Tegaserod for the treatment of irritable bowel syndrome and chronic constipation.

BACKGROUND: IBS is a complex disorder that encompasses a wide profile of symptoms. The symptoms of chronic constipation frequently resemble those of constipation-predominant IBS. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS and chronic constipation. OBJECTIVES: The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS and chronic constipation in adults and adolescents aged 12 years and above. SEARCH STRATEGY: MEDLINE 1966-December 2006 and EMBASE 1980 to December 2006 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", "constipation" and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, and the Inflammatory Bowel Disease Review Group Specialized Trials Register were also searched. Searches stopped on 15th December 2006. Relevant articles were retrieved, and their reference lists were also reviewed. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS or chronic constipation, focusing on clinical endpoints were considered for review. DATA COLLECTION AND ANALYSIS: Study inclusion and exclusion, data extraction and quality assessment was undertaken by two authors independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistics relative risk for dichotomous data and weighted mean difference for continuous data, both with 95% CI. Thirteen short-term placebo-controlled studies fulfilled the inclusion criteria. These were predominantly conducted in women. Ten studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. Two studies evaluated the effectiveness of tegaserod for the treatment of chronic constipation. MAIN RESULTS: In patients with C-IBS, the relative risk (RR) of being a responder in terms of global relief of GI symptoms during the last 4 weeks of treatment was significantly higher with both tegaserod 12 mg and 4 mg doses compared with placebo. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of three studies were not reached. The responder rate for this endpoint was also higher when considered for the first 4 weeks of treatment (tegaserod 12 mg only). Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in this outcome in favour of tegaserod 12 mg. In patients with chronic constipation, the RR of being a responder in terms of complete spontaneous bowel movements per week with tegaserod 12 mg was 1.54 (95% CI 1.35 to 1.75), WMD for this endpoint compared with placebo 0.6 (95% CI 0.42 to 0.78). Differences between tegaserod and placebo in increases in frequency of bowel movements were small (less than one per week). The proportion of patients with either diagnosis who experienced diarrhea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.80, 95% CI 2.13 to 3.68), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies. AUTHORS' CONCLUSIONS: Tegaserod appears to improve the overall symptomatology of IBS, and the frequency of bowel movements in those with chronic constipation. The clinical importance of these modest improvements is not clear. There are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of these conditions.

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of newer antiepileptic drugs (AEDs) for epilepsy in children: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin. DATA SOURCES: Electronic databases. Drug company submissions. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria. Data extraction and quality assessment were also undertaken. A decision-analytic model was constructed to estimate the cost-effectiveness of the newer agents in children with partial seizures, the only condition where there were sufficient trial data to inform a model. RESULTS: The quality of the randomised controlled trial (RCT) data was generally poor. For each of the epilepsy subtypes considered in RCTs identified for this review (partial epilepsy with or without secondary generalisation, Lennox-Gastaut syndrome, infantile spasms, absence epilepsy and benign epilepsy with centrotemporal spikes), there is some evidence from placebo-controlled trials that the newer agents tested are of some value in the treatment of these conditions. Where active controls have been used, the limited evidence available does not indicate a difference in effectiveness between newer and older drugs. The data are not sufficient to inform a prescribing strategy for any of the newer agents in any of these conditions. In particular, there is no clinical evidence to suggest that the newer agents should be considered as a first-choice treatment in any form of epilepsy in children. Annual drug costs of the newer agents ranges from around 400 pound to 1200 pound, depending on age and concomitant medications. An AED that is ineffective or has intolerable side-effects will only be used for a short period of time, and many patients achieving seizure freedom will successfully withdraw from drug treatment without relapsing. The results of the decision-analytic model do not suggest that the use of the newer agents in any of the scenarios considered is clearly cost-effective but, similarly, do not indicate that they are clearly not cost-effective. CONCLUSIONS: The prognosis for children diagnosed with epilepsy is generally good, with a large proportion responding well to the first treatment given. A substantial proportion, however, will not respond well to treatment, and for these patients the clinical goal is to find an optimal balance between the benefits and side-effects of any treatment given. For the newly, or recently, diagnosed population, the key question for the newer drugs is how soon they should be tried. The cost-effectiveness of using these agents early, in place of one of the older agents, will depend on the effectiveness and tolerability of these agents compared with the older agents; the evidence from the available trial data so far suggests that the newer agents are no more effective but may be somewhat better tolerated than the older agents, and so the cost-effectiveness for early use will depend on the trade-off between effectiveness and tolerability, both in terms of overall (long-term) treatment retention and overall utility associated with effects on seizure rate and side-effects. There are insufficient data available to estimate accurately the nature of this trade off either in terms of long-term treatment retention or utility. Better information is required from RCTs before any rational evidence-based prescribing strategy could be developed. Ideally, RCTs should be conducted from a 'public health' perspective, making relevant comparisons and incorporating outcomes of interest to clinicians and patients, with sufficiently long-term follow-up to determine reliably the clinical utility of different treatments, particularly with respect to treatment retention and the balance between effectiveness and tolerability. RCTs should mirror clinical practice with respect to diagnosis, focusing on defined syndromes or, where no syndrome is identified, on groups defined by specific seizure type(s) and aetiology. Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options and outcomes. Diagnosis-specific decision-analytic models are required; further research may be required to inform parameter values adequately with respect to epidemiology and clinical practice.

