Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination.

By conferring systemic protection and durable benefits, cancer immunotherapies are emerging as long-term solutions for cancer treatment. One such approach that is currently undergoing clinical testing is a therapeutic anti-cancer vaccine that uses two different viruses expressing the same tumor antigen to prime and boost anti-tumor immunity. By providing the additional advantage of directly killing cancer cells, oncolytic viruses (OVs) constitute ideal platforms for such treatment strategy. However, given that the targeted tumor antigen is encoded into the viral genomes, its production requires robust infection and therefore, the vaccination efficiency partially depends on the unpredictable and highly variable intrinsic sensitivity of each tumor to OV infection. In this study, we demonstrate that anti-cancer vaccination using OVs (Adenovirus (Ad), Maraba virus (MRB), Vesicular stomatitis virus (VSV) and Vaccinia virus (VV)) co-administered with antigenic peptides is as efficient as antigen-engineered OVs and does not depend on viral replication. Our strategy is particularly attractive for personalized anti-cancer vaccines targeting patient-specific mutations. We suggest that the use of OVs as adjuvant platforms for therapeutic anti-cancer vaccination warrants testing for cancer treatment.

Lactate quantitation in a gerbil brain stroke model by GSLIM of multiple-quantum-filtered signals. Generalized spectral localization by imaging.

Quantitative magnetic resonance imaging of lactate using a zero-quantum/double-quantum filter and generalized spectral localization by imaging (GSLIM) was applied to a model of unilateral stroke in gerbil brain. GSLIM lactate images at 4T clearly reveal elevated concentrations of lactate in the ischemic compared with the normal hemisphere 100-175 minutes after unilateral carotid ligation. These results indicate that the technique is capable of studies of brain infarcts, and that application to human ischemic pathology in brain and other tissues may be possible.

Quantitative lactate-specific MR imaging and 1H spectroscopy of skeletal muscle at macroscopic and microscopic resolutions using a zero-quantum/double-quantum coherence filter and SLIM/GSLIM localization.

Quantitative lactate imaging and spectroscopy were performed on phantoms and on electrically stimulated, excised frog skeletal muscle at macroscopic and microscopic resolutions. Lactate selectivity was achieved by use of a zero-quantum/double-quantum coherence (ZQC/DQC) lactate filter, which suppressed all signals besides lactate, including water and lipid, to below noise level. Three-dimensional lactate data sets were acquired in 1-3 h; one of these spatial dimensions was frequency-encoded and the other two were phase-encoded. High-resolution images were reconstructed using the spectral localization by imaging (SLIM) and generalized SLIM (GSLIM) techniques. Lactate quantitation was achieved by employing an external lactate concentration standard and was verified by comparison to quantitative STEAM-localized and nonlocalized spectra that used total creatine as an internal concentration reference. Additionally, quantitatively accurate behavior of the SLIM and GSLIM techniques as applied to data sets of low signal-to-noise ratio and to macroscopically heterogeneous objects was verified using simulations and real muscle lactate data sets with known heterogeneity.

[Etiology and pathogenesis of urolithiasis]. / Etiologia i patogeneza kamicy ukladu moczowego.

For ages nephrolithiasis has been a widespread disease and clinical statistics prove that its morbidity index is still increasing, thus it becomes a social problem. Peak morbidity usually occurs at the age between 30 and 40, that is why many patients professionally active and creative have to leave their jobs for a long period. In contrast to earlier years, frequency of the disease occurrence in females is systematically increasing and nowadays it is only slightly lower from that in males. Etiology and pathogenesis of the disease is also not entirely explained. It is generally accepted that urinary stone formation is determined by multiple factors which affect first of all chemical composition and physical features of urine. Individual properties of the kidneys and urinary tract and infections especially with urease producing pathogens as well as environmental factors are also taken into account. The most favourable circumstances for nephrolithiasis occurrence is co-existence of all these factors.

[Diagnosis, prophylaxis and treatment of urolithiasis]. / Diagnostyka, profilaktyka i leczenie kamicy ukladu moczowego.

Urolithiasis is a disease with complex and not fully explained etiology and pathogenesis. In its development there play role multiple factors, such as individual features of the kidneys and urinary tract, co-existing infections with urease-producing pathogens and environmental factors. Advance in the field of organ imaging has enabled development of new harmless diagnostic procedures that allowed for fast diagnosis, and current methods of treatment (USR, PCNL and ESWL) have significantly limited the number of surgical procedures performed because of urolithiasis. Introduction of these treatment methods markedly disturbed used for a long time scheme of management and in many cases it limited invasiveness of the treatment and shortened hospitalisation time. Unfortunately, not all urology departments in Poland have access to the newest methods of treatment, thus a percentage of patients treated with traditional methods is still high. Used nowadays methods of diagnosis and treatment have not fully solved a problem of urolithiasis metaphylaxis, and urolithiasis still remains a serious disease that requests close cooperation of the patients, nephrologist and urologist.

