The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.

BACKGROUND: The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560). METHODS: Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment. RESULTS: Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12-0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08-0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60-3.19) and OS HR of 1.33 (95% CI, 0.56-3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers. CONCLUSION: These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.

A 12-month prospective cohort study of injury in international rowers.

OBJECTIVE: In this study, the injury incidence and association with type and volume of training in international rowers were described. DESIGN: A prospective cohort design was used over a 12-month period. PATIENTS: 20 international rowers who were competing as part of the Irish Amateur Rowing Union squad system. METHODS: The rowers were interviewed monthly, and data were collected regarding their training and competition exposure as well as their injury experience. RESULTS: A mean injury rate of 3.67 per 1000 exposure hours was reported with a total of 44 injuries reported in a 12-month period. The mean number of injuries sustained per athlete was 2.2 (1.24) over the 12-month period. The area where the greatest number of injuries were reported was the lumbar spine (31.82% of total injuries, 95% CI 20 to 50) (fig 2) followed by the knee (15.91% of total injuries, 95% CI 10 to 30) and the cervical spine (11.36% of total injuries, 95% CI 5 to 24). Half of the injuries (22 injuries, 50% of total reported injuries) were to the spine (chi(2) = 30.8, df = 9, p = 0.0003). Ergometer training load was the most significantly associated with injury risk (r = 0.68, p = 0.01). CONCLUSION: International rowers are at higher risk of injury than most non-contact sports and some contact sports. The high risk of lumbar spine injury and the significant association of high volume of ergometer training merit further research to reduce time and competition lost to injury.

Relationship between the intensity of physical activity, inactivity, cardiorespiratory fitness and body composition in 7-10-year-old Dublin children.

OBJECTIVE: To investigate the relationships between the time spent in specific intensities of activity and inactivity, cardiorespiratory fitness and body composition in children. METHODS: A cross-sectional study was conducted in a random sample of schools. Height, weight and waist circumference were measured in 224 children aged 7-10 years. Cardiorespiratory fitness was estimated by the 20 m multistage running test, and physical activity was measured over 4 days by the RT3 (a triaxial accelerometer). Time each day spent in moderate and vigorous intensities of activity was calculated. RESULTS: Twelve schools agreed to participate in the study. Body composition and fitness data were obtained for 224 children and activity data for 152 children. Boys were found to take part in about twice as much vigorous and hard activity as girls (mean (95% confidence interval) 64.3 (53.2 to 75.4) min in boys compared with 37 (33.1 to 40.9) min in girls; p<0.001). In boys there was significant difference between those defined as normal, overweight and obese in the time spent in vigorous activity (p<0.05), but no such difference was found in girls. A significant negative correlation between waist circumference and time spent in vigorous activity (r = -0.31, p<0.05) was found in boys but not in girls. Time spent sedentary was positively correlated with waist circumference in boys (r = 0.33, p<0.01) but not in girls. In both boys and girls there were significant negative correlations between fitness and both body mass index (r = -0.274, p<0.001) and waist circumference (boys: r = -0.503, p<0.01; girls: r = -0.286, p<0.01). CONCLUSION: In boys, body composition was inversely related to fitness and to vigorous activity and was positively related to inactivity. In girls, body composition was related to fitness but not to specific components of physical activity.

Exercise tolerance and physical activity levels in children referred to a weight reduction clinic.

The aim of this study was to investigate exercise tolerance and physical activity levels in children with exogenous obesity. Measures included BMI, waist circumference, exercise tolerance and self reported physical activity. Exercise tolerance was measured by the Modified Balke Treadmill Protocol and results were compared to normal values. Physical activity levels were assessed by measuring energy expended in regular activities each week over the past year and number of hours spent watching TV/video using an adaptation of the 'Modifiable Activity Questionnaire for Adolescents'. Details on transport to school were also obtained. Forty five children between September 2002 and June 2004 were assessed. This group comprised of 25 girls and 20 boys with mean ages (standard deviation) of 11.9 +/- 3.0 years and 13.7 +/- 2.5 years respectively. Exercise tolerance as a percentage of normal was below minimal levels in 64% girls and 75% boys. Energy expended in regular activity was less than the minimal recommendation in 80% girls and 65% boys. Seventy six percent of girls and 70% of boys spent 2 hours or more per day watching television and 40% of girls and 70% of boys walked to school. The low levels of activity and exercise tolerance need to be addressed in the managemeni of children with obesity

Development and application of a quality control procedure for short-wave diathermy units.

