Clinical Remission Disease Research Articles

Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis

We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA. We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients. Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro- and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease. Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.

Comparison Between Handgrip Strength, Subjective Global Assessment, Anthropometry, and Biochemical Markers in Assessing Nutritional Status of Patients with Crohn’s Disease in Clinical Remission

Crohn's disease (CD) may lead to protein and calorie malnutrition (PCM) secondary to impaired digestive and absorptive functions of the small intestine and sometimes to the influence of diet taboos. The earlier the PCM is diagnosed, the higher are the odds of reversal. The objective of this study was to compare different methods of nutritional assessment in patients with CD and correlate them with the disease characteristics. The sample comprised 75 patients with CD from the Gastroenterology Service at the Hospital de Clínicas de Porto Alegre; 37 were male, with a mean age of 38.2 years old (SD = 13.3). All patients had been in clinical remission (CDAI <150) for over 3 months. They were not receiving enteral or parenteral nutrition. The nutritional assessment was considered: body mass index (BMI), triceps skin fold (TSF), arm circumference (MAC), arm muscle circumference (MAMC), subjective global assessment (SGA), non-dominating handgrip strength (HGS) and food intake inquiries. When comparing the different nutritional assessment methods, 26.7% of the patients were malnourished according to the MAC, 29.3% according to the MAMC, 18.7% according to the SGA, 6.7% according to the BMI, 37.3% according to the TSF and 73.3% according to the HGS. No statistically significant associations were found for disease location, its behavior, drugs utilized, ESR, CRP, age of patients and disease time with the nutritional state verified by HGS, TSF, MAMC and SGA. The prevalence of malnutrition is significant in patients with CD, even in clinical remission. The BMI should not be used as reference in this population. The HGS detected a high prevalence of nutritional risk in patients with CD in remission. Studies are required that correlate it with more sensitive methods, for the patients' effective nutritional state assessment.

Autonomic Dysfunctions in Patients with Inflammatory Bowel Disease in Clinical Remission

The autonomic nervous system, especially the parasympathetic system, has been reported to modulate the immune response in chronic inflammatory disorders. Autonomic dysfunctions have been reported earlier in patients with inflammatory bowel disease; however, the results have been conflicting. We therefore evaluated autonomic functions in patients with inflammatory bowel disease (IBD) in clinical remission. Heart rate variability, a marker of autonomic functions, which included time-domain, frequency-domain, and nonlinear indices (Poincaré plot) was assessed using Nevrokard, version 6.4.0 Slovenia, in 118 patients with IBD (ulcerative colitis [UC] 62, and Crohn's disease [CD] 56) and 58 healthy controls. There was no difference in mean of R-R intervals in patients with UC, CD, and healthy controls. Frequency domain indices (absolute values of total power, high-frequency power, and low-frequency power) were lower in patients with UC and CD vs. healthy controls. High-frequency (HFnu) (expressed in normalized units) was significantly lower in UC compared to healthy controls. There was no significant difference in the low-frequency (LFnu) and LF/HF ratio in UC, CD, and healthy controls. Amongst the Poincaré plot indices, while standard deviation of the instantaneous R-R interval variability (SD1nu) was lower in UC and CD vs. healthy controls, there was no significant difference in the long-term R-R interval variability (SD2nu). Patients with inflammatory bowel disease have lower autonomic functions. Patients with UC have significantly lower parasympathetic function in comparison to those with CD and healthy controls. These autonomic dysfunctions in patients with IBD may have a bearing on the pathogenesis of IBD.

Microinflammation in patients with Crohn's disease in clinical remission

Background and aims It is not clear whether Crohn's disease patients in clinical remission (Crohn's disease activity index < 150) display normal concentrations of inflammation sensitive biomarkers. Our goal in this work was to explore the intensity of the microinflammatory response in a group of Crohn's disease patients in clinical remission. Methods High sensitivity C-reactive protein, quantitative fibrinogen, erythrocyte sedimentation rate as well as platelet and leukocyte counts were examined in a group of 76 patients with Crohn's disease in remission and in 228 matched controls. Results Crohn's disease patients in clinical remission displayed a statistically significant ( p < 0.001) elevated concentration of hs-CRP (4.83 ± 3.8 mg/l) compared to controls (1.05 ± 2.9 mg/l). All other bio-markers were also significantly higher in Crohn's disease patients in remission compared to controls. Similar results were obtained in a subgroup of Crohn's disease patients with very low disease activity — CDAI < 75. Conclusions Clinical remission is not equivalent to biochemical remission raising a question concerning the true definition of remission in Crohn's disease.

Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission

Objective This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. Methods Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 ± 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 ± 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th–75th percentile). Results Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8–28.7, P = 0.021) and UC (22.6 kg, 21.0–28.0, P = 0.041) compared with controls (25.0 kg, 22.0–32.5). Handgrip strength correlated with BCM ( r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0–41.1, P = 0.005) and UC (31.0 kg, 27.3–37.8, P = 0.001) compared with controls (36.0 kg, 31.0–52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. Conclusion In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.

Sarcopenia is prevalent in patients with Crohnʼs disease in clinical remission

Patients with Crohn's disease (CD) are prone to osteoporosis. A loss of muscle mass, called sarcopenia, is responsible for an increased risk of disability. Many factors associated with osteopenia also decrease muscle mass. The aim of the present study was to measure the prevalence of sarcopenia in CD patients in remission and uncover its relationship with osteopenia. In all, 82 CD patients (43 female/39 male; 36 +/- 14 years; body mass index [BMI] 21.1 +/- 3.4) and 50 healthy volunteers (30F/20M; 39 +/- 13 years; BMI 22.2 +/- 2.5) were studied. Body composition was assessed using dual-energy x-ray absorptiometry. Sarcopenia was defined as an appendicular skeletal muscle index (ASMI) below 5.45 kg/m(2) for women and 7.26 for men. Osteopenia was defined as a T-score for bone mineral density (BMD) (g/cm(2)) below -1.0. In all, 60% of CD patients were found to be sarcopenic and 30% osteopenic, compared to 16% and 4% of controls, respectively (P < 0.01). ASMI was significantly lower in patients than in controls (6.0 +/- 1.1 versus 6.5 +/- 1.2; P < 0.05). Sarcopenic patients had significantly (P < 0.01) lower BMI (20.0 +/- 3.5 versus 22.7 +/- 2.8 kg/m(2)), lean mass (41.5 +/- 9.1 versus 48.1 +/- 9.1 kg), and BMD (1.09 +/- 0.12 versus 1.15 +/- 0.08 g/cm(2)) than nonsarcopenic patients; 91% of sarcopenic patients were also osteopenic. ASMI correlated with BMD (r = 0.46; P < 0.01) and BMI (r = 0.38; P < 0.01). The prevalence of sarcopenia is high in young CD patients and strongly related to osteopenia. These 2 phenomena may share similar mechanisms. Simultaneous screening for sarcopenia and osteopenia may be useful in CD patients.

Comparison between handgrip strength, subjective global assessment, anthropometry, and biochemical markers in assessing nutritional status of patients with Crohnʼs disease in clinical remission

Comparison between handgrip strength, subjective global assessment, anthropometry, and biochemical markers in assessing nutritional status of patients with Crohnʼs disease in clinical remission

Comparison between handgrip strength, subjective global assessment, anthropometry, and biochemical markers in assessing nutritional status of patients with Crohnʼs disease in clinical remission

Comparison between handgrip strength, subjective global assessment, anthropometry, and biochemical markers in assessing nutritional status of patients with Crohnʼs disease in clinical remission

Current perspectives of autologous stem cell transplantation for severe juvenile idiopathic arthritis

The majority of children with Juvenile Idiopathic Arthritis can nowadays be treated adequately. However despite the use of combinations of antirheumatic drugs, corticosteroids and the newer so called biologicals (blocking the TNF, Interleukin 1 or Interleukin 6 pathways) a proportion of children with arthritis remain resistant also to these therapies and suffer from a very severe, debilitating and potentially fatal disease. For such children autologous stem cell transplantation (ASCT) is successfully performed since 1997. Here we describe the long term outcome of the initial cohort of children with resistant Juvenile Idiopathic arthritis, treated with ASCT. The initial cohort of children was treated with a conditioning regimen containing Cyclophosphamide, anti thymocyte globulins and low dose Total Body irradiation. Overall favourable responses were seen, with a drug free remission rate of 50–55 %. In the more recent years late relapses were noted with lower percentages for drug free long term outcome. Special emphasis is given on 2 cases showing very late relapses, occurring after 7 and 9 years. The observed relapses are often less severe compared to the situation before SCT and can be treated successfully with conventional drugs in the majority of cases. More recently, ASCT was performed in 4 JIA children with a fludarabin containing regimen in stead of low dose TBI. With a 4 to 5 year follow up, these 4 patients are all in drug free full remission. Allogeneic transplant with an HLA matched family donor was reported in 2 JIA cases. Follow up of 1 and 3 year is sofar show clinical disease remission and tapering of medition. In conclusion, given the favourable long term outcome, SCT remains a valuable treatment option for children with drug resistant JIA.

