Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study.

BACKGROUND: Progesterone receptor (PR) expression assessment in early invasive breast cancer remains controversial. This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer; particularly in oestrogen receptor (ER)-positive, lymph node (LN)-negative disease. METHODS: A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years (2000-2004) underwent surgery for primary invasive breast cancer with curative intent. Prospective data collection included patient demographics, pathology, ER and PR expression, HER2 status, adjuvant chemotherapy and endocrine therapy. Progesterone receptor expression was compared with (all causes) overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). RESULTS: Overall survival was 71.0% and BCSS was 83.0% at median follow-up of 8.34 years. Absent PR expression was significantly associated with poorer prognosis for OS, BCSS and DFS (P<0.0001, log-rank), even within the ER-positive, LN-negative group (hazard ratio for BCSS 3.17, 95% CI 1.43-7.01) and was not influenced by endocrine therapy. Cox's regression analysis demonstrated that PR expression was an independent prognostic variable. CONCLUSION: Absence of PR expression is a powerful, independent prognostic variable in operable, primary breast cancer even in ER-positive, LN-negative patients receiving endocrine therapy. Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy.

Multiparameter DNA content analysis identifies distinct groups in primary breast cancer.

BACKGROUND: Multiparameter flow cytometry is a robust and reliable method for determining tumour DNA content applicable to formalin-fixed paraffin-embedded (FFPE) tissue. This study examined the clinical and pathological associations of DNA content in primary breast cancer using an improved multiparametric technique. METHODS: The FFPE tissue from 201 primary breast cancers was examined and the cancers categorised according to their DNA content using multiparametric flow cytometry incorporating differential labelling of stromal and tumour cell populations. Mathematical modelling software (ModFit 3.2.1) was used to calculate the DNA index (DI) and percentage S-phase fraction (SPF%) for each tumour. Independent associations with clinical and pathological parameters were sought using backward stepwise Binary Logistic Regression (BLR) and Cox's Regression (CR) analysis. RESULTS: Tumours were grouped into four categories based on the DI of the tumour cell population. Low DI tumours (DI=0.76-1.14) associated with progesterone receptor-positive status (P=0.012, BLR), intermediate DI (DI=1.18-1.79) associated with p53 mutant tumours (P=0.001, BLR), high DI (DI1.80) tumours with human epidermal growth factor receptor 2 (HER2)-positive status (P=0.004, BLR) and 'multiploid tumours' (two or more tumour DNA peaks) did not show any significant associations. Tumours with high SPF% (10%) independently associated with poor overall survival (P=0.027, CR). CONCLUSION: Multiparametric flow analysis of FFPE tissue can accurately assess tumour DNA content. Tumour sub-populations associated with biomarkers of prognosis or likely response to therapy. The alterations in DNA content present the potential for greater understanding of the mechanisms underlying clinically significant biomarker changes in primary breast cancer.

Pilot task-based assessment of noise levels among firefighters.

PURPOSE: Over one million American firefighters are routinely exposed to various occupational hazards agents. While efforts have been made to identify and reduce some causes of injuries and illnesses among firefighters, relatively little has been done to evaluate and understand occupational noise exposures in this group. The purpose of this pilot study was to apply a task-based noise exposure assessment methodology to firefighting operations to evaluate potential noise exposure sources, and to use collected task-based noise levels to create noise exposure estimates for evaluation of risk of noise-induced hearing loss by comparison to the 8-hr and 24-hr recommended exposure limits (RELs) for noise of 85 and 80.3 dBA, respectively. METHODS: Task-based noise exposures (n=100 measurements) were measured in three different fire departments (a rural department in Southeast Michigan and suburban and urban departments in Northern California). These levels were then combined with time-at-task information collected from firefighters to estimate 8-hr noise exposures for the rural and suburban fire departments (n=6 estimates for each department). Data from 24-hr dosimetry measurements and crude self-reported activity categories from the urban fire department (n=4 measurements) were used to create 24-hr exposure estimates to evaluate the bias associated with the task-based estimates. RESULTS: Task-based noise levels were found to range from 82-109 dBA, with the highest levels resulting from use of saws and pneumatic chisels. Some short (e.g., 30 min) sequences of common tasks were found to result in nearly an entire allowable daily exposure. The majority of estimated 8-hr and 24-hr exposures exceeded the relevant recommended exposure limit. Predicted 24-hr exposures showed substantial imprecision in some cases, suggesting the need for increased task specificity. CONCLUSIONS: The results indicate potential for overexposure to noise from a variety of firefighting tasks and equipment, and suggest a need for further exposure characterization and additional hearing loss prevention efforts. RELEVANCE TO INDUSTRY: Firefighters may be at risk of noise-induced hearing loss, which can affect their fitness for duty and ability to respond effectively to emergencies. The results of this study suggest that additional efforts at hearing loss prevention among firefighters are warranted.

