Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study.

BACKGROUND: Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine. METHODS: A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea. RESULTS: A total of 746 patients were included. Median age was 64 years (interquartile range 57-71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54-7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85-5.87) were the only risk factors for severe diarrhea. CONCLUSIONS: Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.

The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet.

BACKGROUND: Inadequate micronutrient intake among older adults is common despite the increased prevalence of fortified/enriched foods in the American diet. Although many older adults take multivitamin supplements in an effort to compensate, studies examining the benefits of this behavior are absent. OBJECTIVE: To determine whether a daily multivitamin/mineral supplement can improve micronutrient status, plasma antioxidant capacity and cytokine production in healthy, free-living older adults already consuming a fortified diet. METHODS: An eight-week double-blind, placebo-controlled clinical trial among 80 adults aged 50 to 87 years (mean = 66.5 +/- 8.6 years). RESULTS: Multivitamin treatment significantly increased (p<0.01, compared to placebo) plasma concentrations of vitamins D (77 to 100 nmol/L), E (27 to 32 micromol/L), pyridoxal phosphate (55.1 to 75.2 nmol/L), folate (23 to 33 nmol/L), B12 (286 to 326 pmol/L)), C (55 to 71 micromol/L), and improved the riboflavin activity coefficient (1.23 to 1.15), but not vitamins A and thiamin. The multivitamin reduced the prevalence of suboptimal plasma levels of vitamins E (p=0.003), B12 (p=0.004), and C (p=0.08). Neither glutathione peroxidase activity nor antioxidant capacity (ORAC) were affected. No changes were observed in interleukin-2, -6 or -10 and prostaglandin E2, proxy measures of immune responses. CONCLUSIONS: Supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of suboptimal vitamin status in older adults and improve their micronutrient status to levels associated with reduced risk for several chronic diseases.

Mechanical properties of the tendinous equine interosseus muscle are affected by in vivo transducer implantation.

Liquid metal strain gauges (LMSGs) were implanted in the tendinous interosseous muscle, also called suspensory ligament (SL), in the forelimbs of 6 ponies in order to quantify in vivo strains and forces. Kinematics and ground reaction forces were recorded simultaneously with LMSG signals at the walk and the trot prior to implantation, and 3 and 4 days thereafter. The ponies were euthanised and tensile and failure tests were performed on the instrumented tendons and on the tendons of the contra lateral limb, which were instrumented post mortem. The origo-insertional (OI) strain of the SL was computed from pre- and post-operative kinematics, using a 2D geometrical model. The LMSG-recorded peak strain of the SL was 5.4+/-0.9% at the walk and 9.1+/-1.3% at the trot. Failure occurred at 15.4+/-2.1% (mean+/-S.D.). The LMSG strain was higher than the simultaneously recorded OI strain 0.5+/-0.7% strain at the walk and 2.2+/-1.1% strain at the trot. Post-operative OI strains were only slightly higher than pre-operative values. Failure strains of in vivo instrumented SLs were 2.0+/-1.2% strain higher, and failure forces were slightly lower, than those of the contra lateral SLs that were instrumented post mortem. SL strains appeared to be considerably higher than those found in earlier acute experiments. Differences between in vivo LMSG and OI strains, supported by lower failure strains comparing in vivo and post mortem instrumented SLs, revealed that local changes in tendon mechanical properties occurred within 3 to 4 days after transducer implantation. Therefore, measurements of normal physiological tendon strains should be performed as soon as possible after transducer implantation.

Responses of circulating urea cycle and branched-chain amino acids to feeding in adult and aged Fischer-344 rats.

Amino acid concentrations in plasma and blood were compared between adult (6 months) and aged (22 months) male rats in fed and food-deprived (fasted) states. Since feeding is known to elevate plasma amino acids, rats were sampled after food had been freely available to them and after food was withheld for 20 hours. Fourteen amino acids increased (8 to 74%) in blood and plasma in fed rats compared to food-deprived rats. Blood concentrations of four amino acids (cystine, aspartate, threonine, and phosphoserine) were increased in aged compared to adult rats, while tyrosine was 10% lower. The interaction between fed state and age was significant for the branched-chain amino acids (BCAA) as they increased 23% in the blood and plasma of fed compared to food-deprived adult rats; however, BCAA were not affected by feeding state in the aged rats. Plasma arginine concentration was 12% lower (p < 0.001) and citrulline was 20% higher (p < 0.005) in aged compared to adult rats, and consequently the citrulline:arginine ratio was elevated by 36% in aged rats. Our results demonstrate that, although the total arginine in whole blood is not altered or is increased with aging, less of the arginine is transported in the plasma of aged compared to adult rats. Furthermore, these results indicate altered metabolism of the urea cycle amino acids and BCAA with aging in the rat.

