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PubMed1999

Quality of life in Korean patients with inflammatory bowel diseases: ulcerative colitis, Crohn's disease and intestinal Behçet's disease.

Health-related quality of life (HRQOL) is an important outcome factor in chronic diseases such as inflammatory bowel disease (IBD). This study used the Korean translation of the disease-specific, self-administered Inflammatory Bowel Disease Questionnaire (IBDQ) to compare HRQOL in ulcerative colitis (UC; n = 98), Crohn's disease (CD; n = 49), and intestinal Behçet's disease (BD; n = 34). In addition to the current status, patients were asked retrospectively to recall their symptoms at the beginning and during the worst period of their disease. Disease activity was measured by St. Mark's Activity Index, Crohn's disease Activity Index (CDAI), and the Harvey-Bradshaw Index (HBI). In all IBD patients, including those with BD, the IBDQ total score during the worst period was significantly lower than that at present and that at the beginning of the disease. However, there were no significant differences between groups regarding the total IBDQ score or its various dimensions. In UC a strong correlation between IBDQ scores and St. Mark's Activity Index was observed (r = -0.708, P < 0.001). IBDQ scores were also highly correlated with CDAI and HBI in both CD (r = -0.506, P < 0.001 for CDAI; r = -0.600, P < 0.001 for HBI) and BD (r = -0.687, P < 0.001 for CDAI; r = -0.531, P < 0.001 for HBI). However, the current IBDQ score was not related to demographic parameters such as gender, age, educational status, economic status, and marital status as well as disease factors such as duration of disease, history of operation or hospital admission, extent of disease in UC, involved region in CD, and clinical type in BD. We conclude that the Korean IBDQ is a responsive and promising instrument for measuring HRQOL of IBD patients in clinical trials. In addition, the IBDQ can be helpful in developing a disease-specific activity index in BD.

Adolescent↗
PubMed2001

Galantamine for Alzheimer's disease.

BACKGROUND: Galantamine (also called galanthamine, marketed as Reminyl (Janssen)) can be isolated from several plants, including daffodil bulbs, and now synthesized. Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor. It is also an allosteric modulator at nicotinic cholinergic receptor sites potentiating cholinergic nicotinic neurotransmission. A small number of early studies showed mild cognitive and global benefits for patients with Alzheimer's disease, and recently several multicentre clinical trials have been published with positive findings. Galantamine has received regulatory approval in Sweden, is available in Austria, and awaits marketing approval in the United States, Europe, and other countries. OBJECTIVES: The objective of this review is to assess the clinical effects of galantamine in patients with probable Alzheimer's disease, and to investigate potential moderators of an effect. SEARCH STRATEGY: The Cochrane Dementia Group specialized register of clinical trials was searched using the terms 'galantamine,' and 'galanthamine' (15 February 2000) as was the Cochrane Controlled Trials Register (2000, Issue 2). These terms were also used to search the following databases: EMBASE, MEDLINE, PsychLit; Combined Health Information Database, NRR (National Research Register), ADEAR (Alzheimer's Disease Education and Referral Centre clinical database, BIOMED (Biomedicine and Health), Glaxo-Wellcome Clinical Trials Register, National Institutes of Health Clinical Trials Databases, Current Controlled Trials, Dissertation Abstracts (mainly North American dissertations) 1961-1994, Index to UK Theses (British dissertations) 1970-1994. Published reviews were inspected for further sources. Additional information was collected from an unpublished investigational brochure for galantamine. SELECTION CRITERIA: Trials selected were randomized, double-blind, parallel-group, and unconfounded comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in people with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers and pooled where appropriate and possible. The pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Intention-to-treat and observed cases data were both reported, if the data were available to be reported. -Outcomes of interest include the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). - Potential moderating variables of a treatment effect included trial duration and dose. MAIN RESULTS: Seven trials were identified that met criteria for entry, with 6 being Phase II or III industry-sponsored multicentre trials. One was of 12 weeks duration; one of 5 months; one of 29 weeks; and the rest of 6 months duration. Trials of 5 months or more were aggregated in the analyses as '6 months'. Overall, galantamine showed significant treatment effects at daily doses of 16-32 mg/d for trials of 3- to 6-months duration. For global ratings, trials of 3 months duration with doses of 24-32mg/d (Odds Ratio (OR) 2.2; 95%CI 1.4 to 3.7) and 36mg/d (OR 3.3; 95%CI 1.2 to 9.3) were statistically significant in favour of treatment. For trials of 6 months duration (5-months to 29 weeks), only doses of 8mg/d failed to be statistically significant (24mg: OR 2.0; 95%CI 1.5 to2.5; 32mg: OR 1.9; 95%CI 1.4 to 2.5). For cognitive function over 6 months duration: at a 24mg/d, improvements measured -3.5 points (k=3; 95%CI -4.3 to -2.8) on weighted mean difference on the ADAS-Cog scale, and -4.0 points at 32mg/d (k=2; 95%CI -5.0 to -3.0). Both observed cases (WMD 3.8; 95%CI 0.3 to 7.3) and intention to treat analyses using the Disability Assessment of Dementia gave statistically significant results in favour of treatment for daily doses of 32mg for 6 months duration. The small number of trials available for analysis, however, limited the power of analyses to detect differences. Galantamine consistently failed to show statistically significant treatment effects at doses of 8mg/day. Galantamine's adverse effects appear similar to those of other cholinesterase inhibitors, in that it tends to produce gastrointestinal effects acutely and with dosage increases. Overall, people treated with galantamine at doses of 24-32 mg/d were more likely to discontinue participation in most trials than were people treated with lower doses or placebo, but in the one trial with a slower rate of titration the discontinuation rate was not significantly greater than placebo for the 16 mg/day dose. (ABSTRACT TRUNCATED)

