Resting energy expenditure in chronic hepatitis C

BACKGROUND/AIMS: Hypermetabolism is considered to be of clinical interest in liver disease and in several chronic viral infections. Whether resting energy expenditure (REE) increases during chronic hepatitis C is not known. Our aims were: (a) to determine the metabolic state of patients with chronic hepatitis C, and (b) to evaluate the effects of interferon therapy on REE. METHODS: Forty-seven patients and 20 controls were studied. Sixteen patients failed to respond to interferon and 12 patients stopped the treatment during the first 2 months for various reasons. The 19 responders all received 1 year of interferon. REE (indirect calorimetry) and fat-free mass (FFM, bioelectric impedance analysis) were evaluated before (day 0) and after 90, 180, and 360 days of interferon. The virus load was evaluated in patients before treatment. RESULTS: On day 0, REE expressed as a ratio of FFM (REE/FFM) was higher in patients than in controls (129.2 +/- 14.7 vs 117.9 +/- 9.6 kJ kg FFM(-1) 24 h(-1), p<0.01), and was positively correlated with the viral load (r=0.45, p=0.01). On day 90, REE/FFM had significantly decreased in responders but it did not decrease in non-responders (p<0.01). In responders, REE/FFM on days 180 and 360 was similar to that of the controls. CONCLUSIONS: Chronic hepatitis C induces hypermetabolism that is normalized by interferon therapy in responders. The underlying mechanisms of chronic hepatitis C-induced hypermetabolism and its clinical relevance remain to be determined.     

Resting energy expenditure in Duchenne patients using home mechanical ventilation.

Nutritional status is both important and difficult to assess in patients with Duchenne muscular dystrophy (DMD), particularly in those requiring mechanical ventilation (MV). The current authors evaluated body composition (bio-impedancemetry), resting energy expenditure (REE; indirect calorimetry) and energy intake in 20 adult patients with DMD using home MV (nocturnal: n = 13; continuous: n = 7) and 12 age-matched healthy controls. The patients were smaller in height than the controls and had a lower body weight. Most of the reduction in body mass index was accounted for by a reduction in fat free mass (FFM). REE (kJ) was significantly reduced in the patients (4559+/-853 kJ x 24 h(-1) versus 7407+/-1312 kJ x 24 h(-1)), but the difference disappeared after correction for FFM. REE and FFM were correlated in both the controls and patients, but less strongly in the latter, the lower strength of the association being due to the patients using continuous MV (REE and FFM uncorrelated). The food intake of the patients was 1.2+/-0.4 greater than their REE. This study shows that patients with advanced forms of Duchenne muscular dystrophy have balanced energy intakes and resting energy expenditure.     

Resting energy expenditure and body composition in bedridden institutionalized elderly women with advanced-stage pressure sores

BACKGROUND: Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size. METHODS: The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured. RESULTS: The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area. CONCLUSION: Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.     

Energy Expenditure, Substrate Oxidation, and Body Composition in Subjects with Chronic Alcoholism: New Findings from Metabolic Assessment

There is some controversy as to the effect of ethanol on body weight and alcohol energy contribution to body mass. The aim of this study was to evaluate the effect of alcohol addiction on resting energy expendhrre (REE) and body composition. Twelve patients with current alcoholism (A) without severe liver disease or lipid and carbohydrate malabsorption were compared with a group of healthy social drinkers (B) matched for sex, age, and height. Their caloric intake was computed on the basis of a food diary. REE was measured with indirect calorimetry, and body composition was assessed by both anthropometry and bioimpedance. A significant decrease in fat mass in A compared with B was found (14.8 ± 5.39 vs. 19.0 ± 3.50 kg; p < 0.05). No significant differences were observed in fat-free mass (FFM) or in total body water between the two groups. A showed higher REE values normalized by FFM than B (35.5 ± 2.97 vs. 33.0 ± 2.95 kcal/kg_FFM; p < 0.05). The nonprotein respiratory quotient was significantly lower in A than in B (0.76 ± 0.03 vs. 0.86 ± 0.03; p < 0.001), and A showed significantly higher lipid oxidation and lower carbohydrate oxidation than B (p < 0.05). The daily caloric intake provided only by food ingestion was found to be significantly higher in controls, but because the percentage of alcohol calories of total energy intake was 46.3 ± 6.80 in alcoholics and 13.6 ± 3.59 in controls (p < 0.0001), the total caloric intake, computed as food intake plus alcohol intake, was higher in alcoholics than in control subjects. No statistical differences were found in urinary nitrogen excretion and fecal loss between groups. Patients with alcoholism showed an increased REE over predicted values and a preferential lipid oxidation with respect to controls; these findings could be related to induction of microsomal ethanol oxidizing system and to mitochondrial function adaptation secondary to chronic alcohol abuse. In either case, the effects of such changes in energy metabolism may contribute to alcohol associated hepatic injury.     

