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Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

At least 55 records · Page 3Linked to original sources
PubMed2003

Effects of maintenance electroconvulsive therapy on cognitive functions.

BACKGROUND: This study examined cognitive side effects of maintenance electroconvulsive (ECT) in comparison with maintenance pharmacotherapy after index ECT. METHOD: Clinical outcome data and neuropsychological measurements were compared in 11 maintenance ECT patients and 13 control patients treated with maintenance pharmacotherapy after index ECT. Data were gathered in a prospective naturalistic study during follow-up. RESULTS: There were no significant differences in patient characteristics and effects of index ECT between groups. In control patients treated with maintenance pharmacotherapy, cognitive function as well as depression ratings remained stable. During maintenance ECT neuropsychological test performance and depression ratings improved slightly but not significantly. CONCLUSIONS: Neuropsychological functioning during the maintenance phase of treatment did not differ between the two treatment groups. Cognitive function remained stable during maintenance ECT.

Aged↗
PubMed2003

Diagnostic strategy for the assessment of rheumatoid vasculitis.

OBJECTIVE: To determine the clinical features associated with histologically proven rheumatoid vasculitis (HRV) and the additional diagnostic value of serological markers in an inception cohort of 81 patients with rheumatoid arthritis (RA) suspected of RV. METHODS: The presence and number of recently developed extra-articular manifestations (EAMs) and a weighted EAM score, as well as the levels of serological markers, were compared between 31 patients with RA with histologically proven vasculitis and 50 patients with RA in whom vasculitis could not be documented histologically. The following markers were evaluated: circulating immune complexes, complement components C3 and C4, class-specific rheumatoid factors (IgM RF, IgG RF, IgA RF), antineutrophil cytoplasmic antibodies, antinuclear antibodies, antiendothelial antibodies, circulating intercellular adhesion molecule-1 and -3, circulating vascular cell adhesion molecule and E-selectin, cellular fibronectin, von Willebrand factor antigen, and C reactive protein. The diagnostic value of these markers, in addition to the clinical features, was evaluated with logistic regression analysis. RESULTS: Peripheral neuropathy or purpura/petechiae, or both, were the most important clinical features to discriminate patients with RA with and without histologically proven RV. The presence of a high number of EAMs and a higher weighted EAM score in patients with RA suspected of vasculitis were also associated with an increased probability of histologically proven RV. After adjustment for EAMs, only the combination of an increased serum IgA RF level and a decreased serum C3 level appeared to make an additional contribution to the diagnosis histologically proven RV. Evidence of systemic vasculitis was found in a muscle biopsy of the rectus femoris in 9/14 (64%) patients with vasculitis with neuropathy and in 3/11 (27%) patients with purpura/petechiae and vasculitis of the skin. CONCLUSIONS: In the diagnostic process of RV the presence of peripheral neuropathy and/or purpura/petechiae or a high weighted EAM score will increase the probability of histologically proven RV. Of the circulating factors previously suggested to be markers for RV only IgA RF and C3 further increase the probability of histologically proven RV and may be useful to guide diagnostic decisions.

Aged↗
PubMed2003

Behaviour at 2 years of age in very preterm infants (gestational age < 32 weeks).

AIM: The objective of this study was to determine behavioural outcome and risk factors for abnormal behaviour at 2 y corrected age in very premature infants in a regionally defined, prospective cohort study. METHODS: The Leiden Follow-Up Project on Prematurity includes all liveborn infants of < 32 wk gestational age, born in 1996/1997 (n = 266). Behaviour was assessed with the Child Behaviour Checklist 2-3. RESULTS: An analysis of 158 questionnaires of 206 survivors (77%) was carried out. Fourteen children (9%) had a total problem score > p90 ("clinical range"). This percentage is comparable with the 10% found in a sample of 2- to 3-y-olds from the Dutch general population. Univariate analysis showed higher syndrome scale scores in one or more of the Child Behaviour Checklist scales in children of lower gestational age, small for gestational age (birthweight < p10), with neurological abnormalities at term or at 2 y and of non-Dutch origin. Lower socioeconomic status and postnatal treatment with dexamethasone were associated with higher scores in the somatic problems scale and lower maternal age at birth with a higher total problem score. After correction for confounding variables, the associations between small for gestational age, neurological abnormalities at 2 y and the anxious/depressed and/or withdrawn scales remained significant. CONCLUSION: The prevalence of behavioural problems at 2 y corrected age in this cohort of very premature infants (gestational age < 32 wk) was comparable with that in a general population sample. Children born small for gestational age or with neurological abnormalities at 2 y of age had higher syndrome scale scores, mainly for anxious/depressed and/or withdrawn behaviour.

