degree RAO view, allowed a true tangential view of the mitral valve and provided a large "clear area" between the mitral valve and descending aorta, which improved the ability to quantify mitral regurgitation. Thus, axial oblique LV angiography improves evaluation of LV regional wall motion and mitral valve function without compromising LV volume quantitation.     

The effects of titanium additions on AF1410 ultra-high-strength steel

The mechanical properties and microstructure of two heats of AF1410 steel were compared. The first heat, heat 811, contained a titanium addition of 0.02 wt pct, while the second heat, heat 91, contained no titanium, manganese, or other strong sulfide formers. The sulfur in heat 811 was gettered as titanium carbosulfide, while in heat 91 the sulfides were chromium sulfide. The toughness of heat 811 was found to be much enhanced compared to heat 91, with Charpy impact energies of 176 J and 79 J and K_IC fracture toughness values of 235 MPa.m^1/2 and 170 MPa.m^1/2, respectively. This significant difference in fracture toughness is attributed to the fact that titanium carbosulfide particles are more resistant to void nucleation than the chromium sulfide particles, which appear to nucleate voids at the onset of plastic strain. In addition to altering the sulfide particle type, the titanium addition also results in the presence of undissolved MC carbides in the titanium-modified steel in addition to the M₂C carbides found in heat 91. These carbides act as grain growth inhibitors, resulting in a finer prior austenite grain size and martensite packet size in heat 811.     

Focused Ultrasound Preconditioning for Augmented Nanoparticle Penetration and Efficacy in the Central Nervous System

Microbubble activation with focused ultrasound (FUS) facilitates the noninvasive and spatially‐targeted delivery of systemically administered therapeutics across the blood–brain barrier (BBB). FUS also augments the penetration of nanoscale therapeutics through brain tissue; however, this secondary effect has not been leveraged. Here, 1 MHz FUS sequences that increase the volume of transfected brain tissue after convection‐enhanced delivery of gene‐vector “brain‐penetrating” nanoparticles were first identified. Next, FUS preconditioning is applied prior to trans‐BBB nanoparticle delivery, yielding up to a fivefold increase in subsequent transgene expression. Magnetic resonance imaging (MRI) analyses of tissue temperature and K_trans confirm that augmented transfection occurs through modulation of parenchymal tissue with FUS. FUS preconditioning represents a simple and effective strategy for markedly improving the efficacy of gene vector nanoparticles in the central nervous system.     

The prevalence and severity of cancer pain: a study of newly-diagnosed cancer patients in Taiwan

In current clinical practice the "double-stapling technique" is the standard for reanastomosis following minimally invasive sigmoid resection. In the present study, we compared the TESA technique (transient endoluminally stented anastomosis) with conventional stapled anastomosis and evaluated the effect of remnant foreign material on follow-up examination with endosonography. Laparoscopic sigmoid resection was performed in 12 pigs (mean weight 63+/-5.9 kg). Animals were randomly divided into two groups: In Group A, reanastomosis was performed following a standard technique using a 29-mm circular stapler. In Group B, the TESA technique using a resorbable radiopaque stent of polyglycolic acid was applied. The anastomosis was examined by plain x-ray on days 1, 7, and 14, and by contrast enema on day 42, respectively. Endosonography, macroscopic inspection, and histological evaluation of the anastomosis were performed on day 42. All anastomoses in group A were patent. In one animal in Group B stent displacement with subsequent leak of the anastomosis was observed. Circumferential length of the anastomosis on day 42 did not differ between the groups (Group A: 8.00+/-0.45 cm vs. Group B: 7.8+/-2.0 cm, p = 0.82). The duration of the operation was 130+/-27 minutes in Group A and 100+/-18 minutes in Group B (p = 0.06). Weight gain was equal: Group A: 24+/-9.6 kg vs. Group B: 24+/-5.0 kg, p = 0.74. Endosonography on day 42 postoperatively in the area of the anastomosis in group A was impaired due to metallic staples. TESA is a competitive method for reanastomosis following laparoscopic sigmoid resection. In contrast to the conventional technique, the anastomosis is free of foreign material 1 month after the operation, which facilitates follow-up examinations with endosonography as well as other imaging diagnostics.     