Measuring body composition in chronic heart failure: a comparison of methods

AIMS: Fat-free mass (FFM) is increasingly recognized as a systemic marker of disease severity in chronic organ failure and is an important target for physiologic and pharmacologic interventions to improve functional status. The aim of this study was therefore to evaluate two clinical methods to assess FFM in patients with chronic heart failure (CHF) using deuterium dilution (DEU) as reference and bromide dilution to assess the ratio between intracellular (ICW) and extracellular water (ECW) as potential confounder. METHODS: Body composition was measured with dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and DEU in 22 stable patients from our heart failure outpatient clinic and 24 healthy age matched controls. RESULTS: FFM values measured by DXA and DEU in patients (r = 0.92, SEE: 3.1 kg) and controls (r = 0.99, SEE: 1.3 kg) were strongly related. In both patients and controls, the inter method difference increased with higher values of FFM (DXA overestimating DEU). The ICW/ECW ratio was within the normal range and comparable between the groups. In patients, a highly significant correlation coefficient was found (r = 0.93, SEE 2.1 p = 0.01) between total body water (DEU) and height squared/resistance (Ht2/R). On multiple regression next to Ht2/R, body weight was an independent predictor of FFM(DEU) (r = 0.95, SEE 2.5 kg, p<0.001; TBWdeu = 0.528 Ht2/R + (0.182 weight) + 8.277). CONCLUSION: DXA and DEU are appropriate and interchangeable laboratory methods for assessment of FFM in clinically stable heart failure patients, however, overestimation of FFM(DXA) should be considered. BIA is a suitable clinical alternative for diagnostic purposes.     

Age-related differences in metabolic adaptations following resistance training in women

The purpose of this study was to determine whether aging alters changes in resting metabolic rate, body composition and insulin sensitivity in response to resistance training (RT) in women. The impact of a 6-month controlled RT program on fat-free mass (FFM), resting energy expenditure (REE), and glucose disposal was examined in 19 younger (27.8+/-3.5 yr; range 18-35) and 12 older (66.6+/-4.9 yr, range 55-70) non-obese caucasian women. For younger women, the RT program increased body weight (59.1+/-6.2 to 60.8+/-6.1 kg, p<0.05) due to an increase in FFM (39.2+/-3.7-40.4+/-3.2 kg, p<0.05). REE increased from 1379+/-114 to 1451+/-140 kcal day(-1), p<0.0001), and glucose disposal (from 364.1+/-91.1 to 402.1+/-87.8 mg min(-1), p<0.05). Neither fat mass nor VO2max changed significantly. On the other hand, older women lost fat mass (24.0+/-4.6-23.2+/-5.4 kg, p<0.05) and tended to gain FFM (from 37.3+/-4.0-38.0+/-4.3 kg, +1.9%; p=0.057), whereas no change occurred in body weight, REE, VO(2)max or glucose disposal. Thus, younger women showed greater metabolic changes in body composition, REE and insulin sensitivity in response to RT than older women. These results suggest an age-related alteration in metabolic changes in response to a 6-month RT program in previously untrained women.     