Child Behavior Disorders↗
PubMed2002

[Favorable current prognosis after HLA-identical bone marrow transplantation for children with required severe aplastic anemia; evaluation of 30 years of bone marrow transplantation at the Leiden University Medical Center].

OBJECTIVE: To evaluate the results of 30 years of allogeneic HLA-identical bone marrow transplantation (BMT) as the treatment for children with acquired severe aplastic anaemia. DESIGN: Retrospective, descriptive. METHOD: Of all patients who underwent an HLA-identical sibling-donor BMT for severe aplastic anaemia at the Department of Paediatrics, Leiden University Medical Center, in the period 1971-2000, and had a follow-up period of at least 1 year, the medical data were reviewed. The patients were split into 2 groups: patients transplanted before 1989 (n = 24), and patients who had their BMT from 1989 onwards (n = 20). This was due to a change in the treatment policy, namely a reduction in the period between diagnosis and BMT, resulting in fewer blood transfusions as well as changes in the prophylaxis against graft-versus-host disease (GvHD) from 1989 onwards (combination therapy using methotrexate and cyclosporin). RESULTS: There was an increase in the 1-year actuarial survival rate from 67% in the period before 1989 to 90% thereafter. The incidence of GvHD has significantly decreased since the introduction, in 1989, of the combination therapy using methotrexate and cyclosporin, with only 1/20 patients suffering from acute GvHD versus 13/24 prior to 1989 (p = 0.002). No patients acquired chronic GvHD after 1989, whereas before 1989, 10 patients had acquired this (p = 0.001). CONCLUSION: The prognosis of allogeneic HLA-identical sibling transplantation for paediatric patients with severe aplastic anaemia has considerably improved over the last 30 years due to improved supportive care, a significant decrease in GvHD and a shorter period between diagnosis and BMT, with the result that less blood transfusions have been required and less sensitisation has occurred. The long-term survival chance has increased to 90%.

Anemia, Aplastic↗
PubMed2002

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

Adult↗
PubMed2002

Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline parameters can predict radiographic damage, disability, and disease course at 12-year followup.

OBJECTIVES: To predict the long-term outcome of rheumatoid arthritis (RA) with respect to radiographic damage, disability, and disease course using baseline variables, and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions. METHODS: The 12-year outcome of 112 female RA patients from a prospective inception cohort was assessed by measuring the tertiles of radiographic damage (measured by the modified Sharp/van der Heijde method, SHS), disability (measured by the Health Assessment Questionnaire, HAQ), and severe disease course as defined by patients with either the 33% highest cumulative disease activity (area under the curve of all observed disease activity scores) or the highest tertile of radiographic damage. Patients in the lowest (mild) and highest tertile (severe) of each outcome measure were identified. All baseline parameters known to be associated with each outcome (demographic and socioeconomic parameters; disease duration; disease activity measures; laboratory measures including rheumatoid factor, HLA typing, percentage agalactosyl IgG, functional and radiographic measures) were entered into cross-validated stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes. Using the results of the logistic regression models, simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group. RESULTS: After 12 years, the lowest and highest tertiles were, respectively, 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ. Fifty-five patients had a severe disease course. Mild and severe radiographic damage could be predicted with an accuracy of 90% and 85%, respectively. Mild and severe HAQ could be predicted with an accuracy of 90% and 84%, respectively, and severe disease course with an accuracy of 81%. The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters: swollen joint count (SJC), Ritchie score, rheumatoid factor (RF), the presence of erosions, and the HAQ score. Additional knowledge of the HLA typing hardly improved the accuracy of the prediction. To predict outcome at the individual level, simple decision trees were constructed using the RF, HAQ, SJC, and presence of erosions at baseline. CONCLUSION: The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters.