High frequency of complex TP53 mutations in CNS metastases from breast cancer.

BACKGROUND: Brain metastasis from breast cancer is usually associated with a poor prognosis and early death. Alteration of p53 may contribute to malignant progression by abrogation of apoptosis induced by oncogene activation and by acquisition of gain-of-function properties, which promote tumour aggression. Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastro-intestinal tract, but is much less frequent, at 25%, in primary breast cancer. The frequency of TP53 alteration in the central nervous system (CNS) metastatic breast cancer is not known. METHODS: In all, 23 cases of histologically confirmed CNS metastatic breast cancer were identified and the coding sequence of TP53 determined. TP53 was also sequenced in two control series of primary breast carcinomas from independent clinical centres. RESULTS: We demonstrate a strikingly high frequency of TP53 mutation in the CNS metastatic lesions with an over-representation of complex mutations (non-sense/deletions/insertions). Complex mutations occur in metastatic lesions in both triple-negative breast cancer and hormone receptor/HER2-positive cases. Analysis of paired primary carcinomas and brain metastatic lesions revealed evidence for both clonal selection and generation of new mutations (missense and complex) in progression from a primary breast carcinoma to brain metastasis. CONCLUSION: Mutation in TP53 is the most common genetic alteration reported during metastasis to the brain in breast cancer.

NT5E CpG island methylation is a favourable breast cancer biomarker.

BACKGROUND: Relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. In the light of existing preclinical and clinical data, we studied NT5E (5'-nucleotidase, ecto) expression and NT5E CpG island methylation in breast cancer. METHODS: We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma cell lines and primary and breast carcinomas. RESULTS: NT5E CpG island methylation was inversely associated with NT5E expression in breast carcinoma cell lines. In clinical series, patients whose primary tumours had NT5E CpG island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95% CI: 0.17-0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and demethylated in CNS metastases. Patients progressing to non-visceral as compared with visceral metastases were more likely to have NT5E CpG island methylation in primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95% CI: 1.31-8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9-20). Moreover, we observed a more favourable outcome to adjuvant chemotherapy in patients whose tumours were positive for NT5E CpG island methylation: DFS (P=0.0016, HR=5.1, 95% CI: 1.8-14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416-23.08). CONCLUSION: NT5E CpG island methylation is a promising breast cancer biomarker.

p53 mutation, deprivation and poor prognosis in primary breast cancer.

BACKGROUND: The deprivation gap for breast cancer survival remains unexplained by stage at presentation, treatment, or co-morbidities. We hypothesised that p53 mutation might contribute to the impaired outcome observed in patients from deprived communities. METHODS: p53 mutation status was determined using the Roche Amplichip research test in 246 women with primary breast cancer attending a single cancer centre and related to deprivation, pathology, overall, and disease-free survival. RESULTS: p53 mutation, identified in 64/246 (26%) of cancers, was most common in 10 out of 17 (58.8%) of the lowest (10th) deprivation decile. Those patients with p53 mutation in the 10th decile had a significantly worse disease-free survival of only 20% at 5 years (Kaplan-Meier logrank chi(2)=6.050, P=0.014) and worse overall survival of 24% at 5 years (Kaplan-Meier logrank chi(2)=6.791, P=0.009) than women of deciles 1-9 with p53 mutation (c.f. 56% and 72%, respectively) or patients in the 10th decile with wild-type p53 (no disease relapse or deaths). CONCLUSION: p53 mutation in breast cancer is associated with socio-economic deprivation and may provide a molecular basis, with therapeutic implications, for the poorer outcome in women from deprived communities.

Increased mortality in HER2 positive, oestrogen receptor positive invasive breast cancer: a population-based study.

