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Biomedical subjects

R D Armstrong

Publications and source records attributed to R D Armstrong.

At least 37 records · Page 2Linked to original sources
PubMed1987

Combined D-penicillamine and chloroquine treatment of rheumatoid arthritis--a comparative study.

Seventy-two patients with relatively early but progressive rheumatoid arthritis were treated with chloroquine sulphate, D-penicillamine or a combination of both drugs over 1 year. Chloroquine resulted in significantly fewer side-effects but combined treatment appeared to increase the risks of toxicity. Significant clinical improvements were seen with each regimen and these were indistinguishable between treatments. However, chloroquine had less impact on haemoglobin, ESR, rheumatoid factor levels and C-reactive protein than the other treatments. Furthermore, radiological deterioration was most frequent amongst those given chloroquine alone. Combination treatment with D-penicillamine and chloroquine thus offered no advantages. Chloroquine caused fewer side-effects than both D-penicillamine and combination treatment but appeared to have a less pronounced effect on the disease process as measured by laboratory and radiological indices.

Adult↗
PubMed1987

Biceps tendon blocks reduction of isolated radial head dislocation.

A case of an unreducible radial head dislocation found in a 7-year-old girl illustrates the frequent delay in diagnosis associated with radial head dislocation. Her initial radiographs showed the radial neck access not passing through the center of the capitulum, which is diagnostic of radial head dislocation. She had no associated injuries to the elbow joint or neurovascular structures. Closed reduction was not stable, and open reduction revealed the biceps tendon displaced posteriorly and laterally from the radial tubercle around the radial neck, which prevented stable reduction of the anteromedial dislocation of the radial head. Once it was reduced through the radial capitular joint to its normal anatomy, the reduction was stable. Following a routine postoperative course, an excellent result was obtained.

Child↗
PubMed1986

Acute effect of 5-fluorouracil on cytoplasmic and nuclear dihydrofolate reductase messenger RNA metabolism.

Studies were completed in C3-L5178Y cells, in which the DNA-coding region for dihydrofolate reductase messenger RNA (DHFR-mRNA) is amplified, to determine the acute effect of 5-fluorouracil (FUra) on DHFR-mRNA metabolism. There was minimal to no effect of 100 microM FUra on total cytoplasmic DHFR-mRNA levels by 6 and 12 h and only a 25% reduction by 24 h. These results contrasted with the nuclear DHFR-mRNA levels which by 6 h following exposure to FUra increased by 80% in a dose-dependent manner. Furthermore, some of the increased nuclear DHFR-mRNA was found to be in a non-polyadenylated form. Under conditions to examine only RNA synthesized during the drug exposure, FUra was found to markedly enhance the level of newly synthesized nuclear DHFR-mRNA in a dose-dependent manner, while also producing an apparent dose-dependent reduction in the cytoplasmic DHFR-mRNA. RNA fractionated by 1.5% agarose-urea gel electrophoresis revealed two major cytoplasmic DHFR-mRNA species approximately 1.8 and 0.8 kilobases in size. Following a 24-h FUra exposure, a dose-dependent loss of the 0.8-kilobase DHFR-mRNA was observed. The combined results of these experiments indicate that FUra treatment reduces the ability of nascent DHFR-mRNA to relocate to the cytoplasm, suggesting either an inhibition of mRNA processing or nuclear-cytoplasmic transport.

Animals↗
PubMed1986

Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.

Chemical Phenomena↗
PubMed1986

Fluoropyrimidine-mediated changes in small nuclear RNA.

Studies were completed to examine the effects of the antineoplastic agent 5-Fluorouridine (FUrd) on the metabolism of the small molecular weight nuclear RNA (snRNA). Cultured Sarcoma-180 murine tumor cells were exposed to FUrd concurrent with [3H]cytidine for 6 h, the drug was removed, and the RNA was isolated at 0, 24, or 48 h following the drug treatment. The results of these studies demonstrated that FUrd produced three dose-dependent changes in snRNA metabolism. The electrophoretic migration of the U4 and U6 snRNA was altered in nondenaturing 10% polyacrylamide slab gels. These results were not observed in denaturing gels or when RNA was extracted at temperatures exceeding 25 degrees C, suggesting that the incorporation of 5-fluorouracil induced secondary structural changes in these RNA. A dose- and time-dependent selective reduction in the turnover of the U1 snRNA synthesized in the presence of FUrd was observed as well, with levels over 100% higher than control cells at 48 h after exposure to 10 microM FUrd. These changes in snRNA metabolism may contribute to the reported alterations in large molecular weight RNA metabolism that also result in fluoropyrimidine-treated cells, or to cytotoxicity.

