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Biomedical subjects

J R Lowe

Publications and source records attributed to J R Lowe.

At least 19 recordsLinked to original sources
PubMed1991

Location of receptor-binding region of protective antigen from Bacillus anthracis.

The pag gene, which codes for protective antigen (PA), a common component of the lethal and edema toxins of Bacillus anthracis, was cloned and expressed in Escherichia coli. Nested deletions of pag were generated into the C-terminus coding region. Recombinant proteins were analyzed by Western blot with either an anti-PA polyclonal antisera or two monoclonal antibodies that neutralized lethal toxin and edema toxin activities by inhibiting the binding of PA to cell receptors. Localization of the receptor binding domain within the C-terminal region of PA was suggested by the inability of the monoclonal antibodies 3B6 and 14B7 to recognize the recombinant proteins expressed by C-terminal deletions of the pag gene.

Antigens, Bacterial↗
PubMed1990

Methylsulphasalazine in rheumatoid arthritis.

Methylsulphasalazine, which differs from sulphasalazine by the addition of one methyl group, may provide the benefits of the parent drug with fewer side-effects in rheumatoid arthritis (RA). We describe the outcome of its use in RA. Of 21 patients entered into the study, 10 successfully completed 6 months of therapy; five developed adverse effects, four withdrew for reasons unrelated to drug treatment and two stopped because of inefficacy. No serious adverse effects were reported. A statistically significant improvement in most clinical assessments was observed from weeks 8-12 onwards. Significant improvement in plasma viscosity was observed and there was a trend towards improvement in serum CRP, histidine and IgM concentrations. There was a good correlation between mean serial changes in clinical and biochemical assessments indicating that the drug may exhibit the properties of a second-line agent. Median steady-state serum concentrations of methylsulphasalazine and methylsulphapyridine were 26.6 micrograms/ml and 2.85 micrograms/ml respectively.

Adult↗
PubMed1988

Sequence and analysis of the DNA encoding protective antigen of Bacillus anthracis.

The nucleotide sequence of the protective antigen (PA) gene from Bacillus anthracis and the 5' and 3' flanking sequences were determined. PA is one of three proteins comprising anthrax toxin; and its nucleotide sequence is the first to be reported from B. anthracis. The open reading frame (ORF) is 2319 bp long, of which 2205 bp encode the 735 amino acids of the secreted protein. This region is preceded by 29 codons, which appear to encode a signal peptide having characteristics in common with those of other secreted proteins. A consensus TATAAT sequence was located at the putative -10 promoter site. A Shine-Dalgarno site similar to that found in genes of other Bacillus sp. was located 7 bp upstream from the ATG start codon. The codon usage for the PA gene reflected its high A + T (69%) base composition and differed from those of genes for bacterial proteins from most other sequences examined. The TAA translation stop codon was followed by an inverted repeat forming a potential termination signal. In addition, a 192-codon ORF of unknown significance, theoretically encoding a 21.6-kDa protein, preceded the 5' end of the PA gene.

Amino Acid Sequence↗
PubMed1988

Caeruloplasmin concentration and oxidase activity in polyarthritis.

Caeruloplasmin (Cp) concentration and oxidase activity have been shown to be elevated in rheumatoid arthritis (RA) and psoriatic arthritis, but normal in Reiter's syndrome, Behcet's syndrome and juvenile seronegative polyarthritis. Synovial fluid Cp was significantly depressed in comparison with serum Cp in RA. During second-line therapy in RA, Cp concentration and activity fell significantly (P less than 0.001), but the change in Cp did not correlate with plasma viscosity.

Acute-Phase Reaction↗
PubMed1988

The effect of indomethacin on the psychomotor function of patients with rheumatic diseases.