BACKGROUND: This study assessed the impact of human epidermal growth factor receptor 2 (HER2) status on the outcomes in an unselected population of breast cancer patients who did not receive HER2-targeted therapy. METHODS: HER2 status by immunohistochemistry and fluorescence in situ hybridisation was compared with clinicopathological data, overall survival (OS) and disease-free survival (DFS) for all patients presenting with breast cancer over 3 years. RESULTS: In 865 patients (median follow up 6.02 years), HER2 positivity was identified in 13.3% of all cancers and was associated with higher tumour grade (P<10(-8)), lymphovascular invasion (P<0.001) and axillary nodal metastasis (P=0.003). There was a negative association with oestrogen-receptor (ER) and progesterone-receptor expression (P<10(-8)), but the majority (57%) of HER2+tumours were ER+HER2 positivity was associated with poorer OS (P=0.0046) and DFS (P=0.0001) confined to the lymph node-positive (LN+) and ER+ subgroups. CONCLUSION: HER2-positive cancers were less common in this population-based cohort than most selected series. The association of HER2 positivity with poor prognosis was confined to the ER+ and LN+ subgroups. The survival deficit for the 7.5% of patients with ER+/HER2+ cancer compared with ER+/HER2- patients points to a significant subgroup of women who may not (currently) be considered for HER2-directed therapy.

The prolyl 3-hydroxylases P3H2 and P3H3 are novel targets for epigenetic silencing in breast cancer.

Expression of P3H2 (Leprel1) and P3H3 (Leprel2) but not P3H1 (Leprecan) is down-regulated in breast cancer by aberrant CpG methylation in the 5' regulatory sequences of each gene. Methylation of P3H2 appears specific to breast cancer as no methylation was detected in a range of cell lines from other epithelial cancers or from primary brain tumours or malignant melanoma. Methylation in P3H2, but not P3H3, was strongly associated with oestrogen-receptor-positive breast cancers, whereas methylation in P3H3 was associated with higher tumour grade and Nottingham Prognostic Index. Ectopic expression of P3H2 and P3H3 in cell lines with silencing of the endogenous gene results in suppression of colony growth. This is the first demonstration of epigenetic inactivation of prolyl hydroxylases in human cancer, implying that this gene family represents a novel class of tumour suppressors. The restriction of silencing in P3H2 to breast carcinomas, and its association with oestrogen-receptor-positive cases, suggests that P3H2 may be a breast-cancer-specific tumour suppressor.

Performance of self-reported occupational exposure compared to a job-exposure matrix approach in asthma and chronic rhinitis.

OBJECTIVES: Self-reported exposure to vapours, gas, dust or fumes (VGDF) has been widely used as an occupational exposure metric in epidemiological studies of chronic lung diseases. Our objective was to characterise the performance of VGDF for repeatability, systematic misclassification, and sensitivity and specificity against exposure likelihood by a job-exposure matrix (JEM). METHODS: We analysed data from two interviews, 24 months apart, of adults with asthma and chronic rhinitis. Using distinct job as the unit of analysis, we tested a single response item (exposure to VGDF) against assignment using a JEM. We further analysed VGDF and the JEM among a subset of 199 subjects who reported the same job at both interviews, using logistic regression analysis to test factors associated with VGDF inconsistency and discordance with the JEM. RESULTS: VGDF was reported for 193 (44%) of 436 distinct jobs held by the 348 subjects studied; moderate to high exposure likelihood by JEM was assigned to 120 jobs (28%). The sensitivity and specificity of VGDF against JEM were 71% and 66%, respectively. Among 199 subjects with the same job at both interviews, 32% had a discordant VGDF status (kappa = 0.35). Those with chronic rhinitis without concomitant asthma compared to asthma alone were more likely to have a VGDF report discordant with the JEM (OR 3.6, 95% CI 1.4 to 9.0; p = 0.01). Rhinitis was also associated with reported VGDF in a job classified by the JEM as low exposure (OR 3.9, 95% CI 1.6 to 9.4; p = 0.003). CONCLUSION: The VGDF item is moderately sensitive measured against JEM as a benchmark. The measure is a useful assessment method for epidemiological studies of occupational exposure risk.

Effect of dietary triacylglycerol structure on lipoprotein metabolism: a comparison of the effects of dioleoylpalmitoylglycerol in which palmitate is esterified to the 2- or 1(3)-position of the glycerol.

