The aim of this study was to compare aerobic and resistance training in children with cystic fibrosis (CF) admitted to hospital with an intercurrent pulmonary infection with a control group. The subjects were randomized into three groups on the first day of admission. The fat-free mass (FFM) was calculated, using the skin fold thickness from four sites (biceps, triceps, subscapular, and iliac crest). Pulmonary function tests were performed within 36 hr of admission and repeated on discharge from the hospital, and again at 1 month after discharge. All subjects performed an incremental treadmill exercise test, using a modified Bruce protocol. Lower limb strength was measured using a Cybex dynamometer. An assessment of quality of life was made using the Quality of Well Being Scale, as previously reported. Activity levels were measured using a 7-day activity diary, and subjects also wore an accelerometer on their hips. There were no significant differences between the three groups in terms of disease severity, and length of stay in hospital. Subjects in all three groups received intravenous antibiotics and nutritional supplementation as determined by the physician. Children randomized to the aerobic training group participated in aerobic activities for five sessions, each of 30-min duration, a week. The children randomized to the resistance training group exercised both upper and lower limbs against a graded resistance machine. Subjects in the control group received standard chest physiotherapy. Our study demonstrated that children who received aerobic training had significantly better peak aerobic capacity, activity levels, and quality of life than children who received the resistance training program. Children who received resistance training had better weight gain (total mass, as well as fat-free mass), lung function, and leg strength than children who received aerobic training. A combination of aerobic and resistance training may be the best training program, and future studies to assess optimal training programs for CF patients are indicated.

Porphyromonas gingivalis is a Gram-negative black-pigmented obligate anaerobe implicated in the aetiology of human periodontal disease. The virulence of P. gingivalis is associated with the elaboration of the cysteine proteases Arg-gingipain (Rgp) and Lys-gingipain (Kgp), which are produced at high bacterial cell densities. To determine whether quorum sensing plays a role in the regulation of Rgp and Kgp, biosensors capable of detecting either Nacylhomoserine lactone (AHLs) or the luxS-dependent autoinducer (AI-2) quorum-sensing signalling molecules in spent culture supernatants were first employed. While no AHLs could be detected, the Vibrio harveyi BB170 biosensor was activated by spent P. gingivalis W50 culture supernatants. The P. gingivalis luxS gene was cloned and demonstrated to restore AI-2 production in the Escherichia coli luxS mutant DH5α. Mutation of luxS abolished AI-2 production in P. gingivalis. Western blotting using antibodies raised against the recombinant protein revealed that LuxS levels increased throughout growth even though AI-2 activity was only maximally detected at the midexponential phase of growth and disappeared by the onset of stationary phase. Similar results were obtained with E. coli DH5α transformed with luxS, suggesting that AI-2 production is not limited by a lack of LuxS protein. Analysis of Rgp and Kgp protease activities revealed that the P. gingivalis luxS mutant produced around 45 % less Rgp and 30 % less Kgp activity than the parent strain. In addition, the luxS mutant exhibited a fourfold reduction in haemagglutinin titre. However, these reductions in virulence determinant levels were insufficient to attenuate the luxS mutant in a murine lesion model of P. gingivalis infection.

Shuttle tests are simple, inexpensive field tests that have been used to estimate the cardiorespiratory status of children. It has yet to be validated in children with CF. The aim of this study was to assess the reproducibility and criterion validity of shuttle tests in children with cystic fibrosis (CF). Ninety-three CF patients aged 6 to 16 years of age with a wide range of disease severity performed the study. The 10-m shuttle test was used for children 7 years of age and younger and those deemed too chronically ill by their physicians to perform the longer test (n = 35.) All other children performed the 20-m shuttle test (n = 58). Reproducibility and criterion validity were assessed for each child over a two week period. Gas analysis was performed throughout testing using a polargraphic gas analyzer. The 10-m shuttle tests were reproducible (mean difference between tests VO(2) 2.41 mL/kg/min, CI 3.46,-0.18) and the difference from treadmill testing was not statistically significant (mean difference VO(2) 5.30 mL/kg/min, CI-7.46, 1.18). The 20-m shuttle tests were reproducible (mean difference between tests VO(2) 2.07 mL/kg/min, CI-3.90,0.60) and the difference from treadmill testing was not statistically significant (mean difference VO(2) 3.50 mL/kg/min, CI-4.90, 1.60). We conclude that when formal exercise testing with treadmill or cycle ergometer cannot be performed, the shuttle tests provide a reproducible and valid alternative.

SUMMARY BackgroundRenzapride, a 5-hydroxytryptamine type-4 (5-HT 4 ) receptor agonist and 5-HT 3 receptor antagonist, has been proposed as a new treatment of irritable bowel syndrome with constipation (IBS-C).

SUMMARY BackgroundRelatively few pharmacological treatment options are available for treating patients with irritable bowel syndrome. New and effective medicines are urgently required.

SUMMARY AimTo investigate the efficacy and safety of renzapride, a potent 5-hydroxytryptamine type-4 receptor full agonist and 5-hydroxytryptamine type-3 receptor antagonist in patients with constipation-predominant irritable bowel syndrome. MethodsIn this dose-escalating pilot study, 17 patients with constipation-predominant irritable bowel syndrome received placebo, renzapride 2 mg o.d. and renzapride 2 mg b.d. sequentially for 28 days. Response was determined by radio-opaque marker measurement of overall gastrointestinal and segmental colonic transit and patients' assessment of their irritable bowel syndrome symptoms. ResultsRenzapride reduced mean overall gastrointestinal transit time (placebo, 2.9 AE 1.6 days; renzapride 2 mg o.d., 2.6 AE 1.4 days; renzapride 2 mg b.d., 1.9 AE 1.6 days) (P ¼ 0.024) and accelerated segmental colonic transit, with statistically significant differences for renzapride 2 mg b.d. over placebo in caecum/ascending colon (P ¼ 0.019) and descending colon (P ¼ 0.022). Renzapride also reduced abdominal pain, increased the number of pain-free days and improved stool consistency. The frequency of reported adverse events was similar on renzapride and placebo. ConclusionsRenzapride is well-tolerated, stimulates gastrointestinal transit and improves symptoms in patients with constipation-predominant irritable bowel syndrome, particularly at the 2 mg b.d. dose, where improvements in gastrointestinal symptoms were evident over placebo. This study has established proof of concept and supports further investigation of renzapride in patients with constipation-predominant irritable bowel syndrome.

This was an exploratory study of renzapride in 168 male and female patients with non-D, non-C irritable bowel syndrome (IBS). Patients were randomized to placebo or renzapride (1, 2, or 4 mg/day) for 8 weeks. The primary efficacy variable was patient-reported satisfactory relief of IBS symptoms. Secondary variables included relief of abdominal pain/discomfort. The proportion of patients reporting satisfactory relief of their IBS symptoms for at least 50% of the time did not differ significantly from those on placebo. However, post hoc analysis in women showed differences in responder rate on renzapride versus placebo of 18.2% (95% CI -5% to 42%; P = 0.066) during weeks 1-4 and 6% (95% CI -21% to 33%; P = 0.339) during weeks 5-8. Renzapride was well tolerated and most adverse events were mild to moderate in intensity. Further studies are warranted to determine whether renzapride is beneficial in this patient population.

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