Longterm effect of methotrexate in Felty's syndrome: a 12 year followup.
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Administration, Oral↗
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[Longterm effects of steroid therapy].
Asthma is a chronic inflammatory disease of the airways play. Anti-inflammatory drugs the fundamental role in the treatment of asthma and among them steroids are the most important. However, oral steroids may cause many serious side effects. A major breakthrough in the treatment of asthma was introducing inhaled steroids. Inhaled steroids have much less side effects than oral steroids, although they have the same anti-inflammatory activity. Long term effect of inhaled steroids can be divided into wanted and unwanted outcome. The desirable anti-inflammatory effect of steroids is reflected by lowering of bronchial hyperresponsiveness and a better control of asthma symptoms. Inhaled corticosteroid may have systemic side effects similar to those observed with oral steroids such as 1) adrenal suppression, 2) effect on bone metabolism, 3) growth suppression in children, 4) impaired skin collagen synthesis, 5) cataract, 6) metabolic disturbances, 7) effect on central nervous system. Topical side effects of inhaled corticosteroid such as oral candidiasis, dysphonia and cough effect about 10 to 30% of patients taking those drugs. Summing up it is advisable to use inhaled corticosteroid in the lower effective dose.
Administration, Inhalation↗
Effect of longterm misoprostol coadministration with non-steroidal anti-inflammatory drugs: a histological study.
Prostaglandins are widely used in the prevention and healing of non-steroidal anti-inflammatory drug (NSAID) induced gastric and duodenal ulcers, but their longterm effect on the human gastric mucosa is unknown. This study assessed the effect of coadministration of prostaglandins with NSAIDs on the histology of the gastroduodenal mucosa. Histological appearances (using the Sydney system) of gastric biopsy specimens from 180 patients receiving longterm NSAID treatment of whom 90 had been receiving misoprostol (400-800 micrograms/day) for one to two years were studied. Both groups of patients were comparable with regard to clinical and demographic details. There was no significant difference (p > 0.1) in the prevalence of chronic gastritis (total, corpus or antrum only) between patients receiving (36 of 90 (40%)) or not receiving misoprostol (35 of 90 (39%)). Chronic gastritis was equally associated with the presence of Helicobacter pylori, 86% and 73% (p > 0.1), respectively, in the two groups. Significantly fewer patients receiving misoprostol had reactive gastritis than those receiving only NSAIDs (8 (9%) versus 27 (30%), p < 0.01). Reactive gastritis was not associated with H pylori. Thirty nine (43%) of the misoprostol treated patients had normal histology compared with 16 (18%) receiving only NSAIDs (p < 0.01). These results show two different patterns of gastric damage in patients receiving NSAIDs, namely chronic and reactive gastritis. Misoprostol treatment was associated with a significantly reduced prevalence of reactive gastritis and it is suggested that this, along with its antisecretory action, may explain the reduced prevalence of gastroduodenal lesions when coadministered with NSAIDs.
Adult↗
[The effects of longterm selection on the genetic structure of populations--a simulation study. II. The effects of selection on genetic variances].
Monte Carlo simulation has been done to study the effects of longterm artificial selection on genetic variances under additive, dominant, and over-dominant models. The effects of population size, linkage, and heritability have been considered. Just as under the additive model, the additive variance under the dominant and over-dominant models has also been decomposed into three components which represent changes in gene frequencies (VT), departure from Hardy-Weinberg equilibrium (VHW) and from linkage equilibrium (VLD) respectively. These present a resonable approach to study the association among multiple genes. In small populations, genetic variance fluctuates wildly over generations and replicates due to the establishment of linkage disequilibrium. Rapid decrease of VT observed. Intense linkage retained a greater additive variance in the small populations while slowing down responses, which makes it difficult to predict responses during longterm selection.
Animals↗
Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year followup on the hydroxychloroquine in early rheumatoid arthritis (HERA) study.
OBJECTIVE: To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA). METHODS: One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units. RESULTS: One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations. CONCLUSION: These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.
