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Biomedical subjects

H E Rugstad

Publications and source records attributed to H E Rugstad.

At least 55 records · Page 3Linked to original sources
PubMed1989

Epidemiology of NSAID-related gastrointestinal side effects.

Finding the true incidence of gastrointestinal side effects due to non-steroidal anti-inflammatory drugs (NSAIDs) is extremely difficult. Included in every clinical trial is the spontaneous and NSAID-unrelated occurrence of gastrointestinal problems. On the basis of several different clinical studies (cohort, case control, case review, and double-blind studies) we feel that the following frequency estimate adequately describes the clinical situation: one-third of all patients using NSAIDs will experience gastrointestinal symptoms during a 3-month course of therapy. When specifically asked for, all kinds of unspecific gastrointestinal symptoms will be encountered, ranging from vague complaints about intestinal distension to typical duodenal ulcer symptoms. In approximately half of the symptomatic patients these symptoms can be classified as dyspeptic. Serious gastrointestinal hemorrhage or perforation can be expected in 1%, and less than half of these patients will have experienced dyspeptic symptoms before the serious incident. More than 10% of all patients will withdraw from the planned treatment owing to intolerable symptoms.

Adult↗
PubMed1989

Renal side effects of high and low cyclosporin A doses in patients with rheumatoid arthritis.

Thirty-nine patients with classical or definite rheumatoid arthritis (RA) entered a randomized double-blind placebo controlled study with low dose cyclosporin A (CyA) (mean whole blood CyA level after 26 weeks 282 +/- 33 micrograms/l) or placebo treatment for 48 weeks. The placebo treatment had to be withdrawn before 48 weeks in 9 out of 19 patients because of a deterioration of their arthritis symptoms. All 20 patients in the CyA group completed 26 weeks of treatment. Fourteen of them were followed up for 48 weeks of treatment on CyA and then 12 weeks after CyA treatment was withdrawn. The side effects in the CyA group were compared with the results from another study with high CyA doses (mean whole blood CyA level 419 +/- 71 micrograms/l) for 26 weeks in 11 other patients with RA. Serum creatinine increased 19.7% (p less than 0.01) in the low CyA dose group after 26 weeks as compared with 59.5% in the high CyA dose group. Creatinine clearance was reduced by 17.9% (low dose) (p less than 0.01) and 26.2% (high dose), respectively. Twelve weeks after withdrawal of the low dose CyA treatment, serum creatinine values were still higher than before treatment (p less than 0.05), but creatinine clearance had normalized. Eight of the 20 patients treated with low CyA doses also started with nonsteroidal anti-inflammatory drugs (NSAIDs) after 20-36 weeks of CyA treatment. Serum creatinine was 16.6% above baseline 4 weeks before NSAIDs compared with an increase of 40.4% (p less than 0.05) 4 weeks after start of NSAID treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Epidemiology of NSAID-induced gastrointestinal problems and the role of cimetidine in their prevention.

It is difficult to ascertain the incidence of gastrointestinal side-effects associated with intake of non-steroidal anti-inflammatory drugs (NSAIDs). In retrospective studies, some NSAIDs have been reported to be associated with a higher incidence of gastrointestinal side-effects than others. However, this has not been verified either in a prospective case-review study or in a large double-blind study. Serious side-effects, such as bleeding, perforation and heart failure, occur in approximately 1% of patients using NSAIDs. One-third of all patients receiving NSAIDs will have gastrointestinal complaints. Since at least 10% of patients terminate treatment with NSAIDs as a result of side-effects, even reduction of those that are not life-threatening would be of great benefit. H2-receptor antagonists have proved effective in ulcer treatment, and their use as prophylaxis against the side-effects of NSAIDs is being widely studied. In a recent study, 63 patients who had experienced serious upper gastrointestinal side-effects were given cimetidine while continuing their NSAID therapy. All but 4 of the 47 who had gastric or duodenal ulcer on first admission were healed at 8 weeks, and none of the remaining 16 with diffuse bleeding gastritis experienced further clinical episodes of bleeding or ulcer-related dyspepsia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Partial cross-resistance between auranofin and sodium aurothiomalate in cultured human cells.

Cross-resistance between auranofin and sodium aurothiomalate was tested in two substrains of cultured human epithelial cells. The HEAF cells were previously made resistant to the otherwise lethal concentration of 2 mumol auranofin per litre of culture medium. The HEmyo cells were made resistant to the otherwise lethal effect of 300 mumol sodium aurothiomalate/l. After 4 days of continuous treatment with 2 mumol auranofin/l, 4.6% of the parent HE cells, 55.7% of the HEAF cells and 51.7% of the HEMyo cells continued to grow, compared with controls grown without drug supplement. After 4 days on 300 mumol sodium aurothiomalate/l, 17.6% of the HE cells, 101.0% of the HEMyo cells and 45.3% of the HEAF cells continued to grow. Thus, there was an almost complete cross-resistance to auranofin in the HEMyo cells, and a relative cross-resistance to sodium aurothiomalate in the HEAF cells. The cross-resistance was not found to be related to decreased cytosolic concentration of total gold in the cross-resistant lines.