Short-wave diathermy (SWD) is a form of radiofrequency (RF) radiation, operating at 27.12 MHz, that is used therapeutically by physiotherapists. Although this form of therapy is widely available, the management of the equipment is not often addressed by either physiotherapists or by medical physics/clinical engineering. A quality control protocol for SWD units, examining power output and electrical and mechanical condition, was developed and applied to 20 units used in clinical practice. In addition, an environmental assessment of where the units were used was also included. Results showed that the power output was generally stable (coefficient of variation range 0-8.8%) and reproducible (coefficient of variation range 0-6.8%). When the outputs from 12 similar units were compared, it was found that the relationship between the units' intensity settings and power output measurements was non-linear. Two units with mechanical timers were found to have inaccuracies that could contribute, under a 'worst-case' scenario, to a dosage error of up to 45%. Environmental analysis found that all treatment plinths in use contained metal parts, which could constitute a fire hazard, and no department examined was equipped with an RF screened room, a facility that would ensure that other persons in the vicinity were not exposed to excessive stray radiation.

Peripheral muscle strength in young males with cystic fibrosis.

BACKGROUND: In children with cystic fibrosis there is a decrease in peak work capacity and oxygen consumption on maximal exercise testing when compared to controls. Previous studies have shown that peripheral muscle force is decreased in children with cystic fibrosis even in those with minimal changes in lung function. However, no studies have examined peripheral muscle strength using isokinetic dynamometry which permits measurement of muscle strength throughout range and is considered the gold standard in orthopaedics and sports medicine. METHODS: Isokinetic muscle strength was measured in the knee flexors and extensors and shoulder flexors and extensors at two speeds of movement in children with cystic fibrosis and matched controls. Activity levels in both groups were calculated. RESULTS: Thirteen subjects and 13 age and height matched controls were assessed. Average peak torque was calculated and expressed in terms of body weight. There was a significant difference in peak torque/body weight in children with cystic fibrosis when compared to controls. FEV1 was significantly correlated with knee muscle strength and shoulder flexion at 90 degrees /s in subjects with CF. CONCLUSION: Children with CF had lower muscle strength than control subjects. Airflow limitation was associated with decreased muscle strength. The relationship between muscle strength and exercise tolerance requires investigation.

Physical activity in Dublin children aged 7-9 years.

OBJECTIVES: To investigate the amount of regular activity and time spent in sedentary occupations in children aged 7--9 years. Sex differences in levels of activity and time and facilities for physical education at school were also examined. METHODS: A 10% sample of Dublin National Schools were selected. Parents of children in second class were surveyed. The questionnaire used was a modification of the Modifiable Activity Questionnaire for Adolescents. Teachers of second class were questioned about the time and facilities for physical education in schools. RESULTS: Some 39% of children were participating in hard exercise for at least 20 minutes three or more times a week, with fewer girls (28%) than boys (53%) contributing to this result. A further 57% of children were engaging in at least 20 minutes of light exercise three or more times a week, with no sex differences. Estimated energy expenditure in regular activity was higher in boys than girls. Most (78%) of the children were spending one to three hours a day sedentary in front of a screen. CONCLUSIONS: This study provides comprehensive data on physical activity levels in Dublin schoolchildren aged 7--9 years. The amount of inactivity is of concern. Even at this young age, boys are reported to participate in more physical activity than girls.

Factitious HIV syndrome in young women.

Factitious HIV infection has been observed at our center in women presenting with a false history of HIV/AIDS. In a 2-year period, 4 women presented for HIV-related care, indicating they were HIV-seropositive, while repeated serologic testing revealed no evidence of HIV infection. In all cases, the women were either quite angry or appeared surprised when told that they did not have HIV infection. A common denominator in all 4 women was a history of prolonged sexual, physical, or emotional abuse. Three of the 4 had been to other physicians, changing doctors as soon as the absence of HIV infection was established. Appropriate psychiatric support is an important aspect in care of these women, although it may not be accepted. All presentations of HIV infection should be confirmed either by identifying hard-copy data of HIV test results or by retesting all patients before evaluation and treatment of presumed HIV-related illnesses.

Dyspnea and the affective response during exercise training in obstructive pulmonary disease.