Adult↗
The effect of longterm treatment with auranofin and gold sodium thiomalate on immune function in the dog.
Although gold compounds are recognized as effective immunomodulatory agents in the treatment of rheumatoid arthritis (RA), their mechanism of action is controversial. We examined the effect of longterm treatment with 0.6-3.6 mg/kg auranofin (AF) per os q24h, or intramuscular injections of 0.5-2.0 mg/kg gold sodium thiomalate (GSTM) q3d, on 13 variables of immune function in normal dogs. None of the changes in these variables previously attributed to treatment with AF or GSTM could be demonstrated after 6-7 years' dosing. As gold compounds are effective in treating spontaneous RA in dogs, these proposed actions may not be responsible for the remittive effects of chrysotherapy in this disease.
Animals↗
Association of vitamin D and estrogen receptor gene polymorphism with the effects of longterm hormone replacement therapy on bone mineral density.
We longitudinally studied whether vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms in Japanese women influenced the effect of longterm hormone replacement therapy (HRT) on bone mineral density (BMD) in the lumbar spine. The 81 subjects were aged 40 to 64 years (mean +/- SEM, 49.5 +/- 0.6 years), and had received sequential or continuous HRT regimens, including 0.625 mg of conjugated equine estrogen and 2.5 to 5 mg of medroxy-progesterone acetate, for at least 3 years. Genomic DNA was extracted from blood cells, and analyzed for restriction fragment length polymorphism, using the restriction endonucleases Taq I, Apa I, and Fok I for VDR, and Pvu II and Xba I for ER. At 1 year, subjects with a Taq I genotype of TT (i.e., site absent) showed a significantly greater increase in BMD with treatment (DeltaBMD) than subjects with the Tt genotype (2.6 +/- 0.5% vs -0.8 +/- 1.4%; P = 0.016). A small difference between genotypes remained at 2 years (3.8 +/- 0.6% vs 0.8 +/- 1.6%; P = 0.069), but no significant difference between genotypes was seen at 3 years. In multiple regression analyses, DeltaBMD at 1 year was significantly affected by VDR- Taq I, Apa I, and ER- Pvu II genotypes and by age at treatment initiation, although at 3 years or more, DeltaBMD was significantly affected only by age. These results indicate that Taq I VDR gene polymorphism predicted the effect on lumbar BMD for the first year of HRT in Japanese women, and that the differences in BMD versus the polymorphism disappeared if the treatment was continued for over 2 years.
Bone Density↗
[Effects of longterm selection on the genetic structure of populations--a simulation study. I. Simulation models and selection responses].
Monte Carlo method has been utilized to investigate responses to longterm selection. The simulation involves 3 gene effect models (additive, dominant, and over-dominant), two population sizes, three linkage intensities, and three heritability levels, thus making 54 combinations. For each combination, 5 replicate populations are selected over 49 consecutive non-overlapping generations. The results demonstrate that under all the gene effect models, linkage is important only in the case of small populations and intense linkage, when it reduces responses significantly due to hampering the fixation of favourable alleles and accelerating their loss. Linkage has no apparent effect if it is not very tight or if the population is large. Much greater responses are achieved in the large populations than in the small ones, especially for traits with low heritability. Among those discussed are problems of crossing selected lines to obtain extra responses, and discrepancy of some theoretic results on selection limits.
Computer Simulation↗
[Long-term therapy with nitrates. Relation between dosage and tolerance effect].