Radiographic evaluation of caudal vena cava size in dogs.

Dilation of the caudal vena cava (CVC) on lateral thoracic radiographs is often interpreted as suggestive of right-sided congestive heart failure. To quantitate the clinical utility of evaluating CVC size as an indicator of right-sided heart disease, we compared the ratio of the diameter of the CVC as measured on a left lateral thoracic radiograph to the descending aorta (Ao), length of the thoracic vertebra above the tracheal bifurcation (VL), and width of the right fourth rib (R4) in 35 dogs with right heart disease and 35 control dogs. Each CVC ratio (CVC/Ao, CVC/VL, CVC/R4) was statistically larger in dogs with right heart disease. Response operating characteristic curves and likelihood ratios were used to determine ratios helpful in identifying dogs with right heart disease. A CVC/Ao > 1.50, CVC/VL > 1.30, or CVC/R4 > 3.50 are strongly suggestive of a right-sided heart abnormality in a patient.

Protein metabolism in rheumatoid arthritis and aging. Effects of muscle strength training and tumor necrosis factor alpha.

OBJECTIVE: To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism. METHODS: We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean +/- SD age 25 +/- 2 years) and 8 healthy elderly (70 +/- 5 years) men and women, and in 8 adults with RA (42 +/- 13 years). An additional 6 healthy elderly subjects (69 +/- 3 years) served as a swimming-only control group. RESULTS: Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 +/- 17.2 versus 60.3 +/- 5.8 and 63.7 +/- 12.4 mumoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident after strength training. In multiple regression analysis, levels of tumor necrosis factor alpha (TNF alpha) (r = 0.47, P = 0.01) and growth hormone (r = -0.51, P = 0.006) were associated with protein breakdown, and plasma glucagon levels were inversely correlated with protein synthesis (r = -0.45, P = 0.02). Growth hormone (r = -0.56, P = 0.002) and glucagon (r = 0.45, P = 0.04, levels were associated with protein oxidation. CONCLUSION: Adults with RA have increased whole-body protein breakdown, which correlates with growth hormone, glucagon, and TNF alpha production.

A comparative evaluation of the in vitro penetration performance of the improved Crest Complete toothbrush versus the Colgate Total toothbrush and the Oral-B Advantage toothbrush.

Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing rippled brush, the original Crest Complete, was modified to offer longer rippled outer tufts to clean along the gumline more effectively. Therefore, this study evaluated the overall and gumline interproximal penetration of three bristle designs: rippled, raised pattern (Improved Crest Complete); and two multi-level patterns (Colgate Total and Oral-B Advantage). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics, and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth with the brush held at both 45 degrees and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on an analysis of consumer brushing patterns. The results of this study indicate that the Improved Crest Complete with longer rippled outer bristles provided significantly superior (p < 0.05) interproximal penetration overall and at the gumline than the Colgate Total and Oral-B Advantage brushes.

Kinematic differences between the distal portions of the forelimbs and hind limbs of horses at the trot.

In literature, it has been hypothesized that the concussion at impact in the equine forelimb is larger than that in the hind limb, and therefore, eventually more clinical lameness may develop in the distal portion of the forelimbs. As the functional anatomy of the distal forelimb and hind limb segments is similar, a study was undertaken to compare the kinematics of hoof and fetlock in the forelimbs and hind limbs. For this purpose, the trot of 24 clinically normal (sound) horses on a treadmill (4 m/s) was recorded, using modern gait analysis equipment. It appeared that vertical hoof velocity at impact and the resulting vertical hoof acceleration were higher in the forelimb than in the hind limb. In contrast, horizontal hoof velocity at impact and the resulting horizontal acceleration were higher in the hind limb. Just after impact, the fetlock was more rapidly extended in the forelimb than the hind limb. The peak maximal and minimal accelerations of that joint also were significantly (P < 0.05) higher in the forelimb than in the hind limb. Results of this study indicate that, at the beginning of the stance phase, the distal portion of the forelimb is subjected to more kinematic stress than the distal portion of the hind limb. The higher angular velocity of the fetlock can be interpreted as more rapid loading of this joint, whereas the higher peak accelerations represent the higher oscillatory changes in fetlock movement. It is known from literature that repetitive impulsive joint loading and rapid oscillations in joint movement, even within physiologic limits, contribute to development of osteoarthrosis. Therefore, the differences between distal forelimb and hind limb kinematics found in this study may be related to the generally known higher incidence of chronic lameness in the forelimbs.