We have compared the effect of single and multiple doses of indomethacin and placebo on objective measurements of psychomotor impairment in patients. Following a single 50 mg dose (n = 8), indomethacin produced psychomotor disturbance in only those patients who had no recent history of NSAID exposure. After multiple doses of indomethacin (25 and 50 mg tid for 5 days), significant psychomotor impairment was observed. We conclude that other NSAIDs may induce cross-tolerance to the psychomotor effects of indomethacin. Tachyphylaxis may develop to the psychomotor disturbance caused by indomethacin.

Arthritis, Rheumatoid↗
PubMed1988

The effect of allopurinol on the steady-state pharmacokinetics of indomethacin.

The effect of 5 days treatment with allopurinol (300 mg) on the pharmacokinetics of indomethacin at steady-state was investigated in eight patients. Allopurinol produced no significant effect on the indomethacin serum concentration-time curve. Allopurinol did not alter significantly the amounts of indomethacin excreted in the urine within 8 h. However, the urinary ratio of N-deschlorobenzoylindomethacin to indomethacin was reduced significantly by allopurinol administration (P less than 0.05).

Adult↗
PubMed1986

Serum and synovial fluid levels of angiotensin converting enzyme in polyarthritis.

Serum levels of angiotensin converting enzyme (ACE) activity in patients with rheumatoid arthritis (RA) (n = 48), osteoarthritis (OA) (n = 11), ankylosing spondylitis (n = 24), psoriatic arthritis (n = 12), and Behçet's syndrome (n = 20) were not significantly different from those of normal controls (n = 26). Synovial fluid ACE activity was lower in OA than in RA but was similar when corrected for protein levels. An increase in serum ACE concentration in patients with RA receiving captopril therapy is in agreement with previous results. There was some correlation of ACE with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) but not with clinical indices in captopril treated patients. It is suggested that the beneficial actions of captopril in the treatment of RA are not due to its activity as an ACE inhibitor, but more probably a result of captopril being an aliphatic thiol.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

A double-blind comparison of tenoxicam (Tilcotil, Mobiflex) at two doses against ibuprofen in rheumatoid arthritis.

Tenoxicam (Tilcotil, Mobiflex), a new non-steroidal anti-inflammatory agent of the oxicam group, has been compared at two dose levels (20 mg/day and 4 mg/day) to ibuprofen 800 mg t.d.s. in a double-blind parallel group study of four weeks duration in rheumatoid arthritis. Efficacy results showed no significant difference between the three treatments at two or four weeks though clinical assessments slightly favoured groups treated with tenoxicam in this 30 patient study. No patients withdrew from tenoxicam because of side-effects and there were no withdrawals because of inefficacy. The higher dose (40 mg) of tenoxicam was as well tolerated as the lower dose (20 mg) though plasma levels of tenoxicam suggested that at the lower dose this drug had barely reached optimum plasma levels in a study of relatively short duration.

Adult↗
PubMed1983

A phenylbutazone dose-finding study in rheumatoid arthritis.

Different doses of phenylbutazone have been compared in a double blind study on 32 patients with rheumatoid arthritis in order to determine the minimum effective dose. Of 8 different dose levels studied (90 mg, 150 mg, 180 mg, 240 mg, 270 mg, 300 mg, 360 mg and 450 mg/day) the most efficacious was found to be 300 mg/day. Doses below this did not produce full benefit; no further improvement occurs with higher doses. Although 7/32 patients developed adverse reactions there was no relationship between these and the plasma levels of either phenylbutazone or oxyphenbutazone. An attempt was made to distinguish 'responders' from 'non-responders'. We found no relationship between response and plasma levels of phenylbutazone or oxyphenbutazone.

Adult↗
PubMed1983

Gastro-intestinal blood loss with high dose tilcotil (Ro 12-0068) and aspirin: an open crossover clinical trial and pharmacokinetic assessment in normal volunteers.