BACKGROUND: Dyspnea (SOB), dyspnea-related anxiety (DA), and exercise performance have been shown to improve after exercise training in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there are no published descriptions of the changes in dyspnea intensity or dyspnea-related anxiety during or across the exercise training sessions. OBJECTIVES: To describe and compare the differences in the patterns of change in SOB, DA, and exercise performance during 12 exercise training sessions with and without nurse coaching. METHODS: Forty-five dyspnea-limited patients with COPD were randomly assigned to nurse-monitored (ME) or nurse-coached exercise (CE). SOB and DA were rated on a 200 mm VAS every 2 minutes during each of 12 treadmill training sessions. RESULTS: Warm-up, peak, cool-down, mean SOB, and peak SOB/stage remained constant over the exercise sessions, with increasing exercise performance for both groups over the 12 sessions (p < .001). There was a significant difference in the pattern of mean SOB over time between the ME and CE group (p < . 05). Mean, peak DA, and peak DA/stage showed a rapid decrease within the first 4 sessions (p < . 05) with no significant differences between the groups. Warm-up and cool-down DA remained constant. There were large intra- and inter-subject variations in the rating of dyspnea and dyspnea-related anxiety within and across sessions. CONCLUSIONS: As theoretically proposed, both groups significantly decreased their DA over the training sessions. This decrease was early in the sessions and was not accompanied by a decrease in the SOB. In contrast, subjects maintained a nearly constant mean and peak SOB with increasing exercise performance, suggesting that people may have a dyspnea threshold above which they are unable to tolerate greater dyspnea. Description of the changes in dyspnea and the affective response during training need to be expanded, while studying the type and timing of strategies to enhance the improvement in dyspnea and dyspnea-related anxiety.

Potent cyclic peptide inhibitors of VLA-4 (alpha4beta1 integrin)-mediated cell adhesion. Discovery of compounds like cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg) (ZD7349) compatible with depot formulation.

Additional structure-activity relationship studies on potent cyclic peptide inhibitors of very late antigen-4 (VLA-4) are reported. The new N- to C-terminal cyclic hexa-, hepta- and octapeptide inhibitors like cyclo(MeIle/MePhe-Leu-Asp-Val-X) (X = 2-4 amino acids containing hydrophobic and/or basic side chains) were synthesized using solid phase peptide synthesis methods. The peptides were evaluated in in vitro cell adhesion assays and in in vivo inflammation models. Many of the peptides like cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg) (ZD7349) (17), cyclo(MeIle-Leu-Asp-Val-D-Arg-D-Arg-D-Phe) (20), cyclo(MeIle-Leu-Asp-Val-D-Arg-D-Arg-MePhe) (21) and cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg-D-Ala-D-Ala) (23) were potent inhibitors of VLA-4-mediated cell adhesion and inhibited ovalbumin-induced delayed type hypersensitivity (DTH) response in mice. The more potent compounds were highly selective and did not affect U937 cell adhesion to fibronectin (VLA-5), phorbolmyristate acetate or PMA-differentiated U937 cell adhesion to intercellular cell adhesion molecule-1 (ICAM-1)-expressing Chinese hamster ovary cells (LFA-1) and adenosine diphosphate (ADP)-induced platelet aggregation (GPIIb/IIIa). In contrast to the inhibitors like Ac-cyclo(D-Lys-D-Ile-Leu-Asp-Val) and cyclo(CH2CO-Ile-Leu-Asp-Val-Pip-CH2CO-Ile-Leu-Asp-Val-Pip) described earlier, the new compounds were much more compatible with the depot formulations based on poly(DL-lactide-co-glycolide) polymers. The hexapeptide cyclo(MePhe-Leu-Asp-Val-D-Arg-D-Arg) (ZD7349) (17) inhibited MOLT-4 cell adhesion to fibronectin and vascular cell adhesion molecule-1 (VCAM-1) with IC50 values of 260 and 330 nM, respectively, and did not show any significant effect against other integrins (IC50 > 300 microM). ZD7349 inhibited ovalbumin-induced DTH response in mice when administered continuously using a mini-pump (ED50 0.01 mg/kg/day) or when given as an s.c. or i.v. bolus injection at a dose of 1-10 mg/kg. ZD7349 was also active in type II collagen-induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE) tests at a dose of 3-10 mg/kg. The peptide was released from some formulations over a period of 10-20 days. ZD7349 is currently undergoing pre-clinical investigation.

Potent cyclic monomeric and dimeric peptide inhibitors of VLA-4 (alpha4beta1 integrin)-mediated cell adhesion based on the Ile-Leu-Asp-Val tetrapeptide.