Influence of fat-free mass and functional status on resting energy expenditure in underweight elders

BACKGROUND: In underweight elders, resting energy expenditure (REE) and its relationship with fat-free mass (FFM) could be modified by sarcopenia, physical activity, and functional limitation. The aims of this study were to investigate REE and its relationship with quantity and metabolic activity of FFM and to evaluate the influence of functional status on REE in underweight elderly subjects. METHODS: Forty-eight underweight elders (BMI < 20) and 54 normal weight elderly subjects (BMI 20-30) as a control group were selected. Body composition was determined by dual energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry. Ability in activities of daily living (ADLs) was assessed by the Katz index. RESULTS: Underweight elders had significantly lower FFM, FFM index (FFM/height(2)), and REE than healthy subjects. REE adjusted for FFM with analysis of covariance remained significantly lower in the underweight group (1287 +/- 85 vs 1715 +/- 139 kcal/day in men, and 1124 +/- 63 vs 1366 +/- 91 kcal/day in women). Katz index in the underweight group was inversely correlated with REE (r = -0.68; p <.001) even after removal of FFM, FM, and gender, by multiple regression analysis. In this model, FFM and Katz index together explained approximately 54% of REE variability. CONCLUSIONS: Underweight elderly subjects show a hypometabolism due to a reduction of both FFM quantity and its metabolic activity. Functional status in ADLs comes out as an important predictor of REE independently from FFM. The limited physical activity might be the underlying determinant of this hypometabolism, but further investigations are necessary to confirm this issue.     

Association of fatigue with an acute phase response in sarcoidosis.

The pathophysiological explanation for fatigue, one of the most common symptoms in sarcoidosis, still has to be elucidated. It was hypothesized that the presence of fatigue is associated with an acute phase response in sarcoidosis. A cross-sectional study was performed in 38 sarcoidosis patients. Resting energy expenditure (REE) was measured in the fasting state by indirect calorimetry using a ventilated hood and adjusted for fat-free mass (FFM). Patients with fatigue (n=25) also suffered more frequently from other symptoms, such as exercise intolerance (p=0.01), the need for sleep (p=0.02) and weight loss (p=0.01), compared to those without fatigue (n=13). However, no relationship was found between fatigue and serum angiotensin-converting enzyme (sACE) or lung function impairment. Patients with fatigue had higher levels of C-reactive protein (CRP) (11.4+/-6.8 microg x mL(-1), p<0.0001) and REE adjusted for FFM (33.0+/-3.7 kcal x kg FFM(-1), p<0.003) compared to those without fatigue (3.2+/-2.2 mg x mL(-1); 29.2+/-2.8 kcal x kg FF(-1)). Furthermore, REE/FFM was significantly related to CRP (r=0.54, p=0.001). This study confirms the presence of an acute phase response as indicated by metabolic derangements and a moderate increase in C-reactive protein levels in sarcoidosis, particularly in those patients with constitutional symptoms. Future studies should focus on the clinical relevance and therapeutic implications of these findings.     

Long-term effects of consumption of a novel fat emulsion in relation to body-weight management

OBJECTIVE: To assess weight maintenance after weight loss by consumption of yoghurt with a novel fat emulsion (Olibra) including effects on body composition, resting energy expenditure (REE), fat oxidation, hunger feelings and satiety hormones. DESIGN: A randomized, placebo-controlled, double-blind, parallel design. A 6-week weight loss period (2.1 MJ/day) was followed by 18 weeks weight maintenance with test (Olibra) or placebo yoghurt. SUBJECTS: Fifty overweight women (age: 18-58 years, body mass index (BMI) 25-32 kg/m2). MEASUREMENTS: In weeks 1, 7 and 25, a satiety test with questionnaires and blood samples for analysis of satiety hormones. In weeks 2, 8 and 26, REE, body weight and body composition. RESULTS: During weight maintenance after significant body weight reduction, there was no significant increase in body weight in the test group (1.1+/-3.4 kg); the placebo group did gain weight (3.0+/-3.1 kg, P<0.001). Compared to the placebo group, the test group was less hungry 4 h after yoghurt consumption in week 25 (P<0.05) and showed increased glucagon like peptide-1 values 180 min after yoghurt consumption (week 25 vs week 1, P<0.05). Measured REE as a function of fat-free mass (FFM) was significantly higher than predicted REE (P<0.05) in week 26 for the test group, but not for the placebo group. Fat mass (FM) was significantly more decreased in the test group (6.5+/-4.1 kg) compared to the placebo group (4.1+/-3.6 kg) (week 26 vs week 2, P<0.05). CONCLUSION: Consumption of Olibra yoghurt improved weight maintenance compared to placebo, which can be explained by the relatively higher REE as a function of FFM, relatively higher decrease in FM and the relatively lower increase in hunger.     