Improvement in human health risk assessment utilizing site- and chemical-specific information: a case study.

This paper provides results of an effort to use site- and chemical-specific data and other factors to characterize and refine risk estimates to a community. The refined assessment illustrated the influence of additional key variables on the risk estimates. Influence of variables associated with meteorological data and decay was relatively low. Influence of exposure assumptions was somewhat higher, approaching an order of magnitude. Of the variables examined, the butadiene slope factor assumption had the greatest impact, contributing nearly three orders of magnitude to the risk estimates separating the Best and Worst Case scenarios. Monte Carlo analysis indicated a high level of uncertainty in the risk estimates. Risk estimates in this paper should be considered in comparison to the approximate 1 in 4 background fatal cancer risk in the US population. In all cases the risk would be zero if butadiene is not carcinogenic in humans at prevailing exposure levels.

Secondary tracheoesophageal puncture: factors predictive of voice quality and prosthesis use.

OBJECTIVE: To identify factors predicting prosthesis use and final speech quality in patients undergoing secondary tracheoesophageal puncture (TEP) for voice restoration alter laryngectomy. METHODS: We undertook a retrospective study of 168 patients who underwent secondary TEP at the Cleveland Clinic between June 1980 and October 1993. Factors examined were: patient demographics, extent of initial surgery, method of pharyngeal preparation, history of irradiation, insufflation test results, pharyngeal stricture, and concurrent medical conditions. Univariate and multivariate statistical analyses were performed to identify predictive factors. RESULTS: At last evaluation, 73.8% (124) of the patients were still using the prosthesis. Quality of speech was the only predictor of prosthesis use (p < .001). Phonation on the first day was achieved in 90% (151) of patients. Speech result improved significantly over the first 6 months (p < .001). Univariate analysis found that the need for reconstruction at laryngectomy (p = .04), the presence of pharyngeal stricture (p = .001), and continued prosthetic use (p < .001) were associated with the speech result. There was no significant advantage to the lack of approximation of the pharyngeal constrictors (p = .31). Stepwise logistic regression showed that only the absence of pharyngeal stricture was associated with a better-quality voice (p = .001). CONCLUSION: Tracheoesophageal puncture is a reliable method for restoring voice after laryngectomy. Prosthesis use decreases with time, and good voice quality is the only predictor of continued prosthesis use. In this series the absence of pharyngeal stricture was the only significant predictor of good to excellent speech.

[Angiomyolipoma--rare renal tumor]. / Angiomyolipoma--rzadki guz nerki.

Three patients with Angiomyolipoma renis treated operatively in Urological Ward in the period April-September 1993 was described. Those renal tumors are rare and sometimes cause spontaneous retroperitoneal bleeding made emergency surgery intervention necessary.

[Posterior urethral valve--etiology, diagnosis and treatment]. / Zastawka cewki tylnej--etiologia, diagnostyka i leczenie.

The problems concerned the etiology, diagnosis treatment of the posterior urethral valves (PUV) were described. The malformation is found in boys and creates multi-infra cystic barrier symptoms during miction. USG examination is very helpful in the diagnosis of PUV, as well as micturating cysto-urethrography and urodynamic examination. In differential diagnosis of PUV, one must take into account the barrier causes in the following portions of the urinary tract: narrowing of the urethral exit anterior urethral valves, polyps, diverticuli, hypertrophy of the seminal cumulus. Surgical treatment includes valvular electro-resection, laser destruction, widening by the use of Fogarty catheter and Foley catheter ended with a NaCl solution filled balloon.

Early haemorrhage from brachiocephalic trunk as a complication of tracheostomy.

A 27-year-old patient suffered injuries to the facial bones and brain contusion in a traffic accident. On the third day after the accident the patient was admitted to an intensive care unit in view of increasing respiratory failure. Tracheostomy was performed for prolonged controlled respiration. On the 6th day after tracheostomy the patient died from a sudden massive hemorrhage from the tracheostomy site. Autopsy findings showed that the direct cause of death was injury to the brachiocephalic trunk communicating with a focus of tissue necrosis in the tracheal wall. The authors stress the early development of this complication and the necessity of the earliest possible commencement of intensive care in cases of injuries to the facial bones.