Towards quantifying the aesthetic outcomes of breast cancer treatment: comparison of clinical photography and colorimetry

Rationale, aims and objectives Scarring is a significant cause of dissatisfaction for women who undergo breast surgery. Scar tissue may be clinically distinguished from normal skin by aberrant colour, rough surface texture, increased thickness (hypertrophy) and firmness. Colorimeters or spectrophotometers can be used to quantitatively assess scar colour, but they require direct patient interaction and can cost thousands of dollars. By comparison, digital photography is already in widespread use to document clinical outcomes and requires less patient interaction. Thus, assessment of scar coloration by digital photography is an attractive alternative. The goal of this study was to compare colour measurements obtained by digital photography and colorimetry. Methods Agreements between photographic and colorimetric measurements of colour were evaluated. Experimental conditions were controlled by performing measurements on artificial scars created by a make‐up artist. The colorimetric measurements of the artificial scars were compared with those reported in the literature for real scars in order to confirm the validity of this approach. We assessed the agreement between the colorimetric and photographic measurements of colour using a hypothesis test for equivalence, the intraclass correlation coefficient and the Bland–Altman method. Results Overall, good agreement was obtained for three parameters (L*a*b*) measured by colorimetry and photography from the results of three statistical analyses. Conclusion Colour measurements obtained by digital photography were equivalent to those obtained using colorimetry. Thus, digital photography is a reliable, cost‐effective measurement method of skin colour and should be further investigated for quantitative analysis of surgical outcomes.     

Elevation increases in moth assemblages over 42 years on a tropical mountain

Physiological research suggests that tropical insects are particularly sensitive to temperature, but information on their responses to climate change has been lacking—even though the majority of all terrestrial species are insects and their diversity is concentrated in the tropics. Here, we provide evidence that tropical insect species have already undertaken altitude increases, confirming the global reach of climate change impacts on biodiversity. In 2007, we repeated a historical altitudinal transect, originally carried out in 1965 on Mount Kinabalu in Borneo, sampling 6 moth assemblages between 1,885 and 3,675 m elevation. We estimate that the average altitudes of individuals of 102 montane moth species, in the family Geometridae, increased by a mean of 67 m over the 42 years. Our findings indicate that tropical species are likely to be as sensitive as temperate species to climate warming, and we urge ecologists to seek other historic tropical samples to carry out similar repeat surveys. These observed changes, in combination with the high diversity and thermal sensitivity of insects, suggest that large numbers of tropical insect species could be affected by climate warming. As the highest mountain in one of the most biodiverse regions of the world, Mount Kinabalu is a globally important refuge for terrestrial species that become restricted to high altitudes by climate warming.     

Association of self-reported alcohol use and hospitalization for an alcohol-related cause in Scotland: a record-linkage study of 23 183 individuals

Aims To investigate the extent to which self‐reported alcohol consumption level in the Scottish population is associated with first‐time hospital admission for an alcohol‐related cause. Design Observational record‐linkage study. Setting Scotland, 1995–2005. Participants A total of 23 183 respondents aged 16 and over who participated in the 1995, 1998 and 2003 Scottish Health Surveys, followed‐up via record‐linkage from interview date until 30 September 2005. Measurements Rate of first‐time hospital admission with at least one alcohol‐related diagnosis. Cox proportional hazards regression analysis was applied to estimate the relative risk of first‐time hospitalization with an alcohol‐related condition associated with usual alcohol consumption level (1–7, 8–14, 15–21, 22–35, 36–49, 50+ units/week and ex‐drinker, compared with <1 unit per week). Findings Of the SHS participants, 527 were hospitalized for an alcohol‐related cause during 135 313 person‐years of follow‐up [39 first admissions per 10 000 person‐years, 95% confidence interval (CI) 36–42]. Alcohol‐related hospitalization rates were considerably higher for males (61/10 000 person‐years, 95% CI 54–67) than for females (22/10 000 person‐years, 95% CI 18–26). Compared with the lowest alcohol consumption category (<1 unit per week), the relative risk of first‐time alcohol‐related admission increased with reported consumption: age‐adjusted hazard ratios ranged from 3 (1–5) for 1–7 units/week to 19 (10–37) for 50+ units/week (males); and from 2 (1–3) for 1–7 units/week to 28 (14–56) for 50+ units/week (females). After adjusting for age and usual alcohol consumption, the relative risk of first‐time alcohol‐related admission remained significantly higher for males reporting binge drinking and for both males and females residing in the most deprived localities. Conclusions Moderate and higher levels of usual alcohol consumption and binge drinking are serious risk factors for alcohol‐related hospitalization in the Scottish population. These findings contribute to our understanding of the relationship between alcohol intake and alcohol‐related morbidity.     