The effect on lipoprotein metabolism of diets enriched in different isomers of dioleoylpalmitoylglycerol was studied. One diet contained fat in which palmitate was esterified to the two outer positions of the glycerol (OOP) and the other in which it was esterified to the middle carbon (OPO). The lipid composition of chylomicrons was similar in rats fed either fat blend. However, triacylglycerol (TAG) in chylomicrons from OPO fed animals was relatively enriched in palmitic acid, at the expense of stearic, oleic and linoleic acids. Silver phase HPLC and 2-positional analysis clearly demonstrated that the identity of the fatty acid in the 2-position was similar in both dietary and chylomicron TAG. No significant differences could be seen in the in vitro hydrolysis of chylomicron TAG from animals fed the two fats labelled with [14C]palmitate. As expected, following hydrolysis, palmitate was released as free fatty acid from chylomicrons isolated from OOP-fed animals but within 2-monoacylglycerol from those fed OPO. The enrichment of chylomicrons with palmitate in animals fed O[14C]PO resulted in increased delivery of [14C]palmitate to the liver. In a further series of experiments Golden Syrian hamsters were fed diets containing the fat blends and either 0.005% or 0.12% (w/w) cholesterol, for 28 days. No differences in fasting plasma lipoprotein concentrations were seen in response to the dietary fats. We conclude that, while these isometric triacylglycerols had transient effects on chylomicron metabolism, no significant longer term effect on plasma concentrations of endogenous lipoproteins could be found.

The neuroendocrine effects of interleukin-2 treatment.

Observations of neuropsychiatric changes in patients receiving interleukin-2 (IL-2) led us to examine the effects of IL-2 administration on the stress-related hormones, beta-endorphin, ACTH, cortisol, and CRH. We evaluated 30 cancer patients who received immunotherapy with IL-2 or IL-2 plus lymphokine-activated killer (LAK) cells. Blood samples were taken immediately before and 4 and 8 h after infusion of IL-2 or IL-2 plus LAK cells. IL-2 stimulated increased hormone levels 4 h after infusion compared with those before therapy and with basal levels in normal volunteers at the following magnitudes: beta-endorphin, 10-fold; ACTH, 20-fold; and cortisol, 2-fold. The effect of IL-2 was not altered in patients also receiving LAK cells. An effect of treatment course was noted, with higher stimulated values seen 4 h after IL-2 in the second treatment course compared with those after the first course [change (delta) in beta-endorphin, 101 vs. 11 fmol/mL; delta ACTH, 138 vs. 8 pmol/L; delta cortisol, 414 vs. 218 nmol/L]. We conclude that IL-2 treatment induces the release of neuroendocrine hormones and that a significant increase in hormonal stimulation occurs upon reexposure to IL-2.

Saturated fatty acid chain length and positional distribution in infant formula: effects on growth and plasma lipids and ketones in piglets.

Human milk contains a large proportion of palmitic acid (16:0) with > 70% esterified to the center sn-2 position of the milk triglyceride. Infant formulas often use 8:0 + 10:0 [medium-chain triglyceride (MCT)] or 12:0 + 14:0 (coconut oil) as the saturated fat. The effect of formula saturated fatty acid composition; 8:0 + 10:0, 12:0 + 14:0, or 16:0 from palm oil or synthesized triglyceride containing predominantly sn-2 16:0 on plasma lipids and fatty acids was studied in piglets. Although the formulas contained similar 18:1 and 18:2n-6, plasma lipid percentages of 18:1 and 18:2n-6 were higher in piglets fed the formula with MCT or coconut oil rather than the formulas with 16:0, or sow milk. The sn-2 16:0 of the synthesized triglyceride had unique properties. Specifically, piglets fed synthesized triglyceride had significantly higher cholesteryl ester 16:0 identical to that in piglets fed sow milk and higher plasma total and high-density-lipoprotein cholesterol than piglets fed the other formulas.

Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization.