Alzheimer Disease↗
PubMed2000

Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants.

BACKGROUND: Many preterm babies who survive, having had respiratory distress syndrome (RDS) or not, go on to develop chronic lung disease (CLD). This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. OBJECTIVES: To determine if late (> 3 weeks) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the treatment of chronic lung disease (CLD) in the preterm infant. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment initiated at > 3 weeks of age in preterm infants with CLD were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality before discharge, failure to extubate, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding, bowel perforation, echodensities on ultrasound scan of brain, need for home oxygen, glycosuria, need for late rescue with dexamethasone, cerebral palsy in survivors and blindness in survivors were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Delayed steroid treatment had no effect on mortality. The only beneficial effects were reductions in failure to extubate by 7 or 28 days, need for late rescue treatment with dexamethasone, chronic lung disease at 36 weeks, and discharge to home on oxygen therapy. There was no increase in risk of infection, necrotising enterocolitis, or gastrointestinal bleeding. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no effect on blindness. There were increases in long-term neurologic sequelae including abnormal neurologic examination and cerebral palsy, the latter of borderline statistical significance. REVIEWER'S CONCLUSIONS: The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. There is a worrying increase in adverse neurological outcomes in infants treated with postnatal steroids (see also Review of Early Postnatal corticosteroids). Corticosteroids should be reserved for infants who cannot be weaned from mechanical ventilation. The dose of dexamethasone and the duration of any course of treatment should be minimised.

Anti-Inflammatory Agents↗
PubMed2000

Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants.

BACKGROUND: Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects. OBJECTIVES: To determine if postnatal corticosteroid treatment is of benefit in the prevention of chronic lung disease (CLD) in the preterm infant. This review examines the outcome of trials where preterm infants at risk of CLD were given postnatal steroids within 96 hours after birth. SEARCH STRATEGY: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. SELECTION CRITERIA: Randomised controlled trials of postnatal corticosteroid treatment within 96 hours of birth (early) in high risk preterm infants were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, failure to extubate, pulmonary air leak, survival without chronic lung disease, CLD defined at 28 days postnatal age and 36 weeks post menstrual age, patent ductus arteriosus (PDA), severe intraventricular hemorrhage (IVH), infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), gastrointestinal bleeding and longterm outcome were abstracted and analysed using Revman 4.0.4. MAIN RESULTS: Fifteen randomised controlled trials of early postnatal corticosteroid treatment of preterm babies at risk of developing CLD were identified. A meta-analysis of these trials demonstrates benefits as regards earlier extubation, decreased risks of CLD at both 28 days and 36 weeks, death or CLD at 28 days, and PDA. There was an almost significant reduction in the risk of pulmonary air leak and in death or CLD at 36 weeks in the babies treated with early corticosteroids. There were no differences in the rates of neonatal mortality, infection, severe ROP, severe IVH, NEC and pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects and the risks of hyperglycaemia and hypertension were also increased. Several adverse neurological effects were found at follow-up examinations of survivors treated with early steroids: abnormal neurological examination, cerebral palsy and developmental delay. REVIEWER'S CONCLUSIONS: The benefits of early postnatal corticosteroid treatment (< 96 hours) may not outweigh the known or potential adverse effects of this treatment. Gastrointestinal effects early in the neonatal period and neurological effects seen at follow-up mean that current use of early postnatal steroids needs to be reconsidered. There is a compelling need for the long term follow-up and reporting of late outcomes, especially neurologic and developmental outcomes, among surviving infants who participated in all randomized trials of early postnatal corticosteroid treatment. The role of inhaled steroids remains to be elucidated.

