A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.     

Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy

Targeted interleukin-2 (IL-2) therapy with a genetically engineered antidisialoganglioside GD2 antibody-IL-2 fusion protein induced a cell-mediated antitumor response that effectively eradicated established bone marrow and liver metastases in a syngeneic model of neuroblastoma. The mechanism involved is exclusively natural killer (NK) cell-dependent, because NK-cell deficiency abrogated the antitumor effect. In contrast, the fusion protein remained completely effective in the T-cell-deficient mice or immunocompetent mice depleted of CD8+ T cells in vivo. A strong stimulation of NK-cell activity was also shown in vitro. Immunohistology of the leukocytic infiltrate of livers from treated mice revealed a strong staining for NK cells but not for CD8+ T cells. The therapeutic effect of the fusion protein was increased when combined with NK-cell-stimulating agents, such as poly I:C or recombinant mouse interferon-gamma. In conclusion, these data show that targeted delivery of cytokines to the tumor microenvironment offers a new strategy to elicit an effective cellular immune response mediated by NK cells against metastatic neuroblastoma. This therapeutic effect may have general clinical implications for the treatment of patients with minimal residual disease who suffer from T-cell suppression after high-dose chemotherapy but are not deficient in NK cells.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.     

Validity of a self-completed questionnaire measuring the physical demands of work

The aim of this study was to compare the results of open retropubic (OC) and laparoscopic (LC) colposuspension to the Cooper's ligament (Burch operation). We matched retrospectively 72 LC and OC according to their ages, the type of associated operations and the clinical stages of their urinary incontinence. We excluded associated prolapsus, previous surgical procedure for urinary incontinence, maximal urethral closure pressure lower than 30 cms of water and instability of the detrusor. We estimated the comparability of our two series about the other criteria which have an effect upon the post operative results in literature. The mean follow up was 17 months for LC and 46 months for OC. LC operative time was longer than (Mean: LC: 89 minutes, OC: 42 minutes), women considered LC less aching than OC. They needed less postoperative analgesia, mostly given only just the day of the procedure. LC length of hospitalization and return to normal activity was shorter than OC (Mean: LC: 3 days--OC: 6, 7 days; LC: 15 days--OC: 21 days). The graphs of the subjective cure and improvement rates made according to the Kaplan-Meier method could be compared with the log rank test. (Cure after one year: LC 79%, OC 69%--Improvement after one year: LC 85%, OC 82%--Cure after two years: LC 68%--OC 64%--Improvement after two years: LC 80%--OC 75%).     

Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I

We have developed an on-line archive of neuronal geometry to encourage the use of realistic dendritic structures in morphometry and for neuronal modeling, located at web address www.neuro.soton.ac.uk. Initially we have included full three-dimensional representations of 87 neurons from the hippocampus, obtained following intracellular staining with biocytin and reconstruction using Neurolucida. The archive system includes a structure editor for correcting any departures from valid branching geometry and which allows simple errors in the digitisation to be corrected. The editor employs a platform-independent file format which enforces the constraints that there should be no isolated branches and no closed loops. It also incorporates software for interconversion between the archive format and those used by various neuronal reconstruction and modelling packages. The raw data from digitisation software can be included in the archive as well as edited reconstructions and any further information available. Cross-referenced tables and indexes are updated automatically and are sorted according to a number of fields including the cell type, contributor, submission date and published reference. Both the archive and the structure editor should facilitate the quantitative use of full three-dimensional reconstructions of neurons from the hippocampus and other brain regions.