Animals↗
PubMed1986

Precursor-dependent differences in the incorporation of fluorouracil in RNA.

The distribution and level of 5-fluorouracil (FUra) incorporation into RNA were studied in S-180 murine tumor cells for two different fluoropyrimidine nucleosides: 5-fluorouridine (FUrd) and 5'-deoxy-5-fluorouridine (5'-dFUrd) under both cytotoxic (thymidine nonreversible) and nontoxic conditions. Exposure of cells to 200 microM 5'-dFUrd for 6 hr resulted in minor thymidine-nonreversible toxicity (11% cell kill) and produced an FUra incorporation level of 12.5 pmol of FUra/microgram of RNA. Exposure of cells to 1 microM FUrd for 6 hr resulted in considerably more toxicity (74% cell kill) but was found to produce less FUra incorporation (7.8 pmol of FUra/microgram of RNA) than the nontoxic concentration of 5'-dFUrd. Subcellular fractionation (i.e., nucleolar, nucleoplasmic, cytoplasmic) was completed, and the density of FUra incorporation from 5'-dFUrd was found to be approximately equally distributed between nucleoplasmic RNA and nucleolar RNA, independent of toxicity or concentration levels (average nucleolar/nucleoplasmic FUra ratio = 0.75). FUrd, however, was preferentially incorporated into nucleolar RNA (average nucleolar/nucleoplasmic FUra ratio = 22). The nontoxic accumulation of FUra in RNA of cells treated with 200 microM 5'-dFUrd was also associated with the mature cytoplasmic 28 S and 18 S rRNA, the levels of which increased considerably with exposure time. In contrast, in cells exposed to 1 microM FUrd, there was very little FUra measured in the mature 28 S and 18 S rRNA, consistent with an inhibition of rRNA processing. It is concluded that 5'-dFUrd can produce large nontoxic levels of FUra accumulation in cellular RNA compared with FUrd because total FUra incorporation in nuclear RNA was almost equally dispersed between nucleoplasmic and nucleolar RNA, whereas nuclear FUra incorporation from FUrd was preferential for nucleolar RNA. Also, for nontoxic doses of 5'-dFUrd, unaltered rRNA processing over time can result in the large accumulation of FUra-containing rRNA in the cytoplasm.

Animals↗
PubMed1985

Fusobacterium necrophorum septicemia without a primary focus.

We have presented a case of Fusobacterium necrophorum septicemia, an uncommon infection whose early course may be typified by vague diffuse symptoms or a seemingly benign upper respiratory tract inflammation mimicking acute viral syndromes or viral pharyngitis. The septicemia is most commonly, but not always preceded by an obvious oropharyngeal focus.

Adolescent↗
PubMed1984

Azapropazone--a treatment for hyperuricaemia and gout?

In a metabolic ward study of five patients, azapropazone lowered plasma uric acid but exerted only a modest and variable uricosuric effect without altering urinary xanthine and hypoxanthine levels. An alternative mechanism other than uricosuria or xanthine oxidase inhibition must account for some of the hypouricaemic action of this drug. During the first day of treatment urine volume and pH declined sharply. In a separate investigation, 22 patients were given azapropazone and 18 were given allopurinol combined with colchicine for 3 months. Allopurinol reduced plasma uric acid more quickly but at the end of the study there was little difference in the hypouricaemic results achieved by both drugs. Recurrent gout occurred more frequently with allopurinol but side-effects were confined to those taking azapropazone. A slight rise in blood urea and creatinine and a fall in haemoglobin were also features of long-term azapropazone treatment.

Adult↗
PubMed1984

A comparison of indoprofen and indomethacin in the treatment of ankylosing spondylitis.