Potent monomeric and dimeric cyclic peptide very late antigen-4 (VLA-4) inhibitors have been designed based on a tetrapeptide (Ile-Leu-Asp-Val) sequence present in a 25-amino acid peptide (CS-1) reported in the literature. The peptides, synthesized by the SPPS techniques, were evaluated in the in vitro cell adhesion assays and in the in vivo inflammation models. The N- to C-terminal cyclic peptides such as cyclo(Ile-Leu-Asp-Val-NH-(CH2)2-S-(CH2)2-CO) (28) and cyclo(MeIle-Leu-Asp-Val-D-Ala-D-Ala) (31), monomeric and dimeric peptides containing piperazine (Pip) or homopiperazine (hPip) residues as linking groups, e.g. cyclo(MeIle-Leu-Asp-Val-Pip-CH2CO-NH-(CH2)2-S-CH2-CO) (49) and cyclo(MeIle-Leu-Asp-Val hPip-CH2CO-MeIle-Leu-Asp-Val-hPip-CH2CO) (58) and cyclic peptides containing an amide bond between the side chain amino group of an amino acid such as Lys and the C-terminal Val carboxyl group, e.g. Ac-cyclo(D-Lys-D-Ile-Leu-Asp-Val) (62) and beta-Ala-cyclo(D-Lys-D-Leu-Leu-Asp-Val) (68) were more potent than CS-1 in inhibiting the adhesion of the VLA-4-expressing MOLT-4 cells to fibronectin. The more potent compounds were highly selective and did not affect U937 cell adhesion to fibronectin (VLA-5), PMA-differentiated U937 cell adhesion to intercellular cell adhesion molecule- 1-expressing Chinese hamster ovary cells (LFA-1) and ADP-induced platelet aggregation (GPIIb/IIIa). A number of the more potent compounds inhibited ovalbumin-induced delayed type hypersensitivity in mice and some were 100-300 times more potent (ED50 = 0.003-0.009 mg/kg/day, s.c.) than CS-1. Two peptides, Ac-cyclo(D-Lys D-Ile-Leu-Asp-Val) (62) and cyclo(CH2CO-Ile-Leu-Asp-Val-Pip-CH2CO-Ile-Leu-Asp-Val-Pip) (55), were formulated in poly(DL-lactide-co-glycolide) depots and the release profile was investigated in vitro over a 30-day period.

C3 activation is inhibited by analogs of compstatin but not by serine protease inhibitors or peptidyl alpha-ketoheterocycles.

C3 convertase is a key enzyme in the complement cascade and is an attractive therapeutic target for drug design. Recent studies have demonstrated that this enzyme is inhibited by compstatin (Morikis, D. , Assa-Munt, N., Sahu, A., Lambris, J.D., 1998. Solution structure of Compstatin, a potent complement inhibitor. Protein Sci. (7) 619-627; Sahu, A., Kay, B.K., Lambris, J.D., 1996. Inhibition of human complement by a C3-binding peptide isolated from a phage-displayed random peptide library. J. Immunol. (157) 884-891), a 13 amino acid cyclic peptide that binds to C3. Since the enzyme exhibits some homology to serine proteases, substrate-based design could be another avenue for drug design. In this study, we confirm the activity of compstatin using different sources of enzyme and different assay systems. We also tested the activity of substituted compstatin analogs and compared the selectivity and toxicity of these compounds to peptidyl alpha-ketoheterocyclic compounds. Our work confirms the activity of compstatin in both alternative and classical complement pathways, describes 11 new active analogs of this cyclic peptide, and provides evidence for key segments of the peptide for activity. Compstatin and related active analogs showed little or no inhibition of clotting or key enzymes in the clotting cascade nor did they appear to have significant cytotoxicity. The characteristics of compstatin suggest that this peptide and its analogs could be attractive candidates for further clinical development. By contrast, known serine protease inhibitors, including peptidyl alpha-ketoheterocycles, did not inhibit C3 convertase illustrating the atypical nature of this enzyme.

A pilot study examining injuries in elite gaelic footballers.

OBJECTIVES: To quantify injuries in elite gaelic footballers and to determine the nature, sites, and outcome of injuries and the possible risk factors involved. METHODS: Information on injuries was collected from six elite gaelic football teams by a questionnaire. The footballers were asked to recall injuries over the preceding six month period. RESULTS: A total of 88 out of 107 subjects sustained injuries over the study period. Ninety five injuries were recorded, giving an incidence rate of 1.78 injuries per subject per year, of which 35% were recurring. It was found that 35% of injuries were sustained during training sessions. Lower body injuries predominated (77%), the ankle being the most commonly injured anatomic site. Most injuries were soft tissue in nature: muscle, 33%; ligament, 32%; tendon, 16%. The most common situations giving rise to injuries were collision (22%) and twist/turn (19%). Foul play only accounted for about 6% of injuries. Mean time off play as a result of injury was 17.3 days, and hospital admission was necessary for 15% of the injuries. CONCLUSION: Despite the limitations of a retrospective of this nature, the study provides useful and important information on injuries in gaelic footballers.