AutoCyte Interactive Screening System. Experience at a university hospital cytology laboratory

The F1-ATPase is a multimeric enzyme (alpha3 beta3 gamma delta epsilon) primarily responsible for the synthesis of ATP under aerobic conditions. The entire coding region of each of the genes was deleted separately in yeast, providing five null mutant strains. Strains with a deletion in the genes encoding alpha-, beta-, gamma- or delta-subunits were unable to grow, while the strain with a null mutation in epsilon was able to grow slowly on medium containing glycerol as the carbon source. In addition, strains with a null mutation in gamma or delta became 100% rho0/rho- and the strain with the null mutation in gamma grew much more slowly on medium containing glucose. These additional phenotypes were not observed in strains with the double mutations: Delta alpha Delta gamma, Delta beta Delta gamma, Deltaatp11 Delta gamma, Delta alpha Delta delta, Delta beta Delta delta or Deltaatp11 Delta delta. These results indicate that epsilon is not an essential component of the ATP synthase and that mutations in the genes encoding the alpha- and beta-subunits and in ATP11 are epistatic to null mutations in the genes encoding the gamma- and delta-subunits. These data suggest that the propensity to form rho0/rho- mutations in the gamma and delta null deletion mutant stains and the slow growing phenotypes of the null gamma mutant strain are due to the assembly of F1 deficient in the corresponding subunit. These results have profound implications for the physiology of normal cells.     

Thickness effects of water overlayer on its explosive evaporation at heated metal surfaces

Molecular dynamics (MD) simulations have been employed to investigate the effect of the thickness of a water overlayer on the character of its ejection from a heated Au surface. The simulations are performed for five systems differing in the thickness of the water overlayer which was adsorbed on a metal substrate heated to 1000 K. For each system, an explosive evaporation occurs in the part of the water film adjacent to the metal surface and the upper part of the film is pushed off by the generated force. The average maximum temperature of the water film decreases as the film thickness increases. In contrast, the temperature achieved by the fast cooling due to the explosive evaporation shows an inverse trend. The significance of these model calculations to matrix-assisted laser desorption and ionization (MALDI) mass spectrometry is discussed.     

Comparison of seven antibiotic treatments with no treatment for bacteriological efficacy against bovine mastitis pathogens.

Milk culture results were retrospectively reviewed from 9007 cases of subclinical mastitis affecting cows housed in dairy herds located in New York and northern Pennsylvania. Cases included in this analysis had at least one mastitis pathogen isolated from the initial milk sample, were recultured within 1 mo, had permanent cow identification, and had records of whether mastitis was treated with an antibiotic or no treatment at all. Overall bacteriological cure rate for 21 mastitis pathogens was 68% (6097 of 9007). Antibiotic treated cases had a higher cure rate (75%) than did untreated cases (65%). Antibiotic treatments that significantly differed from the untreated cure rate of 65% were amoxicillin (82%), erythromycin (76%), cloxacillin (73%), and pirlimycin (44%). Cure rates for antibiotic treatments with cephapirin, hetacillin, or penicillin did not differ from the untreated cure rate. Agents for which some antibiotics were associated with increased cure rates compared with no treatment were Streptococcus agalactiae, streptococci other than Strep. agalactiae, and coagulase-negative staphylococci. The antibiotic most commonly associated with higher cure rates was amoxicillin. Most of the 21 mastitis agents showed no difference in bacteriologic cure rates between any of the 7 antibiotic treatments and no treatment.     

Intraindividual relations between the intensity and disclosure of daily emotional events: The moderating role of depressive symptoms.

Individuals with high levels of depressive symptoms tend to engage in lower levels of emotional disclosure than individuals who are lower in depressive symptoms. However, little is known about how depressive symptoms relate to the intraindividual relation between daily disclosure and the intensity of the daily events. The authors addressed these relations using a daily diary methodology. College students (N = 239) completed a measure of depression symptoms. They then completed measures of the intensity of the day’s most unpleasant event and their disclosure of that event each day for 7 days. Results indicated that depression moderated the intensity–disclosure relation such that depression symptoms were associated with diminished emotional disclosure for high-intensity events but not for low-intensity events. Individuals with relatively higher levels of depressive symptoms also experienced unpleasant daily events at a higher intensity level than did individuals with relatively fewer symptoms. Sex differences emerged such that men were less likely than women to disclose high-intensity negative events. These findings extend the use of the diary methodology to the study of emotional disclosure and also suggest possible interventions for counseling psychology practitioners. (PsycINFO Database Record (c) 2010 APA, all rights reserved)