Predictive value of foal kinematics for the locomotor performance of adult horses.

The gait of 24 horses was recorded on a treadmill when they were trotting at 4 m sec-1, first when they were four months old and again when they were 26 months. The data recorded at four months were used to predict the locomotion of the adult horses, and the predictions were assessed against the data recorded at 26 months. The locomotion of the foals and the adults appeared to be closely related, when the differences in segment length and joint angles due to growth were taken into account. The duration of swing, the total range of protraction and retraction, and the maximum tarsal flexion could be used to predict adult locomotion, because they correlated very well between the foals and adults. The durations of stance and stride in the foals had to be linearly and dynamically scaled to the height at the withers to become predictive for the adult values. The duration of swing, and the total range of protraction and retraction and the maximum tarsal flexion are also indicators of the quality of gait and as a result studies of foal kinematics can be used objectively to predict the locomotor performance of adult horses.

Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study.

Hyperhomocysteinemia occurs frequently in end-stage renal disease (ESRD), but its prevalence in comparison with traditional cardiovascular disease (CVD) risk factors is unknown. Fasting total plasma homocysteine, potential determinants of plasma homocysteine (i.e., plasma B-vitamins and serine), total and HDL cholesterol, glucose, and creatinine, were determined in 24 ESRD patients on dialysis, and 24 age, gender, and race matched Framingham Offspring Study controls with normal renal function. Presence of clinical CVD and CVD risk factors was established by standardized methods. Mean plasma homocysteine was markedly higher in the ESRD patients versus controls (22.7 vs. 9.5 mumol/l). ESRD patients were 33 times more likely than controls to have hyperhomocysteinemia (> 15.8 mumol/l) (95% confidence interval, 5.7-189.6). Hyperhomocysteinemia persisted in the ESRD patients despite normal to supernormal B-vitamin status. Plasma serine levels below the tenth percentile of the control distribution were found in 75% of the ESRD patients. Oral serine supplementation caused a 37% increase in mean plasma serine, but had no effect on plasma homocysteine in four ESRD patients with supernormal plasma folate, low plasma serine, and hyperhomocysteinemia. Given its unusually high prevalence, improved management of hyperhomocysteinemia might reduce CVD sequelae in ESRD.

How the horse moves: 1. Significance of graphical representations of equine forelimb kinematics.

The kinematics of 24 two-year-old Dutch Warmblood horses were recorded at the trot (4 m/s) on a high-speed treadmill to study the coordination of joints within the equine forelimb. Joint angle-time, angle-angle, stick, and marker diagrams were used to show forelimb motion graphically. Because the kinematic data referred to the joint angles of the horse standing squarely and were time-standardised to the duration of the stride cycle, mean joint curves could be calculated for the total group. The motion of each segment in the equine forelimb during a complete stride is described and its function in intralimb coordination evaluated. It appeared that the rotation of the scapula and the cranio-caudal movement of the distal forelimb are synchronous and pendular. The carpal joint rapidly snaps into overextension at the beginning of the stance phase to enable the forelimb to work as a propulsive strut. The fetlock joint acts as an elastic spring, thereby conserving energy and, at the same time, absorbs oscillations generated by initial ground contact. Furthermore, the coordination between carpal and fetlock joints in the swing phase appears to be strongly influenced by inertia. Using the graphic tools evaluated in this paper, we were able to visualise the kinematics of the equine forelimb and relate these to specific functions of the forelimb in locomotion. This information can be used to select kinematic variables for clinical studies in which equine forelimb function has to be described and quantified.

How the horse moves: 2. Significance of graphical representations of equine hind limb kinematics.

Kinematic data of the equine hind limb are presented graphically and related to functional aspects of the hind limb in locomotion. The trot of 24 two-year-old Dutch Warmblood horses was recorded at 4 m/s on a high-speed treadmill using kinematic analysis equipment. Joint angle-time, angle-angle, stick and marker diagrams were used to present graphically the data following standardised procedures. As the kinematic data were expressed with reference to the joint angles of the horse standing squarely and were time-standardised to the duration of the stride cycle, mean joint curves for the total group could be calculated and therefore describe the function of the different segments of the equine hind limb. The motion of the hind limb in the sagittal plane appeared to be pendular around a rotation point in the acetabulum. During the stance phase the extension of the fetlock joint and stance flexion of the stifle, tarsal and coffin joints illustrate the shock absorption of the hind limb. In the swing phase the reciprocal apparatus, which forms the coupling mechanism between stifle and tarsal joint, also influences the fetlock joint because synchronous flexion and extension between these 3 joints were demonstrated. By graphically presenting hind limb motion we were able to illustrate the relation between kinematics and function. This graphic analysis can be used in clinical studies involving quantification of equine hind limb coordination in the sagittal plane.