Tegaserod for the treatment of irritable bowel syndrome.

BACKGROUND: IBS is a complex disorder that encompasses a wide profile of symptoms. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS. OBJECTIVES: The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS in adults and adolescents aged 12 years and above. SEARCH STRATEGY: MEDLINE 1966-November 2002 and EMBASE 1980-November 2002 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, the Inflammatory Bowel Disease Review Group Specialized Trials Register, and Science Citation Index were also searched. Proceedings from the British Society of Gastroenterology Annual Meeting, and Digestive Disease Week (1998-2002) were hand searched. The manufacturer of tegaserod was contacted. Relevant articles were retrieved, and their reference lists were also reviewed. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS, focusing on clinical endpoints were considered for review. DATA COLLECTION AND ANALYSIS: Study inclusion and exclusion, data extraction and quality assessment was undertaken by two reviewers independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistic relative risk with 95% CI. Eight short-term placebo-controlled studies fulfilled our inclusion criteria. These were predominantly conducted in women. Seven studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. MAIN RESULTS: The relative risk (RR) of being a responder in terms of global relief of GI symptoms was significantly higher with tegaserod 12 mg (RR 1.19, 95% CI 1.09, 1.29) and tegaserod 4 mg (RR 1.15, 95% CI 1.02, 1.31) compared with placebo, with a number needed to treat (NNT) of 14 and 20 respectively. When all tegaserod doses were combined and compared with placebo (n=4040), the RR of being a responder was 1.17 (95% CI 1.08, 1.27), with a NNT of 17. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of the four pooled studies were not reached. Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in favour of tegaserod 12 mg. When GI symptoms were assessed separately, those indicative of GI motility such as number of bowel movements and days without bowel movements were generally improved with tegaserod although the proportion of patients experiencing diarrhoea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.75, 95% CI 1.90, 3.97), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies. REVIEWER'S CONCLUSIONS: Tegaserod appears to improve the overall symptomatology of IBS but there are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of this condition.

Lignification in relation to the biennial growth habit in brassicas.

The forage brassicas are a useful model system for the study of wood formation because the thickened cell walls of their vascular tissue can vary widely in lignin content. Solid-state 13C NMR spectroscopy was used to quantify lignin, and determine features of its structure, in the vascular cell walls of forage rape (Brassica napus L.), and Thousandhead and marrowstem cultivars of kale (Brassica oleracea L. var. acephala). During the first season of vegetative growth, lignin levels in these cell walls remained low in the upper part of the stems despite the physical resemblance of this tissue to wood. The extended flowering stems produced in the following year were thinner and their vascular tissue contained much more strongly lignified cell walls. The structure of the lignin was typical of angiosperm wood. It showed only small variations in syringyl/guaiacyl ratio, but this ratio increased with lignin content and thus with the proportion of the lignin that was associated with secondary cell-wall layers.

Creation of a fully active, cytosolic form of human type I 3beta-hydroxysteroid dehydrogenase/isomerase by the deletion of a membrane-spanning domain.

Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding domains (residues 72-89 and 283-310) have been predicted by analyses of hydrophobicity in the type I and II isoenzymes (90% regional homology). These putative membrane domains were deleted in the cDNA by PCR-based mutagenesis, and the two mutant enzymes were expressed by baculovirus in insect Sf9 cells. Differential centrifugation of the Sf9 cell homogenate containing the 283-310 deletion mutant revealed that 94% of the 3beta-HSD and isomerase activities were in the cell cytosol, 6% of the activities were in the microsomes, and no activity was in the mitochondria. This is the opposite of the subcellular distribution of the wild-type enzyme with 94% of the activities in the microsomes and mitochondria and only 6% activity in the cytosol. The organelle distribution of the 72-89 deletion mutant lies between these two extremes with 72% of the enzyme activity in the cytosol and 28% in the microsomes/mitochondria. The integrity of the subcellular organelle preparations was confirmed by electron microscopy. Western immunoblots confirmed the presence of the 283-310 deletion mutant enzyme and the absence of the wild-type enzyme in the insect cell cytosol. The unpurified, cytosolic 383-310 deletion mutant exhibited 3beta-HSD (22 nmol/min per mg) and isomerase (33 nmol/min per mg) specific activities that were comparable with those of the membrane-bound, wild-type enzyme. The isomerase reaction of the cytosolic 283-311 deletion mutant requires activation by NADH just like the isomerase of the microsomal or mitochondrial wild-type enzyme. In contrast, the 72-89 deletion mutant had low 3beta-HSD and isomerase specific activities that were only 12% of the wild-type levels. This innovative study identifies the 283-310 region as the critical membrane domain of 3beta-HSD/isomerase that can be deleted without compromising enzyme function. The shorter 72-89 region is also a membrane domain, but deletion of this NH(2)-terminal region markedly diminishes the enzyme activities. Purification of the active, cytosolic 283-310 deletion mutant will produce a valuable tool for crystallographic studies that may ultimately determine the tertiary/quaternary structure of this key steroidogenic enzyme.

Site-directed mutagenesis identifies amino acid residues associated with the dehydrogenase and isomerase activities of human type I (placental) 3beta-hydroxysteroid dehydrogenase/isomerase.

3beta-hydroxysteroid dehydrogenase/steroid delta5-->4-isomerase (3beta-HSD/isomerase) was expressed by baculovirus in Spodoptera fungiperda (Sf9) insect cells from cDNA sequences encoding human wild-type I (placental) and the human type I mutants - H261R, Y253F and Y253,254F. Western blots of SDS-polyacrylamide gels showed that the baculovirus-infected Sf9 cells expressed the immunoreactive wild-type, H261R, Y253F or Y253,254F protein that co-migrated with purified placental 3beta-HSD/isomerase (monomeric Mr=42,000 Da). The wild-type, H261R and Y253F enzymes were each purified as a single, homogeneous protein from a suspension of the Sf9 cells (5.01). In kinetic studies with purified enzyme, the H261R mutant enzyme had no 3beta-HSD activity, whereas the Km and Vmax values of the isomerase substrate were similar to the values obtained with the wild-type and native enzymes. The Vmax (88 nmol/min/mg) for the conversion of 5-androstene-3,17-dione to androstenedione by the Y253F isomerase activity was 7.0-fold less than the mean Vmax (620 nmol/min/mg) measured for the isomerase activity of the wild-type and native placental enzymes. In microsomal preparations, isomerase activity was completely abolished in the Y253,254F mutant enzyme, but Y253,254F had 45% of the 3beta-HSD activity of the wild-type enzyme. In contrast, the purified Y253F, wild-type and native enzymes had similar Vmax values for substrate oxidation by the 3beta-HSD activity. The 3beta-HSD activities of the Y253F, Y253,254F and wild-type enzymes reduced NAD+ with similar kinetic values. Although NADH activated the isomerase activities of the H261R and wild-type enzymes with similar kinetics, the activation of the isomerase activity of H261R by NAD+ was dramatically decreased. Based on these kinetic measurements, His261 appears to be a critical amino acid residue for the 3beta-HSD activity, and Tyr253 or Tyr254 participates in the isomerase activity of human type I (placental) enzyme.

Functional activity of 3beta-hydroxysteroid dehydrogenase/isomerase.

