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.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

TREATMENT OF SUPERFICIAL MYCOSES IN THE TROPICS: WHITFIELD'S OINTMENT VERSUS CLOTRIMAZOLE

Background. In tropical primary health care, essential drugs should be safe, effective, and as inexpensive as possible. To treat the very common dermatophyte infections of the skin, one may use inexpensive Whitfield's preparations, more expensive topical imidazole derivatives, or extremely expensive oral antifungals. Because a cream base is felt to be more appropriate than an ointment in tropical conditions, we wanted to compare the effectiveness of Whitfield's cream and a topical imidazole derivative in field conditions in the tropics. Methods. A double-blind trial was performed involving 153 patients with a dermatophyte infection of the skin in Karonga District, Northern Malawi, including 25 patients who were Hiv-i-seropositive, comparing Whitfieid's cream with clotrimazole cream. Results. 75 patients were treated with Whitfield's cream and 78 with clotrimazole cream for a period of 6 weeks. Cure rates ranged from 80% to over 90% depending on the definition of cure. If positive cultures after treatment were used as criterion for treatment failure, six were found in each treatment group. One in each treatment failure group was an mv-i-seropositive patient. Conclusions. The great majority of patients in the tropics with a dermatophyte infection of the skin can be cured with a topical antimycotic preparation and do not need expensive oral therapy. This also proved to be valid for HIV-I-seropositive patients. Whitfield's cream and clotrimazole cream are both very effective. The lower cost makes Whitfield's cream the treatment of choice in dermatophyte infections of the skin in tropical primary health care.     

Serum levels of insulin-like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity

Burren CP, Wanek D, Mohan S, Cohen P, Guevara-Aguirre J, Rosenfeld RG. Serum levels of insulin-like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity. Acta Pædiatr 1999; Suppl 428: 185–91. Stockholm. ISSN 0803–5326
Although insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the action of insulin-like growth factors (IGFs), regulation of their production in vivo is not completely understood. Serum concentrations of IGFBP-3, -4 and -5 and acid-labile subunit (ALS) were therefore examined in 20 children with growth hormone (GH) insensitivity before and after 6 months of therapy with recombinant human IGF-I (80 or 120 ug/kg twice daily). The IGFBP concentrations in these children were compared with those in 62 GH-deficient children receiving GH therapy for 3 months. Serum levels of IGFBP-3, -4 and -5 and ALS all increased significantly ( p < 0.0001) in GH-deficient children in response to GH therapy, whereas no significant increases occurred in the children with GH insensitivity. These findings indicate that GH is responsible for the regulation of serum levels of IGFBP-3, -4 and -5 and ALS, and that IGF-I does not directly regulate the concentrations of these circulating IGFBPs. □ Growth hormone, growth hormone insensitivity, insulin-like growth factor I, insulin-like growth factor binding protein     

Fibre composition in the interosseous nerve of the pigeon

The interosseous nerve of birds innervates a string of Herbst corpuscles located near the interosseous membrane between the tibia and fibula. Fibre composition of this nerve was assessed including both myelinated and unmyelinated axons. The diameter of the whole nerve is ∼100 μm. Complete data were obtained for 3 nerves. The mean total number of myelinated fibres and unmyelinated axons was 2872±53. The mean number of myelinated fibres was 280±20 and that for unmyelinated axons was 2600±47. There was a broad distribution of diameters for myelinated fibres ranging from ∼2 μm to 10 μm with a distinct peak at ∼3–5 μm and a less prominent second peak at 6–8 μm. Similarly, myelin sheath thickness distribution showed 2 peaks, one at 0.6–0.8 μm and another at 1.4–1.6 μm. It is suggested that the group represented by the second peak innervates the Herbst corpuscles. The group of smaller myelinated fibres and the unmyelinated axons are assumed to innervate other types of receptors, some of which may be nociceptors.