A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

The current study was conducted to determine the effect of goserelin and bicalutamide on progression-free survival (PFS) in patients with epithelial ovarian cancer who were in second or greater complete disease remission. Patients received bicalutamide at a dose of 50 mg orally daily and goserelin at a dose of 3.6 mg subcutaneously every 4 weeks. CA 125 was obtained monthly, with computed tomography performed every 3 months. Correlative studies included serum luteinizing hormone, follicle-stimulating hormone, vascular endothelial growth factor, free testosterone, and androstenedione and the germline polymorphisms CYP19A1 and androgen receptor. Between October of 2000 and October of 2002, 35 patients were enrolled. Three patients (9%) received therapy at the time of first disease remission and were removed from the study, and 1 patient (3%) was removed for liver function test abnormalities. The most frequent toxicities were grade 1 alkaline phosphatase (54%), fatigue (57%), and hot flashes (42%) based on the National Cancer Institute common toxicity scale, version 2.0. The PFS for patients receiving protocol therapy in second disease remission (21 patients) was 11.4 months (95% confidence interval [95% CI], 10.2-12.6 months). The PFS for patients receiving protocol therapy in third or fourth disease remission (11 patients) was 11.9 months (95% CI, 10.8-14.1 months). The percentage of patients remaining in second disease remission at given times are: 100% at 3 months, 100% at 6 months, 72% at 9 months, 47% at 12 months, 28% at 15 months, 22% at 18 months, 19% at 21 months, and 13% at 24 months. There were no associations noted between androgen receptor repeat number, genotype, allelotype, or haplotypes and PFS. The use of goserelin and bicalutamide did not appear to prolong PFS in patients with epithelial ovarian cancer in second or greater complete disease remission. The number of patients in disease remission at given time points may serve as a clinical trial endpoint for future studies of consolidation therapy.

Effect of moderate acute aerobic exercise in patients with Crohn's disease in clinical remission

Effect of moderate acute aerobic exercise in patients with Crohn's disease in clinical remission

Muscle Performance in Patients With Crohnʼs Disease in Clinical Remission

Because patients with Crohn's disease (CD) often show increased energy expenditure, nutritional deficiencies, and general fatigue, all which may persist after a flare, we hypothesized that CD could alter muscle mass and function. This study aimed to assess muscle strength and endurance in CD patients in clinical remission and the influencing factors. Forty-one outpatients (17 men and 24 women; age, 37 +/- 10 yr), in remission (CD Activity Index < 150) for > 3 months, and 25 age-matched healthy controls (10 men and 15 women; age, 37 +/- 13 yr) were evaluated. Evaluation included a sit-up test, hand-grip strength test, hand-grip endurance test, lower limb strength test, and lower limb endurance test (LE), as well as a measure of physical activity. No significant difference was found between CD and control groups regarding weight, height, body mass index, fat mass, and fat-free mass. Strength performance was lower in CD subjects compared with controls, particularly for lower limb indexes: lower limb strength test (-24.6%, P < 0.001), LE (-25.8%, P < 0.001), and sit-up test (-25.1%, P < 0.001). Previous disease severity, disease duration, the cumulative dose of glucocorticosteroids, current inflammation, and global habitual physical activity did not affect muscle performance. A recent use of steroids improved LE. CD patients in clinical remission have decreased muscle function that may affect their quality of life. This pattern is reflected by reduced strength and endurance indexes, particularly for lower limbs. The reasons for these changes need further study. Strength training should be assessed in these patients.