3Beta-hydroxysteroid dehydrogenase/steroid delta5-isomerase (3beta-HSD/isomerase) was expressed by baculovirus in Spodoptera fungiperda (Sf9) insect cells from cDNA sequences encoding the human wild-type I (placental) enzyme and the human type I mutant- Y253F. The wild-type and Y253F enzymes were each purified as a single, homogeneous protein from a suspension of the Sf9 cells. Ultraviolet (UV) spectral analyses showed that the wild-type enzyme induced changes in the UV spectrum of the competitive isomerase inhibitor, 19-nortestosterone, and the Y253F mutant did not. The wild-type isomerase required activation by coenzyme to produce the spectral shift. Activation of isomerase by NADH produced a greater change in the 19-nortestosterone spectrum than activation by NAD+. These observations provide direct evidence that Tyr253 functions as the general acid (proton donor) in the isomerase reaction mechanism. Furthermore, the coenzyme-activation profiles support our proposed two-step enzyme mechanism in which NADH produced by the 3beta-HSD activity induces the enzyme to assume the isomerase conformation.

Fine structure in cellulose microfibrils: NMR evidence from onion and quince.

It has been controversial for many years whether in the cellulose of higher plants, the microfibrils are aggregates of 'elementary fibrils', which have been suggested to be about 3.5 nm in diameter. Solid-state NMR spectroscopy was used to examine two celluloses whose fibril diameters had been established by electron microscopy: onion (8-10 nm, but containing 40% of xyloglucan as well as cellulose) and quince (2 nm cellulose core). Both of these forms of cellulose contained crystalline units of similar size, as estimated from the ratio of surface to interior chains, and the time required for proton magnetisation to diffuse from the surface to the interior. It is suggested that the onion microfibrils must therefore be constructed from a number of cellulose subunits 2 nm in diameter, smaller than the 'elementary fibrils' envisaged previously. The size of these subunits would permit a hexagonal arrangement resembling the cellulose synthase complex.

Affinity radiolabeling identifies peptides associated with the isomerase activity of human type I (placental) 3beta-hydroxysteroid dehydrogenase/isomerase.

3beta-Hydroxysteroid dehydrogenase and steroid Delta5-->4-isomerase (3beta-HSD/isomerase) were purified as a single protein from human term placenta. The affinity alkylator, 5,10-secoestr-4-yne-3,10, 17-trione (secosteroid), was incubated with the purified enzyme (30/1 secosteroid/enzyme molar ratio) to produce an 80% loss of initial isomerase activity over 90 min in a time-dependent, irreversible manner. The secosteroid inactivated 3beta-HSD by only 20% during the same 90 min. Incubations containing the isomerase substrate steroid, 5-androstene-3,17-dione, completely protected the isomerase activity from inactivation by the secosteroid and did not slow the inactivation of 3beta-HSD. The enzyme containing covalently bound steroid was separated from unreacted secosteroid by reversed phase HPLC. Ketones on the protein-bound secosteroid were radiolabeled by reduction with sodium boro[3H]hydride (specific radioactivity 50 microCi/micromol for the transferred tritium). After removal of the unreacted sodium boro[3H]hydride, the affinity-radiolabeled enzyme was digested with trypsin-TPCK, and the peptides were isolated by reversed phase HPLC. The radiolabeled peptide fractions were sequenced. The secosteroid alkylated three tryptic peptides: 251GQFYYISDDTPHQSYDNLNYTLSK274, tritiated His262; 176NGGTLYTCALR186, tritiated Cys183; and 353TVEWVGSLVDR363, tritiated Trp356. Coincubation with the isomerase substrate blocked the labeling of these three peptides and shifted the alkylation by secosteroid to a single tryptic peptide (135EIIQNGHEEEPLENTWPAPYPHSK159, tritiated His142). Using substrate protection to validate specificity, the affinity labeling secosteroid has identified peptides in the enzyme that are associated with isomerase activity.

Assessment of lifetime patterns of dairy food intake and physical activity.

Patterns of nutrition and exercise throughout the life span may account for differences in health problems of aging. The purpose of this study was to develop and validate a simple life span history questionnaire of dairy food intake and to assess recalled levels of leisure time physical activity over the life span. Volunteers, 98 women and 49 men, completed two nutritional surveys (Criterion Questionnaire, ¿CRIQ¿ and Diary Food Index, ¿INDX¿) and a physical activity questionnaire (P-ACTQ) in a test re-test design. The INDX and P-ACTQ consisted of a one to four scale (low to high intake). Dairy food intake averaged 1.4 to 2.3 servings per day with no significant differences in current dairy food intake between decade age categories. When compared to their own recalled 20's decade, dairy food intake declined slightly with age, except for the 80-89 age group which showed an increased intake. Test retest reliability for the INDX was r = 0.64. Validity of the INDX compared to the CRIQ was r = 0.64. All groups showed a decrease in physical activity levels across the life span. The Dairy Food Index holds promise as a simple "global" assessment of dairy food intake for the study of lifetime trends in advancing our understanding of the role of lifetime habits in chronic "lifestyle" diseases.