Adult↗
PubMed2002

ABCA1 regulatory variants influence coronary artery disease independent of effects on plasma lipid levels.

The authors have previously shown that individuals heterozygous for ABCA1 mutations have decreased high density lipoprotein cholesterol, increased triglycerides and an increased frequency of coronary artery disease (CAD), and that single nucleotide polymorphisms (SNPs) in the coding region of the ABCA1 gene significantly impact plasma lipid levels and the severity of CAD in the general population. They have now identified several SNPs in non-coding regions of ABCA1 which may be important for the appropriate regulation of ABCA1 expression (i.e. in the promoter, intron 1 and the 5' untranslated region), and have examined the phenotypic effects of these SNPs in the REGRESS population. Out of 12 SNPs, four were associated with a clinical outcome. A threefold increase in coronary events with an increased family history of CAD was evident for the G-191C variant. Similarly, the C69T SNP was associated with a twofold increase in events. In contrast, the C-17G was associated with a decrease in coronary events and the InsG319 was associated with less atherosclerosis. For all these SNPs, the changes in atherosclerosis and CAD occurred without detectable changes in plasma lipid levels. These data suggest that common variation in non-coding regions of ABCA1 may significantly alter the severity of atherosclerosis, without necessarily influencing plasma lipid levels.

5' Untranslated Regions↗
PubMed2002

Body weight recovery, eating difficulties and compliance with dietary advice in the first year after stem cell transplantation: a prospective study.

Among healthcare professionals there is no consensus about the best policy to increase oral intake and promote recovery in the post-hospital phase after bone marrow or blood stem cell transplantation. In order to evaluate body weight recovery and compliance with dietary advice among these patients, we performed a prospective longitudinal study in the first year post transplant. At five time intervals (days 50, 75, 125, 200 and 350) patients received a nutritional questionnaire with items on nutrition-related symptoms, physical condition, body weight recovery and compliance with dietary advice. From the initial cohort of 135 patients 69 completed the study. Prevalence of eating difficulties was high (66% at day 50). Anorexia, dry mouth, altered taste, nausea and tiredness were the symptoms most strongly associated with eating difficulties. Compliance with dietary advice was poor. Conditioning regimen was found to be a prognostic factor for body weight status at day 350. In more than 50% of the TBI-treated patients body weight was not restored to 95% of the pretreatment value within 1 year after transplant. Future studies should focus on increasing energy and protein intake in the TBI-treated subgroup.

Adult↗
PubMed2002

Skin fibroblasts of children with idiopathic short stature show an increased mitogenic response to IGF-I and secrete more IGFBP-3.

OBJECTIVE AND PATIENTS: To study differences in cellular parameters of GH and IGF-I responsiveness in skin fibroblasts of 14 children with idiopathic short stature (ISS) treated with recombinant human GH and 13 children with normal height. Secondly, to investigate whether these cellular parameters can predict the growth response to GH treatment in children with ISS. DESIGN AND MEASUREMENTS: The mitogenic responsiveness to GH and IGF-I was investigated by 3H-Thymidine incorporation. Insulin-like growth factor binding protein-3 (IGFBP-3) levels in the media were measured by radioimmunoassay (RIA). RESULTS: No significant mitogenic responses were observed to various doses of GH (1000, 5000 or 50.000 ng/ml) in children with ISS or controls. ISS fibroblasts showed an increased mitogenic response to IGF-I (10 ng/ml) compared to controls (mean +/- SD 5.9 +/- 2.4- vs. 4.2 +/- 1.5-fold stimulation, P < 0.05), and GH enhanced this effect in both groups. IGFBP-3 secretion was increased in ISS fibroblasts when compared to controls under all conditions examined (basal, 200 and 5000 ng/ml GH, 10 ng/ml IGF-I for 24 and 48 h). High IGFBP-3 levels were related to low mitogenic responses to IGF-I or to GH + IGF-I in children with ISS (r = -0.7, P < 0.05), but not in controls. Within the ISS group, an enhanced mitogenic response to IGF-I in vitro was related to more extreme short stature before GH treatment (r = -0.70, P < 0.05) and to a relatively impaired response to high dose GH treatment in vivo (r = -0.52, P < 0.05). CONCLUSION: The demonstration of high IGFBP-3 levels and enhanced mitogenic response to IGF-I shows that ISS fibroblasts have different cellular characteristics compared to controls of normal height. It is hypothesized that in ISS an alteration of the signal transduction pathway between the GH receptor and IGFBP-3 synthesis results in a local imbalance with high IGFBP-3 levels and lower IGF-I availability for the IGF-I receptor. This may be reflected by an increased IGF-I responsiveness in vitro which is associated with an impaired capacity to grow in vivo.

