Biomedical subjects
Publications and source records attributed to P Davis.
We have used a rapid, sensitive technique to assay penicillamine and its disulphide metabolites in body fluids. Penicillamine in serum is rapidly oxidized and the serum levels of the reduced material found in a pilot study of 10 patients ranged between 0.07 to 0.28 mg%. This technique may prove useful in allowing closer monitoring of therapy with this agent.
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The effect of sodium aurothiomalate (GSTM) and auranofin (AF) on polymorphonuclear (PMN) leukocytes has been assessed using a Candida albicans phagocytosis method and by the generation of chemiluminescence of activated cells. Both compounds inhibited the phagocytosis of Candida albicans but at therapeutic concentrations this was only consistent and significant with AF. This drug, but not GSTM, also had a suppressive effect on the generation of chemiluminescence. These results suggest that AF has a more potent effect on PMN function than GSTM. They also suggest that the effect of these compounds in vitro may differ from each other and from the effects previously reported with other phagocytic cells, notably peripheral blood mononuclear cells.
Therapeutic serum concentrations of auranofin, expressed as elemental gold, range from 0.25 - 1.0 micrograms/ml. Monocyte antibody dependent cellular cytotoxicity (ADCC) could be reduced by up to 50% at a gold concentration of 0.125 micrograms/ml. Lymphocyte ADCC was much less dramatically affected although 2.5 micrograms/ml produced virtually complete inhibition. The most surprising finding is a marked stimulation of natural killer (NK) cell activity using a variety of targets. NK activity was markedly enhanced by concentrations of 0.125 to 0.5 micrograms/ml (range 2-500%). This is a biphasic dose dependent response. 1.0 micrograms/ml was depressive and 2.5 micrograms/ml completely abolished NK cell activity. Whether these selected in vitro responses play a role in modulating tissue damage in vivo is yet to be determined.
One hundred and twelve patients with classical or definite rheumatoid arthritis (RA) were randomly assigned to receive either sodium aurothiomalate (GSTM) or auranofin (AF). Monthly clinical assessments (morning stiffness, grip strength, articular index, pain, quality of life) and concurrent hematological, biochemical, and urine studies were performed to monitor the efficacy/toxicity (E/T) ratio. Ninety-two patients have completed 3 months; 65, 6 months; 47, 9 months; and 30, 12 months. The groups were numerically balanced at each time period. Analysis of the 0-6 month period suggests that both drugs were equally and significantly beneficial after 3 months and that this was maintained at 6 months. Toxicity was as frequent in both groups but more serious in the GSTM group. The main side effects were gastrointestinal (diarrhea) in the AF group and mucocutaneous in the GSTM group. Half of the withdrawals (14 in each group) were because of side effects in the GSTM group and for inadequate therapeutic efficacy in the AF group. This study suggests that after 6 months of treatment the E/T ratio of AF is greater than or equal to that of GSTM. These conclusions will need to be confirmed during the ongoing longer observation period. A significant clinical difference between the 2 drugs is that in a given patient treated with GSTM, the onset of toxicity coincides with a good therapeutic effect. This relationship does not appear to exist during AF treatment.
Splenic reticuloendothelial function was assessed in 20 patients with active rheumatoid arthritis by measuring the clearance of autologous heat-damaged labeled erythrocytes from the circulation. Eight patients (40%) had delayed clearance but in contrast to previous reports, we found no correlation between disease activity, levels of circulating immune complexes and splenic hypofunction. The absence of IgM rheumatoid factor was noted in 7 of 8 patients with delayed clearance times.
Sarcoidosis may be associated with an arthritis primarily of the legs, usually accompanied by hilar adenopathy and marked systemic symptoms. We retrospectively reviewed 16 Caucasian patients referred because of rheumatologic complaints with an associated asymptomatic hilar adenopathy in 8 (50%) and the presence of erythema nodosum in 12 (75%). Investigations, including pulmonary function tests and angiotensin converting enzyme, were normal. Clinical course was generally benign and self-limited with median duration of 3 months for the hilar adenopathy and arthritis. HLA typing revealed a significant increased prevalence of HLA A1 B8 haplotype.
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OBJECTIVES: We have reviewed 11 women post-augmentation mammoplasty who were referred to our clinic with diffuse rheumatic complaints. All patients had undergone mammoplasty with silicone gel-filled implants prior to the onset of their locomotor symptoms (mean latency time 7.8 years). One physician interviewed and examined each of these patients following a standardized format for clinical retrieval. RESULTS: Of the patients reviewed, 6 patients had clinical fibromyalgia based on the ACR criteria, and the remaining 5 patients had symptoms consistent with the "chronic fatigue syndrome." None of our patients were found to have evidence of a defined connective tissue disease. Antinuclear antibodies were detected in 4 (36%) patients and low level titres of extractable nuclear antigens in only 2 (18%). CONCLUSIONS: Previously a causal relationship between the use of silicone gel-filled breast implants and the subsequent development of symptoms referred to as human adjuvant disease (HAD) has been proposed. On the basis of currently accepted criteria we have preferred to diagnose our post-mammoplasty patients without specific connective tissue disease, as having chronic fatigue syndrome (CFS), or when tender points are present, as having fibromyalgia (FMS), rather than implying that such cases represent a separate and unique rheumatological disease entity. In the light of our current understanding of CFS and FMS, a relationship between them and the previous silicone mammoplasty seems possible.
A case report of spindle cell carcinoma of the right mandibular alveolus is reported, which clinically mimicked a squamous cell carcinoma. Careful histological interpretation is necessary for successful treatment of such tumors. The use of radiation therapy after radical neck dissection is also stressed upon.