A glucose reference curve is the optimum method to determine the glycemic glucose equivalent values of foods in humans

The glycemic index ranks carbohydrates in foods on the basis of the blood glucose response they produce for a given amount of carbohydrate. The glycemic glucose equivalents (GGEs) is the blood glucose response to a defined portion of food. The purpose of this study was to determine the best method by which to measure the GGE of a food; whether it can be estimated from 1 or 2 glucose references or if a range of glucose references should be measured. Twenty individuals without diabetes participated. The incremental area under the curve (iAUC) from fasting to at least 120 minutes after consumption of 5 foods was determined. The iAUC for different glucose amounts was also determined and a standard glucose curve of glucose level against iAUC generated. The GGE of each food was estimated from iAUC of test food using the standard curve. The study found that using a glucose reference closest to the available carbohydrate content of the food gave a mean difference (95% confidence interval) in GGEs of 3.4 (2.0-4.8) g in comparison to the standard curve. Using a 50-g glucose reference gave a mean difference in GGEs of 5.2 (4.7-5.6) g and interpolating from 2 glucose references, 3.5 (1.9-5.2) g in comparison to the standard curve. In conclusion, the best method to determine the GGE value of a food is to use the standard glucose reference curve and estimate the response of the food directly from this.     

Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study

PURPOSE: AQ4N is a novel bioreductive prodrug under clinical investigation. Preclinical evidence shows that AQ4N penetrates deeply within tumors and undergoes selective activation to form AQ4, a potent topoisomerase II inhibitor, in hypoxic regions of solid tumors. This proof-of-principle, phase I study evaluated the activation, hypoxic selectivity, and safety of AQ4N in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Thirty-two patients with cancer (8 glioblastoma, 9 bladder, 8 head and neck, 6 breast, and 1 cervix) received a single 200 mg/m(2) dose of AQ4N before elective surgery. AQ4 and AQ4N levels in 95 tissues (tumor, healthy tissue) were assessed by liquid chromatography-tandem mass spectrometry. Tissue sections were also analyzed for AQ4 fluorescence using confocal microscopy, and for expression of the hypoxia-regulated glucose transporter, Glut-1. RESULTS: Activated AQ4 was detected in all tumor samples with highest levels present in glioblastoma (mean 1.2 microg/g) and head and neck (mean 0.65 microg/g) tumors; 22 of 32 patients had tumor AQ4 concentrations > or = 0.2 microg/g, levels previously shown to be active in preclinical studies. In 24 of 30 tumor samples, AQ4 was detected at higher concentrations than in adjacent normal tissue (tumor to normal ratio range 1.1-63.6); distant skin samples contained very low concentrations of AQ4 (mean 0.037 microg/g). Microscopic evaluation of tumor sections revealed that AQ4 colocalized within regions of Glut-1+ hypoxic cells. CONCLUSIONS: AQ4N was activated selectively in hypoxic regions in human solid tumors. Intratumoral concentrations of AQ4 exceeded those required for activity in animal models and support the evaluation of AQ4N as a novel tumor-targeting agent in future clinical studies.     

Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function.

PURPOSE: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. EXPERIMENTAL DESIGN: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. RESULTS: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). CONCLUSIONS: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.     

A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer.

PURPOSE: The primary aim of this study was to measure the objective tumor response rate following treatment with indisulam [E7070; N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] as second-line therapy in patients with advanced non-small cell lung cancer. The secondary aims were to determine progression-free survival, to assess the safety and tolerability of indisulam, and to study its pharmacokinetic and pharmacodynamic profile. EXPERIMENTAL DESIGN: Patients were randomized to receive indisulam every 3 weeks either as a single i.v. dose of 700 mg/m(2) on day one (dx1) or 130 mg/m(2) given on days 1 to 5 inclusive as a daily infusion (dx5). All patients had previously received platinum-based chemotherapy. RESULTS: Forty-four patients were randomized. Only minor responses were seen. Myelosuppression, gastrointestinal symptoms, and lethargy were the most common toxicities and were more frequent in the dx1 arm. The pharmacokinetics of indisulam in each treatment schedule were adequately described using a previously developed population pharmacokinetic model and were mostly consistent with the results of the phase I program. Flow cytometric analysis of endobronchial and metastatic disease revealed a reduction in the fraction of cycling cells and an increase in apoptosis following indisulam compared with pretreatment levels. CONCLUSIONS: We conclude that, despite evidence of tumor-specific indisulam-induced apoptosis, neither of these treatment schedules has single-agent activity as second-line treatment of non-small cell lung cancer.