Dietary citrulline but not ornithine counteracts dietary arginine deficiency in rats by increasing splanchnic release of citrulline.

Ornithine and citrulline have different arginine-sparing capabilities when provided in an arginine-deficient diet. Rats were fed arginine-deficient diets containing ornithine or citrulline to see the effect on net fluxes of free arginine, ornithine and citrulline across the portal-drained viscera (PDV) and liver. The diets contained either 10 g arginine/kg diet (+Arg) or no arginine: the -Arg/+Ala diet contained additional alanine and the -Arg/+Orn and -Arg/+Cit diets contained ornithine and citrulline, respectively, in amounts isomolar to the amount of arginine in the control (+Arg) diet. Blood arginine concentrations were 50% lower than control values (P < 0.001) in rats fed the -Arg/+Ala or the -Arg/+Orn diet. However, addition of citrulline to the arginine-deficient diet restored blood arginine concentrations. The source of the circulating arginine in the rats fed the -Arg/+Cit diet was neither the PDV nor the liver; net splanchnic uptake of arginine was 0.3 mumol/min. Net citrulline release was substantial from the PDV (0.65 mumol/min) as well as from the splanchnic bed (0.67 mumol/min) of rats fed the -Arg/+Cit diet, such that blood citrulline concentrations were more than double (P < 0.001) those in rats fed the +Arg or -Arg/+Orn diet. Splanchnic release of citrulline in rats fed the -Arg/+Cit diet but not in rats fed the -Arg/+Orn diet supported the production of arginine in non-splanchnic organs such as, presumably, the kidney.

Kinematic detection of superior gait quality in young trotting warmbloods.

This study was conducted to identify objective criteria to select young horses with a good gait, which is a prerequisite for good performance in adult horses. The trot of 24 26-month-old Dutch Warmbloods, led on a loose shank, was subjectively scored by a judge and objectively assessed on a treadmill by using kinematic analysis equipment. It appeared that forelimb and hind limb stride and swing duration, scapula rotation, forelimb maximal fetlock extension, forelimb maximal retraction, hind limb maximal protraction, maximal stifle flexion, and maximal tarsal flexion significantly correlated with a generally accepted gait score in which length, suppleness, and strength are judged. Moreover, the ranking of the individual horses on the basis of gait quality according to their objectively measured kinematic variables was similar to the subjective ranking given by the judge. Thus, a complete picture was obtained of the variables in equine locomotion that determine the quality of the trot in warmbloods.

Supplemental arginine and ornithine do not affect splenocyte proliferation in surgically treated rats.

The present study was designed to determine whether arginine or ornithine supplementation enhanced immune responsiveness in surgically stressed rats. Young rats (130 to 150 g; n = 72) were fed one of three nonpurified diets: control, arginine-supplemented (30 g/kg of diet), or supplemented with ornithine on an equimolar basis to supplemental arginine. Control and ornithine-supplemented diets were made isonitrogenous to the arginine-supplemented diet with alanine. Food intake and body weight were monitored throughout the experimental period. Eight days after initiation of dietary treatments, 36 rats were given dorsal skin wounds. Rats were killed 7 days later. Blood was collected, spleen and thymus were weighed, and splenocytes were isolated to measure proliferation in response to mitogens and interleukin-2 production. Food intake, body weight gain, and thymus weight were lower in rats subjected to surgery than in controls rats (p < .01). Neither supplemental dietary arginine nor ornithine affected food intake, body weight gain, thymus weight, splenocyte proliferation, or splenocyte interleukin-2 production in any treatment group (p < .1). These data suggest that low-level dietary supplementation of arginine and ornithine did not ameliorate detrimental effects of minor surgery in rats.

Long-term maintenance of weight loss following supplemented fasting.

One hundred two obese subjects were evaluated 2-3 years following treatment in a combined behavior therapy and very low calorie diet (VLCD) program. Average weight loss after VLCD was 27.2 kg; average weight loss at follow-up was 11.3 kg. Subjects who reported high levels of exercise were more successful in maintaining weight loss (17.5 kg at follow-up) than were those who exercised only moderately (9.3 kg), or not at all (5.6 kg). Enrolling in a weight loss maintenance program also minimized weight regain. Subjects who participated in maintenance for more than 8 months sustained more average weight loss at follow-up (19.1 kg) than did subjects who participated for 8 months or less (10.6 kg), or subjects who did not participate in maintenance (6.6 kg).