Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study.

PURPOSE: To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test. METHODS: Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR). RESULTS: On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml  kg  min-1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC. CONCLUSION: These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions.

Group therapy for people with bulimia nervosa: systematic review and meta-analysis.

BACKGROUND: Approximately 25% of people with bulimia nervosa (BN) who undertake therapy are treated in groups. National guidelines do not discriminate between group and individual therapy, yet each has potential advantages and disadvantages and it is unclear how their effects compare. We therefore evaluated how group therapy for BN compares with individual therapy, no treatment, or other therapies, in terms of remission from binges and binge frequency. METHOD: We performed a systematic review and meta-analysis of randomized controlled trials of group therapies for BN, following standard guidelines. RESULTS: A total of 10 studies were included. Studies were generally small with unclear risk of bias. There was low-quality evidence of a clinically relevant advantage for group cognitive behavioural therapy (CBT) over no treatment at therapy end. Remission was more likely with group CBT versus no treatment [relative risk (RR) 0.77, 95% confidence interval (CI) 0.62-0.96]. Mean weekly binges were lower with group CBT versus no treatment (2.9 v. 6.9, standardized mean difference = -0.56, 95% CI -0.96 to -0.15). One study provided low-quality evidence that group CBT was inferior compared with individual CBT to a clinically relevant degree for remission at therapy end (RR 1.24, 95% CI 1.03-1.50); there was insufficient evidence regarding frequency of binges. CONCLUSIONS: Conclusions could only be reached for CBT. Low-quality evidence suggests that group CBT is effective compared with no treatment, but there was insufficient or very limited evidence about how group and individual CBT compared. The risk of bias and imprecise estimates of effect invite further research to refine and increase confidence in these findings.

Pharmacoscintigraphy confirms consistent tamsulosin release from a novel triple-layered tablet.

Conventional modified release preparations of tamsulosin HCl have been linked to increased incidence of cardiovascular adverse events, possibly due to rapid drug peaks soon after ingestion. A 'flattened' absorption profile has been shown to reduce the occurrence of these unwanted effects while improving symptom control. The potential of a novel triple-layered tablet to effect prolonged release and continuous absorption of tamsulosin HCl in the gastrointestinal tract was investigated in this clinical study. Gastrointestinal (GI) transit behaviour was monitored by scintigraphic imaging of technetium-labelled tablets. Drug absorption levels were simultaneously determined through pharmacokinetic analysis of blood samples. A mean Cmax of 6 ± 3 ng/nL was achieved after 324 ± 184 min (mean tmax). The mean AUC0-24 was noted as 4,359 ± 1,880 ng/mL min. The mean gastric emptying and colon arrival times of the tablets were 105.2 ± 68.9 and 270.1 ± 32.0 min post-dose; giving a mean small intestine transit time of 164.9 ± 83.6 min. Variations in gastrointestinal transit did not appear to influence drug absorption. Correlation of scintigraphic and PK data indicated that tamsulosin HCl is released steadily throughout the entire GI tract, suggesting that the mechanism of drug release is independent of GI site allowing drug release even in the low moisture environment of the colon.

Informing future research priorities into the psychological and social problems faced by cancer survivors: a rapid review and synthesis of the literature.

PURPOSE: To establish what is known regarding the psychological and social problems faced by adult cancer survivors (people who are living with and beyond a diagnosis of cancer) and identify areas future research should address. METHOD: A rapid search of published literature reviews held in electronic data bases was under taken. Inclusion and exclusion criteria, and removal of duplicated papers, reduced the initial number of papers from 4051 to 38. Twenty-two review papers were excluded on grounds of quality and 16 review papers were selected for appraisal. RESULTS: The psychological and social problems for cancer survivors are identified as depression, anxiety, distress, fear of recurrence, social support/function, relationships and impact on family, and quality of life. A substantial minority of people surviving cancer experience depression, anxiety, and distress or fear associated with recurrence or follow up. There is some indication that social support is positively associated with better outcomes. Quality of life for survivors of cancer appears generally good for most people, but an important minority experience a reduction in quality of life, especially those with more advanced disease and reduced social and economic resources. The majority of research knowledge is based on women with breast cancer. The longer term implications of cancer survival have not been adequately explored. CONCLUSIONS: Focussing well designed research in the identified areas where less is already known about the psychological and social impact of cancer survival is likely to have the greatest impact on the wellbeing of people surviving cancer.

Modulation of gastric pH by a buffered soluble effervescent formulation: A possible means of improving gastric tolerability of alendronate.