Energetic cost of protein turnover in healthy elderly humans

OBJECTIVE: Whole body protein turnover (PTO) and resting energy expenditure (REE) are both correlated to fat-free mass (FFM), in young and elderly subjects, and REE is positively correlated to PTO in young adults. Thus, the aim of this study was to compare the energetic cost of PTO in young (n=39, 23.4+/-3.1 y) and elderly (n=41, 67.5+/-3.6 y) healthy volunteers. MEASUREMENTS: REE (indirect calorimetry), PTO ((13)C-leucine isotopic dilution) and body composition (bioelectrical impedance analysis with age-specific equations) were measured in the postabsorptive state. RESULTS: Elderly subjects had a higher fatness (30.5+/-7.1 vs 18.2+/-5.5%, elderly vs young, P<0.001), a similar REE (0.97+/-0.13 vs 1.06+/-0.15 kcal min(-1)), and a lower PTO (1.28+/-0.22 vs 1.44+/-0.18 micromol kg(-1) min(-1), P<0.001). PTO, REE and FFM were significantly correlated and after adjustment for FFM, REE was positively correlated to PTO (r=0.61, P<0.001). The slope of this relationship was the same in both groups, while the adjusted mean REE was lower in elderly subjects (0.97+/-0.09 vs 1.05+/-0.07 kcal min(-1), P<0.01). CONCLUSION: In comparison with young subjects, the energetic cost associated with PTO in elderly subjects is not different, but the proportion of REE not associated with PTO is lower.     

Effect of chronic treatment with beta-blockers on resting energy expenditure in obese hypertensive patients during a low-calorie and physical training program

BACKGROUND AND AIM: To evaluate whether chronic treatment with beta-blockers influences resting energy expenditure (REE) and weight loss after a period of diet and physical activity in obese hypertensive patients. METHODS AND RESULTS: Seventy-eight obese hypertensive patients (24 males and 54 females) aged 53.7 +/- 11.1 years with mean BMI of 42.4 +/- 5.8 kg/m2 were enrolled. Thirty-eight patients were using beta-blockers while 40 patients who had not received beta-blockers in the past 6 months were the control group. REE was measured with indirect calorimetric method. Total body fat mass, total body fat-free mass (FFM) and total body water (W) were determined by bioelectrical impedance analysis. Patients and controls underwent a structured physical training program and a hypocaloric diet for a period of 31.6 +/- 10.6 days. Measured REE in patients taking beta-blockers was 1818 +/- 309 kcal/24 h and 1853 +/- 348 kcal/24 h in patients not taking beta-blockers; p = non significant. Weight and BMI loss were similar between the two groups and were respectively -6.43 +/- 2.62 kg and -2.42 +/- 0.91 kg/m2 in the beta-blocker group and -7.49 +/- 3.10 kg, -2.78 +/- 1.03 kg/m2 in the non beta-blocker group. Body composition was similar in the two groups. In the comparison between patients treated with selective beta 1-adrenoceptors blockers and non selective beta-blockers we found a significant difference in REE (1704 +/- 283 vs 1974 +/- 278; p = 0.012) and in weight loss (-5.6 +/- 2.4 vs -7.5 +/- 2.7; p = 0.048) at the end of study. CONCLUSIONS: Beta-blockers are not associated with a lower REE in obese subjects compared to other antihypertensive treatment. Use of non selective beta-adrenergic blockers is associated with a higher REE and weight loss compared to use of selective beta 1-adrenergic blockers. Non selective beta-blockers could be indicated among first choice drugs in hypertensive severely obese subjects without contraindications to beta-blockade.     