Using heart rate and ratings of perceived exertion to monitor intensity in runners.

This investigation examined using heart rate (HR), central rating of perceived exertion (C-RPE) and peripheral rating of perceived exertion (P-RPE) values obtained during a graded exercise test (GXT) for monitoring intensity during a 5000 m field run. Ten trained runners performed a GXT to determine HR, C-RPE and P-RPE values at a blood lactate concentration ([La]) > or = 4.0 mM. Three randomly assigned 5000 m runs were performed on an outdoor track using the HR, C-RPE and P-RPE values from the GXT. [La] was assessed at 1000 m, 3000 m and 5000 m and running velocity (RV) at each 1000 m interval. No significant interaction effect was observed for [La] or RV among trials. A significant time effect was found among trials for [La] and RV. The 5000 m [La] was significantly different from the GXT for the C-RPE and P-RPE trials, but not the HR trial. The 1000 m RV for each trial was significantly different from the RV of the GXT. The 2000 m and 5000 m RV for P-RPE were significantly different from the RV of the GXT. The data indicate that using HR values from a GXT were better than using RPE values for maintaining exercise intensity at a [La] of 4.0 mM during a 5000 m field run in trained runners.

Effect of acute potassium-magnesium aspartate supplementation on ammonia concentrations during and after resistance training.

This study examined the effects of aspartate supplementation (ASP) on plasma ammonia concentrations ([NH4+]) during and after a resistance training workout (RTW). Twelve male weight trainers were randomly administered ASP or vitamin C in a crossover, double blind protocol, each trial separated by 1 wk. ASP and vitamin C were given over a 2-hr period beginning 5 hr prior to the RTW. The RTW consisted of bench, incline, shoulder, and triceps presses, and biceps curls at 70% of one repetition maximum (1-RM). After the RTW a bench press test (BPT) to failure at 65% of 1-RM was used to assess performance. [NH4+] was determined preexercise, 20 and 40 min midworkout, immediately postexercise, and 15 min postexercise. Treatment-by-time ANOVAs, paired t tests, and contrast comparisons were used to identify mean differences. No significant differences were observed between treatments for [NH4+] or BPT. [NH4+] increased significantly from Pre to immediately postexercise for both the ASP and vitamin C trials. Acute ASP supplementation does not reduce [NH4+] during and after a high intensity RTW in weight trained subjects.

Metabolic and ventilatory responses to submaximal and maximal exercise using different breathing assemblies.

This study compared ventilatory and metabolic responses during exercise using three breathing assemblies: mouthpiece/noseclip (BV); mouth/face mask (MM); and facemask (FM). Ten male runners completed three maximal treadmill tests with breathing assembly randomly assigned. Metabolic and ventilatory data were recorded every 15s, and heart rate (HR) and rating of perceived exertion (RPE) each min. No significant differences were found for treadmill run time, HRmax, respiratory exchange ratio (RER), and RPE, indicating similar efforts on all trials. No significant differences were found at maximal exercise for VO2 minute ventilation (VE), tidal volume (VT), and breathing frequency (f). At ventilatory threshold (TVENT), VO2, VE, and f were not significantly different. However, peak flow (PF) was significantly higher for BV than FM, and VT was significantly higher for BV than MM and FM. Results indicate alterations in ventilatory mechanics occur at TVENT, but type of breathing assembly does not significantly affect maximal values.

Metabolic and hemodynamic responses to walking with hand weights in older individuals.