Anti-Inflammatory Agents↗
PubMed2000

Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review was to assess the risks and benefits of administration of a diuretic acting on the loop of Henle (loop diuretic) in preterm infants with or developing chronic lung disease (CLD). Primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least 5 days of age were all randomly allocated to receive a loop diuretic either enterally or intravenously. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included toxicity and pulmonary mechanics (e.g., lung compliance and airway resistance). DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: The only loop diuretic used in the studies which met the selection criteria was furosemide. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for 1 hour. Chronic administration of furosemide improves both oxygenation and lung compliance. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of furosemide improve lung compliance. Chronic administration of intravenous or enteral furosemide improves oxygenation. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.

Chronic Disease↗
PubMed1995

Serum interleukin-6 is related to disease activity but not disease specificity in inflammatory bowel disease.

Interleukin-6 (IL-6) has a major function in the regulation of the inflammatory process. We aimed to define its role as a parameter of disease activity and extent in inflammatory bowel disease. Serum concentrations of IL-6 were measured in 28 patients with Crohn's disease (CD) and in 15 with ulcerative colitis (UC) before starting corticosteroid treatment. Disease activity was measured by standard activity indexes. Serum IL-6 levels were increased in patients with CD (36 +/- 8 pg/ml; p < 0.001) and UC (10 +/- 4 pg/ml; p < 0.05) as compared with 25 control patients. A significant correlation between serum IL-6 concentrations and disease activity was found in patients with CD as well as in patients with UC (active CD: 73 +/- 14 pg/ml, inactive disease: < 10 pg/ml, p = 0.003; active UC: 26 +/- 10 pg/ml, inactive disease: < 10 pg/ml, p = 0.004). IL-6 serum levels were related to the acute-phase reactant c-reactive protein (r = 0.51, p < 0.01) in CD patients. The serum IL-6 concentrations were more pronounced in CD of the colon than in disease limited to the small bowel (p < 0.05). In patients with CD as well as in patients with UC, IL-6 serum concentrations showed a higher sensitivity for disease activity (94 and 83%) than serum c-reactive protein levels. In patients without corticosteroid treatment, the IL-6 serum concentration is related to disease activity in CD as well as UC. Serum IL-6 levels show a higher correlation with disease activity than c-reactive protein levels.

Adult↗
PubMed1989

Noninfectious diseases, metabolic diseases, toxicities, and neoplastic diseases of South American camelids.

Although the SAC generally are healthy and tolerant of a wide variety of management schemes, a number of noninfectious diseases have been documented to occur, affecting all body systems. Gastrointestinal diseases appear to be the most common afflictions, particularly dental diseases, indigestion, ulceration of the third compartment, and the various causes of colic, such as enteritis, peritonitis, and intestinal accidents. Diseases of the urinary system (urolithiasis, amyloidosis, and glomerulonephritis in particular), the nervous system (especially various compressive lesions of the spinal cord), and the respiratory system (such as obstructive pulmonary diseases) are not uncommon. Diseases of the cardiovascular system (other than congenital defects), hemolymphatic system, and nonsurgical diseases of the musculoskeletal system only rarely are encountered. Heat stress appears to be a very common problem in certain areas, but other metabolic diseases (ketosis, hypocalcemia, and hypothyroidism) are of minor importance. It is assumed that SAC are susceptible to most of the same toxicities that affect domestic livestock species. The best documented examples appear to be the Ericaceae family of plants (laurels, rhododendrons, and so on) and the organophosphate chlorpyrifos. Neoplasia occasionally is seen; examples include lymphosarcoma, gastric squamous cell carcinoma, and adenocarcinoma. As the longevity of these species increases because of their pet status, neoplasia can be expected to become more common. The treatment of most of these conditions is based upon extrapolation from domestic ruminants.

