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.     

Congestive Heart Failure: A Case of Protein Misfolding

This article describes an interesting case of a patient presenting with congestive heart failure found to have restrictive cardiomyopathy with initial laboratory evaluation showing hypogammaglobuminemia without a monoclonal band on serum and urine electrophoresis. This case highlights the clinically significant cardiac manifestation caused by protein misfolding, a defect in protein homeostasis. In addition, the utility of a relatively newer laboratory test, serum free light chains as well as the importance of clinical and pathophysiologic correlation is also discussed. We present a relatively uncommon cause of heart disease, cardiac amyloidosis in a patient with a systemic plasma cell dyscrasia, and multiple myeloma.     

IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections     

Impact of Welfare Reform on Mortality: An Evaluation of the Connecticut Jobs First Program,A Randomized Controlled Trial

Objectives. We examined whether Jobs First, a multicenter randomized trial of a welfare reform program conducted in Connecticut, demonstrated increases in employment, income, and health insurance relative to traditional welfare (Aid to Families with Dependent Children). We also investigated if higher earnings and employment improved mortality of the participants.Methods. We revisited the Jobs First randomized trial, successfully linking 4612 participant identifiers to 15 years of prospective mortality follow-up data through 2010, producing 240 deaths. The analysis was powered to detect a 20% change in mortality hazards.Results. Significant employment and income benefits were realized among Jobs First recipients relative to traditional welfare recipients, particularly for the most disadvantaged groups. However, although none of these reached statistical significance, all participants in Jobs First (overall, across centers, and all subgroups) experienced higher mortality hazards than traditional welfare recipients.Conclusions. Increases in income and employment produced by Jobs First relative to traditional welfare improved socioeconomic status but did not improve survival.Randomized welfare experiments, which were often large and conducted in multiple locations in the United States, sought to study the effect of limits on the amount of time a participant could receive cash welfare benefits.1 These studies contributed to the end of “welfare as we know it” under the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) enacted in 1996. The majority of the randomized experiments leading up to PRWORA, and PRWORA itself, showed beneficial effects of welfare reform on earnings and employment.1,2Earnings and employment are thought to increase human longevity by improving material and psychosocial circumstances, and by increasing health insurance coverage.3–7 However, welfare reform essentially works by cutting income benefits and thereby forcing recipients of welfare back into the job market. This could produce stressors on the families receiving these benefits, particularly single mothers with multiple children who must balance family obligations with new employment commitments.2,8–11 It is also plausible that employment brings with it occupational exposures and dangers associated with increased travel (e.g., traffic accidents). In this study, we linked participant identifiers in one successful welfare reform experiment—Connecticut Jobs First—to mortality data. We explored the mortality experiences of participants overall, as well as those of various subgroups, including Blacks, Latinos, and families with more or less than 2 children.     

Reinforced reasoning in medicine

Some philosophers have argued that evidence of underlying mechanisms does not provide evidence for the effectiveness of a medical intervention. One such argument appeals to the unreliability of mechanistic reasoning. However, mechanistic reasoning is not the only way that evidence of mechanisms might provide evidence of effectiveness. A more reliable type of reasoning may be distinguished by appealing to recent work on evidential pluralism in the epistemology of medicine. A case study from virology provides an example of this so‐called reinforced reasoning in medicine. It is argued that in this case study, the available evidence of underlying mechanisms did in fact play a role in providing evidence in favour of a medical intervention. This paper therefore adds a novel and recent case study to the literature in support of evidential pluralism in medicine.     

Whom should we treat with novel agents? Specific indications for specific and challenging populations

Open in a separate window