BACKGROUND: The low sn-2 palmitate content of infant formulas results in formation of fatty acid calcium soaps in the stools and reduced calcium absorption. OBJECTIVE: Our objective was to test the hypotheses that increasing the proportion of sn-2 palmitate in formula for term infants would result in greater skeletal mineral deposition and reduced stool hardness. DESIGN: Healthy term neonates were randomly assigned to receive standard formula (n = 103) or formula containing 50% sn-2 palmitate (high-sn-2 formula; n = 100) for 12 wk. One hundred twenty breast-fed infants were also studied. The main outcome measures were 1) radial (single-photon absorptiometry) and whole-body (dual-energy X-ray absorptiometry) bone mineral content (WBBMC) at 12 wk and 2) stool frequency, volume, and consistency at 6 and 12 wk. Secondary outcome measures included stool fatty acid content. RESULTS: Infants receiving high-sn-2 formula had higher WBBMC (128.1 +/- 9.7 compared with 122.7 +/- 10.1 g, adjusted for size and sex), softer stools at 6 and 12 wk, and a lower proportion of stool soap fatty acids than did infants receiving the control formula. Breast-fed infants had adjusted WBBMC values (128.3 +/- 9.1 g) similar to those of infants fed high-sn-2 formula and significantly higher than those of infants fed the control formula. CONCLUSIONS: Changing the stereoisomeric structure of palmitate in infant formula resulted in higher WBBMC, reduced stool soap fatty acids, and softer stools more like those of breast-fed infants. The greater bone mass measured could be important if it persists beyond the trial period; this merits further investigation.

Differing approaches to two-dimensional shape recognition.

This article reviews a number of approaches that perceptual psychologists have taken in attempting to understand 2-dimensional (2-D) shape recognition. Various strands in the literature are traced and current theoretical accounts are discussed in light of the earlier work. Today, it is generally accepted that the internal representation of shape is in the form of a structural description. Such a description is, in turn, couched in some form of abstract code. There is increasing interest in the notion that structural descriptions are critically determined by the imposition of a frame of reference. Although the discussion primarily deals with work on 2-D shapes, the underlying assumption is that this work is fundamental for theories of visual object recognition.

Human pulmonary responses to experimental inhalation of high concentration fine and ultrafine magnesium oxide particles.

Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles. We quantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. We compared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter). There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. We conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.

Formate in serum and urine after controlled methanol exposure at the threshold limit value.

Methanol will be present as a new air pollutant when methanol-powered vehicles are introduced in the United States. Little is known about the effect of low-dose methanol exposure. It is controversial whether or not formate, the main metabolite responsible for methanol's acute toxicity, is a sensitive biological marker of toxicity or exposure. We studied the effect of a 4-hr exposure at rest to 200 ppm of methanol vapors on endogenous serum formate and on urinary formic acid excretion. A randomized, double-blind study of human exposure to a constant concentration of methanol was performed in a whole-body exposure chamber. Twenty-six healthy volunteers, each serving as his or her own control, participated in sham and methanol exposures. Urine (at 0, 4, 8 hr) and serum specimens (15 time points over 8 hr) collected before, during, and after the exposure were measured for formate. We found no significant differences in serum formate concentration between exposure and control conditions either at any time point or for area under the curve. Mean concentrations at the end of the exposure were: exposed 14.28 +/- 8.90 mg/l and control 12.68 +/- 6.43 mg/l. A slight, but nonsignificant (p = 0.08), increase in urine formate excretion rate was found at 4 hr (exposed 2.17 +/- 1.69 mg/4 hr and control 1.67 +/- 1.02 mg/4 hr). Age, sex, folic acid level, and smoking were not significant covariates. At 200 ppm, methanol exposure does not contribute substantially to endogenous formate quantities. Serum and urine formate determinations are not sensitive biological markers of methanol exposure at the threshold limit value.

Grouping processes in visual search: effects with single- and combined-feature targets.

We report evidence for spatially parallel visual search for targets defined by combinations of form elements in visual search. In Section 1, we show that flat search functions occur for combined-form targets when distractor forms are homogeneous and can be grouped together, thus segmenting the target from the distractors. Introducing heterogeneous distractors lessens distractor grouping and can produce serial search. These results cannot be easily attributed to subjects' use of local feature information to discriminate targets. Instead, they suggest that grouping can operate at a level at which combined form information is represented. In Section 2 we show that these grouping effects are spatially scaled by the size of the stimuli. In Section 3 we show that heterogeneity does not prevent flat search functions when the target has a unique defining feature. The data are interpreted in terms of a hierarchical processing system involving both devoted single-feature and combined-feature (junction) maps. Grouping processes can operate at both the single-feature and the combined-form levels. Selection in visual search remains confined to one object description at a time, but this description can be at various spatial scales, including that at the level of grouped forms.

The cup-to-disc ratio and central retinal vein occlusion.