An open crossover study was carried out in 8 normal volunteer subjects to compare faecal blood loss resulting from tilcotil (Ro12-0068), a new anti-inflammatory agent, and from enteric-coated aspirin. After a 1-week run-in period, subjects were allocated at random to receive treatment for 2 weeks with either 40 mg tilcotil as a single dose per day or aspirin, 900 mg 4-times daily, reduced if necessary to a maximum tolerated dose. Subjects were then crossed over to the alternative treatment for a further 2 weeks. The results showed that tilcotil produced less blood loss, assessed by a radioactive labelling method, and was better tolerated than aspirin. Plasma concentrations of tilcotil showed that the drug's half-life was approximately 50 hours, compatible with once daily dosage, and steady state concentrations on multiple dosing were reached after 10 to 12 days.

Adult↗
PubMed1982

A pharmacological and clinical comparison of prednisolone and betamethasone in rheumatoid arthritis.

1. Two oral corticosteroids, prednisolone (8 mg/day) and betamethasone (1 mg/day) have been compared in terms of efficacy and adrenal suppressive activity when used in chronic oral dosage in rheumatoid arthritis. 2. 20 patients were entered to a single blind crossover study receiving each drug for a two-week period. Clinical and laboratory assessments were performed. 3. At this dosage there was no significant difference between any of the clinical parameters assessed for either drug though patient preference was 13 for prednisolone and 7 for betamethasone. 4. At this dosage adrenal suppression was not equivalent, being significantly more marked with betamethasone. 5. The results suggest that prednisolone is the drug of choice for chronic dosage.

Adult↗
PubMed1981

A pharmacokinetic and tolerance study of Ro13-9904, a new cephalosporin antibiotic.

1 Six healthy male volunteers received a total of 2500 mg of a new cephalosporin antibiotic Ro13-9904 by intramuscular injection in five divided doses at intervals of 12 h. 2 No significant systemic side-effects were observed and this was confirmed haematologically and biochemically. 3 The drug was distributed following intramuscular injection reaching a mean peak plasma concentration of 55 micrograms ml-1 (range 46-66) 1 to 2 h after the first injection. 4 Monoexponential elimination of drug was demonstrated. No significant difference was recorded in the plasma half-life after the initial dose (mean 6.7 h) and at steady state (mean 6.7 h). The half-life is long compared with other cephalosporin antibiotics. 5 On the basis of the observed half-life, steady state should be reached within 48 h. A mean peak plasma concentration of 74 micrograms ml-1 (range 65-87) was recorded at steady state. Steady state plasma concentrations of Ro13-9904 with a dose of 500 mg every 13 h may be predicted from the pharmacokinetics of a single dose.

Adult↗
PubMed1981

Bioavailability of aspirin in the presence of dextropropoxyphene/paracetamol combination.

The effect of 2 doses of a combination analgesic preparation (each dose containing 65 mg dextropropoxyphene hydrochloride and 650 mg paracetamol) upon plasma salicylate concentration after a single dose of soluble aspirin (1.2 g) or enteric-coated aspirin (1.2 g) was examined in 6 normal volunteers and compared with the effect of placebo. The dextropropoxyphene/paracetamol caused no reduction in the plasma salicylate level after absorption of soluble aspirin compared with placebo and, although a reduction in plasma salicylate was seen after enteric-coated aspirin in a single subject, this may reflect erratic absorption rather than a drug interaction.

Acetaminophen↗
PubMed1980

Discriminatory indices of response of patients with rheumatoid arthritis treated with D-penicillamine.

A long-term study is being undertaken to classify drugs used as specific agents in the treatment of rheumatoid arthritis in terms of their effects on biochemical and clinical characteristics of the disease. In particular is hoped to establish those indices which are most relevant to the response of RA to treatment. Fifteen patients were treated with D-penicillamine after an initial period of 2 weeks on aspirin alone, when the baseline investigations were made. The dose of penicillamine was increased gradually to a maximum of 500 mg a day over the period of 6 months, and changes in 8 clinical and 25 laboratory indices were measured on 8 separate occasions in the 6-month period. Marked clinical improvement took place, and this was mirrored by changes in a wide range of biochemical parametaers. ESR and C-reactive protein were shown to be the most suitable indices of disease improvement with penicillamine treatment.

Adult↗