Pregnancy in Wegener?s granulomatosis: successful treatment with intravenous immunoglobulin

We present the case of a women diagnosed with Wegener's disease at the age of 26 years, refractory to corticosteroid and cyclophosphamide therapy. Treatment with intravenous immunoglobulin (IVIg) was started, leading to partial clinical remission of disease. During IVIg treatment she became pregnant. IVIg therapy was continued, the disease went into remission, and after 40 weeks the patient delivered a healthy boy. After 6 months from the delivery, the patient became pregnant again. Now she is at the 22nd week of pregnancy and she is doing very well. This case supports the beneficial effect of IVIg in Wegener's granulomatosis and illustrates its safety and efficacy during pregnancy.

Wegener's Granulomatosis: CT Evolution of Pulmonary Parenchymal Findings in Treated Disease

To determine the computed tomography (CT) evolution of various pulmonary manifestations of Wegener's Granulomatosis (WG) following appropriate pharmacologic treatment of the disease. Eleven patients with WG were identified, each of whom had had at least two CT examinations. CTs were reviewed retrospectively to identify pulmonary lesions of WG. Lesions were categorized as nodules, cavities, lobar atelectasis, pulmonary bands, or infiltrates. To determine the evolution of each individual lesion following pharmacologic treatment, the authors compared the lesions at presentation to their appearances on follow-up CT examinations. A total of 112 lesions were identified (nodules = 70, cavities = 25, lobar atelectasis = 7, pulmonary bands = 6, infiltrates = 4). The mean time interval between CT examinations was 34 weeks (range: 3-248 weeks). Treated nodules tended to become smaller (33/70, 47%), to resolve (14/70, 20%), or to remain unchanged (8/70, 11%). However, the nodules became larger or cavitated in a substantial minority of cases (13/70, 19% and 2/70, 3%, respectively). Although more than half of the treated cavities became smaller (13/25, 52%) or resolved (1/25, 4%), many evolved into nodules (6/25, 24%) or enlarged (5/25, 20%). All cases of lobar atelectasis (14/14, 100%) and transpulmonary bands (6/6, 100%) were unchanged at follow-up. All infiltrates were either resolved (3/4, 75%) or substantially improved (1/4, 25%). WG has a wide spectrum of pulmonary manifestations. Nodules, cavities, and infiltrates are among the most common lesions seen on CT. Although these findings tend to improve with treatment, mixed responses are not uncommon. Lobar atelectasis and transpulmonary bands tend not to improve, even with the occurrence of clinical disease remission.

Wegener's Granulomatosis: CT Evolution of Pulmonary Parenchymal Findings in Treated Disease

Objective: To determine the computed tomography (CT) evolution of various pulmonary manifestations of Wegener's Granulomatosis (WG) following appropriate pharmacologic treatment of the disease. Methods: Eleven patients with WG were identified, each of whom had had at least two CT examinations. CTs were reviewed retrospectively to identify pulmonary lesions of WG. Lesions were categorized as nodules, cavities, lobar atelectasis, pulmonary bands, or infiltrates. To determine the evolution of each individual lesion following pharmacologic treatment, the authors compared the lesions at presentation to their appearances on follow-up CT examinations. Results: A total of 112 lesions were identified (nodules = 70, cavities = 25, lobar atelectasis = 7, pulmonary bands = 6, infiltrates = 4). The mean time interval between CT examinations was 34 weeks (range: 3–248 weeks). Treated nodules tended to become smaller (33/70, 47%), to resolve (14/70, 20%), or to remain unchanged (8/70, 11%). However, the nodules became larger or cavitated in a substantial minority of cases (13/70, 19% and 2/70, 3%, respectively). Although more than half of the treated cavities became smaller (13/25, 52%) or resolved (1/25, 4%), many evolved into nodules (6/25, 24%) or enlarged (5/25, 20%). All cases of lobar atelectasis (14/14, 100%) and transpulmonary bands (6/6, 100%) were unchanged at follow-up. All infiltrates were either resolved (3/4, 75%) or substantially improved (1/4, 25%). Conclusion: WG has a wide spectrum of pulmonary manifestations. Nodules, cavities, and infiltrates are among the most common lesions seen on CT. Although these findings tend to improve with treatment, mixed responses are not uncommon. Lobar atelectasis and transpulmonary bands tend not to improve, even with the occurrence of clinical disease remission.