Gastrointestinal side-effects of alendronate (ALN) are believed to be associated with oesophageal lodging of tablets and perhaps reflux of gastric contents with alendronate under strongly acidic pH conditions. This leads to unfavourable posture restrictions when dosing. This clinical study evaluated gastric emptying and gastric pH after administration of Fosamax(®) tablets and a novel effervescent ALN formulation with a high buffering capacity. This novel formulation, EX101, was developed to potentially improve gastric tolerance. Gastric pH was monitored by nasogastric probes. Gastric emptying was determined simultaneously by scintigraphic imaging of (99m)Tc-DTPA labelled formulations. Both formulations tested rapidly cleared the oesophagus and there were no statistically significant or physiologically relevant differences in gastric emptying times. Mean pH at time to 50% gastric emptying of the radiolabel was significantly higher in EX101-treated subjects compared to those treated with Fosamax(®). At time to 90% gastric emptying of the radiolabel, mean pH values were comparable. Mucosal exposure to ALN at pH less than 3 is irritating to gastro-oesophageal tissue. Ingestion of Fosamax(®) resulted in ALN being present in the stomach at a pH below 3 within minutes. EX101 minimised the possibility of exposing the oesophagus (in case of reflux) to acidified ALN.

Knowledge, ignorance and priorities for research in key areas of cancer survivorship: findings from a scoping review.

BACKGROUND: Patients who have completed initial cancer treatment (cancer survivors) have been relatively neglected. We need data to help us better understand the needs of this group and to underpin evidence-based service development. METHODS: Scoping reviews of research published in the last two decades focussing on the problems faced by cancer survivors, and the effectiveness of interventions for these problems were undertaken. The aim was to identify what we know, what we do not know and opportunities where research could provide new information. We searched for, retrieved and rapidly appraised systematic reviews sourced from the most common electronic databases supplemented by more recently published individual studies. RESULTS: The research evidence is surprisingly limited. We have some knowledge of the prevalence and nature of depression, pain and fatigue in cancer survivors. We know much less about cognitive and physical impairment, employment, financial well-being and relationships. Even where we have evidence, it is mostly of only moderate quality, is most often only for breast cancer and focuses almost exclusively on the early phase of survivorship. We have good evidence for the effectiveness of drug treatments for pain and moderate evidence for fatigue and depression, but not for other symptoms. Interventions based on rehabilitative and self-management approaches remain in the early stages of evaluation. INTERPRETATION: There has been a substantial amount of research describing many of the problems experienced by the cancer survivors. This is strongest in the area of symptoms in the period soon after treatment. However, the quality of the evidence is often poor, and some topics have been little examined. We urgently need data on the natural evolution and scale of the problems of cancer survivors obtained from well-designed, large-scale cohort studies and the robust testing of interventions in clinical trials. Given the current financially constrained research funding environment, we suggest areas in which strategic investment might give findings that have the potential to make a major impact on patient well-being in a 5-year time scale.

The physical and practical problems experienced by cancer survivors: a rapid review and synthesis of the literature.

PURPOSE: A rapid and comprehensive review to identify what is known and not known about the physical and practical problems faced by adult cancer survivors. METHODS: A systematic literature review process was used. This focused on published reviews to enable a fast but rigorous identification of both the gaps and well-researched areas within survivorship. RESULTS: The search identified 5121 reviews, of which 42 were screened and 9 met the quality and inclusion criteria. The majority of papers focused on physical well being (n = 6) with the remaining papers focusing on practical well being (employment and finance). The quality of the reviews varied (ranging from weak to good). Gaps identified include sexual function, lower-limb lymphoedema, peripheral neuropathy, bladder and GI problems, hormonal sequelae, older cancer survivors, work impact of cancer and context-specific unmet supportive care needs. The review found a lack of standardised nomenclature for survivorship and methodological limitations. CONCLUSIONS: Four main gaps in knowledge relating to the practical and physical problems associated with cancer survivorship have been identified. These are key symptoms, unmet supportive care needs, employment and older cancer survivors, and should be addressed by future research and systematic literature reviews. Work is also needed to address the nomenclature of survivorship and to improve the methodology of research into cancer survivors (including standardised measures, theoretical frameworks, longitudinal design, inclusion of older survivors and age-matched controls for comparison). The review highlighted the need for better research within the identified areas in order to improve the experiences of cancer survivors.

Most-probable-number rapid viability PCR method to detect viable spores of Bacillus anthracis in swab samples.