Adolescent↗
PubMed2002

Biochemical markers of growth hormone (GH) sensitivity in children with idiopathic short stature: individual capacity of IGF-I generation after high-dose GH treatment determines the growth response to GH.

OBJECTIVE AND PATIENTS: To assess multiple dose-response relationships between three GH doses (1.5, 3.0 and 6.0 IU/m2) and nine different biochemical markers of GH sensitivity in a well-defined group of 17 children with idiopathic short stature (ISS). DESIGN AND MEASUREMENTS: Serum levels of IGF-I, IGF-II and IGFBP-3, and peripheral markers leptin, C-terminal propeptide of type I collagen (PICP) and N-terminal propeptide of type III collagen (PIIINP), alkaline phosphatase (AP) and osteocalcin (OC) were measured at the start and after 2 and 12 weeks of periods of no treatment, GH 1.5 IU/m2 and GH 3.0 IU/m2. Twelve-week washout periods were applied between the 12-week GH-treatment periods. High-dose GH treatment was given during the second year of study and all serum markers were measured at start, after 2 and 12 weeks and 1 year of GH 6.0 IU/m2. In 18 non-GH-treated children with ISS the same parameters were measured yearly. The bone resorption marker urinary deoxypyridinoline (DPD) was measured during 12-h day and night periods at start and after 2 weeks GH 1.5, 3.0 and 6.0 IU/m2. RESULTS: All markers were GH dependent, but the timing of maximal response varied among different markers. Height SDS at start, age at start and IGF-II at baseline were inversely related to the first-year growth response (r = -0.73, P = 0.001; r = -0.53, P = 0.03; and r = -0.53, P = 0.03, respectively). Some statistically significant correlations between biochemical responses on low GH doses (1.5 or 3.0 IU/m2) and second-year growth response were found, but these showed no consistent pattern. However, all changes in IGF-I SDS after GH 6.0 IU/m2 measured either after 2 or 12 weeks or 1 year correlated significantly with the second-year growth response (r = 0.55, P = 0.02; r = 0.81, P = 0.001; and r = 0.86, P < 0.001, respectively). Baseline or GH-stimulated levels of peripheral markers did not correlate with the growth response. CONCLUSION: The individual capacity of IGF-I generation after high-dose GH treatment (6.0 IU/m2) determines the growth response on high-dose GH treatment. Peripheral markers do not seem to play a role in growth prediction of children with ISS.

Biomarkers↗
PubMed2002

High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature.

BACKGROUND: Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3-9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period. AIMS: To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset. METHODS: Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment). RESULTS: In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls. CONCLUSIONS: High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.

Bone Development↗
PubMed2002

Pregnancy and oral contraceptive use do not significantly influence outcome in long term rheumatoid arthritis.

