Uptake and localisation of mTHPC (Foscan®) and its14C-labelled form in normal and tumour tissues of the hamster squamous cell carcinoma model: a comparative study

The aim of this study was to evaluate the pharmacokinetics of meta(tetrahydroxyphenyl)chlorin (mTHPC) on different tissues of interest in a hamster tumour model and to confirm our earlier animal studies on semi-quantitative fluorescence microscopy. The results obtained by three different evaluation methods were compared: in vivo spectrofluorometry, ex vivo fluorescence microscopy and chemical extraction of 14C-labelled mTHPC. Following intracardiac injection of 0.5 mg kg−1 mTHPC, groups of five tumour-bearing animals were used for in situ light-induced fluorescence spectroscopy. Afterwards, the biopsies were taken and snap frozen for fluorescence microscopy. The presence of radioactivity in serum and tissues was determined after chemical digestion in scintillation fluid using a scintillation counter. For each analysed tissue, a good correlation was observed between the three evaluation methods. The highest fluorescence intensity and quantities of mTHPC were observed between 12 and 24 h in liver, kidney, serum, vascular endothelium and advanced neoplasia. The majority of mTHPC was found at around 48 h in smooth muscle and at 96 h in healthy cheek pouch mucosa and early malignant lesions. The lowest level of mTHPC was noted in striated muscle at all times. No selectivity in dye localisation was observed between early squamous cell carcinoma and healthy mucosa. Soon after the injection, a significant selectivity was noted for advanced squamous cell carcinoma as compared to healthy cheek pouch mucosa or striated muscle. A significant difference in mTHPC localisation and quantity was also observed between striated and smooth muscle during the first 48 h following the injection. Finally, this study demonstrated the usefulness of non-invasive in situ spectroscopic measurements to be performed systematically prior to photodynamic therapy as a real-time monitoring for each treated patient in order to individualise and adapt the light dosimetry and avoid over or under treatments

Tempo and the TFR

Tempo effects in period fertility indicators are widely regarded as a source of bias or distortion. But is this always the case? Whether tempo change results in bias depends, in the view advanced here, on the measure used, the meaning of bias/distortion, and the objective of analysis. Two ways of construing bias in period measures are suggested, and their relevance is discussed in the context of five broad purposes for measuring period fertility: describing and explaining fertility time trends, anticipating future prospects, providing input parameters for formal models, and communicating with nonspecialist audiences. Genuine timing effects are not biasing when period fertility is the explanandum but are distorting when the aim is to estimate cohort fertility. Alternatives to tempo adjustment are available that are a more defensible solution to the issue of timing change. Tempo adjustment could be more fruitfully considered a form of modeling rather than empirical measurement. The measurement of period fertility could be improved by relying more on a statistical approach and less on indicators based on stable assumptions. Future progress will depend on integrating research on measurement with substantive investigation

Nationalism and Ethnicity in Nepal

Gellner D, Pfaff-Czarnecka J, Whelpton J, eds. Nationalism and Ethnicity in Nepal. Kathmandu: Vajra Publ.; 2008

New Nepal, New Ethnicities: Changes since the mid-1990s

Pfaff-Czarnecka J. New Nepal, New Ethnicities: Changes since the mid-1990s. In: Pfaff-Czarnecka J, Gellner D, Whelpton J, eds. Nationalism and Ethnicity in Nepal. Kathmandu: Vajra Publishers; 2008: I-XXXIII