Auranofin↗
PubMed1988

Mapping of synovial fibroblast proteins by high resolution two-dimensional polyacrylamide electrophoresis.

The highly sensitive protein separation technique two-dimensional polyacrylamide gel electrophoresis was used to study the cellular protein synthesis in 1) cultured human rheumatoid and 2) normal synovial fibroblasts and 3) normal skin fibroblasts. No reproducible differences were found that could be ascribed to cellular origin, the disease or in vitro cellular aging. The reasons for that probably were related to the cell cultures and not to failure of protein detection.

Arthritis, Rheumatoid↗
PubMed1988

Antiinflammatory and immunoregulatory effects of glucocorticoids: mode of action.

In this review emphasis is put on the mechanisms for the antiinflammatory and immunoregulatory role of glucocorticoids in man. Glucocorticoids have numerous effects some of which are permissive; steroids are thus important not only for what they do, but also for what they permit or enable other hormones and signal molecules to do. Some important effects are the result of altered protein synthesis due to steroidreceptor complex formation. One such protein is macrocortin which is induced by glucocorticoids. Macrocortin inhibits the enzyme phospholipase A2, thereby reducing the formation of prostaglandins and leukotriens. Steroids also reduce the release or synthesis of plasminogen activator and certain cytokines such as interleukin 1 and macrophage migration inhibitory factor. Glucocorticoids inhibit the release of histamin and lysosomal constituents of possible importance for the inflammatory response. In addition, steroids have profound effects on the circulation and distribution of white blood cells.

Adjuvants, Immunologic↗
PubMed1987

An open, controlled, randomized comparison of cyclosporine and azathioprine in the treatment of rheumatoid arthritis: a preliminary report.

Cyclosporine (10 mg/kg/day) and azathioprine (2.5-3 mg/kg/day) were compared for 26 weeks in an open, controlled, randomized study of 24 patients with rheumatoid arthritis. Each treatment group consisted of 12 patients. Those patients who took cyclosporine improved significantly in the 50-foot walk time, circumferences of proximal interphalangeal joints, Ritchie articular index, global assessment by investigator, and grip strength, when compared with baseline findings. In the azathioprine group, there was improvement only in grip strength.

Arthritis, Rheumatoid↗
PubMed1987

Protective function of metallothionein against certain anticancer agents.

The possible role of metallothioneins (MT) in the cellular protection against ionizing radiation and alkylating agent cytotoxicity has been investigated by the use of cultured cells with either low or high levels of MT. The cytotoxic activity of the drugs cis-dichlorodiammineplatinum (cis-DDP), chlorambucil and prednimustine was reduced 1,5-3 fold in cells containing high levels of MT, and furthermore about 70% of platinum and 30% chlorambucil was shown to be associated with the protein. Increased resistance was also demonstrated in MT-rich cells during exposure to ionizing radiation. Evidence that MT also may play a role in vivo as a resistance mechanism, was provided in studies of tumors derived from either the MT-rich or MT-poor cells which had been inoculated in nude mice. During treatment of the animals with cis-DDP, the MT-rich tumors exhibited a significant degree of resistance. These results indicate that MT may play an important role in the intrinsic protection of cells against these agents, and raises the question whether it also may be a factor in the acquired resistance of tumors against chemotherapy.

Animals↗
PubMed1986

The Norway study: plasma concentrations, efficacy, and adverse events.

In the Norwegian comparative trials of piroxicam and naproxen in osteoarthritis, conducted by Husby and co-workers and Rugstad et al, relationships between plasma drug concentrations and the following were examined: efficacy in patients with osteoarthritis; all adverse reactions; and serious adverse events, which included gastrointestinal ulceration or bleeding and congestive heart failure. Increased plasma concentrations were correlated with age and female sex, but efficacy, overall side effects, and serious adverse events were not correlated with increasing plasma levels.

Adult↗
PubMed1986

Metallothionein in cultured human epithelial cells and synovial rheumatoid fibroblasts after in vitro treatment with auranofin.

Radioimmunoassay (RIA) and reversed-phase high-pressure liquid chromatography (HPLC) were used to investigate gold-binding proteins of possible metallothionein (MT) nature occurring upon auranofin exposure of cultured human cells. An epithelial cell line (HE) and two sub-strains were examined. The HEAF sub-strain had been made resistant to 2 mumole auranofin/l culture medium. The resistance was associated with the appearance of gold-binding substances with gel filtration characteristics like MT. The HE100 sub-strain had been made resistant to 100 mumole CdCl2/l and contained high amounts of cytosolic Cd-induced MT. In addition, cultured synovial fibroblasts, derived from normal (SN) and rheumatoid (SRA) synovial tissues, were investigated. Evidence was obtained by RIA that the low molecular weight (mol.wt. 6000-7000) gold-binding proteins occurring in the HEAF cells and SRA cells following auranofin exposure, were of MT nature. The relative amounts of MT in the epithelial cell lines were: HE:HEAF:HE100 = 1:18:100. The relative amounts in the synovial fibroblasts were: SN:SRA:SRA treated with auranofin = 1:3:10. The HPLC methods used were found suitable for isolation of Cd-MT in the HE100 cells, but not for the Au-MT in the HEAF cells. By HPLC, the Cd-MT in the HE100 cells was resolved into 3 MT-1 and 1 MT-2 iso-proteins exhibiting the amino acid composition typical of MT. Judged by HPLC, the MT in these cells constituted 0.4% of the cytosolic proteins.