A double-blind, crossover trial was carried out to compare the effectiveness and tolerance of indoprofen with indomethacin in the treatment of ankylosing spondylitis. Nineteen patients entered the study and 1 was withdrawn for reasons unrelated to therapy. Patients received 4-weeks' treatment in random order, with 200 mg indoprofen 4-times daily and 25 mg indomethacin 4-times daily. Most subjective and objective clinical measurements of disease activity showed a comparable degree of improvement with either drug although few statistically significant changes were observed. There was no statistically significant difference between treatments and, although gastro-intestinal side-effects occurred more commonly with indoprofen, patients known to be intolerant of indomethacin had been excluded from this trial.

Adult↗
PubMed1984

Immunoglobulin allotypes in psoriasis, psoriatic arthropathy and ankylosing spondylitis.

Immunoglobulin allotyping carried out on patients with ankylosing spondylitis, psoriatic arthritis and psoriasis alone showed increase in the phenotype G1m(1,2,3);G3m(5,11,21) in the psoriasis patients in general (p less than 0.05). In patients with psoriasis alone this increase was of greater significance (p less than 0.01). No significant deviation from the normal controls was found in ankylosing spondylitis.

Arthritis, Psoriatic↗
PubMed1983

Mechanism of cytotoxic activity of 5'-deoxy-5-fluorouridine.

The purpose of these studies was to characterize the effect of the new fluoropyrimidine nucleoside 5'-deoxy-5-fluorouridine (5'dFUrd) on macromolecular processes in correlation with its cytotoxicity in Ehrlich ascites tumor cells. Following a 2-h exposure, 5'-dFUrd exhibited an LD50 (as determined by clonogenicity) of 48 microM. In cells supplemented with 10 microM dThd, the LD50 for 5'-dFUrd increased to 660 microM. DNA synthesis was markedly and rapidly suppressed by all cytotoxic concentrations of 5'-dFUrd. There was no apparent direct measurable effect of 5'-dFUrd on either RNA or protein synthesis, although both were suppressed 24 h after the drug exposure. Thymidylate synthetase activity was completely inhibited by all cytotoxic concentrations of 5'-dFUrd. FUra incorporation into RNA was also measured and appeared to correlate with the dThd-nonreversible toxicity of 5'-dFUrd. These studies indicate that the mechanism of 5'-dFUrd cytotoxicity is directly analogous to that reported for 5-fluorouracil. The inhibition of thymidylate synthetase leading to an inhibition of DNA synthesis was the most potent cytotoxic mechanism (i.e., dThd-reversible) for 5'-dFUrd, and was found to be highly time-dependent. Higher concentrations of 5'-dFUrd resulted in dThd-nonreversible toxicity, which appeared to be related to the incorporation of FUra into RNA.

Animals↗
PubMed1983

Gold-induced thrombocytopenia: detection of anti-platelet antibody.

We describe a patient with rheumatoid arthritis who developed a sudden, severe thrombocytopenia during the early stages of treatment with sodium aurothiomalate. There were no haemorrhagic manifestations and the thrombocytopenia was rapidly corrected by corticosteroid treatment. The presence of anti-platelet IgG was demonstrated in serial serum specimens by an enzyme-linked immunosorbent assay (ELISA). Although most of this reactivity proved to be directed against allogeneic antigens on donor platelets, IgG reactive with autologous platelets was detected in the first serum sample obtained.

Adult↗
PubMed1983

Natural killer cell activity in inflammatory joint disease.

The natural killer (NK) cell activity of unfractionated peripheral blood and synovial fluid mononuclear cells from patients with inflammatory joint disease was measured in a short-term assay using the human tumour cell line, K562, as the target. The mean values for peripheral blood NK activity of the various groups (controls, rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA] were similar although the rheumatoid group showed the widest range. However, the NK activity of PsA patients (23.74 +/- 10.14) was significantly lower than that of the controls (31.63 +/- 10.8, 0.05 greater than P greater than 0.01). Almost without exception, NK activity was found to be considerably lower in synovial fluid than in paired blood samples (p less than 0.01).

Arthritis↗