The purpose of this study was to examine metabolic and hemodynamic responses of older adults (age = 66.2 +/- 5.6 yr) to walking with hand-held weights (HHW). Nineteen volunteers participated in eight randomly assigned, 10-min, submaximal, self-selected constant speed (CSP) or constant heart rate (CHR) exercise bouts using the following HHW conditions: no weight, W0; 0.45 kg, W1; 1.36 kg, W3; 2.27 kg, W5. Oxygen uptake (VO2) was recorded every 30 s, heart rate (HR) each minute, and blood pressure (BP) every 2 min. Mean values for the last 5 min of exercise were analyzed using repeated measures ANOVA. Contrast comparison tests were used to determine differences among means. During CS, significant differences between means (P < or = 0.05) existed for: VO2 (W0, W1 < W3, W5); HR, SBP, DBP, SBPmax, DBPmax (W0 < W1, W3, W5); HR, rate pressure product (RPP), DBPmax (W1 < W5); SBP, DBP, SBPmax, RPP (W3 < W5). During CHR, significant differences (P < or = 0.05) between means existed for: SBP, DBP, RPP (W0, W1, W3 < W5); DBP (W0 < W3; W1, W3 < W5). These results indicate that the use of HHW significantly increases metabolic responses at W3 and W5 during CS exercise in older adults, while hemodynamic responses increase significantly across HHW for both CS and CHR. Due to the increases in hemodynamic responses, the use of HHW may be contraindicated for older individuals with suspected or diagnosed cardiovascular disease.

Cycling program effects on one rheumatoid arthritic.

These researchers investigated the effects of a progressive resistive, cycle ergometric exercise program on cardio-vascular endurance in one rheumatoid arthritic. The 46 yr. old, male subject exercised three days/week for 14 weeks. Workouts included interval-type training using 5 minute intervals for a total of 20-30 minutes (work rate set at 50-75 watts for each interval), not including 3-minute warm-up and cool-down periods (work rate set at zero resistance). Maximal exercise stress testing on the cycle ergometer was completed and blood samples collected before and after the exercise program. Also, psychological and physical health and lifestyle data were gathered before, during and after completion of the program. The conditioning program produced a training effect (greater than 75% of the HR max after the second exercise session) and blood values improved (10-28%) from the beginning to the end of the program. Finally, the program appeared to have a positive influence on various physical and psychological parameters as perceived by the subject and his wife.

Effect of physical conditioning on blood lactate disappearance after supramaximal exercise.

The purpose of this study was to investigate the effect of physical conditioning on the rate of blood lactate disappearance during recovery from supramaximal exercise. The rate of blood lactate disappearance was determined in 11 female and 4 male subjects before and after a 6-week conditioning programme. Blood samples were taken during the 30 minutes following supramaximal exercise during both passive (resting) and active recoveries. Pre-test active recovery was performed at 25% VO2 max; post-test active recovery was performed at both the same absolute and relative intensities (% VO2 max) as during the pre-test. Eight of the subjects trained 4 days/week for 6 weeks with high-intensity interval bicycle ergometer exercise, and 7 subjects served as controls. The conditioning programme significantly (p less than .05) increased VO2 max by 6.7 ml/kg.min (15%) and work capacity on the cycle ergometer by 2.8 minutes (27%). Physical conditioning did not affect significantly (p less than .05) the rate of blood lactate disappearance measured during passive recovery or during active recovery at the same absolute intensity, but increased significantly (p less than .05) the rate of blood lactate disappearance during active recovery performed at the same relative exercise intensity. The increased disappearance rate following conditioning was attributed to the higher absolute intensity of recovery work performed.

Effect of experimental alterations in excess weight on aerobic capacity and distance running performance.

To experimentally investigate the effect of excess body weight or fat on maximal oxygen uptake (Vo2 max) and distance running performance, the metabolic response to maximal and submaximal treadmill running and the 12-min run performance were measured in six subjects under each of four added-weight (AW) conditions: normal body weight and 5, 10, and 15% additional external weight, added to the trunk. AW was found to systematically and significantly decrease Vo2 max expressed relative to the total weight carried (ml/min.dg TW), maximal treadmill (TM) run time and 12-min run distance, but not to systematically affect Vo2 max (1/min) or Vo2 max (ml/min.kg FFW). An increase of 5% AW was found, on the average, to decrease Vo2 max (ml/min.kg TW) 2.4 ml, the TM run time 35 sec and the 12-min run distance 89 m. These decreases were a direct consequence of the increased energy cost of running at submaximal speeds. It was concluded that changes in excess body weight can influence Vo2 max expressed relative to body weight and distance run performance independent of any change in cardiovascular capacity. Failure to distinguish the metabolic effects of body fatness from the influence of cardiorespiratory capacity may result in misleading interpretation of distance run test scores.