Recent reports have suggested that a small optic cup may contribute to the development of certain optic disc disorders, such as anterior ischemic optic neuropathy. In a masked fashion, the cup-to-disc ratios from the fellow eyes of 55 patients with central retinal vein occlusion (CRVO) were compared with 55 controls to determine whether a similar association could be established for CRVO. Controls came from two population-based surveys, and they were matched to cases for age, race, and sex. The mean cup-to-disc ratios for the CRVO fellow eyes and controls were 0.39 and 0.40, respectively; the distribution of the sizes of the cup-to-disc ratios was nearly identical in the two groups. These results suggested that the cup-to-disc ratio is not a useful predictor of the development of CRVO.

Effects of hot tea, coffee and water ingestion on physiological responses and mood: the role of caffeine, water and beverage type.

Psychopharmacological studies using caffeinated beverages or caffeine have rarely considered temporal effects on psychological and physiological function or the specific contribution of caffeine, hot water, or beverage type to the observed effects. The effect of 400 ml hot tea, coffee, and water consumption on systolic and diastolic blood pressure (SBP and DBP), heart rate, skin conductance (a measure of sympathetic nervous system activation), skin temperature, salivary cortisol, and mood were monitored in 16 healthy caffeine-withdrawn (14 h) subjects in a complete crossover design. Beverages were ingested with/without 100 mg caffeine and milk (tea/coffee only). Hot beverage ingestion rapidly increased skin conductance and temperature (+1.7 degrees C) with peak effects observed only 10-30 min post-consumption. Caffeine in the beverage rapidly augmented skin conductance responses but, in contrast to the effect of hot water, reduced the skin temperature response and increased SBP (+2.8 mmHg) and DBP (+2.1 mmHg) 30-60 min post-consumption. Both caffeine and milk addition to beverages independently improved mood and reduced anxiety 30 and 60 min post-consumption. Milk addition had no other effects apart from attenuating the transient increase in physiological responses associated with the drinking phase. There were no effects of beverage consumption on salivary cortisol or of beverage vehicle on salivary caffeine levels, the latter indicating that caffeine pharmacokinetics was similar in both tea and coffee, and not different from caffeinated water. In keeping with this, the responses to tea and coffee ingestion were similar and largely accounted for by the effects of hot water and caffeine. However, tea potentiated the increase in skin temperature compared to coffee and water indicative of a greater vasodilatory response plausibly related to the presence of flavonoids in tea. We conclude that ingestion of hot caffeinated beverages stimulates physiological processes faster than hitherto described, primarily via the effects of hot water and caffeine, but with beverage type and milk playing important modulatory roles.

The effects of black tea and other beverages on aspects of cognition and psychomotor performance.

Nineteen healthy volunteers ingested 400 ml black tea, coffee, caffeinated water, decaffeinated tea or plain water on three occasions through the day (0900, 1400 and 1900 hours). A 2 x 2 factorial design with caffeine (0, 100 mg) and beverage type (water, tea) was employed, with coffee (100 mg caffeine) as a positive internal control, based on a five-way crossover. A psychometric test battery comprising critical flicker fusion (CFF), choice reaction time (CRT), short-term memory (STM) and subjective sedation (LARS) was performed at regular intervals throughout the day, and intensively so immediately following each beverage. Consumption of tea compared to water was associated with transient improvements in performance (CFF) within 10 min of ingestion and was not affected by the time of day. Caffeine ingestion was associated with a rapid (10 min) and persistent reduction in subjective sedation values (LARS), again independent of time of day, but did not acutely alter CFF threshold. Over the whole day, consumption of tea rather than water, and of caffeinated compared to decaffeinated beverages, largely prevented the steady decline in alertness (LARS) and cognitive capacity observed with water ingestion. The effects of tea and coffee were similar on all measures, except that tea consumption was associated with less variation in CFF over the whole day. No significant treatment effects were apparent in the data for the STM. Tea ingestion is associated with rapid increases in alertness and information processing capacity and tea drinking throughout the day largely prevents the diurnal pattern of performance decrements found with the placebo (no caffeine) condition. It appears that the effects of tea and coffee were not entirely due to caffeine per se; other factors either intrinsic to the beverage (e.g. sensory attributes or the presence of other biologically active substances) or of a psychological nature (e.g. expectancy) are likely to play a significant role in mediating the responses observed in this study.