Measurements of wavelength dependent scattering and backscattering coefficients by low-coherence spectroscopy

Quantitative measurements of scattering properties are invaluable for optical techniques in medicine. However, noninvasive, quantitative measurements of scattering properties over a large wavelength range remain challenging. We introduce low-coherence spectroscopy as a noninvasive method to locally and simultaneously measure scattering μs and backscattering μb coefficients from 480 to 700 nm with 8 nm spectral resolution. The method is tested on media with varying scattering properties (μs = 1 to 34 mm−1 and μb = 2.10−6 to 2.10−3 mm−1), containing different sized polystyrene spheres. The results are in excellent agreement with Mie theor

Irinotecan-Induced Dysarthria

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria

The Impact of Curriculum Design in the Acquisition of Knowledge of Oncology: Comparison Among Four Medical Schools

Over the past 5years, cancer has replaced coronary heart disease as the leading cause of death in the Netherlands. It is thus paramount that medical doctors acquire a knowledge of cancer, since most of them will face many patients with cancer. Studies, however, have indicated that there is a deficit in knowledge of oncology among medical students, which may be due not only to the content but also to the structure of the curriculum. In this study, we compared students' knowledge acquisition in four different undergraduate medical programs. Further, we investigated possible factors that might influence students' knowledge growth as related to oncology. The participants comprised 1440 medical students distributed over four universities in the Netherlands. To measure students' knowledge of oncology, we used their progress test results from 2007 to 2013. The progress test consists of 200 multiple-choice questions; this test is taken simultaneously four times a year by all students. All questions regarding oncology were selected. We first compared the growth of knowledge of oncology using mixed models. Then, we interviewed the oncology coordinator of each university to arrive at a better insight of each curriculum. Two schools showed similar patterns of knowledge growth, with a slight decrease in the growth rate for one of them in year 6. The third school had a faster initial growth with a faster decrease over time compared to other medical schools. The fourth school showed a steep decrease in knowledge growth during years 5 and 6. The interviews showed that the two higher-scoring schools had a more focused semester on oncology, whereas in the others, oncology was scattered throughout the curriculum. Furthermore, the absence of a pre-internship training program seemed to hinder knowledge growth in one school. Our findings suggest that curricula have an influence on students' knowledge acquisition. A focused semester on oncology and a pre-internship preparatory training program are likely to have a positive impact on students' progress in terms of knowledge of oncology

Quantitative measurements of absorption spectra in scattering media by low-coherence spectroscopy

Low-coherence spectroscopy (LCS) is a spectroscopic method that allows for quantitative and localized assessment of absorption spectra by combining reflection spectroscopy with low-coherence interferometry. We describe absorption coefficient (µa) measurements by LCS in tissue simulating phantoms with varying scattering and absorbing properties. We used LCS in the 455–680 nm wavelength range with a spectral resolution of 8 nmto obtain µa spectra with ±0.5 mm−1 accuracy. We conclude that LCS is a promising technique for the in vivo determination of tissue chromophore concentrations

Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold based xenograft model

While NOD-SCID IL2Rγ(-/-) (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary AML and ALL. Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis CML patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche, but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL(+) and MLL-AF9(+) leukemias can be studied in detail. Accepted article preview online 29 April 2016; Advance online publication 17 May 2016This work was supported by grants from the Dutch Cancer Society (2009-4411; VU2011-5127) and by the EU (ITN EuroCSC). I-BET151 was kindly provided by Nicholas Smithers (GSK R&D, UK)

A phase I and pharmacokinetic study of intraperitoneal topotecan

Purpose: To evaluate the feasibility and pharmacology of intraperitoneal (IP) topotecan. Patients and methods: Fifteen patients with recurrent ovarian cancer in a phase I trial were treated with escalating IP topotecan doses (5–30 mg/m2) for pharmacokinetic analysis. Results: Dose limiting toxicity (DLT) was acute hypotension, chills and fever at the 30 mg/m2 dose level. Haematological toxicity and abdominal pain were mild for all dose levels studied. Pharmacokinetics: Peak plasma levels of total topotecan were reached at 2.7 ± 1.1 h after IP instillation. The apparent V ss was 69.9 ± 25.4 L/m2, plasma clearance 13.4 ± 2.5 L/h/m2 and plasma T1/2 3.7 ± 1.3 h. The plasma AUC was correlated with the dose (R = 0.95, P < 0.01). The plasma AUC ratio of lactone versus total topotecan (lactone + carboxy-forms) increased with the dose from 16% to 55%, (R = 0.84, P < 0.01). Peritoneal total topotecan was cleared from the peritoneal cavity at 0.4 ± 0.3 L/h.m2 with a T1/2 = 2.7 ± 1.7 h. The mean peritoneal/plasma AUC ratio for total topotecan was 54 ± 34. Conclusion: A substantial dose of topotecan can be delivered by the IP route, achieving cytotoxic plasma levels of topotecan, with acceptable toxicity. The recommended dose for further phase II trials is 20 mg/m2 IP, which enables combination with active doses of other cytotoxic drugs, in view of its limited myelotoxicity when given by this route. © 2001 Cancer Research Campaign http://www.bjcancer.co