Animals↗
PubMed1995

Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease.

Recent evidence, based upon immunocytochemical and histochemical analysis of brain cortical tissue from alzheimer's disease patients, has suggested that altered activity and/or distribution of the lysosomal proteases cathepsins B and D may be implicated in the abnormal protein processing pathway resulting in formation of the neurotoxic amyloid A4 peptide, characteristic of this neurodegenerative disorder. We have therefore compared, via biochemical assay techniques using conventional or specially synthesised (corresponding to protein cleavage points of relevant to A4 peptide formation) fluorogenic substrates, the levels of activity of the lysosomal proteases cathepsins B, D, H and L, and dipeptidyl aminopeptidases I and II in frontal cortex (grey/white matter) from control and Alzheimer's disease patients. For comparative purposes, activity levels of the above enzymes were also determined in frontal cortex tissue from cases with Lewy body dementia and Parkinson's disease, and in caudate tissue from control and Huntington's disease cases. There was no significant difference in activity for any protease types in tissue from control cases and cases with Alzheimer's disease, Lewy body dementia or Parkinson's disease, with the exception of reduced dipeptidyl aminopeptidase II activity in Lewy body dementia and Parkinson's cases. We have therefore been unable to confirm a potential role for lysosomal cathepsins in the characteristic neurodegeneration associated with Alzheimer's disease; however the finding of significant increases in activity of dipeptidyl aminopeptidase II, cathepsin H and cathepsin D specifically in cases with Huntington's disease is of particular note. We therefore suggest the potential role of the latter enzymes in the pathogenesis of Huntington's disease requires further investigation.

Aged↗
PubMed2001

Production of reactive oxygen species from aggregating proteins implicated in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases.

The deposition of abnormal protein fibrils is a prominent pathological feature of many different 'protein conformational' diseases, including some important neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), motor neurone disease and the 'prion' dementias. Some of the fibril-forming proteins or peptides associated with these diseases have been shown to be toxic to cells in culture. A clear understanding of the molecular mechanisms responsible for this toxicity should shed light on the probable link between protein deposition and cell loss in these diseases. In the case of the beta-amyloid (Abeta), which accumulates in the brain in AD, there is good evidence that the toxic mechanism involves the production of reactive oxygen species (ROS). By means of an electron spin resonance (ESR) spin-trapping method, we have shown recently that solutions of Abeta liberate readily detectable amounts of hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). We have also obtained similar results with alpha-synuclein, which accumulates in Lewy bodies in PD. Our data suggest that hydrogen peroxide accumulates during Abeta or alpha-synuclein incubation and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fenton's reaction. Consequently, we now support the idea that one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD, PD, and possibly some other protein conformational diseases, could be the direct production of ROS during formation of the abnormal protein aggregates. This hypothesis suggests a novel approach to the therapy of this group of diseases.

Alzheimer Disease↗
PubMed1999

Disease steps in multiple sclerosis: a longitudinal study comparing disease steps and EDSS to evaluate disease progression.

Clinical assessment of outcome in multiple sclerosis (MS) patients is problematic since the disease can affect different aspects of the central nervous system and follow a variable course. Recently, we developed Disease Steps, a simple approach for evaluating disease progression. Previously, we found that Disease Steps was easy to use, had uniformly distributed scores and low inter-rater variability. Our current objective was to test the long-term use of Disease Steps together with the most widely utilized clinical outcome measure in MS, the Expanded Disability Status Scale (EDSS) in assessing clinical progression. Over 4 years, 804 patients were classified using both EDSS and Disease Steps. Each patient was assessed at least twice. Follow-up results included annual status and time-to-event analysis examining median staying times within a level of Disease Steps or EDSS. We found that the two scales behaved similarly and correlated strongly with each other. For both Disease Steps and EDSS, patients with milder levels of disability and relapsing-remitting disease demonstrated a higher likelihood of changing scores over time and shorter median staying times compared to more disabled, chronic progressive patients. These findings have important implications for patient selection in clinical trials and for the design of future measurements of clinical outcome in MS. Furthermore, Disease Steps may serve as a simple, practical tool for the nonspecialty neurologist to follow patients over time and serve as a guide in therapeutic decision making. Our findings further document the general progressive nature of MS when a large cohort is followed in an MS specialty clinic over time.