In 56 patients with angiographically-documented coronary artery disease, the longterm effects of isosorbide dinitrate (ISDN) and isosorbide 5-mononitrate (5-ISMN) on exercise hemodynamics and exercise capacity were assessed. The hemodynamic and antianginal acute and longterm effects of the respective agents were objectively analyzed on the basis of the tested parameters of mean pulmonary artery pressure and work capacity (watts X minutes). These parameters are unaffected by placebo and show reproducible changes at rest and during exercise after drug administration. After the standard 20 mg dose of ISDN or 5-ISMN, both at rest and during exercise, there was a marked decrease in pulmonary artery pressure as well as an increase in exercise capacity. The acute effects of 60 mg ISDN or 50 mg 5-ISMN were not substantially more marked than those of the 20 mg doses. During longterm treatment with 20 mg ISDN or 5-ISMN three times daily there was no attenuation of the hemodynamic effects, that is, no tolerance development; the increase in exercise capacity was maintained. In contrast, at the end of the four-week treatment period with 60 mg ISDN or 50 mg 5-ISMN three times daily there was a marked attenuation of the hemodynamic effects as well as the associated exercise capacity. The results of this study do not enable delineation of the mechanism responsible for the attenuated effect during high-dose treatment. Most probably, it is due to a complex process, in which, in addition to pharmacokinetics and pharmacodynamics, alterations in various reflex and adaptive mechanisms also play a role.
Adult↗
Effects of longterm epidermal growth factor treatment on the normal rat colon.
BACKGROUND: Epidermal growth factor (EGF) exerts trophic effects on the mucosa of damaged and defunctioned colon, but the effects on the normal large bowel wall are not known. AIMS: To investigate the effect of systemic EGF treatment on growth and morphology of normal rat colon. METHODS: Rats were treated with subcutaneous biosynthetic EGF injections of 150 micrograms/kg/day for 28 days. The weight of the histological colonic wall layers and the luminal surface area were measured using quantitative morphometric analysis (stereology). The colon was subdivided into proximal and distal parts. RESULTS: EGF treatment increased the total colon wet weight by 23% compared with controls (p < 0.005). The weight increase occurred in the mucosal (33%) and the submucosal layers of the bowel wall (36%) and there was a 69% increase of the total luminal surface area (p = 0.001). In the proximal part of colon of EGF rats there was a 68% increase in mucosal weight (p < 0.005) accompanied by a 79% increase in the mucosal surface area compared with controls (p < 0.005), whereas submucosal and muscularis propria weights were identical. In distal colon, the mucosal weight increased 28% in the EGF group (p < 0.005), the mucosal surface area increased by 72% after treatment (p < 0.01). Furthermore there was a 34% increase in the weight of submucosa (p < 0.001) in the distal colon among EGF rats. CONCLUSIONS: Treatment of rats with EGF has a stimulating role on the mucosa and luminal surface area of the entire functioning colon and a trophic effect on the submucosa of the distal colon.
Animals↗
Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function.
OBJECTIVE: To document the effectiveness, including the longterm effect, of a course of intravenous (IV) pulses of methylprednisolone (MP) and cyclophosphamide (CYC) in patients with scleroderma (SSc) who had evidence of lung inflammation on high resolution computer tomographic (HRCT) scan of the chest. METHODS: Fourteen consecutive patients with SSc and lung involvement were treated with 6 pulses of IV MP (10 mg/kg) and IV CYC (15 mg/kg) given at 3-4 weekly intervals. HRCT scans and lung function tests were performed at baseline and after the 6th pulse. Further lung function tests were repeated at 12 months and annually thereafter. RESULTS: Modified Rodnan skin scores improved significantly by 35% from a median baseline score of 17 (IQR 14-26.5) to a posttreatment score of 13 (IQR 10.5-18.5; p = 0.0058). HRCT scan scores improved significantly (p = 0.04). Twelve of 13 patients experienced either improvement or stabilization of the HRCT score. Median DLCO and lung volumes remained stable during the first 12 months. After a median followup of 26 months (IQR 19-43), 67% of patients experienced deterioration in DLCO. Median deterioration was 23% (IQR 44-0.6), with the median rate of deterioration of the predicted value of the DLCO/month being 0.87% (IQR 1.24-0.02). The treatment was safe and well tolerated. CONCLUSION: This IV regimen stabilized lung disease in patients with SSc. When treatment was stopped, or reduced in intensity, a deterioration in lung function occurred in the majority of patients. Rate of deterioration of DLCO may be a useful marker for determining the intensity of treatment. These findings have implications for treating lung disease and designing clinical trials in patients with SSc.