Paradoxical weight loss with extra energy expenditure at brown adipose tissue in adolescent patients with Duchenne muscular dystrophy

We examined the energy expenditure in patients with Duchenne muscular dystrophy(DMD) to evaluate the cause of the paradoxical weight loss observed in large numbers of adolescent patients before any obvious impairment of their swallowing function. In the morning, resting energy expenditure (REE)/m(2) was almost the same as that in normal controls despite a reduction in fat-free mass (FFM); thus, REE/m(2)/FFM was significantly increased in patients (median, 21.2 kcal/m(2)/FFM kg; range, 17.7 to 44.2, P =.012). A thermographic examination in the morning showed an obvious elevation of the body surface temperature on the back. This phenomenon was consistent with a paradoxical fall in the low frequency (LF)/high frequency (HF) ratio at night analyzed using the inter-RR spectrum by 24-hour electrocardiogram, which indicated relative activation of the sympathetic nervous system. The urinary secretion of norepinephrine at night was also significantly greater in patients (median, 0.119 microg/kg/h; range, 0.061 to 0.219, P =.011). These results suggest that paradoxical activation of the sympathetic nervous system may accelerate the production of heat in brown adipose tissue (BAT) and increase the level of energy consumption in patients, and that adolescent DMD patients may require greater caloric intake than expected to maintain body weight, which is important to improve the prognosis of their respiratory function.     

Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing

Summary HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-calssified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P>0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course.     

Body composition in coeliac disease adolescents on a gluten-free diet: a longitudinal study

Our aim was to evaluate body composition in a group of coeliac disease adolescents on a gluten-free diet and to re-examine them at the end of the adolescence spurt. We studied 48 patients (group 1A), 30 age-matched healthy controls (group 2A), 11 group 1A patients after 4 years (group 1B) and 11 adolescents who were age- and sex-matched with group 1B (group 2B). Weight, height, bone mineral content, fat mass, fat-free mass (FFM) and bone mineral density were evaluated using dual-energy X-ray absorptiometry. All parameters were lower in group 1A than in group 2A subjects ( p<0.001). After 4 years, the body compartments of group 1B coeliac disease patients normalised, except for weight and FFM which remained lower than in group 2B subjects ( p<0.005). In conclusion, our study demonstrates that adolescence is a period where some parameters of body composition can still be recovered.     

The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery

BACKGROUND: Although candidates for lung reduction surgery (LRS) include malnourished patients with severe chronic obstructive pulmonary disease (COPD), the impact of preoperative nutritional status on surgical outcome has not been clearly elucidated. METHODS: We investigated the relationship between preoperative nutritional status and postoperative morbidity in 23 consecutive patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were measured using a bioelectrical impedance analyzer. FFM and FM were expressed as height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin were also determined. RESULTS: 8 patients had major complications. Preoperative %IBW and FFMI were significantly lower among patients with major complications, while no significant differences were observed in pulmonary function, FMI or serum protein. The complication rate was significantly higher among patients with low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results suggest that FFM depletion is an excellent predictor of unacceptable postoperative complication following LRS.     

Increased circulating vascular endothelial growth factor is correlated with disease activity in polyarticular juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the relevance of vascular endothelial growth factor (VEGF) in the pathogenesis of juvenile rheumatoid arthritis (JRA). METHODS: Serum VEGF levels in 58 patients with JRA (systemic in 17, polyarticular in 29, pauciarticular in 12) were measured by ELISA and compared with those of 21 patients with infectious diseases and 50 healthy children. Correlations of VEGF levels with number of joints with active arthritis, erythrocyte sedimentation rate (ESR), and hyaluronic acid (HA) were examined. RESULTS: Serum levels of VEGF in patients with JRA were significantly higher than in healthy controls. Patients with systemic and polyarticular JRA showed statistically higher levels of VEGF than those with infectious diseases. VEGF levels correlated statistically with C-reactive protein (CRP) in patients with both infectious diseases and polyarticular JRA, but the regression slope (VEGF/CRP) was much steeper in polyarticular JRA than in infectious diseases. Serum VEGF levels correlated with disease activity variables such as the number of joints with active arthritis, ESR, and serum HA levels in polyarticular JRA. CONCLUSION: The correlation of serum VEGF levels and disease activity in polyarticular JRA suggests that VEGF may take an active part in joint inflammation.     

