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Biomedical subjects

P Davis

Publications and source records attributed to P Davis.

At least 361 records · Page 20Linked to original sources

The efficacy of diflunisal in osteoarthritis of the knee. A Canadian Multicenter Study.

Diflunisal, a long acting antiinflammatory analgesic was compared in high (1000 mg daily) and low (750 mg daily) doses with placebo in a randomized, double blind study of 6 weeks' duration in patients with osteoarthritis of the knee. Two hundred twenty-seven patients from 47 centers completed the study--high dose 69, low dose 88 and placebo 70. Pain relief was significantly greater with both doses of diflunisal than with placebo. Both patient and investigator global opinions reflected significantly greater efficacy with diflunisal. Although there was a trend in favour of the higher dose, no statistically significant differences in efficacy were found between the 2 doses of diflunisal studied. Overall adverse reactions with diflunisal were no more frequent than with placebo, but gastrointestinal side effects were significantly greater with the higher dose.

Adult↗

One-year comparative study of gold sodium thiomalate and auranofin in the treatment of rheumatoid arthritis.

The therapeutic benefits and toxicity profile of auranofin (AF) have been compared with that of gold sodium thiomalate (GSTM) over a one-year period in 120 patients with rheumatoid arthritis. A similar number of patients on both drugs remained in the study at one year (approximately 60%), and showed similar statistically significant improvement (p less than 0.01) in all clinical variables measured. At no time during the study was there a statistically significant difference in the clinical benefit obtained with either drug. Withdrawal from the study through lack of therapeutic benefit was twice as frequent with AF as with GSTM (11 compared to 6). Withdrawal due to a toxic reaction was twice as frequent and were potentially more serious with GSTM than with AF (15 compared to 9). We conclude that AF has a therapeutic potential similar to that of GSTM, however side effects were less prevalent and, when they did cause withdrawal of the drug, were potentially less serious.

Arthritis, Rheumatoid↗

Neutropenia occurring during the course of chrysotherapy: a review of 25 cases.

The records of 25 patients who developed neutropenia (granulocyte count less than or equal to 2500 mm3) while receiving intramuscular gold sodium aurothiomalate (GSTM) were reviewed. According to commonly used clinical criteria, 3 patients developed Felty's syndrome, 8 gold myelotoxicity, and 14 mild, chronic benign granulocytopenia. Myelotoxicity occurred exclusively during the initial course of therapy (less than or equal to 1 g GSTM). Twelve of the patients with chronic granulocytopenia continue to receive gold without other signs of serious toxicity. We conclude that Felty's syndrome can develop during gold administration, and that many patients may continue safely to receive gold despite neutropenia.

Agranulocytosis↗

Health patterns in New Zealand: class, ethnicity and the impact of economic development.

In the broad sweep the experience of New Zealand in health trends and patterns is similar to that of other advanced industrial societies, yet there are some important differences that draw on the country's colonial past and, more particularly, on its location in the South Pacific. Of special note is the historical experience of the indigenous Polynesian minority--the Maori--in their passage through the demographic transition to their current position in the modern urban environment. It is this dual phase of development--industrialisation for the European majority, 'westernisation' for the Polynesians--that provides the special interest of the New Zealand setting, particularly in the analysis of class and ethnicity in the shaping of health patterns.

Adolescent↗

Auranofin.

It has been widely accepted for a number of years that chrysotherapy is a valuable therapeutic agent in the treatment of progressive rheumatoid disease. This therapeutic benefit has, to some extent, been offset by the potential toxicity associated with gold compounds. The development of a gold compound with a greater therapeutic to toxicity ratio would be of considerable interest and benefit, to both patients and physicians. Initial studies with auranofin suggested that this compound was a reliably absorbed agent and that its use would avoid regular gold thiol injections. Its initial therapeutic profile was considered to be similar to that of injectable gold compounds, but with a significantly greater safety margin. The further information that has accrued from the clinical studies reported so far would tend to support these early suggestions in that auranofin has compared very favourably with gold thiols and other disease-remittive agents and that the prevalence of side effects requiring withdrawal of therapy has been approximately 25-30 per cent less. In addition, the reasons for withdrawal have often been less potentially serious side effects, notably nephrotoxicity and haematological reactions. In a review of over 3000 patients treated with auranofin, compared to 465 patients treated with injectable gold, the frequency of withdrawal from studies due to inefficacy of auranofin was approximately two to three times higher than with the gold thiols. It would appear, therefore, that in those patients continuing on therapy, auranofin is similar to injectable gold, but that a higher proportion of patients will fail to get a response within three to six months to the therapy. This potential lack of therapeutic effect is offset by the increased safety margin. In time, it is possible that auranofin will be accepted for earlier treatment in the course of rheumatoid disease than perhaps would normally have been considered. The in vivo and in vitro studies of auranofin on its mechanism of action are of considerable interest. They provide theoretical and valuable information on the mechanism of action of gold compounds and the cellular functions and interactions which may be involved in the pathogenesis of rheumatoid disease. It is interesting to note that auranofin appears to be more potent and have different effects than gold thiols, despite the fact that in terms of clinical therapeutic profile the compounds are similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Penicillamine metal chelates and their possible importance in rheumatoid arthritis--a brief review.

Complexes formed between penicillamine and metal ions have in vitro effects that may have implications regarding the therapeutic action of D-penicillamine in rheumatoid arthritis. Penicillamine-copper (I) complexes suppress arthritis in animal models and suppress or inhibit mediators of inflammation such as lysosomal enzymes, prostaglandins and the oxidative metabolites of the respiratory burst; whether the inhibition of certain in vitro immunologic responses by the same complexes has any in vivo significance remains to be determined.

Arthritis, Rheumatoid↗

Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxide radical generation by tripeptide-activated polymorphonuclear leukocytes.

The effect of sodium aurothiomalate and triethylphosphine gold on the generation of superoxide radicals by chemotactic tripeptide-activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 micrograms/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 microgram/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 micrograms/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease.

Binding Sites↗

Comparative biological properties of some synthetic olivanic acid analogues.

A series of olivanic acid/thienamycin analogues have been prepared by total synthesis. Particular attention was given to the effect of the side-chain substituents on the chemical, beta-lactamase and metabolic stability of the final products. All of the compounds possessed a broad and high level of in vitro antibacterial activity against Gram-positive and Gram-negative organisms including beta-lactamase-producing strains. Two derivatives (8c) and (8j) were selected for further evaluation on the basis of in vitro activity, ease of synthesis and stability parameters. The improved metabolic stability of the selected analogues, relative to the naturally-occurring olivanic acid, MM 13902, could be demonstrated in terms of better activity, higher blood levels and improved urinary recovery in in vivo studies in mice.

Animals↗