Adult↗
[Consensus for infliximab treatment of patients with Crohn's disease].
Very recently infliximab--a tumour necrosis factor blocking antibody--was registered as an important novel immunomodulating therapy for active Crohn's disease in the Netherlands. Although this treatment can have a very significant and sometimes dramatic effect (on remission induction), its longterm effects are still uncertain and the high cost is a major drawback. An expert committee of specialists in inflammatory bowel disease (IBD) in the Netherlands therefore produced a consensus report on specific treatment indications for its use. It is stated that only immunosuppressive-resistant patients or patients with incompatibilities and allergies to prednisone, azathioprine and methotrexate should be candidates, a second indication being patients with serious enterocutaneous fistulae not reacting to a full course of conventional therapy. Its use is not indicated in patients with stenosing disease. It is also stated that the effect of longterm repeated therapy in active Crohn's disease still has to be established. Since budget limitations for medications are a major disadvantage, the formation of expert committees (with an expert in the treatment of complicated inflammatory bowel disease) in each hospital should be stimulated to limit the treatment to only cases with real immunosuppressive-resistant disease.
Adjuvants, Immunologic↗
Effect of longterm cetirizine treatment on the cutaneous hypersensitivity reaction in patients with grass pollen allergy.
In short-term studies cetirizine effectively reduces the early and late phases of the cutaneous hypersensitivity reaction. The aim of this study was to determine its long-term effects on both the vascular and cellular components of the reaction. The skin blister technique was used to collect inflammatory cells after intradermal administration of grass pollen antigen to 10 atopic volunteers. They were treated for 3 months with 10 mg cetirizine twice daily. Tests were done at baseline, before, and 7, 30 and 90 days after initiation of treatment. Blister fluid containing cells was collected on microscope slides at 6 and 24 hours. The area of induration was measured at 0.25, 1, 6, 10 and 24 h. Cetirizine significantly reduced the peripheral blood eosinophil count at 30 and 90 days (75% and 40% reduction respectively); there was no significant change after only one week's therapy. Eosinophil recruitment to and activation in the area of antigen administration were already maximally reduced after 7 days, namely a reduction of 54, 52 and 59% at 10 h, and of 55, 68 and 66% at 24 h, respectively, at 7, 30 and 90 days. The area of induration was significantly reduced after one week of therapy. There was a general tendency towards an increase in the reduction at 30 and 90 days, which reached significance only at the 24 h observation; there was a 24, 51 and 48% reduction from baseline at, respectively, 7, 30 and 90 days. The data clearly show a progressive reduction of induration as well as of cellular events over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of longterm exposure to mercury on the bacterial community in marine sediment.
The aim of this study was to investigate the effect of mercury contamination on bacterial community structure and function. Bacterial communities from two sites, a mercury-contaminated site inside the harbor of Copenhagen, Denmark (CH) and a unpolluted control site, Koge Buge (KB), were compared with respect to diversity indices, of antibiotic- and heavy metal-resistance patterns, abundance and self transmissibility of plasmids in resistant isolates (endogenous isolation). Furthermore, the potential for gene transfer between indigenous bacteria was assessed by the exogenous plasmid isolation approach. It was found that resistance to all the tested compounds was higher in the mercury-polluted sediment than the control sediment. The abundance of plasmids was higher at the polluted site, where 62% of the isolates contained plasmids, whereas only 29% of the isolates from the control sediment contained plasmids. Furthermore, the frequencies of large plasmids and plasmids per isolates were found to be higher in the contaminated sediment. Exogenous plasmid isolations revealed high occurrence of Hg and tetracycline resistance, self-transmissible plasmids in CH sediment (1.8 x 10(-5) transconjugants per recipients) relative to KB sediment (3.0 x 10(-8) T/R). Shannon-Weaver diversity indices showed no difference in the diversity of the isolates from the two sites, and Hg-resistant isolates from CH were found to be as diverse as the CH isolates in total. This may be owing to high level of self-transmissible Hg resistance plasmids found in CH.