BACKGROUND: Oral contraceptives (OC) and pregnancy are known to have an influence on the risk of onset of rheumatoid arthritis (RA). Pregnancy itself has beneficial effects on the activity of the disease, with relapses post partum. It is not known, however, whether OC and pregnancies influence the ultimate outcome of RA. OBJECTIVES: To explore whether OC use and pregnancies influence the 12 year outcome in RA as measured by radiological damage and disability. METHODS: In a prospective inception cohort of 132 female patients with recent RA according to the 1987 American College of Rheumatology criteria-a cohort initially gathered to study the association between hormonal factors and the onset of RA-outcome was assessed in a follow up after 12 years. The outcome was evaluated in 112 (85%) women by the radiological damage of hands and feet as measured with the Sharp score modification van der Heijde (SHS), the damage of the large joints measured with the Larsen score (LS) of large joints (0-60), and the disability measured with the Health Assessment Questionnaire (HAQ). The median values of each outcome variable were calculated for several subgroups of patients stratified for OC use and pregnancies before and after onset of the disease and the tertiles of the total number of months of OC use and of pregnancies. The association of OC use and pregnancies before and after onset of the disease with the outcome variables was calculated using Spearman's rank correlation (r(s)). The combined influence of OC use and pregnancies on the SHS, LS, and HAQ at 12 years was estimated using ordinal polytomous logistic regression. RESULTS: The median values of the SHS, LS, and HAQ showed a trend towards less radiological joint damage and less disability in women with long term OC use and multiple pregnancies. This difference, however, was not significant, except for the HAQ score in women with three or more pregnancies in life. There was no association between pregnancies, however defined, and any parameter of RA outcome after 12 years (maximum r(s)=-0.10). The only significant correlation was found between OC use before symptom onset and the LS (r(s)=-0.22, p<0.05). The combination of hormonal variables explained no more than a maximum of 3% of the variance of the 12 year outcome as measured by the SHS. CONCLUSION: OC use and pregnancy do not significantly influence outcome in long term RA. There is, however, a trend for patients with multiple pregnancies and long term OC use to have less radiographic joint damage and a better functional level.

Adult↗
PubMed2002

Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by several immunological abnormalities. The pathogenic importance of T cells in this disease is well established. Interleukin-16 (IL-16) is a cytokine which is mainly produced by CD8+ T cells and induces chemotaxis of CD4+ T cells and monocytes. IL-16 levels have been shown to be elevated in SLE patients in a cross-sectional study, but the mechanism is unknown. To explore whether the increased IL-16 levels are associated with genetic background or the disease itself, we investigated the IL-16 level in healthy first-degree family members of SLE patients and SLE patients who were followed over time with regard to disease activity. We observed high IL-16 levels in SLE patients with severe disease compared to SLE patients with non-severe disease and healthy controls. Furthermore, IL-16 levels in first-degree relatives were not different from those in healthy controls. These results suggest that high IL-16 levels are associated with severity of SLE, but not with genetic susceptibility to SLE. Finally, we followed the disease activity of SLE patients over time, which showed significant correlation between the SLE disease activity index and IL-16, ESR and the complement components C3, C4 and CH50. In conclusion, these results implicate an association of IL-16 with SLE.

Adult↗
PubMed2001

Chemotherapy-induced chromosomal damage in peripheral blood lymphocytes of cancer patients supplemented with antioxidants or placebo.

A total of 27 patients with various types of cancer were treated with cisplatin-based combination chemotherapy. Out of these, 13 patients were randomized to receive supplementation treatment with a beverage containing the antioxidants vitamins C and E, plus selenium, during chemotherapy. The antioxidant mixture was administered to investigate whether it could reduce the potential genotoxic and nephrotoxic effect of the applied chemotherapy. A placebo group of 14 cancer patients received a beverage without selenium or antioxidants. Micronuclei (MN) in cytochalasin B-blocked binucleate (BN) peripheral blood lymphocytes (PBLs) and hypoxanthine phosphoribosyl transferase (HPRT) mutants in PBLs were studied before, during and after chemotherapy as a measure for chemotherapy-induced genotoxic effects. Before chemotherapy, patients mean frequencies of MN and HPRT mutants did not differ from those in a group of 10 healthy subjects. The mean frequency of MN in patients increased significantly after one cycle of chemotherapy (P=0.002). This frequency was still elevated at 2 months after the completion of chemotherapy (not significantly). There was no significant difference in micronuclei frequency (MNF) between the antioxidant and placebo group of patients. Chemotherapy-induced frequencies of MN after three cycles of chemotherapy correlated significantly with the cumulative dose of cisplatin (r=0.58, P=0.012) and the cisplatin-mediated loss of renal function (r=0.53, P=0.03). No consistent change in HPRT mutant frequency following chemotherapy was observed in the placebo and antioxidant group of patients. In conclusion, cisplatin-combination chemotherapy resulted in a cisplatin dose-related increase of the frequency of chromosomal damage. Supplementation with antioxidants did not prevent or reduce this effect.