A comparison of Most-Probable-Number Rapid Viability (MPN RV) PCR and traditional culture methods for the quantification of Bacillus anthracis Sterne spores in macrofoam swabs from a multi-center validation study was performed. The purpose of the study was to compare environmental swab processing methods for recovery, detection, and quantification of viable B. anthracis spores from surfaces. Results show that spore numbers provided by the MPN RV-PCR method were typically within 1-log of the values from a plate count method for all three levels of spores tested (3.1x10(4), 400, and 40 spores sampled from surfaces with swabs) even in the presence of debris. The MPN method tended to overestimate the expected result, especially at lower spore levels. Blind negative samples were correctly identified using both methods showing a lack of cross contamination. In addition to detecting low levels of spores in environmental conditions, the MPN RV-PCR method is specific, and compatible with automated high-throughput sample processing and analysis protocols, enhancing its utility for characterization and clearance following a biothreat agent release.

Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion.

The CO2-SFE crude lipid extract and the free fatty acid extract from Perna canaliculus have anti-inflammatory effects on adjuvant-induced arthritis in rats.

The anti-inflammatory (AI) activity of a supercritical fluid extract (CO(2)-SFE) of tartaric acid-stabilised Perna canaliculus mussel powder, and of the free fatty acid (FFA) class separated from the CO(2)-SFE extract by column chromatography, was investigated in the rat adjuvant arthritis model. Administration of the CO(2)-SFE extract (100 mg/kg BW/day s.c.) for 15 days post-adjuvant inoculation significantly reduced rear paw swelling by 34% and the deterioration in total body condition by 52% in arthritic rats, compared to vehicle controls. These observations were accompanied by a decreased serum ceruloplasmin oxidase activity, and reduced inflammatory response of the spleen. The mussel FFA extract given at one third of the dose (30 mg/kg BW/day s.c.) and for a shorter treatment period (5 days during the inflammatory phase) achieved an even greater AI activity, and was equipotent to piroxicam (2 mg/kg BW/day s.c.). Preliminary toxicology assessment using both arthritic and non-arthritic (healthy) rats revealed no significant differences between the mussel treatment groups and respective vehicle controls in either organ weights, tissue histology or selected biochemical parameters. These results indicate the CO(2)-SFE crude lipid extract and its FFA components from stabilised P. canaliculus mussel powder contain biologically significant AI activity in vivo, with no apparent adverse side effects.

Randomized controlled trial of supervised exercise to evaluate changes in cardiac function in patients with peripheral atherosclerotic disease.

INTRODUCTION: Peripheral atherosclerotic disease (PAD) is a condition characterized by low functional capacity which is associated with impaired free living, ambulation and low exercise tolerance. The purpose of this randomized controlled study was to evaluate whether changes in maximal walking time are associated with adaptations in cardiovascular function following supervised exercise. METHODS: After ethics approval, 28 patients (63 +/- 11 years) completed a graded treadmill test (2 min stages, 3.2 km h(-1), with gradient increasing 2% every 2 min) until they reached level three or four on the claudication pain scale. Peak oxygen consumption was assessed on a breath-by-breath basis, by online expiratory gas analysis. Following a 40-min recovery period, peak cardiac output was measured using the non-invasive carbon dioxide rebreathing method described by Defares (J Appl Physiol, 13, 1958, 159). Peak cardiac power output was then computed using the equation described by Cooke et al. (Heart, 1998, 79, 289). Patients were randomly assigned to one of two groups: supervised, who exercised at the hospital twice weekly for 12 weeks or control, who received normal treatment which included encouragement to walk regularly. RESULTS: After 12 weeks, there were no significant changes in body mass, peak oxygen consumption, peak cardiac output, peak heart rate, peak cardiac power output, respiratory exchange ratio or rating of perceived exertion in both the supervised and control group. There was a significant improvement (91%) in maximal walking distance following the supervised exercise programme. Although patients' peak cardiovascular measurements were unchanged, the patients in the supervised exercise group were able to complete a higher workload at the end of the 12 weeks of exercise, for the equivalent demands on the circulation system. CONCLUSIONS: The findings from this study suggest that a short-term period of supervised exercise training results in an improved walking time in patients with limiting claudication because of PAD. It also demonstrated that the cardiovascular system becomes more efficient in meeting the demands of exercise. It is recommended that individuals with PAD should undertake exercise as a form of treatment.

The temporal relationship between erectile dysfunction and cardiovascular disease.