Bacteria↗
[Side-effects on longterm treatment with antihypertensives (author's transl)].
Unspecific complaints as a result of lowering the blood pressure and substance-specific side-effects may occur during antihypertensive therapy. The frequency of the side-effects depends on the substance used (10 to 50%) and on the dose. An individual therapy, which in most cases involves the use of several substances, can reduce the frequency of side-effects decisively. With optimal therapy the ratio of benefits (= prevention of cardiovascular diseases) to side-effects (= sum of undesirable reactions) is completely acceptable in the treatment of high blood pressure.
Age Factors↗
Longterm favorable effect of oxygen administration on a patient with primary pulmonary hypertension.
A 17-year-old girl with primary pulmonary hypertension was treated with longterm administration of oxygen. Oxygen was delivered only at night for eight hours daily. Her clinical status has been improved for more than 17 months. Cardiac catheterization revealed almost 50 percent reduction of pulmonary vascular resistance. This is the first known report of successful treatment of primary pulmonary hypertension with oxygen administration.
Adolescent↗
Evaluation of the trophic effect of longterm treatment with the histamine H2 receptor antagonist loxtidine on rat oxyntic mucosa by differential counting of dispersed cells.
To evaluate whether the general trophic effect of gastrin on the oxyntic mucosa is an indirect effect mediated by histamine H2 receptors, sustained 24 hour hypergastrinaemia was induced in Sprague-Dawley rats by treatment with the long acting and potent histamine H2 antagonist loxtidine for five months. The trophic effect was assessed by weight, enumeration of total mucosal cells, parietal cells, and enterochromaffin like cells in smears stained for the actual cells after enzymatic dispersion of the mucosa, and by biochemical analysis of oxyntic mucosal homogenates. The weight of the whole stomach and the oxyntic mucosa increased by 12.7% (p = 0.016) and 27.5% (p = 0.006), respectively. Total oxyntic mucosal protein content increased by 28.7% (p = 0.058). Total numbers of mucosal cells and parietal cells increased by 11.9% (NS) and 24.1% (NS), respectively. The amount of the parietal cell specific enzyme H+,K(+)-ATPase was unchanged. On the other hand, the number of enterochromaffin like cells and related parameters, histidine decarboxylase activity and histamine content of the oxyntic mucosa, showed a pronounced and significant increase. It is concluded that the general trophic effect of gastrin on the oxyntic mucosa is not mediated by the histamine H2 receptor. The tropic effect of gastrin on the parietal cell seems, in contrast with that on the enterochromaffin like cell, not to be specific but only reflecting the general trophic effect on the oxyntic mucosa.
Animals↗
Effect of longterm placebo controlled calcium supplementation on sigmoidal cell proliferation in patients with sporadic adenomatous polyps.
A longterm, double blind intervention trial was undertaken in patients with sporadic adenoma treated by polypectomy to investigate the putative role of calcium as a protective factor in colon carcinogenesis. The aim of the study was to assess the effect of a daily dietary supplementation of 2 g calcium over nine months on cell proliferation measured as proliferation index in colonic mucosa. A total of 48 patients were entered into the study of which 30 were fully compliant. After intervention proliferation index % (mean (SEM) in colonic epithelium was decreased in both the calcium (13.5 (1.5) to 11.4 (1.2)) and the placebo group (13.7 (0.9) to 10.8 (1.1)). The difference in the change between the two groups was not significant (p = 0.7). Changes in proliferation index % of crypt compartments were also not significantly different between the two groups. A significantly positive correlation between soluble calcium in faeces and the total proliferation index % in colonic epithelium at baseline and after intervention (r = 0.54, p < 0.01, r = 0.50, p < 0.01 respectively) suggests that an increase of free luminal calcium alone is insufficient for inhibition of cellular proliferation.
Adenomatous Polyposis Coli↗