Longitudinal growth attainments of Indian boys with Juvenile Rheumatoid Arthritis

The objective is to study the pattern of distance and velocity growth in terms of weight and height in adolescent boys with Juvenile Rheumatoid Arthritis (JRA). This study was conducted on children diagnosed to have JRA (Cassidy and Petty in Juvenile Rheumatoid Arthritis, WB Saunders Co., Philadelphia, 2005) at the Pediatric Rheumatology and Immunology Clinic of Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 203 observations made on 70 boys with JRA, between 9 and 17 years of age, comprised the sample for this prospective mixed-longitudinal growth study. Each subject was measured for body weight and standing height using standardized anthropometric techniques (Eveleth and Tanner in Worldwide variation in human growth, Cambridge University Press, New York, 1990) at half yearly age intervals. All anthropometric measurements were carried out in the Growth Laboratory of Advanced Pediatrics Centre. Boys with polyarticular and systemic onset types of JRA in general measured lighter than their pauciarticular counterparts throughout the period of study. Height attainments in boys with polyarticular and systemic onset JRA measured shorter than their pauciarticular counterparts till 15 years and 12 years, respectively, where-after they became comparable to boys with pauciarticular JRA. As compared to normal Indian (Bhalla and Kumar in Int J Anthropol 18:113–125, 2003; Aggarwal et al. in Indian Pediatr 29:1203–1282, 1992) and American (Ogden et al. in Pediatrics 109:45–60, 2002) counterparts boys representing all categories of JRA remained lighter and shorter. Onset of Peak Height Velocity (PHV) in boys with polyarticular JRA (i.e. 12.5 years) was delayed by 1 year as compared to boys with pauciarticular JRA (i.e. 11.5 years). Attainment of Peak Weight Velocity (PWV) in boys with polyarticular JRA (i.e. 13.5 years) was also delayed by 1 year when compared to those with pauciarticular type (i.e. 12.5 years). In conclusion, weight and height growth attainments in Indian adolescent boys afflicted with different categories of JRA in general remained impaired as compared to their normal counterparts. However, the magnitude of growth deficit experienced by them appears to be a disease severity related phenomenon. This is the first study of its kind from a developing country.     

Blockade of tumour necrosis factor-alpha in rheumatoid arthritis: effects on components of rheumatoid cachexia

OBJECTIVES: Rheumatoid arthritis (RA) is accompanied by increased resting energy expenditure (REE) and decreased fat-free mass (FFM). This is referred to as rheumatoid cachexia and is attributed to high levels of tumour necrosis factor-alpha (TNF-alpha). This study aimed to investigate the effects of anti-TNF-alpha therapy on REE, body composition, physical activity and protein intake in RA patients. METHODS: Twenty RA patients [50% female; age: (mean +/- s.d.) 61.1 +/- 6.8 yrs; body mass index (BMI): 28.3 +/- 3.7 kg/m2] and 12 age-sex-BMI-matched healthy controls were assessed. REE (indirect calorimetry), body composition (bioelectrical impedance), the International Physical Activity Questionnaire (IPAQ), diet, Health Assessment Questionnaire (HAQ), disease activity [disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein] and serum TNF-alpha were measured before (Baseline) as well as 2 weeks (Time-1) and 12 weeks (Time-2) after initiation of anti-TNF-alpha treatment. Controls were only assessed at Baseline. RESULTS: RA patients had significantly higher REE than controls at Baseline (1799.4 +/- 292.0 vs 1502.9 +/- 114.5 kcal/day, P = 0.002). Within the RA group, REE increased significantly between Time-1 and Time-2 (P = 0.001) but not between Baseline and Time-2. Sustained significant increases were observed in IPAQ (P = 0.001) and protein intake (P = 0.001). There were no significant changes in FFM or body fat. ESR (P = 0.002), DAS28 (P < 0.001), HAQ (P < 0.001) and TNF-alpha (P = 0.024) improved significantly. Physical activity (P = 0.001) and protein intake (P = 0.024) were significant between-subject factors for the elevation of REE. CONCLUSIONS: After 12 weeks of anti-TNF-alpha therapy, there were significant improvements in disease activity and physical function, as well as physical activity and protein intake, but no significant changes in REE or FFM. There is a need for longer-term studies in this field.     

Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis

OBJECTIVE: To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity. METHODS: Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity. RESULTS: Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions. CONCLUSION: The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.