BACKGROUND: Erectile dysfunction (ED) and cardiovascular disease (CVD) share similar risk factors, and ED may be a marker of CVD progression. The study assessed: (i) the temporal relationship between ED and CVD and (ii) the UK incidence of ED, in patients with CVD and an age-matched control group. DESIGN: After ethics approval, 207 patients (CVD group) attending cardiovascular rehabilitation programmes and 165 age-matched subjects (control group), from GP practices across the UK, completed up to four questionnaires [ED details, The International Index of Erectile Function (IIEF) (before and after a cardiovascular event) and ED related Quality of Life]. A health professional also completed a medical details questionnaire. RESULTS: Erectile dysfunction was reported by 66% of individuals with CVD, with a mean duration of 5 +/- 5.3 years. The control group was significantly different (p < 0.05) in both incidence (37%) and mean duration (6.6 +/- 6.8 years). Only 53% of the CVD group and 43% of the control group had discussed their symptoms of ED with a health professional. The IIEF demonstrated that ED became significantly worse (p < 0.05) after a cardiovascular event, changing from moderate to severe (13-10). CONCLUSIONS: From these data, it is now evident that ED may precede a cardiovascular event by as much as 5 years. In almost half of the men with ED, there were missed opportunities to undertake a CVD risk assessment and provide an intervention, because the men did not acknowledge the problem. Men with ED should be specifically targeted for CVD preventative strategies in terms of lifestyle changes, and appropriate pharmacological treatments.

Novel anti-inflammatory omega-3 PUFAs from the New Zealand green-lipped mussel, Perna canaliculus.

The present study has identified in the marine mollusc, Perna canaliculus, an homologous series of novel omega 3 polyunsaturated fatty acids (omega-3 PUFA) with significant anti-inflammatory (AI) activity. The free fatty acid (FFA) class was isolated from a supercritical-CO2 lipid extract of the tartaric acid-stabilised freeze-dried mussel powder by normal phase chromatography, followed by reversed-phase high performance liquid chromatography (RP-HPLC). The RP-HPLC involved separation based on carbon numbers, followed by argentation-HPLC (Ag-HPLC) of the methyl esters based on degree of unsaturation. Identification of the FFA components was performed using gas chromatography (GC) with flame ionisation detection, and individual structures were assigned by GC-mass spectroscopy (GC-MS). Inhibition of leukotriene production by stimulated human neutrophils was used as an in vitro screening method to test the AI activity of the purified PUFAs. A structurally related family of omega-3 PUFAs was identified in the most bioactive fractions, which included C18:4, C19:4, C20:4, and C21:5 PUFA. The C20:4 was the predominant PUFA in the extract, and was a structural isomer of arachidonic acid (AA). The novel compounds may be biologically significant as AI agents, as a result of their in vitro inhibition of lipoxygenase products of the AA pathway.

Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped mussel, Perna canaliculus.

Total lipid extracts of P. canaliculus (a bivalve marine mollusc native to New Zealand, commonly called the green-lipped mussel) and Mytilus edulis (commonly called the common blue mussel) moderately inhibited ovine COX-1 and COX-2 pure enzymes in vitro. The inhibition was increased after the mussel extracts were saponified by KOH hydrolysis. Protease- and protease-lipase-hydrolysed lipid extracts of P. canaliculus exhibited similarly strong COX inhibition as the KOH-hydrolysed extract. Lyprinol(R) (a commercial extract from P. canaliculus) also exhibited strong inhibition of both COX isoforms, an effect that was increased 10-fold upon subsequent hydrolysis. In contrast, fish oil was not as anti-COX active as Lyprinol. The Lyprinol free fatty acid fraction, and to a lesser extent the Lyprinol triglyceride fraction, were the only lipid classes of Lyprinol to exhibit strong inhibition of the COX isoforms. The purified PUFA extracts were all bioactive, potently inhibiting COX-1 and COX-2. Incubation of Lyprinol in the absence of exogenous arachidonic acid (AA) showed the appearance of alternate prostaglandin metabolites, confirming Lyprinol PUFA as a competitive substrate inhibitor of AA metabolism.

Evaluation of a macrofoam swab protocol for the recovery of Bacillus anthracis spores from a steel surface.

A protocol to recover Bacillus anthracis spores from a steel surface using macrofoam swabs was evaluated for its accuracy, precision, reproducibility, and limit of detection. Macrofoam swabs recovered 31.7 to 49.1% of spores from 10-cm2 steel surfaces with a < or =32.7% coefficient of variation in sampling precision and reproducibility for inocula of > or =38 spores.

Cardiac pumping capability in patients with peripheral vascular disease.