National school teachers' knowledge of asthma and its management.

Asthma is the most common chronic medical condition that school teachers may encounter among their pupils. However management of asthma in schools and the role school teachers adopt in this condition has only recently been explored. The aim of this study was to determine teachers' knowledge of asthma and its management. A postal questionnaire was circulated to 199 school teachers from 46 schools in Dublin City. A 74 per cent response rate was obtained. The number of children with asthma as identified by teachers was 7.8 per cent which suggests that asthma may be unrecognised in a number of pupils. Knowledge on signs and symptoms of asthma, provoking factors of asthma and the nature of the disease was generally satisfactory. However, knowledge on asthma medications, the purpose of inhalers and teachers' understanding of the treatment and management of asthma was considered poor. Knowledge on exercise-induced asthma was limited. There is a need to provide school teachers with education on asthma and its management. School policies on asthma also need to be developed with particular reference to action necessary in the event of an acute severe attack of asthma.

Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) suppression and efavirenz drug concentrations in HIV-1-infected patients receiving combination therapy.

Efavirenz, a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, is a promising addition to the antiretroviral armamentarium. Efavirenz levels and HIV-1 RNA levels were measured in cerebrospinal fluid (CSF) and plasma of 10 HIV-1-infected patients taking efavirenz, 600 mg daily, in combination with other antiretroviral medications. Efavirenz was detected in the CSF at a mean concentration of 35.1 nM (range, 6. 6-58.9 nM), which was above the IC95 for wild-type HIV-1. The mean CSF-to-plasma ratio was 0.61% (range, 0.26%-0.99%). CSF HIV-1 RNA levels were ascertained in 9 of the patients; all were <400 copies/mL after a mean of 26 weeks on therapy. Eight of the 9 patients had no detectable virus in plasma. These results indicate that efavirenz is present in the CSF at low levels and is effective in suppressing CSF viral levels when used in combination therapy.

Accuracy of recall of dyspnea after exercise training sessions.

BACKGROUND: Although clinicians often rely on patients' retrospective reporting of dyspnea, it is not known if dyspnea scores recalled after exercise are equivalent to dyspnea scores during exercise. The objective of this study was to determine whether patients could accurately recall after exercise the maximum ratings of the intensity of dyspnea and the anxiety associated with it that they experienced during exercise. METHODS: Forty-nine patients with chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second 0.92 +/- 0.23 L) participating in a randomized clinical trial of the impact of coached versus monitored exercise training on dyspnea rated dyspnea intensity (shortness of breath [SOB]) and dyspnea-related anxiety (DA) on a visual analog scale every 2 minutes during treadmill exercise. After each of 12 training sessions each subject was asked to rate the worst level of the two sensations that they recalled having experienced during exercise. RESULTS: For the groups as a whole, actual maximum scores for SOB and DA during exercise were highly correlated with recalled maximum values after exercise (r > or = 0.85, P < 0.0001) and the average differences were small (0-10.9 mm on a 200-mm scale). However, individual variation was substantial, limiting predictability for individual ratings. CONCLUSIONS: After exercise, patients with COPD as a group can accurately recall the worst SOB and DA that they experienced during exercise. This finding supports the further study and use of retrospective symptom ratings as a method for dyspnea assessment during exercise training in pulmonary rehabilitation.

Anti-inflammatory activity of c(ILDV-NH(CH2)5CO), a novel, selective, cyclic peptide inhibitor of VLA-4-mediated cell adhesion.

