Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine

BACKGROUND: Cancer-related cachexia is caused by a diverse combination of accelerated protein breakdown and slowed protein synthesis. The hypothesis proposed in this study is that supplementation of specific nutrients known to positively support protein synthesis and reduce protein breakdown will reverse the cachexia process in advanced cancer patients. METHODS: Patients with solid tumors who had demonstrated a weight loss of at least 5% were considered for the study. Patients were randomly assigned in a double-blind fashion to either an isonitrogenous control mixture of nonessential amino acids or an experimental treatment containing beta-hydroxy-beta-methylbutyrate (3 g/d), L-arginine (14 g/d), and L-glutamine (14 g/d [HMB/Arg/Gln]). The primary outcomes measured were the change in body mass and fat-free mass (FFM), which were assessed at 0, 4, 8, 12, 16, 20, and 24 weeks. RESULTS: Thirty-two patients (14 control, 18 HMB/Arg/Gln) were evaluated at the 4-week visit. The patients supplemented with HMB/Arg/Gln gained 0.95 +/- 0.66 kg of body mass in 4 weeks, whereas control subjects lost 0.26 +/- 0.78 kg during the same time period. This gain was the result of a significant increase in FFM in the HMB/Arg/Gln-supplemented group (1.12 +/- 0.68 kg), whereas the subjects supplemented with the control lost 1.34 +/- 0.78 kg of FFM (P = 0.02). The response to 24-weeks of supplementation was evaluated by an intent-to-treat statistical analysis. The effect of HMB/Arg/Gln on FFM increase was maintained over the 24 weeks (1.60 +/- 0.98 kg; quadratic contrast over time, P <0.05). There was no negative effect of treatment on the incidence of adverse effects or quality of life measures. CONCLUSIONS: The mixture of HMB/Arg/Gln was effective in increasing FFM of advanced (stage IV) cancer. The exact reasons for this improvement will require further investigation, but could be attributed to the observed effects of HMB on slowing rates of protein breakdown, with improvements in protein synthesis observed with arginine and glutamine.     

A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials

PURPOSE: Overactive bladder (OAB) is a syndrome consisting of urinary urgency with or without urge incontinence, usually with increased urinary frequency and nocturia. In response to current limitations in OAB clinical research a new patient reported measure of urgency severity associated with OAB has been developed, namely the Indevus Urgency Severity Scale (IUSS). We report the measurement properties of the IUSS. MATERIALS AND METHODS: Validation study data were collected alongside a phase III clinical trial of 20 mg trospium chloride twice daily vs placebo in patients with OAB associated with urge incontinence. We evaluated IUSS item variability, known group, content, criterion and construct validity, test-retest reliability, responsiveness and respondent burden. RESULTS: A total of 658 patients were evaluated at baseline and 579 were reevaluated at week 12. IUSS demonstrated good item variability. Greater urgency severity was associated with increased symptom bother and worse health related quality of life, as measured by the OAB QOL questionnaire. IUSS had a significant positive association with essential clinical and quality of life outcomes, demonstrating content validity. IUSS was highly responsive to a decrease in the average number of patient toilet voids per 24 hours to 7 or fewer toilet voids and average urge incontinence episodes per 24 hours to zero. It discriminated between patients who had above and below the median number of toilet voids and urge incontinence episodes per 24 hours. IUSS also had good test-retest reliability and content validity, and it created minimal respondent burden. CONCLUSIONS: IUSS is a validated patient reported measure of urgency severity for collecting event specific information in the context of a clinical trial.     

Motor control of the costal and crural diaphragm--insights from transcranial magnetic stimulation in man

The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks.     

Inter-university cooperation in Flanders--an academic point of view on peer review

Peer review as a possibility for discussion among practising dentists was introduced in Belgium in 1998 in the framework of a quality ensuring program. The 'Interuniversitary Cooperation', an initiative of Flemish universities active in teaching, research and patient treatment in dentistry has been involved in this program since its beginning to set up a dialogue between academia and dental practitioners and to gather information on scientific and educational matters. In this article the principles and organisation are described and thought is given to the attitude of the participants and future possibilities.     

A new method for semiautomatic analysis of surface EMG in patients with oral parafunctions

Sleep-related phenomena or disorders, including snoring and tooth grinding, can be investigated using polysomnography. This method, however, generates large amounts of synchronically recorded data that are often analyzed visually with subjective interpretation. The purpose of this study was to minimize the need for subjective evaluation by developing a computer program for analysis of EMG data linked with polysomnographic recordings in a standardized and semi-automatic way. The selected algorithm differs from the Root Mean Square (RMS) method by being based on the theory of "differentiated EMG" (DIFEMG), which relies on two principles. The first says that the activation of a larger number of motor units results in a greater force production. The second principle says that the force production will continue for some time after the muscle is no longer stimulated. After a visual check for artifacts in the basic EMG recordings, the computer program is used to analyze the corrected basic EMG signal. The results were that both methods yield identical results as far as the detected number of events is concerned. There is, however, a significant difference when the duration of the events is considered, because the start and end of an event can be more accurately determined with the new method presented here. The computer program described will make comparison of data from different studies easier.     

Measuring risk perception among low-income minority primary care patients

Studying patients' risk perceptions by ascertaining the probabilities of developing a disease is suboptimal, as patients might have difficulty using numerical expressions to depict the probabilities/chances of developing a disease. We surveyed patients at 2 community health centers and assessed risk perception by patients' self-reported chance of developing a disease (expressed in percentages), patients' relative chance of developing a disease compared to others' chance of developing a disease, and patients' ranked chances of developing different diseases. Many patients had difficulties understanding percentages and most patients overestimated their absolute risk. However, most patients indicated that they had a lower chance of developing diseases when compared to others. Patients with known risk factors (smoking) indicated a higher relative risk of developing an associated disease (lung cancer). Patients' ranked chances of developing different diseases were consistent with the actual frequency of developing a disease. Although patients had difficulty expressing risk in percentages, they estimated their risks well through comparisons with others and by ranking of disease frequencies.