Corticosteroids for maintaining remission of Crohn's disease.

To evaluate the effectiveness and safety of conventional systemic corticosteroid therapy in maintaining clinical remission in Crohn's disease. A computer-assisted search of the on-line bibliographic database MEDLINE of studies published in English, French, Spanish, Italian and German between 1966 and May, 1998. Manual searches of the reference lists from the potentially relevant studies were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Proceedings from major gastrointestinal meetings were also manually searched from 1985 to 1997 in order to identify unpublished studies. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. Randomized double-blind placebo-controlled trials involving patients of any age with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the presence of no symptoms or only mild symptoms at the time of entry into the trial. The experimental treatment consisted of oral conventional corticosteroid therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was used as the outcome measure of interest. Eligible studies were selected by 4 reviewers and data were extracted onto standardized data extraction forms. Disagreements in eligibility or data extraction were resolved by consensus. Data were converted into individual 2x2 tables for each study. The presence of significant heterogeneity among studies was tested using the chi-square test. The 2x2 tables were synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed effects model was used for the pooling of data. Four studies were initially judged as being eligible for inclusion. After obtaining additional information on one of the studies it was excluded because it was not double-blind. The total number of subjects included in the analysis at the time points of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161, 138 and 87 for the control group. The odds ratios for relapse on active treatment and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82 (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. The numbers needed to treat with corticosteroids to prevent one additional relapse were 24, 35, 15 respectively. The use of conventional systemic corticosteroids in patients with clinically quiescent Crohn's disease does not appear to reduce the risk of relapse over a 24 month period of follow-up.

Is Helicobacter pylori infection associated with chronic idiopathic urticaria?

BackgroundChronic idiopathic urticaria (CIU) is one of the most frequent skin diseases, however its causes remain unknown in the vast majority of cases. There is increasing evidence for systemic effects of gastric Helicobacter pylori infection, which may result in extra gastrointestinal disorders. Although CIU can result from several causes, a possible relationship between chronic urticaria and Helicobacter pylori has been recently suggested ObjectiveThe aim of this study is to determine the prevalence of Helicobacter pylori infection in a series of patients with CIU, and measure the effectiveness of eradication therapy on the skin disease MethodWe assess Helicobacter pylori infection by 13C urea breath test (UBT) in 21 CIU patients. Amoxicillin, clarithromycin, and omeprazole were given to infected patients for seven days. The results of therapy were assessed by urea breath test one month after therapy. Urticaria and gastrointestinal symptoms were assessed on enrolment and for six months after eradication ResultsPrevalence of Helicobacter pylori infection was of 71.4 % (15/21). There were no differences concerning age (31.83 vs. 33.82 years) and duration of symptoms (38.40 vs. 35.38 months) in patients with respectively positive and negative UBT. Helicobacter pylori eradication rate was of 80% (12/14). Three patients had clinical improvement with total resolution of urticaria starting immediately after eradication therapy, being able to completely withdrawn antihistamine and corticosteroids therapy without complaints. In relation to the rest of the patients, these three had smaller duration of urticaria disease (14.3 vs. 43.7 months; p = 0.038) and greater titters in the UBT results (42.39 vs. 25.81; p = 0.073) DiscussionAlthough some authors found convincing evidence of the involvement of Helicobacter pylori as one possible cause of chronic urticaria, our results have failed to confirm the existence of this etiological association. The most remarkable finding was that those patients who had clinical remission of disease were the ones with greater UBT titters suggesting a role for the amount of colonization by Hp in the pathogenesis of urticaria disease

Detection of cell free Epstein-Barr virus DNA in sera from patients with nasopharyngeal carcinoma.