1. Small, N- to C-terminal cyclized peptides containing the leucyl-aspartyl-valine (LDV) motif from fibronectin connecting segment-1 (CS-1) have been investigated for their effects on the adhesion of human T-lymphoblastic leukaemia cells (MOLT-4) to human plasma fibronectin in vitro mediated by the integrin Very Late Antigen (VLA)-4 (alpha4beta1, CD49d/CD29). 2. Cyclo(-isoleucyl-leucyl-aspartyl-valyl-aminohexanoyl-) (c(ILDV-NH(CH2)5CO)) was approximately 5 fold more potent (IC50 3.6+/-0.44 microM) than the 25-amino acid linear CS-1 peptide. Cyclic peptides containing two more or one less methylene groups had similar potency to c(ILDV-NH(CH2)5CO) while a compound containing three less methylene groups, c(ILDV-NH(CH2)2CO), was inactive at 100 microM. 3. c(ILDV-NH(CH2)5CO) had little effect on cell adhesion mediated by two other integrins, VLA-5 (alpha5,beta1, CD49e/CD29) (K562 cell adhesion to fibronectin) or Leukocyte Function Associated molecule-1 (LFA-1, alphabeta2, CD11a/CD18) (U937 cell adhesion to Chinese hamster ovary cells transfected with intercellular adhesion molecule-1) at concentrations up to 300 microM. 4. c(ILDV-NH(CH2)5CO) inhibited ovalbumin delayed-type hypersensitivity or oxazolone contact hypersensitivity in Balb/c mice when dosed continuously from subcutaneous osmotic mini-pumps (0.1-10 mg kg(-1) day(-1)). Maximum inhibition (approximately 40%) was similar to that caused by the monoclonal antibody PS/2 (7.5 mg kg(-1) i.v.) directed against the alpha4 integrin subunit. 5. c(ILDV-NH(CH2)5CO) also inhibited oxazolone contact hypersensitivity when dosed intravenously 20 h after oxazolone challenge (1-10 mg kg(-1)). Ear swelling was reduced at 3 h and 4 h but not at 1 h and 2 h post-dose (10 mg kg(-1)). 6. Small molecule VLA-4 inhibitors derived from c(ILDV-NH(CH2)5CO) may be useful as anti-inflammatory agents.

Lower arch crowding in the third decade.

Lower arch crowding and dimensions were measured on study models of 46 untreated subjects, 20 male and 26 female, at age 18 years (T1), 21 years (T2), and 28 years (T3), and the changes during the observation periods calculated. Only very small changes, few of them detectable clinically, were found. The findings are discussed in relation to the changes reported in untreated subjects in other age groups and in orthodontically-treated subjects after retention.

Training for lifting; an unresolved ergonomic issue?

The paper describes a nine year project on lifting training which included nine trans-Australia consensus conferences attended by more than 900 health professionals. Major outcomes were: (1) The essence of lifting work is the need for the performer to cope with variability in task, environment, and self, and the essence of lifting skill is therefore adaptability; (2) the semi-squat approach provides the safest and most effective basis for lifting training; (3) for lifting training to be effective, the basic principles of skill learning must be systematically applied, with adaptability as a specific goal; (4) physical work capacity (aerobic power, strength, endurance, joint mobility) is a decisive ingredient of safe and effective lifting and, in addition to skill learning, should be incorporated in the training of people engaging regularly in heavy manual work; (5) if effective compliance with recommended skilled behaviour is to be achieved, then training must apply the principles and methods appropriate to adult learning and behaviour modification.

Exercise training decreases dyspnea and the distress and anxiety associated with it. Monitoring alone may be as effective as coaching.

STUDY OBJECTIVE: To determine whether exercise training with coaching is more effective than exercise training alone in reducing dyspnea and the anxiety and distress associated with it and improving exercise performance, self-efficacy for walking, and dyspnea with activities of daily living. DESIGN: Randomized clinical trial of 51 dyspnea-limited patients with COPD assigned to monitored (n = 27) or coached (n = 24) exercise groups. SETTING: Outpatient area of university teaching hospital. INTERVENTION: Both groups completed 12 supervised treadmill training sessions (phase 1) over 4 weeks followed by 8 weeks of home walking (phase 2). The CE group also received coaching during training. MEASUREMENTS: Perceived work of breathing, dyspnea intensity, distress associated with dyspnea, and anxiety associated with dyspnea were rated on a visual analog scale during incremental treadmill testing and after 6-min walks before and after phase 1. Dyspnea with activities of daily living, self-efficacy for walking, state anxiety, and 6-min walks were measured before and after both phases. RESULTS: Dyspnea and the associated distress and anxiety improved significantly for both groups relative to work performed and in relation to ventilation (p < 0.05). There were no significant differences between groups in any outcomes. The phase 1 improvement in laboratory dyspnea was accompanied by improvements in dyspnea with activities of daily living (p < 0.01) and self-efficacy for home walking (p < 0.01) that were sustained during the home phase. CONCLUSIONS: Coaching with exercise training was no more effective than exercise training alone in improving exercise performance, dyspnea, and the anxiety and distress associated with it, dyspnea with activities, and self-efficacy for walking.