Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.     

Noncardiogenic pulmonary edema caused by decompression sickness: rapid resolution following hyperbaric therapy

Noncardiogenic pulmonary edema is a recognized but uncommon manifestation of type 2 decompression sickness. It typically occurs within 6 hours of a dive. Because the adult respiratory distress syndrome in this setting is believed to be due to microbubbles in the pulmonary vasculature, recompression in a hyperbaric chamber has been recommended as a form of therapy. A patient developed noncardiogenic pulmonary edema following a seawater dive to 75 feet. There was complete radiologic and clinical resolution within 5 hours of hyperbaric therapy.     

Balanitis xerotica obliterans in children

This report is based on 7 children with balanitis xerotica obliterans. Of these patients 5 had stenosis of the urethral meatus that required meatotomy and the postoperative results were good. The frequency of balanitis xerotica obliterans in children at our center, as well as the findings of other authors, suggests that possibly more cases would be diagnosed during infancy if all dried foreskin were examined systematically.     

Inside-out kidney: unilateral herniation. Complication of cutaneous pyelostomy

A case of unilateral kidney herniation through a cutaneous pyelostomy stoma is reported. Our purpose is to point out the likely causes of this complication and its correction.     

Efficiency of endoscopic treatment for vesico‐ureteric reflux in adults

OBJECTIVE

To evaluate the results of our experience with endoscopic management of vesico‐ureteric reflux (VUR) in adults, and to describe factors and complications that might contribute to the failure of the technique.

PATIENTS AND METHODS

Between 1992 and 2006, 21 patients (17 women and four men; mean age 32.1 years, sd 15.6) had endoscopic treatment for VUR (14 unilateral and seven bilateral ureteric units, UU). Patients previously operated for VUR were excluded. The VUR grades were II, III, IV and V in 10, 12, five and one UUs, respectively. The main indication for treatment was a history of repeated episodes of acute pyelonephritis (61%). Complications after surgery were evaluated.

RESULTS

The success rate of the first endoscopic treatment was 69%, and was 81% after the second. Two UUs with grade IV VUR were endoscopically managed for a third time with complete resolution. Only one UU with grade V VUR required open surgery. The success rate for VUR grades II, III and IV after the first treatment was five of eight, 12/12 and one of five, respectively. After the second treatment the success rate increased to seven of eight and two of five for grades II and IV, respectively. There were no complications related to the intervention. Factors related to a failure of technique were duplex ureter and dysfunctional voiding in eight UUs (seven patients).

CONCLUSIONS

The endoscopic management of VUR in previously untreated adult patients is a simple and efficient technique, with low comorbidity.     

Chemical resistance of the gram-negative bacteria to different sanitizers in a water purification system

Background  

Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined.     

Intérêt et nature de la prise en charge dite psychologique du patient et son entourage dans le suivi hospitalier des tumeurs du système nerveux. À propos de l’expérience d’une équipe dédiée

The main interest of Neuro-Oncology is central nervous system tumors (mostly malignant). Significant improvements have recently been observed, however, difficult situations with gradual increase of potentially life-threatening functional deficits causing dependence still remain. The psychological impact is significant for the patient, his entourage and the caregivers. We describe the teams’ adaptation to this situation and the pragmatic care offered at the different phases of the disease.