Adult↗
PubMed1982

Juvenile nephronophthisis and medullary cystic disease--the same disease (report of a large family with medullary cystic disease associated with gout and epilepsy).

A large family with medullary cystic disease is described to show that juvenile nephronophthisis and medullary cystic disease should not be differentiated by age of onset and type of inheritance. The age at diagnosis of six family members with medullary cystic disease ranged from 4-32 years, and age at death from renal failure or commencement of dialysis from 7-48 years. A mother of two children with renal failure in early childhood has histological evidence of medullary cystic disease with normal renal function. We suggest that juvenile nephronophthisis and medullary cystic disease are the same conditions and that the disease be classified as medullary cystic disease, autosomal dominant or recessive form. When undertaking genetic counselling in the parents of children with medullary cystic disease, we suggest that renal biopsy may need to be considered even if their renal function is normal. Three patients presented with gout, and the possibility of an association with medullary cystic disease should be considered when more than one member of a family develops gout. Two patients died of status epilepticus, and epilepsy is probably an added association of medullary cystic disease.

Adolescent↗
PubMed1999

Adult linear IgA disease and chronic bullous disease of childhood: the association with human lymphocyte antigens Cw7, B8, DR3 and tumour necrosis factor influences disease expression.

Linear IgA disease and chronic bullous disease of childhood are both subepidermal autoimmune blistering diseases. Class I and II major histocompatibility locus (MHC) antigen typing was performed on 60 patients (26 chronic bullous disease of childhood, 34 adult linear IgA disease), and the findings were correlated with the clinical course. The typing was performed using a lymphocyte microcytotoxicity assay, and the results were compared with a reference population of U.K. organ donors. Analysis of the tumour necrosis factor (TNF) locus was performed using sequence-specific oligonucleotides on a dot blot in 51 patients and compared with a random control population and human lymphocyte antigen (HLA) DR3 matched controls. The disease was found to be significantly associated with HLA Cw7 (chi2 = 19.24, P = 0.001), B8 (chi2 = 9.89, P = 0.04) and DR3 (chi2 = 10.47, P = 0.014), all components of the common Caucasian haplotype. There was also a close association between the disease and possession of HLA DR2 or 3 (chi2 = 16.34, P = 0.001). A reduction in the incidence of DR1 and DR4 (alleles carrying the rheumatoid motif) was observed, which is more marked in the children (chi2 = 8.34, P = 0.039). In the childhood group there was an increased frequency of B8, DR3 and DQ2 compared with the adults which included five of 26 who were homozygous for these antigens, a feature not seen in the adults, which may account for the differences seen between the two groups. Possession of HLA B8, DR3 and DQ2 probably facilitates earlier presentation of the disease as there is no evidence from our results that the adults and children differ fundamentally in their MHC associations. The rare TNF2 allele was found in 29 of 51 patients (expected 8.2, chi2 = 18. 3, P = 0.0001). This was more marked in the children (19 of 26). Patients with the TNF2 allele had a longer disease duration (5.3 years TNF2, 3.0 years TNF1).

Adolescent↗
PubMed2000

The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis).

BACKGROUND: The membrane bound receptor OX40 (CD134) - a member of the TNF-R/NGF-R superfamily - is expressed on activated CD4+-T cells in humans and rodents. The interaction of OX40 with its ligand (OX40L) has been shown to be important in T-cell dependent B cell-stimulation and T-cell costimulation in vitro and in vivo. Several studies in experimental animal models for immunologically mediated GI-diseases have stressed the important role of the OX40-OX40L interaction for their manifestations. To assess if the OX40-OX40L interaction is also crucial in the pathogenesis of immunologically mediated diseases of the human gastrointestinal tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated, in a first line of experiments, the expression of OX40 in biopsy specimens of patients suffering from these diseases. METHODS: The biopsies were formalin fixed and paraffin-embedded and cut into 5 microm slides. To demask the antigen, the slides were consecutively cooked in citrate buffer for 20 min. Binding of anti-OX40 antibody was detected using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. RESULTS: Nine of 11 biopsy specimens of patients with celiac disease were OX40-positive; none of the 20 control duodenal biopsies demonstrated OX40-positivity; and all biopsies of patients with ulcerative colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively for OX40. One of the 20 control biopsies showed OX40 staining. DISCUSSION: OX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.

