Results do not support the theory that early separation from the dam leads to future development of separation anxiety. Hyperattachment to the owner was significantly associated with separation anxiety; extreme following of the owner, departure cue anxiety, and excessive greeting may help clinicians distinguish between canine separation anxiety and other separation-related problems.

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH. © 2001 Cancer Research Campaign   http://www.bjcancer.com

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The cost-efficiency and time-saving associated with out-patient flexible cystoscopy have propagated its use nationwide. However, only minimal attention has been paid to the feelings of patients exposed to this physically and emotionally invasive technique. We studied 53 consecutive patients attending for check cystoscopy at the time of their first flexible cystoscopy. Acting as their own historical controls, their feelings about rigid cystoscopy under general anaesthesia and subsequent flexible cystoscopy under local anaesthesia were assessed: 6/53 (11%) preferred rigid cystoscopy under general anaesthesia. The only significant association with their dislike of flexible cystoscopy, was their desire to stay in hospital overnight. It was concluded that with careful counselling and attention to individual needs, the preference for flexible cystoscopy over rigid cystoscopy under general anaesthesia can approach 100%.

A central theme within the concept of enzyme-directed bioreductive drug development is the potential to predict tumour response based on the profiling of enzymes involved in the bioreductive activation process. Mitomycin C (MMC) is the prototypical bioreductive drug that is reduced to active intermediates by several reductases including NAD(P)H:quinone oxidoreductase (NQO1) and NADPH cytochrome P450 reductase (P450R). The purpose of our study was to determine whether NQO1 and P450R protein expression in a panel of low-grade, human superficial bladder tumours correlates with clinical response to MMC. A retrospective clinical study was conducted in which the response to MMC of 92 bladder cancer patients was compared to the immunohistochemical expression of NQO1 and P450R protein in archived paraffin-embedded bladder tumour specimens. A broad spectrum of NQO1 protein levels exists in bladder tumours between individual patients, ranging from intense to no immunohistochemical staining. In contrast, levels of P450R were similar with most tumours having moderate to high levels. All patients were chemotherapy naïve prior to receiving MMC and clinical response was defined as the time to first recurrence. Key words: NQO1; cytochrome P450 reductase; mitomycin C; bladder cancerThe ability to predict tumour response to chemotherapy has been and continues to be a major objective in cancer research with the emphasis currently being placed on the identification of molecular markers of tumour response. 1,2 Within the field of bioreductive drug development, the ability to individualise chemotherapy based on the activity of specific reductases and hypoxia in tumours forms one of the cornerstones of a concept known as enzyme-directed bioreductive drug development. 3 The key requirements for the successful clinical application of this concept include the development of drugs that are bioreductively activated by specific reductases and good correlations between tumour response and enzymology in experimental tumour models. Mitomycin C (MMC) is a clinically active agent used to treat a number of tumours and is regarded as the prototypical bioreductive drug. 4 Its mechanism of action has been extensively reviewed elsewhere [5][6][7][8] and involves a complex interplay between tumour physiology (oxygen tension and extracellular pH) and several reductase enzymes (both 1 and 2 electron reductases). The ability to predict cellular and tumour response to MMC based on tumour enzymology has been addressed by several research groups but the results are controversial, and there are conflicting reports on the relationship between tumour enzymology and chemosensitivity in the literature. This is particularly true in the case of the 2 electron reductase NAD(P)H:quinone oxidoreductase-1 (NQO1), which has been implicated in the bioreductive activation of MMC, especially under aerobic conditions. 5,6,9 Reports of good correlations between NQO1 activity (and mRNA expression) and response to MMC contrast sharply with reports of poor correlations in bot...