Amino Acids↗
PubMed1986

A double-blind multicentre trial of piroxicam and naproxen in osteoarthritis.

A multicentre, double-blind study of unprecedented size was conducted to compare the safety and efficacy of piroxicam and naproxen in the treatment of osteoarthritis. The study comprised 2,035 patients and a treatment period of 12 weeks. The dosage was 20 mg piroxicam and 750 mg naproxen daily with the option to reduce to 10 and 500 mg, respectively, at week 4 or 8. No major difference between the drugs was observed with regard to overall incidence of adverse events. The frequency of serious adverse events was about 1% for both drugs. A statistically significant decline of adverse events with age was found in both sexes. Piroxicam was significantly superior to naproxen for pain at rest and pain on movement at 12 weeks and degree of restriction in daily activity at 4 weeks. A significantly increasing beneficial effect was observed with both drugs between 4 and 12 weeks of treatment. The comparable safety observed for the two drugs is in contrast to perceptions based on spontaneous reports to official monitoring systems.

Aged↗
PubMed1986

Piroxicam and naproxen plasma concentrations in patients with osteoarthritis: relation to age, sex, efficacy and adverse events.

Piroxicam and naproxen plasma concentrations were obtained after 4 weeks active therapy between 3 and 12 hours post-dose in 640 and 629 patients, respectively. These patients are a subset of 2,035 patients with osteoarthritis on whom we have reported previously (11) in a double-blind multicentre safety and efficacy trial comparing piroxicam 20 mg/day and naproxen 750 mg/day. The purpose of the present study was to look for an association of plasma drug concentration with the variables of: age, sex, adverse events and efficacy. There was a statistically significant increase in plasma concentrations of both drugs with increasing age and females had higher concentrations than males. The increase in plasma concentration seen with increasing age was of a magnitude of 25% for piroxicam and 20% for naproxen when comparing a 50 year old to an 80 year old. However, less than 15% of the variability in plasma concentrations seen between patients is accounted for by age and sex. Within the plasma concentrations achieved with these doses, no association with adverse events, non-serious or serious, and efficacy was noted.

Age Factors↗
PubMed1986

Side effects of cyclosporin A treatment in patients with rheumatoid arthritis.

Cyclosporin A (CyA) and azathioprine (Aza) were compared with respect to renal side effects in an open controlled, randomized study of patients with rheumatoid arthritis. Twelve patients were treated with CyA (mean dose 7.8 +/- 1.2 mg/kg/day) and 12 with azathioprine for 26 weeks. All patients also received prednisolone 5 mg/day. The patients had normal serum creatinine (less than 120 mumoles/liter) and protein-free urine before the trial. CyA increased serum creatinine in nine out of the 11 patients followed for 26 weeks, the mean increase was approximately 50%. Creatinine clearance was reduced by 31%. Mean arterial pressure (MAP) and serum potassium were significantly increased by CyA. Urinary beta 2-microglobulin excretion was significantly increased by CyA, in five of the patients more than ten times. Urinary kallikrein excretion was reduced by more than 50% and urinary albumin excretion was doubled. All these parameters remained normal and unchanged in the azathioprine group. CyA was withdrawn in seven patients after 26 weeks. Urinary beta 2-microglobulin was still increased by 85% nine months after CyA treatment. The other parameters were gradually normalized after three to nine months except for one patient who developed renal failure. Urinary beta 2-microglobulin excretion was a very sensitive parameter for renal tubular damage in this study.

Albuminuria↗
PubMed1986

Interaction of cyclosporin and its solvent, Cremophor, with atracurium and vecuronium. Studies in the cat.

Interactions between Sandimmun (formulated as cyclosporin (CyA) in Cremophor and ethanol) and atracurium or vecuronium were investigated in anaesthetized cats. During stable 50% blockade and with a constant rate of infusion of the neuromuscular blocking drugs, Sandimmun 0.8 mg kg-1 or an equivalent amount of its solvent moiety was injected over 5 min. Sandimmun potentiated the blockade induced by vecuronium (median infusion rate 110 micrograms kg-1 h-1) from 50.7% before injection to maximum 95.2% 17.3 min after injection (median values), whereas the median blockade in cats receiving atracurium (median 250 micrograms kg-1 h-1) increased from 51.3% to 72.4% after 32.9 min. At 45 min after the injection the median blockades were 93.1% and 69.8%, respectively. In cats receiving vecuronium (median 104 micrograms kg-1 h-1) the solvent produced an increase in effect of from 51.1% to maximum 78.0% blockade after 5.4 min and 61.5% after 45 min (median values). Interaction with solvent was negligible in cats receiving atracurium. We attribute the effect of the solvent to the Cremophor component. The mechanism of the interaction related to the cyclosporin is unknown.

Animals↗