Adolescent↗
PubMed2003

Lupus headaches in childhood-onset systemic lupus erythematosus: relationship to disease activity as measured by the systemic lupus erythematosus disease activity index (SLEDAI) and disease damage.

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus (SLE). For headaches to be scored in the SLEDAI as a symptom of active disease, they have to be nonresponsive to narcotic analgesia. This may affect the overall estimation of disease activity, especially because headaches are common among children with SLE and narcotic analgesia is rarely used for headache therapy in paediatrics. Moreover, the importance of headaches for the development of damage and their relation to other clinical parameters and outcomes has not been well described for children with SLE. We reviewed the medical charts of an inception cohort of children (n = 63) who were newly diagnosed with SLE. Information on headaches and other disease parameters was obtained. Disease activity and damage were measured using the SLEDAI and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI), respectively. It has been shown that the accumulated burden of active disease as measured by serial SLEDAI scores over time is one of the best predictors of eventual damage to children with SLE. New-onset or significant increase of severe and/or persistent headaches (LHA) were reported in 43% of the patients during a mean follow-up of 3.6 years. LHA occurred preferentially among patients with elevated levels of antiphospholipid antibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with narcotics and thus considered for the measurement of disease activity in the SLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the need to intensify therapies. When used in children, the insensitivity of the SLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI to detect clinically important worsening of disease, or negatively impact on its ability to predict damage.

Adolescent↗
PubMed1994

Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease.

Subgroups of PsA have been described but their relationship to the mode of onset of arthritis, to DIP joint disease and to nail and skin disease remains controversial. Therefore, the pattern of disease was documented in 100 patients with PsA in whom the mode of onset was known. The patients were divided into six subgroups: monoarthritis; DIP joint disease only; oligoarthritis; polyarthritis; spondyloarthropathy and arthritis mutilans. Sixty-four patients changed pattern. Nail disease (67% of total) was more common in patients with DIP joint disease (27% of total) and was significantly associated with adjacent DIP joint disease. Skin and nail disease severity did not correlate with joint severity, joint activity or functional status, nor differ between subgroups. Therefore, the mode of onset does not predict outcome in the majority. The topographic association of nail disease and involvement of the adjacent DIP joints suggests a common local inflammatory mechanism.

Adolescent↗
PubMed2003

Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not a specific disease per se.

Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.

Adolescent↗
PubMed1988

[Clinical studies on abnormal thyroid stimulators in patients with Graves' disease. II. Clinical significance of measuring TSAb and TBII in patients with euthyroid Graves' disease and patients with hyperthyroid Graves' disease during antithyroid drug treatment].

To evaluate the clinical significance of TBII and TSAb activities in euthyroid and hyperthyroid Graves' disease, these two activities were measured in 8 patients with euthyroid Graves' disease and 29 patients with hyperthyroid Graves' disease during treatment with antithyroid drugs. In 8 patients with euthyroid Graves' disease, TBII activity was detectable only in one patient and TSAb activity detected in 3 patients, these detectabilities being much lower than those in hyperthyroid Graves' disease. However, 2 of 4 patients who had either TSAb or TBII came to have both activities, and one of them became overt hyperthyroid. In patients with hyperthyroid Graves' disease, detectabilities of these activities became lower as they became euthyroid with antithyroid drug treatment, but TSAb tended to be higher than TBII when they remained euthyroid for more than 4 months. Although the majority of the patients who had TSAb and/or TBII activities were T3 non-suppressible, patients with no TSAb and TBII activities did not necessarily show remission of the disease. The present results suggest that patients with euthyroid Graves' disease with both TBII and TSAb may be apt to become hyperthyroid, and that TSAb and TBII activities and T3 suppressibility may not be a definite criteria for the remission of Graves' disease.

Adolescent↗