Adolescent↗
PubMed2001

Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies.

PURPOSE: To compare the effect of delayed and early treatment strategies on disease outcome in patients with rheumatoid arthritis. SUBJECTS AND METHODS: Between 1993 and 1995, 109 patients diagnosed with probable or definite rheumatoid arthritis of recent onset were initially treated with analgesics; if they had persistent active disease, they were treated subsequently with the disease-modifying drugs chloroquine or salazopyrine (delayed treatment). Between 1996 and 1998, similar patients (n = 97) were promptly treated with either chloroquine or salazopyrine (early treatment). RESULTS: The median lag to the initiation of disease-modifying treatment was 15 days in the early treatment group and 123 days in the delayed treatment group. There was less radiologic joint damage after 2 years in the early treatment group (median Sharp score, 3.5; 95% confidence interval [CI]: 1 to 7) compared with the delayed treatment group (median Sharp score, 10; 95% CI: 5 to 15; P <0.05). The median area under the curve of the 2-year disease activity score was lower in the early treatment group (64 units; 95% CI: 59 to 69 units) compared with the delayed treatment group (73 units; 95% CI: 69 to 77 units; P = 0.002). CONCLUSION: In this nonrandomized comparison, early introduction of disease-modifying antirheumatic drugs was associated with a better disease outcome after 2 years.

Activities of Daily Living↗
PubMed2001

Sputum induction in severe asthma by a standardized protocol: predictors of excessive bronchoconstriction.

Sputum induction is a noninvasive method to evaluate airway inflammation. We investigated whether it can be safely and successfully performed in patients with severe, difficult-to-control asthma, and whether the patients at risk can be identified. Ninety-three severe asthmatics were included, all symptomatic despite inhaled corticosteroids (> or = 1,600 microg/d) and long-acting beta(2)-agonists > 1 yr. Patients with a postbronchodilator FEV(1) < 1 L and < 50% predicted were excluded from participation. Sputum induction was performed according to a strict protocol, using 0.9%, 3.0%, and 4.5% NaCl inhalation. In 74% (CI: 64 to 83%) of patients an adequate sputum sample could be obtained. Twenty-two percent (CI: 14 to 33%) developed excessive bronchoconstriction (decrease in FEV(1) > 15% from baseline) despite the continuing use of long-acting bronchodilators and pretreatment with 400 microg salbutamol. The decrease in FEV(1) was associated with increased use of rescue short-acting beta(2)-agonists in the previous 2 d (r(s) = 0.51, p = 0.002), lower postbronchodilator FEV(1) (r(s) = -0.31, p = 0.004), and lower provocative concentration of histamine causing a 20% reduction in FEV(1) (PC(20)) (r(s) = -0.52, p < 0.001). Recent use of short-acting beta(2)-agonist increased the risk for excessive bronchoconstriction 10.2-fold (CI: 1.2 to 109.8). In conclusion, sputum induction can be safely and successfully performed in patients with severe, difficult-to-control asthma if a standardized protocol is used. However, severe bronchoconstriction may occur despite regular use of long-acting beta(2)-agonist and pretreatment with salbutamol 400 microg. In particular, patients who have used additional short-acting beta(2)-agonists as rescue medication during the days preceding the induction, are at high risk.

Asthma↗