The detection of tumor-derived DNA within the circulation of patients with malignant disease using polymerase chain reaction (PCR)-based strategies has opened a new avenue for the diagnosis and monitoring of these patients. Because of the universal association of Epstein-Barr virus (EBV) with the nonsquamous type of nasopharyngeal carcinoma (NPC; World Health Organization types II and III), the detection of cell free EBV DNA in sera from patients with NPC may be a valuable tool for monitoring the progress of tumors or to provide advanced warning of tumor recurrence. Serum samples were obtained from different patients, and cell free EBV DNA was detected with a conventional PCR approach. A total of 134 patients were sampled, including 36 patients with primary NPC, 28 control patients, 18 patients suffering from locoregional recurrence, 7 patients with distant metastasis, and 45 patients with NPC in clinical remission. A conventional PCR approach employing standard 35-cycle and 50-cycle reactions was used to detect cell free EBV genomes. Results from the two PCR cycles were compared to provide a semiquantitative picture of the relative quantity of EBV genome in each serum sample. The EBV DNA detection rates, i.e., the rates of positive detection, for 35-cycle and 50-cycle PCR analyses, respectively, were 38.9% and 75% for patients with primary NPC, 3.5% and 10.7% for control patients, 27.8% and 88.9% for patients with locoregional disease recurrence, 71.4% and 100% for patients with distant metastasis, and 7.1% and 36.5% for patients with disease in clinical remission. The rates of positive detection among patients with active disease all appeared to be significantly greater compared with the rates among patients with disease in clinical remission. Longitudinal data for six patients with recurrent tumors revealed a close correlation between the relative quantity of circulating cell free EBV genomes and the disease course of these patients. The sensitivity, specificity, positive predictive value, and negative predictive value of the 50-cycle PCR analysis for detecting recurrent disease were 92%, 63.5%, 42.6%, and 96.4%, respectively. This study demonstrated that, by using a 50-cycle PCR-based approach, high sensitivity and high negative predictive value for detecting recurrent disease can be obtained from the detection of the cell free EBV genome in sera from patients with NPC. The 50-cycle PCR analysis, therefore, may provide a simple, clinically useful adjuvant method for monitoring patients with NPC.

Abnormal bone turnover in long-standing Crohn's disease in remission.

A high prevalence of osteoporosis is found in patients with Crohn's disease. The pathogenesis of this condition seems to be multifactorial and its pathophysiology is still not completely understood. To elucidate the pathophysiology of osteopenia in quiescent Crohn's disease. Bone turnover was studied in 26 patients (13 males and 13 females) with long-standing quiescent Crohn's disease and small bowel involvement. Bone mineral density was assessed by dual energy X-ray absorptiometry. Biochemical markers for bone formation (osteocalcin and bone-specific alkaline phosphatase) and for bone resorption (deoxypyridinoline and collagen type I C-terminal crosslinks) were measured. Urinary calcium excretion was determined. Markers for bone formation were significantly lower in patients than in controls (osteocalcin: P= 0.027, bone-specific alkaline phosphatase: P < 0.001), but both bone resorption markers were not significantly different. Urine calcium excretion was significantly decreased in patients (P=0.002) compared to controls. Bone mineral density of the lumbar spine was significantly and inversely correlated with bone-specific alkaline phosphatase and collagen type I C-terminal crosslinks. Bone turnover in long-standing Crohn's disease in clinical remission is characterized by suppressed bone formation and normal bone resorption. Urine calcium excretion is decreased. Hence, interventions and therapy should be directed towards the improvement of bone formation.

Oral nutritional supplementation is effective in the maintenance of remission in Crohn's disease

Background. Enteral feeding with either elemental or polymeric diets is an established primary therapy for active Crohn's disease. However, the role of supplementing normal food with elemental diet in the long-term management of Crohn's disease has hitherto not been explored. Patients and methods. A series of 39 consecutive patients with Crohn's disease in clinical remission were studied. Of these, 21 patients (Group 1) received oral nutritional supplementation, taken in addition to their normal diet. Their outcome (relapse rate, Crohn's disease activity index, inflammatory markers) was compared with that of 18 patients (Group 2), who were maintained on a normal unrestricted diet over an observation period of 12 months. Results. A total of 17 patients (81%) tolerated the nutritional supplementation. On an intention-to-treat basis, 10 patients (48%) remained in remission for 12 months, compared to 4 18 (22%) patients in Group 2, p<0.0003. Their Crohn's disease activity index and CRP remained stable while their weight and body mass index improved during the period of nutrition therapy. Seven patients in Group 1 and 14 in Group 2 relapsed at a mean of 7.4±0.9 and 6.2±0.4 months, respectively. The response to nutrition supplement was independent of age, sex, disease duration or location. Four patients (1945) were intolerant to enteral feeding. Conclusions. Nutritional supplementation is safe, well tolerated and effective in the long-term management of patients with quiescent Crohn's disease.