INTRODUCTION: Peripheral vascular disease (PVD) is a condition characterized by atherosclerotic occlusive disease of the lower extremities, low functional capacity and low exercise tolerance. Less empirical data are available concerning the cardiovascular response to maximum exercise tests in patients with PVD. The purpose of this study was to examine cardiovascular variables in patients with peripheral vascular disease. METHODS: Fifty patients (67 +/- 9 years) completed an incremental exercise test (2 min stages, 3.2 km h(-1), with increases of 2% every 2 min) to maximum claudication pain. Maximal oxygen consumption (VO2) was assessed on a breath-by-breath basis by online expiratory gas analysis (CardiO2, Medical Graphics Co.). Blood pressure was recorded at peak exercise. Following a 30-min rest period, patients exercised at the highest level attained during the first test and cardiac output (QT) was measured using the exponential non-invasive rebreathing method. Cardiac power output peak (CPOpeak) in Watts (W), was then computed. RESULTS: Mean +/- SD values were; 13.85 +/- 4.14 ml kg min(-1); maximal walk time 357 +/- 227 s; peak mean arterial pressure 127 +/- 15 mmHg; 9.8 +/- 2.39 (l min(-1)); CPO 2.86 +/- 0.87 W. CONCLUSION: Patients with peripheral vascular disease demonstrate attenuated levels of cardiovascular capacity. This group of patients should be given exercise therapy in order to improve cardiovascular status and ambulatory function.

Validity and reliability of selected commercially available metabolic analyzer systems.

Automated metabolic gas analysis systems have advanced considerably over the past decade. They provide an abundance of information, which is not possible by using the traditional Douglas bag method and have become an essential tool in both physiological monitoring and in the diagnosis of cardiopulmonary disease. The validity and reliability of the different online metabolic analyzer systems are not well known, with relatively few independent studies being published. The purpose of this review was to examine and evaluate current literature regarding the validity and reliability of commercially available metabolic analyzer systems. This review reveals significant differences between the available systems in the way that they capture and process basic respiratory measurements. Online metabolic analyzer systems were found to vary significantly when compared with Douglas bag methods. These variations have the potential to introduce error into the accuracy with which the health of cardiovascular system can be assessed or training loads can be assigned. Compounding this is the fact that many automated systems are a "black box", which makes it easy to generate data without the user having much understanding of how the data were generated. In conclusion automated metabolic analyser systems are a scientifically robust method for the evaluation of cardiopulmonary function. Individual researchers and clinicians must, however, be able to make their own decisions about the level of error that is tolerable for their individual needs. This presents a significant practical challenge in light of the speed with which technical developments in the field occur and we make some suggestions for the formulation of intersystem comparison studies.

Effects of vibrissae removal on search accuracy in the water maze.

In two experiments, the vibrissae were clipped on either the left, the right, or both sides, and the rats were trained to find a submerged platform in the Morris water maze. In both experiments, animals without vibrissae on both sides or on the left consistently spent significantly more time in the "counter" area twice the platform diameter in size, surrounding the submerged platform, than intact controls. Counter preference was not as consistent across experiments in rats with right vibrissae removed. These results suggest that the vibrissae are required for proprioceptive location of the platform itself, but not for proximal search accuracy. Since ischemic damage to hippocampal CA1 pyramidal cells has also been reported to prolong counter search during training, the results support the suggestion that impaired hippocampal processing of proprioceptive information from the vibrissae may contribute to the increased latency to find the platform shown by ischemic rats.

A meta-analytic investigation of the relationship between the psychological distress of cancer patients and their carers.

The identification of factors that might affect the relationship between patients' and carers' psychological distress has received insufficient attention to date. A meta-analysis was conducted with 21 independent samples of cancer patients and their carers, to quantify the relationship and difference between respective measures of psychological distress. Correlation coefficients and standard differences were extracted from 21 studies that met pre-defined inclusion criteria. Random effects models were used. Variables that modified this relationship were examined with potential causes of heterogeneity explored. Analysis confirmed the positive association between patient and carer psychological distress (r = 0.35, P<0.0001), and indicated that patients and carers did not experience significantly more or less psychological distress than one another (P = 0.64). Subgroup analysis was performed to explore potential sources of heterogeneity, and initial findings indicated a relationship between time since diagnosis and the strength of correlation between patient and carer psychological distress. The meta-analysis was limited by the large clinical and methodological variability between studies, and further systematic prospective research is required. This preliminary evidence suggests that early intervention with the patient and their carer could prevent later development of psychological distress in both members.